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Conservation Physiology 2017Evaluating how predators metabolize energy is increasingly useful for conservation physiology, as it can provide information on their current nutritional condition....
Evaluating how predators metabolize energy is increasingly useful for conservation physiology, as it can provide information on their current nutritional condition. However, obtaining metabolic information from mobile marine predators is inherently challenging owing to their relative rarity, cryptic nature and often wide-ranging underwater movements. Here, we investigate aspects of energy metabolism in four free-ranging shark species ( = 281; blacktip, bull, nurse, and tiger) by measuring three metabolic parameters [plasma triglycerides (TAG), free fatty acids (FFA) and cholesterol (CHOL)] via non-lethal biopsy sampling. Plasma TAG, FFA and total CHOL concentrations (in millimoles per litre) varied inter-specifically and with season, year, and shark length varied within a species. The TAG were highest in the plasma of less active species (nurse and tiger sharks), whereas FFA were highest among species with relatively high energetic demands (blacktip and bull sharks), and CHOL concentrations were highest in bull sharks. Although temporal patterns in all metabolites were varied among species, there appeared to be peaks in the spring and summer, with ratios of TAG/CHOL (a proxy for condition) in all species displaying a notable peak in summer. These results provide baseline information of energy metabolism in large sharks and are an important step in understanding how the metabolic parameters can be assessed through non-lethal sampling in the future. In particular, this study emphasizes the importance of accounting for intra-specific and temporal variability in sampling designs seeking to monitor the nutritional condition and metabolic responses of shark populations.
PubMed: 28852506
DOI: 10.1093/conphys/cox002 -
Science Advances Aug 2022Carbon capture and sequestration reduces carbon dioxide emissions and is critical in accomplishing carbon neutrality targets. Here, we demonstrate new sustainable,...
Carbon capture and sequestration reduces carbon dioxide emissions and is critical in accomplishing carbon neutrality targets. Here, we demonstrate new sustainable, solid-state, polyamine-appended, cyanuric acid-stabilized melamine nanoporous networks (MNNs) via dynamic combinatorial chemistry (DCC) at the kilogram scale toward effective and high-capacity carbon dioxide capture. Polyamine-appended MNNs reaction mechanisms with carbon dioxide were elucidated with double-level DCC where two-dimensional heteronuclear chemical shift correlation nuclear magnetic resonance spectroscopy was performed to demonstrate the interatomic interactions. We distinguished ammonium carbamate pairs and a mix of ammonium carbamate and carbamic acid during carbon dioxide chemisorption. The coordination of polyamine and cyanuric acid modification endows MNNs with high adsorption capacity (1.82 millimoles per gram at 1 bar), fast adsorption time (less than 1 minute), low price, and extraordinary stability to cycling by flue gas. This work creates a general industrialization method toward carbon dioxide capture via DCC atomic-level design strategies.
PubMed: 35921416
DOI: 10.1126/sciadv.abo6849 -
JAMA Pediatrics Oct 2019The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear.
IMPORTANCE
The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear.
OBJECTIVE
To examine the association between fluoride exposure during pregnancy and IQ scores in a prospective birth cohort.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, multicenter birth cohort study used information from the Maternal-Infant Research on Environmental Chemicals cohort. Children were born between 2008 and 2012; 41% lived in communities supplied with fluoridated municipal water. The study sample included 601 mother-child pairs recruited from 6 major cities in Canada; children were between ages 3 and 4 years at testing. Data were analyzed between March 2017 and January 2019.
EXPOSURES
Maternal urinary fluoride (MUFSG), adjusted for specific gravity and averaged across 3 trimesters available for 512 pregnant women, as well as self-reported maternal daily fluoride intake from water and beverage consumption available for 400 pregnant women.
MAIN OUTCOMES AND MEASURES
Children's IQ was assessed at ages 3 to 4 years using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses were used to examine covariate-adjusted associations between each fluoride exposure measure and IQ score.
