Genetic parameters for predicted methane production and laser methane detector measurements.
Enteric ruminant methane is the most important greenhouse gas emitted from the pastoral agricultural systems. Genetic improvement of livestock provides a cumulative and permanent impact on performance, and using high-density SNP panels can increase the speed of improvement for most traits. In this study, a data set of 1,726 dairy cows, collected since 1990, was used to calculate a predicted methane emission (PME) trait from feed and energy intake and requirements based on milk yield, live weight, feed intake, and condition score data. Repeated measurements from laser methane detector (LMD) data were also available from 57 cows. The estimated heritabilities for PME, milk yield, DMI, live weight, condition score, and LMD data were 0.13, 0.25, 0.11, 0.92, 0.38, and 0.05, respectively. There was a high genetic correlation between DMI and PME. No SNP reached the Bonferroni significance threshold for the PME traits. One SNP was within the 3 best SNP for PME at wk 10, 20, 30, and 40. Genomic prediction accuracies between dependent variable and molecular breeding value ranged between 0.26 and 0.30. These results are encouraging; however, more work is required before a PME trait can be implemented in a breeding program.


Intradural spinal metastases: a surgical series of 15 patients.
Intradural spinal metastases are rare, and little is known regarding surgical indications and outcomes. A retrospective search identified adults with intradural spinal metastases operated on at the Mayo Clinic from 1994-2011. Data were collected regarding demographics, tumor type and location, and outcomes. Fifteen patients with intradural spinal metastases were investigated. The age range was 38-74 years (mean = 55 years; ±SD = 11.1). Predominant tumor location and type were lumbosacral and adenocarcinoma, respectively: 3 intramedullary and 12 extramedullary. Patients were operated on to relieve or prevent progressive/intractable neurological sequelae and/or pain. Of 13 who underwent resection, gross total removal was reported in 10; simple biopsy was performed in 2. There was one surgical complication, no medical complications, and no surgical mortality. At median follow-up of 1 month postoperatively, 10 of 15 patients were stable or improved. Of 13 patients who underwent resection, 10 were stable or improved. Of two patients who underwent biopsy, neither was stable or improved at follow-up. Using the Modified McCormick Scale, 11 of 15 patients were "functional" preoperatively and 4 went from "functional" preoperatively to "non-functional" postoperatively. Three of those four died within 60 days of surgery from systemic disease progression. Median hospital stay was 8 days. Ten of 15 patients died by the end of the study period, and the median survival of 15 patients was 5 months. With improved outcomes in metastatic cancer, more patients are encountered in practice. An aggressive surgical approach is warranted for extramedullary lesions, whereas caution is advised for intramedullary lesions. Postoperative functional decline is more likely due to systemic disease progression rather than surgery.


Missense mutations in disease genes: a Bayesian approach to evaluate causality.
The problem of interpreting missense mutations of disease-causing genes is an increasingly important one. Because these point mutations result in alteration of only a single amino acid of the protein product, it is often unclear whether this change alone is sufficient to cause disease. We propose a Bayesian approach that utilizes genetic information on affected relatives in families ascertained through known missense-mutation carriers. This method is useful in evaluating known disease genes for common disease phenotypes, such as breast cancer or colorectal cancer. The posterior probability that a missense mutation is disease causing is conditioned on the relationship of the relatives to the proband, the population frequency of the mutation, and the phenocopy rate of the disease. The approach is demonstrated in two cancer data sets: BRCA1 R841W and APC I1307K. In both examples, this method helps establish that these mutations are likely to be disease causing, with Bayes factors in favor of causality of 5.09 and 66.97, respectively, and posterior probabilities of .836 and .985. We also develop a simple approximation for rare alleles and consider the case of unknown penetrance and allele frequency.


Remineralization of eroded enamel lesions by simulated saliva in vitro.
The purpose of this study was to evaluate the effects of two simulated saliva (SS) remineralization solutions comprising different calcium-inorganic phosphate (Ca/P(i)) ratios on eroded enamel. 3 mm diameter enamel cores were extracted from bovine teeth, mounted in acrylic rods, ground and polished,and initially demineralized with either 0.3% (120 minutes) or 1.0% (30 minutes) citric acid solutions (pH 3.8). Both sets of initially eroded specimens were evaluated for surface microhardness (N=10) and treated with either 0.3 or 1.6 Ca/P(i) ratio SS. Groups were first exposed to a seven-day remineralization period and then were cycled in a three-day regimen consisting daily of three rounds of two-hour plus overnight SS treatments and three 10-minute static immersions in demineralization solution. Specimens were assessed using surface microhardness and scanning electron microscopy. Initial erosion from 0.3% citric acid led to elliptical-shaped pore openings several microns in length and in depth and contrasted significantly with respect to 1% citric acid. The greatest remineralization was observed from the 0.3 Ca/P(i) SS, while the 1.6 Ca/P(i) SS produced the least. This study demonstrated the nature of remineralization of eroded enamel depends on both initial erosive conditions and the Ca/P(i) ratio of simulated saliva.


Dexamethasone suppression test in first-episode schizophrenia.
Higher rates of dexamethasone test (DST) nonsuppression in schizophrenia have been attributed to depressive symptoms, suicidality and negative symptoms. No study concerning first-episode schizophrenia has yet been published. In patients hospitalised for the first time with first-episode schizophrenia the DST has been performed before, at the end of the acute treatment and after one year. At the same time the clinical evaluation with PANSS was performed. A cortisol value >5 microgram/dl in either of the postdexamethasone samples indicated nonsuppression of cortisol. A total of 56 males were included. 18% of pts were DST nonsuppressors at medication-free baseline, 5% and 16% after acute treatment and after one year respectively. After 1 year 42/56 of patients fulfilled the criteria of remission. The rate of nonsuppression was 21.4%, 5% and 16.4% in remitters and 7%, 7% and 14.3% in nonremitters. Significant differences in the whole group were found between postdexamethasone cortisolemia at discharge on the one hand and on admission and at the one-year follow-up on the other. Significant correlations were observed between postdexamethasone cortisolemia and negative symptoms at the end of acute treatment. In first-episode schizophrenia the short-term treatment led to a decrease in cortisolemia and rates of nonsuppression and an increase at a one-year follow-up. Rates of DST nonsuppression in schizophrenia including first-episode schizophrenia are influenced by the stage of illness and medication status. The impairment of feedback regulation of cortisol secretion may be related to different biopathogenetic mechanisms depending on the phase of the illness.


Translating the genomic architecture of breast cancer into clinical applications.
The genetic alterations in breast cancer have in recent years been studied through a variety of techniques: analysis of alterations in individual oncogenes and tumor suppressor genes; gene expression profiling of both messenger RNA and microRNA; global analysis of DNA copy number changes; and most recently, whole-genome sequence analysis. Analysis of the association between genetic alterations and gene expression profiles with prognosis and response to specific treatments will lead to improved possibilities for patient-tailored treatment. Russnes et al. now add an additional view on the complex genetic makeup of breast carcinomas by developing algorithms that can be used to subclassify tumors based on their patterns of genome-wide DNA copy number gains and losses, which vary from very simple (only a few gains and losses) to complex. The algorithms provide indices that can be used in conjunction with results from other genetic analyses to subclassify breast cancer, with the aim of defining subgroups of patients that differ with respect to prognosis and response to therapy.


Dual action of bacteriocin PLNC8 αβ through inhibition of Porphyromonas gingivalis infection and promotion of cell proliferation.
Periodontitis is a chronic inflammatory disease that is characterised by accumulation of pathogenic bacteria, including Porphyromonas gingivalis, in periodontal pockets. The lack of effective treatments has emphasised in an intense search for alternative methods to prevent bacterial colonisation and disease progression. Bacteriocins are bacterially produced antimicrobial peptides gaining increased consideration as alternatives to traditional antibiotics. We show rapid permeabilisation and aggregation of P. gingivalis by the two-peptide bacteriocin PLNC8 αβ. In a cell culture model, P. gingivalis was cytotoxic against gingival fibroblasts. The proteome profile of fibroblasts is severely affected by P. gingivalis, including induction of the ubiquitin-proteasome pathway. PLNC8 αβ enhanced the expression of growth factors and promoted cell proliferation, and suppressed proteins associated with apoptosis. PLNC8 αβ efficiently counteracted P. gingivalis-mediated cytotoxicity, increased expression of a large number of proteins and restored the levels of inflammatory mediators. In conclusion, we show that bacteriocin PLNC8 αβ displays dual effects by acting as a potent antimicrobial agent killing P. gingivalis and as a stimulatory factor promoting cell proliferation. We suggest preventive and therapeutical applications of PLNC8 αβ in periodontitis to supplement the host immune defence against P. gingivalis infection and support wound healing processes.


Identification of novel and conserved microRNA and their expression in the gray mouse lemur, Microcebus murinus, a primate capable of daily torpor.
MicroRNA (miRNA) are endogenous small noncoding RNA gene products, on average 22 nt long, that play important regulatory roles in mediating gene expression by binding to and targeting mRNAs for degradation or translational repression. In this paper we identify both novel and conserved miRNA sequences present in the genome of the gray mouse lemur, Microcebus marinus. In total, 122 conserved and 44 novel miRNA were identified with high confidence from the lemur genome (Mmur_2.0) and were used for expression analysis. All conserved and novel miRNA were subjected to relative quantification by RT-qPCR in liver samples from control and torpid lemurs. A total of 26 miRNA (16 conserved and 10 novel) showed increased levels during primate torpor, whereas 31 (30 conserved and 1 novel) decreased. Additional in silico mapping of the predicted mRNA targets of torpor-responsive mature miRNA suggested that miRNA that increased during torpor were collectively involved in cell development and survival pathways, while miRNA that decreased were enriched in targeting immune function. Overall, the study suggests new regulatory mechanisms of primate torpor via miRNA action.


Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers.
Caffeine is present in many widely consumed drinks and some foods. In the fairly extensive literature on the psychostimulant effects of caffeine, there are few dose-response studies and even fewer studies of the effects of doses of caffeine lower than 50 mg (the range of the amounts of caffeine contained in, for example, a typical serving of tea or cola). This study measured the effects of 0, 12.5, 25, 50 and 100 mg caffeine on cognitive performance, mood and thirst in adults with low and moderate to high habitual caffeine intakes. This was a double-blind, within-subjects study. Following overnight caffeine abstinence, participants (n=23) completed a test battery once before and three times after placebo or caffeine administration. The test battery consisted of two performance tests, a long duration simple reaction time task and a rapid visual information processing task, and a mood questionnaire (including also an item on thirst). Effects on performance and mood confirmed a psychostimulant action of caffeine. All doses of caffeine significantly affected cognitive performance, and the dose-response relationships for these effects were rather flat. The effects on performance were more marked in individuals with a higher level of habitual caffeine intake, whereas caffeine increased thirst only in low caffeine consumers. After overnight caffeine abstinence, caffeine can significantly affect cognitive performance, mood and thirst at doses within and even lower than the range of amounts of caffeine contained in a single serving of popular caffeine-containing drinks. Regular caffeine consumers appear to show substantial tolerance to the thirst-increasing but not to the performance and mood effects of caffeine.


Nonredundant, isoform-specific roles of HDAC1 in glioma stem cells.
Glioblastoma (GBM) is characterized by an aberrant yet druggable epigenetic landscape. One major family of epigenetic regulators, the histone deacetylases (HDACs), are considered promising therapeutic targets for GBM due to their repressive influences on transcription. Although HDACs share redundant functions and common substrates, the unique isoform-specific roles of different HDACs in GBM remain unclear. In neural stem cells, HDAC2 is the indispensable deacetylase to ensure normal brain development and survival in the absence of HDAC1. Surprisingly, we find that HDAC1 is the essential class I deacetylase in glioma stem cells, and its loss is not compensated for by HDAC2. Using cell-based and biochemical assays, transcriptomic analyses, and patient-derived xenograft models, we find that knockdown of HDAC1 alone has profound effects on the glioma stem cell phenotype in a p53-dependent manner. We demonstrate marked suppression in tumor growth upon targeting of HDAC1 and identify compensatory pathways that provide insights into combination therapies for GBM. Our study highlights the importance of HDAC1 in GBM and the need to develop isoform-specific drugs.


Antenatal uterine activity monitoring of women at increased risk of preterm labour.
The aim of the study was to investigate the usefulness of antenatal uterine activity monitoring in the management of women at increased risk of preterm labour on the basis of a past history of preterm birth or mid-trimester abortion. Uterine activity was recorded every 2 weeks between 20 and 28 weeks gestation. Activity was considered to be increased if pressure changes > 15 mmHg were detected. Fifty-eight women had uterine activity monitoring. Of them, 39 had normal uterine activity. Nineteen women had increased activity and they were randomized to either a study group (9) where the findings were revealed to the clinicians caring for them or a control group (10) where the findings were not revealed. There was no standard regimen of management for the study group except that additional uterine activity monitoring was performed to provide feed back to the clinicians about their interventions. The sensitivity, specificity, positive predictive value and negative predictive value of uterine activity monitoring for preterm births and for preterm births before 32 weeks were disappointing. Uterine activity monitoring was not useful for predicting births prior to 32 weeks; most of these were preceded by prelabour rupture of the membranes. The pregnancy outcome of women with increased uterine activity was not better if clinicians were aware of that increased activity than if they were not.


Slow pace of dietary change in Scotland: 2001-9.
Monitoring changes in the food and nutrient intake of a nation is important for informing the design and evaluation of policy. Surveys of household food consumption have been carried out annually in the UK since 1940 and, despite some changes over the years 1940-2000, the method used for the Expenditure and Food Survey (Living Costs and Food Survey from 2008) has been fundamentally the same since 2001. Using these surveys an analytical procedure was devised to compare food consumption and nutrient intake in Scotland with the Scottish dietary targets, and monitor change. This method takes into account contributions to composite foods and losses due to food preparation, as well as inedible and edible waste. There were few consistent improvements in consumption of foods or nutrients targeted for change over the period 2001-9. A significant but small increase was seen in mean fruit and vegetable consumption (259 g/d in 2001, 279 g/d in 2009, equating to an increase of less than 3 g/person per year). There was also a significant decrease in the percentage of food energy from SFA (15·5 % in 2001, 15·1 % in 2009) and from non-milk extrinsic sugars (15·5 % in 2001, 14·8 % in 2009), concurrent with a reduction in whole milk consumption and soft drink consumption, respectively. These small changes are encouraging, but highlight the time taken for even modest changes in diet to occur. To achieve a significant impact on the health of the present Scottish population, the improvements in diet will need to be greater and more rapid.


Clinical review 129: Oral cholecystographic agents and the thyroid.
Oral cholecystographic agents (OCAs) are known to affect thyroid hormone metabolism by acting as potent inhibitors of type I and type II deiodinases, blocking the conversion of T(4) to T(3) and rT(3) to T(2). In addition, iodine released from the drug blocks thyroid gland secretion of thyroid hormone. These properties make OCAs a potentially useful drug therapy in patients with hyperthyroidism and other thyrotoxic disorders. Short-term treatment with OCAs rapidly reduces serum T(3) levels, with a lesser effect on T(4) levels. OCAs are not useful for long-term treatment, which is usually followed by exacerbation of hyperthyroidism with continued use. The lack of significant side effects makes these drugs an excellent short-term option in situations where a rapid clinical improvement is critical.


Prognostic value of numerical chromosome aberrations in multiple myeloma: A FISH analysis of 15 different chromosomes.
Recent observations indicate that chromosome aberrations are important prognostic factors in patients with multiple myeloma (MM) treated with high-dose chemotherapy. Nevertheless, the inherent problems of conventional cytogenetics have hampered the systematic evaluation of this parameter in series of patients treated with conventional chemotherapy. Fluorescence in situ hybridization (FISH) analysis is an attractive alternative for evaluation of numerical chromosomal changes. In the present study, we analyze the relationship between aneuploidies of 15 different chromosomes assessed by FISH and prognosis in a series of 63 patients with MM treated with conventional chemotherapy. After a median follow-up of 61 months (range, 6 to 109), 49% of patients are still alive with a median survival of 33 months. The overall incidence of numerical chromosome abnormalities was 70%. This incidence significantly increased when seven or more chromosomes were analyzed (53 patients), reaching 81%. Trisomies of chromosomes 6, 9, and 17 were associated with prolonged survival (P = .033, P = .035, and P = .026, respectively); by contrast, overall survival (OS) was lower in cases with monosomy 13 (as assessed by deletion of Rb gene, P = .0012). From the clinical point of view, loss of Rb gene was associated with a poor performance status; low hemoglobin levels; high creatinine, C-reactive protein, and lactic dehydrogenase serum levels; high percentage of bone marrow plasma cells (BMPC); extensive bone lytic lesions; and advanced clinical stage. Other chromosome abnormalities such as trisomy of chromosome 9 and 17 were associated with good prognostic features including high hemoglobin levels, early clinical stage, beta2microglobulin less than 6 micro/mL, and low percentage of BMPC. A multivariate analysis for OS showed that S-phase PC greater than 3% (P = .010) and beta2microglobulin serum levels greater than 6 micro/mL (P = .024), together with monosomy of chromosome 13 (P = .031) and nontrisomy of chromosome 6 (P = .048) was the best combination of independent parameters for predicting survival in patients with MM. According to these results, chromosomal analysis is of great use in patients with MM at diagnosis to have a correct prognostic evaluation for clinical decision making.


alpha 4 integrin plays a critical role in early stages of T lymphocyte migration in Peyer's patches of rats.
Lymphocyte recirculation through the blood flow circuit and lymphoid organs is important for the maintenance of immune defense, and is defined as lymphocyte homing. During the homing process, several adhesion molecules have been postulated to play an important role in lymphocyte recruitment from the vascular space. In the present study, we investigated the effect of a novel mAb against rat alpha 4 integrin (MR alpha 4-1) on the interaction of T lymphocytes with postcapillary venules (PCV) and their subsequent migration into the interstitium of Peyer's patches, using intravital video microscopy. T lymphocytes collected from intestinal lymph were labeled with a fluorochrome carboxyfluorescein diacetate succinimidyl ester and were than injected into the jugular vein of recipient rats. The microvasculature in the ileal Peyer's patches of recipient rats was observed sequentially by intravital fluorescence microscopy. In controls, lymphocytes exhibited rolling behavior which was followed by firm adhesion to the endothelium of PCV. The density of sticking lymphocytes gradually increased during the first 30 min. These initial interactions of lymphocytes with the PCV (rolling and adherence) were drastically inhibited by treatment with MR alpha 4-1, both when MR alpha 4-1 was preinfused into rats and when T cells were preincubated in vitro with MR alpha 4-1 before administration. MR alpha 4-1 also significantly inhibited the transendothelial migration of T lymphocytes, associated by the ratio of migration to adherence. However, once T lymphocytes migrated into the interstitium, treatment with MR alpha 4-1 did not affect the pattern of travel of these lymphocytes in the interstitium or their transport into the microlymphatics in the parafollicular area. Therefore, we conclude that alpha 4 integrins play a critical role in the rolling and sticking of T cells and their transendothelial migration in PCV of Peyer's patches.


The role of spectral resolution, working memory, and audibility in explaining variance in susceptibility to temporal envelope distortion.
Several studies have shown that hearing thresholds alone cannot adequately predict listeners' success with hearing-aid amplification. Furthermore, previous studies have shown marked differences in listeners' susceptibility to distortions introduced by certain nonlinear amplification parameters. The purpose of this study was to examine the role of spectral resolution, working memory, and audibility in explaining perceptual susceptibility to temporal envelope and other hearing-aid compression-induced distortions for listeners with mild to moderate and moderate to severe hearing loss. A between-subjects repeated-measures design was used to compare speech recognition scores with linear versus compression amplification, for listeners with mild to moderate and moderate to severe hearing loss. The study included 15 adult listeners with mild to moderate hearing loss and 13 adults with moderate to severe hearing loss. Speech recognition scores were measured for vowel-consonant-vowel syllables processed with linear, moderate compression, and extreme compression amplification. Perceptual susceptibility to compression-induced temporal envelope distortion was defined as the difference in scores between linear and compression amplification. Both overall scores and consonant feature scores (i.e., place, manner, and voicing) were analyzed. Narrowband spectral resolution was measured using individual measures of auditory filter bandwidth at 2000 Hz. Working memory was measured using the reading span test. Signal audibility was quantified using the Aided Audibility Index. Multiple linear regression was used to determine the predictive role of spectral resolution, working memory, and audibility benefit on listeners' susceptibility to compression-induced distortions. For all listeners, spectral resolution, working memory, and audibility benefit were significant predictors of overall distortion scores. For listeners with moderate to severe hearing loss, spectral resolution and audibility benefit predicted distortion scores for consonant place and manner of articulation features, and audibility benefit predicted distortion scores for consonant voicing features. For listeners with mild to moderate hearing loss, the model did not predict distortion scores for overall or consonant feature scores. The results from this study suggest that when audibility is adequately controlled, measures of spectral resolution may identify the listeners who are most susceptible to compression-induced distortions. Working memory appears to modulate the negative effect of these distortions for listeners with moderate to severe hearing loss.


