Optimizing analytical precision in the identification of synthetic cathinones and isomers: a comparative assessment of diverse GC-MS operating parameters.

Analyzing new psychoactive substances (NPSs) in forensic laboratories present a formidable challenge globally. Within illicit drug analysis, gas chromatography-mass spectrometry (GC-MS) emerges as a robust analytical tool. This study endeavors to assess and compare peak resolution in the analysis of illicit drugs, specifically focusing on 21 synthetic cathinones, encompassing 9 cathinone isomers. Varied GC-MS operating conditions, including distinct GC-MS columns and thermal gradients, were systematically employed for the simultaneous analysis of these synthetic cathinones. The study utilized HP-1 nonpolar and HP-5MS low-bleed columns to achieve optimal analyte resolution through modulation of GC-MS oven conditions. Mass spectra were meticulously recorded within a mass-to-charge (m/z) range spanning from 40 to 500 in full scan mode. The data showed that the cathinone isomers slightly differed in retention times and mass spectra. The GC oven conditions affected the peak resolution for chromatographic separation even with the same column. The peak resolution improved using a slower thermal gradient heat speed with a prolonged analysis time. Conclusively, the interplay of GC columns and thermal gradients emerged as pivotal factors impacting peak resolution in the analysis of illicit drugs. These empirical insights contribute to a nuanced understanding of peak resolution dynamics and facilitate the identification of synthetic cathinones, including their isomers, in seized materials through the judicious application of GC-MS methodologies.

Financial toxicity among patients undergoing resectional surgery for inflammatory bowel disease in the United States.

AIM: Financial toxicity describes the financial burden and distress that patients experience due to medical treatment. Financial toxicity has yet to be characterized among patients with inflammatory bowel disease (IBD) undergoing surgical management of their disease. This study investigated the risk of financial toxicity associated with undergoing surgery for IBD. METHODS: This study used a retrospective analysis using the National Inpatient Sample from 2015 to 2019. Adult patients who underwent IBD-related surgery were identified using the International Classification of Diseases (10th Revision) diagnostic and procedure codes and stratified into privately insured and uninsured groups. The primary outcome was risk of financial toxicity, defined as hospital admission charges that constituted 40% or more of patient's post-subsistence income. Secondary outcomes included total hospital admission cost and predictors of financial toxicity. RESULTS: The analytical cohort consisted of 6412 privately insured and 3694 uninsured patients. Overall median hospital charges were $21 628 (interquartile range $14 758-$35 386). Risk of financial toxicity was 86.5% among uninsured patients and 0% among insured patients. Predictors of financial toxicity included emergency admission, being in the lowest residential income quartile and having ulcerative colitis (compared to Crohn's disease). Additional predictors were being of Black race or male sex. CONCLUSION: Financial toxicity is a serious consequence of IBD-related surgery among uninsured patients. Given the pervasive nature of this consequence, future steps to support uninsured patients receiving surgery, in particular emergency surgery, related to their IBD are needed to protect this group from financial risk.

Disparities in access to minimally invasive surgery for inflammatory bowel disease and outcomes by insurance status: analysis of the 2015 to 2019 National Inpatient Sample.

INTRODUCTION: Despite being the preferred modality for treatment of colorectal cancer and diverticular disease, minimally invasive surgery (MIS) has been adopted slowly for treatment of inflammatory bowel disease (IBD) due to its technical challenges. The present study aims to assess the disparities in use of MIS for patients with IBD. METHODS: A retrospective analysis of the National Inpatient Sample (NIS) database from October 2015 to December 2019 was conducted. Patients < 65 years of age were stratified by either private insurance or Medicaid. The primary outcome was access to MIS and secondary outcomes were in-hospital mortality, complications, length of stay (LOS), and total admission cost. Univariate and multivariate regression was utilized to determine the association between insurance status and outcomes. RESULTS: The NIS sample population included 7866 patients with private insurance and 1689 with Medicaid. Medicaid patients had lower odds of receiving MIS than private insurance patients (OR 0.85, 95% CI [0.74-0.97], p = 0.017), and experienced more postoperative genitourinary complications (OR 1.36, 95% CI [1.08-1.71], p = 0.009). In addition, LOS was longer by 1.76 days (p < 0.001) and the total cost was higher by $5043 USD (p < 0.001) in the Medicaid group. Independent predictors of receiving MIS were age < 40 years old, female sex, highest income quartile, diagnosis of ulcerative colitis, elective admission, and care at teaching hospitals. CONCLUSIONS: Patients with Medicaid are less likely to receive MIS, have longer lengths of stay, and incur higher costs for the surgical management of their IBD. Further investigations into disparities in inflammatory bowel disease care for Medicaid patients are warranted.

