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Expression of the Alzheimer's disease associated polypeptide Aβ42 and the human polypeptide hormon islet amyloid polypeptide (hIAPP) and the prohormone precursor (hproIAPP) in neurons of Drosophila melanogaster leads to the formation of protein aggregates in the fat body tissue surrounding the brain. We determined the structure of these membrane-encircled protein aggregates using transmission electron microscopy (TEM) and observed the dissolution of protein aggregates after starvation. Electron tomography (ET) as an extension of transmission electron microscopy revealed that these aggregates were comprised of granular subunits having a diameter of 20 nm aligned into highly ordered structures in all three dimensions. The three dimensional (3D) lattice of hIAPP granules were constructed of two unit cells, a body centered tetragonal (BCT) and a triclinic unit cell. A 5-fold twinned structure was observed consisting of the cyclic twinning of the BCT and triclinic unit cells. The interaction between the two nearest hIAPP granules in both unit cells is not only governed by the van der Waals forces and the dipole-dipole interaction but potentially also by filament-like structures that can connect the nearest neighbors. Hence, our 3D structural analysis provides novel insight into the aggregation process of hIAPP in the fat body tissue of Drosophila melanogaster. [ABSTRACT FROM AUTHOR]

Grafting has been widely applied to melon (Cucumis melo L.) production to alleviate obstacles of continuous cropping and control soil-borne diseases. However, grafting often leads to a decline of fruit quality. For example, sometimes bitter fruits are produced on grafted plants. However, the underlying physiological mechanism still remains unclear. This study investigated the effects of different rootstocks on the taste of fruits of the Balengcui, an oriental melon cultivar, during summer production. The results showed that all grafted plants with Cucurbita maxima Duch. rootstocks produced bitter fruits, while non-grafted plants and plants grafted onto muskmelon rootstocks produced no bitter fruits. Liquid chromatography–mass spectrometry and metabonomic analysis were performed to investigate the mechanism underlying the occurrence of bitter fruits. Metabolite comparisons of fruits from plants grafted onto Ribenxuesong rootstocks both with non-grafted plants and plants grafted onto muskmelon rootstocks showed that 17 metabolites including phospholipids, cucurbitacins and flavonoids, exhibited changes. The three Cucurbitacins, Cucurbitacin O, Cucurbitacin C, and Cucurbitacin S, increased dramatically. The 10 phospholipids PS(18:1(9Z)/18:2(9Z,12Z)), PS(P-18:0/15:0), PA(18:1(11Z)/18:1(11Z)), PE(16:0/18:0), PS(O-16:0/17:2(9Z,12Z)), PI(16:0/18:2(9Z,12Z)), PA(15:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PS(P-16:0/17:2(9Z,12Z)), PS(22:0/22:1(11Z)), and PA(17:1(9Z)/0:0)) were significantly decreased, while two PA (16:0/18:2 (9Z, 12Z) and 16:0/18:1 (11Z)), two flavonoids (pelargonidin 3-(6''-malonylglucoside)-5-glucoside and malvidin 3-rutinoside) significantly increased in fruits of plants grafted onto Cucurbita maxima Duch. rootstocks. These metabolites were involved in the glycerophospholipid metabolic pathway, the mevalonate pathway, and the phenylpropanoid pathway. In summary, these results showed that the bitter fruits of grafted Balengcui were caused by Cucurbita maxima Duch. rootstocks. Phospholipids, cucurbitacins, and flavonoids were the key contributors for the occurrence of bitter fruits in Balengcui melon after grafting onto Cucurbita maxima Duch. rootstocks. [ABSTRACT FROM AUTHOR]

Conjugated linoleic acid was detected in rabbit caecotrophs, due to the presence of microbial lipid activity in rabbit cecum. However, the effect of CLA as a functional food in growing rabbit is not well established. Therefore, this study was conducted to determine the effect of CLA on production, meat quality, and its nutrigenomic effect on edible parts of rabbit carcass including skeletal muscle, liver, and adipose tissue. Therefore, seventy five weaned V-Line male rabbits, 30 days old, were randomly allocated into three dietary treatments receiving either basal control diet, diet supplemented with 0.5% (CLAL), or 1% CLA (CLAH). Total experimental period (63 d) was segmented into 7 days adaptation and 56 days experimental period. Dietary supplementation of CLA did not alter growth performance, however, the fat percentage of longissimus lumborum muscle was decreased, with an increase in protein and polyunsaturated fatty acids (PUFA) percentage. Saturated fatty acids (SFA) and mono unsaturated fatty acids (MUFA) were not increased in CLA treated groups. There was tissue specific sensing of CLA, since subcutaneous adipose tissue gene expression of PPARA was downregulated, however, CPT1A tended to be upregulated in liver of CLAL group only (P = 0.09). In skeletal muscle, FASN and PPARG were upregulated in CLAH group only (P ≤0.01). Marked cytoplasmic vacuolation was noticed in liver of CLAH group without altering hepatocyte structure. Adipocyte size was decreased in CLA fed groups, in a dose dependent manner (P <0.01). Cell proliferation determined by PCNA was lower (P <0.01) in adipose tissue of CLA groups. Our data indicate that dietary supplementation of CLA (c9,t11-CLA and t10,c12- CLA) at a dose of 0.5% in growing rabbit diet produce rabbit meat rich in PUFA and lower fat % without altering growth performance and hepatocyte structure. [ABSTRACT FROM AUTHOR]

We recently introduced a MαCD-based method to efficiently replace virtually the entire population of plasma membrane outer leaflet phospholipids and sphingolipids of cultured mammalian cells with exogenous lipids (Li et al, (2016) Proc. Natl. Acad. Sci USA 113:14025–14030). Here, we show if the lipid-to- MαCD ratio is too high or low, cells can round up and develop membrane leakiness. We found that this cell damage can be reversed/prevented if cells are allowed to recover from the exchange step by incubation in complete growth medium. After exchange and transfer to complete growth medium cell growth was similar to that of untreated cells. In some cases, cell damage was also prevented by carrying out exchange at close to room temperature (rather than at 37°C). Exchange with lipids that do (sphingomyelin) or do not (unsaturated phosphatidylcholine) support a high level of membrane order in lipid vesicles had the analogous effect on plasma membrane order, confirming exogenous lipid localization in the plasma membrane. Importantly, changes in lipid composition and plasma membrane properties after exchange and recovery persisted for several hours. Thus, it should be possible to use lipid exchange to investigate the effect of plasma membrane lipid composition upon several aspects of membrane structure and function. [ABSTRACT FROM AUTHOR]

Introduction: Propofol causes a profound inhibition of fatty acid oxidation and reduces spare electron transfer chain capacity in a range of human and rodent cells and tissues–a feature that might be related to the pathogenesis of Propofol Infusion Syndrome. We aimed to explore the mechanism of propofol-induced alteration of bioenergetic pathways by describing its kinetic characteristics. Methods: We obtained samples of skeletal and cardiac muscle from Wistar rat (n = 3) and human subjects: vastus lateralis from hip surgery patients (n = 11) and myocardium from brain-dead organ donors (n = 10). We assessed mitochondrial functional indices using standard SUIT protocol and high resolution respirometry in fresh tissue homogenates with or without short-term exposure to a range of propofol concentration (2.5–100 μg/ml). After finding concentrations of propofol causing partial inhibition of a particular pathways, we used that concentration to construct kinetic curves by plotting oxygen flux against substrate concentration during its stepwise titration in the presence or absence of propofol. By spectrophotometry we also measured the influence of the same propofol concentrations on the activity of isolated respiratory complexes. Results: We found that human muscle and cardiac tissues are more sensitive to propofol-mediated inhibition of bioenergetic pathways than rat’s tissue. In human homogenates, palmitoyl carnitine-driven respiration was inhibited at much lower concentrations of propofol than that required for a reduction of electron transfer chain capacity, suggesting FAO inhibition mechanism different from downstream limitation or carnitine-palmitoyl transferase-1 inhibition. Inhibition of Complex I was characterised by more marked reduction of Vmax, in keeping with non-competitive nature of the inhibition and the pattern was similar to the inhibition of Complex II or electron transfer chain capacity. There was neither inhibition of Complex IV nor increased leak through inner mitochondrial membrane with up to 100 μg/ml of propofol. If measured in isolation by spectrophotometry, propofol 10 μg/ml did not affect the activity of any respiratory complexes. Conclusion: In human skeletal and heart muscle homogenates, propofol in concentrations that are achieved in propofol-anaesthetized patients, causes a direct inhibition of fatty acid oxidation, in addition to inhibiting flux of electrons through inner mitochondrial membrane. The inhibition is more marked in human as compared to rodent tissues. [ABSTRACT FROM AUTHOR]

Background: Physical exercise has been shown to be effective in relation to fatigue, aerobic fitness, and lower body strength in men with prostate cancer. However, research into the clinically relevant effects of interventions conducted in heterogeneous patient populations and in real-life clinical practice settings is warranted.Methods and Findings: We conducted a pragmatic, multicentre, parallel randomised controlled trial in 5 Danish urological departments. Recruitment began in May 2015, the first participant was randomised in June 2015, and the last participant was included in February 2017. In total, 214 men with prostate cancer were randomly assigned to either 6 months of free-of-charge football training twice weekly at a local club (football group [FG]) (n = 109) or usual care (usual care group [UG]) (n = 105), including brief information on physical activity recommendations at randomisation. Participants were on average 68.4 (SD 6.2) years old, 157 (73%) were retired, 87 (41%) were on castration-based treatment, 19 (9%) had received chemotherapy, and 41 (19%) had skeletal metastases at baseline. In this 1-year follow-up study, we evaluated the effects of community-based football training on the following outcomes: primary outcome, quality of life; secondary outcomes: continuation of football after 6 months, hip and lumbar spine bone mineral density (BMD), mental health score, fat and lean body mass, and safety outcomes, i.e., fractures, falls, and hospital admissions. Intention to treat (ITT) and per protocol (PP) analyses were conducted. No statistically significant between-group difference was observed in change in prostate-cancer-specific quality of life (ITT: 1.9 points [95% CI -1.9 to 5.8], p = 0.325; PP: 3.6 points [95% CI -0.9 to 8.2], p = 0.119). A statistically significant between-group difference was observed in change in total hip BMD, in favour of FG (0.007 g/cm2 [95% CI 0.004 to 0.013], p = 0.037). No differences were observed in change in lumbar spine BMD or lean body mass. Among patients allocated to football, 59% chose to continue playing football after the end of the 6-month intervention period. At 1-year follow-up in the PP population, FG participants had more improvement on the Mental Component Summary (2.9 [95% CI 0.0 to 5.7], p = 0.048 points higher) than UG participants, as well as a greater loss of fat mass (-0.9 kg [95% CI -1.7 to -0.1], p = 0.029). There were no differences between groups in relation to fractures or falls. Hospital admissions were more frequent in UG compared to FG (33 versus 20; the odds ratio based on PP analysis was 0.34 for FG compared to UG). There were 3 deaths in FG and 4 in UG. Main limitations of the study were the physically active control group and assessment of physical activity by means of self-report.Conclusions: In this trial, participants allocated to football appeared to have improved hip BMD and fewer hospital admissions. Men who played football more than once a week for 1 year lost fat mass and reported improved mental health. Community-based football proved to be acceptable, even when club membership was not subsidised.Trial Registration: ClinicalTrials.gov NCT02430792. [ABSTRACT FROM AUTHOR]