A novel off-center paddle impeller (OPI) dissolution testing system for reproducible dissolution testing of solid dosage forms.
Dissolution testing is routinely conducted in the pharmaceutical industry to provide in vitro drug release information for quality control purposes. The most common dissolution testing system for solid dosage forms is the United States Pharmacopeia (USP) Dissolution Testing Apparatus 2. This apparatus is very sensitive to the initial location of the tablet, which cannot be controlled because the tablet is dropped into the vessel at the beginning of the test and it may rest at random locations at the vessel's bottom. In this work, a modified Apparatus 2 in which the impeller was placed 8 mm off center in the vessel was designed and tested. This new design was termed "OPI" for "off-center paddle impeller." Dissolution tests were conducted with the OPI apparatus for nine different tablet locations using both disintegrating tablets (prednisone) and nondisintegrating tablets (salicylic acid). The dissolution profiles in the OPI apparatus were largely independent of the tablet location at the vessel's bottom, whereas those obtained in the Standard System generated statistically different profiles depending on the tablet location. The newly proposed OPI system can effectively eliminate artifacts generated by random settling of the tablet at the vessel's bottom, thus making the test more robust.


Religion, Spirituality and Risk of Coronary Heart Disease: A Matched Case-Control Study and Meta-Analysis.
Although the association between religion/spirituality (R/S) and psychological outcomes is well established, current understanding of the association with cardiovascular disease remains limited. We sought to investigate the association between Islamic R/S and coronary heart disease (CHD), and place these findings in light of a meta-analysis. In this case-control study, 190 cases with non-fatal CHD were identified and individually matched with 383 hospital-based controls. R/S was measured by self-administered 102 items questionnaire. A tabular meta-analysis was performed of observational studies on R/S (high level versus low level) and CHD. In addition, a dose-response meta-analysis was conducted using generalized least-squares regression. Participants in the top quartile had decreased odds of CHD comparing to participants in the lowest quartile of religious belief (OR 0.20, 95% confidence interval (CI) 0.06-0.59), religious commitment (OR 0.36, CI 95% 0.13-0.99), religious emotions (OR 0.39, CI 95% 0.18-0.87), and total R/S score (OR 0.30, CI 95% 0.13-0.67). The meta-analysis study showed a significant relative risk of 0.88 (CI 95% 0.77-1.00) comparing individuals in high level versus low level of R/S. In dose-response meta-analysis, comparing people with no religious services attendance, the relative risks of CHD were 0.77 (CI 95% 0.65-0.91) for one times attendance and 0.27 (CI 95% 0.11-0.65) for five times attendance per month. R/S was associated with a significantly decreased risk of CHD. The possible causal nature of the observed associations warrants randomized clinical trial with large sample size.


Membrane directed expression in Escherichia coli of BBA57 and other virulence factors from the Lyme disease agent Borrelia burgdorferi.
Membrane-embedded proteins are critical to the establishment, survival and persistence in the host of the Lyme disease bacterium Borrelia burgdorferi (Bb), but to date, there are no solved structures of transmembrane proteins representing these attractive therapeutic targets. All available structures from the genus Borrelia represent proteins expressed without a membrane-targeting signal peptide, thus avoiding conserved pathways that modify, fold and assemble membrane protein complexes. Towards elucidating structure and function of these critical proteins, we directed translocation of eleven expression-optimized Bb virulence factors, including the signal sequence, to the Escherichia coli membrane, of which five, BBA57, HtrA, BB0238, BB0323, and DipA, were expressed with C-terminal His-tags. P66 was also expressed using the PelB signal sequence fused to maltose binding protein. Membrane-associated BBA57 lipoprotein was solubilized by non-ionic and zwitterionic detergents. We show BBA57 translocation to the outer membrane, purification at a level sufficient for structural studies, and evidence for an α-helical multimer. Previous studies showed multiple critical roles of BBA57 in transmission, joint arthritis, carditis, weakening immune responses, and regulating other Bb outer surface proteins. In describing the first purification of membrane-translocated BBA57, this work will support subsequent studies that reveal the precise mechanisms of this important Lyme disease virulence factor.


Achilles' heel of sociality revealed by energetic poverty trap in cursorial hunters.
This study empirically tests two foundation ecological theories: (1) pack hunting is a driver for the evolution of sociality; and (2) species have a finite energy potential, whereby increased maintenance costs result in decreased reproductive effort. Using activity and prey data from 22 packs of African wild dogs (Lycaon pictus), we parameterized a model detailing the energetic cost/benefit of cooperative hunting. Larger pack size increased foraging time, prey size, and capture probability while reducing chase distance, resulting in a rapidly increasing net rate of energy intake up to a pack size of five, which peaked at 10 individuals and then declined. With a streamlined body plan necessary for hypercursoriality limiting stomach capacity in smaller packs, it was demonstrated that the group hunting benefit will rather accrue to widely foraging predators than to "sit-and-wait" ones. Reproductive effort, measured by the number of pups born, revealed smaller litters with decreasing pack size, validated finite energy theory, and highlighted a "poverty trap" where smaller groups have lower foraging gains, smaller litters, and increased vulnerability to extirpation. Consequently, these results demonstrated a mechanistic example of pervasive selection for maximal body size (Cope's rule), leading to a macroevolutionary ratchet, where sociality linked to hypercursoriality is betrayed by an Achilles' heel.


Is international agricultural research a global public good? The case of rice biofortification.
The status of international agricultural research as a global public good (GPG) has been widely accepted since the Green Revolution of the 1960s and 1970s. While the term was not used at the time of its creation, the Consultative Group on International Agricultural Research (CGIAR) system that evolved at that time has been described as a 'prime example of the promise, performance and perils of an international approach to providing GPGs'. Contemporary literature on international agricultural research as a GPG tends to support this view and focuses on how to operationalize the concept. This paper adopts a different starting point and questions this conceptualization of the CGIAR and its outputs. It questions the appropriateness of such a 'neutral' concept to a system born of the imperatives of Cold War geopolitics, and shaped by a history of attempts to secure its relevance in a changing world. This paper draws on a multi-sited, ethnographic study of a research effort highlighted by the CGIAR as an exemplar of GPG-oriented research. Behind the ubiquitous language of GPGs, 'partnership' and 'consensus', however, new forms of exclusion and restriction are emerging within everyday practice, reproducing North-South inequalities and undermining the ability of these programmes to respond to the needs of projected beneficiaries.


Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss.
Rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) appear before disease onset and are associated with bone destruction. We aimed to dissect the role of ACPAs in osteoclast (OC) activation and to identify key cellular mediators in this process. Polyclonal ACPA were isolated from the synovial fluid (SF) and peripheral blood of patients with RA. Monoclonal ACPAs were isolated from single SF B-cells of patients with RA. OCs were developed from blood cell precursors with or without ACPAs. We analysed expression of citrullinated targets and peptidylarginine deiminases (PAD) enzymes by immunohistochemistry and cell supernatants by cytometric bead array. The effect of an anti-interleukin (IL)-8 neutralising antibody and a pan-PAD inhibitor was tested in the OC cultures. Monoclonal ACPAs were injected into mice and bone structure was analysed by micro-CT before and after CXCR1/2 blocking with reparixin. Protein citrullination by PADs is essential for OC differentiation. Polyclonal ACPAs enhance OC differentiation through a PAD-dependent IL-8-mediated autocrine loop that is completely abolished by IL-8 neutralisation. Some, but not all, human monoclonal ACPAs derived from single SF B-cells of patients with RA and exhibiting distinct epitope specificities promote OC differentiation in cell cultures. Transfer of the monoclonal ACPAs into mice induced bone loss that was completely reversed by the IL-8 antagonist reparixin. We provide novel insights into the key role of citrullination and PAD enzymes during OC differentiation and ACPA-induced OC activation. Our findings suggest that IL8-dependent OC activation may constitute an early event in the initiation of the joint specific inflammation in ACPA-positive RA.


Mediterranean Aquaculture in a Changing Climate: Temperature Effects on Pathogens and Diseases of Three Farmed Fish Species.
Climate change is expected to have a drastic effect on aquaculture worldwide. As we move forward with the agenda to increase and diversify aquaculture production, rising temperatures will have a progressively relevant impact on fish farming, linked to a multitude of issues associated with fish welfare. Temperature affects the physiology of both fish and pathogens, and has the potential to lead to significant increases in disease outbreaks within aquaculture systems, resulting in severe financial impacts. Significant shifts in future temperature regimes are projected for the Mediterranean Sea. We therefore aim to review and discuss the existing knowledge relating to disease outbreaks in the context of climate change in Mediterranean finfish aquaculture. The objective is to describe the effects of temperature on the physiology of both fish and pathogens, and moreover to list and discuss the principal diseases of the three main fish species farmed in the Mediterranean, namely gilthead seabream (Sparus aurata), European seabass (Dicentrarchus labrax), and meagre (Argyrosomus regius). We will attempt to link the pathology of each disease to a specific temperature range, while discussing potential future disease threats associated with the available climate change trends for the Mediterranean Sea.


