Tag: pubmed

Mol Carcinog. 2022 Jun 21. doi: 10.1002/mc.23437. Online ahead of print.

ABSTRACT

Research has shown extensive metabolic remodeling in clear cell renal cell carcinoma (ccRCC), with increased glutathione (GSH) levels. We hypothesized that activating transcription factor-4 (ATF4) and the integrated stress response (ISR) induce a metabolic shift, including increased GSH accumulation, and that Vitamin A deficiency (VAD), found in ccRCCs, can also activate ATF4 signaling in the kidney. To determine the role of ATF4, we used publicly available RNA sequencing (RNA-seq) data sets from The Cancer Genomics Atlas. Subsequently, we performed RNA-seq and liquid chromatography-mass spectrometry-based metabolomics analysis of the murine TRAnsgenic Cancer of the Kidney (TRACK) model for early-stage ccRCC. To validate our findings, we generated RCC4 cell lines with ATF4 gene edits (ATF4-knockout [KO]) and subjected these cells to metabolic isotope tracing. Analysis of variance, the two-sided Student’s t test, and gene set enrichment analysis were used (p < 0.05) to determine statistical significance. Here we show that most human ccRCC tumors exhibit activation of the transcription factor ATF4. Activation of ATF4 is concomitant with enrichment of the ATF4 gene set and elevated expression of ATF4 target genes ASNS, ALDH1L2, MTHFD2, DDIT3 (CHOP), DDIT4, TRIB3, EIF4EBP1, SLC7A11, and PPP1R15A (GADD34). Transcript profiling and metabolomics analyses show that activated hypoxia-inducible factor-1α (HIF1α) signaling in our TRACK ccRCC murine model also induces an ATF4-mediated ISR. Notably, both normoxic HIF1α signaling in TRACK kidneys and VAD in wild-type kidneys diminish amino acid levels, increase ASNS, TRIB3, and MTHFD2 messenger RNA levels, and increase levels of lipids and GSH. By metabolic isotope tracing in human RCC4 kidney cancer parental and ATF4 gene-edited (ATF4-KO) cell lines, we show that ATF4 increases GSH accumulation in part via activation of the mitochondrial one-carbon metabolism pathway. Our results demonstrate for the first time that activation of ATF4 enhances GSH accumulation, increases purine and pyrimidine biosynthesis, and contributes to transcriptional and metabolic remodeling in ccRCC. Moreover, constitutive HIF1α expressed only in murine kidney proximal tubules activates ATF4, leading to the metabolic changes associated with the ISR. Our data indicate that HIF1α can promote ccRCC via ATF4 activation. Moreover, lack of Vitamin A in the kidney recapitulates aspects of the ISR.

PMID:35726553 | DOI:10.1002/mc.23437

Anat Histol Embryol. 2022 Jun 21. doi: 10.1111/ahe.12827. Online ahead of print.

ABSTRACT

The aim of the study is to protect and preserve the cross-sectional diagnostic characteristics of the anatomy samples by using silicone plastination method, to examine them both macroscopically and microscopically, and to use them as an educational material. After the dissection procedures of 10 total sheep heads obtained from the slaughterhouse were completed, they were freshly frozen and sliced to prepare cross-sectional samples. Then, statistical analysis was performed after the colorimetric measurements. For microscopic examination, 30 brain samples were divided into three groups (Fresh-F, plastination-P, plastination/deplastination-P/D). Of the total brain samples, 20 were subject to routine plastination protocol. After the plastination/deplastination procedure, the changes occurring in cerebral histology were compared. In terms of tissue preservation, the effect of plastination and deplastination was examined using a light microscope. Plastinates subject to silicone plastination under room temperature were very similar to their natural appearance, and it was observed that they preserved their morphological features. Colour changes in the tissues were statistically evaluated. Volumetric shrinkages were observed as qualitative, especially in the brain. As a result of the evaluation done, it was seen that deplastination with toluene is not possible for the brain tissues. In addition, it was not possible to take cross sections of the plastinated tissues that were not deplastinated. On the contrary, findings regarding that deplastination with 5% sodium methoxide dissolved in methanol can allow microscopic examination in long-term preserved plastinated brain tissues were obtained.