Financial toxicity risk among patients with gastric banding complications in the United States: analysis of the National Inpatient Sample.

BACKGROUND: Laparoscopic adjustable gastric banding (AGB) was historically among the most performed bariatric procedures but has fallen out of favor in recent years due to poor long-term weight loss and high revisional surgery rates. Significant financial hardship of medical care, known as "financial toxicity," can occur from experiencing unexpected complications of AGB. OBJECTIVE: To investigate the risk of financial toxicity among patients being admitted for AGB complications. SETTING: United States. METHODS: All uninsured and privately-insured patients who were admitted for AGB complications were identified from the National Inpatient Sample 2015-2019. Publicly available government data (U.S. Census Bureau, Bureau of Labor, The Centers for Medicare and Medicaid Services) were utilized to estimate patient income, food expenditures, and average maximum out-of-pocket expenditures. Financial toxicity was defined as total admission cost from AGB complications ≥40% of postsubsistence income. RESULTS: Among 28,005 patients, 66% patients had private insurance and 44% patients were uninsured. Median total admission cost was $12,443 (interquartile range $7959-$19,859) and $15,182 for those who received revisional bariatric surgery. Approximately 55% of the uninsured patients and 1% of insured patients were at risk of financial toxicity after admission for banding-related complications. Patients who had an emergency admission, revisional surgery, or postoperative intensive care unit admission were more likely to experience financial catastrophe following admission (P < .01). CONCLUSIONS: About 1 in 2 uninsured patients admitted for AGB-related complications were at risk of financial toxicity. In addition to surgical risks, providers should consider the potential financial consequences of AGB when counselling patients on their choice of surgery.

Clinical outcomes and cumulative healthcare costs of TAVR vs. SAVR in Asia.

Objectives: This study compared transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in terms of short- and long-term effectiveness. Methods: This retrospective cohort study based on nationwide National Health Insurance claims data and Cause of Death data focused on adult patients (n = 3,643) who received SAVR (79%) or TAVR (21%) between 2015 and 2019. Propensity score overlap weighting was applied to account for selection bias. Primary outcomes included all-cause mortality (ACM), hospitalization for heart failure, and a composite endpoint of major adverse cardiac events (MACE). Secondary outcomes included medical utilization, hospital stay, and total medical costs at index admission for the procedure and in various post-procedure periods. The Cox proportional-hazard model with competing risk was used to investigate survival and incidental health outcomes. Generalized estimation equation (GEE) models were used to estimate differences in the utilization of medical resources and overall costs. Results: After weighting, the mean age of the patients was 77.98 ± 5.86 years in the TAVR group and 77.98 ± 2.55 years in the SAVR group. More than half of the patients were female (53.94%). The incidence of negative outcomes was lower in the TAVR group than in the SAVR group, including 1-year ACM (11.39 vs. 17.98%) and 3-year ACM (15.77 vs. 23.85%). The risk of ACM was lower in the TAVR group (HR [95% CI]: 0.61 [0.44-0.84]; P = 0.002) as was the risk of CV death (HR [95% CI]: 0.47 [0.30-0.74]; P = 0.001) or MACE (HR [95% CI]: 0.66 [0.46-0.96]; P = 0.0274). Total medical costs were significantly higher in the TAVR group than in the SAVR in the first year after the procedure ($1,271.89 ± 4,048.36 vs. $887.20 ± 978.51; P = 0.0266); however, costs were similar in the second and third years after the procedure. The cumulative total medical costs after the procedure were significantly higher in the TAVR group than in the SAVR group (adjusted difference: $420.49 ± 176.48; P = 0.0172). Conclusion: In this real-world cohort of patients with aortic stenosis, TAVR proved superior to SAVR in terms of clinical outcomes and survival with comparable medical utilization after the procedure.