Dilemma for enhancing psychiatrists' adherence to guideline (evidence)-based practice.
Bipolar disorder (BD) is a prevalent and chronic devastating disorder that is associated with considerable psychosocial and economic morbidity. However, its complexity in the clinical course and manifestation of bipolar disorder is still a significant barrier to accurate differential diagnosis from unipolar depression (UD), by which it is still underdiagnosed and undertreated in clinical practice. In community studies, first onset of BD is usually in the adolescent ages, and the occurrence of UD is usually its first clinical manifestation. In addition, reliable criteria for differentiating UD from BD along with validated treatment guidelines for BD are currently not sufficient or adequate, commonly resulting in misdiagnosis and mismanagement of both clinical conditions. Therefore, the study under evaluation results from clinician practice patterns in the real world will substantially enhance the current understanding on the actual situation and unmet needs for accurate and proper diagnosis and management of bipolar depression.


Hair and Scalp Disorders in Children below 2 Years: An Unremarked Sphere.
Hairs contribute significantly to our appearance and are mirror to many systemic diseases. Hair and scalp disorders in children are associated with profound psychological effects arising from concerns of chronicity, severity, and contagiousness, in addition to cosmetic outline. Studies have documented children below 2 years as the most common age group affected by hair and scalp disorders in the pediatric population; however, to the best of our knowledge, none has been carried out exclusively on this age group, so far. To determine the pattern of hair and scalp disorders and their underlying etiologies in children below 2 years. Observational and analytical. Fifty consecutive patients, aged 0-24 months presenting with complaints of hair and scalp disorder, to the outpatient department of dermatology of a tertiary care hospital in North India, constituted the study population. The most common disorder was seborrheic dermatitis (SD) 56%, followed by transient neonatal hair loss 22%. We also came across interesting cases of plica neuropathica (PN) 4%, trichotillomania 2%, and traction alopecia 6%, apart from a list of other disorders noted. The most common age group was 0-6 months. Hair and scalp disorders vary greatly with different demographic areas. In this region of the world, we came across cases of PN due to religious practices. SD was the most prevalent disorder as seen elsewhere. Trichotillomania noted in such a young child was not as a mere habit (as popularly believed), rather an act of anger. Hence, with this study, we want to emphasize the role of detailed history and examination, besides outlining the spectrum of disorders in this age group.


Feasibility, safety and preliminary evidence of the effectiveness of a home-based exercise programme for older people with Alzheimer's disease: a pilot randomized controlled trial.
To evaluate the feasibility and safety of a home-based exercise programme for people with Alzheimer's disease, and to provide preliminary evidence of programme effectiveness in improving balance and mobility and reducing falls risk. A randomized controlled trial. Community. Forty people with mild to moderate Alzheimer's disease (mean age 81.9, SD 5.72; 62.5% female). Participants were randomized to a six-month home-based individually tailored balance, strengthening and walking exercise programme (physiotherapist) or a six-month home-based education programme (control) (occupational therapist). Both programmes provided six home-visits and five follow-up phone calls. Balance, mobility, falls and falls risk were measured at baseline and programme completion. Intention-to-treat analysis using a generalized linear model with group allocation as a predictor variable was performed to evaluate programme effectiveness. Feasibility and adverse events were systematically recorded at each contact. Fifty-eight per cent of the exercise group finished the programme, completing an average of 83% of prescribed sessions, with no adverse events reported. Functional Reach improved significantly (P = 0.002) in the exercise group (mean (SD), 2.28 (4.36)) compared to the control group (-2.99 (4.87)). Significant improvement was also observed for the Falls Risk for Older People - Community score (P = 0.008) and trends for improvement on several other balance, mobility, falls and falls risk measures for the exercise group compared to the control group. The exercise programme was feasible and safe and may help improve balance and mobility performance and reduce falls risk in people with Alzheimer's disease.


Allicin Attenuates Myocardial Ischemia Reperfusion Injury in Rats by Inhibition of Inflammation and Oxidative Stress.
To explore the protective effect and underlying mechanism of allicin (ALC) on myocardial ischemia reperfusion (MI/R) injury in rats. The model of MI/R injury in rats was induced by ligating the left anterior descending branch of the coronary artery. Thirty male Sprague-Dawley rats were randomly divided into 3 equal groups (n = 10): sham group, MI/R injury group, and ALC precondition group. Enzyme-linked immunosorbent assay was used to examine the expression of cardiac troponin I, CK-MB, interleukin-6, tumor necrosis factor-α, and interleukin-8 in the rats' serum. Hematoxylin and eosin staining was used to observe the myocardial pathologic morphology. A physiological recorder was used to measure cardiac systolic and diastolic function. Western blot analysis was used for detecting the expression of p38 and p-p38 in myocardium. The content of malondialdehyde and the activity of superoxide dismutase, catalase, and glutathione peroxidase in myocardium were examined by automatic analysis with the thiobarbituric acid chromogenic and dinitrobenzoic acid methods, respectively. ALC can significantly decrease the expression of cardiac troponin I, CK-MB, interleukin-6, tumor necrosis factor-α, and interleukin-8 in the serum and reduce the myocardial pathologic injury and the expression of malondialdehyde and p-p38 in myocardial tissue. Moreover, ALC can upregulate the activity of superoxide dismutase, catalase, and glutathione peroxidase and improve myocardial systolic and diastolic function with no influence on the expression of p38. ALC can protect rats against MI/R injury by suppressing inflammation and oxidative stress. The mechanism is associated with alleviating the activation of p38 signaling.


Design and Integration of an Inexpensive Wearable Mechanotactile Feedback System for Myoelectric Prostheses.
The aim of this paper was to demonstrate the functionality of an inexpensive mechanotactile sensory feedback system for transhumeral myoelectric prostheses. We summarize the development of a tactile-integrated prosthesis, including 1) evaluation of sensors that were retrofit onto existing commercial terminal devices; 2) design of two custom mechanotactile tactors that were integrated into a socket without compromising suction suspension; 3) design of a modular controller which translated sensor input to tactor output, was wirelessly adjusted, and fit within a prosthetic forearm; and 4) evaluation of the system with a single transhumeral participant. Prosthesis functionality was demonstrated over three test sessions; the participant was able to identify tactor stimulation location and demonstrated a reduction in grasp force with the mechanotactile stimulation. This system offers an inexpensive and modular solution for integration of a mechanotactile sensory feedback system into a prosthetic socket without compromising the suction seal. These principles can be applied in future studies to investigate the direct impact of sensory feedback on tangible outcomes for prosthetic users, thereby reducing barriers to clinical translation.


The Escherichia coli FtsH protein is a prokaryotic member of a protein family of putative ATPases involved in membrane functions, cell cycle control, and gene expression.
The ftsH gene is essential for cell viability in Escherichia coli. We cloned and sequenced the wild-type ftsH gene and the temperature-sensitive ftsH1(Ts) gene. It was suggested that FtsH protein was an integral membrane protein of 70.7 kDa (644 amino acid residues) with a putative ATP-binding domain. The ftsH1(Ts) gene was found to have two base substitutions within the coding sequence corresponding to the amino acid substitutions Glu-463 by Lys and Pro-587 by Ala. Homology search revealed that an approximately 200-amino-acid domain, including the putative ATP-binding sequence, is highly homologous (35 to 48% identical) to the domain found in members of a novel, eukaryotic family of putative ATPases, e.g., Sec18p, Pas1p, CDC48p, and TBP-1, which function in protein transport pathways, peroxisome assembly, cell division cycle, and gene expression, respectively. Possible implications of these observations are discussed.


The use of reflectance confocal microscopy for examination of benign and malignant skin tumors.
Reflectance confocal microscopy (RCM) is a modern, non-invasive diagnostic method that enables real-time imaging of epidermis and upper layers of the dermis with a nearly histological precision and high contrast. The application of this technology in skin imaging in the last few years has resulted in the progress of dermatological diagnosis, providing virtual access to the living skin erasing the need for conventional histopathology. The RCM has a potential of wide application in the dermatological diagnostic process with a particular reference to benign and malignant skin tumors. This article provides a summary of the latest reports and previous achievements in the field of RCM application in the diagnostic process of skin neoplasms. A range of dermatological indications and general characteristics of confocal images in various types of tumors are presented.


Racial differences in subcutaneous and visceral fat distribution in postmenopausal black and white women.
Most studies examining racial disparities in abdominal fat distribution have focused on premenopausal women. The purpose of this report was to determine if racial differences exist in the abdominal fat distribution in postmenopausal white and black women. Fifty-four women (33 white and 21 black) were scanned by magnetic resonance imaging (MRI) to determine abdominal fat distribution, were measured by hydrostatic weighing for percent body fat, and had their fasting blood lipids, glucose, and insulin levels measured. These women were matched for age (mean age, 53.5 +/- 0.9 years) and percent body fat (black: 39.6% +/- 2.3%, white: 37.3% +/- 1.2%). When adjusted for total body fat mass and hormone replacement therapy (HRT), total abdominal fat (white: 10,352.1 +/- 535.2, black: 11,220.4 +/- 670.1 cm(3)) was not statistically different between groups, but the visceral fat content was significantly higher in the white women (white: 2,943.5 +/- 220.4, black: 2,332.6 +/- 176.1 cm(3)). The percent visceral fat was also higher in these women (white: 30.5% +/- 1.3%, black: 22.1% +/- 1.6%, P <.01). Subcutaneous adipose tissue (SAT) was significantly higher in the black women (white: 7,408.6 +/- 450.2, black: 8,887 +/- 563.1 cm(3), P <.05). No significant differences were found in the insulin concentrations or the blood lipid profile of these women. Regardless of race, visceral fat was a significant predictor of log triglyceride, low-density lipoprotein-cholesterol (LDL-C), cholesterol/LDL-C, insulin levels, and insulin resistance. Race was only found to contribute to 8% of the variability of LDL-C. HRT use had no effect on abdominal fat distribution or the blood lipid profile in this cohort of women. In conclusion, disparities in abdominal fat distribution between black and white women continue to exist in the early postmenopausal years, and the regression results indicate that the absolute amount of visceral fat, and not the relative amounts of visceral fat, is the best predictor of the blood lipid profile and insulin sensitivity. HRT use did not result in differences in abdominal fat distribution in these women. Factors, such as genetics and lifestyle, must play a larger role in explaining the increased health risk in black women.


