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Porcine reproductive and respiratory syndrome (PRRS) is an extremely contagious disease that causes great damage to the U.S. pork industry. PRRS is not subject to official control in the U.S., but most producers adopt control strategies, including vaccination. However, the PRRS virus mutates frequently, facilitating its ability to infect even vaccinated animals. In this paper we analyze how increased vaccination on sow farms reduces PRRS losses and when vaccination is profitable. We develop a SIR model to simulate the spread of an outbreak between and within swine farms located in a region of Minnesota. Then, we estimate economic losses due to PRRS and calculate the benefits of vaccination. We find that increased vaccination of sow farms increases the private profitability of vaccination, and also transmits positive externalities to farms that do not vaccinate. Although vaccination reduces industry losses, a low to moderate vaccine efficacy implies that large PRRS losses remain, even on vaccinated farms. Our approach provides useful insight into the dynamics of an endemic animal disease and the benefits of different vaccination regimens.

Most U.S. states that have regulated and taxed cannabis have imposed some form of mandatory safety testing requirements. In California, the country's largest and oldest legal cannabis market, mandatory testing was first enforced by state regulators in July 2018, and additional mandatory tests were introduced at the end of 2018. All cannabis must be tested and labeled as certified by a state-licensed cannabis testing laboratory before it can be legally marketed in California. Every batch that is sold by licensed retailers must be tested for more than 100 contaminants, including 66 pesticides with tolerance levels lower than the levels allowable for any other agricultural product in California. This paper estimates the costs of compliance with mandatory cannabis testing laws and regulations, using California's testing regime as a case study. We use state government data, data collected from testing laboratories, and data collected from lab equipment suppliers to run a set of Monte Carlo simulations and estimate the cost per pound of compliance with California's new cannabis testing regulations. We find that cost per pound is highly sensitive to average batch size and testing failure rates. We present results under a variety of different assumptions about batch size and failure rates. We also find that under realistic assumptions, the loss of cannabis that must be destroyed if a batch fails testing accounts for a larger share of total testing costs than does the cost of the lab tests. Using our best estimates of average batch size (8 pounds) and failure rate (4%) in the 2019 California market, we estimate testing cost at $136 per pound of dried cannabis flower, or about 10 percent of the reported average wholesale price of legal cannabis in the state. Our findings explain effects of the testing standards on the cost of supplying legal licensed cannabis, in California, other U.S. states, and foreign jurisdictions with similar testing regimes.

Exposure to stressful events is linked to anxiety symptoms in children, although research examining this association in the first five years of life is limited. We sought to examine the role of various aspects of family stressful experiences such as the total accumulation, impact, and type (measured longitudinally in the first five years of life) on child anxiety symptoms at age 5 years. A community sample of children and their parents (N = 399) enrolled in a longitudinal study of emotion processing were assessed when the children were infants and at ages 2 years, 3 years, and 5 years. Parents completed the Revised Life Events Questionnaire (all visits) to assess family exposures to stressful life events and the Child Behavior Checklist (5 years) to assess child emotional and behavioral symptoms. Analyses showed that total stressful events accumulated by 4 years were significantly associated with child anxiety symptoms at 5 years (r = 0.118, p = 0.045). Total stressful events accumulated at earlier time points (by 1 year, 2 years, and 3 years of age) were not significantly associated with child anxiety symptoms at 5 years. Events reported as being impactful by families appeared to be more sensitive than total events, with accumulated impactful events as early as 1 year being significantly associated with child anxiety symptoms at 5 years (r = 0.112, p = 0.042). When considering types of stressors, cumulative exposure from the prenatal period to 5 years to financial stressors (β = 0.12, p =.035) was most saliently and significantly associated with child anxiety symptoms at 5 years (after adjusting for other categories of stress such as health, interpersonal, and logistical stressors). Together, these findings suggest that stressful life events accumulated in early life, particularly those rated as impactful for the family and those related to finances, are associated with child anxiety symptoms at 5 years. [ABSTRACT FROM AUTHOR]

BackgroundMeningiomas are stratified according to tumor grade and extent of resection, often in isolation of other clinical variables. Here, we use machine learning (ML) to integrate demographic, clinical, radiographic and pathologic data to develop predictive models for meningioma outcomes.Methods and findingsWe developed a comprehensive database containing information from 235 patients who underwent surgery for 257 meningiomas at a single institution from 1990 to 2015. The median follow-up was 4.3 years, and resection specimens were re-evaluated according to current diagnostic criteria, revealing 128 WHO grade I, 104 grade II and 25 grade III meningiomas. A series of ML algorithms were trained and tuned by nested resampling to create models based on preoperative features, conventional postoperative features, or both. We compared different algorithms' accuracy as well as the unique insights they offered into the data. Machine learning models restricted to preoperative information, such as patient demographics and radiographic features, had similar accuracy for predicting local failure (AUC = 0.74) or overall survival (AUC = 0.68) as models based on meningioma grade and extent of resection (AUC = 0.73 and AUC = 0.72, respectively). Integrated models incorporating all available demographic, clinical, radiographic and pathologic data provided the most accurate estimates (AUC = 0.78 and AUC = 0.74, respectively). From these models, we developed decision trees and nomograms to estimate the risks of local failure or overall survival for meningioma patients.ConclusionsClinical information has been historically underutilized in the prediction of meningioma outcomes. Predictive models trained on preoperative clinical data perform comparably to conventional models trained on meningioma grade and extent of resection. Combination of all available information can help stratify meningioma patients more accurately.

