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The rapid spread of electric vehicles is pushing for more and more compact and reliable e-axle architectures. In this scenario, the integration of the on-board battery charger with the traction drive can be a feasible way to reduce the embedded volume and number of components. Anyway, integrated chargers often present safety issues due to the absence of an isolation stage. In this work, a solution is proposed for integrating the on-board battery charger with the traction drive of road electric vehicles equipped with a 6-phase traction motor drive. The proposed charger is deeply integrated within the e-drive powertrain, to reduce the cost and volume of the e-axle with respect to non-integrated solutions, but still providing galvanic insulation, differently from all fully integrated charger in the literature. Dedicated control strategies are developed and tested for regulating the AC grid current at unitary power factor and low THD, and to avoid torque production or rotor movement during charging independently from the rotor position. Extensive simulation results show the feasibility of the proposed solution, together with a proof-of-concept validation on a commercial traction motor.

A woman in her 60s was brought to the emergency department due to a new-onset seizure. She was drowsy on arrival and unable to provide a clinical history. She had a medical history of advanced endometrial cancer, for which she was under the therapeutic protocol pembrolizumab plus lenvatinib. Laboratorial investigations were unremarkable. The brain CT angiography provided further insight into the case by detecting a bilateral convexal subarachnoid haemorrhage with discrete bilateral opercular vasogenic oedema, without other noticeable structural changes. Cerebrospinal fluid analysis was macroscopically haemorrhagic, but otherwise unremarkable. The brain MRI did not provide additional information. Although considered a rare adverse reaction, cerebral haemorrhage has been described for both pembrolizumab and lenvatinib. We cautiously assumed a probable drug aetiology after a thorough review of potential causes. Following discontinuation of these drugs and under anticonvulsive therapy, the patient remained asymptomatic and was discharged home. [ABSTRACT FROM AUTHOR]

Teak (Tectona grandis) is one of the most important wood sources, and it is cultivated in tropical regions with a significant market around the world. Abiotic stresses are an increasingly common and worrying environmental phenomenon because it causes production losses in both agriculture and forestry. Plants adapt to these stress conditions by activation or repression of specific genes, and they synthesize numerous stress proteins to maintain their cellular function. For example, APETALA2/ethylene response factor (AP2/ERF) was found to be involved in stress signal transduction. A search in the teak transcriptome database identified an AP2/ERF gene named TgERF1 with a key AP2/ERF domain. We then verified that the TgERF1 expression is rapidly induced by Polyethylene Glycol (PEG), NaCl, and exogenous phytohormone treatments, suggesting a potential role in drought and salt stress tolerance in teak. The full-length coding sequence of TgERF1 gene was isolated from teak young stems, characterized, cloned, and constitutively overexpressed in tobacco plants. In transgenic tobacco plants, the overexpressed TgERF1 protein was localized exclusively in the cell nucleus, as expected for a transcription factor. Furthermore, functional characterization of TgERF1 provided evidence that TgERF1 is a promising candidate gene to be used as selective marker on plant breeding intending to improve plant stress tolerance. [ABSTRACT FROM AUTHOR]

A clear understanding of how diet alters gastrointestinal communities is important given the suggested link between gut community composition and a wide variety of disease pathologies. To characterize this link for commonly consumed dietary fiber sources, we investigated the change in the fecal community of rats fed diets containing 5% nonnutritive fiber (control), 3% (wt:wt) oat bran plus 2% nonnutritive fiber (OB), or 5% (w/w) wheat bran (WB) over a 28-d feeding trial using both molecular- and cultivation-based methodologies. Pooled fecal samples from 8 rats fed the same diet were analyzed at 4 time points. On d 28, bran-fed rats had approximately twice the total cultivable bacteria than rats fed the control diet. Over the course of feeding, the cultivable community was initially dominated by bacteroides, then by bifidobacteria, lactobacilli, enterococci, and various enterics. In contrast, molecular analysis revealed the appearance of new operational taxonomic units (phylotypes) that were both temporally and inequitably distributed throughout the fecal community. The majority of change occurred in 2 major lineages within the Firmicutes: the Clostridium coccoides group and the Clostridium leptum subgroup. The time course of change depended on the source of bran, with the majority of new phylotypes appearing by d 14 (OB) or d 28 (WB), although adaptation of the fecal community was slow and continued over the entire feeding trial. Bacterial community richness was higher in bran-fed rats than in those fed the control diet. Change within the C. coccoides and C. leptum lineages likely reflect their high abundance within the gut bacterial community and the role of clostridia in fiber digestion. The results illustrate the limitations of relying solely on cultivation to assess bacterial changes and illustrate that community changes are complex in an ecosystem containing high numbers of interdependent and competing species of bacteria. J. Nutr. 139: 2024-2031, 2009. doi: 10.3945/jn.109.109470