The impact of androgen receptor CAG repeat polymorphism on andropausal symptoms in different serum testosterone levels.
In addition to a depletion of androgen, attenuated action of androgen receptor (AR) might also contribute to andropausal symptoms. To evaluate the interaction of AR cytosine adenine guanine (CAG) repeat polymorphism and serum testosterone levels and their effect on andropausal symptoms in aging Taiwanese men. From August 2007 to April 2008, a free health screening for men older than 40 years was conducted by a medical center in Kaohsiung City, Taiwan. All participants received physical examination, answered questionnaires to collect their demographic information and medical histories, completed the Androgen Deficiency in the Aging Male (ADAM) questionnaire, and provided 20-cm(3) whole blood samples for biochemical and genetic evaluation. The ADAM questionnaire was used to evaluate andropausal symptoms. Serum albumin, total testosterone (TT), and sex hormone-binding globulin levels were measured. Free testosterone level was calculated. AR gene CAG repeat polymorphism was determined by direct sequencing. Seven hundred two men with the mean age of 57.2 ± 6.5 years were included. There was no significant association between TT levels and the distribution of AR CAG repeat polymorphism. When TT levels were above 340 ng/dL, subjects with AR CAG repeat lengths ~25 showed significantly higher risk of developing andropausal symptoms, as compared with those with AR CAG repeat lengths ~22 (P = 0.006), but this was not observed when TT levels were 340 ng/dL or below. Age and number of comorbidities were also independent risk factors for andropausal symptoms. In subjects with normal TT concentration, those with longer AR CAG repeat lengths have a higher risk of developing andropausal symptoms. Age and number of comorbidities can also influence the appearance of andropausal symptoms. In clinical practice, a multifactorial approach to evaluate andropausal symptoms and the interactions between those risk factors is suggested.


Promoting interpersonal skills and cultural sensitivity among dental students.
This study evaluated interpersonal communication skills among third- and fourth-year dental students during two clinical communications training programs. Students participated in two clinical communications (CC) training sessions, each comprised of four encounters with patient instructors (PIs) who were trained to enact standardized patient scenarios. Scenarios in CC1 addressed straightforward patient care situations in dentistry (e.g., bridge adjustment), while CC2 added cultural sensitivity issues to the dental scenarios. After each encounter, patient instructors used the Arizona Clinical Interviewing Rating Scale (ACIR) to rate the students' interpersonal skills and gave the students feedback on their performance. The students also received feedback and coaching from dental school faculty in debriefings after encounters with the PIs. Students anonymously rated the program at the end of each session. To evaluate the program, students' performance was compared within and between the two training sessions. Analysis showed statistically significant increases in interpersonal communication skills within each training session (p<0.05) from unsatisfactory to above satisfactory levels. Performance scores at the start of CC2 were statistically lower than at the end of CC1, suggesting that performance wanes without practice. Student evaluations of the program were very positive. Interpersonal communication skills improved during this patient instructor program.


Metabolomic markers of altered nucleotide metabolism in early stage adenocarcinoma.
Adenocarcinoma, a type of non-small cell lung cancer, is the most frequently diagnosed lung cancer and the leading cause of lung cancer mortality in the United States. It is well documented that biochemical changes occur early in the transition from normal to cancer cells, but the extent to which these alterations affect tumorigenesis in adenocarcinoma remains largely unknown. Herein, we describe the application of mass spectrometry and multivariate statistical analysis in one of the largest biomarker research studies to date aimed at distinguishing metabolic differences between malignant and nonmalignant lung tissue. Gas chromatography time-of-flight mass spectrometry was used to measure 462 metabolites in 39 malignant and nonmalignant lung tissue pairs from current or former smokers with early stage (stage IA-IB) adenocarcinoma. Statistical mixed effects models, orthogonal partial least squares discriminant analysis and network integration, were used to identify key cancer-associated metabolic perturbations in adenocarcinoma compared with nonmalignant tissue. Cancer-associated biochemical alterations were characterized by (i) decreased glucose levels, consistent with the Warburg effect, (ii) changes in cellular redox status highlighted by elevations in cysteine and antioxidants, alpha- and gamma-tocopherol, (iii) elevations in nucleotide metabolites 5,6-dihydrouracil and xanthine suggestive of increased dihydropyrimidine dehydrogenase and xanthine oxidoreductase activity, (iv) increased 5'-deoxy-5'-methylthioadenosine levels indicative of reduced purine salvage and increased de novo purine synthesis, and (v) coordinated elevations in glutamate and UDP-N-acetylglucosamine suggesting increased protein glycosylation. The present study revealed distinct metabolic perturbations associated with early stage lung adenocarcinoma, which may provide candidate molecular targets for personalizing therapeutic interventions and treatment efficacy monitoring.


Lower rotational inertia and larger leg muscles indicate more rapid turns in tyrannosaurids than in other large theropods.
Tyrannosaurid dinosaurs had large preserved leg muscle attachments and low rotational inertia relative to their body mass, indicating that they could turn more quickly than other large theropods. To compare turning capability in theropods, we regressed agility estimates against body mass, incorporating superellipse-based modeled mass, centers of mass, and rotational inertia (mass moment of inertia). Muscle force relative to body mass is a direct correlate of agility in humans, and torque gives potential angular acceleration. Agility scores therefore include rotational inertia values divided by proxies for (1) muscle force (ilium area and estimates of m. caudofemoralis longus cross-section), and (2) musculoskeletal torque. Phylogenetic ANCOVA (phylANCOVA) allow assessment of differences in agility between tyrannosaurids and non-tyrannosaurid theropods (accounting for both ontogeny and phylogeny). We applied conditional error probabilities a(p) to stringently test the null hypothesis of equal agility. Tyrannosaurids consistently have agility index magnitudes twice those of allosauroids and some other theropods of equivalent mass, turning the body with both legs planted or pivoting over a stance leg. PhylANCOVA demonstrates definitively greater agilities in tyrannosaurids, and phylogeny explains nearly all covariance. Mass property results are consistent with those of other studies based on skeletal mounts, and between different figure-based methods (our main mathematical slicing procedures, lofted 3D computer models, and simplified graphical double integration). The capacity for relatively rapid turns in tyrannosaurids is ecologically intriguing in light of their monopolization of large (>400 kg), toothed dinosaurian predator niches in their habitats.


Nanoscale, electrified liquid jets for high-resolution printing of charge.
Nearly all research in micro- and nanofabrication focuses on the formation of solid structures of materials that perform some mechanical, electrical, optical, or related function. Fabricating patterns of charges, by contrast, is a much less well explored area that is of separate and growing interesting because the associated electric fields can be exploited to control the behavior of nanoscale electronic and mechanical devices, guide the assembly of nanomaterials, or modulate the properties of biological systems. This paper describes a versatile technique that uses fine, electrified liquid jets formed by electrohydrodynamics at micro- and nanoscale nozzles to print complex patterns of both positive and negative charges, with resolution that can extend into the submicrometer and nanometer regime. The reported results establish the basic aspects of this process and demonstrate the capabilities through printed patterns with diverse geometries and charge configurations in a variety of liquid inks, including suspensions of nanoparticles and nanowires. The use of printed charge to control the properties of silicon nanomembrane transistors provides an application example.


Defining the degree of intravesical prostatic protrusion in association with bladder outlet obstruction.
The present study was done to define the degree of intravesical prostatic protrusion (IPP) causing bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms. We retrospectively evaluated 239 patients with BPH, analyzing age, IPP, prostate volume, International Prostate Symptom Score (IPSS), and the results from a pressure-flow study. Urethral resistance was quantified by using the BOO index (BOOI), according to the formula BOOI=PdetQmax-2×Qmax (where Pdet is detrusor pressure at the peak flow rate and Qmax is peak flow rate). BOO was defined by a BOOI above 40. Patients with a BOOI below 20 were excluded. Patients were classified into two groups (obstructed and unobstructed groups) by the BOOI. Correlations were determined by logistic regression analysis, and receiver operating characteristic curves were plotted to estimate the optimal cutoff for IPP. There were significant differences in total prostate volume, postvoiding residual urine (PVR), IPP, and Qmax (p<0.001, p<0.001, p<0.001, and p=0.026, respectively) between the obstructed and unobstructed groups, but there were no significant differences in age (p=0.653), IPSS total score (p=0.624), or quality of life score (p=0.138). IPP had a significant prognosis (p<0.001) but was weakly correlated with prostate volume (p=0.026). The correlation coefficients between IPP and Qmax, PVR, prostate volume, and BOO were 0.551, -0.159, 0.225, and 0.391, respectively. For IPP, the area under the curve was 0.759 (95% confidence interval, 0.657 to 0.861) and the cutoff to indicate BOO was 5.5 mm with 66.7% sensitivity and 80.5% specificity. An IPP exceeding 5.5 mm was significantly associated with BOO.


A federal survey deficiency citation is needed for resident-to-resident aggression in U.S. nursing homes.
Resident-to-resident aggression (RRA) in nursing homes is a prevalent and concerning public health problem. A rapid growth in the number of research studies has led to advancements in understanding and awareness of these incidents. However, no state survey deficiency citation (F-Tag) currently exists to capture RRA in a structured way in the Centers for Medicare & Medicaid Services' (CMS) nursing homes F-Tags Coding System. This omission represents a major barrier to State Survey Agencies, CMS, consumers, and care advocacy organizations' efforts to keep vulnerable and frail residents safe and free from psychological harm. The commentary makes the case for development and implementation of a new RRA-specific F-Tag by identifying 20 problem areas and the ways in which this F-Tag could address them. The new F-Tags Coding System (part of the new Federal Nursing Home regulations) represents a rare and time-sensitive opportunity to bridge this major gap in practice, research, and policy.