Due to the highly transmissible nature of porcine reproductive and respiratory syndrome (PRRS), implementation of regional programs to control the disease may be critical. Because PRRS is not reported in the US, numerous voluntary regional control projects (RCPs) have been established. However, the effect of RCPs on PRRS control has not been assessed yet. This study aims to quantify the extent to which RCPs contribute to PRRS control by proposing a methodological framework to evaluate the progress of RCPs. Information collected between July 2012 and June 2015 from the Minnesota Voluntary Regional PRRS Elimination Project (RCP-N212) was used. Demography of premises (e.g. composition of farms with sows = SS and without sows = NSS) was assessed by a repeated analysis of variance. By using general linear mixed-effects models, active participation of farms enrolled in the RCP-N212, defined as the decision to share (or not to share) PRRS status, was evaluated and used as a predictor, along with other variables, to assess the PRRS trend over time. Additionally, spatial and temporal patterns of farmers' participation and the disease dynamics were investigated. The number of farms enrolled in RCP-N212 and its geographical coverage increased, but the proportion of SS and NSS did not vary significantly over time. A significant increasing (p

Tuberculosis (TB) in people living with HIV (PLHIV) is usually paucibacillary and the smear microscopy has limitations and may lead to high proportions of non-confirmed pulmonary tuberculosis (NC-PTB). Despite culture being the reference method, it usually takes 6 to 8 weeks to produce the results. This study aimed to analyze the effect of a rapid molecular test (Xpert) in the confirmatory rate of PTB among PLHIV, from 2010 to 2020, in São Paulo state, Brazil. This is an ecological study with time series analysis of the trend and the NC-PTB rates before and after Xpert implementation in 21 municipalities. The use of Xpert started and gradually increased after 2014, while the rate of NC-PTB in PLHIV decreased over this time, being more significant between late 2015 and mid-2017. The city of Ribeirão Preto stands out for having the highest percentage (75.0%) of Xpert testing among PLHIV and for showing two reductions in the NC-PTB rate. The cities with low Xpert coverage had a slower and smaller decrease in the NC-PTB rate. Despite being available since 2014, a significant proportion of PLHIV suspected of PTB in the state of São Paulo did not have an Xpert ordered by the doctors. The implementation of Xpert reduced the NC-PTB rates with growing effect as the coverage increased in the municipality. [ABSTRACT FROM AUTHOR]

Conidia of Aspergillus fumigatus are inhaled by humans on daily basis. As a consequence, these conidia can cause infections that differ in severity ranging from allergic bronchopulmonary aspergillosis to invasive aspergillosis. In this study we compared virulence of five A. fumigatus isolates in four different infection models to address the predictive value of different model systems. Two of the A. fumigatus strains were isolated from dogs with a non-invasive sino-nasal aspergillosis (DTO271-B5 and DTO303-F3), while three strains were isolated from human patients with invasive aspergillosis (Af293, ATCC46645 and CEA10). Infection models used encompassed cultured type II A549 lung epithelial cells, Protostelium aurantium amoeba, Galleria melonella larvae and zebrafish embryos. No major differences in virulence between these five strains were observed in the lung epithelial cell model. In contrast, strain ATCC46645 was most virulent in the amoeba and zebrafish model, whereas it was much less virulent in the Galleria infection model. DTO303-F3 was most virulent in the latter model. In general, reference strain Af293 was less virulent as compared to the other strains. Genome sequence analysis showed that this latter strain differed from the other four strains in 136 SNPs in virulence-related genes. Together, our results show that virulence of individual A. fumigatus strains show significant differences between infection models. We conclude that the predictive value of different model systems varies since the relative virulence across fungal strains does not hold up across different infection model systems.

[This corrects the article DOI: 10.1371/journal.pone.0252948.].