Artificial Intelligence for Contrast-Free MRI: Scar Assessment in Myocardial Infarction Using Deep Learning-Based Virtual Native Enhancement.

BACKGROUND: Myocardial scars are assessed noninvasively using cardiovascular magnetic resonance late gadolinium enhancement (LGE) as an imaging gold standard. A contrast-free approach would provide many advantages, including a faster and cheaper scan without contrast-associated problems. METHODS: Virtual native enhancement (VNE) is a novel technology that can produce virtual LGE-like images without the need for contrast. VNE combines cine imaging and native T1 maps to produce LGE-like images using artificial intelligence. VNE was developed for patients with previous myocardial infarction from 4271 data sets (912 patients); each data set comprises slice position-matched cine, T1 maps, and LGE images. After quality control, 3002 data sets (775 patients) were used for development and 291 data sets (68 patients) for testing. The VNE generator was trained using generative adversarial networks, using 2 adversarial discriminators to improve the image quality. The left ventricle was contoured semiautomatically. Myocardial scar volume was quantified using the full width at half maximum method. Scar transmurality was measured using the centerline chord method and visualized on bull's-eye plots. Lesion quantification by VNE and LGE was compared using linear regression, Pearson correlation (R), and intraclass correlation coefficients. Proof-of-principle histopathologic comparison of VNE in a porcine model of myocardial infarction also was performed. RESULTS: VNE provided significantly better image quality than LGE on blinded analysis by 5 independent operators on 291 data sets (all P<0.001). VNE correlated strongly with LGE in quantifying scar size (R, 0.89; intraclass correlation coefficient, 0.94) and transmurality (R, 0.84; intraclass correlation coefficient, 0.90) in 66 patients (277 test data sets). Two cardiovascular magnetic resonance experts reviewed all test image slices and reported an overall accuracy of 84% for VNE in detecting scars when compared with LGE, with specificity of 100% and sensitivity of 77%. VNE also showed excellent visuospatial agreement with histopathology in 2 cases of a porcine model of myocardial infarction. CONCLUSIONS: VNE demonstrated high agreement with LGE cardiovascular magnetic resonance for myocardial scar assessment in patients with previous myocardial infarction in visuospatial distribution and lesion quantification with superior image quality. VNE is a potentially transformative artificial intelligence-based technology with promise in reducing scan times and costs, increasing clinical throughput, and improving the accessibility of cardiovascular magnetic resonance in the near future.

The socioeconomic landscape of the exposome during pregnancy.

BACKGROUND: While socioeconomic position (SEP) is consistently related to pregnancy and birth outcome disparities, relevant biological mechanisms are manifold, thus necessitating more comprehensive characterization of SEP-exposome associations during pregnancy. OBJECTIVES: We implemented an exposomic approach to systematically characterize the socioeconomic landscape of prenatal exposures in a setting where social segregation was less distinct in a hypotheses-generating manner. METHODS: We described the correlation structure of 134 prenatal exogenous and endogenous sources (e.g., micronutrients, hormones, immunomodulatory metabolites, environmental pollutants) collected in a diverse, population-representative, urban, high-income longitudinal mother-offspring cohort (N = 1341; 2009-2011). We examined the associations between maternal, paternal, household, and areal level SEP indicators and 134 exposures using multiple regressions adjusted for precision variables, as well as potential effect measure modification by ethnicity and nativity. Finally, we generated summary SEP indices using Multiple Correspondence Analysis to further explore possible curved relationships. RESULTS: Individual and household SEP were associated with anthropometric/adiposity measures, folate, omega-3 fatty acids, insulin-like growth factor-II, fasting glucose, and neopterin, an inflammatory marker. We observed paternal education was more strongly and consistently related to maternal exposures than maternal education. This was most apparent amongst couples discordant on education. Analyses revealed additional non-linear associations between areal composite SEP and particulate matter. Environmental contaminants (e.g., per- and polyfluoroalkyl substances) and micronutrients (e.g., folate and copper) showed opposing associations by ethnicity and nativity, respectively. DISCUSSION: SEP-exposome relationships are complex, non-linear, and context specific. Our findings reinforce the potential role of paternal contributions and context-specific modifiers of associations, such as between ethnicity and maternal diet-related exposures. Despite weak presumed areal clustering of individual exposures in our context, our approach reinforces subtle non-linearities in areal-level exposures.

