In vivo and in vitro effects of genistein as obesogenic/anti-obesogenic compound in the lipid metabolism of rainbow trout (Oncorhynchus mykiss)

Nowadays, soy is one of the most used ingredients in the formulation of fish feed, due to the ample market supply, lower market price, high protein concentration and favorable amino acid composition. Nevertheless, soybean meal products are rich and primary diet source of phytoestrogens, as genistein, which may have a potential negative impact on growth, hormonal regulation and lipid metabolism in fish. The principal aim of this study was to better understand in vivo and in vitro genistein’s effects on lipid metabolism of rainbow trout. In adipose tissue it was showed an unclear role of genistein on lipid metabolism in rainbow trout, and in liver an anti-obesogenic effect, with an up-regulation of autophagy-related genes LC3b (in adipose tissue) and ATG4b (in liver and adipose tissue), a down-regulation of apoptosis-related genes CASP3 (in adipose tissue) and CASP8 (in liver). An increase of VTG mRNA levels in liver was also observed. Genistein partially exerted these effects via estrogen- receptor dependent mechanism. In white muscle, genistein seemed to promote lipid turnover, up-regulating lipogenic (FAS and LXR) and lipolytic (HSL, PPARα and PPARβ) genes. It seemed that genistein could exert its lipolytic role via autophagic way (up-regulation of ATG4b and ATG12l), not through an apoptotic pathway (down-regulation of CASP3). The effects of genistein on lipid-metabolism and apoptosis-related genes in trout muscle were not dose-dependent, only on autophagy-related genes ATG4B and ATG12l. Moreover, a partial estrogenic activity of this phytoestrogen was also seen. Through in vitro analysis (MTT and ORO assay), instead, it was observed an anti-obesogenic effect of genistein on rainbow trout adipocytes, and this effect was not mediated by ERs. Both in vivo and in vitro, genistein exerted its effects in a dose-dependent manner.

The Art of Aidagara: Ethics, Aesthetics, and the Quest for an Ontology of Social Existence in Watsuji Tetsurō’s Rinrigaku

This paper provides an analysis of the key term aidagara (“betweenness”) in the philosophical ethics of Watsuji Tetsurō (1889-1960), in response to and in light of the recent movement in Japanese Buddhist studies known as “Critical Buddhism.” The Critical Buddhist call for a turn away from “topical” or intuitionist thinking and towards (properly Buddhist) “critical” thinking, while problematic in its bipolarity, raises the important issue of the place of “reason” versus “intuition” in Japanese Buddhist ethics. In this paper, a comparison of Watsuji’s “ontological quest” with that of Martin Heidegger (1889-1976), Watsuji’s primary Western source and foil, is followed by an evaluation of a corresponding search for an “ontology of social existence” undertaken by Tanabe Hajime (1885-1962). Ultimately, the philosophico-religious writings of Watsuji Tetsurō allow for the “return” of aesthesis as a modality of social being that is truly dimensionalized, and thus falls prey neither to the verticality of topicalism nor the limiting objectivity of criticalism.

Solder doped polycaprolactone scaffold enables reproducible laser tissue soldering

BACKGROUND AND OBJECTIVES: In this in vitro feasibility study we analyzed tissue fusion using bovine serum albumin (BSA) and Indocyanine green (ICG) doped polycaprolactone (PCL) scaffolds in combination with a diode laser as energy source while focusing on the influence of irradiation power and albumin concentration on the resulting tensile strength and induced tissue damage. MATERIALS AND METHODS: A porous PCL scaffold doped with either 25% or 40% (w/w) of BSA in combination with 0.1% (w/w) ICG was used to fuse rabbit aortas. Soldering energy was delivered through the vessel from the endoluminal side using a continuous wave diode laser at 808 nm via a 400 microm core fiber. Scaffold surface temperatures were analyzed with an infrared camera. Optimum parameters such as irradiation time, radiation power and temperature were determined in view of maximum tensile strength but simultaneously minimum thermally induced tissue damage. Differential scanning calorimetry (DSC) was performed to measure the influence of PCL on the denaturation temperature of BSA. RESULTS: Optimum parameter settings were found to be 60 seconds irradiation time and 1.5 W irradiation power resulting in tensile strengths of around 2,000 mN. Corresponding scaffold surface temperature was 117.4+/- 12 degrees C. Comparison of the two BSA concentration revealed that 40% BSA scaffold resulted in significant higher tensile strength compared to the 25%. At optimum parameter settings, thermal damage was restricted to the adventitia and its interface with the outermost layer of the tunica media. The DSC showed two endothermic peaks in BSA containing samples, both strongly depending on the water content and the presence of PCL and/or ICG. CONCLUSIONS: Diode laser soldering of vascular tissue using BSA-ICG-PCL-scaffolds leads to strong and reproducible tissue bonds, with vessel damage limited to the adventitia. Higher BSA content results in higher tensile strengths. The DSC-measurements showed that BSA denaturation temperature is lowered by addition of water and/or ICG-PCL.