Liver fluke in Irish sheep: prevalence and associations with management practices and co-infection with rumen fluke.
The present study aimed to identify the national prevalence of Fasciola hepatica in Irish sheep and to conduct a risk analysis assessment based on management and treatment practices in participating flocks. Also, co-infection with rumen fluke was quantified and its association with liver fluke and management practices was assessed. A total of 305 sheep flocks were selected ensuring even national representation of the sheep population. Participating farms were asked to complete a survey questionnaire on farm management practices and submit faecal samples during the winter of 2014-2015. Pooled faecal samples were analysed for the presence of F. hepatica and co-infection with rumen fluke. Apparent and true prevalence were calculated, additionally, the rate of co-infection with rumen fluke was also obtained. Correlation and regression analyses were used for assessing associations between management practices, liver fluke infection and co-infection with rumen fluke. The national true prevalence of F. hepatica was 50.4% (n = 305). Regional prevalence varied from 41% in the east to 52% in the south. Co-infection with rumen fluke was observed in 40% of the studied population and correlated with increased F. hepatica egg counts (OR = 2.9; P ≤ 0.001). Predominant breeds were Suffolk, Texel and Horned Mountain breeds. Beef cattle were the most frequent type of other livestock present on farms and mixed species grazing was frequently reported (73%). More than half of the flocks reported a mid-to-late lambing period (March-April). Use of mountain land for grazing was of 32%. Flukicides were most commonly used twice over the autumn-winter period. Regression analyses highlighted significant association of F. hepatica status, with the presence of other livestock on farm, frequency of flukicides used during the winter and clinical presentation of liver fluke. A significant increase in eggs per gram of faeces was observed in Charollais sheep in comparison with all other breeds. Co-infection with F. hepatica and Calicophoron daubneyi was also significantly associated with the presence of other livestock on the farm, type of flukicide used and clinical fasciolosis. The present study provides up-to-date information on the prevalence of F. hepatica in Irish sheep and adds insight to the epidemiology of the disease. These findings will be useful for designing new holistic control measures for F. hepatica infection.


The effect of gum chewing on sensitivity associated with in-office whitening procedures.
Tooth sensitivity is the most common side effect of in-office tooth-whitening procedures. The purpose of this study was to determine whether chewing gum containing 0.6% casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) before tooth whitening would reduce tooth sensitivity during an in-office whitening procedure. Thirty participants were enrolled and randomized into three groups as follows: group 1 was instructed to not chew gum during the study period; group 2 chewed five pieces of gum (with 0.6% CPP-ACP) for 10 min each day 1 week before whitening; and group 3 chewed five pieces of gum (without CPP-ACP) for 10 min each day 1 week before whitening. All participants had their teeth whitened with a 30% hydrogen peroxide in-office whitening procedure. The participants' shades of teeth were evaluated with a spectrophotometer four times during the study: at the initial screening visit, immediately before whitening, immediately after whitening and 1 week after whitening. Participants' sensitivity levels were evaluated each time the shades were evaluated and additionally at 24 h after whitening using a 100-mm visual analogue scale. Thirty participants were enrolled in the study. The average shade change was -2.27 (± 2.07). The average sensitivity for all groups at visit 1 was 5.12 (± 13.94). The average sensitivity for all groups after whitening was 19.81 (± 13.95). There were significant differences in sensitivity between groups 2 and 3 (P = 0.02), but neither group was significantly different from the control group (P = 0.86, P = 0.07). Chewing gum before whitening, including gum with CPP-ACP, did not reduce sensitivity during in-office whitening procedures.


Phagosome-lysosome fusion inhibited by algal symbionts of Hydra viridis.
Certain species of Chlorella live within the digestive cells of the fresh water cnidarian Hydra viridis. When introduced into the hydra gut, these symbiotic algae are phagocytized by digestive cells but avoid host digestion and persist at relatively constant numbers within host cells. In contrast, heat-killed symbionts are rapidly degraded after phagocytosis. Live symbionts appear to persist because host lysosomes fail to fuse with phagosomes containing live symbionts. Neither acid phosphatase nor ferritin was delivered via lysosomes into phagosomes containing live symbionts, whereas these lysosomal markers were found in 50% of the vacuoles containing heat-killed symbionts 1 h after phagocytosis. Treatment of symbiotic algae before phagocytosis with polycationic polypeptides abolishes algal persistence and perturbs the ability of these algae to control the release of photosynthate in vitro. Similarly, inhibition of photosynthesis and hence of the release of photosynthetic products as a result of prolonged darkness and 3-(3,4-dichlorophenyl)-1,1-dimethyl urea (DCMU) treatment also abolishes persistence. Symbiotic algae are not only protected from host digestive attack but are also selectively transported within host cells, moving from the apical site of phagocytosis to a basal position of permanent residence. This process too is disrupted by polycationic polypeptides, DCMU and darkness. Both algal persistence and transport may, therefore, be a function of the release of products from living, photosynthesizing symbionts. Vinblastine treatment of host animals blocked the movement of algae within host cells but did not perturb algal persistence: algal persistence and the transport of algae may be initiated by the same signal, but they are not interdependent processes.


Toxic impacts of cypermethrin on behavior and histology of certain tissues of albino rats.
In the present investigation, the behavioral, morphological, and histopathological effects of cypermethrin, a widely used synthetic pyrethroid insecticide, was ascertained in male and female albino rats (Rattus norvegicus). Cypermethrin administered at repeated oral doses of 5 and 20 mg/kg/day for 30 days produced varying degree of mild to moderate toxic symptoms and behavioral changes in both male and female rats. The lower dose produced very mild toxicosis characterized by intermittent diarrhea, decreased feed intake, and thick eye discharge, whereas higher dose displayed mild to moderate toxicosis with diarrhea, decreased feed intake, loss of body weight, dyspnoea, ataxia, eye discharge, and salivation. Two female and one male albino rats died between 23 to 28 days after displaying signs of incoordination and tremors. Repeated oral doses of cypermethrin for 30 days enhanced the relative weight of liver and heart, but significantly decreased that of brain, kidneys, and testes. Microscopically, cypermethrin produced neuronal degeneration and increase in glial cells in brain, and disorganization of hepatic laminae, increase in sinusoid, and necrosis of hepatocytes in liver. Section of kidney displayed hemorrhage and sloughing off renal epithelial cell in the convoluted tubules, shrinkage of glomeruli, and necrosis of renal tubules. Repeated administration of cypermethrin also produced hemorrhages within myocardium, disruption of branching structure, and loss of striation of cardiac tissue; thickening of alveolar septa in lungs, partial to extensive loss of various stages of spermatogenesis in testes, and loss of follicular cells and oocytes in ovaries. The study suggested that repeated oral exposure of cypermethrin has considerable harmful effects on body organs in R. norvegicus.


Clinical assessment of percutaneous lumbar pedicle screw placement using theO-arm multidimensional surgical imaging system.
Increasing popularity of minimally invasive surgery for lumbar fusion has led to dependence upon intraoperative fluoroscopy for pedicle screw placement, because limited muscle dissection does not expose the bony anatomy necessary for traditional, freehand techniques nor for registration steps in image-guidance techniques. This has raised concerns about cumulative radiation exposure for both surgeon and operating room staff. The recent introduction of the O-arm Multidimensional Surgical Imaging System allows for percutaneous placement of pedicle screws, but there is limited clinical experience with the technique and data examining its accuracy. We present the first large clinical series of percutaneous screw placement using navigation of O-arm imaging and compare the results with the fluoroscopy-guided method. A retrospective review of a 24-month period identified patients undergoing minimally invasive lumbar interbody fusion. The O-arm was introduced in the middle of this period and was used for all subsequent patients. Accuracy of screw placement was assessed by examination of axial computed tomography or O-arm scans. The fluoroscopy group included 141 screws in 42 patients, and the O-arm group included 205 screws in 52 patients. The perforation rate was 12.8% in the fluoroscopy group and 3% in the O-arm group (P < .001). Single-level O-arm procedures took a mean 200 (153-241) minutes, whereas fluoroscopy took 221 (178-302) minutes (P < .03). Percutaneous pedicle screw placement with the O-arm Multidimensional Intraoperative Imaging System is a safe and effective technique and provided improved overall accuracy and reduced operative time compared with conventional fluoroscopic techniques.


Seroprevalence of herpes simplex virus 1 and 2 in a population-based cohort in Japan.
There have been few population-based studies of the seroprevalence and correlates of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Japan. We enrolled a total of 1244 adults, aged 18-59 years, from a population-based cohort in southern Japan, and tested their serum samples using an ELISA kit containing HSV type-specific antigens to glycoproteins G1 and G2. The seroprevalence of HSV-1 and HSV-2 was 55.4% and 7.4% in men and 63.3% and 9.3% in women, respectively. Overall, 4 percent of the participants (2.3% of men and 5.0% of women) were co-infected with HSV-1 and HSV-2. The seroprevalences of both HSV-1 and HSV-2 increased with age in both sexes, and were always higher among women than among men in each age bracket. The prevalence of HSV-2 infection among HSV-1 infected individuals was lower than that among uninfected individuals, both in men and women. Male current drinkers, and male and female current smokers, were more likely to be infected with HSV-1 and HSV-2, as compared to never drinkers and never smokers, respectively. It is hoped that the estimates produced in this study will help in understanding the burden of these infections in Japan.


Significance of AT1 receptor independent activation of mineralocorticoid receptor in murine diabetic cardiomyopathy.
Diabetes mellitus (DM) has deleterious influence on cardiac performance independent of coronary artery disease and hypertension. The objective of the present study was to investigate the role of the renin-angiotensin-aldosterone system, especially angiotensin II type 1a receptor (AT1aR) and mineralocorticoid receptor (MR) signaling, in left ventricular (LV) dysfunction induced by diabetes mellitus (DM). DM was induced by intraperitoneal injection of streptozotocin (200 mg/kg BW) in wild-type (WT) or AT1aR knockout (KO) male mice, and they were bred during 6 or 12 weeks. Some KO mice were administered the MR antagonist eplerenone (100 mg/kg body weight). At 6 weeks, LV diastolic function was impaired in WT-DM, but preserved in KO-DM. At that time point MR mRNA expression was upregulated, NADPH oxidase subunit (p47phox) and glutathione peroxidase (GPx1) mRNA expression were upregulated, the staining intensities of LV tissue for 4-hydroxy-2-nonenal was stronger in immunohistochemistry, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive cells was increased, Bcl-2 protein expression was significantly downregulated, and the expression of SERCA2a and phosphorylated phospholamban was depressed in WT-DM, while these changes were not seen in KO-DM. At 12 weeks, however, these changes were also noted in KO-DM. Eplerenone arrested those changes. The plasma aldosterone concentration was elevated in WT-DM but not in KO-DM at 6 weeks. It showed 3.7-fold elevation at 12 weeks even in KO-DM, which suggests "aldosterone breakthrough" phenomenon. However, the aldosterone content in LV tissue was unchanged in KO-DM. DM induced diastolic dysfunction was observed even in KO at 12 weeks, which was ameliorated by minelarocorticoid receptor antagonist, eplerenone. AT1-independent MR activation in the LV might be responsible for the pathogenesis of diabetic cardiomyopathy.


