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Abstract Synovial membrane mesenchymal stem cells (SMSCs) often serve as in vitro model for bone disease, but the molecular mechanisms driving osteogenesis in SMSCs from different donor cells of various sources and breeds remain unclear. In this study, porcine SMSCs isolated from adipose synovium (FP) and fibrous synovium (FS) of Angeln Saddleback (AS) and German Landrace (DL) were used to discover the signaling network change after osteogenic induction. During osteogenic differentiation, mineral deposition was first observed at day 14 and further increased until day 21. Transcriptional changes between day 1 and day 21 were enriched in several signaling pathways, including Wnt, PI3K-Akt, and TGF-beta pathway. Certain pathways related to osteogenesis, including osteoblast differentiation, regulation of bone mineralization, and BMP signaling pathway, were enriched at late time points, as confirmed by the osteogenic markers ALPL, COL1A1, and NANOG. A fraction of differentially expressed genes (DEGs) were found between FP and FS, while DEGs between AS and DL increased during the differentiation phase until day 7 and then decreased from day 14 to day 21. These genes are involved in several important signaling pathways, including TGF-beta, Wnt, and lipid-related signaling pathways, suggesting that SMSCs from these two breeds have different osteogenic capabilities.

Abstract Currently, applying uniform distribution of chemical herbicide through a sprayer without considering the spatial distribution information of crops and weeds is the most common method of controlling weeds in commercial agricultural production system. This kind of weed management practice lead to excessive amounts of chemical herbicides being applied in a given field. The objective of this study was to perform site-specific weed control (SSWC) in a corn field by: (1) using a unmanned aerial system (UAS) to map the spatial distribution information of weeds in the field; (2) creating a prescription map based on the weed distribution map, and (3) spraying the field using the prescription map and a commercial size sprayer. In this study, we assumed that plants growing outside the corn rows are weeds and they need to be controlled. The first step in implementing such an approach is identifying the corn rows. For that, we are proposing a Crop Row Identification algorithm, a computer vision algorithm that identifies corn rows on UAS imagery. After being identified, the corn rows were then removed from the imagery and remaining vegetation fraction was classified as weeds. Based on that information, a grid-based weed prescription map was created and the weed control application was implemented through a commercial-size sprayer. The decision of spraying herbicides on a particular grid was based on the presence of weeds in that grid cell. All the grids that contained at least one weed were sprayed, while the grids free of weeds were not. Using our SSWC approach, we were able to save 26.2% of the acreage from being sprayed with herbicide compared to the current method. This study presents a full workflow from UAS image collection to field weed control implementation using a commercial size sprayer, and it shows that some level of savings can potentially be obtained even in a situation with high weed infestation, which might provide an opportunity to reduce chemical usage in corn production systems.

Abstract New insecticides have recently been produced to help control pyrethroid-resistant malaria vectors including the pyrrole, chlorfenapyr. Monitoring the susceptibility of mosquito populations against this new product and potential cross-resistance with current insecticides is vital for better resistance management. In this study, we assessed the resistance status of the major malaria vectors Anopheles gambiae and Anopheles funestus to chlorfenapyr across Africa and explored potential cross-resistance with known pyrethroid resistance markers. Efficacy of chlorfenapyr 100 µg/ml against An. gambiae and An. funestus from five Cameroonian locations, the Democratic Republic of Congo, Ghana, Uganda, and Malawi was assessed using CDC bottle assays. Synergist assays were performed with PBO (4%), DEM (8%) and DEF (0.25%) and several pyrethroid-resistant markers were genotyped in both species to assess potential cross-resistance between pyrethroids and chlorfenapyr. Resistance to chlorfenapyr was detected in An. gambiae populations from DRC (Kinshasa) (mortality rate: 64.3 ± 7.1%) Ghana (Obuasi) (65.9 ± 7.4%), Cameroon (Mangoum; 75.2 ± 7.7% and Nkolondom; 86.1 ± 7.4). In contrast, all An. funestus populations were fully susceptible. A negative association was observed between the L1014F-kdr mutation and chlorfenapyr resistance with a greater frequency of homozygote resistant mosquitoes among the dead mosquitoes after exposure compared to alive (OR 0.5; P = 0.02) whereas no association was found between GSTe2 (I114T in An. gambiae; L119F in An. funestus) and resistance to chlorfenapyr. A significant increase of mortality to chlorfenapyr 10 µg/ml was observed in An. funestus after to PBO, DEM and DEF whereas a trend for a decreased mortality was observed in An. gambiae after PBO pre-exposure. This study reveals a greater risk of chlorfenapyr resistance in An. gambiae populations than in An. funestus. However, the higher susceptibility in kdr-resistant mosquitoes points to higher efficacy of chlorfenapyr against the widespread kdr-based pyrethroid resistance.