Determining associations between intestinal bacteria and continuously measured physiological outcomes is important for understanding the bacteria-host relationship but is not straightforward since abundance data (compositional data) are not normally distributed. To address this issue, we developed a fully Bayesian linear regression model (BRACoD; Bayesian Regression Analysis of Compositional Data) with physiological measurements (continuous data) as a function of a matrix of relative bacterial abundances. Bacteria can be classified as operational taxonomic units or by taxonomy (genus, family, etc.). Bacteria associated with the physiological measurement were identified using a Bayesian variable selection method: Stochastic Search Variable Selection. The output is a list of inclusion probabilities (p^) and coefficients that indicate the strength of the association (β^included) for each bacterial taxa. Tests with simulated communities showed that adopting a cut point value of p^ ≥ 0.3 for identifying included bacteria optimized the true positive rate (TPR) while maintaining a false positive rate (FPR) of ≤ 5%. At this point, the chances of identifying non-contributing bacteria were low and all well-established contributors were included. Comparison with other methods showed that BRACoD (at p^ ≥ 0.3) had higher precision and a higher TPR than a commonly used center log transformed LASSO procedure (clr-LASSO) as well as higher TPR than an off-the-shelf Spike and Slab method after center log transformation (clr-SS). BRACoD was also less likely to include non-contributing bacteria that merely correlate with contributing bacteria. Analysis of a rat microbiome experiment identified 47 operational taxonomic units that contributed to fecal butyrate levels. Of these, 31 were positively and 16 negatively associated with butyrate. Consistent with their known role in butyrate metabolism, most of these fell within the Lachnospiraceae and Ruminococcaceae. We conclude that BRACoD provides a more precise and accurate method for determining bacteria associated with a continuous physiological outcome compared to clr-LASSO. It is more sensitive than a generalized clr-SS algorithm, although it has a higher FPR. Its ability to distinguish genuine contributors from correlated bacteria makes it better suited to discriminating bacteria that directly contribute to an outcome. The algorithm corrects for the distortions arising from compositional data making it appropriate for analysis of microbiome data. Author summary: We present a fully Bayesian linear regression model to identify associations between physiological measurements (continuous data) and intestinal bacteria (relative bacterial abundances; compositional data). The BRACoD (Bayesian Regression Analysis of Compositional Data) algorithm corrects for the compositional nature of the bacterial data to provide a list of inclusion probabilities and regression coefficients that indicate the strength of the association. If desired, the user can specify a cut point to select only the bacteria that meet predetermined performance characteristics. Analysis of a simulated dataset based on data from a rat microbiome study indicated that an inclusion probability cut point value ≥ 0.3 minimized the false positive rate while maintaining a reasonably high sensitivity (true positive rate). The identified associations form a starting point for generating hypotheses about the relationship between the gut microbial community and physiological outcomes. [ABSTRACT FROM AUTHOR]