BackgroundTelomeres shorten as cells divide. This shortening is compensated by the enzyme telomerase. We evaluated the effect of common variants in the telomerase RNA component (TERC) gene on telomere length (TL) in the population-based Health Aging and Body Composition (Health ABC) Study and in two replication samples (the TwinsUK Study and the Amish Family Osteoporosis Study, AFOS).MethodologyFive variants were identified in the TERC region by sequence analysis and only one SNP was common (rs2293607, G/A). The frequency of the G allele was 0.26 and 0.07 in white and black, respectively. Testing for association between TL and rs2293607 was performed using linear regression models or variance component analysis conditioning on relatedness among subjects.ResultsThe adjusted mean TL was significantly shorter in 665 white carriers of the G allele compared to 887 non-carriers from the Health ABC Study (4.69±0.05 kbp vs. 4.86±0.04 kbp, measured by quantitative PCR, p = 0.005). This association was replicated in another white sample from the TwinsUK Study (6.90±0.03 kbp in 301 carriers compared to 7.06±0.03 kbp in 395 non-carriers, measured by Southern blots, p = 0.009). A similar pattern of association was observed in whites from the family-based AFOS and blacks from the Health ABC cohort, although not statistically significant, possibly due to the lower allele frequency in these populations. Combined analysis using 2,953 white subjects from 3 studies showed a significant association between TL and rs2293607 (β = -0.19±0.04 kbp, p = 0.001).ConclusionOur study shows a significant association between a common variant in TERC and TL in humans, suggesting that TERC may play a role in telomere homeostasis.

Most U.S. states that have regulated and taxed cannabis have imposed some form of mandatory safety testing requirements. In California, the country's largest and oldest legal cannabis market, mandatory testing was first enforced by state regulators in July 2018, and additional mandatory tests were introduced at the end of 2018. All cannabis must be tested and labeled as certified by a state-licensed cannabis testing laboratory before it can be legally marketed in California. Every batch that is sold by licensed retailers must be tested for more than 100 contaminants, including 66 pesticides with tolerance levels lower than the levels allowable for any other agricultural product in California. This paper estimates the costs of compliance with mandatory cannabis testing laws and regulations, using California's testing regime as a case study. We use state government data, data collected from testing laboratories, and data collected from lab equipment suppliers to run a set of Monte Carlo simulations and estimate the cost per pound of compliance with California's new cannabis testing regulations. We find that cost per pound is highly sensitive to average batch size and testing failure rates. We present results under a variety of different assumptions about batch size and failure rates. We also find that under realistic assumptions, the loss of cannabis that must be destroyed if a batch fails testing accounts for a larger share of total testing costs than does the cost of the lab tests. Using our best estimates of average batch size (8 pounds) and failure rate (4%) in the 2019 California market, we estimate testing cost at $136 per pound of dried cannabis flower, or about 10 percent of the reported average wholesale price of legal cannabis in the state. Our findings explain effects of the testing standards on the cost of supplying legal licensed cannabis, in California, other U.S. states, and foreign jurisdictions with similar testing regimes.

[This corrects the article DOI: 10.1371/journal.pone.0044256.].

ObjectiveIn this exploratory longitudinal study we assessed cognitive development in a community sample of infants born into predominantly low-income families from two different urban sites, to identify family and community factors that may associate with outcomes by 1 year of age.MethodInfant-mother dyads (n = 109) were recruited in Boston and Los Angeles community pediatric practices. Infant cognition was measured using the Mullen Scales of Early Learning when the infant was aged 2, 6, 9, and 12 months. Longitudinal linear mixed effects modeling and linear regression models explored potential predictors of cognitive outcomes.ResultsCognitive scores were lower than the reference population mean at both 6 and 12 months. There were site differences in demographics and cognitive performance. Maternal education predicted expressive language in Boston, and speaking Spanish and lower rates of community poverty were associated with greater increases in overall cognition in Los Angeles.ConclusionThis exploratory study identified a number of drivers of child development that are both shared across cohorts and unique to specific community samples. Factors influencing heterogeneity within and across populations both may be important contributors to prevention and intervention in supporting healthy development among children.

The Liolaemus montanus group is a diverse group of lizards that ranges from central Peru to southwestern Mendoza, Argentina, including much of the Plurinational State of Bolivia ("Bolivia") and Chile. The species of this group mainly inhabit high elevation areas with cold temperatures. In the last years, several species of this group have been described, mostly in Argentina and Chile. In Bolivia, there are at least thirteen valid species belonging to the L. montanus group. In this study, we describe a new species of the L. montanus group with a marked endemism in the Cordillera de Sama of the Tarija Department, Bolivia, and a combination of unique character states that allows its formal description as a new species. The phylogenetic relationships based on analysis of 159 morphological characters suggest that it belongs to the L. montanus group, and that it is closest to Liolaemus pulcherrimus, which is found allopatrically in a small area of the Jujuy Province, Argentina. The multivariate analyses of 66 morphological characters support the phylogenetic relationships. Statistical analyses of inter-species comparisons of morphological characters are not considered the only methods due to the non-independence of some characters states among species; thus, a phylogenetic analysis is recommended. The detailed revision of specimens of the L. montanus group held in the collections of Bolivia is filling major geographic gaps and improving our understanding of the phylogenetic and biogeographic relationships of this widely distributed group of South American lizards.