Summary: The emergence of the SARS-CoV-2 Omicron variant altered patient risk profiles and shifted the trajectory of the COVID-19 pandemic. Therefore, sensitive serological tests capable of analyzing patient IgG responses to multiple variants in parallel are highly desirable. Here, we present an adaptable serological test based on yeast surface display and serum biopanning that characterizes immune profiles against SARS-CoV-2 Wuhan (B lineage), Delta (B.1.617.2 lineage), and Omicron (B.1.1.529 lineage) receptor-binding domain (RBD) variants. We examined IgG titers from 30 serum samples from COVID-19-convalescent and vaccinated cohorts in Switzerland, and assessed the relative affinity of polyclonal serum IgG for RBD domains. We demonstrate that serum IgGs from patients recovered from severe COVID-19 between March-June 2021 bound tightly to both original Wuhan and Delta RBD variants, but failed to recognize Omicron RBDs, representing an affinity loss of >10– to 20-fold. Our yeast immunoassay is easily tailored, expandable and parallelized with newly emerging RBD variants.

BackgroundBlood cultures (BC) are critical for the diagnosis of bloodstream infections, pathogen identification, and resistance testing. Guidelines recommend a blood volume of 8-10 mL per bottle as lower volumes result in decreased sensitivity. We aimed to evaluate factors for non-adherence to recommended volumes and assess the effects on diagnostic performance.MethodsFrom February to April 2020, we measured collected blood volumes by weighing all BC containers from inpatient samples at the University Hospital Basel. Information on BC volumes was merged with clinical and microbiological data, as well as nursing staff schedules. We analyzed factors associated with (i) BC sampling volume, (ii) reaching recommended volumes (≥8 mL), (iii) BC positivity, and (iv) time to positivity using linear and generalized linear mixed effect models.ResultsWe evaluated a total of 4'118 BC bottles collected from 686 patients. A total of 1'495 (36.3%) of all bottles contained the recommended filling volume of ≥8 mL. Using a central venous and arterial catheter for drawing blood resulted in an increase of filling volume by 0.26 mL (95% CI 0.10, 0.41) and 0.50 mL (95% CI 0.31, 0.69) compared to peripheral venipuncture, respectively. Each additional nursing staff working at the time of blood drawing was associated with 6% higher odds of achieving the recommended filling volume. We found no significant correlation between the filling volume and the positivity rate.ConclusionOur results indicate critical pre-analytical quality markers linked to BC collection procedures to reach recommended collection volumes. No significant impact on the positivity rate was found.

Abstract The jejunum plays crucial roles for the digestion and absorption of nutrients and minerals and for barrier functions that are essential for a healthy, productive life cycle of farm animals, including laying hens. Accordingly, knowledge of the molecular pathways that emerge in the intestine during development, and particularly at the beginning of laying activity, will help to derive strategies for improving nutrient efficiency in laying hens. In this study, jejunal samples were obtained from two high-yielding layer strains at five developmental stages (weeks 10, 16, 24, 30 and 60 of life) for RNA-sequencing, alongside the profiling of blood plasma parameters to approximate the dynamics of mineral homeostasis. The results reflected a marked distinction between the pre-laying and laying phase as inferred from levels of parathyroid hormone, triiodothyronine, estradiol, vitamin D, and calcium. Moreover, the expression patterns of the intestinal mucosa responded directly to the changing metabolic and nutritional profiles at the beginning of the laying phase in maturing high-yielding strains of laying hens. These comprise signaling events namely RANK/RANKL signaling and cellular senescence. Taken together, the timing of sexual maturity of laying hens demands closer examination to unravel metabolic requirements and associated endogenous mechanisms.