The effect of pay for performance on risk incidence of hip fracture in type 2 diabetic patients: a nationwide population-based cohort study.

OBJECTIVES: Diabetes mellitus (DM) increases the risk of hip fracture. The literature rarely discusses the importance of pay-for-performance (P4P) programs for the incidence of hip fractures in patients with type 2 DM (T2DM). This study aimed to examine the impact of the P4P program on hip fracture risk in patients with T2DM. METHODS: This retrospective cohort study focused on data from T2DM patients aged 45 and older between 2001 and 2012. We continued to track these data until 2013. The data were collected from the National Health Insurance Research Database in Taiwan. To minimize selection bias, T2DM patients were divided into P4P enrollees and non-enrollees. Propensity score matching by greedy matching technique (1:1 ratio) was used to include 252,266 participants. A Cox proportional hazard model was performed to examine the impact of the P4P program on hip fracture risk. We used the bootstrap method to perform sensitivity analysis by random sampling with replacement. RESULTS: Our results showed that the risk of hip fracture in P4P enrollees was 0.92 times that of non-enrollees. (hazards ratio [HR] = 0.92; 95% confidence interval [CI]: 0.85-0.99). P4P enrollees who received regular treatment had lower risk in the first 4 years (HR = 0.90; 95%CI: 0.84-0.96) but no statistically significant difference after 4-year enrollment (HR = 0.99; 95%CI: 0.93-1.06). There was no statistically significant difference in the effect of hip fractures between P4P non-enrollees and P4P enrollees with irregular treatment (HR = 0.94, 95%CI: 0.87-1.03). Through sensitivity analysis, the results also showed P4P enrollees had a lower risk of hip fracture compared to P4P non-enrollees (mean HR = 0.919; 95% CI: 0.912-0.926). Stratified analysis showed that patients without DM complications (DCSI = 0) who enrolled in P4P had lower risks of hip fractures than the non-enrollees (HR = 0.90; 95% CI: 0.82-0.98). CONCLUSION: T2DM patients enrolled in P4P program can reduce the risks of hip fracture incidence. Early inclusion of patients without DM complications in the P4P program can effectively reduce hip fractures.

A Toxicokinetic Framework and Analysis Tool for Interpreting Organisation for Economic Co-operation and Development Guideline 305 Dietary Bioaccumulation Tests.

The Organisation for Economic Co-operation and Development guideline 305 for bioaccumulation testing in fish includes the option to conduct a dietary test for assessing a chemical's bioaccumulation behavior. However, the one-compartment toxicokinetic model that is used in the guidelines to analyze the results from dietary bioaccumulation tests is not consistent with the current state of the science, experimental practices, and information needs for bioaccumulation and risk assessment. The present study presents 1) a 2-compartment toxicokinetic modeling framework for describing the bioaccumulation of neutral hydrophobic organic chemicals in fish and 2) an associated toxicokinetic analysis tool (absorption, distribution, metabolism, and excretion [ADME] B calculator) for the analysis and interpretation of dietary bioaccumulation test data from OECD-305 dietary tests. The model framework and ADME-B calculator are illustrated by analysis of fish dietary bioaccumulation test data for 238 substances representing different structural classes and susceptibilities to biotransformation. The ADME of the chemicals is determined from dietary bioaccumulation tests and bioconcentration factors, biomagnification factors, and somatic and intestinal biotransformation rates. The 2-compartment fish toxicokinetic model can account for the effect of the exposure pathway on bioaccumulation, which the one-compartment model cannot. This insight is important for applying a weight-of-evidence approach to bioaccumulation assessment where information from aqueous and dietary test endpoints can be integrated to improve the evaluation of a chemical's bioaccumulation potential. Environ Toxicol Chem 2019;39:171-188. © 2019 SETAC.

Vulnerability and ecological footprint: a comparison between urban Taipei and rural Yunlin, Taiwan.