NAC transcription factors play critical roles in xylem secondary development and in regulation of stress response in plants. NAC proteins related to secondary cell wall development were recently identified and characterized in Tectona grandis (teak), one of the hardwood trees of highest economic importance in the world. In this work, we characterized the novel TgNAC01 gene, which is involved in signaling pathways that mediate teak response to stress. Abscisic acid (ABA) increases TgNAC01 expression in teak plants. Therefore, this gene may have a role in signaling events that mediate ABA-dependent osmotic stress responsive in this plant species. Stable expression in tobacco plants showed that the TgNAC01 protein is localized in the cell nucleus. Overexpression of TgNAC01 in two out three independent transgenic tobacco lines resulted in increased growth, leaf senescence and salt tolerance compared to wild type (WT) plants. Moreover, the stress tolerance of transgenic plants was affected by levels of TgNAC01 gene expression. Water potential, gas exchange and chlorophyll fluorescence were used to determine salt stress tolerance. The 35S:TgNAC01-6 line under 300 mM NaCl stress responded with a significant increase in photosynthesis rate, stomatal conductance, transpiration and carboxylation efficiency, but lower water potential compared to WT plants. The data indicate that the TgNAC01 transcription factor acts as a transcriptional activator of the ABA-mediated regulation and induces leaf senescence. [ABSTRACT FROM AUTHOR]

Abstract Background Off-pump coronary artery bypass grafting has been accused of possibly compromising graft patency. Sixteen slice computed tomography has shown good diagnostic accuracy in the assessment of coronary bypass graft patency when compared with conventional coronary artery angiography and is less invasive. The study hypothesis is that coronary artery bypass grafting (CABG) performed without cardiopulmonary bypass (Off-Pump) has equivalent early graft patency as if performed with cardiopulmonary bypass (On-Pump) and may have reduced complication rate. Methods/Design The Prospective Randomized Comparison of Off-Pump and On-Pump MultI-vessel Coronary Artery BypasS Surgery (PROMISS) is a controlled, single blinded, single centre clinical trial, comparing early graft patency using 16-slice computed tomography in patients with multi-vessel coronary artery disease operated either without or with extracorporeal circulation. Inclusion criteria are multivessel disease with an indication for first time, isolated, non emergent coronary artery bypass grafting with a minimum of three distal anastomoses. Secondary end points are peri-operative mortality, combined morbidity, length of stay, neuro-cognitive testing at 6 weeks and adverse events, stress test and quality of life at 6 months and one year. The sample size of one hundred and fifty patients was calculated in order to enable the detection of a 5% difference in graft patency, with 80% power, considering a minimum of 3 distal anastomoses per patient. Enrolment started in April 2005 and ended July 2007 with study closure in July 2008. Conclusion The PROMISS trial aims to shed new light on the effect of Off-Pump as compared to On-Pump coronary artery bypass surgery on graft patency, assessed by multidetector computed tomography, in unselected patients with multivessel coronary artery disease. Trial Registration Current Controlled Trials ISRCTN58800729

In order to develop approaches for reducing the carbon footprint of the swine and dairy industries, it is important first to identify the methanogenic communities that drive methane emissions from stored manure. In this study, the metabolically active methanogens in substrate-starved manure samples taken from two dairy and one swine manure storage tanks were identified using [ 13 C]-acetate and DNA stable-isotope probing (DNA-SIP). Molecular analysis of recovered genomic [ 13 C]-DNA revealed that two distinct clusters of unclassified methanogen populations affiliated with the Methanoculleus genus, and the populations affiliated with Methanoculleus chikugoensis assimilated acetate-derived carbon (acetate-C) in swine and dairy starved manure samples, respectively. Furthermore, carbon flow calculations indicated that these populations were the primary contributors to methane emissions during these anoxic SIP incubations. Comparative analysis of mcrA gene abundance (coding for a key enzyme of methanogenesis) for Methanoculleus spp. in fresh feces and a wider range of stored dairy or swine manure samples, by real-time quantitative PCR using newly designed specific primers, demonstrated that the abundance of this genus significantly increased during storage. The findings supported the involvement of these particular methanogen populations as methane emitters from swine and dairy manure storage tanks. The study revealed that the ability to assimilate acetate-C for growth in manure differed within the Methanoculleus genus. [ABSTRACT FROM AUTHOR]