Small-scale fisheries are economically and culturally important throughout the world’s coastal waters. These fisheries, however, often have high bycatch rates of protected marine species. Bycatch in small scale gillnet fisheries is thought to be a major driver behind the declines of several sea turtle populations. Recent studies addressing this issue have identified net illumination as a potentially effective bycatch reduction technology (BRT) to reduce sea turtle interactions with gillnet fisheries. In Southeast Asia, small-scale gillnet fisheries make up a large components of fishing effort often in areas that overlap with important sea turtle habitat. We conducted controlled experiments of net illumination as a potential BRT to reduce sea turtle bycatch in a coastal gillnet fishery based in Paloh, West Kalimantan, Indonesia. Results indicated that net illumination significantly reduced multi-species sea turtle bycatch by 61.4% and specifically green sea turtles (Chelonia mydas) by 59.5%, while the CPUE of total catch and target species remained similar. Moreover, this study suggests that Indonesian fishers can increase their overall market value when using net illumination as the market value per unit effort (MVPUE) of both the total catch and target catch showed significant increases. These results suggest that net illumination could be an effective sea turtle conservation tool for small-scale coastal gillnet fisheries in Indonesia and potentially throughout Southeast Asia. In addition, data from the control treatments of this study also provided the first observer based sea turtle bycatch estimate for a small-scale gillnet fishery in Southeast Asia. Challenges to the broad scale implementation of net illumination to reduce this bycatch of sea turtles include the cost, availability of the technology, socialization of the BRT to fishers, and government interest and support for net illumination as a tool for bycatch reduction.

Abstract Phosphorus (P) and calcium (Ca) are critical for egg production in laying hens. Most of P in plant-based poultry diet is bound as phytic acid and needs to be hydrolysed before absorption. To increase P bioavailability, exogenous phytases or bioavailable rock phosphate is added in feed. There is growing evidence of the importance of miRNAs as the epicentre of intestinal homeostasis and functional properties. Therefore, we demonstrated the expression of miRNA profiles and the corresponding target genes due to the different levels of P (recommended vs. 20% reduction) and/or Ca (recommended vs. 15% reduction) in feed. Jejunal miRNA profiles of Lohmann Selected Leghorn (LSL) and Lohmann Brown (LB) laying hens strains were used (n = 80). A total of 34 and 76 miRNAs were differentially expressed (DE) in the different diet groups within LSL and LB strains respectively. In LSL, the DE miRNAs and their targets were involved in calcium signaling pathway, inositol phosphate metabolism, and mitochondrial dysfunction. Similarly, in LB miRNAs targets were enriched in metabolic pathways such as glutathione metabolism, phosphonate metabolism and vitamin B6 metabolism. Our results suggest that both strains employ different intrinsic strategies to cope with modulated P and Ca supply and maintain mineral homeostasis.

Arrays of tidal turbines are being considered for tidally energetic coastal sites which can be important habitat for many species of marine mammal. Understanding risks to marine mammals from collisions with moving turbine blades must be overcome before regulators can issue licenses for many developments. To understand these risks, it is necessary to understand how animals move around operational turbines and to document the rate at which interactions occur. We report on the design, and performance, of a seabed mounted sensor platform for monitoring the fine scale movements of cetaceans and pinnipeds around operational tidal turbines. The system comprises two high-frequency multibeam active sonars, which can accurately track animals in the horizontal plane. By offsetting the vertical angle of the sonars, the relative intensity of targets on the two sonars can also be used to resolve a vertical component of the animal location. For regularly vocalizing species, i.e., small cetaceans, a tetrahedral array of high frequency hydrophones mounted close to the sonars is used to measure both horizontal and vertical angles to cetacean echolocation clicks. This provides additional localization and tracking information for cetaceans and can also be used to distinguish between pinnipeds and cetaceans detected in the sonar data, based on the presence or absence of echolocation clicks. The system is cabled to shore for power, data transfer, and communications using turbine infrastructure. This allows for continuous operation over many months or years, which will be required to capture what may be rare interactions. The system was tested during a series of multi-week field tests, designed to test system integrity, carry out system calibrations, and test the efficiency of data collection, analyses, and archiving procedures. Overall, the system proved highly reliable, with the PAM system providing bearing accuracies to synthetic sounds of around 4.2 degrees for echolocation clicks with a signal to noise ratio above 15 dB. The system will be deployed close to an operational turbine in early 2022.