Low extracellular (ECF) glucose affects the neurochemical profile in severe head-injured patients

Glucose (Gluc) is the main energy source for the brain. After severe head-injury energy demand is massively increased and supply is often decreased. In pilot microdialysis studies, many patients with severe head-injury had undetectable glucose concentrations, probably reflecting changes in metabolism and/or reduced supply. We therefore investigated whether patients with low ECF glucose (criterion: < 50 microM for > or = 5 hrs), LOWgluc, differ from patients with higher glucose levels (NORMALgluc) We also tested the interrelationships between other parameters such as lactate, glutamate, K+, brain O2 and CO2, ICP, CPP, and CBF in these two groups. We found that patients with low ECF glucose, LOWgluc, have significantly lower lactate concentrations than patients with "normal" glucose, NORMALgluc, levels do. Spearman correlations between glucose and most other parameters were similar in both patient groups. However, glutamate correlated positively with glucose, lactate, brain CO2 and negatively with brain O2 in the NORMALgluc patient group, whereas glutamate did not significantly correlate with any of these parameters in the LOWgluc group. There was also no correlation between outcome and the dialysate glucose. The results indicate that low ECF glucose is almost always present in severe head-injury. Moreover, the lack of correlation between low glucose and outcome, however, suggests that other energy substrates, such as lactate, are important after TBI.

REMEDIATION OF TETRACYCLINE FROM WATER SOURCES USING VETIVER GRASS (Chrysopogon zizanioides L. Nash) AND TETRACYCLINE-TOLERANT ROOT-ASSOCIATED BACTERIA

Antibiotics are emerging contaminants worldwide. Due to insufficient policy regulations, public awareness, and the constant exposure of the environment to antibiotic sources has created a major environmental concern. Wastewater treatment plants (WWTP) are not equipped to filter-out these compounds before the discharge of the disinfected effluent into water sources (e.g., lakes and streams) and current available technologies are not equipped to remediate these compounds from environmental sources. Hence, the challenge remains to establish a biological system to remove these antibiotics from wastewater. An invitro hydroponic remediation system was developed using vetiver grass (Chrysopogon zizanioides L. Nash) to remediate tetracycline (TC) from water. Comparative metabolomics studies were conducted to investigate the metabolites/pathways associated with tetracycline metabolism in plants and TC-degrading bacteria. The results show that vetiver plants effectively uptake tetracycline from water sources. Vetiver root-associated bacteria recovered during the hydroponic remediation trial were highly tolerant to TC (as high as 600 ppm) and could use TC as a sole carbon and energy source. Growth conditions (pH, temperature, and oxygen requirement) for TC-tolerant bacteria were optimized for higher TC remediation capability from water sources. The plant (roots and shoots) and bacterial species were further characterized for the metabolites produced during the TC degradation process using GC-MS to identify the possible biochemical mechanism involved. Also, the plant root zone was screened for metabolites/enzymes that were secreted during antibiotic degradation and could potentially enhance the degradation process. The root zone was selected for this analysis because this region of the plant has shown a greater capacity for antibiotic degradation compared to the shoot zone. The role of antioxidant enzymes in TC degradation process revealed glutathione-S-transferase (GSTs) as an important group of enzymes in both plant and bacteria potentially involved in TC degradation process. Metabolomics results also suggest potential GST activity in the TC remediation/ transformation process used by plants. This information could be useful in gaining insights for the application of biological remediation systems for the mitigation of antibiotics from waste-water.