PMID:35726566 | DOI:10.1111/ahe.12827

J Glob Health. 2022 Jun 20;12:11004. doi: 10.7189/jogh.12.11004.

ABSTRACT

BACKGROUND: Measuring infant and young child feeding (IYCF) indicators is important in evaluating child health programs and making evidence-based decisions. With Internet and new media rapidly developing, communication apps such as WeChat (the most popular mobile social media platform in China) are widely used and can potentially be used as an alternative way to collect infant and young child feeding information. This study compares data agreement between a WeChat-based self-administered and an interviewer-administered survey on infant and young child feeding information.

METHODS: We recruited 297 mothers of children aged 6-23 months in Fenxi County, Shanxi Province, China. Using the Test-Retest method, we first collected data through a self-administered survey using a WeChat-based electronic questionnaire and asked 36 questions on breastfeeding and complementary feeding knowledge, practices, and information sources. We then conducted an interviewer-administered survey using the same questionnaire and compared the data agreement between the two survey methods during the same day. Cohen’s kappa score (κ) and intraclass correlation coefficients (ICC) were used for data agreement analysis for all 36 questions and six key IYCF indicators. The McNemar test was used to identify differences between the two survey methods for the six key indicators.

RESULTS: There was substantial or almost perfect agreement for 33 questions (κ/ICC>0.60), and slight or fair agreement for the other 3 questions (κ/ICC<0.40). Agreement of all six key IYCF indicators was substantial or almost perfect (κ = 0.78-0.94), while two indicators showed statistical differences between the two survey methods (P = 0.03 for “Minimum meal frequency” and P = 0.001 for “Minimum accepted diet”). Analysis of reasons for inconsistencies showed that 43.6% of all the inconsistencies were not caused by the self-administered survey method. The cost of the interviewer-administered survey was much higher than that of the self-administered survey: ¥45.9 (US$6.8) vs ¥19.7 (US$2.9) per questionnaire.

CONCLUSIONS: The WeChat-based self-administered method can be used for future data collection of infant and young child feeding information in China. Most of the questions and key indicators showed very good agreement without statistical differences between the two methods.

PMID:35726544 | DOI:10.7189/jogh.12.11004

PM R. 2022 Jun 21. doi: 10.1002/pmrj.12866. Online ahead of print.

ABSTRACT

INTRODUCTION: There are an increasing number of individuals with long-term symptoms of coronavirus-19 disease (COVID-19); however, the prognosis for recovery of physical function and fatigue after COVID-19 is uncertain. Here we report the changes in functional recovery between 1- and 6-months after hospitalization of adults hospitalized for COVID-19 and explore the baseline factors associated with physical function recovery.

METHODS: A prospective cohort study was performed of adult COVID-19 survivors 1-month and 6-months after hospital discharge. Participants completed standardized telephone interviews assessing three outcome domains: basic and instrumental activities of daily living (ADLs) performance, fatigue, and general physical function (Health Assessment Questionnaire [HAQ]). Statistical analysis included t-tests for continuous measures and chi-square or Fisher’s Exact tests for categorical measures.

RESULTS: The age of participants (n = 92) ranged from 22 to 95 (54.3 ± 17.2) years. Across outcome domains, a majority (63-67%) of participants developed new ADL impairment, fatigue, or worsening HAQ severity by 1 month. Of those, 50-79% partially or fully recovered by 6 months, but 21-50% did not recover at least partially. Fifteen to 30% developed new impairment between 1-and 6-months. For those without any improvement in ADL impairments at 6 months, lower socioeconomic status was significantly more common (p = 0.01) and age ≥ 65 (p = 0.06), trending towards being more common.

CONCLUSIONS: In our cohort, a substantial proportion of the participants who developed new ADL impairment, worsening fatigue, or HAQ severity after hospitalization for COVID-19 did not recover at least partially by 6-months after discharge. Evaluating functional status one month after discharge may be important in understanding functional prognosis and recovery after hospitalization for COVID-19. This article is protected by copyright. All rights reserved.

PMID:35726518 | DOI:10.1002/pmrj.12866

J Med Econ. 2022 Jun 21:1-22. doi: 10.1080/13696998.2022.2090734. Online ahead of print.