Tigernut (Cyperus esculentus Lativum) is an important but understudied and underutilized crop in Ghana. The tubers are highly appreciated for their health benefits and nutritive value. To contribute to the conservation process of tiger nut and identify elite genotypes, this study was conducted to assess phenotypic variability in tiger nut genotypes in Ghana. Sixty-four (64) genotypes were collected from major tiger nut growing areas in Ghana. The genotypes were field-grown and characterized based on phenotypic and yield traits. Similarity coefficient (Bray-Curtis) was between 0.82 and 0.98, indicating low variability in both qualitative and quantitative characters. The cophenetic correlation coefficient was 0.64. The genotypes were mainly brown with only a few black (6) tubers from the central region. Materials collected from parts of the eastern region (Aduamoah) generally recorded the highest tuber weight. Tuber weight depended on plant height and number of tillers. There were high tillering genetic materials among the genotypes. Tubers were categorised as oval (10), ovoid (33), or oblong (15). The genotypes clustered into two groups based on shoot and tuber characteristics, rather than on geographical origin. The low genetic diversity among the genotypes suggested either the possible existence of a network among tiger nut farmers in Ghana in circulating the planting material or some form of seed sorting for uniform and homogenous planting materials has been carried out over the years. Our results point to the imperativeness to expand the genetic base of the tiger nuts to facilitate its improvement in Ghana.

The foundation of contemporary weed management practices in many parts of the world is glyphosate. However, dependency on the effectiveness of herbicide practices has led to overuse through continuous growth of crops resistant to a single mode of action. In order to provide a cost-effective weed management strategy that does not promote glyphosate-resistant weed biotypes, differences between resistant and susceptible biotypes have to be identified accurately in the field conditions. Unmanned Aerial Vehicle (UAV)-assisted thermal and multispectral remote sensing has potential for detecting biophysical characteristics of weed biotypes during the growing season, which includes distinguishing glyphosate-susceptible and glyphosate-resistant weed populations based on canopy temperature and deep learning driven weed identification algorithms. The objective of this study was to identify herbicide resistance after glyphosate application in true field conditions by analyzing the UAV-acquired thermal and multispectral response of kochia, waterhemp, redroot pigweed, and common ragweed. The data were processed in ArcGIS for raster classification as well as spectral comparison of glyphosate-resistant and glyphosate-susceptible weeds. The classification accuracy between the sensors and classification methods of maximum likelihood, random trees, and Support Vector Machine (SVM) were compared. The random trees classifier performed the best at 4 days after application (DAA) for kochia with 62.9% accuracy. The maximum likelihood classifier provided the highest performing result out of all classification methods with an accuracy of 75.2%. A commendable classification was made at 8 DAA where the random trees classifier attained an accuracy of 87.2%. However, thermal reflectance measurements as a predictor for glyphosate resistance within weed populations in field condition was unreliable due to its susceptibility to environmental conditions. Normalized Difference Vegetation Index (NDVI) and a composite reflectance of 842 nm, 705 nm, and 740 nm wavelength managed to provide better classification results than thermal in most cases.

The invasive fall armyworm (FAW) is threatening maize production and the livelihoods of millions of smallholder farmers in the newly invaded areas in Africa and Asia. To control this new key pest and to overcome health, environmental, and resistance problems related to the indiscriminate use of insecticides, effective and sustainable alternative pest control approaches are needed. Here, we report on field trials that tested maltodextrin, neem-based products, ash, and soil, as well as the locally produced alata samina soap, in the Upper West and Greater Accra regions, Ghana. Significant reductions of larval numbers and crop damage, together with increased yields, were mostly achieved by applying the insecticide emamectin benzoate, which was considered the positive control in this set of trials. However, high efficiency and cost–benefit ratios were also achieved with two neem-based products. Maltodextrin was only efficient at one of the two sites, with a clear dose-dependent effect, while the higher dosage was nearly as effective as emamectin benzoate. Due to its relatively high product cost, maltodextrin is generally less cost-efficient. Ash and soil, as well as alata samina soap treatments, did not efficiently reduce FAW larval numbers or crop damage at the dosages tested; thus, they also did not significantly increase maize yields.