WATER ACCESS AND MAINTENANCE IN KARONGA, MALAWI

This report is a case study of how Mwangalala community accesses water and how that access is maintained. Mwangalala community is located in the northern tip of Karonga district in Malawi, Africa. The case study evaluates how close the community is to meeting target 10 of the Millennium Development Goals, sustainable access to safe drinking water, and evaluates the current water system through Human Centered Design’s criteria of desirability, feasibility, and viability. It also makes recommendations to improve water security in Mwangalala community. Data was collected through two years of immersive observation, interviews with 30 families, and observing two wells on three separate occasions. The 30 interviews provided a sample size of over 10% of the community’s population. Participants were initially self-selected and then invited to participate in the research. I walked along community pathways and accepted invitations to join casual conversations in family compounds. After conversing I asked the family members if they would be willing to participate in my research by talking with me about water. Data collected from the interviews and the observations of two wells were compared and analyzed for common themes. Shallow wells or open wells represented the primary water source for 93% of interview participants. Boreholes were also present in the community, but produced unpalatable water due to high concentrations of dissolved iron and were not used as primary water sources. During observations 75% of community members who used the shallow well, primarily used for consumptive uses like cooking or dinking, were females. Boreholes were primarily used for non-consumptive uses such as watering crops or bathing and 77% of the users were male. Shallow wells could remain in disrepair for two months because the repairman was a volunteer, who was not compensated for the skilled labor required to repair the wells. Community members thought the maintenance fee went towards his salary, so did not compensate the repairman when he performed work. This miscommunication provided no incentive for the repairman to make well repairs a priority, and left community members frustrated with untimely repairs. Shallow wells with functional pumps failed to provide water when the water table levels drop during dry season, forcing community members to seek secondary or tertiary water sources. Open wells, converted from shallow wells after community members did not pay for repairs to the pump, represented 44% of the wells originally installed with Mark V hand pumps. These wells whose pumps were not repaired were located in fields and one beside a church. The functional wells were all located on school grounds or in family compounds, where responsibility for the well’s maintenance is clearly defined. Mwangalala community fails to meet Millennium Development goals because the wells used by the community do not provide sustainable access to safe drinking water. Open wells, used by half the participants in the study, lack a top covering to prevent contamination from debris and wildlife. Shallow well repair times are unsustainable, taking longer than two weeks to be repaired, primarily because the repair persons are expected to provide skilled labor to repair the wells without compensation. Improving water security for Mwangalala can be achieved by improving repair times on shallow wells and making water from boreholes palatable. There are no incentives for a volunteer repair person to fix wells in a timely manner. Repair times can be improved by reducing the number of wells a repair person is responsible for and compensating the person for the skilled labor provided. Water security would be further improved by removing iron particulates from borehole water, thus rendering it palatable. This is possible through point of use filtration utilizing ceramic candles; this would make pumped water available year-round.

CAN CHINA USE ALTERNATIVE ENERGIES INSTEAD OF COAL TO PROVIDE MORE ELECTRICITY BY 2030?

Following the rapid growth of China's economy, energy consumption, especially electricity consumption of China, has made a huge increase in the past 30 years. Since China has been using coal as the major energy source to produce electricity during these years, environmental problems have become more and more serious. The research question for this paper is: "Can China use alternative energies instead of coal to produce more electricity in 2030?" Hydro power, nuclear power, natural gas, wind power and solar power are considered as the possible and most popular alternative energies for the current situation of China. To answer the research question above, there are two things to know: How much is the total electricity consumption in China by 2030? And how much electricity can the alternative energies provide in China by 2030? For a more reliable forecast, an econometric model using the Ordinary Least Squares Method is established on this paper to predict the total electricity consumption by 2030. The predicted electricity coming from alternative energy sources by 2030 in China can be calculated from the existing literature. The research results of this paper are analyzed under a reference scenario and a max tech scenario. In the reference scenario, the combination of the alternative energies can provide 47.71% of the total electricity consumption by 2030. In the max tech scenario, it provides 57.96% of the total electricity consumption by 2030. These results are important not only because they indicate the government's long term goal is reachable, but also implies that the natural environment of China could have an inspiring future.