In Mexico, the increase in childhood obesity is alarming. Thus, improving the precision of its diagnosis is expected to impact on disease prevention. We estimated obesity prevalence by bioimpedance-based percent body fat (%BF) and body mass index (BMI) in 1061 girls and 1121 boys, from 3 to 17 years old. Multiple regressions and area under receiver operating curves (AUC) were used to determine the predictive value of BMI on %BF and percentile curves were constructed. Overall obesity prevalence estimated by %BF was 43.7%, and by BMI it was 20.1%; it means that the diagnosis by BMI underestimated around 50% of children diagnosed with obesity by %BF (≥30% for girls, ≥25% for boys). The fat mass excess is further underestimated in boys than in girls when using the standard BMI classification. The relationship between %BF and BMI was strong in school children and adolescents (all cases R2>0.70), but not in preschool children (girls R2 = 0.57, boys R2 = 0.23). AUCs showed greater discriminative power of BMI to detect %BF obesity in school children and adolescents (all cases AUC≥0.90) than in preschool children (girls AUC = 0.86; boys AUC = 0.70). Growth percentile charts showed that girls aged 9-17 years and boys aged 8-17 years presented fat excess from the 50th percentile and above. We suggested to change the BMI cut-off for them, considering values at the 75th percentile as overweight, and values at the 85th percentile as obesity, as previously recommended for Mexican children. Improving obesity diagnosis will allow greater efficiency when searching for comorbidities in clinical practice.

Fluorescence microscopy is one of the workhorses of biomedical research and laboratory diagnosis; however, their cost, size, maintenance, and fragility has prevented their adoption in developing countries or low-resource settings. Although significant advances have decreased their size, cost and accessibility, their designs and assembly remain rather complex. Here, inspired on the simple mechanism from a nut and a bolt, we report the construction of a portable fluorescence microscope that operates in bright-field mode and in three fluorescence channels: UV, green, and red. It is assembled in under 10 min from only six 3D printed parts, basic electronic components, a microcomputer (Raspberry Pi) and a camera, all of which can be readily purchased in most locations or online for US $122. The microcomputer was programmed in Python language to capture time-lapse images and videos. Resolution and illumination conditions of the microscope were characterized, and its performance was compared with a high-end fluorescence microscope in bright-field and fluorescence mode. We demonstrate that our miniature microscope can resolve and track single cells in both modes. The instructions on how to assemble the microscope are shown in a video, and the software to control it and the design files of the 3D-printed parts are freely available online. Our portable microscope is ideal in applications where space is at a premium, such as lab-on-a-chips or space missions, and can find applications in basic and clinical research, diagnostics, telemedicine and in educational settings.

Acute hepatopancreatic necrosis disease (AHPND), caused by marine bacteria Vibrio Parahaemolyticus, is a huge problem in shrimp farms. The V. parahaemolyticus infecting material is contained in a plasmid which encodes for the lethal toxins PirABVp, whose primary target tissue is the hepatopancreas, causing sloughing of epithelial cells, necrosis, and massive hemocyte infiltration. To get a better understanding of the hepatopancreas response during AHPND, juvenile shrimp Litopenaeus vannamei were infected by immersion with V. parahaemolyticus. We performed transcriptomic mRNA sequencing of infected shrimp hepatopancreas, at 24 hours post-infection, to identify novel differentially expressed genes a total of 174,098 transcripts were examined of which 915 transcripts were found differentially expressed after comparative transcriptomic analysis: 442 up-regulated and 473 down-regulated transcripts. Gene Ontology term enrichment analysis for up-regulated transcripts includes metabolic process, regulation of programmed cell death, carbohydrate metabolic process, and biological adhesion, whereas for down-regulated transcripts include, microtubule-based process, cell activation, and chitin metabolic process. The analysis of protein- protein network between up and down-regulated genes indicates that the first gene interactions are connected to oxidation-processes and sarcomere organization. Additionally, protein-protein networks analysis identified 20-top highly connected hub nodes. Based on their immunological or metabolic function, ten candidate transcripts were selected to measure their mRNA relative expression levels in AHPND infected shrimp hepatopancreas by RT-qPCR. Our results indicate a close connection between the immune and metabolism systems during AHPND infection. Our RNA-Seq and RT-qPCR data provide the possible immunological and physiological scenario as well as the molecular pathways that take place in the shrimp hepatopancreas in response to an infectious disease.

Several studies suggest that low birthweight resulting from restricted intrauterine growth can leave a metabolic footprint which may persist into adulthood. To investigate this, we performed metabolomic profiling on 5036 female twins, aged 18-80, with weight at birth information available from the TwinsUK cohort and performed independent replication in two additional cohorts. Out of 422 compounds tested, 25 metabolites associated with birthweight in these twins, replicated in 1951 men and women from the Hertfordshire Cohort Study (HCS, aged 66) and in 2391 men and women from the North Finland Birth 1986 cohort (NFBC, aged 16). We found distinct heterogeneity between sexes and, after adjusting for multiple tests and heterogeneity, two metabolites were reproducible overall (propionylcarnitine and 3-4-hydroxyphenyllactate). Testing women only, we found other metabolites associated with lower birthweight from the meta-analysis of the three cohorts (2-hydroxy-butyric acid and γ-glutamylleucine). Higher levels of all these metabolites can be linked to insulin resistance, oxidative stress or a dysfunction of energy metabolism, suggesting that low birthweight in both twins and singletons are having an impact on these pathways in adulthood.