BACKGROUND:Food insecurity and poverty rates in Ghana are highest in the districts from latitude 8° N upwards. These have motivated several interventions aimed at addressing the food insecurity via promoting agricultural growth. An assessment of the overall impact of these interventions on food security is necessary to guide policy design and future interventions. METHODS AND FINDINGS:A systematic review was used to assess the cumulative evidence of the effect of development interventions, implemented from 2006 to 2016 on food security, especially in Northern Ghana. Information were retrieved from over 20 Government and non-Governmental organisations through online search and actual visits. The number of studies included in systematic review was 22. The study showed that a large number of interventions have been implemented in Northern Ghana over the study period. Access to quality extension services, training and capacity building was a major intervention strategy. About 82% of studies considered increasing production but only 14% of the studies reported on changes in yield. About 42% of the included studies used market access as a strategy but about 44% reported increase in incomes of beneficiaries (with only seven studies providing numerical evidence for this claim). The ranking of frequency of intervention strategies was in the order extension and capacity building > production > postharvest value addition > water and irrigation facilities > storage facilities > input supply. A substantial number of the studies had no counterfactuals, weakening confidence in attributing impacts on food security for even the beneficiaries. CONCLUSIONS:It is concluded that evidence for impacts of the interventions on food security was weak, or largely assumed. A logical recommendation is the need for development partners to synchronise their measurement and indicators of food security outcomes. It is also recommended that some food security indicators are explicitly incorporated into intervention design while bearing in mind the potential need for counterfactuals.

Fairness, through its many forms and definitions, has become an important issue facing the machine learning community. In this work, we consider how to incorporate group fairness constraints into kernel regression methods, applicable to Gaussian processes, support vector machines, neural network regression and decision tree regression. Further, we focus on examining the effect of incorporating these constraints in decision tree regression, with direct applications to random forests and boosted trees amongst other widespread popular inference techniques. We show that the order of complexity of memory and computation is preserved for such models and tightly binds the expected perturbations to the model in terms of the number of leaves of the trees. Importantly, the approach works on trained models and hence can be easily applied to models in current use and group labels are only required on training data.

Efficient approximation lies at the heart of large-scale machine learning problems. In this paper, we propose a novel, robust maximum entropy algorithm, which is capable of dealing with hundreds of moments and allows for computationally efficient approximations. We showcase the usefulness of the proposed method, its equivalence to constrained Bayesian variational inference and demonstrate its superiority over existing approaches in two applications, namely, fast log determinant estimation and information-theoretic Bayesian optimisation.

INTRODUCTION:Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far. MATERIALS AND METHODS:Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed. RESULTS:At 12 months, the mean BLL of infants was 7.41 μg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 μg/dL. Lead poisoning, defined as BLL>10 μg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin

OBJECTIVES:Social factors have profound effects on health. Children are especially vulnerable to social influences, particularly in their early years. Adverse social exposures in childhood can lead to chronic disorders later in life. Here, we sought to identify and evaluate the impact of social factors on child health in Ghana. As Ghana is unlikely to achieve the Millennium Development Goals' target of reducing child mortality by two-thirds between 1990 and 2015, we deemed it necessary to identify social determinants that might have contributed to the non-realisation of this goal. METHODS:ScienceDirect, PubMed, MEDLINE via EBSCO and Google Scholar were searched for published articles reporting on the influence of social factors on child health in Ghana. After screening the 98 articles identified, 34 of them that met our inclusion criteria were selected for qualitative review. RESULTS:Major social factors influencing child health in the country include maternal education, rural-urban disparities (place of residence), family income (wealth/poverty) and high dependency (multiparousity). These factors are associated with child mortality, nutritional status of children, completion of immunisation programmes, health-seeking behaviour and hygiene practices. CONCLUSIONS:Several social factors influence child health outcomes in Ghana. Developing more effective responses to these social determinants would require sustainable efforts from all stakeholders including the Government, healthcare providers and families. We recommend the development of interventions that would support families through direct social support initiatives aimed at alleviating poverty and inequality, and indirect approaches targeted at eliminating the dependence of poor health outcomes on social factors. Importantly, the expansion of quality free education interventions to improve would-be-mother's health knowledge is emphasised.

Defining phenotypes according to molecular features would promote the knowledge of functional traits like behaviour in both human and animal research. Beside physiological states or environmental factors, an innate predisposition of individual coping strategies was discussed, including the proactive and reactive pattern. According to backtest reactivity, animals assigned as high-resisting (proactive) and low-resisting (reactive) were immune challenged with tetanus toxoid in a time course experiment. Using the Affymetrix platform and qPCR, individual coping characteristics were reflected as gene expression signatures in porcine peripheral blood mononuclear cells (PBMC) at naïve state (day 0) and in response to the model antigen (day 14, day 28, and day 140). Further, the blood cell count was analysed at all stages. On the transcriptional level, processes acting on cell communication, vasculogenesis, and blood coagulation were highlighted in high-resisting animals at naïve state (day 0), temporarily blurred due to immune challenge (day 14) but subsequently restored and intensified (day 28). Notably, similar amounts of white and red blood cells, platelets and haematocrit between high-resisting and low-resisting samples suggest coping-specific expression patterns rather than alterations in blood cell distribution. Taken together, the gene expression patterns indicate that proactive pigs might favour molecular pathways enabling an effective strategy for defence and recovery. This corroborates the previously suggested belief, that proactive animals are prone to an increased number of injuries as an evolutionary inherited mechanism. In contrast to previous assumptions, coping-specific immunity in pigs lacks inherited shifts between cellular and humoral immune responses.