Climate change issues and adaptation strategies have drawn much attention from many fields in recent years. Taiwan, an island state, is deeply threatened by the multiple threats posed by climate change. However, different urban and rural areas have numerous adaptation approaches due to their differences in vulnerability. In Taipei City (urban), its biophysical vulnerability is mainly affected by flooded areas and high flood depths caused by landslides and heavy rains. Its social vulnerability is affected by economic development, high household assets, and population concentration. In Yunlin County (rural), its biophysical vulnerability is also affected by flooded areas and high flood depths caused by heavy rains. Its social vulnerability is affected by the elderly living alone, low household assets, and low healthcare. In order to propose appropriate adaptation strategies of urban and rural areas under different vulnerabilities, this study uses an overlapping method to examine the relationship between the integrated vulnerability (biophysical and social) of Taipei and Yunlin along with the ecological footprint (EF), a measurement of human demands for resources and ecological services. This study reviews the literature and uses Taiwan's NCDR (National Science and Technology Center for Disaster Reduction) data to analyze the biophysical vulnerability and the social vulnerability and further calculate the integrated vulnerability. In this study, questionnaire surveys were conducted. In Taipei, 446 valid questionnaires were collected, while 393 were collected in Yunlin. The results show that personal EF in Taipei is higher than that in Yunlin. In the end, this study elucidates the relationship between integrated vulnerability and personal EF of Taipei and Yunlin. Four types of risk areas in urban Taipei and rural Yunlin are sorted out (high vulnerability/high EF, high vulnerability/low EF, low vulnerability/high EF, and low vulnerability/low EF). The empirical results can be adopted by local governments, communities, and NGOs to establish appropriate strategies for mitigation and adaptation in the different risk areas.

The hidden cost of an extensive preoperative work-up: predictors of attrition after referral for bariatric surgery in a universal healthcare system.

BACKGROUND: Bariatric surgery is in high demand and patients generally undergo an extensive work-up process to maximize the success of surgery, especially in universal healthcare systems. Although valuable, this work-up process can lead to attrition before surgery. Therefore, we aim to assess patient and health system factors associated with attrition after bariatric surgery referral in a universal healthcare system. METHODS: This was a population-based study of all patients aged ≥ 18 referred for bariatric surgery in Ontario, Canada from 2009 to 2015. Primary outcome was patients who dropped out of bariatric surgery after referral. Predictors of attrition after referral included patient demographics, clinical, institutional, and socioeconomic variables. Odds ratios and 95% CIs were estimated by multilevel logistic regression models. RESULTS: From 17,703 patients that were referred for bariatric surgery, 4122 patients dropped after the initial referral. Male patients, increasing age, and longer wait times for surgery were significantly (P < 0.0001) associated with higher odds of attrition. Additionally, smoker status, immigration status, unemployment, and disability were significant factors (P < 0.0001) predicting attrition. Patients who lived in lowest income quintile neighborhoods, when compared to those from the richest neighborhoods, had significantly higher odds of attrition (P = 0.02). Sleep apnea was associated with lower odds of attrition while diabetes and heart failure both with higher odds of attrition. CONCLUSION: Even in a universal healthcare system, there are various factors that could lead to increased odds of attrition before bariatric surgery. Clear disparities exist for certain marginalized populations. Further studies are warranted to ensure equitable utilization of bariatric surgery for all patients.

Association of sugar-sweetened beverage intake at 18 months and 5 years of age with adiposity outcomes at 6 years of age: the Singapore GUSTO mother-offspring cohort.