Sweet spot in music-Is predictability preferred among persons with psychotic-like experiences or autistic traits?
People prefer music with an intermediate level of predictability; not so predictable as to be boring, yet not so unpredictable that it ceases to be music. This sweet spot for predictability varies due to differences in the perception of predictability. The symptoms of both psychosis and Autism Spectrum Disorder have been attributed to overestimation of uncertainty, which predicts a preference for predictable stimuli and environments. In a pre-registered study, we tested this prediction by investigating whether psychotic and autistic traits were associated with a higher preference for predictability in music. Participants from the general population were presented with twenty-nine pre-composed music excerpts, scored on their complexity by musical experts. A participant's preferred level of predictability corresponded to the peak of the inverted U-shaped curve between music complexity and liking (i.e., a Wundt curve). We found that the sweet spot for predictability did indeed vary between individuals. Contrary to predictions, we did not find support for these variations being associated with autistic and psychotic traits. The findings are discussed in the context of the Wundt curve and the use of naturalistic stimuli. We also provide recommendations for further exploration.


Image analysis techniques for characterizing disc space narrowing in cervical vertebrae interfaces.
Image analysis techniques are introduced for evaluating disc space narrowing of cervical vertebrae interfaces from X-ray images. Four scale-invariant, distance transform-based features are presented for characterizing the spacing between adjacent vertebrae. K-means and self-organizing map clustering techniques are applied to estimate the degree of disc space narrowing using a four grade (0-3) scoring system, where 0 and 3 represent normal spacing and significant narrowing, respectively. For a data set of 294 vertebrae interfaces, experimental results yield average correct grade assignment of greater than 82.10% for each of the four grades using a one grade window around the correct grade.


Identification and regulation of c-Myb target genes in MCF-7 cells.
The c-Myb transcription factor regulates differentiation and proliferation in hematopoietic cells, stem cells and epithelial cells. Although oncogenic versions of c-Myb were first associated with leukemias, over expression or rearrangement of the c-myb gene is common in several types of solid tumors, including breast cancers. Expression of the c-myb gene in human breast cancer cells is dependent on estrogen stimulation, but little is known about the activities of the c-Myb protein or what genes it regulates in estrogen-stimulated cells. We used chromatin immunoprecipitation coupled with whole genome promoter tiling microarrays to identify endogenous c-Myb target genes in human MCF-7 breast cancer cells and characterized the activity of c-Myb at a panel of target genes during different stages of estrogen deprivation and stimulation. By using different antibodies and different growth conditions, the c-Myb protein was found associated with over 10,000 promoters in MCF-7 cells, including many genes that encode cell cycle regulators or transcription factors and more than 60 genes that encode microRNAs. Several previously identified c-Myb target genes were identified, including CCNB1, MYC and CXCR4 and novel targets such as JUN, KLF4, NANOG and SND1. By studying a panel of these targets to validate the results, we found that estradiol stimulation triggered the association of c-Myb with promoters and that association correlated with increased target gene expression. We studied one target gene, CXCR4, in detail, showing that c-Myb associated with the CXCR4 gene promoter and activated a CXCR4 reporter gene in transfection assays. Our results show that c-Myb associates with a surprisingly large number of promoters in human cells. The results also suggest that estradiol stimulation leads to large-scale, genome-wide changes in c-Myb activity and subsequent changes in gene expression in human breast cancer cells.


Activity of moxifloxacin, administered once a day, against Streptococcus pneumoniae in an in vitro pharmacodynamic model of infection.
The antibacterial effect of moxifloxacin was studied by using an in vitro pharmacodynamic model of infection with dosing simulations of 400 mg every 24 h for 48 h. Streptococcus pneumoniae was tested by using four wild-type strains for which the moxifloxacin MICs were 0. 008, 0.12, 0.14, and 3.6 mg/liter. In addition, two isogenic mutants, generated from the strains for which the moxifloxacin MICs were </=0.12 mg/liter and for which the MICs were 1.0 and 1.6 mg/liter, were also used. Antibacterial efficacy was measured by the following indices: log change in viable count at 12, 24, 36, and 48 h; area under the bacterial kill curve (AUBKC); and time to kill 99.9% of the initial inoculum. With the three strains for which the moxifloxacin MICs were </=0.14 mg/liter, there was a marked reduction in viable count over 12 to 36 h; in contrast, with strains for which the MICs were >/=1.0 mg/liter, little killing occurred over 48 h. A sigmoid dose-response model indicated that the area under the curve/MIC ratio was strongly related to the log change in viable count at 24 and 48 h and to the AUBKC. These data indicate that moxifloxacin may have a role in management of S. pneumoniae infection.


Enhancement of mesenchymal stem cell angiogenic capacity and stemness by a biomimetic hydrogel scaffold.
In this study, we examined the capacity of a biomimetic pullulan-collagen hydrogel to create a functional biomaterial-based stem cell niche for the delivery of mesenchymal stem cells (MSCs) into wounds. Murine bone marrow-derived MSCs were seeded into hydrogels and compared to MSCs grown in standard culture conditions. Hydrogels induced MSC secretion of angiogenic cytokines and expression of transcription factors associated with maintenance of pluripotency and self-renewal (Oct4, Sox2, Klf4) when compared to MSCs grown in standard conditions. An excisonal wound healing model was used to compare the ability of MSC-hydrogel constructs versus MSC injection alone to accelerate wound healing. Injection of MSCs did not significantly improve time to wound closure. In contrast, wounds treated with MSC-seeded hydrogels showed significantly accelerated healing and a return of skin appendages. Bioluminescence imaging and FACS analysis of luciferase+/GFP+ MSCs indicated that stem cells delivered within the hydrogel remained viable longer and demonstrated enhanced engraftment efficiency than those delivered via injection. Engrafted MSCs were found to differentiate into fibroblasts, pericytes and endothelial cells but did not contribute to the epidermis. Wounds treated with MSC-seeded hydrogels demonstrated significantly enhanced angiogenesis, which was associated with increased levels of VEGF and other angiogenic cytokines within the wounds. Our data suggest that biomimetic hydrogels provide a functional niche capable of augmenting MSC regenerative potential and enhancing wound healing.


Cervilenz assessment of cervical length compared to fetal fibronectin in the prediction of preterm delivery in women with threatened preterm labor.
To determine whether cervical length (CL) measured by the Cervilenz™ measuring device is an effective screening tool for the prediction of preterm delivery (PTD) compared to fetal fibronectin (fFN). We evaluated fFN and CL among women who enrolled into a randomized control trial (RCT) comparing management algorithms for threatened preterm labor between 24 and 34 weeks' gestation. In all subjects, fFN was collected, with CL determined in blinded fashion. The sensitivity, specificity, and positive and negative predictive values (NPV) for fFN or Cervilenz in prediction of PTD within 7 days or prior to 37 weeks were determined. Fifty-two subjects were evaluated. CL <30 mm correlated with PTD <7 days (r = 0.31, p = 0.04) and fFN positivity (r = 0.43, p = 0.006). CL <30 mm and fFN had excellent NPV for PTD <7 days (97.1 vs. 97.3%), and the area under the receiver operator characteristic curves were similar for prediction of PTD <7 days (76.6 vs. 75.2%, p = 0.71) or <37 weeks (56.7 vs. 55.2%, p = 0.71). Measurement of CL with Cervilenz appears to be equivalent to fFN in screening symptomatic women for PTD within 7 days or prior to 37 weeks. Given cost and turnaround time with fFN testing, Cervilenz represents a promising new tool for real time, clinically useful results in the management of women with threatened preterm labor.


Treatment considerations in painful HIV-related neuropathy.
Human immunodeficiency virus (HIV)-related distal sensory polyneuropathy (DSP) is the most common HIV-associated sensory neuropathy. The envelope glycoprotein of HIV-1, gp 120, appears to contribute to this painful neuropathy. Two standard treatments for HIV infection/HIV-related painful DSP (e.g., antiviral therapy [e.g., nucleoside reverse transcriptase inhibitors (NRTI)] opioids) should each be carefully evaluated prior to being utilized to ameliorate the pain of DSP, since they may actually promote nociception. Nucleoside reverse transcriptase inhibitors require activation in the cell via the addition of 3 phosphate groups (by cellular kinases) to their deoxyribose moiety, to form NRTI triphosphates. Subsequently, these deoxynucleotide analogs compete with natural deoxynucleotides for incorporation into the growing viral DNA chain. The incorporation of NRTIs into the viral DNA chain leads to chain termination; since the nucleoside reverse transcriptase inhibitors lack a 3'-hydroxyl group on the deoxyribose moiety (unlike natural deoxynucleotides), so that the next incoming deoxynucleotide cannot form the next 5'-3' phosphodiester bond needed to extend the DNA chain. Unfortunately, many conventional agents utilized as pharmacologic therapy for neuropathic pain are not effective for providing satisfactory analgesia in painful HIV-related distal sensory polyneuropathy. Although there is no robust data, there does seem to be information which would support the notion of opioids having increased risk of being particularly pronociceptive when being used to treat painful HIV-related neuropathy. It thus appears conceivable that the use of at least certain opioids in efforts to achieve analgesia in patients with painful HIV-related neuropathy may be less than ideal since at least certain opioid analgesics themselves may potentially contribute to "fueling the fire" of HIV enhanced pain hypersensitivity; at least in part via upregulation of specific chemokine receptors (e.g., CXCR4) which seem to be vitally important in promoting HIV-related pain facilitation. The risk benefit ratio of treatment with agents such as NRTIs as well as opioids should be reviewed for specific individual patients, prior to clinicians initiating these agents. To raise awareness of the theoretical potential downside that opioids may possess if they are used for the treatment of painful HIV-related neuropathy. A narrative review of selected literature. Hypothetical in nature. Clinicians should consider all aspects of various therapeutic options, carefully weighing the risk/benefit ratios of each potential treatment before initiating opioids for painful HIV-related neuropathy.