RESULTS
Of 512 mother-child pairs, the mean (SD) age for enrollment for mothers was 32.3 (5.1) years, 463 (90%) were white, and 264 children (52%) were female. Data on MUFSG concentrations, IQ scores, and complete covariates were available for 512 mother-child pairs; data on maternal fluoride intake and children's IQ were available for 400 of 601 mother-child pairs. Women living in areas with fluoridated tap water (n = 141) compared with nonfluoridated water (n = 228) had significantly higher mean (SD) MUFSG concentrations (0.69 [0.42] mg/L vs 0.40 [0.27] mg/L; P = .001; to convert to millimoles per liter, multiply by 0.05263) and fluoride intake levels (0.93 [0.43] vs 0.30 [0.26] mg of fluoride per day; P = .001). Children had mean (SD) Full Scale IQ scores of 107.16 (13.26), range 52-143, with girls showing significantly higher mean (SD) scores than boys: 109.56 (11.96) vs 104.61 (14.09); P = .001. There was a significant interaction (P = .02) between child sex and MUFSG (6.89; 95% CI, 0.96-12.82) indicating a differential association between boys and girls. A 1-mg/L increase in MUFSG was associated with a 4.49-point lower IQ score (95% CI, -8.38 to -0.60) in boys, but there was no statistically significant association with IQ scores in girls (B = 2.40; 95% CI, -2.53 to 7.33). A 1-mg higher daily intake of fluoride among pregnant women was associated with a 3.66 lower IQ score (95% CI, -7.16 to -0.14) in boys and girls.
CONCLUSIONS AND RELEVANCE
In this study, maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years. These findings indicate the possible need to reduce fluoride intake during pregnancy.
PubMed: 31424532
DOI: 10.1001/jamapediatrics.2019.1729 -
The Journal of Clinical Investigation May 1974The present studies were performed to determine whether dipeptide absorption in human jejunum exhibits the characteristics of carrier-mediated transport. 15-cm jejunal...
The present studies were performed to determine whether dipeptide absorption in human jejunum exhibits the characteristics of carrier-mediated transport. 15-cm jejunal segments from human volunteers were perfused with test solutions containing varying amounts of either glycylglycine, glycylleucine, glycine, leucine, glycylglycine with leucine or glycine, glycylglycine with glycylleucine, or glycylleucine with an equimolar mixture of free glycine and leucine. Jejunal absorption rates of both glycylglycine and glycylleucine followed the kinetics of a saturable process. The K(m) value in millimoles/liter of glycylglycine was significantly greater than the K(m) value of glycylleucine (43.3+/-2.6 vs. 26.8+/-5.9, P < 0.05); and the K(m) value of glycine was also significantly greater than the K(m) value of leucine (42.7+/-7.5 vs. 20.4+/-5.4, P < 0.05). While overlapping occurred among the K(m) values of free amino acids and dipeptides, the transport kinetics of dipeptides were characterized by higher V(max) values (in micromoles per minute per 15 centimeters) than those of free amino acids. For example, the V(max) values for glycylglycine and glycine were 837+/-62 and 590+/-56, respectively (P < 0.02). While jejunal absorption rates of glycylglycine were not significantly affected by free leucine or free glycine, they were competitively inhibited by glycylleucine. The jejunal absorption rate of glycylleucine was not significantly altered by an equimolar mixture of free glycine and leucine. The selective absorption of dipeptides was investigated by infusing three equimolar mixtures, each containing two different dipeptides. Among the three dipeptides examined, glycylglycine was the least absorbed. There was no significant difference between the absorption of glycylleucine and leucylglycine. The above studies suggest that absorption of both glycylglycine and glycylleucine is mediated by a carrier which is not shared with free neutral amino acids; and that both COOH- and NH(2)-terminal amino acids appear to be influential in imposing the affinity of a dipeptide for the absorption sites.
Topics: Biological Transport; Dipeptides; Glycine; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Jejunum; Kinetics; Leucine; Male
PubMed: 4825229
DOI: 10.1172/JCI107685 -
European Radiology Jun 2020To assess the additional value of quantitative tCho evaluation to diagnose malignancy and lymph node metastases in suspicious lesions on multiparametric breast MRI...
PURPOSE
To assess the additional value of quantitative tCho evaluation to diagnose malignancy and lymph node metastases in suspicious lesions on multiparametric breast MRI (mpMRI, BI-RADS 4, and BI-RADS 5).