Objective: Although previous studies have reported a negative relationship between serum bilirubin concentration and the development of diabetes mellitus (DM), the relationship between bilirubin and insulin resistance has not been thoroughly assessed. This study was designed to determine the relationships between bilirubin, body fat distribution, and adipose tissue inflammation in patients with type 2 DM and the effect of bilirubin in an obese animal model. Method: Body fat distribution was measured using an abdominal dual bioelectrical impedance analyzer in patients with type 2 DM. We also measured glycemic control, lipid profile, serum bilirubin concentration and other clinical characteristics, and determined their relationships with body fat distribution. In the animal study, biliverdin (20 mg/kg daily) was orally administered to high-fat diet (HFD)-induced obese (DIO) mice for 2 weeks, after which intraperitoneal insulin tolerance testing was performed. Then, adipocyte area, adipocytokine expression, and macrophage polarization were evaluated in epididymal adipose tissues. Results: In the clinical study, univariate analysis showed that a lower bilirubin concentration was significantly correlated with higher body mass index, waist circumference, triglyceride, uric acid, creatinine, visceral fat area and lower HDL-C. In multivariate analyses, bilirubin concentration significantly correlated with diastolic blood pressure, creatinine, and visceral fat area. However, there was no association between bilirubin concentration and subcutaneous fat area. In the animal study, DIO mice treated with biliverdin had smaller adipocytes than untreated DIO mice and biliverdin improved HFD-induced insulin resistance. Biliverdin treatment reversed the higher gene expression of Cd11c, encoding an M1 macrophage marker, and Tnfa, encoding the proinflammatory cytokine tumor necrosis factor-α, in the adipose tissues of DIO mice. These data suggest biliverdin administration alleviates insulin resistance by ameliorating inflammation and the dysregulation of adipocytokine expression in adipose tissues of DIO mice. Conclusions: Bilirubin may protect against insulin resistance by ameliorating visceral obesity and adipose tissue inflammation. [ABSTRACT FROM AUTHOR]

Background and objectives: The construction of whole-body magnetic resonance (MR) imaging atlases allows to perform statistical analysis with applications in anomaly detection, longitudinal, and correlation studies. Atlas-based methods require a common coordinate system to which all the subjects are mapped through image registration. Optimisation of the reference space is an important aspect that affects the subsequent analysis of the registered data, and having a reference space that is neutral with respect to local tissue volume is valuable in correlation studies. The purpose of this work is to generate a reference space for whole-body imaging that has zero voxel-wise average volume change when mapped to a cohort. Methods: This work proposes an approach to register multiple whole-body images to a common template using volume changes to generate a synthetic reference space, starting with an initial reference and refining it by warping it with a deformation that brings the voxel-wise average volume change associated to the mappings of all the images in the cohort to zero. Results: Experiments on fat/water separated whole-body MR images show how the method effectively generates a reference space neutral with respect to volume changes, without reducing the quality of the registration nor introducing artefacts in the anatomy, while providing better alignment when compared to an implicit reference groupwise approach. Conclusions: The proposed method allows to quickly generate a reference space neutral with respect to local volume changes, that retains the registration quality of a sharp template, and that can be used for statistical analysis of voxel-wise correlations in large datasets of whole-body image data. [ABSTRACT FROM AUTHOR]

The use of biopolymers as elicitors in controlling plant diseases is gaining momentum world-wide due to their eco-friendly and non-toxic nature. In the present study, we have used an algal biopolymer (sodium alginate) and tested its applicability as an elicitor in inducing resistance factors against Alternaria solani, which causes early blight disease in Solanum lycopersicum (tomato plant). We have pre-treated tomato plants with different concentrations of sodium alginate (0.2%, 0.4%, and 0.6%) before A. solani infection. We found that sodium alginate has effectively controlled the growth of A. solani. In addition, a significant increase in the expression levels of SOD was observed in response to pathogen infection. The increased protease inhibitors activity further suggest that sodium alginate restrict the development of A. solani infection symptoms in tomato leaves. This corroborates well with the cell death analysis wherein increased sodium alginate pre-treatment results in decreased cell death. Also, the expression profile analyses reveal the induction of genes only in sodium alginate-pretreated tomato leaves, which are implicated in plant defense mechanism. Taken together, our results suggest that sodium alginate can be used as an elicitor to induce resistance against A. solani in tomato plants. [ABSTRACT FROM AUTHOR]

Genetic divergence is impacted by many factors, including phylogenetic history, gene flow, genetic drift, and divergent selection. Rotifers are an important component of aquatic ecosystems, and genetic variation is essential to their ongoing adaptive diversification and local adaptation. In addition to coding sequence divergence, variation in gene expression may relate to variable heat tolerance, and can impose ecological barriers within species. Temperature plays a significant role in aquatic ecosystems by affecting species abundance, spatio-temporal distribution, and habitat colonization. Recently described (formerly cryptic) species of the Brachionus calyciflorus complex exhibit different temperature tolerance both in natural and in laboratory studies, and show that B. calyciflorus sensu stricto (s.s.) is a thermotolerant species. Even within B. calyciflorus s.s., there is a tendency for further temperature specializations. Comparison of expressed genes allows us to assess the impact of stressors on both expression and sequence divergence among disparate populations within a single species. Here, we have used RNA-seq to explore expressed genetic diversity in B. calyciflorus s.s. in two mitochondrial DNA lineages with different phylogenetic histories and differences in thermotolerance. We identify a suite of candidate genes that may underlie local adaptation, with a particular focus on the response to sustained high or low temperatures. We do not find adaptive divergence in established candidate genes for thermal adaptation. Rather, we detect divergent selection among our two lineages in genes related to metabolism (lipid metabolism, metabolism of xenobiotics). [ABSTRACT FROM AUTHOR]

Radiological biomarkers have been reported for multiple system atrophy and progressive supranuclear palsy, but serum/plasma biomarkers for each disorder have not been established. In this context, we performed a pilot study to identify disease-specific plasma biomarkers for multiple system atrophy and progressive supranuclear palsy. Plasma samples collected from 20 progressive supranuclear palsy patients, 16 multiple system atrophy patients and 20 controls were investigated by comprehensive metabolome analysis using capillary electrophoresis mass spectrometry and liquid chromatography mass spectrometry. Medication data were obtained from patients with multiple system atrophy and progressive supranuclear palsy, and correlations with associated metabolites were examined. Receiver operating characteristics curve analyses were used to investigate diagnostic values for each disorder. The levels of 15 and eight metabolites were significantly changed in multiple system atrophy and progressive supranuclear palsy, respectively. Multiple system atrophy was mainly characterized by elevation of long-chain fatty acids and neurosteroids, whereas progressive supranuclear palsy was characterized by changes in the level of oxidative stress-associated metabolites. Receiver operating characteristic curve analyses revealed that patients with multiple system atrophy or progressive supranuclear palsy were effectively differentiated from controls by 15 or 7 metabolites, respectively. Disease-specific metabolic changes of multiple system atrophy and progressive supranuclear palsy were identified. These biomarker sets should be replicated in a larger sample. [ABSTRACT FROM AUTHOR]

The reduction of synthetic fungicides in agriculture is necessary to guarantee a sustainable production that protects the environment and consumers’ health. Downy mildew caused by the oomycete Plasmopara viticola is the major pathogen in viticulture worldwide and responsible for up to 60% of pesticide treatments. Alternatives to reduce fungicides are thus utterly needed to ensure sustainable vineyard-ecosystems, consumer health and public acceptance. Essential oils (EOs) are amongst the most promising natural plant protection alternatives and have shown their antibacterial, antiviral and antifungal properties on several agricultural crops. However, the efficiency of EOs highly depends on timing, application method and the molecular interactions between the host, the pathogen and EO. Despite proven EO efficiency, the underlying processes are still not understood and remain a black box. The objectives of the present study were: a) to evaluate whether a continuous fumigation of a particular EO can control downy mildew in order to circumvent the drawbacks of direct application, b) to decipher molecular mechanisms that could be triggered in the host and the pathogen by EO application and c) to try to differentiate whether essential oils directly repress the oomycete or act as plant resistance primers. To achieve this a custom-made climatic chamber was constructed that enabled a continuous fumigation of potted vines with different EOs during long-term experiments. The grapevine (Vitis vinifera) cv Chasselas was chosen in reason of its high susceptibility to Plasmopara viticola. Grapevine cuttings were infected with P. viticola and subsequently exposed to continuous fumigation of different EOs at different concentrations, during 2 application time spans (24 hours and 10 days). Experiments were stopped when infection symptoms were clearly observed on the leaves of the control plants. Plant physiology (photosynthesis and growth rate parameters) were recorded and leaves were sampled at different time points for subsequent RNA extraction and transcriptomics analysis. Strikingly, the Oregano vulgare EO vapour treatment during 24h post-infection proved to be sufficient to reduce downy mildew development by 95%. Total RNA was extracted from leaves of 24h and 10d treatments and used for whole transcriptome shotgun sequencing (RNA-seq). Sequenced reads were then mapped onto the V. vinifera and P. viticola genomes. Less than 1% of reads could be mapped onto the P. viticola genome from treated samples, whereas up to 30% reads from the controls mapped onto the P. viticola genome, thereby confirming the visual observation of P. viticola absence in the treated plants. On average, 80% of reads could be mapped onto the V. vinifera genome for differential expression analysis, which yielded 4800 modulated genes. Transcriptomic data clearly showed that the treatment triggered the plant’s innate immune system with genes involved in salicylic, jasmonic acid and ethylene synthesis and signaling, activating Pathogenesis-Related-proteins as well as phytoalexin synthesis. These results elucidate EO-host-pathogen interactions for the first time and indicate that the antifungal efficiency of EO is mainly due to the triggering of resistance pathways inside the host plants. This is of major importance for the production and research on biopesticides, plant stimulation products and for resistance-breeding strategies. [ABSTRACT FROM AUTHOR]