In age-related macular degeneration (AMD) the complement system is thought to be activated by chronic oxidative damage with genetic variants identified in the alternative pathway as susceptibility factors. However, the involvement of the lectin pathway of complement, a key mediator of oxidative damage, is controversial. This study investigated whether mannose-binding lectin (MBL) levels and genetic variants in lectin pathway proteins, are associated with the predisposition to and severity of AMD.MBL levels and single nucleotide polymorphisms (SNPs) in the MBL2 and the ficolin-2 (FCN2) gene were determined in 109 patients with AMD and 109 age- and sex-matched controls.MBL expression levels were equally distributed in both cases (early and late AMD) and controls (p>0.05). However, there was a trend towards higher median MBL levels in cases with late AMD compared to cases with early AMD (1.0 vs. 0.4 μg/ml, p = 0.09) and MBL deficiency (0.05 for all analyses) as were MBL2 genotypes. Similarly, there was no significant difference in allele frequencies in any SNPs in either the MBL2 or FCN2 gene in cases with early vs. late AMD.SNPs of lectin pathway proteins investigated in this study were not associated with AMD or AMD severity. However, MBL levels deserve further study in a larger cohort of early vs. late AMD patients to elucidate any real effect on AMD severity.

BACKGROUND: In HIV-infected patients, prediction of Cytomegalovirus (CMV) disease remains difficult. A protective role of mannan-binding lectin (MBL) and ficolins against CMV disease has been reported after transplantation, but the impact in HIV-infected patients is unclear. METHODS: In a case-control study nested within the Swiss HIV Cohort Study, we investigated associations between plasma levels of MBL/ficolins and CMV disease. We compared HIV-infected patients with CMV disease (cases) to CMV-seropositive patients without CMV disease (controls) matched for CD4 T-cells, sampling time, and use of combination antiretroviral therapy. MBL and M-ficolin, L-ficolin, and H-ficolin were quantified using ELISA. RESULTS: We analysed 105 cases and 105 matched controls. CMV disease was neither associated with MBL (odds ratio [OR] 1.03 per log(10) ng/mL increase (95% CI 0.73-1.45)) nor with ficolins (OR per log(10) ng/mL increase 0.66 (95% CI 0.28-1.52), 2.34 (95% CI 0.44-12.36), and 0.89 (95% CI 0.26-3.03) for M-ficolin, L-ficolin, and H-ficolin, respectively). We found no evidence of a greater association between MBL and CMV disease in patients with low CD4 counts; however in the multivariable analysis, CMV disease was more likely in patients with an increased HIV RNA (OR 1.53 per log(10) copies/mL; 95% CI 1.08-2.16), or a shorter duration of HIV-infection (OR 0.91 per year; 95% CI 0.84-0.98). CONCLUSIONS: CMV disease is not associated with low levels of MBL/ficolins, suggesting a lack of a protective role in HIV-infected patients.

BACKGROUND: Pathways coordinated by innate pattern recognition receptors like mannose-binding lectin (MBL) and nucleotide-binding oligomerization domain 2 (NOD2) are among the first immune responses to Staphylococcus aureus (S. aureus) bloodstream infections (BSI) in animal models, but human data are limited. Here, we investigated the role of MBL deficiency and NOD2 mutations in the predisposition to and severity of S. aureus BSI. PATIENTS AND METHODS: A matched case-control study was undertaken involving 70 patients with S. aureus BSI and 70 age- and sex-matched hospitalized controls. MBL levels, MBL2 and NOD2 polymorphisms were analyzed. RESULTS: After adjusting for potential confounders, MBL deficiency (