Abstract: Despite the high level of effectiveness of natalizumab (NTZ) in the treatment of patients with multiple sclerosis (MS), concerns about its high direct cost and its safety have restricted its use. Our aim was to identify and quantify the clinical factors that predict an optimal response to NTZ. Patients with MS undergoing treatment with NTZ for at least 12months were classified as optimal responders if, during treatment, they sustained a reduction in their Kurtzke Expanded Disability Status Scale (EDSS) score of 1 point or more or experienced a reduction in annualised relapse rate (ARR) of more than 1. The remaining patients were classified as suboptimal responders and non-responders. Our subject pool included 48 patients. The variables associated with optimal response included: ARR in the previous year of at least 2, an age at first administration of 37.5years or less, a baseline EDSS score of 4.5 points or less, a disease duration of 9.5years or less and, in patients with secondary-progressive MS, a progressive-phase duration of 4.5years or less. The characteristics of the disease at its onset did not affect responsiveness, indicating that patients with highly active disease and low disability are the ideal candidates for NTZ treatment, regardless of previous clinical characteristics. [Copyright &y& Elsevier]

Greenhouse gas emissions represent a major problem associated with manure management in the livestock industry. A prerequisite to mitigate methane emissions occurring during manure storage is a clearer understanding of how the microbial consortia involved in methanogenesis function. Here, we have examined manure stored in outdoor tanks from two different farms, at different locations and depths. Physico-chemical and microbiological characterization of these samples indicated differences between each tank, as well as differences within each tank dependent on the depth of sampling. The dynamics of both the bacterial and archaeal communities within these samples were monitored over a 150-day period of anaerobic incubation to identify and track emerging microorganisms, which may be temporally important in the methanogenesis process. Analyses based on DNA fingerprinting of microbial communities identified trends common among all samples as well as trends specific to certain samples. All archaeal communities became enriched with Methanoculleus spp. over time, indicating that the hydrogenotrophic pathway of methanogenesis predominated. Although the emerging species differed in samples obtained from shallow depths compared to deep samples, the temporal enrichment of Methanoculleus suggests that this genus may represent a relevant indicator of methanogenic activity in swine manure storage tanks. [ABSTRACT FROM AUTHOR]

Modal selection induced by parallel polarized optical injection in a vertical-cavity surface-emitting laser (VCSEL) emitting in two transverse modes is analyzed from a theoretical point of view. We show that the selection of the fundamental transverse mode can be achieved when the two transverse modes have parallel polarizations. This selection is accompanied by locking of the fundamental mode to the optically injected signal for large enough values of the wavelength detuning between the fundamental mode and the externally injected signal. The injected power needed to induce modal selection grows as the VCSEL bias current is increased for small positive wavelength detunings, while it is independent on the bias current for larger wavelength detunings. That power exhibits a minimum with respect to the injection wavelength at a value \lambdamin that is slightly longer than the wavelength of the fundamental mode of the solitary VCSEL. We also show that the selection process exhibits bistable behavior when the wavelength of the optically injected signal increases beyond \lambdamin. The width of the bistable region increases linearly with the wavelength of the optically injected signal. Our results show that \lambdamin also increases linearly with the VCSEL bias current. Higher order transverse mode selection and bistability, similar to those found for the fundamental mode, are obtained when the optical injection wavelength is close to that of the higher order mode. Our results are in agreement with the experimental results reported earlier. [ABSTRACT FROM PUBLISHER]

Proximal colon epithelial gene responses to diets containing increasing levels of dietary fermentable material (FM) from 2 different sources were measured to determine whether gene expression patterns were independent of the source of FM. Male Fischer 344 rats (10/group) were fed for 6 wk a control diet containing 10% (g/g) cellulose (0% FM); or a 2, 5, or 10% wheat bran (WB) diet (1 2, 5% FM); or a 2, 5, or 8% fructooligosaccharides (FOS) diet (2, 5, 8% FM). WB and FOS were substituted for cellulose to give a final 10% nondigestible material content including FM. Gene responses were relative to expression in rats fed the control diet. The gene response patterns associated with feeding ∼2% FM 15% WB and 2% FOS) were similar (∼10 gene changes ⩾ 1.6-fold; P ⩽ 0.01) and involved genes associated with transport (Scnn 1g. Mt1a), transcription (Zbtb16, Egr1), immunity (Fkbp5), a gut hormone (Retn1β), and lipid metabolism (Scd2, Insig1). These changes were also similar to those associated with 5% FM but only in rats fed the 10% WB diet. In contrast, the 5% FOS diet (∼5% FM) was associated with 68 gene expression changes ⩾1.6-fold (P ⩽ 0.01). The diet with the highest level of fermentation (8% FOS, ∼-8% FM) was associated with 132 changes ⩾1.6-fold (P ⩽ 0.01), including genes associated with transport, cellular proliferation, oncogene and tumor metastasis, the cell cycle, apoptosis, signal transduction, transcript regulation, immunity, gut hormones, and lipid metabolic processes. These results show that both the amount and source of FM determine proximal colon epithelial gene response patterns in rats. [ABSTRACT FROM AUTHOR]