Consumption of sugar-sweetened beverages (SSB) by infants and young children are less explored in Asian populations. The Growing Up in Singapore Towards healthy Outcomes cohort study examined associations between SSB intake at 18 months and 5 years of age, with adiposity measures at 6 years of age. We studied Singaporean infants/children with SSB intake assessed by FFQ at 18 months of age (n 555) and 5 years of age (n 767). The median for SSB intakes is 28 (interquartile range 5·5-98) ml at 18 months of age and 111 (interquartile range 57-198) ml at 5 years of age. Association between SSB intake (100 ml/d increments and tertile categories) and adiposity measures (BMI standard deviation scores (sd units), sum of skinfolds (SSF)) and overweight/obesity status were examined using multivariable linear and Poisson regression models, respectively. After adjusting for confounders and additionally for energy intake, SSB intake at age 18 months were not significantly associated with later adiposity measures and overweight/obesity outcomes. In contrast, at age 5 years, SSB intake when modelled as 100 ml/d increments were associated with higher BMI by 0·09 (95 % CI 0·02, 0·16) sd units, higher SSF thickness by 0·68 (95 % CI 0·06, 1·44) mm and increased risk of overweight/obesity by 1·2 (95 % CI 1·07, 1·23) times at age 6 years. Trends were consistent with SSB intake modelled as categorical tertiles. In summary, SSB intake in young childhood is associated with higher risks of adiposity and overweight/obesity. Public health policies working to reduce SSB consumption need to focus on prevention programmes targeted at young children.

The Impact of Resident and Fellow Participation in Transsphenoidal Pituitary Surgery.

OBJECTIVES/HYPOTHESIS: Postoperative complications is an important marker of healthcare quality. The aim of this study was to analyze the impact of resident and fellow participation on postoperative complications in transsphenoidal pituitary surgery in a multi-institutional setting. STUDY DESIGN: Retrospective analysis of population-based surgical registry. SETTING: Academic medical center. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was utilized to generate transsphenoidal pituitary surgery patient cohorts. The attending with resident and/or fellow group was compared to the attending alone based on demographics and preoperative and postoperative variables. RESULTS: A total of 469 cases were included in the analysis, with 315 performed with resident participation and 154 by attendings alone. The attending group had higher rates of diabetics (20.1% vs. 11.7%, P = 0.015) and patients with a history of previous percutaneous coronary intervention (6.0 vs. 1.6%, P = 0.009). Although the attending group demonstrated higher rates of surgical complications, and the resident/fellow group showed increased incidence in medical and overall complication rates, there was no statistical difference between the two groups. Multivariate analysis further demonstrated lack of significance in complication rates between attendings and residents/fellows. CONCLUSION: Resident and fellow participation in transsphenoidal surgery is not associated with significant differences in surgical complications, medical complications, mortality, operating time, reoperation rates, or readmission rates when compared to attendings. LEVEL OF EVIDENCE: 4 Laryngoscope, 128:2707-2713, 2018.

Growth Assessment and Monitoring during Childhood.

Growth is an indicator of the health and nutritional status of infants and children. Health organisations and professionals worldwide advocate monitoring the growth of children with the primary aim of identifying and preventing malnutrition and/or obesity. Growth monitoring should be part of every health care consultation for children. However, physicians during health care consultations are often so busy addressing acute health issues, that they miss the opportunity to monitor the child's growth and provide anticipatory guidance. Appropriate growth monitoring would enable health care providers to detect abnormal growth in a timely manner, as well as to reassure parents if their concerns are unfounded. To perform this effectively, physicians need to be familiar with measurement methods, use of appropriate growth charts and interpretation of results. As weight, height and growth rates may vary among children, physicians also need to understand what constitutes normal growth. This paper aims to clarify the purpose of growth monitoring and provide recommendations for physicians to assess, monitor and manage growth in infants and children in a primary care setting.

Ethanol oxidation and the inhibition by drugs in human liver, stomach and small intestine: Quantitative assessment with numerical organ modeling of alcohol dehydrogenase isozymes.