Vergleich der umweltrelevanten Faktoren von Holzfurnierlagenverbundwerkstoffen (WVC – Wood Veneer Composite) und metallischen Werkstoffen am Praxisbeispiel eines Skidfördersystems

Für eine Beurteilung von Produkten bzw. Produktsystemen im Maschinenbau spielen neben technischen Kennwerten immer mehr die Umweltauswirkungen der Systeme eine wichtige Rolle. Diese Anforderungen haben die Nachfrage für nachhaltige und umweltfreundliche Konstruktionswerkstoffe im Maschinenbau erhöht. Eine Möglichkeit für solche ökologisch vorteilhaften Werkstoffe stellen ausgewählte Holzwerkstoffe dar. Mit diesen Holzwerkstoffen sollen technische Produkte entwickelt werden, welche den Unternehmen die Möglichkeit eröffnet, ihren unternehmerischen Beitrag zur Nachhaltigkeit zu steigern und wirtschaftliche Vorteile zu erzielen. Durch diesen Ansatz ist ein gewisses Maß an Ressourcen- und Energieeffizienz verbunden, dass sich kurzfristig und / oder langfristig wirtschaftlich lohnt. Ein damit verbundener gesellschaftlicher Imagegewinn erzeugt einen zusätzlichen Nutzen. Als sogenannte GLP (Green Logistics Plant) wird diese Art der Holzkonstruktion gegenwärtig im Bereich der Fördertechnik entwickelt und angewendet. Ein Anwendungsbeispiel innerhalb der GLP stellt das Gestellsystem für einen Skidförderer dar. Um die ökologische Wirkung der Konstruktionswerkstoffe transparent und nachvollziehbar zu untersuchen, werden vordergründig die Kategorien des Treibhauspotenzials und des (Primär-) Energieaufwandes genutzt. Weiterhin werden die Wirkungskategorien Versauerung, Eutrophierung, Sommersmog und Ozonabbau analysiert. Ergänzend zu bestehenden Untersuchungen soll die ökologische Vorteilhaftigkeit von Holzfurnierlagenverbundwerkstoffe (Wood Veneer Composite – WVC), Baustahl, verzinktem Stahl und Aluminiumlegierungen in der Lebensphase Produktion untersucht werden. Anschließend werden die Ergebnisse auf das Gestell eines Skid-Fördersystems aus WVC und Baustahl übertragen.

Different Land Use Intensities in Grassland Ecosystems Drive Ecology of Microbial Communities Involved in Nitrogen Turnover in Soil

Understanding factors driving the ecology of N cycling microbial communities is of central importance for sustainable land use. In this study we report changes of abundance of denitrifiers, nitrifiers and nitrogen-fixing microorganisms (based on qPCR data for selected functional genes) in response to different land use intensity levels and the consequences for potential turnover rates. We investigated selected grassland sites being comparable with respect to soil type and climatic conditions, which have been continuously treated for many years as intensely used meadows (IM), intensely used mown pastures (IP) and extensively used pastures (EP), respectively. The obtained data were linked to above ground biodiversity pattern as well as water extractable fractions of nitrogen and carbon in soil. Shifts in land use intensity changed plant community composition from systems dominated by s-strategists in extensive managed grasslands to c-strategist dominated communities in intensive managed grasslands. Along the different types of land use intensity, the availability of inorganic nitrogen regulated the abundance of bacterial and archaeal ammonia oxidizers. In contrast, the amount of dissolved organic nitrogen determined the abundance of denitrifiers (nirS and nirK). The high abundance of nifH carrying bacteria at intensive managed sites gave evidence that the amounts of substrates as energy source outcompete the high availability of inorganic nitrogen in these sites. Overall, we revealed that abundance and function of microorganisms involved in key processes of inorganic N cycling (nitrification, denitrification and N fixation) might be independently regulated by different abiotic and biotic factors in response to land use intensity.

Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor. OBJECTIVE To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression. DESIGN Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300). SETTING Academic and private hospitals. PARTICIPANTS Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans. INTERVENTION Ambrisentan, 10 mg/d, or placebo. MEASUREMENTS Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function. RESULTS The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point. LIMITATION The study was terminated early. CONCLUSION Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations. PRIMARY FUNDING SOURCE Gilead Sciences.

Human placental lactogen enhancer: Tissue specificity and binding with specific proteins