Folate and choline are interconnected metabolically. The MTHFD1 R653Q SNP is a risk factor for birth defects and there are concerns that choline deficiency may interact with this SNP and exacerbate health risks. 80–90% of women do not meet the Adequate Intake (AI) for choline. The objective of this study was to assess the effects of choline deficiency on maternal one-carbon metabolism and reproductive outcomes in the MTHFD1-synthetase deficient mouse (Mthfd1S), a model for MTHFD1 R653Q. Mthfd1S+/+ and Mthfd1S+/− females were fed control (CD) or choline-deficient diets (ChDD; 1/3 the amount of choline) before mating and during pregnancy. Embryos were evaluated for delays and defects at 10.5 days gestation. Choline metabolites were measured in the maternal liver, and total folate measured in maternal plasma and liver. ChDD significantly decreased choline, betaine, phosphocholine, and dimethylglycine in maternal liver (p < 0.05, ANOVA), and altered phosphatidylcholine metabolism. Maternal and embryonic genotype, and diet-genotype interactions had significant effects on defect incidence. Mild choline deficiency and Mthfd1S+/− genotype alter maternal one-carbon metabolism and increase incidence of developmental defects. Further study is required to determine if low choline intakes contribute to developmental defects in humans, particularly in 653QQ women. [ABSTRACT FROM AUTHOR]

Background: Off-pump coronary artery bypass grafting has been accused of possibly compromising graft patency. Sixteen slice computed tomography has shown good diagnostic accuracy in the assessment of coronary bypass graft patency when compared with conventional coronary artery angiography and is less invasive. The study hypothesis is that coronary artery bypass grafting (CABG) performed without cardiopulmonary bypass (Off-Pump) has equivalent early graft patency as if performed with cardiopulmonary bypass (On-Pump) and may have reduced complication rate. Methods/Design: The Prospective Randomized Comparison of Off-Pump and On-Pump Mult-Ivessel Coronary Artery BypasS Surgery (PROMISS) is a controlled, single blinded, single centre clinical trial, comparing early graft patency using 16-slice computed tomography in patients with multi-vessel coronary artery disease operated either without or with extracorporeal circulation. Inclusion criteria are multivessel disease with an indication for first time, isolated, non emergent coronary artery bypass grafting with a minimum of three distal anastomoses. Secondary end points are peri-operative mortality, combined morbidity, length of stay, neuro-cognitive testing at 6 weeks and adverse events, stress test and quality of life at 6 months and one year. The sample size of one hundred and fifty patients was calculated in order to enable the detection of a 5% difference in graft patency, with 80% power, considering a minimum of 3 distal anastomoses per patient. Enrolment started in April 2005 and ended July 2007 with study closure in July 2008. Conclusion: The PROMISS trial aims to shed new light on the effect of Off-Pump as compared to On-Pump coronary artery bypass surgery on graft patency, assessed by multidetector computed tomography, in unselected patients with multivessel coronary artery disease. Trial Registration: Current Controlled Trials ISRCTN58800729 [ABSTRACT FROM AUTHOR]