Alcohol dehydrogenase (ADH) is the principal enzyme responsible for metabolism of ethanol. Human ADH constitutes a complex isozyme family with striking variations in kinetic function and tissue distribution. Liver and gastrointestinal tract are the major sites for first-pass metabolism (FPM). Their relative contributions to alcohol FPM and degrees of the inhibitions by aspirin and its metabolite salicylate, acetaminophen and cimetidine remain controversial. To address this issue, mathematical organ modeling of ethanol-oxidizing activities in target tissues and that of the ethanol-drug interactions were constructed by linear combination of the corresponding numerical rate equations of tissue constituent ADH isozymes with the documented isozyme protein contents, kinetic parameters for ethanol oxidation and the drug inhibitions of ADH isozymes/allozymes that were determined in 0.1 M sodium phosphate at pH 7.5 and 25 °C containing 0.5 mM NAD(+). The organ simulations reveal that the ADH activities in mucosae of the stomach, duodenum and jejunum with ADH1C*1/*1 genotype are less than 1%, respectively, that of the ADH1B*1/*1-ADH1C*1/*1 liver at 1-200 mM ethanol, indicating that liver is major site of the FPM. The apparent hepatic KM and Vmax for ethanol oxidation are simulated to be 0.093 ± 0.019 mM and 4.0 ± 0.1 mmol/min, respectively. At 95% clearance in liver, the logarithmic average sinusoidal ethanol concentration is determined to be 0.80 mM in accordance with the flow-limited gradient perfusion model. The organ simulations indicate that higher therapeutic acetaminophen (0.5 mM) inhibits 16% of ADH1B*1/*1 hepatic ADH activity at 2-20 mM ethanol and that therapeutic salicylate (1.5 mM) inhibits 30-31% of the ADH1B*2/*2 activity, suggesting potential significant inhibitions of ethanol FPM in these allelotypes. The result provides systematic evaluations and predictions by computer simulation on potential ethanol FPM in target tissues and hepatic ethanol-drug interactions in the context of tissue ADH isozymes.

Dietary Pattern Trajectories from 6 to 12 Months of Age in a Multi-Ethnic Asian Cohort.

UNLABELLED: Little is known about the dietary patterns of Asian infants in the first year of life, nor of their associations with maternal socio-demographic factors. Based on the Growing Up in Singapore towards healthy Outcomes (GUSTO) mother-offspring cohort, cross-sectional dietary patterns were derived by factor analysis using 24-h recalls and food diaries of infants at 6-, 9- and 12-months of age. Dietary pattern trajectories were modeled by mapping similar dietary patterns across each age using multilevel mixed models. Associations with maternal socio-demographic variables, collected through questionnaires during pregnancy, were assessed using general linear models. In n = 486 infants, four dietary pattern trajectories were established from 6- to 12-months. Predominantly breastmilk: mainly breastmilk and less formula milk, GUIDELINES: rice porridge, vegetables, fruits and low-fat fish and meat, Easy-to-prepare foods: infant cereals, juices, cakes and biscuits and Noodles (in soup) and seafood: noodle and common accompaniments. In adjusted models, higher maternal education attainment was correlated with higher start scores on Predominantly breastmilk, but lowest education attainment increased its adherence over time. Older mothers had higher start scores on Easy-to-prepare foods, but younger mothers had increased adherence over time. Chinese mothers had higher start scores on Predominantly breastmilk but greater adherence to GUIDELINES over time, while Indian mothers had higher start scores on Easy-to-prepare foods but greater adherence to Predominantly breastmilk with time (p < 0.05 for all). Changes in trajectories over time were small. Hence, dietary patterns established during weaning are strongly influenced by maternal socio-demographic factors and remain stable over the first year of life.

Abdominal adipose tissue compartments vary with ethnicity in Asian neonates: Growing Up in Singapore Toward Healthy Outcomes birth cohort study.

BACKGROUND: A susceptibility to metabolic diseases is associated with abdominal adipose tissue distribution and varies between ethnic groups. The distribution of abdominal adipose tissue at birth may give insights into whether ethnicity-associated variations in metabolic risk originate partly in utero. OBJECTIVE: We assessed the influence of ethnicity on abdominal adipose tissue compartments in Asian neonates in the Growing Up in Singapore Toward Healthy Outcomes mother-offspring cohort. DESIGN: MRI was performed at ≤2 wk after birth in 333 neonates born at ≥34 wk of gestation and with birth weights ≥2000 g. Abdominal superficial subcutaneous tissue (sSAT), deep subcutaneous tissue (dSAT), and internal adipose tissue (IAT) compartment volumes (absolute and as a percentage of the total abdominal volume) were quantified. RESULTS: In multivariate analyses that were controlled for sex, age, and parity, the absolute and percentage of dSAT and the percentage of sSAT (but not absolute sSAT) were greater, whereas absolute IAT (but not the percentage of IAT) was lower, in Indian neonates than in Chinese neonates. Compared with Chinese neonates, Malay neonates had greater percentages of sSAT and dSAT but similar percentages of IAT. Marginal structural model analyses largely confirmed the results on the basis of volume percentages with controlled direct effects of ethnicity on abdominal adipose tissue; dSAT was significantly greater (1.45 mL; 95% CI: 0.49, 2.41 mL, P = 0.003) in non-Chinese (Indian or Malay) neonates than in Chinese neonates. However, ethnic differences in sSAT and IAT were NS [3.06 mL (95% CI:-0.27, 6.39 mL; P = 0.0712) for sSAT and -1.30 mL (95% CI: -2.64, 0.04 mL; P = 0.057) for IAT in non-Chinese compared with Chinese neonates, respectively]. CONCLUSIONS: Indian and Malay neonates have a greater dSAT volume than do Chinese neonates. This finding supports the notion that in utero influences may contribute to higher cardiometabolic risk observed in Indian and Malay persons in our population. If such differences persist in the longitudinal tracking of adipose tissue growth, these differences may contribute to the ethnic disparities in risks of cardiometabolic diseases. This trial was registered at clinicaltrials.gov as NCT01174875.

