Concentration andpH dependent steady-state volume of distribution of methotrexate estimated by a simple physiologically based method

The effects of plasma concentration and pH on the steady-state volume of distribution, V_ss,of methotrexate (MTX) were studied in five conditioned male beagle-mongrel dogs. Steady-state plasma MTX concentrations of approximately 1, 20, and 100g/ml were targeted for by i.v. bolus doses followed by i.v. infusions. An isotonic solution of sodium bicarbonate or ammonium chloride was simultaneously infused for the purpose of inducing plasma pH change, while the infusion of an isotonic solution of sodium chloride served as a control. Plasma and urine concentrations of MTX were quantitated by a sensitive high-performance liquid chromatographic method, and the V_ss of MTX was estimated by a recently reported physiologically based method of Chiou and Lam. Statistically significant (p<0.05) concentration and plasma pHdependent V_ss of MTX were observed. Concentration dependence of V_ss was noted in sodium chloride and ammonium chloride infused dogs, but not in bicarbonate treated dogs. There was an average 50.0 and 44.8% increase in V_ss at 1 g/ ml relative to the two higher concentrations (20 and 100 g/ ml) for dogs treated with ammonium and sodium chloride, respectively. However, V_ss of MTX at the targeted concentrations of 20 and 100 g/ml was relatively constant. Plasma pHdependence of V_ss was observed only at the plasma concentration of 1 g/ml, and on the average, ammonium chloride and sodium chloride treatments resulted in 50.0 and 31.3% higher V_ss,respectively, when compared with the bicarbonate treatment. These phenomena appear to be adequately explained by the reported tissue uptake kinetics of MTX.This research was supported in part by a grant from the National Cancer Institute, CA-29754.Abstracted from a dissertation submitted in 1984 by Chung Y. Lui to the Graduate College, University of Illinois at Chicago, in partial fulfillment of Doctor of Philosophy Degree requirements.     

Relational continuity of care in community pharmacy: A systematic review

Relational continuity of care (COC) is becoming an important concept related to improving healthcare quality, reducing medical costs and increasing patient satisfaction with primary care. While community pharmacy (CP) has a considerable role in primary care, there are few reports dedicated to the role of relational COC in CP. This study reviewed the existing evidence of relational COC in CP and its effect on patients. PubMed, Embase, CINAHL, Cochrane Library CENTRAL and Google Scholar were used to search for relevant studies from the date of database inception through to January 2021, which were appraised according to eligibility criteria. There were no limitations on the primary outcome or language. Case reports and studies without control groups were excluded. The Newcastle–Ottawa quality assessment scale was used to assess the quality of the studies. Database searches identified 13 records. Relational COC measures in the included studies were grouped in three kinds; pharmacy-visiting pattern, Continuity of Care Index and loyalty. The assessed outcomes were medication adherence behaviour (e.g., the proportion of days covered, medication possession ratio), adverse drug reactions, potentially inappropriate drug prescribing and clinical outcomes. The odds of patients adhering to their medication regimen were about 1.1~2.5 times higher among those who consistently visited a single pharmacy compared to patients visiting multiple pharmacies. Additionally, the care provision with a high level of relational continuity could lower inappropriate drug use by 21~32 per cent and the use of other costly services by 12~29 per cent. This study suggests that a high degree of relational COC in CP could improve safe use of medications among patients. Future research is needed to employ more rigorous methods to reduce heterogeneity and to measure effects on clinical outcomes.     

Primary social factors and smoking in Korean adolescents

Journal of Public Health - The present study aimed to examine the effects of primary social factors on the smoking behaviors according to the smoking stages—initiation and...     

Efficacy of a Family-Based Intervention for HIV Prevention with Hispanic Adolescents with Same Gender Sexual Behaviors

Prevention Science - Despite the availability of efficacious and effective family-based interventions, such interventions are scarce for sexual minority adolescents, particularly among...     