Abstract: Background: The value of symptoms and signs in the diagnosis of CHF has rarely been tested in large numbers of patients in the community. The aim of this study was to evaluate the importance of symptoms, signs, and past medical history in the diagnosis of CHF in primary care. Methods: Data on a sample of Portuguese men and women attending 365 primary care centres for any condition other than the treatment of acute infection, metabolic conditions or pregnancy were collected. All subjects who scored three or more points in the sum of categories one and two of the Boston questionnaire (history and physical examination) and those being treated for heart failure with loop or thiazide diuretics were considered to have possible heart failure and referred for further assessment including a resting echocardiogram. The sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio (LR) for the diagnosis of heart failure were calculated. Results: A total of 5434 subjects were identified, of whom 1058 fulfilled the criteria for further assessment; 551 subjects had cardiac dysfunction at rest, of which 35.5% were in NYHA class I and 4.9% in class IV. Prior use of digoxin (LR 24.9) and/or diuretics (LR 10.6), a history of coronary artery disease (LR 7.1) or of pulmonary oedema (LR 54.2), were associated with a greater likelihood of having heart failure. Amongst current symptoms, a history of paroxysmal nocturnal dyspnoea (LR 35.5), orthopnea (LR 39.1) and breathlessness when walking on the flat (LR 25.8) were associated with a diagnosis of heart failure. However, these symptoms were not frequent amongst patients with heart failure within this population (sensitivity <36%). Jugular pressure > 6 cm with hepatic enlargement, and oedema of the lower limbs (LR 130.3), a ventricular gallop (LR 30.0), a heart rate above 110 bpm (LR 26.7), and rales at pulmonary auscultation (LR 23.3) were all associated with a diagnosis of heart failure, but were infrequent findings in patients with heart failure (sensitivity <10%). Conclusions: Symptoms and signs, and clinical history had limited value in diagnosing heart failure when used alone. The signs and symptoms that best predicted a diagnosis of heart failure were those associated with more severe disease. If investigation is limited to patients with more definite symptoms and signs of heart failure, fewer than 50% of cases will be identified and a large number of patients with mild symptoms will be missed. [Copyright &y& Elsevier]

Abstract: Background: There is a common assumption that a normal ECG or a normal heart size on chest X-ray virtually rules out a diagnosis of heart failure. Aims: To assess the value of the electrocardiogram and chest X-ray in identifying patients with chronic heart failure in the community. Methods and results: This study was a secondary analysis of data prospectively collected at the time of patient''s enrolment in the EPICA study, an epidemiological study of the prevalence of heart failure in Portugal. A total of 6300 subjects were clinically evaluated. Patients who presented with symptoms or signs of heart failure, and/or were receiving diuretics for chronic heart failure (CHF) had a chest X-ray, ECG, and echocardiogram. The diagnosis of heart failure was confirmed in 551 cases. Patients with right atrial enlargement, atrial flutter, atrial fibrillation, 2nd degree-Mobitz I atrioventricular block, 1st degree atrioventricular block, left bundle branch block, lung interstitial oedema, and bilateral pleural effusion were more likely to be diagnosed with heart failure. For the diagnosis of heart failure, in the Portuguese population aged over 25 years, an abnormal electrocardiogram had an estimated sensitivity of 81%, and negative predictive value of 75%; an abnormal chest X-ray had an estimated sensitivity of 57%, and negative predictive value of 83%. Twenty five percent of patients with CHF had a normal ECG or chest X-ray. Conclusion: Our results show that electrocardiographic and roentgenographic features are not sufficient to allow heart failure to be reliably predicted in the community and support the recommendation that all patients with suspected heart failure should undergo echocardiography. [Copyright &y& Elsevier]

Abstract: Aim: To validate and estimate the performance statistics and concordance of seven clinical questionnaires for the diagnosis of chronic heart failure (HF). Methods: Community-based epidemiological survey of patients aged >25 years attending a random sample of primary health care centers in Portugal. Heart failure was identified according to the Guidelines of the European Society of Cardiology (ESC). Results: A total of 5434 subjects evaluated by 365 investigators were eligible for analysis, 551 of which had criteria for heart failure. Overall, the questionnaires had high specificity, usually above 90%, but low sensitivity, providing an increase in the likelihood of heart failure from 4.3% pre-test to 25–35% post-test in most cases. The Göteborg questionnaire was the most balanced regarding sensitivity (84%) and specificity (81%) but this may reflect its use of prescription of digoxin or diuretics as diagnostic criteria for diagnosis. The Walma, Framingham and NHANES-I questionnaires performed similarly (Sensitivity: 63%, Specificity: 93%), while the Boston and the Gheorghiade questionnaires had a somewhat lower sensitivity (55%). Concordance was good between the Boston, Framingham, Gheorghiade, NHANES-I and Walma questionnaires. Conclusions: This study evaluated seven clinical questionnaires for the diagnosis of heart failure in the community. Their low sensitivity impairs their usefulness as diagnostic instruments, but their high specificity makes them useful for the identification of patients with fluid retention and/or exercise intolerance from non-cardiac causes. [Copyright &y& Elsevier]