Background: Variability in spine kinematics is a common motor adaptation to pain, which has been measured in various ways. However, it remains unclear whether low back pain (LBP) is typically characterised by increased, decreased or unchanged kinematic variability. Therefore, the aim of this review was to synthesise the evidence on whether the amount and structure of spine kinematic variability is altered in people with chronic non-specific LBP (CNSLBP). Methods: Electronic databases, grey literature, and key journals were searched from inception up to August 2022, following a published and registered protocol. Eligible studies must investigated kinematic variability in CNSLBP people (adults ≥18 years) while preforming repetitive functional tasks. Two reviewers conducted screening, data extraction, and quality assessment independently. Data synthesis was conducted per task type and individual results were presented quantitatively to provide a narrative synthesis. The overall strength of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation guidelines. Findings: Fourteen observational studies were included in this review. To facilitate the interpretation of the results, the included studies were grouped into four categories according to the task preformed (i.e., repeated flexion and extension, lifting, gait, and sit to stand to sit task). The overall quality of evidence was rated as a very low, primarily due to the inclusion criteria that limited the review to observational studies. In addition, the use of heterogeneous metrics for analysis and varying effect sizes contributed to the downgrade of evidence to a very low level. Interpretation: Individuals with chronic non-specific LBP exhibited altered motor adaptability, as evidenced by differences in kinematic movement variability during the performance of various repetitive functional tasks. However, the direction of the changes in movement variability was not consistent across studies. [ABSTRACT FROM AUTHOR]

Ultrasonography is a powerful tool to non-invasively monitor in real time the development of the human fetus in utero. Although genetically engineered mice have served as valuable in vivo models to study both embryo implantation and pregnancy progression, such studies usually require sacrifice of parous mice for subsequent phenotypic analysis. To address this issue, we used three-dimensional (3-D) reconstruction in silico of high-frequency ultrasound (HFUS) imaging data for early detection and characterization of murine embryo implantation sites and their development in utero. With HFUS imaging followed by 3-D reconstruction, we were able to precisely quantify embryo implantation site number and embryonic developmental progression in pregnant C57BL6J/129S mice from as early as 5.5 days post coitus (d.p.c.) through to 9.5 d.p.c. using a VisualSonics Vevo 2100 (MS550S) transducer. In addition to measurements of implantation site number, location, volume and spacing, embryo viability via cardiac activity monitoring was also achieved. A total of 12 dams were imaged with HFUS with approximately 100 embryos examined per embryonic day. For the post-implantation period (5.5 to 8.5 d.p.c.), 3-D reconstruction of the gravid uterus in mesh or solid overlay format enabled visual representation in silico of implantation site location, number, spacing distances, and site volume within each uterine horn. Therefore, this short technical report describes the feasibility of using 3-D HFUS imaging for early detection and analysis of post-implantation events in the pregnant mouse with the ability to longitudinally monitor the development of these early pregnancy events in a non-invasive manner. As genetically engineered mice continue to be used to characterize female reproductive phenotypes, we believe this reliable and non-invasive method to detect, quantify, and characterize early implantation events will prove to be an invaluable investigative tool for the study of female infertility and subfertility phenotypes based on a defective uterus.

Targeted sequencing of PCR amplicons generated from bisulfite deaminated DNA is a flexible, cost-effective way to study methylation of a sample at single CpG resolution and perform subsequent multi-target, multi-sample comparisons. Currently, no platform specific protocol, support, or analysis solution is provided to perform targeted bisulfite sequencing on a Personal Genome Machine (PGM). Here, we present a novel tool, called TABSAT, for analyzing targeted bisulfite sequencing data generated on Ion Torrent sequencers. The workflow starts with raw sequencing data, performs quality assessment, and uses a tailored version of Bismark to map the reads to a reference genome. The pipeline visualizes results as lollipop plots and is able to deduce specific methylation-patterns present in a sample. The obtained profiles are then summarized and compared between samples. In order to assess the performance of the targeted bisulfite sequencing workflow, 48 samples were used to generate 53 different Bisulfite-Sequencing PCR amplicons from each sample, resulting in 2,544 amplicon targets. We obtained a mean coverage of 282X using 1,196,822 aligned reads. Next, we compared the sequencing results of these targets to the methylation level of the corresponding sites on an Illumina 450k methylation chip. The calculated average Pearson correlation coefficient of 0.91 confirms the sequencing results with one of the industry-leading CpG methylation platforms and shows that targeted amplicon bisulfite sequencing provides an accurate and cost-efficient method for DNA methylation studies, e.g., to provide platform-independent confirmation of Illumina Infinium 450k methylation data. TABSAT offers a novel way to analyze data generated by Ion Torrent instruments and can also be used with data from the Illumina MiSeq platform. It can be easily accessed via the Platomics platform, which offers a web-based graphical user interface along with sample and parameter storage. TABSAT is freely available under a GNU General Public License version 3.0 (GPLv3) at https://github.com/tadkeys/tabsat/ and http://demo.platomics.com/.