Serum vitamin D status and metabolic syndrome: a systematic review and dose-response meta-analysis

BACKGROUD/OBJECTIVESEvidence has suggested an association between serum vitamin D and metabolic syndrome (MetS), but prospective studies are very limited. The objective was to assess the dose-response association between serum vitamin D concentration and MetS risk using a systematic review and meta-analysis of updated observational studies.MATERIALS/METHODSUsing MEDLINE, PubMed, and Embase, a systematic literature search was conducted through February 2020 and the references of relevant articles were reviewed. A random-effects model was used to estimate the summary odds ratio/relative risk and 95% confidence interval (CI). Heterogeneity among studies was evaluated with I² statistic. In total, 23 observational studies (19 cross-sectional studies, and four cohort studies) were included in the meta-analysis.RESULTSThe pooled estimates (95% CI) for MetS per 25-nmol/L increment in serum vitamin D concentration were 0.80 (95% CI, 0.76–0.84; I² = 53.5) in cross-sectional studies, and 0.85 (95% CI, 0.72–0.98; I² = 85.8) in cohort studies. Similar results were observed, irrespectively of age of study population, study location, MetS criteria, and adjustment factors. There was no publication bias for the dose-response meta-analysis of serum vitamin D concentrations and MetS.CONCLUSIONSDose-response meta-analysis demonstrated that a 25-nmol/L increment in the serum vitamin D concentration was associated with 20% and 15% lower risks of MetS in cross-sectional studies and cohort studies, respectively.     

Associations Between Thyroid Hormone Levels and Urinary Concentrations of Bisphenol A,F, and S in 6-Year-old Children in Korea

ObjectivesBisphenol A (BPA) is used in the electrical, mechanical, medical, and food industries. Previous studies have suggested that BPA is an endocrine disruptor. Regulation of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). However, few studies have investigated the associations of BPF and BPS with thyroid dysfunction in children. Our study investigated the associations of prenatal BPA and early childhood BPA, BPF, and BPS exposure with thyroid function in 6-year-old children.MethodsPrenatal BPA concentrations were measured during the second trimester of pregnancy in an established prospective birth cohort. We measured urinary BPA, BPF, and BPS concentrations and thyroid hormone levels (thyroid-stimulating hormone, total T₃, and free T₄) in 6-year-old children (n=574). We examined the associations between urinary bisphenol concentrations and percentage change of thyroid hormone concentrations using multivariate linear regression. We also compared thyroid hormone levels by dividing the cohort according to BPA, BPF, and BPS concentrations.ResultsThe associations between prenatal BPA and total T₃ levels were statistically significant in all models, except for girls when using a crude model. The associations between urinary BPA and BPS concentrations and levels of all thyroid hormones were not statistically significant. However, we observed that lower free T₄ levels (−1.94%; 95% confidence interval, −3.82 to −0.03) were associated with higher urinary BPF concentrations in girls only.ConclusionsOur findings identified significant associations between prenatal BPA exposure and total T₃ levels in all children and between BPF exposure and free T₄ levels in girls only.     

Optimal Household Water Access Fosters the Attainment of Minimum Dietary Diversity among Children Aged 6–23 Months in Malawi

Along with sanitation and hygiene, water is a well-known driver of child undernutrition. However, a more direct role of household (HH) water access in shaping dietary diversity remains unexplored. We assessed the association between HH water access and achievement of minimum dietary diversity (MDD) among young children. We utilized nationally-representative cross-sectional data from the 2015/16 Malawi Demographic and Health Survey, which included 4727 mother–child dyads, respectively, (26.8 ± 6.8 years, range 15–49 years) and (13.9 ± 4.9 months, range 6–23 months). HH water access was categorized as (1) basic or no access, (2) intermediate, or (3) optimal. MDD was defined as feeding a child, during the previous day, at least four of the food groups defined by the World Health Organization. Only 27.7% of the children achieved MDD standards; most of the children who achieved MDD were from HHs with optimal water access (58.4%, p < 0.001). However, only 5.9% of the mother–child dyads were from HHs with optimal water access. After adjusting for covariates, children from HHs with optimal water access had higher odds of achieving MDD than those from HHs with basic or no water access (aOR = 1.74, CI = 1.24–2.46). Our results highlight the need to incorporate water-based strategies into national nutritional policies to increase dietary diversity among Malawian infants and young children.     