Inhibition of human alcohol and aldehyde dehydrogenases by aspirin and salicylate: assessment of the effects on first-pass metabolism of ethanol.

Previous studies have reported that aspirin significantly reduced the first-pass metabolism (FPM) of ethanol in humans thereby increasing adverse effects of alcohol. The underlying causes, however, remain poorly understood. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), principal enzymes responsible for metabolism of ethanol, are complex enzyme families that exhibit functional polymorphisms among ethnic groups and distinct tissue distributions. We investigated the inhibition profiles by aspirin and its major metabolite salicylate of ethanol oxidation by recombinant human ADH1A, ADH1B1, ADH1B2, ADH1B3, ADH1C1, ADH1C2, ADH2, and ADH4, and acetaldehyde oxidation by ALDH1A1 and ALDH2, at pH 7.5 and 0.5 mM NAD(+). Competitive inhibition pattern was found to be a predominant type among the ADHs and ALDHs studied, although noncompetitive and uncompetitive inhibitions were also detected in a few cases. The inhibition constants of salicylate for the ADHs and ALDHs were considerably lower than that of aspirin with the exception of ADH1A that can be ascribed to a substitution of Ala-93 at the bottom of substrate pocket as revealed by molecular docking experiments. Kinetic inhibition equation-based simulations show at higher therapeutic levels of blood plasma salicylate (1.5 mM) that the decrease of activities at 2-10 mM ethanol for ADH1A/ADH2 and ADH1B2/ADH1B3 are predicted to be 75-86% and 31-52%, respectively, and that the activity decline for ALDH1A1 and ALDH2 at 10-50 µM acetaldehyde to be 62-73%. Our findings suggest that salicylate may substantially inhibit hepatic FPM of alcohol at both the ADH and ALDH steps when concurrent intaking aspirin.

Validation of prediction equations for resting energy expenditure in Singaporean Chinese men.

Accurate prediction of resting energy expenditure (REE) is important in establishing adequate dietary intake goals for effective weight management. Previous studies have shown that the validity of an energy prediction equation may depend on the ethnicity of the population. Validation studies are lacking in the Singaporean Chinese population. A total of 96 healthy Singaporean Chinese males of age 21­40 years and body mass index (BMI) 18.5­30.0 kg/m2 participated in this study. REE was measured by indirect calorimetry and compared with REE predicted using existing equations. Validity was evaluated on the basis of mean bias and percentage of subjects predicted within ±10% of REE measured. In addition, Bland and Altman analyses were performed. No significant difference was observed between the mean levels of measured and predicted REE derived from the Owen equation. The Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU), Harris­Benedict and Mifflin equations significantly overestimated the mean measured REE by 7.5%, 6.0% and 2.4% respectively. Percentage of valid predictions for FAO/WHO/UNU, Harris­Benedict, Mifflin and Owen equations were 60%, 67%, 75% and 73% respectively. Bland and Altman analyses demonstrated poor agreement for all equations. The Owen equation provided a valid estimation of REE in Singaporean Chinese men at a group level. However, the individual errors of the equations were unacceptable high and may have limited utility in making clinical decisions on nutritional requirements.