Metabolism of deltamethrin and cis- and trans-permethrin by human expressed cytochrome P450 and carboxylesterase enzymes

1. The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes.

2. DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CL_int) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5. None of the pyrethroids were metabolised by CYP2A6, CYP2E1, CYP3A7 or CYP4A11.

3. DLM, CPM and TPM were metabolised by both human CES1 and CES2 enzymes.

4. Apparent CL_int values for pyrethroid metabolism by CYP and CES enzymes were scaled to per gram of adult human liver using abundance values for microsomal CYP enzymes and for CES enzymes in liver microsomes and cytosol. TPM had the highest and CPM the lowest apparent CL_int values for total metabolism (CYP and CES enzymes) per gram of adult human liver.

5. Due to their higher abundance, all three pyrethroids were extensively metabolised by CES enzymes in adult human liver, with CYP enzymes only accounting for 2%, 10% and 1% of total metabolism for DLM, CPM and TPM, respectively.

     

Opportunities and barriers to effective operation and maintenance of public toilets in informal settlements: perspectives from toilet operators in Kampala

Although classified by the Joint Monitoring Programme (JMP) as unimproved sanitation facilities, public toilets still play a critical role in eliminating open defecation in informal settlements. We explored perspectives of toilet operators on opportunities and barriers to operation and maintenance (O&M) of public toilets in informal settlements. A cross-sectional study design was used. Up to 20 in-depth interviews were used to obtain data on the experiences of public toilet operators. Thematic content analysis was used.

Ressults show that opportunities for improving O&M include; operation of public toilets is a source of livelihood; operators are knowledgeable on occupational risks, and the community is involvedin sanitation activities. Barriers to effective O&M include; high operation costs, failure to break even and a lack of investments in occupational health Therefore, there is need to recognise the significance of public toilets as a viable alternative to open defecation in areas where ownership of private sanitation facilities is difficult. Failure to observe the health and safety of toilet operators may further compromise O&M.     

Trabecular Bone Score Reference Values for Children and Adolescents According to Age,Sex, and Ancestry

Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z-scores, tracking of TBS Z-scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual-energy X-ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n = 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non-African Americans. We provide sex-specific TBS reference ranges and LMS values for calculation of TBS Z-scores by age and means and SD for calculation of Z-scores by pubertal stage. TBS Z-scores were positively associated with height Z-scores at some ages. TBS Z-scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z-scores. Tracking of TBS Z-scores over 6 years was lower (r = 0.47) than for aBMD or BMAD Z-scores (r = 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z-scores provide information distinct from spine aBMD and BMAD Z-scores. Our robust reference ranges for TBS in a well-characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Confidentiality Discussions and Private Time With a Health-Care Provider for Youth,United States, 2016

Purpose

The objective of the study was to define factors associated with adolescent and young adult (AYA) experiences with private time and having discussed confidentiality and the impact of these experiences on improving delivery of clinical preventive services.

Quantification of 5-HT1A and 5-HT2A receptor Binding in Depressed Suicide Attempters and Non-Attempters

Objective: To determine serotonin system abnormalities related to major depression or previous suicidal behavior.

Methods: [¹¹C]WAY100635, [¹⁸F]altanserin and positron emission tomography were used to compare 5-HT_1A and 5-HT_2A binding in MDD patients divided into eight past suicide attempters (>4yrs prior to scanning) and eight lifetime non-attempters, and both groups were compared to eight healthy volunteers.

Results: The two receptor types differed in binding pattern across brain regions from each other, but there were no differences in binding between healthy volunteers and the two depressed groups or between depressed suicide attempters and non-attempters. No effects of depression severity or lifetime aggression were observed for either receptor.

Conclusion: Limitations of this study include small sample size and absence of high lethality suicide attempts in the depressed attempter group. No trait-like binding correlations with past suicide attempt or current depression were observed. Given the heterogeneity of nonfatal suicidal behavior, a larger sample study emphasizing higher lethality suicide attempts may find the serotonin biological phenotype seen in suicide decedents.     

A Multi-Scale DNN Algorithm for Nonlinear Elliptic Equations with Multiple Scales

Algorithms based on deep neural networks (DNNs) have attracted increasing attention from the scientific computing community. DNN based algorithms are easy to implement, natural for nonlinear problems, and have shown great potential to overcome the curse of dimensionality. In this work, we utilize the multi-scale DNN-based algorithm (MscaleDNN) proposed by Liu, Cai and Xu (2020) to solve multi-scale elliptic problems with possible nonlinearity, for example, the p-Laplacian problem. We improve the MscaleDNN algorithm by a smooth and localized activation function. Several numerical examples of multi-scale elliptic problems with separable or non-separable scales in low-dimensional and high-dimensional Euclidean spaces are used to demonstrate the effectiveness and accuracy of the MscaleDNN numerical scheme.