Human placental lactogen (hPL) is a 22,000 dalton protein hormone produced in the placenta. The physiological actions of hPL are not well understood but its major activity is to regulate both maternal and fetal metabolism. hPL stimulates maternal lipolysis increasing free fatty acids in the maternal blood, allowing their use as an energy source by the mother, and sparing glucose for the fetus. It may also act as a growth promoting hormone for the fetus. hPL is produced in increasing amounts as pregnancy progresses. At term, hPL accounts for 10% of protein and 5% of total RNA in the placenta. This high level of hPL production is tissue-specific, as hPL is only produced in the placenta by syncytiotrophoblast cells.^ The objective of this work was to understand the mechanism by which such high levels of hPL are produced in a tissue-specific manner. A transcriptional enhancer found 2.2 kb 3$\sp\prime$ to one of the hPL genes (hPL$\sb3$) may explain the regulation of hPL expression. Transient transfection experiments using the hPL-producing human choriocarcinoma cell line JEG-3 localized the hPL enhancer to a 138 bp core element. This 138 bp sequence was found to be tissue specific in its actions as it did not promote transcription in heterologous cell lines. Gel mobility shift assays showed the hPL enhancer interacts specifically with nuclear proteins unique to hPL-producing cells. Within the 138 bp enhancer a 22 bp region was shown to be protected from DNase I digestion due to binding of proteins derived from placental nuclear extracts. Proteins binding this region of the enhancer may be instrumental in the tissue specific activity of the hPL enhancer. ^

Safety and Feasibility of a Diagnostic Algorithm Combining Clinical Probability, d-Dimer Testing, and Ultrasonography for Suspected Upper Extremity Deep Venous Thrombosis: A Prospective Management Study.

BACKGROUND Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, d-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT). OBJECTIVE To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. DESIGN Diagnostic management study. (ClinicalTrials.gov: NCT01324037) SETTING: 16 hospitals in Europe and the United States. PATIENTS 406 inpatients and outpatients with suspected UEDVT. MEASUREMENTS The algorithm consisted of the sequential application of a clinical decision score, d-dimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up. RESULTS The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%). LIMITATIONS This study was not powered to show the safety of the substrategies. d-Dimer testing was done locally. CONCLUSION The combination of a clinical decision score, d-dimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT. PRIMARY FUNDING SOURCE None.

A Numerical Investigation of the Gulf Stream and Its Meanders in Response to Cold Air Outbreaks

The three-dimensional Princeton Ocean Model is used to examine the modification of the Gulf Stream and its meanders by cold air outbreaks. Two types of Gulf Stream meanders are found in the model. Meanders on the shoreward side of the Gulf Stream are baroclinically unstable. They are affected little by the atmospheric forcing because their energy source is stored at the permanent thermocline, well below the influence of the surface forcing. Meanders on the seaward side of the stream are both barotropically and baroclinically unstable. The energy feeding these meanders is stored at the surface front separating the Gulf Stream and the Sargasso Seal which is greatly reduced in case of cold air outbreaks. Thus, meanders there reduce strength and also seem to slow their downstream propagation due to the southward Ekman flow. Heat budget calculations suggest two almost separable processes. The oceanic heal released to the atmosphere during these severe cooling episodes comes almost exclusively from the upper water column. Transport of heat by meanders from the Gulf Stream to the shelf, though it is large, does not disrupt the principal balance. It is balanced nicely with the net heat transport in the downstream direction.

Metabolic adaptations and changes of the mammary immune response during beta-hydroxybutyrate administration