BACKGROUND:Highly active antiretroviral therapy (HAART) can cause side effects in HIV patients, as the metabolic syndrome. Early identification of risk for development of cardiovascular diseases using available reliable and practical methods is fundamental. On this basis, the aim of this study was to compare the effectiveness of anthropometric indicators to identify metabolic syndrome in HIV patients on HAART. METHODS:It is a cross-sectional study. A number of 280 stable HIV patients were studied. It measured weight, height, waist circumference (WC), hip circumference (HP), thigh circumference (TC) and calculated body mass index (BMI), body adiposity index (BAI), waist to hip ratio (WHR) and waist to thigh ratio (WTR). There was also a performance of biochemical tests of lipid profile and fasting glucose. Systemic blood pressure was measured. The criteria proposed by the National Cholesterol Education Program III (NCEP-ATP III) to metabolic syndrome classification was used. Individuals were divided in groups with or without metabolic alterations and their anthropometric indicators were compared. Receiver operating characteristic (ROC) curves were designed for each anthropometric indicator using the metabolic syndrome classification to identify sensitivity and specificity. RESULTS:WC was a good tool to identify each metabolic disorder separately: total cholesterol (only females, p

In addition to an increase in mean temperature, climate change models predict decreasing amplitudes of daily temperature fluctuations. In temperate regions, where daily and seasonal fluctuations are prominent, such decreases in daily temperature fluctuations can have a pronounced effect on the fitness of species and on the outcome of species interactions. In this study, the effect of a temperature regime with daily fluctuations versus a constant temperature on the fitness and interspecific interactions of three cryptic species of the marine nematode species complex of Litoditis marina (Pm I, Pm III and Pm IV) were investigated. In a lab experiment, different combinations of species (monospecific treatment: Pm I and Pm IV and Pm III alone; two-species treatment: Pm I + Pm IV; three-species treatment: Pm I + Pm IV + Pm III) were subjected to two different temperature regimes: one constant and one fluctuating temperature. Our results showed that fluctuating temperature had minor or no effects on the population fitness of the three species in monocultures. In contrast, interspecific interactions clearly influenced the fitness of all three species, both positively and negatively. Temperature regime did have a substantial effect on the interactions between the species. In the two-species treatment, temperature regime altered the interaction from a sort of mutualism to commensalism. In addition, the strength of the interspecific interactions changed depending on the temperature regime in the three-species treatment. This experiment confirms that interactions between the species can change depending on the abiotic environment; these results show that it is important to incorporate the effect of fluctuations on interspecific interactions to predict the effect of climate change on biodiversity.

Cuba is an HBsAg low-prevalence country with a high coverage of anti-hepatitis B vaccine. Its population is essentially the result of the population mix of Spanish descendants and former African slaves. Information about genetic characteristics of hepatitis B virus (HBV) strains circulating in the country is scarce. The HBV genotypes/subgenotypes, serotypes, mixed infections, and S gene mutations of 172 Cuban HBsAg and HBV-DNA positive patients were determined by direct sequencing and phylogenetic analysis. Phylogenetic analysis of HBV S gene sequences showed a predominance of genotype A (92.4%), subgenotype A2 (84.9%) and A1 (7.6%). Genotype D (7.0%) and subgenotype C1 (0.6%) were also detected but typical (sub)genotypes of contemporary West-Africa (E, A3) were conspicuously absent. All genotype A, D, and C strains exhibited sequence characteristics of the adw2, ayw2, and adrq serotypes, respectively. Thirty-three (19.1%) patients showed single, double, or multiple point mutations inside the Major Hydrophilic domain associated with vaccine escape; eighteen (10.5%) patients had mutations in the T-cell epitope (amino acids 28-51), and there were another 111 point mutations downstream of the S gene. One patient had an HBV A1/A2 mixed infection. This first genetic study of Cuban HBV viruses revealed only strains that were interspersed with strains from particularly Europe, America, and Asia. The absence of genotype E supports previous hypotheses about an only recent introduction of this genotype into the general population in Africa. The presence of well-known vaccine escape (3.5%) and viral resistance mutants (2.9%) warrants strain surveillance to guide vaccination and treatment strategies.