METHODS
One hundred twenty-one patients that demonstrated suspicious multiparametric breast MRI lesions using DCE, T2w, and diffusion-weighted (DW) images were prospectively enrolled in this IRB-approved study. All underwent single-voxel proton MR spectroscopy (H-MRS, point-resolved spectroscopy sequence, TR 2000 ms, TE 272 ms) with and without water suppression. The total choline (tCho) amplitude was measured and normalized to millimoles/liter according to established methodology by two independent readers (R1, R2). ROC-analysis was employed to predict malignancy and lymph node status by tCho results.
RESULTS
One hundred three patients with 74 malignant and 29 benign lesions had full H-MRS data. The area under the ROC curve (AUC) for prediction of malignancy was 0.816 (R1) and 0.809 (R2). A cutoff of 0.8 mmol/l tCho could diagnose malignancy with a sensitivity of > 95%. For prediction of lymph node metastases, tCho measurements achieved an AUC of 0.760 (R1) and 0.788 (R2). At tCho levels < 2.4 mmol/l, no metastatic lymph nodes were found.
CONCLUSION
Quantitative tCho evaluation from H-MRS allowed diagnose malignancy and lymph node status in breast lesions suspicious on multiparametric breast MRI. tCho therefore demonstrated the potential to downgrade suspicious mpMRI lesions and stratify the risk of lymph node metastases for improved patient management.
KEY POINTS
• Quantitative tCho evaluation can distinguish benign from malignant breast lesions suspicious after multiparametric MRI assessment. • Quantitative tCho levels are associated with lymph node status in breast cancer. • Quantitative tCho levels are higher in hormonal receptor positive compared to hormonal receptor negative lesions.
Topics: Adult; Aged; Aged, 80 and over; Breast; Breast Diseases; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Choline; Diffusion Magnetic Resonance Imaging; Female; Humans; Lymph Nodes; Middle Aged; Multiparametric Magnetic Resonance Imaging; Proton Magnetic Resonance Spectroscopy; ROC Curve; Sensitivity and Specificity; Young Adult
PubMed: 32065286
DOI: 10.1007/s00330-020-06678-z -
Journal of Clinical and Experimental... 2022Potential indications for surgery frequently arise in patients awaiting liver transplantation. There is a risk of hepatic decompensation and death triggered by surgical...
BACKGROUND
Potential indications for surgery frequently arise in patients awaiting liver transplantation. There is a risk of hepatic decompensation and death triggered by surgical trauma, but this has not been studied in detail in this unique population. We aimed to quantify the impact of surgical interventions in patients awaiting liver transplantation on hepatic function and identify risk factors for decompensation.
METHODS
All surgeries between 2000 and 2018 in patients awaiting liver transplantation in a highvolume German liver transplant center were analyzed retrospectively. Change in liver function measured as indicated by MELD score was assessed and complication rates recorded. The primary endpoint was a composite of an increase in MELD score by > 5 points or death. A logistic regression model was used for multivariate analysis to identify risk factors.
RESULTS
In total, 177 surgical procedures in 148 patients were analyzed. The primary endpoint was reached in 42 cases (23.7%). The overall in-hospital complication rate (including death) was 44.1%. Multivariate analysis identified elevated leukocyte count, perioperative blood transfusion, preoperative presence of ascites, and preoperative circulatory support as independent risk factors for a decline in liver function or death.
CONCLUSION
Surgery in patients awaiting liver transplantation carries a relevant risk of hepatic decompensation and death that needs to be considered when deciding whether to perform elective surgery prior to or defer until after liver transplantation.
PubMed: 35068787
DOI: 10.1016/j.jceh.2021.03.011 -
JAMA Cardiology Oct 2017The proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab has been demonstrated to reduce the composite of myocardial infarction, stroke, or cardiovascular...
IMPORTANCE
The proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab has been demonstrated to reduce the composite of myocardial infarction, stroke, or cardiovascular death in patients with established atherosclerotic cardiovascular disease. To our knowledge, long-term cost-effectiveness of this therapy has not been evaluated using clinical trial efficacy data.
OBJECTIVE
To evaluate the cost-effectiveness of evolocumab in patients with atherosclerotic cardiovascular disease when added to standard background therapy.