Effect of Heat-Killed Lactobacillus casei DKGF7 on a Rat Model of Irritable Bowel Syndrome

Non-viable bacteria, referred to as “paraprobiotics,” have attracted attention as potentially safer alternatives to probiotics. The aim of this study was to investigate the efficacy of heat-killed Lactobacillus casei DKGF7 on the symptomatic improvement of irritable bowel syndrome (IBS) in a rat disease model and to elucidate the underlying mechanisms that contribute to the beneficial effects of heat-killed probiotics. Seven male Wistar rats were induced with IBS by restraint stress and administered heat-killed L. casei DKGF7 for four weeks and then compared with seven rats in the control group. Stool consistency measured four weeks after initial treatment was the primary outcome measure. To investigate the mechanism of action of the heat-killed bacteria on IBS, we measured serum corticosterone levels, inflammatory cytokines in colon tissue, and expression of tight junction proteins (TJPs) in the epithelium. The treatment group showed significantly better stool consistency scores than the control group at week 4, as well as at every measured time point (all p values < 0.05). The treatment group showed lower serum corticosterone levels, lower colonic inflammatory cytokine levels, and higher expression of TJPs compared with the control group. Paraprobiotics such as heat-killed L. casei DKGF7 can improve stool consistency in a rat IBS model, which may indicate a potential therapeutic strategy for IBS treatment.     

Psychological Resilience,Experimentally Manipulated Social Status,and Dietary Intake among Adolescents

Relative to other racial/ethnic groups in the United States, Hispanic American (HA) youth have higher rates of overweight and obesity. Previous work suggests that low perceived social status (SS) promotes excess caloric intake and, thereby, development of obesity. Psychological resilience may play a role in reducing adverse eating behaviors and risk for obesity. The objective of this study was to investigate whether resilience (as measured by the Connor Davidson Resilience Scale) interacts with experimentally manipulated SS to affect dietary intake among HA adolescents (n = 132). Using a rigged game of Monopoly (Hasbro, Inc.), participants were randomized to a high or low SS condition. Following the Monopoly game, participants consumed an ad libitum lunch and their dietary intake was assessed. There was a significant interaction between resilience and experimentally manipulated SS for total energy intake (p = 0.006), percent energy needs consumed (p = 0.005), and sugar intake (p = 0.004). For the high SS condition, for each increase in resilience score, total energy intake decreased by 7.165 ± 2.866 kcal (p = 0.014) and percent energy needs consumed decreased by 0.394 ± 0.153 (p = 0.011). In the low SS condition, sugar intake increased by 0.621 ± 0.240 g for each increase in resilience score (p = 0.011). After correction for multiple comparisons, the aforementioned interactions, but not simple slopes, were statistically significant.     

Associations between Circulating Markers of Cholesterol Homeostasis and Macrovascular Events among Patients Undergoing Hemodialysis

Current strategies targeting serum cholesterol bring limited benefits to mortality and macrovascular events prevention among hemodialysis patients. Direct measurements and analysis on circulating markers of cholesterol homeostasis could be promising solutions to this bottleneck. We prospectively enrolled 90 maintenance hemodialysis patients and 9 healthy controls in 2019 for 1 year. We measured circulating desmosterol and lathosterol as markers for cholesterol synthesis and campesterol and sitosterol for cholesterol absorption. At baseline, hemodialysis patients showed higher levels of campesterol (p = 0.023) compared to healthy controls. During follow-up, we identified 14 (15.4%) patients who experienced macrovascular events. Comparisons of cholesterol homeostasis markers between cohorts with and without macrovascular events showed no significant differences in markers of cholesterol synthesis or absorption. Using logistic regression analysis, the odds ratio was not statistically significant for the prediction of macrovascular events after full-adjusting for age, sex, diabetes, serum albumin, cholesterol, and triglyceride. We concluded that hemodialysis patients demonstrated higher level of cholesterols absorption, indicated by circulating campesterol compared to healthy subjects. Markers for cholesterol homeostasis were not significantly associated with macrovascular events during a 1-year follow-up. Our results shed light on the novel therapeutic target of modulating cholesterol absorption in HD patients.