Elevation of ketone bodies occurs frequently after parturition during negative energy balance in high yielding dairy cows. Previous studies illustrated that hyperketonemia interferes with metabolism and it is assumed that it impairs the immune response. However, a causative effect of ketone bodies could not be shown in vivo before, because spontaneous hyperketonemia comes usually along with high NEFA and low glucose concentrations. The objective was to study effects of beta-hydroxybutyrate (BHBA) infusion and an additional intramammary lipopolysaccharide (LPS) challenge on metabolism and immune response in dairy cows. Thirteen dairy cows received intravenously either a BHBA infusion (group BHBA, n=5) to induce hyperketonemia (1.7 mmol/L), or an infusion with a 0.9 % saline solution (Control, n=8) for 56 h. Infusions started at 0900 on day 1 and continue up to 1700 two days later. Two udder quarters were challenged with 200 μg Escherichia coli-LPS 48 h after the start of infusion. Blood samples were taken one week and 2 h before the start of infusions as reference samples and hourly during the infusion. Liver and mammary gland biopsies were taken one week before the start of the infusion, 48 h after the start of the infusion, and mammary tissues was additionally taken 8 h after LPS challenge (56 h after the start of infusions). Rectal temperature (RT) and somatic cell count (SCC) was measured before and 48 h after the start of infusions and hourly during LPS challenge. Blood samples were analyzed for plasma glucose, BHBA, NEFA, triglyceride, urea, insulin, glucagon, and cortisol concentration. The mRNA abundance of factors related to potential adaptations of metabolism and immune system was measured in liver and mammary tissue biopsies. Differences between blood constituents, RT, SCC, and mRNA abundance before and 48 h after the start of infusions, and differences between mRNA abundance before and after LPS challenges were tested for significance by GLM of SAS procedure with treatment as fixed effect. Area under the curve was calculated for blood variables during 48 h BHBA infusion and during the LPS challenge, and additionally for RT and SCC during the LPS challenge. Most surprisingly, both plasma glucose and glucagon concentration decreased during the 48 h of BHBA infusion (P<0.05). During the 48 h of BHBA infusion, serum amyloid A mRNA abundance in mammary gland was increased (P<0.01), and haptoglobin (Hp) mRNA abundance tended to increase in cows treated with BHBA compared to control group (P= 0.07). RT, SCC, and candidate genes related to immune response in the liver were not affected by BHBA infusion. However, during LPS challenge the expected increase of both plasma glucose and glucagon concentration was much less pronounced in the animals treated with BHBA (P<0.05) and also SCC increased much less pronounced in the animals infused with BHBA (P<0.05) than in the controls. An increased BHBA infusion rate to maintain plasma BHBA constant could not fully compensate for the decreased plasma BHBA during the LPS challenge which indicates that BHBA is used as an energy source during the immune response. In addition, BHBA infused animals showed a more pronounced increase of mRNA abundance of IL-8, IL-10, and citrate synthase in the mammary tissue of LPS challenged quarters (P<0.05) than control animals. Results demonstrate that infusion of BHBA affects metabolism through decreased plasma glucose concentration which is likely related to a decreased release of glucagon during hyperketonemia and during additional inflammation. It also affects the systemic and mammary immune response which may reflect the increased susceptibility for mastitis during spontaneous hyperketonemia. The obviously reduced gluconeogenesis in response to BHBA infusion may be a mechanism to stimulated the use of BHBA as an energy source instead of glucose, and/or to save oxaloacetate for the citric acid cycle instead of gluconeogenesis and as a consequence to reduce ketogenesis.

Subclinical thyroid dysfunction and the risk for fractures: a systematic review and meta-analysis.

BACKGROUND Data on the association between subclinical thyroid dysfunction and fractures conflict. PURPOSE To assess the risk for hip and nonspine fractures associated with subclinical thyroid dysfunction among prospective cohorts. DATA SOURCES Search of MEDLINE and EMBASE (1946 to 16 March 2014) and reference lists of retrieved articles without language restriction. STUDY SELECTION Two physicians screened and identified prospective cohorts that measured thyroid function and followed participants to assess fracture outcomes. DATA EXTRACTION One reviewer extracted data using a standardized protocol, and another verified data. Both reviewers independently assessed methodological quality of the studies. DATA SYNTHESIS The 7 population-based cohorts of heterogeneous quality included 50,245 participants with 1966 hip and 3281 nonspine fractures. In random-effects models that included the 5 higher-quality studies, the pooled adjusted hazard ratios (HRs) of participants with subclinical hyperthyroidism versus euthyrodism were 1.38 (95% CI, 0.92 to 2.07) for hip fractures and 1.20 (CI, 0.83 to 1.72) for nonspine fractures without statistical heterogeneity (P = 0.82 and 0.52, respectively; I2= 0%). Pooled estimates for the 7 cohorts were 1.26 (CI, 0.96 to 1.65) for hip fractures and 1.16 (CI, 0.95 to 1.42) for nonspine fractures. When thyroxine recipients were excluded, the HRs for participants with subclinical hyperthyroidism were 2.16 (CI, 0.87 to 5.37) for hip fractures and 1.43 (CI, 0.73 to 2.78) for nonspine fractures. For participants with subclinical hypothyroidism, HRs from higher-quality studies were 1.12 (CI, 0.83 to 1.51) for hip fractures and 1.04 (CI, 0.76 to 1.42) for nonspine fractures (P for heterogeneity = 0.69 and 0.88, respectively; I2 = 0%). LIMITATIONS Selective reporting cannot be excluded. Adjustment for potential common confounders varied and was not adequately done across all studies. CONCLUSION Subclinical hyperthyroidism might be associated with an increased risk for hip and nonspine fractures, but additional large, high-quality studies are needed. PRIMARY FUNDING SOURCE Swiss National Science Foundation.