DESIGN, SETTING, AND PARTICIPANTS
A Markov cohort state-transition model was used, integrating US population-specific demographics, risk factors, background therapy, and event rates along with trial-based event risk reduction. Costs, including price of drug, utilities, and transitional probabilities, were included from published sources.
EXPOSURES
Addition of evolocumab to standard background therapy including statins.
MAIN OUTCOMES AND MEASURES
Cardiovascular events including myocardial infarction, ischemic stroke and cardiovascular death, quality-adjusted life-year (QALY), incremental cost-effectiveness ratio (ICER), and net value-based price.
RESULTS
In the base case, using US clinical practice patients with atherosclerotic cardiovascular disease with low-density lipoprotein cholesterol levels of at least 70 mg/dL (to convert to millimoles per liter, multiply by 0.0259) and an annual events rate of 6.4 per 100 patient-years, evolocumab was associated with increased cost and improved QALY: incremental cost, $105 398; incremental QALY, 0.39, with an ICER of $268 637 per QALY gained ($165 689 with discounted price of $10 311 based on mean rebate of 29% for branded pharmaceuticals). Sensitivity and scenario analyses demonstrated ICERs ranging from $100 193 to $488 642 per QALY, with ICER of $413 579 per QALY for trial patient characteristics and event rate of 4.2 per 100 patient-years ($270 192 with discounted price of $10 311) and $483 800 if no cardiovascular mortality reduction emerges. Evolocumab treatment exceeded $150 000 per QALY in most scenarios but would meet this threshold at an annual net price of $9669 ($6780 for the trial participants) or with the discounted net price of $10 311 in patients with low-density lipoprotein cholesterol levels of at least 80 mg/dL.
CONCLUSIONS AND RELEVANCE
At its current list price of $14 523, the addition of evolocumab to standard background therapy in patients with atherosclerotic cardiovascular disease exceeds generally accepted cost-effectiveness thresholds. To achieve an ICER of $150 000 per QALY, the annual net price would need to be substantially lower ($9669 for US clinical practice and $6780 for trial participants), or a higher-risk population would need to be treated.
Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Atherosclerosis; Cost-Benefit Analysis; Female; Humans; Male; Markov Chains; Myocardial Infarction; Quality-Adjusted Life Years; Risk Factors; Stroke; United States
PubMed: 28832867
DOI: 10.1001/jamacardio.2017.2762 -
Cancers Mar 2022Low- and moderate-intensity exercise is safe and feasible during childhood cancer treatment. The feasibility of a bout of high-intensity interval training (HIIT) in this...
Low- and moderate-intensity exercise is safe and feasible during childhood cancer treatment. The feasibility of a bout of high-intensity interval training (HIIT) in this population has not been analyzed to date. Pediatric cancer patients aged between 6 and 18 years were selected based on clinical conditions to perform ten sets of 15 s HIIT (>90% of estimated maximal heart rate (HRmax)) and 1 min active recovery on a bicycle ergometer within the first three chemotherapy courses. We assessed safety and feasibility criteria and the following parameters: perceived exertion rate, heart rate, and lactate and adrenaline concentrations. Out of 212 eligible patients, 11 patients aged 13.9 ± 3.6 years (n = 7 ♂) with lymphoma, leukemia, rhabdomyosarcoma, nephroblastoma, and synovial sarcoma completed the bout of HIIT without serious adverse events. During exercise, patients reached a BORG value maxima of 16 ± 1.2, and their heart rates rose from 78 ± 17 beats per minute (bpm) at rest to 178 ± 12 bpm after exercise (90 ± 6% estimated HRmax). The power-to-weight ratio was 2 ± 0.5 W/kg (watt per kilogram). Blood lactate concentrations increased from 1.09 ± 0.50 mmol/L (millimole per liter) at rest to 5.05 ± 1.88 mmol/L post-exercise. Our preliminary data suggest that HIIT is applicable only in a small number of childhood cancer patients. Individually adapted exercise protocols for patients with multiple impairments are needed.
PubMed: 35326619
DOI: 10.3390/cancers14061468 -
JAMA Pediatrics Dec 2015There is a well-described association between maternal diabetes mellitus and risk of congenital heart disease (CHD) in offspring. Although the clinical diagnoses of type...