A newly-described syndrome called Aneurysm-Osteoarthritis Syndrome (AOS) was recently reported. AOS presents with early onset osteoarthritis (OA) in multiple joints, together with aneurysms in major arteries, and is caused by rare mutations in SMAD3. Because of the similarity of AOS to idiopathic generalized OA (GOA), we hypothesized that SMAD3 is also associated with GOA and tested the hypothesis in a population-based cohort.Study participants were derived from the Chingford study. Kellgren-Lawrence (KL) grades and the individual features of osteophytes and joint space narrowing (JSN) were scored from radiographs of hands, knees, hips, and lumbar spines. The total KL score, osteophyte score, and JSN score were calculated and used as indicators of the total burden of radiographic OA. Forty-one common SNPs within SMAD3 were genotyped using the Illumina HumanHap610Q array. Linear regression modelling was used to test the association between the total KL score, osteophyte score, and JSN score and each of the 41 SNPs, with adjustment for patient age and BMI. Permutation testing was used to control the false positive rate.A total of 609 individuals were included in the analysis. All were Caucasian females with a mean age of 60.9±5.8. We found that rs3825977, with a minor allele (T) frequency of 20%, in the last intron of SMAD3, was significantly associated with total KL score (β = 0.14, Ppermutation = 0.002). This association was stronger for the total JSN score (β = 0.19, Ppermutation = 0.002) than for total osteophyte score (β = 0.11, Ppermutation = 0.02). The T allele is associated with a 1.47-fold increased odds for people with 5 or more joints to be affected by radiographic OA (Ppermutation = 0.046).We found that SMAD3 is significantly associated with the total burden of radiographic OA. Further studies are required to reveal the mechanism of the association.

Cochlear implants (CIs) can partially restore functional hearing in deaf individuals. However, multiple factors affect CI listener's speech perception, resulting in large performance differences. Non-speech based tests, such as spectral ripple discrimination, measure acoustic processing capabilities that are highly correlated with speech perception. Currently spectral ripple discrimination is measured using standard psychoacoustic methods, which require attentive listening and active response that can be difficult or even impossible in special patient populations. Here, a completely objective cortical evoked potential based method is developed and validated to assess spectral ripple discrimination in CI listeners. In 19 CI listeners, using an oddball paradigm, cortical evoked potential responses to standard and inverted spectrally rippled stimuli were measured. In the same subjects, psychoacoustic spectral ripple discrimination thresholds were also measured. A neural discrimination threshold was determined by systematically increasing the number of ripples per octave and determining the point at which there was no longer a significant difference between the evoked potential response to the standard and inverted stimuli. A correlation was found between the neural and the psychoacoustic discrimination thresholds (R2=0.60, p

Whereas fossil evidence indicates extensive treeless vegetation and diverse grazing megafauna in Europe and northern Asia during the last glacial, experiments combining vegetation models and climate models have to-date simulated widespread persistence of trees. Resolving this conflict is key to understanding both last glacial ecosystems and extinction of most of the mega-herbivores. Using a dynamic vegetation model (DVM) we explored the implications of the differing climatic conditions generated by a general circulation model (GCM) in "normal" and "hosing" experiments. Whilst the former approximate interstadial conditions, the latter, designed to mimic Heinrich Events, approximate stadial conditions. The "hosing" experiments gave simulated European vegetation much closer in composition to that inferred from fossil evidence than did the "normal" experiments. Given the short duration of interstadials, and the rate at which forest cover expanded during the late-glacial and early Holocene, our results demonstrate the importance of millennial variability in determining the character of last glacial ecosystems.

Incidental findings in neuroimaging occur in 3% of volunteers. Most data come from young subjects. Data on their occurrence in older subjects and their medical, lifestyle and financial consequences are lacking. We determined the prevalence and medical consequences of incidental findings found in community-dwelling older subjects on brain magnetic resonance imaging.Prospective cohort observational study.Single centre study with input from secondary care.Lothian Birth Cohort 1936, a study of cognitive ageing.Incidental findings identified by two consultant neuroradiologists on structural brain magnetic resonance imaging at age 73 years; resulting medical referrals and interventions.PREVALENCE OF INCIDENTAL FINDINGS BY INDIVIDUAL CATEGORIES: neoplasms, cysts, vascular lesions, developmental, ear, nose or throat anomalies, by intra- and extracranial location; visual rating of white matter hyperintensities and brain atrophy.There were 281 incidental findings in 223 (32%) of 700 subjects, including 14 intra- or extracranial neoplasms (2%), 15 intracranial vascular anomalies (2%), and 137 infarcts or haemorrhages (20%). Additionally, 153 had moderate/severe deep white matter hyperintensities (22%) and 176 had cerebral atrophy at, or above, the upper limit of normal (25%) compared with a normative population template. The incidental findings were unrelated to white matter hyperintensities or atrophy; about a third of subjects had both incidental findings and moderate or severe WMH and a quarter had incidental findings and atrophy. The incidental findings resulted in one urgent and nine non-urgent referrals for further medical assessment, but ultimately in no new treatments.In community-dwelling older subjects, incidental findings, including white matter hyperintensities and atrophy, were common. However, many findings were not of medical importance and, in this age group, most did not result in further assessment and none in change of treatment.