Background: Very few data are available on treatment in HIV Late presenter population that still represents a clinical challenge. Methods: Prospective, multicenter, randomized open-label, 2 arm, phase-3 trial comparing the 48-week virological response of two different regimens: abacavir/lamivudine + darunavir/r vs abacavir/lamivudine + raltegravir in antiretroviral naive with CD4+ counts < 200/mm3 and a viral load (VL)<500,000 copies/mL. The primary Endpoint was the proportion of patients with undetectable viremia (VL<50 copies/mL) after 48 weeks. The planned sample size for this trial was 350 patients. Results: In 3 years, 53 patients were screened and 46 enrolled: 22 randomized to raltegravir and 24 to darunavir/r; 7 patients were excluded, 4 because of a VL >500,000 copies/mL and 3 for HLAB5701 positivity. The snapshot analysis at 48 weeks showed a virologic success of 77.3% in raltegravir and 66.7% in darunavir/r. Time to starting treatment was 34.5 days in raltegravir and 53 days in darunavir/r. At the as treated analysis, the median CD4 counts at 48 weeks was 297 cells/μL in raltegravir and 239 cells/μL in darunavir/r. No difference in total cholesterol, while triglycerides were higher in the darunavir/r arm. No statistical analyses were performed due to the low number of patients enrolled. Conclusions: Late presenter patients are frequent but very difficult to enroll in clinical trials, especially in western countries. These regimens and the conditions of many patients could not allow the test and treat strategy. The rate of virologic success was higher than 65% in both arms with a median CD4 cell count >200/μL at week 48. Trial registration: EUDRACT number: [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) patients are predisposed to several diabetes-related complications. Dysregulation of the haemostatic mechanisms have been implicated. There are however no current studies assessing the levels and activity of protein C (PC), protein S (PS), and antithrombin III (AT III), which are essential in haemostatic regulation, in a single cohort of T2DM patients. This study evaluated the effect of poorly-managed T2DM on the levels and activity of PC, PS, and AT III. Methods: This cross-sectional study was conducted at the Diabetes Clinic, Cocoa Clinic in Kumasi, Ghana. A total of 242 T2DM patients, comprising 152 patients with poorly-managed diabetes and 90 well-managed diabetes patients, were recruited for the study. Fasting blood glucose, liver function tests and lipid profile were performed for each respondent. Glycated haemoglobin (HbA1c) was estimated by turbidimetric inhibition immunoassay. The levels and activity of PC, PS and AT III were measured by solid phase sandwich ELISA method. Results: There was a negative correlation between HbA1c and the levels and activity of PC, PS and AT III. The levels and activity of PC [(5.78 vs 4.64 μg/ml, p<0.0001) and (42.22 vs 36.21 U/ml, p = 0.01) respectively], PS [(22.55 vs 20.29 μg/ml, p = 0.010) and (235.94 vs 211.67 U/ml, p<0.0001) respectively] and AT III [(16.28 vs 14.41μg/ml, p<0.0001) and (176.01 vs 160.09 U/ml, p = 0.03) respectively] were significantly increased in patients with well-managed T2DM compared to the poorly-managed diabetes patients. Likewise, the levels and activity of PC, PS, and AT III was higher among T2DM patients using statins than patients who were statin-naïve. Among patients with well-managed T2DM, those who were on statins had significantly higher levels and activities of PC, PS, and AT III compared to well-managed T2DM patients not on statins. However, there no statistically significant differences between the level and activity of PC, PS, and AT III among poorly-managed T2DM patients with respect to statin status. Conclusion: Poorly-managed type 2 diabetes mellitus is associated with reduced levels and activity of PC, PS and AT III compared to well-managed T2DM. Though use of statins may improve the levels and activity of the PC, PS and AT III in T2DM, their effect is limited in the presence of poorly-controlled T2DM. Proper management of diabetes is essential to reduce the likelihood of thrombotic events among T2DM patients. [ABSTRACT FROM AUTHOR]

Ascorbic acid was used for the first time to synthesize cellulose nanoparticles (CNP) extracted from okra mucilage. The physical properties of the CNP including their size distribution, and crystalline structures were investigated. The rheological properties of the cellulose nanofluid (CNF) were compared with the bulk okra mucilage and commercial polymer xanthan. The interfacial properties of the CNF at the interface of oil-water (O/W) system were investigated at different concentrations and temperatures. The effects of the interaction between the electrolyte and ultrasonic were determined. Core flooding experiment was conducted at reservoir condition to justify the effect of the flow behaviour and disperse phase behaviour of CNF on additional oil recovery. The performance of the CNF was compared to conventional EOR chemical. The combined method of ultrasonic, weak-acid hydrolysis and nanoprecipitation were effective in producing spherical and polygonal nanoparticles with a mean diameter of 100 nm, increased yield of 51% and preserved crystallinity respectively. The zeta potential result shows that the CNF was stable, and the surface charge signifies long term stability of the fluid when injected into oil field reservoirs. The CNF, okra and xanthan exhibited shear-thinning and pseudoplastic behaviour. The IFT decreased with increase in concentration of CNF, electrolyte and temperature. The pressure drop data confirmed the stability of CNF at 120°C and the formation of oil bank was enough to increase the oil recovery by 20%. CNF was found to be very effective in mobilizing residual oil at high-temperature high-pressure (HTHP) reservoir condition. The energy and cost estimations have shown that investing in ultrasonic-assisted weak-acid hydrolysis is easier, cost-effective, and can reduce energy consumption making the method economically advantageous compared to conventional methods. [ABSTRACT FROM AUTHOR]

Although animal trials are the most accurate approach to determine the metabolisable energy (ME) content of pet food, these are expensive and labour-intensive. Instead, various equations have been proposed to predict ME content, but no single method is universally recommended. Data from canine and feline feeding studies, conducted according to Association of American Feed Control Officials recommendations, over a 6-year period at a single research site, were utilised to determine the performance of different predictive equations. Predictive equations tested included the modified Atwater (MA equation), NRC 2006 equations using both crude fibre (NRC 2006cf) and total dietary fibre (NRC 2006tdf), and new equations reported in the most recent study assessing ME predictive equations (Hall equations; PLoS ONE 8(1): e54405). Where appropriate, equations were tested using both predicted gross energy (GE) and GE measured by bomb calorimetry. Associations between measured and predicted ME were compared with Deming regression, whilst agreement was assessed with Bland-Altman plots. 335 feeding trials were included, comprising 207 canine (182 dry food; 25 wet food) and 128 feline trials (104 dry food, 24 wet food). Predicted ME was positively associated with measured ME whatever the equation used (P<0.001 for all). Agreement between predicted and actual ME was worst for the MA equation, for all food types, with evidence of both a systematic bias and proportional errors evident for all food types. The NRC 2006cf and Hall equations were intermediate in performance, whilst the NRC 2006tdf equations performed best especially when using measured rather than predicted GE, with the narrowest 95% limits of agreement, minimal bias and proportional error. In conclusion, when predicting ME content of pet food, veterinarians, nutritionists, pet food manufacturers and regulatory bodies are strongly advised to use the NRC 2006tdf equations and using measured rather than predicted GE. [ABSTRACT FROM AUTHOR]

Background: Somatic migration of Toxocara canis- and T. cati-larvae in humans may cause neurotoxocarosis (NT) when larvae accumulate and persist in the central nervous system (CNS). Host- or parasite-induced immunoregulatory processes contribute to the pathogenesis; however, detailed data on involvement of bioactive lipid mediators, e.g. oxylipins or eico-/docosanoids, which are involved in the complex molecular signalling network during infection and inflammation, are lacking. Methodology/Principal findings: To elucidate if T. canis- and T. cati-induced NT affects the homeostasis of oxylipins during the course of infection, a comprehensive lipidomic profiling in brains (cerebra and cerebella) of experimentally infected C57BL/6J mice was conducted at six different time points post infection (pi) by liquid-chromatography coupled to electrospray tandem mass spectrometry (LC-ESI-MS/MS). Only minor changes were detected regarding pro-inflammatory prostaglandins (cyclooxygenase pathway). In contrast, a significant increase of metabolites resulting from lipoxygenase pathways was observed for both infection groups and brain regions, implicating a predominantly anti-inflammatory driven immune response. This observation was supported by a significantly increased 13-hydroxyoctadecadienoic acid (HODE)/9-HODE ratio during the subacute phase of infection, indicating an anti-inflammatory response to neuroinfection. Except for the specialised pro-resolving mediator (SPM) neuroprotectin D1 (NPD1), which was detected in mice infected with both pathogens during the subacute phase of infection, no other SPMs were detected. Conclusions/Significance: The obtained results demonstrate the influence of Toxocara spp. on oxylipins as part of the immune response of the paratenic hosts. Furthermore, this study shows differences in the alteration of the oxylipin composition between T. canis- and T. cati-brain infection. Results contribute to a further understanding of the largely unknown pathogenesis and mechanisms of host-parasite interactions during NT. [ABSTRACT FROM AUTHOR]