IMPORTANCE
There is a well-described association between maternal diabetes mellitus and risk of congenital heart disease (CHD) in offspring. Although the clinical diagnoses of type 2 diabetes or gestational diabetes are strong risk factors for CHD, subclinical abnormalities of glucose and insulin metabolism are common within the general population and could also confer risk for CHD. We hypothesize that continuous measures of blood analytes related to maternal diabetes are related to odds of cardiac malformations.
OBJECTIVE
To explore the potential association of 2 different CHD phenotypes in offspring with maternal midpregnancy measures of glucose and insulin.
DESIGN, SETTING, AND PARTICIPANTS
Case-control study from a population-based cohort of 277 pregnant women in southern and central California carrying infants with tetralogy of Fallot (TOF) (n = 55), dextrotransposition of the great arteries (dTGA) (n = 42), or healthy infants without CHD (n = 180). Serum samples were collected from 2003 through 2007. The analysis was conducted from March through June 2015.
MAIN OUTCOMES AND MEASURES
Blood analytes related to maternal glucose metabolism were measured from random nonfasting second-trimester blood samples. We measured serum insulin levels by a validated radioimmunoassay, and we measured glucose levels. Multivariable logistic regression models estimated the association between these levels and case status.
RESULTS
Serum glucose values were elevated in the maternal samples for offspring with TOF (median, 97.0 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) relative to controls (median, 91.5 mg/dL) (P = .01, Wilcoxon rank sum test), a phenomenon not observed in the maternal samples for offspring with dTGA (median, 90.0 mg/dL) relative to controls (P = .18, Wilcoxon rank sum test). Serum insulin levels were significantly different between controls (median, 18.8 μIU/mL [to convert to picomoles per liter, multiply by 6.945]) and maternal samples for offspring with dTGA (median, 13.1 μIU/mL; P = .048, Wilcoxon rank sum test) but not with TOF (median, 14.3 μIU/mL; P = .35, Wilcoxon rank sum test). Relative to maternal blood glucose levels of infants without cardiac malformations, we observed that maternal blood glucose levels in models including insulin were strongly associated with odds of TOF (adjusted odds ratio = 7.54; 95% CI, 2.30-24.69) but not with dTGA (adjusted odds ratio = 1.16; 95% CI, 0.28-4.79).
CONCLUSIONS AND RELEVANCE
These results represent a direct correlation of glucose as a continuous variable to odds of specific cardiac malformations. The association between serum glucose and odds of TOF indicates the need for additional epidemiological and mechanistic investigations into the risk conferred by insulin signaling and glucose metabolism during early pregnancy.
Topics: Adult; Blood Glucose; California; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Heart Defects, Congenital; Humans; Insulin; Odds Ratio; Pregnancy; Risk Factors; Young Adult
PubMed: 26457543
DOI: 10.1001/jamapediatrics.2015.2831 -
Journal de Gynecologie, Obstetrique Et... 1997Despite many international conferences, there is no consensus on gestational diabetes mellitus and many groups only screen those women who present risk factors or who... (Review)
Review
Despite many international conferences, there is no consensus on gestational diabetes mellitus and many groups only screen those women who present risk factors or who present during pregnancy complications attributable to this condition. Nevertheless, complications secondary to gestational diabetes are equally frequent whether the mother presents risk factor or not, and these risk factors are only present in 30 to 45% of gestational diabetes. Therefore, all pregnant women should be screened ... or none at all. The type of screening test to be used is just as controversial. The test proposed by the WHO alone allows screening and diagnosing simultaneously, but the cut-off value at 7.8 millimoles for post-charge glycemia seems to be too low for a pregnant woman, at the end of the second trimester. The real question of whether screening for and treating gestational diabetes will actually decrease perinatal morbidity and long-term complications for the mother and the infant cannot be answered as of yet. A large prospective study would be needed, including a control group that would not be treated despite pathological glucose levels, which is ethically inconceivable.
Topics: Diabetes, Gestational; Female; Humans; Mass Screening; Patient Selection; Pregnancy; Pregnancy Outcome; Risk Factors; Sensitivity and Specificity; Time Factors; World Health Organization
PubMed: 9509316
DOI: No ID Found