The functional origin of the foreign accent: evidence from the syllable-frequency effect in bilingual speakers.
Individuals who speak more than one language often do so with a foreign accent in their second language. Previous investigations have focused on the acoustic phonetic properties of speech, showing how language-learning history shapes the occurrence of accent. By contrast, little is known about the phonological and phonetic representations that allow the production of each language within one speaker. We investigated this issue via the syllable-frequency effect, thought to index the retrieval of syllable-size representations during speech production. We tested French-Spanish early and late bilinguals in a task in which the materials' syllabic frequency in both languages was manipulated. The frequency of syllables in the nonspoken language affected performance only with late bilinguals. This is interpreted as evidence that syllabic representations are shared across languages in late bilinguals but are separate in early bilinguals. One of the functional origins of foreign accent in late bilinguals may be the retrieval of syllabic representations shared across languages.


Cognitive-Behavioral-Based Physical Therapy for Patients With Chronic Pain Undergoing Lumbar Spine Surgery: A Randomized Controlled Trial.
The purpose of this study was to determine the efficacy of a cognitive-behavioral-based physical therapy (CBPT) program for improving outcomes in patients after lumbar spine surgery. A randomized controlled trial was conducted on 86 adults undergoing a laminectomy with or without arthrodesis for a lumbar degenerative condition. Patients were screened preoperatively for high fear of movement using the Tampa Scale for Kinesiophobia. Randomization to either CBPT or an education program occurred at 6 weeks after surgery. Assessments were completed pretreatment, posttreatment and at 3-month follow-up. The primary outcomes were pain and disability measured by the Brief Pain Inventory and Oswestry Disability Index. Secondary outcomes included general health (SF-12) and performance-based tests (5-Chair Stand, Timed Up and Go, 10-Meter Walk). Multivariable linear regression analyses found that CBPT participants had significantly greater decreases in pain and disability and increases in general health and physical performance compared with the education group at the 3-month follow-up. Results suggest a targeted CBPT program may result in significant and clinically meaningful improvement in postoperative outcomes. CBPT has the potential to be an evidence-based program that clinicians can recommend for patients at risk for poor recovery after spine surgery. This study investigated a targeted cognitive-behavioral-based physical therapy program for patients after lumbar spine surgery. Findings lend support to the hypothesis that incorporating cognitive-behavioral strategies into postoperative physical therapy may address psychosocial risk factors and improve pain, disability, general health, and physical performance outcomes.


Workplace violence against doctors involved in clinical care at a tertiary care hospital in Pakistan.
A study was conducted to determine perceptions, attitudes and experience of workplace violence among residents and faculty at a tertiary care centre in Karachi, Pakistan. An anonymous, electronic, self-administered questionnaire was circulated among all residents and faculty members working at Aga Khan University Hospital, Karachi. A standard questionnaire was devised and used, and workplace violence and its types were defined as per World Health Organization (WHO) definitions. An overall response rate of 44.9% was achieved. A total of 53.4% of the respondents reported being victims of some form of workplace violence with verbal abuse being the most prevalent (41.6%) followed by bullying and threat. Most frequent perpetrators were found to be faculty members followed by patients or their attendants. Specialty of respondents was found to be significantly associated with verbal abuse and significantly more females were subjected to sexual harassment, while ethnicity was found to be significantly associated with racial harassment. The results correspond to previously available literature, while they also highlight some findings unique to our culture. We suggest that measures should be taken as per WHO and Joint Commission International Accreditation ( J CIA) recommendations to prevent workplace violence across the country.


A model for chondrogenic condensations in the developing limb: the role of extracellular matrix and cell tractions.
The hyaluronate component of the extracellular matrix is a powerfully hydrophilic polymer, capable of osmotically swelling and deswelling by a volume factor of 5 or more. At the time of cartilage condensation in the limb bud the chondrocytes start to produce hyaluronidase, an enzyme which degrades hyaluronate. The consequent deswelling brings the chondrocytes closer together - close enough for intercellular cell tractions to become effective and intercellular junctions to form. By analysing the physicochemical situation we show how these processes, principally the coupling of the osmotic deswelling with cellular traction forces, can produce cartilage condensation patterns resembling those in the early limb bud. In distinction from our earlier model for chondrogenic condensations this mechanism does not depend on cell motions other than convective transport by contraction.


Secondary evolutionary escalation between brachiopods and enemies of other prey.
The fossil record of predation indicates that attacks on Paleozoic brachiopods were very rare, especially compared to those on post-Paleozoic mollusks, yet stratigraphically and geographically widespread. Drilling frequencies were very low in the early Paleozoic (<<1%) and went up slightly in the mid-to-late Paleozoic. Present-day brachiopods revealed frequencies only slightly higher. The persistent rarity of drilling suggests that brachiopods were the secondary casualties of mistaken or opportunistic attacks by the enemies of other taxa. Such sporadic attacks became slightly more frequent as trophic systems escalated and predators diversified. Some evolutionarily persistent biotic interactions may be incidental rather than coevolutionary or escalatory in nature.


An in vitro 3D evaluation of the accuracy of 4 intraoral optical scanners on a 6-implant model.
Although numerous studies have been performed on the accuracy of intraoral scanners, determining the clinical significance of the results is problematic. The purpose of this in vitro study was to evaluate the trueness and precision of 4 intraoral optical scanners (IOSs) on a 6-implant model and provide a method to help determine clinical significance. A polymer mandibular edentulous model with 6 hexagonal scan bodies (Ritter) was fabricated, and a control scan was made by using an industrial laser line probe (FARO Edge HD Arm). Four IOSs (True Definition, TRIOS, CEREC Omnicam, Emerald Scanner) were used to scan the same model 5 times: the 20 standard tessellation language (STL) files were individually imported to a 3D inspection software program (Geomagic Control X) and superimposed over the computer-aided design (CAD) control scan. The tolerance was set at a limit of ±0.01 mm. None of the tested scanners were true even 10% of the time at the ±0.01-mm tolerance, and the Emerald scanner was true less than 5% of the time. Within scanners, results were precise, showing variations of no more than 2% over repeated scans. When a ±0.05-mm tolerance was selected, the percentage within tolerance increased dramatically. This made the performance of the scanners to appear better but obscured valuable information. The 3D color map was the best method for understanding the data. The color maps showed how much was within tolerance and, equally important, the amount and direction of out of tolerance, providing an easily understandable qualitative and quantitative image. No statistical or clinical differences were found among the scanners tested. The 3D map was the best method for observing the data.


Prevention and control of noncommunicable diseases through evidence-based public health: implementing the NCD 2020 action plan.
The control of noncommunicable diseases (NCDs) was addressed by the declaration of the 66th United Nations (UN) General Assembly followed by the World Health Organization's (WHO) NCD 2020 action plan. There is a clear need to better apply evidence in public health settings to tackle both behaviour-related factors and the underlying social and economic conditions. This article describes concepts of evidence-based public health (EBPH) and outlines a set of actions that are essential for successful global NCD prevention. The authors describe the importance of knowledge translation with the goal of increasing the effectiveness of public health services, relying on both quantitative and qualitative evidence. In particular, the role of capacity building is highlighted because it is fundamental to progress in controlling NCDs. Important challenges for capacity building include the need to bridge diverse disciplines, build the evidence base across countries and the lack of formal training in public health sciences. As brief case examples, several successful capacity-building efforts are highlighted to address challenges and further evidence-based decision making. The need for a more comprehensive public health approach, addressing social, environmental and cultural conditions, has led to government-wide and society-wide strategies that are now on the agenda due to efforts such as the WHO's NCD 2020 action plan and Health 2020: the European Policy for Health and Wellbeing. These efforts need research to generate evidence in new areas (e.g. equity and sustainability), training to build public health capacity and a continuous process of improvement and knowledge generation and translation.


Active energy harvesting from microbial fuel cells at the maximum power point without using resistors.
Microbial fuel cell (MFC) technology offers a sustainable approach to harvest electricity from biodegradable materials. Energy production from MFCs has been demonstrated using external resistors or charge pumps, but such methods can only dissipate energy through heat or receive electrons passively from the MFC without any controllability. This study developed a new approach and system that can actively extract energy from MFC reactors at any operating point without using any resistors, especially at the peak power point to maximize energy production. Results show that power harvesting from a recirculating-flow MFC can be well maintained by the maximum power point circuit (MPPC) at its peak power point, while a charge pump was not able to change operating point due to current limitation. Within 18-h test, the energy gained from the MPPC was 76.8 J, 76 times higher than the charge pump (1.0 J) that was commonly used in MFC studies. Both conditions resulted in similar organic removal, but the Coulombic efficiency obtained from the MPPC was 21 times higher than that of the charge pump. Different numbers of capacitors could be used in the MPPC for various energy storage requirements and power supply, and the energy conversion efficiency of the MPPC was further characterized to identify key factors for system improvement. This active energy harvesting approach provides a new perspective for energy harvesting that can maximize MFC energy generation and system controllability.


Pathway discovery in metabolic networks by subgraph extraction.
Subgraph extraction is a powerful technique to predict pathways from biological networks and a set of query items (e.g. genes, proteins, compounds, etc.). It can be applied to a variety of different data types, such as gene expression, protein levels, operons or phylogenetic profiles. In this article, we investigate different approaches to extract relevant pathways from metabolic networks. Although these approaches have been adapted to metabolic networks, they are generic enough to be adjusted to other biological networks as well. We comparatively evaluated seven sub-network extraction approaches on 71 known metabolic pathways from Saccharomyces cerevisiae and a metabolic network obtained from MetaCyc. The best performing approach is a novel hybrid strategy, which combines a random walk-based reduction of the graph with a shortest paths-based algorithm, and which recovers the reference pathways with an accuracy of approximately 77%. Most of the presented algorithms are available as part of the network analysis tool set (NeAT). The kWalks method is released under the GPL3 license.