Background: Asians are predisposed to a lean heart failure (HF) phenotype. Data on the 'obesity paradox', reported in Western populations, are scarce in Asia and have only utilised the traditional classification of body mass index (BMI). We aimed to investigate the association between obesity (defined by BMI and abdominal measures) and HF outcomes in Asia.Methods and Findings: Utilising the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry (11 Asian regions including Taiwan, Hong Kong, China, India, Malaysia, Thailand, Singapore, Indonesia, Philippines, Japan, and Korea; 46 centres with enrolment between 1 October 2012 and 6 October 2016), we prospectively examined 5,964 patients with symptomatic HF (mean age 61.3 ± 13.3 years, 26% women, mean BMI 25.3 ± 5.3 kg/m2, 16% with HF with preserved ejection fraction [HFpEF; ejection fraction ≥ 50%]), among whom 2,051 also had waist-to-height ratio (WHtR) measurements (mean age 60.8 ± 12.9 years, 24% women, mean BMI 25.0 ± 5.2 kg/m2, 7% HFpEF). Patients were categorised by BMI quartiles or WHtR quartiles or 4 combined groups of BMI (low, <24.5 kg/m2 [lean], or high, ≥24.5 kg/m2 [obese]) and WHtR (low, <0.55 [thin], or high, ≥0.55 [fat]). Cox proportional hazards models were used to examine a 1-year composite outcome (HF hospitalisation or mortality). Across BMI quartiles, higher BMI was associated with lower risk of the composite outcome (ptrend < 0.001). Contrastingly, higher WHtR was associated with higher risk of the composite outcome. Individuals in the lean-fat group, with low BMI and high WHtR (13.9%), were more likely to be women (35.4%) and to be from low-income countries (47.7%) (predominantly in South/Southeast Asia), and had higher prevalence of diabetes (46%), worse quality of life scores (63.3 ± 24.2), and a higher rate of the composite outcome (51/232; 22%), compared to the other groups (p < 0.05 for all). Following multivariable adjustment, the lean-fat group had higher adjusted risk of the composite outcome (hazard ratio 1.93, 95% CI 1.17-3.18, p = 0.01), compared to the obese-thin group, with high BMI and low WHtR. Results were consistent across both HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]; pinteraction = 0.355). Selection bias and residual confounding are potential limitations of such multinational observational registries.Conclusions: In this cohort of Asian patients with HF, the 'obesity paradox' is observed only when defined using BMI, with WHtR showing the opposite association with the composite outcome. Lean-fat patients, with high WHtR and low BMI, have the worst outcomes. A direct correlation between high WHtR and the composite outcome is apparent in both HFpEF and HFrEF.Trial Registration: Asian Sudden Cardiac Death in HF (ASIAN-HF) Registry ClinicalTrials.gov Identifier: NCT01633398. [ABSTRACT FROM AUTHOR]

We hypothesized that postnatal development of the vagina is impacted by early nutritional environment. Our objective was to determine if lipid profiles of vaginal swabs were different between postnatal gilts suckled by sow or fed milk replacer the first 48 h after birth, with or without a lard-based fat supplement. Gilts (>1.3 kg) were selected at birth across 8 litters and assigned to one of four treatments: 1) suckled by sow (S, n = 8); 2) suckled by sow plus administration of a fat supplement (SF, n = 5); 3) bottle-fed solely milk replacer (B, n = 8); or 4) bottle-fed solely milk replacer plus administration of a fat supplement (BF, n = 7). At 48 h postnatal, vaginal swabs of gilts were taken with a cytology brush, and lipids were extracted for analysis using multiple reaction monitoring (MRM)-profiling. Lipids extracted from serum collected at 48 h from gilts, milk collected at 24 h from sows, and milk replacer were also analyzed with MRM-profiling. Receiver operating characteristic curve analysis found 18 lipids recovered from vaginal swabs that highly distinguished between S and B gilts [area-under-the-curve (AUC) > 0.9], including phosphatidylethanolamine with 34 carbons and four unsaturations in the fatty acyl residues [PE (34:4)]. Twelve lipids from vaginal swabs highly correlated (r > 0.6; p < 0.01) with nutrition source. Lipids with greater abundance in milk replacer drove association. For example, mean intensity of PE (34:4) was 149-fold higher in milk replacer than colostrum. Consequently, PE (34:4) was found to have 1.6- and 2.12-fold higher levels in serum and vaginal swab samples (p < 0.001), respectively, of B gilts as compared to S gilts. Findings support that vaginal swabs can be used to noninvasively study effects of perinatal nutrition on tissue composition. [ABSTRACT FROM AUTHOR]

The severity of negative energy balance (NEB) in high-producing dairy cows has a high incidence among health diseases. The cow’s energy status during early lactation critically affects metabolic and reproductive parameters. The first objective of this study was to investigate by RNA-seq analysis and RT-qPCR the gene expression profile in white adipose tissue and by gene ontology and upstream regulation tools the relationships with energy metabolism and reproduction in two groups of primiparous dairy cows with extreme NEB statuses (NEB < -9 Mcal/day vs. NEB > -9 Mcal/day) around parturition. The second objective was to determine the potential involvement of a new adipokine identified as a candidate for the regulation of ovarian function in our RNA-seq analysis by using bovine primary granulosa culture, thymidine incorporation to determine cell proliferation and ELISA assays to measure progesterone secretion. The RNA-seq analysis revealed that 514 genes were over-expressed and 695 were under-expressed in the adipose tissue of cows with severe NEB (SNEB) and cows with moderate NEB (MNEB) during the -4 and 16 wkpp period. In addition, 491 genes were over-expressed and 705 genes were under-expressed in the adipose tissue of SNEB cows compared to MNEB cows. Among these differently expressed genes (DEGs), 298 were related to metabolic functions and 264 to reproductive traits. A set of 19 DEGs were validated by RT-qPCR, including CCL21 (C-C motif chemokine ligand 21). Moreover, CCL21, a gene known to be secreted by adipose tissue, was chosen for further analysis in plasma and ovaries. The use of next-generation sequencing technologies allowed us to characterise the transcriptome of white adipose tissue from primiparous cows with different levels of NEB during lactation. This study highlighted the alteration of the expression of genes related to lipid metabolism, including CCL21, which is released in the bloodstream and associated with the in vitro regulation of ovarian functions. [ABSTRACT FROM AUTHOR]

Introduction: 3D non-contact surface scanners capture highly accurate, calibrated images of surface topography for 3D structures. This study sought to establish the efficacy and accuracy of using 3D surface scanning to characterise spinal curvature and sagittal plane contour. Methods: 10 healthy female adults with a mean age of 25 years, (standard deviation: 3.6 years) underwent both MRI and 3D surface scanning (3DSS) (Artec Eva, Artec Group Inc., Luxembourg) while lying in the lateral decubitus position on a rigid substrate. Prior to 3DSS, anatomical landmarks on the spinous processes of each participant were demarcated using stickers attached to the skin surface. Following 3DSS, oil capsules (fiducial markers) were overlaid on the stickers and the subject underwent MRI. MRI stacks were processed to measure the thoracolumbar spinous process locations, providing an anatomical reference. 3D coordinates for the markers (surface stickers and MRI oil capsules) and for the spinous processes mapped the spinal column profiles and were compared to assess the quality of fit between the 3DSS and MRI marker positions. Results: The RMSE for the polynomials fit to the spinous process, fiducial and surface marker profiles ranged from 0.17–1.15mm for all subjects. The MRI fiducial marker location was well aligned with the spinous process profile in the thoracic and upper lumbar spine for nine of the subjects. Over the 10 subjects, the mean RMSE between the MRI and 3D scan sagittal profiles for all surface markers was 9.8mm (SD 4.2mm). Curvature was well matched for seven of the subjects, with two showing differing curvatures across the lumbar spine due to inconsistent subject positioning. Conclusion: Comparison of the observed trends for vertebral position measured from MRI and 3DSS, suggested the surface markers may provide a useful method for measuring internal changes in sagittal curvature or skeletal changes. [ABSTRACT FROM AUTHOR]

Background: Seasonality of food availability, physical activity, and infections commonly occurs within rural communities in low and middle-income countries with distinct rainy seasons. To better understand the implications of these regularly occurring environmental stressors for maternal and child health, this study examined seasonal variation in nutrition and health care access of pregnant women and infants in rural South Africa. Methods: We analyzed data from the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) birth cohort study of 752 mother-infant pairs recruited at delivery from August 2012 to December 2013 in the Vhembe District of Limpopo Province, the northernmost region of South Africa. We used truncated Fourier series regression to assess seasonality of antenatal care (ANC) attendance, dietary intake, and birth size. We additionally regressed ANC attendance on daily rainfall values. Models included adjustment for sociodemographic characteristics. Results: Maternal ANC attendance, dietary composition, and infant birth size exhibited significant seasonal variation in both unadjusted and adjusted analyses. Adequate frequency of ANC attendance during pregnancy (≥ 4 visits) was highest among women delivering during the gardening season and lowest during the lean (rainy) season. High rainfall during the third trimester was also negatively associated with adequate ANC attendance (adjusted OR = 0.59, 95% CI: 0.40, 0.86). Carbohydrate intake declined during the harvest season and increased during the vegetable gardening and lean seasons, while fat intake followed the opposite trend. Infant birth weight, length, and head circumference z-scores peaked following the gardening season and were lowest after the harvest season. Maternal protein intake and ANC ≤ 12 weeks did not significantly vary by season or rainfall. Conclusions: Seasonal patterns were apparent in ANC utilization, dietary intake, and fetal growth in rural South Africa. Interventions to promote maternal and child health in similar settings should consider seasonal factors. [ABSTRACT FROM AUTHOR]

We identified a mouse strain, HLB444, carrying an N-ethyl-N-nitrosourea (ENU)-induced mutation in a highly conserved C2H2 zinc-finger DNA binding motif of the transcriptional regulator KLF15 that exhibits resistance to diet-induced obesity. Characterization of the HLB444 mutant model on high-fat and chow diets revealed a number of phenotypic differences compared to wild-type controls. When fed a high fat diet, HLB444 had lower body fat, resistance to hepatosteatosis, lower circulating glucose and improved insulin sensitivity compared to C57BL/6J controls. Gut microbial profiles in HLB444 generated from 16S rRNA sequencing of fecal samples differed from controls under both chow and high fat diets. HLB444 shares similar phenotypic traits with engineered full- and adipose-specific Klf15 knockout strains; however, some phenotypic differences between this mutant and the other models suggest that the Klf15 mutation in HLB444 is a hypomorphic variant. The HLB444 model will inform further annotation of transcriptional functions of KLF15, especially with respect to the role of the first zinc-finger domain. [ABSTRACT FROM AUTHOR]