This is the first published report examining the combined effect of diet and genotype on body iron content using a classical twin study design. The aim of this study was to determine the relative contribution of genetic and environmental factors in determining iron status. The population was comprised of 200 BMI- and age-matched pairs of MZ and DZ healthy twins, characterised for habitual diet and 15 iron-related candidate genetic markers. Variance components analysis demonstrated that the heritability of serum ferritin (SF) and soluble transferrin receptor was 44% and 54% respectively. Measured single nucleotide polymorphisms explained 5% and selected dietary factors 6% of the variance in iron status; there was a negative association between calcium intake and body iron (p = 0.02) and SF (p = 0.04).

Understanding the pathology resulting from Staphylococcus aureus and Pseudomonas aeruginosa polymicrobial wound infections is of great importance due to their ubiquitous nature, increasing prevalence, growing resistance to antimicrobial agents, and ability to delay healing. Methicillin-resistant S. aureus USA300 is the leading cause of community-associated bacterial infections resulting in increased morbidity and mortality. We utilized a well-established porcine partial thickness wound healing model to study the synergistic effects of USA300 and P. aeruginosa on wound healing. Wound re-epithelialization was significantly delayed by mixed-species biofilms through suppression of keratinocyte growth factor 1. Pseudomonas showed an inhibitory effect on USA300 growth in vitro while both species co-existed in cutaneous wounds in vivo. Polymicrobial wound infection in the presence of P. aeruginosa resulted in induced expression of USA300 virulence factors Panton-Valentine leukocidin and α-hemolysin. These results provide evidence for the interaction of bacterial species within mixed-species biofilms in vivo and for the first time, the contribution of virulence factors to the severity of polymicrobial wound infections.

OBJECTIVE:To determine the extent to which genetic and epigenetic factors contribute to variations in glycosylation of immunoglobulin G (IgG) in humans. METHODS:76 N-glycan traits in circulating IgG were analyzed by UPLC in 220 monozygotic and 310 dizygotic twin pairs from TwinsUK. A classical twin study design was used to derive the additive genetic, common and unique environmental components defining the variance in these traits. Epigenome-wide association analysis was performed using the Illumina 27k chip. RESULTS:51 of the 76 glycan traits studied have an additive genetic component (heritability, h (2) ) ≥ 0.5. In contrast, 12 glycan traits had a low genetic contribution (h(2)

The mitochondrial theory of ageing proposes that damage to mitochondria and diminished mitochondrial DNA (mtDNA) repair are major contributors to cellular dysfunction and age-related diseases. We investigate the prevalence of heteroplasmy in the mtDNA control region in buccal swab and blood derived samples for 178 women from the TwinsUK cohort (41 DZ pair 39 MZ pairs, 18 singletons, mean age 57.5 range 28-82) and its relationship to age, BMI and fasting insulin and glucose serum levels. The overall estimated prevalence of heteroplasmy for both tissues in the control region measured for 37 sites was 17%. The prevalence of heteroplasmy was higher among the older half of the study subjects than in the younger half (23% vs 10% p

Recent advances in bioinformatics have made it possible to predict the B cell and T cell epitopes of antigenic proteins. This has led to design of peptide based vaccines that are more specific, safe, and easy to produce. The obligately intracellular gram negative bacteria Ehrlichia cause ehrlichioses in humans and animals. As yet there are no vaccines to protect against Ehrlichia infection.We applied the principle of structural vaccinology to design peptides to the epitopes of Ehrlichia muris outer membrane P28-19 (OMP-1/P28) and Ehrlichia Heat shock protein 60 (Hsp60/GroEL) antigenic proteins. Both P28-19 and Ehrlichia Hsp60 peptides reacted with polyclonal antibodies against E. canis and E. chaffeensis and could be used as a diagnostic tool for ehrlichiosis. In addition, we demonstrated that mice vaccinated with Ehrlichia P28-19 and Hsp60 peptides and later challenged with E. muris were protected against the pathogen.Our results demonstrate the power of structural vaccines and could be a new strategy in the development of vaccines to provide protection against pathogenic microorganisms.

BACKGROUND:The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of the Kennedy branch of synthesis of phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKalpha and ChoKbeta isoforms, the first one with two different variants of splicing. Recently ChoKalpha has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKbeta in carcinogenesis has been reported. METHODOLOGY/PRINCIPAL FINDINGS:Here we compare the in vitro and in vivo properties of ChoKalpha1 and ChoKbeta in lipid metabolism, and their potential role in carcinogenesis. Both ChoKalpha1 and ChoKbeta showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKbeta display an ethanolamine kinase role, ChoKalpha1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKalpha1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKbeta overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKalpha1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKbeta mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKalpha1 than ChoKbeta. CONCLUSION/SIGNIFICANCE:This study represents the first evidence of the distinct metabolic role of ChoKalpha and ChoKbeta isoforms, suggesting different physiological roles and implications in human carcinogenesis. These findings constitute a step forward in the design of an antitumoral strategy based on ChoK inhibition.