BACKGROUND: In various animal models pregnancy diets have been shown to affect offspring phenotype. Indeed, the underlying programming of development is associated with modulations in birth weight, body composition, and continual diet-dependent modifications of offspring metabolism until adulthood, producing the hypothesis that the offspring's transcriptome is permanently altered depending on maternal diet. METHODOLOGY/PRINCIPAL FINDINGS: To assess alterations of the offspring's transcriptome due to gestational protein supply, German Landrace sows were fed isoenergetic diets containing protein levels of either 30% (high protein--HP) or 12% (adequate protein--AP) throughout their pregnancy. Offspring muscle tissue (M. longissimus dorsi) was collected at 94 days post conception (dpc), and 1, 28, and 188 days post natum (dpn) for use with Affymetrix GeneChip Porcine Genome Arrays and subsequent statistical and Ingenuity pathway analyses. Numerous transcripts were found to have altered abundance at 94 dpc and 1 dpn; at 28 dpn no transcripts were altered, and at 188 dpn only a few transcripts showed a different abundance between diet groups. However, when assessing transcriptional changes across developmental time points, marked differences were obvious among the dietary groups. Depending on the gestational dietary exposure, short- and long-term effects were observed for mRNA expression of genes related to cell cycle regulation, energy metabolism, growth factor signaling pathways, and nucleic acid metabolism. In particular, the abundance of transcripts related to cell cycle remained divergent among the groups during development. CONCLUSION: Expression analysis indicates that maternal protein supply induced programming of the offspring's genome; early postnatal compensation of the slight growth retardation obvious at birth in HP piglets resulted, as did a permanently different developmental alteration and responsiveness to the common environment of the transcriptome. The transcriptome modulations are interpreted as the molecular equivalent of developmental plasticity of the offspring that necessitates adaptation and maintenance of the organismal phenotype.

BackgroundThe Mannose-binding lectin (MBL) pathway of complement plays a pivotal role in the pathogenesis of ischemia/reperfusion (I/R) injury after experimental ischemic stroke. As comparable data in human ischemic stroke are limited, we investigated in more detail the association of MBL deficiency with infarction volume and functional outcome in a large cohort of patients receiving intravenous thrombolysis or conservative treatment.Methodology/principal findingsIn a post hoc analysis of a prospective cohort study, admission MBL concentrations were determined in 353 consecutive patients with an acute ischemic stroke of whom 287 and 66 patients received conservative and thrombolytic treatment, respectively. Stroke severity, infarction volume, and functional outcome were studied in relation to MBL concentrations at presentation to the emergency department. MBL levels on admission were not influenced by the time from symptom onset to presentation (p = 0.53). In the conservative treatment group patients with mild strokes at presentation, small infarction volumes or favorable outcomes after three months demonstrated 1.5 to 2.6-fold lower median MBL levels (p = 0.025, p = 0.0027 and p = 0.046, respectively) compared to patients with more severe strokes. Moreover, MBL deficient patients (ConclusionsMBL deficiency is associated with smaller cerebral infarcts and favorable outcome in patients receiving conservative treatment. Our data suggest an important role of the lectin pathway in the pathophysiology of cerebral I/R injury and might pave the way for new therapeutic interventions.

In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. The underlying programming of fetal development was shown to be associated with an increased risk of degenerative diseases in adulthood, including the metabolic syndrome. There are clues that diet-dependent modifications of the metabolism during fetal life can persist until adulthood. This leads to the hypothesis that the offspring's transcriptomes show short-term and long-term changes depending on the maternal diet. To this end pregnant German landrace gilts were fed either a high protein diet (HP, 30% CP) or an adequate protein diet (AP, 12% CP) throughout pregnancy. Hepatic transcriptome profiles of the offspring were analyzed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn). Depending on the gestational dietary exposure, mRNA expression levels of genes related to energy metabolism, N-metabolism, growth factor signaling pathways, lipid metabolism, nucleic acid metabolism and stress/immune response were affected either in a short-term or in a long-term manner. Gene expression profiles at fetal stage 94 dpc were almost unchanged between the diets. The gestational HP diet affected the hepatic expression profiles at prenatal and postnatal stages. The effects encompassed a modulation of the genome in terms of an altered responsiveness of energy and nutrient sensing pathways. Differential expression of genes related to energy production and nutrient utilization contribute to the maintenance of development and growth performance within physiological norms, however the modulation of these pathways may be accompanied by a predisposition for metabolic disturbances up to adult stages.