Lipid and fatty acid composition of female Pacific bluefin tuna (PBF, Thunnus orientalis) reproductive and somatic tissues in southwestern North Pacific and Sea of Japan spawning grounds are compared. Total lipid (TL) levels are higher in liver than white muscle tissues. An increased gonadosomatic index (GSI) during the early spawning season coincided with decreased TL. Levels of triacylglycerols (TAG) in PBF liver tissues from the Nansei Islands and Sea of Japan, and white muscle in fishes from the Sea of Japan, decreased during the spawning season, while TAG in ovary tissues did not. Concurrent reductions in TL and increases in GSI early in the spawning season suggest TAG depletion was caused by allocation from liver and white muscle tissues to oocytes, that the liver is one of the important lipid-storage organs in PBF, and this species mostly reliant on capital deposits as a mixed capital-income breeder. Differences of docosahexaenoic acid (DHA) levels between spawning grounds were lower in ovary than in muscle and liver tissues. However, eicosapentaenoic (EPA) and arachidonic acid (ARA) levels that influence egg development and embryo and larval growth are significantly higher in PBF tissues from the Sea of Japan than Nansei Islands, which coincided with larval quality. These suggest a maternal effect exists, with egg quality influencing offspring survival, and that the reproductive strategy of PBF varies according to local variation at each spawning ground. [ABSTRACT FROM AUTHOR]

Several heart rate variability (HRV) studies show abnormalities in autonomic nervous control in obese and overweight subjects. However, some of the results appear to be controversial. Here we investigate the HRV profile in seventy adult normotensive women and its association with general and visceral adiposity. Specifically, we recorded the electrocardiographic (ECG) activity in subjects during a supine resting state for five minutes in a quiet room late in the morning. Total fat mass (TFM) and visceral adipose tissue (VAT) were instead estimated using dual-energy X-ray absorptiometry (DXA). Finally, we used simple a linear regression analysis of frequency and time-domain parameters to study the relationship between HRV and adiposity. Our data showed an overall reduction of the HRV related to an increase of TFM although this regression appeared significant only for high frequencies (HF). When the linear regression was applied between HRV variables and VAT, the slope of the line increases, thus unveiling a statistically significant relation (i.e. the more VAT, the lower HRV). Finally, a control analysis showed that age does not alter the relation between HRV and VAT when used as a confounding factor in multiple regression. To conclude, these findings point to abnormal activity of the autonomic nervous system (ANS) in subjects with an excess of VAT and represent a starting point to determine a non-invasive index of cardiac wellness for clinical and nutritional application. [ABSTRACT FROM AUTHOR]

Objective: Thresholds defining medication adherence are rarely evidence-based. A threshold of 0.8 is typically presumed to achieve improved outcomes. We aimed to assess the optimal threshold of adherence to lipid-lowering drugs (LLD) in predicting cardiovascular-related (CV) outcomes in patients with hypertension. Design: Cohort study of new users of LLDs. Setting: Comprehensive healthcare administrative databases of the province of Alberta (Canada) from 2008 to 2016. Participants: Patients with hypertension, who were new users of LLDs. Patients who had the outcomes prior to the initiation of LLD were excluded. Main outcomes measures: Hospitalization for acute coronary syndrome (ACS)/stroke, CV-related mortality and all-cause mortality. Statistical analysis: Adherence to LLDs was assessed as the proportion of days covered (PDC) by any LLD, from drug initiation to censoring, outcome, or study end. Three methods were used to assess the threshold: Contal and O'Quigley method, minimum distance method, and Youden's J index. Cox regressions were used to assess the risk associated with each method-specific threshold and Akaike information criteria were used to retain the optimal threshold after adjustment. Results: 52229 patients were included; 4.0% were hospitalized for ACS/stroke, 3.4% died, and 1.3% died from CV-related cause. In predicting ACS/stroke, CV-related and all-cause mortality, the optimal adherence threshold was 0.52 (range: 0.51–0.54), 0.79 (0.45–0.87), and 0.84 (0.79–0.89), respectively. These results were consistent among patients aged ≥ 65 years (n = 19804). However, the results varied among those aged < 65 years, where the incidence rates of outcomes were low. Conclusion: In new-users of LLDs with hypertension, approximately 50% days covered by LLDs may be enough to prevent long-term occurrence of ACS, or stroke. However, a threshold near 0.80 may be needed to prevent or reduce the risk of all-cause or CV-related mortality. [ABSTRACT FROM AUTHOR]

A fatty acid analogue, 2-(tridec-12-yn-1-ylthio)acetic acid (1-triple TTA), was previously shown to have hypolipidemic effects in rats by targeting mitochondrial activity predominantly in liver. This study aimed to determine if 1-triple TTA could influence carbohydrate metabolism. Male Wistar rats were treated for three weeks with oral supplementation of 100 mg/kg body weight 1-triple TTA. Blood glucose and insulin levels, and liver carbohydrate metabolism gene expression and enzyme activities were determined. In addition, human myotubes and Huh7 liver cells were treated with 1-triple TTA, and glucose and fatty acid oxidation were determined. The level of plasma insulin was significantly reduced in 1-triple TTA-treated rats, resulting in a 32% reduction in the insulin/glucose ratio. The hepatic glucose and glycogen levels were lowered by 22% and 49%, respectively, compared to control. This was accompanied by lower hepatic gene expression of phosphenolpyruvate carboxykinase, the rate-limiting enzyme in gluconeogenesis, and Hnf4A, a regulator of gluconeogenesis. Gene expression of pyruvate kinase, catalysing the final step of glycolysis, was also reduced by 1-triple TTA. In addition, pyruvate dehydrogenase activity was reduced, accompanied by 10-15-fold increased gene expression of its regulator pyruvate dehydrogenase kinase 4 compared to control, suggesting reduced entry of pyruvate into the TCA cycle. Indeed, the NADPH-generating enzyme malic enzyme 1 (ME1) catalysing production of pyruvate from malate, was increased 13-fold at the gene expression level. Despite the decreased glycogen level, genes involved in glycogen synthesis were not affected in livers of 1-triple TTA treated rats. In contrast, the pentose phosphate pathway seemed to be increased as the hepatic gene expression of glucose-6-phosphate dehydrogenase (G6PD) was higher in 1-triple TTA treated rats compared to controls. In human Huh7 liver cells, but not in myotubes, 1-triple-TTA reduced glucose oxidation and induced fatty acid oxidation, in line with previous observations of increased hepatic mitochondrial palmitoyl-CoA oxidation in rats. Importantly, this work recognizes the liver as an important organ in glucose homeostasis. The mitochondrially targeted fatty acid analogue 1-triple TTA seemed to lower hepatic glucose and glycogen levels by inhibition of gluconeogenesis. This was also linked to a reduction in glucose oxidation accompanied by reduced PHD activity and stimulation of ME1 and G6PD, favouring a shift from glucose- to fatty acid oxidation. The reduced plasma insulin/glucose ratio indicate that 1-triple TTA may improve glucose tolerance in rats. [ABSTRACT FROM AUTHOR]

Objectives: Traits of metabolic syndrome (MetS) and biomarkers of inflammation and endothelial dysfunction were examined. We investigated the differences of various biomarkers among individuals with or without Mets in a gender-specific manner. The gender-specific associations between E-selectin and MetS were further evaluated. Methods: A total of 205 patients were recruited from the outpatient clinics of Tri-Service General Hospital, Taipei, Taiwan. Inclusion criteria were age between 20–75 years and BMI < 35 kg/m2. Demographic, anthropometric and MetS index data were compared between genders. Markers of inflammation and endothelial dysfunction were compared between individuals with or without MetS by gender. Results: Age-adjusted E-selectin values showed significant positive correlations with BMI, waist-hip ratio, fasting plasma glucose, systolic and diastolic blood pressure, triglycerides, TNF-α, hsCRP and ICAM-1, and inverse correlation with HDL cholesterol. E-selectin levels were positively correlated with numbers of MetS components in females (P < 0.001) but not in males (P = 0.125). Conclusions: Increased E-selectin levels are significantly associated with increased MetS risk in females, but not in males. [ABSTRACT FROM AUTHOR]

The osmotic stability of the erythrocyte membrane (OSEM) has been associated with changes in lipid profile, blood glucose and blood pressure. Changes in these parameters are very frequent in shift workers, possibly because of the lack of synchronization of biological rhythms, which results in the social jetlag. However, the existence of association between OSEM and circadian misalignment has not been investigated in this population. Therefore, this study investigated whether shift work, sleep time and social jetlag (SJL) are associated with biochemical and hematological variables. A population consisting of 79 men working at night (n = 37) or during the day (n = 42), aged between 21 and 65 years and with a mean BMI of 27.56 ± 4.0 kg/m2, was investigated cross-sectionally in relation to sleep time, SJL, anthropometric (height, weight and waist circumference) and blood variables, with emphasis on the OSEM. SJL was calculated by the absolute difference between the midpoint of sleep on work and rest days. The Generalized Linear Model (GzLM) was used to investigate the existence of associations between SJL and average sleep time in relation to the analyzed variables. Workers without SJL presented lower baseline lysis values of erythrocytes in isotonic medium in relation to workers with SJL. In addition, workers who slept on average less than 6 hours had higher OSEM, and higher total and LDL-cholesterol in relation to those who slept more than 6 hours, regardless of the shift. It is possible that the association of sleep deprivation and SJL with erythrocyte membrane stability is mediated through changes in the lipid profile. [ABSTRACT FROM AUTHOR]

Introduction: Prader-Willi syndrome (PWS) is a complex genetic condition characterized by hyperphagia, hypotonia, low muscle mass, excess body fat, developmental delays, intellectual disability, behavioral problems, and growth hormone deficiency. This study evaluated the safety and efficacy of orally administered Diazoxide Choline Controlled-Release Tablets (DCCR) in subjects with PWS. Method: This was a single-center, Phase II study and included a 10-week Open-Label Treatment Period during which subjects were dose escalated, followed by a 4-week Double-Blind, Placebo-Controlled Treatment Period. Results: Five female and eight male overweight or obese, adolescent and adult subjects with genetically-confirmed PWS with an average age of 15.5±2.9 years were enrolled in the study. There was a statistically significant reduction in hyperphagia at the end of the Open-Label Treatment Period (-4.32, n = 11, p = 0.006). The onset of effect on hyperphagia was rapid and greater reductions in hyperphagia were seen in subjects with moderate to severe Baseline hyperphagia (-5.50, n = 6, p = 0.03), in subjects treated with the highest dose (-6.25, n = 4, p = 0.08), and in subjects with moderate to severe Baseline hyperphagia treated with the highest dose (-7.83, n = 3, p = 0.09). DCCR treatment resulted in a reduction in the number of subjects displaying aggressive behaviors (-57.1%, n = 10, p = 0.01), clinically-relevant reductions in fat mass (-1.58 kg, n = 11, p = 0.02) and increases in lean body mass (2.26 kg, n = 11, p = 0.003). There was a corresponding decrease in waist circumference, and trends for improvements in lipids and insulin resistance. The most common adverse events were peripheral edema and transient increases in glucose. Many of the adverse events were common medical complications of PWS and diazoxide. Conclusion: DCCR treatment appears to address various unmet needs associated with PWS, including hyperphagia and aggressive behaviors in this proof-of-concept study. If the results were replicated in a larger scale study, DCCR may be a preferred therapeutic option for patients with PWS. [ABSTRACT FROM AUTHOR]