Abstract: Background: Chronic heart failure (CHF) is common and is frequently managed by primary care physicians (PCPs). Despite the European Society of Cardiology (ESC) Guidelines, standard treatments for CHF are frequently underutilised, particularly in primary care. Aim: To evaluate current drug therapy for CHF in adults with HF diagnosed according to ESC guidelines in the context of the EPICA study. Aetiological features and therapy relevant comorbidities were also analysed. Methods: EPICA was a community-based epidemiological study conducted in mainland Portugal. The study involved 365 primary care physicians, who evaluated 6300 primary care attendees aged over 25 years. CHF was diagnosed by clinical and echocardiography criteria according to ESC guidelines. Results: Total of 551 cases of CHF were identified, with a mean age of 65±9 years. The estimated overall prevalence of CHF in the Portuguese population was 4.4%; 1.3% with and 1.7% without left ventricular systolic dysfunction (LVSD). There are 6,280,792 people aged >25 years in Portugal, which extrapolates to 261,400 cases of heart failure. About 80% of patients had a history of hypertension, 39% had a history of coronary artery disease and 15% had atrial fibrillation. Only 58% of patients were on angiotensin-converting enzyme (ACE) inhibitors and 7% on beta-blockers. The type of ventricular dysfunction, age and presence of renal failure had little effect on prescription rates. Diuretics were prescribed in 78%. Thiazides were used more frequently in those with preserved systolic function and frusemide in those with left ventricular systolic dysfunction. Digoxin was prescribed more often to patients with than without left ventricular systolic dysfunction (34% vs. 17%; p=0.02). Long-acting nitrates were prescribed to 20% and amiodarone to 8% of patients. Conclusion: The EPICA study, as in other studies in primary care in Europe, particularly the IMPROVEMENT study, suggests that greater efforts are required to improve training of primary care teams in the management of CHF. [Copyright &y& Elsevier]

Aim: To estimate the prevalence of chronic heart failure (CHF) in mainland Portugal in 1998. Methods and population: A community-based epidemiological survey involving subjects attending primary care centres selected by a combined two-stage sampling and stratified procedure. General practitioners (GPs) randomly selected in proportion to the population of the District, evaluated subjects attending primary care centres aged over 25 years, recruited consecutively and stratified by age. CHF cases were identified according to the Guidelines of the European Society of Cardiology for CHF diagnosis. Results: 5434 eligible subjects were evaluated by 365 GPs; 551 patients with CHF were identified. The overall prevalence and 95% CI of CHF in mainland Portugal is 4.36% (3.69–5.02%), 4.33% in males (3.19–5.46%), and 4.38% in females (3.64–5.13%). Age-specific CHF prevalence was as follows: 1.36% in the 25–49 years-old group (0.39–2.33%), 2.93% in the 50–59 years-old group (5.58–9.37%), 7.63% in the 60–69 years-old group (5.58–9.37%), 12.67% in the 70–79 years-old group (10.73–14.6%), and 16.14% in group over 80 years old (13.81–18.47%). The prevalence of CHF due to systolic dysfunction was 1.3% and the prevalence of CHF with normal systolic function was 1.7%. Conclusions: The overall prevalence of CHF in Portugal was slightly higher than that of other European studies and increases sharply with age. The prevalence of CHF due to systolic dysfunction is very similar to that reported by other recent European studies. The differences found may correspond to differences in methodology rather than actual differences in the population. [Copyright &y& Elsevier]