Oxalate, a ubiquitous compound in many plant-based foods, is absorbed through the intestine and precipitates with calcium in the kidneys to form stones. Over 80% of diagnosed kidney stones are found to be calcium oxalate. People who form these stones often experience a high rate of recurrence and treatment options remain limited despite decades of dedicated research. Recently, the intestinal microbiome has become a new focus for novel therapies. Studies have shown that select species of Lactobacillus, the most commonly included genus in modern probiotic supplements, can degrade oxalate in vitro and even decrease urinary oxalate in animal models of Primary Hyperoxaluria. Although the purported health benefits of Lactobacillus probiotics vary significantly between species, there is supporting evidence for their potential use as probiotics for oxalate diseases. Defining the unique metabolic properties of Lactobacillus is essential to define how these bacteria interact with the host intestine and influence overall health. We addressed this need by characterizing and comparing the metabolome and lipidome of the oxalate-degrading Lactobacillus acidophilus and Lactobacillus gasseri using ultra-high-performance liquid chromatography-high resolution mass spectrometry. We report many species-specific differences in the metabolic profiles of these Lactobacillus species and discuss potential probiotic relevance and function resulting from their differential expression. Also described is our validation of the oxalate-degrading ability of Lactobacillus acidophilus and Lactobacillus gasseri, even in the presence of other preferred carbon sources, measuring in vitro 14C-oxalate consumption via liquid scintillation counting. [ABSTRACT FROM AUTHOR]

Goat fat is one of the best sources of conjugated linoleic acid (CLA), a fatty acid which has health benefits. However, though CLA is generated in ruminants, CLA consumption is limited to meats and milk products. This study aimed to replace vegetable fat with goat milk fat enriched with CLA. From differing fat sources, four cookie recipes were developed: CVF–vegetable fat cookies; CB–butter cookies; CG–goat milk fat cookies without CLA; CGCLA–goat milk fat cookies with CLA. The cookies were evaluated using physical (color and texture), physical-chemical parameters (lipids, proteins, total sugars, fiber, ash, moisture and Aw), consumer testing (n = 123), and lipid profiles. The CGCLA presented higher values in the color parameters. The highest and the lowest scores obtained for hardness were respectively 5.54 (CB) and 2.21 (CVF). Lipids and total sugars varied inversely; the highest percentages of lipids were in the CVF and CG samples which obtained lower total sugar content. There were no differences in acceptance or preference for the four formulations. The goat cream formulations (CG and CGCLA) were as well accepted as the CFV formulation. For lipid profiles, CFV presented the highest percentage of trans-fatty acids (TFA) at 16.76%. CGCLA presented 70% more CLA than either CB or CG, certifying that CGCLA presents CLA in relevant quantities, even after cooking. The CGCLA presented higher levels of CLA, and in this study it was verified that goat milk cream enriched with CLA can be used in producing cookies, adding functional and nutritional properties, and offering another alternative(s) to produce food from goat milk fat. [ABSTRACT FROM AUTHOR]

Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide. While it has been suggested to cause nervous impairment, its neurophysiological basis remains unknown. Therefore, the aim of this study is to unravel the effects of NASH, through the interrelationship of liver, gut microbiota, and nervous system, on the brain and human behavior. To this end, 40 Sprague-Dawley rats were divided into a control group that received normal chow and a NASH group that received a high-fat, high-cholesterol diet. Our results show that 14 weeks of the high-fat, high-cholesterol diet induced clinical conditions such as NASH, including steatosis and increased levels of ammonia. Rats in the NASH group also demonstrated evidence of gut dysbiosis and decreased levels of short-chain fatty acids in the gut. This may explain the deficits in cognitive ability observed in the NASH group, including their depressive-like behavior and short-term memory impairment characterized in part by deficits in social recognition and prefrontal cortex-dependent spatial working memory. We also reported the impact of this NASH-like condition on metabolic and functional processes. Brain tissue demonstrated lower levels of metabolic brain activity in the prefrontal cortex, thalamus, hippocampus, amygdala, and mammillary bodies, accompanied by a decrease in dopamine levels in the prefrontal cortex and cerebellum and a decrease in noradrenalin in the striatum. In this article, we emphasize the important role of ammonia and gut-derived bacterial toxins in liver-gut-brain neurodegeneration and discuss the metabolic and functional brain regional deficits and behavioral impairments in NASH. [ABSTRACT FROM AUTHOR]

Objectives: The association of obstructive sleep apnea (OSA) with hypothalamic pituitary adrenal (HPA) axis activation has not been fully understood from results of previous studies using hormonal assessments. We aimed to investigate the relationship between adrenal size, a potential marker reflecting HPA axis activity, and sleep parameters related to OSA. Methods: We retrospectively reviewed data on 284 consecutive adult patients aged 20 to 80 y who had undergone polysomnography and abdominal computed tomography (CT). OSA was defined as none/mild (apnea-hypopnea index [AHI] <15, n = 75), moderate (AHI 15 to 30, n = 80), and severe OSA (AHI ≥30, n = 129). Widths of adrenal body and limbs were measured by abdominal CT. Results: Adrenal size was greater in participants with severe OSA than in those with none/mild or moderate OSA (adrenal body width: 6.03 mm, none/mild OSA; 6.09 mm, moderate OSA; 6.78 mm, severe OSA; p <0.001; adrenal limb width: 3.75 mm, none/mild OSA; 3.95 mm, moderate OSA; 4.26 mm, severe OSA, p <0.001). Multivariate regression analysis showed that not the 3% oxygen desaturation index and time of SpO2 <90% but a higher arousal index was the only determinant factor for increased adrenal limb width (β = 0.27, p <0.001) after adjusting for other variables that could affect adrenal size. Neither the arousal index nor hypoxic parameters were associated with adrenal body width. Conclusions: Results indicated that adrenal glands may enlarge in response to longstanding sleep fragmentation, suggesting the involvement of OSA in HPA axis augmentation. [ABSTRACT FROM AUTHOR]

Background: Quantification of abdominal muscle mass by cross-sectional imaging has been increasingly used to diagnose sarcopenia; however, the technical method for quantification has not been standardized yet. We aimed to determine an optimal method to measure the abdominal muscle area. Methods: Among 50 consecutive subjects who underwent abdominal CT and MRI for possible liver donation, total abdominal muscle area (TAMA) and total psoas muscle area (TPA) at the L3 inferior endplate level were measured by two blinded readers. Inter-scan agreement between CT and MRI and inter-reader agreement between the two readers were evaluated using intraclass correlation coefficient (ICC) and within-subject coefficient of variation (WSCV). To evaluate the effect of measurement level, one reader measured TAMA and TPA at six levels from the L2 to L4 vertebral bodies. Results: TAMA was a more reliable biomarker than TPA in terms of inter-scan agreement (ICC: 0.928 vs. 0.788 for reader 1 and 0.853 vs. 0.821 for reader 2, respectively; WSCV: 8.3% vs. 23.4% for reader 1 and 10.4% vs. 22.3% for reader 2, respectively) and inter-reader agreement (ICC: 0.986 vs. 0.886 for CT and 0.865 vs. 0.669 for MRI, respectively; WSCV: 8.2% vs. 16.0% for CT and 11.6% vs. 29.7% for MRI, respectively). In terms of the measurement level, TAMA did not differ from the L2inf to L4inf levels, whereas TPA increased with a decrease in measurement level. Conclusions: TAMA is a better biomarker than TPA in terms of inter-scan and inter-reader agreement and robustness to the measurement level. CT was a more reliable imaging modality than MRI. Our results support the use of TAMA measured by CT as a standard biomarker for abdominal muscle area measurement. [ABSTRACT FROM AUTHOR]

Objective: Previous reports have highlighted the suboptimal utilization and prescription of statin therapy among patients with type 2 diabetes mellitus (T2DM) in the Malaysian clinical practice. This study aims to test the impact of a pharmacist-led academic detailing program on improving the overall statin therapy prescribing in Malaysian hospital and primary care settings. Methods: As a quasi-experimental design with a control group and pre-tests., we examined 1,598 medical records of T2DM subjects in six healthcare facilities in the state of Pahang, Malaysia. In all study sites, there was a pre and post-intervention assessment of the percentage of appropriate statin therapy prescribing that complied with the clinical guidelines with no potential safety issues. The intervention was an academic detailing program offered to the health care providers in three study sites, while the other three sites served as the control group. A comparison of the overall percentage of appropriate statin therapy prescribing before and after the academic detailing was performed in all intervention and control sites. Results: Overall, 797 medical records were examined in the pre-intervention phase, and 801 records were evaluated in the post-intervention phase. The academic detailing program was associated with a statistically significant difference in the proportion of appropriate statin therapy prescribing between the post-intervention phase compared to the pre-intervention phase (n = 246, 61.7% versus n = 188, 47.1%), p = 0.001. Whereas, the appropriate statin therapy prescribing in the control study sites experienced a modest change from 53.8% (214/398) to 56.7% (228/402), p = 0.220. The academic detailing showed significant increases in the proportions of appropriate statin therapy prescribing in both hospital and primary care settings. Conclusions: The academic detailing program was found to be significantly associated with a positive impact on the overall statin therapy prescribing among patients with T2DM in Malaysian hospital and primary care settings. [ABSTRACT FROM AUTHOR]

Background: Most manufacturer manuals do not verify the use of dual energy X-ray absorptiometry for body composition analysis in subjects with a metal implant. This study aimed to quantify the effects of a spinal implant on body composition, and to determine whether unadjusted lean mass estimates are valid for patients with a spinal implant. Methods: A total of 30 healthy subjects were recruited. Three consecutive scans were performed for each participant, one with and two without extraneous spinal implant, without repositioning between scans. Lean, fat and bone estimates in the total body, trunk and limb were measured. Results: Precision errors for all total and regional body compositions were within the recommended ranges. Bone masses in the trunk and total body were significantly increased with spinal implant, and the increases exceeded the least significant change. For total and regional lean and fat estimates, the measurements between subjects with and without metal implants were in substantial to almost perfect agreement and the differences were not significant and did not exceed the least significant change. Conclusions: Spinal metal artifacts significantly increased the total body and trunk bone mass but the differences in lean- and fat-related estimates at total and regional body levels and all estimates in the extremity remained within the clinical acceptable range. Thus, a spinal implant may not compromise screening of patients for fat and lean masses using dual energy X-ray absorptiometry. Application of image reconstruction or a filtering algorithm may help reduce the effect of metallic artifacts and further study is needed. [ABSTRACT FROM AUTHOR]

High-throughput multi-omics studies and corresponding network analyses of multi-omic data have rapidly expanded their impact over the last 10 years. As biological features of different types (e.g. transcripts, proteins, metabolites) interact within cellular systems, the greatest amount of knowledge can be gained from networks that incorporate multiple types of -omic data. However, biological and technical sources of variation diminish the ability to detect cross-type associations, yielding networks dominated by communities comprised of nodes of the same type. We describe here network building methods that can maximize edges between nodes of different data types leading to integrated networks, networks that have a large number of edges that link nodes of different–omic types (transcripts, proteins, lipids etc). We systematically rank several network inference methods and demonstrate that, in many cases, using a random forest method, GENIE3, produces the most integrated networks. This increase in integration does not come at the cost of accuracy as GENIE3 produces networks of approximately the same quality as the other network inference methods tested here. Using GENIE3, we also infer networks representing antibody-mediated Dengue virus cell invasion and receptor-mediated Dengue virus invasion. A number of functional pathways showed centrality differences between the two networks including genes responding to both GM-CSF and IL-4, which had a higher centrality value in an antibody-mediated vs. receptor-mediated Dengue network. Because a biological system involves the interplay of many different types of molecules, incorporating multiple data types into networks will improve their use as models of biological systems. The methods explored here are some of the first to specifically highlight and address the challenges associated with how such multi-omic networks can be assembled and how the greatest number of interactions can be inferred from different data types. The resulting networks can lead to the discovery of new host response patterns and interactions during viral infection, generate new hypotheses of pathogenic mechanisms and confirm mechanisms of disease. [ABSTRACT FROM AUTHOR]

Zika virus infection is associated with the development of Guillain-Barré syndrome (GBS), a neurological autoimmune disorder caused by immune recognition of gangliosides and other components at nerve membranes. Using a high-throughput ELISA, we have analyzed the anti-glycolipid antibody profile, including gangliosides, of plasma samples from patients with Zika infections associated or not with GBS in Salvador, Brazil. We have observed that Zika patients that develop GBS present higher levels of anti-ganglioside antibodies when compared to Zika patients without GBS. We also observed that a broad repertoire of gangliosides was targeted by both IgM and IgG anti-self antibodies in these patients. Since Zika virus infects neurons, which contain membrane gangliosides, antigen presentation of these infected cells may trigger the observed autoimmune anti-ganglioside antibodies suggesting direct infection-induced autoantibodies as a cause leading to GBS development. Collectively, our results establish a link between anti-ganglioside antibodies and Zika-associated GBS in patients. [ABSTRACT FROM AUTHOR]

Cotton gin trash (CGT), a waste product of cotton gins, make up about 10% of each bale of cotton bolls ginned. The current study investigates high value volatile compounds in CGT to add value to this by-product. The volatile compounds in CGT and different parts of the cotton plant were extracted using various methods, identified by gas chromatography-mass spectrometry (GC-MS) or nuclear magnetic resonance (NMR) spectroscopy, and then quantified by gas chromatography-flame ionisation detection (GC-FID) against available standards. Terpenoids including monoterpenoids and sesquiterpenoids were found to be the most abundant, making up 64.66% (area under peak) of total volatiles extracted by hydro-distillation. The major extractable terpenoids in CGT were α-pinene (13.69–23.05 μg/g), β-caryophyllene (3.99–74.32 μg/g), α-humulene (2.00–25.71 μg/g), caryophyllene oxide (41.50–102.08 μg/g) and β-bisabolol (40.05–137.32 μg/g). Recoveries varied between different extraction methods. The terpenoids were found to be more abundant in the calyx (659.12 μg/g) and leaves (627.72 μg/g) than in stalks (112.97 μg/g) and stems (24.24 μg/g) of the cotton plant, indicating the possible biological origin of CGT volatiles. This study is the first to identify and quantify the different terpenoids present in CGT and significantly, β-bisabolol, an abundant compound (sesquiterpene alcohol) which may have valuable biological prospects. These findings therefore contribute to identifying alternative management strategies and uses of CGT. [ABSTRACT FROM AUTHOR]

Menopause is an endocrine-related transition that induces a number of physiological and potentially pathological changes in middle-aged and elderly women. The intention of this research was to investigate the influence of menopause on the intricate relationships between major biochemical metabolites. The study involved metabolic profiling of 186 metabolic markers measured in blood plasma collected from 120 healthy female participants. We developed a method of network analysis using differential correlation that enabled us to detect and characterize differences in metabolites and changes in inter-relationships in pre- and post-menopausal women. A topological analysis was performed on the differential network that uncovered metabolite differences in pre-and post-menopausal women. In this analysis, our method identified two key metabolites, sphingomyelins and phosphatidylcholines, which may be useful in directing further studies into menopause-specific differences in the metabolome, and how these differences may underlie the body's response to stress and disease following the transition from pre- to post-menopausal status for women. [ABSTRACT FROM AUTHOR]

Background: The double-blind OMEGA-REMODEL placebo-controlled randomized trial of high-dose omega-3 fatty acids (O-3FA) post-acute myocardial infarction (AMI) reported improved cardiac remodeling and attenuation of non-infarct myocardial fibrosis. Fatty acid desaturase 2 (FADS2) gene cluster encodes key enzymes in the conversion of essential omega-3 and omega-6 fatty acids into active arachidonic (ArA) and eicosapentaenoic acids (EPA), which influence cardiovascular outcomes. Methods and results: We tested the hypothesis that the genotypic status of FADS2 (rs1535) modifies therapeutic response of O-3FA in post-AMI cardiac remodeling in 312 patients. Consistent with known genetic polymorphism of FADS2, patients in our cohort with the guanine-guanine (GG) genotype had the lowest FADS2 activity assessed by arachidonic acid/linoleic acid (ArA/LA) ratio, compared with patients with the adenine-adenine (AA) and adenine-guanine (AG) genotypes (GG:1.62±0.35 vs. AA: 2.01±0.36, p<0.0001; vs. AG: 1.76±0.35, p = 0.03). When randomized to 6-months of O-3FA treatment, GG patients demonstrated significant lowering of LV end-systolic volume index (LVESVi), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and galectin-3 levels compared to placebo (-4.4 vs. 1.2 ml/m2, -733 vs. -181 pg/mL, and -2.0 vs. 0.5 ng/mL; p = 0.006, 0.006, and 0.03, respectively). In contrast, patients with either AA or AG genotype did not demonstrate significant lowering of LVESVi, NT-proBNP, or galectin-3 levels from O-3FA treatment, compared to placebo. The odds ratios for improving LVESVi by 10% with O-3FA treatment was 7.2, 1.6, and 1.2 in patients with GG, AG, and AA genotypes, respectively. Conclusion: Genetic profiling using FADS2 genotype can predict the therapeutic benefits of O-3FA treatment against adverse cardiac remodeling during the convalescent phase of AMI. Clinical trial registration information: clinicaltrials.gov Identifier: . [ABSTRACT FROM AUTHOR]

Choline geranate (also described as Choline And GEranic acid, or CAGE) has been developed as a novel biocompatible antiseptic material capable of penetrating skin and aiding the transdermal delivery of co-administered antibiotics. The antibacterial properties of CAGE were analyzed against 24 and 72 hour old biofilms of 11 clinically isolated ESKAPE pathogens (defined as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter sp, respectively), including multidrug resistant (MDR) isolates. CAGE was observed to eradicate in vitro biofilms at concentrations as low as 3.56 mM (0.156% v:v) in as little as 2 hours, which represents both an improved potency and rate of biofilm eradication relative to that reported for most common standard-of-care topical antiseptics in current use. In vitro time-kill studies on 24 hour old Staphylococcus aureus biofilms indicate that CAGE exerts its antibacterial effect upon contact and a 0.1% v:v solution reduced biofilm viability by over three orders of magnitude (a 3log10 reduction) in 15 minutes. Furthermore, disruption of the protective layer of exopolymeric substances in mature biofilms of Staphylococcus aureus by CAGE (0.1% v:v) was observed in 120 minutes. Insight into the mechanism of action of CAGE was provided with molecular modeling studies alongside in vitro antibiofilm assays. The geranate ion and geranic acid components of CAGE are predicted to act in concert to integrate into bacterial membranes, affect membrane thinning and perturb membrane homeostasis. Taken together, our results show that CAGE demonstrates all properties required of an effective topical antiseptic and the data also provides insight into how its observed antibiofilm properties may manifest. [ABSTRACT FROM AUTHOR]

Magnetic Resonance Imaging (MRI) has become a valuable imaging modality in ophthalmology, especially for the diagnosis and treatment planning of patients with uveal melanoma, the most common primary intra-ocular tumor. We aim to develop and evaluate the value of silent Zero Echo Time (ZTE) MRI to image patients with ocular tumors at 7Tesla. Therefore, ZTE and different types of magnetization-prepared ZTE (FLAIR, SPIR, T2 and Saturation recovery), have been developed. After an initial validation with 7 healthy subjects, nine patients with an eye tumor have been evaluated. The ZTE scans were compared to their Cartesian equivalent in terms of contrast, motion-sensitivity, diagnostic quality and patient comfort. All volunteers and especially the patients reported a more comfortable experience during the ZTE scans, which had at least a 10 dB lower sound pressure. The image contrast in the native ZTE was poor, but in the different magnetization-prepared ZTE, the eye lens, cornea and retina were clearly discriminated. Overall the T2-prepared scan yielded the best contrast, especially between tumor and healthy tissue, and proved to be robust against eye motion. Although the intrinsic 3D nature of the ZTE-technique provides an accurate analysis of the tumor morphology, the quality of the ZTE-images is lower than their Cartesian equivalent. In conclusion, the quality of magnetization-prepared ZTE images is sufficient to assess the 3D tumor morphology, but insufficient for more detailed evaluations. As such this technique can be an option for patients who cannot comply with the sound-levels of Cartesian scans, but for other patients the conventional Cartesian scans offer a better image quality. [ABSTRACT FROM AUTHOR]