Methane emissions represent a major environmental concern associated with manure management in the livestock industry. A more thorough understanding of how microbial communities function in manure storage tanks is a prerequisite for mitigating methane emissions. Identifying the microorganisms that are metabolically active is an important first step. Methanogenic archaea are major contributors to methanogenesis in stored swine manure, and we investigated active methanogenic populations by DNA stable isotope probing (DNA-SIP). Following a preincubation of manure samples under anoxic conditions to induce substrate starvation, [U-13C] acetate was added as a labeled substrate. Fingerprint analysis of density-fractionated DNA, using length-heterogeneity analysis of PCR-amplified mcrA genes (encoding the alpha subunit of methyl coenzyme M reductase), showed that the incorporation of 13C into DNA was detectable at in situ acetate concentrations (~7 g/liter). Fingerprints of DNA retrieved from heavy fractions of the 13C treatment were primarily enriched in a 483-bp amplicon and, to a lesser extent, in a 481-bp amplicon. Analyses based on clone libraries of the mcrA and 16S rRNA genes revealed that both of these heavy DNA amplicons corresponded to Methanoculleus spp. Our results demonstrate that uncultivated methanogenic archaea related to Methanoculleus spp. were major contributors to acetate-C assimilation during the anoxic incubation of swine manure storage tank samples. Carbon assimilation and dissimilation rate estimations suggested that Methanoculleus spp. were also major contributors to methane emissions and that the hydrogenotrophic pathway predominated during methanogenesis. [ABSTRACT FROM AUTHOR]

Assisted reproductive technologies (ART) account for 1-6% of births in developed countries. While most children conceived are healthy, increases in birth and genomic imprinting defects have been reported; such abnormal outcomes have been attributed to underlying parental infertility and/or the ART used. Here, we assessed whether paternal genetic and lifestyle factors, that are associated with male infertility and affect the sperm epigenome, can influence ART outcomes. We examined how paternal factors, haploinsufficiency for Dnmt3L, an important co-factor for DNA methylation reactions, and/or diet-induced obesity, in combination with ART (superovulation, in vitro fertilization, embryo culture and embryo transfer), could adversely influence embryo development and DNA methylation patterning in mice. While male mice fed high-fat diets (HFD) gained weight and showed perturbed metabolic health, their sperm DNA methylation was minimally affected by the diet. In contrast, Dnmt3L haploinsufficiency induced a marked loss of DNA methylation in sperm; notably, regions affected were associated with neurodevelopmental pathways and enriched in young retrotransposons, sequences that can have functional consequences in the next generation. Following ART, placental imprinted gene methylation and growth parameters were impacted by one or both paternal factors. For embryos conceived by natural conception, abnormality rates were similar for WT and Dnmt3L+/- fathers. In contrast, paternal Dnmt3L+/- genotype, as compared to WT fathers, resulted in a 3-fold increase in the incidence of morphological abnormalities in embryos generated by ART. Together, the results indicate that embryonic morphological and epigenetic defects associated with ART may be exacerbated in offspring conceived by fathers with sperm epimutations., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Folate and choline are interconnected metabolically. The MTHFD1 R653Q SNP is a risk factor for birth defects and there are concerns that choline deficiency may interact with this SNP and exacerbate health risks. 80-90% of women do not meet the Adequate Intake (AI) for choline. The objective of this study was to assess the effects of choline deficiency on maternal one-carbon metabolism and reproductive outcomes in the MTHFD1-synthetase deficient mouse ( Mthfd1S ), a model for MTHFD1 R653Q. Mthfd1S +/+ and Mthfd1S +/- females were fed control (CD) or choline-deficient diets (ChDD; 1/3 the amount of choline) before mating and during pregnancy. Embryos were evaluated for delays and defects at 10.5 days gestation. Choline metabolites were measured in the maternal liver, and total folate measured in maternal plasma and liver. ChDD significantly decreased choline, betaine, phosphocholine, and dimethylglycine in maternal liver ( p < 0.05, ANOVA), and altered phosphatidylcholine metabolism. Maternal and embryonic genotype, and diet-genotype interactions had significant effects on defect incidence. Mild choline deficiency and Mthfd1S +/- genotype alter maternal one-carbon metabolism and increase incidence of developmental defects. Further study is required to determine if low choline intakes contribute to developmental defects in humans, particularly in 653QQ women.