Oil impacting the northern Gulf of Mexico shoreline from the 2010 Deepwater Horizon accident was predominantly in the form of water-in-oil emulsions (WOE), a chemically weathered, highly viscous, neutrally buoyant material. Once formed, WOE are extremely difficult to destabilize. Commercially-available oil dispersants are largely ineffective de-emulsifiers as a result of the inability of dispersant surfactants to displace asphaltenes stabilizing the oil-water interface. This study investigated the effectiveness of the commercially-available dispersant Corexit 9500A, modified to enhance its polar fraction, in destabilizing WOE. Results suggest that Corexit modified to include between 20–60% fractional amount of either polar additive (1-octanol or hexylamine) will produce a modest increase in WOE instability, with a Corexit to hexylamine ratio of approximately 80/20 providing the most effective enhanced destabilization. Results support the hypothesis that modifying the fraction of polar constituents in commercial dispersants will increase asphaltene solubility, decrease oil-water interface stability, and enhance WOE instability. [ABSTRACT FROM AUTHOR]

The literature lacks studies investigating the performance of supplemented replacement heifers grazing on intensively managed warm-season pasture. Our objective was to evaluate the effects of supplement composition (energetic or protein) on the performance, muscle development, thermogenisis, nutrient intake, and digestibility of replacement Holstein heifers grazing Mombaça grass. Eighteen Holstein heifers with an average age and initial body weight (BW) of 12.57 ± 2.54 mo and 218.76 ±47.6 kg, respectively, were submitted to a randomized block design, with six replicates on a rotational grazing system of Panicum maximum cv. Mombaça pasture. Treatments were: control (CON; mineral salt ad libitum); energy supplement (ENE; corn meal as supplement, 8% CP and 3.78 Mcal/kg DE); and protein supplement (PRO; corn and soybean meal, 25% CP and 3.66 Mcal/kg DE). Supplements were individually fed at 0.5% BW. The experiment lasted 120 days, subdivided into three periods. Titanium dioxide and indigestible neutral detergent fiber (iNDF) were used to estimate the intakes and digestibility of the nutrients. BW, wither height, thoracic circumference, body length, and ultrasound of ribeye fat thickness measurements were taken once per period. Body condition score (BCS) was assessed twice during the experiment. The MIXED procedure of SAS, including period as a repeated measure, was used and significance was declared at P ≤ 0.05. Dry matter intake (DMI), CP intake (CPI) and DE intake were greater in heifers fed PRO compared to CON and ENE. Heifers supplemented with ENE had the lowest DMI. Treatment affected pasture intake/BW; it was similar between PRO and CON heifers, and lower for the ENE treatment. A treatment × period interaction was observed for NDF intake (%BW), in which heifers fed PRO and CON had the greatest NDF intake and ENE had the lowest. The digestibility of DM was the greatest in PRO-supplemented heifers and the lowest in CON heifers. Heifers fed ENE had decreased CP digestibility compared to PRO and CON heifers. Average daily gain (ADG) and thoracic circumference gain were greatest in the PRO treatment. BCS was greater in PRO compared to CON and ENE heifers. Supplementing Holstein heifers at 0.5% BW using PRO supplementation resulted in better animal performance, primarily greater ADG, than feeding ENE or not supplementing (CON). In conclusion, our results indicate that dairy heifers should be fed a protein supplement when grazing intensively managed Mombaça grass pasture. [ABSTRACT FROM AUTHOR]

China’s transport sector is facing enormous challenges from soaring energy consumption and greenhouse gas (GHG) emissions. Transport electrification has been viewed as a major solution to transportation decarbonization, and electric vehicles (EVs) have attracted considerable attention from policymakers. This paper analyzes the effects of the introduction of EVs in China. A system dynamics model is developed and applied to assess the energy-saving and emission-reducing impacts of the projected penetration of EVs until the year 2030. Five types of scenarios of various EV penetration rates, electricity generation mixes, and the speed of technological improvement are discussed. Results confirm that reductions in transport GHG emissions and gasoline and diesel consumption by 3.0%–16.2%, 4.4%–16.1%, and 15.8%–34.3%, respectively, will be achieved by 2030 under China’s projected EV penetration scenarios. Results also confirm that if EV penetration is accompanied by decarbonized electricity generation, that is, the use of 55% coal by 2030, then total transport GHG emissions will be further reduced by 0.8%–4.4%. Moreover, further reductions of GHG emissions of up to 5.6% could be achieved through technological improvement. The promotion of EVs could substantially affect the reduction of transport GHG emissions in China, despite the uncertainty of the influence intensity, which is dependent on the penetration rate of EVs, the decarbonization of the power sector, and the technological improvement efficiency of EVs and internal combustion engine vehicles. [ABSTRACT FROM AUTHOR]

The present study investigates the wound healing potential of three chitosan-based topical preparations loaded with either tea tree essential oil, rosemary essential oil or a mixture of both oils in vivo. Essential oils of M. alternifolia and R. officinalis were analyzed using GC/MS. Essential oil-loaded chitosan topical preparations were formulated. Wound healing potential was evaluated in vivo using an excision wound model in rats. GC/MS analysis of M. alternifolia and R. officinalis essential oils revealed richness in oxygenated monoterpenes, representing 51.06% and 69.61% of the total oil composition, respectively. Topical application of chitosan-based formulation loaded with a mixture of tea tree and rosemary oils resulted in a significant increase in wound contraction percentage compared to either group treated with individual essential oils and the untreated group. Histopathological examination revealed that topical application of tea tree and rosemary oil combination demonstrated complete re-epithelialization associated with activated hair follicles. The high percentage of oxygenated monoterpenes in both essential oils play an important role in the antioxidant and wound healing potential observed herein. Incorporation of tea tree and rosemary essential oils in chitosan-based preparations in appropriate combination could efficiently promote different stages of wound healing. [ABSTRACT FROM AUTHOR]

Condition indices aim to evaluate the physiological status of fish larvae by estimating both the level of starvation and potential of survival. Histological indices reveal direct effects of starvation whereas biochemical indices such as lipid classes or RNA:DNA ratios are used as proxies of condition, giving information on the amount of energy reserves and growth rate, respectively. We combined these three indices to evaluate ontogenetic variations of growth performance, lipid dynamics and nutritional condition of plaice larvae caught in the field during winter 2017 in the eastern English Channel and the Southern Bight of the North Sea. RNA:DNA ratios showed that larvae at the beginning of metamorphosis (stage 4) had a lower growth rate than younger individuals (stages 2 and 3). A significant increase in the proportion of triglycerides also occurred at stage 4, indicating energy storage. Histological indices indicated that most of the larvae were in good condition, even younger ones with low lipid reserves. There was, however, an increase in the proportion of healthy individuals over ontogeny, especially with respect to liver vacuoles which were larger and more numerous for stage 4 larvae. Combined together, these condition indices revealed the ontogenetic shift in the energy allocation strategy of plaice larvae. Young larvae (stages 2 and 3) primarily allocate energy towards somatic growth. The decrease in growth performance for stage 4 was not related to poor condition, but linked to a higher proportion of energy stored as lipids. Since the quantity of lipid reserves is particularly important for plaice larvae to withstand starvation during metamorphosis, this could be considered as a second critical period after the one of exogenous feeding for larval survival and recruitment success. [ABSTRACT FROM AUTHOR]

Background: Despite dietary recommendations of polyunsaturated fatty acids (PUFAs) for cardiometabolic health, n-3 and n-6 PUFAs and their interplay in relation to diabetes risk remain debated. Importantly, data among pregnant women are scarce. We investigated individual plasma phospholipid n-3 and n-6 PUFAs in early to midpregnancy in relation to subsequent risk of gestational diabetes mellitus (GDM).Methods and Findings: Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort (n = 2,802), individual plasma phospholipid n-3 and n-6 PUFAs levels were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used, adjusting for major risk factors for GDM. After adjusting for covariates, individual n-3 eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) were inversely correlated with insulin-resistance markers, whereas individual n-6 dihomo-gamma-linolenic acid (DGLA) was positively correlated with insulin-resistance markers. At GW 15-26, a standard deviation (SD) increase in total n-3 PUFAs and individual n-3 DPA was associated with a 36% (adjusted odds ratio 0.64; 95% CI 0.42-0.96; P = 0.042) and 33% (0.67; 95% CI 0.45-0.99; P = 0.047) lower risk of GDM, respectively; however, the significance did not persist after post hoc false-discovery rate (FDR) correction (FDR-corrected P values > 0.05). Associations between total n-6 PUFAs and GDM were null, whereas associations with individual n-6 PUFAs were differential. Per SD increase, gamma-linolenic acid (GLA) at GWs 10-14 and DGLA at GWs 10-14 and 15-26 were significantly associated with a 1.40- to 1.95-fold higher risk of GDM, whereas docosatetraenoic acid (DTA) at GW 15-26 was associated with a 45% (0.55; 95% CI 0.37-0.83) lower risk of GDM (all FDR-corrected P values < 0.05). Null associations were observed for linoleic acid (LA) in either gestational window in relation to risk of GDM. Women with high (≥median) n-3 PUFAs and low (Conclusions: Our findings may suggest a potential role of primarily endogenously metabolized plasma phospholipid n-6 PUFAs including GLA, DGLA, and DTA in early to midpregnancy in the development of GDM. Null findings on primarily diet-derived n-3 EPA and DHA and n-6 LA do not provide strong evidence to suggest a beneficial role in prevention of GDM, although not excluding the potential benefit of EPA and DHA on glucose-insulin homeostasis given the inverse associations with insulin-resistance markers. Our findings highlight the importance of assessing individual circulating PUFAs to investigate their distinct pathophysiologic roles in glucose homeostasis in pregnancy. [ABSTRACT FROM AUTHOR]