ABSTRACT

OBJECTIVE: Accurate and up-to-date figures of the cost of community-acquired pneumonia (CAP) hospitalization are needed to understand the associated economic burden for public health decision makers. Recent estimates are lacking, and previously published estimates differ markedly. Our objective was to estimate the current mean cost to the NHS for adult CAP hospitalization.

METHODS: All CAP hospitalizations in 2019 for those aged >18 years were identified from English Hospital Episode Statistics (HES). Each hospitalization was mapped to the tariff cost paid to the care provider within the NHS, including critical care costs and accounting for length of stay and complexity of the case. Mean hospitalization costs were estimated in total and in individuals with defined underlying comorbidities.

RESULTS: A mean cost of £3,904 was estimated for 187,251 CAP admissions providing a total cost of approximately £731 million per annum. The mean cost was £3,402 excluding critical care costs, and £11,654 for critical care episodes in the 4.4% of admissions receiving this care. Groups at high risk of CAP had higher mean costs ranging from £4,458 for people with diabetes to £5,215 with heart disease for those <65 years and £4,356 with heart disease to £4,751 with liver disease in those aged >65 years who comprised 74.3% admissions overall.

CONCLUSION: This estimate of the cost of hospitalization for CAP from the total population and in those with certain underlying comorbidities will allow a valid understanding of the cost-benefit of vaccination and evidence-based prioritization of pneumococcal vaccination to those at highest risk.

PMID:35726515 | DOI:10.1080/13696998.2022.2090734

J Cosmet Dermatol. 2022 Jun 21. doi: 10.1111/jocd.15173. Online ahead of print.

ABSTRACT

BACKGROUND: Management of multiple recalcitrant common warts represents a therapeutic challenge. Both oral isotretinoin and acitretin have shown a promising efficacy in the treatment of various types of warts. However, a comparative study of the two medicines in wart treatment hasn’t yet been conducted.

OBJECTIVE: The aim of this study was to assess the efficacy and adverse effects of oral isotretinoin versus acitretin in the treatment of multiple recalcitrant common warts.

METHODS: This study was conducted on 75 adult male patients with recalcitrant multiple common warts. The patients were randomly assigned to 3 groups: group 1(30 patients) received oral isotretinoin, group 2 (30 patients) received acitretin and group 3 received oral placebo (15 patients). The treatment was given daily until complete clearance or for a maximum of 3 months.

RESULTS: Complete clearance of the treated lesions was observed in 18 patients (60%) of the isotretinoin group, in 22 patients (73.3%) of the acitretin group and in 0 patients (0%) of the placebo group. A statistically significant difference was observed in the therapeutic response between the treatment groups and the placebo group was observed. Adverse effects of the used drugs were mild and transient.

CONCLUSION: Oral isotretinoin and acitretin are promising effective modalities with minimal side effects for the treatment male patients with multiple recalcitrant common warts with a relative superiority of acitretin.

PMID:35726506 | DOI:10.1111/jocd.15173

J Public Health Dent. 2022 Mar;82 Suppl 1:53-62. doi: 10.1111/jphd.12520.

ABSTRACT

OBJECTIVE: There is a lack of diversity in the dental workforce. Efforts to enhance underrepresented minority (URM) recruitment and retention within dental school exist, but little effort has been made to track URM providers through education and practice. This study assesses the status of workforce diversity in the dental specialties and the predictors of URM dentist specialization.

METHODS: The primary data used were a 2012 national sample survey of Hispanic/Latino (H/L), Black, or American Indian/Alaska Native (AI/AN) dentists in the US, supplemented by publicly available workforce data. Descriptive and multivariate statistical analyses were performed to describe the demographic composition of URM clinical general and specialist dentists and analyze changes in proportions of URMs specializing among age cohorts, differences in specific type of specialization, and racial concordance between specialists and their patients.

RESULTS: The pathway continues to winnow with fewer URM dentists in specialty practice. Among all URM clinical dentists being first in his/her family to obtain a college degree, having a strong desire to work in his/her own cultural community or joining a loan repayment program due to debt load independently predicted lower odds of specialization. Alternatively, being initially foreign trained as a dentist and valuing professional training were independently predictive of higher odds of specialization.

CONCLUSION: The lack of diversity within the dental specialties is a critical flaw in our education and care delivery systems demanding clear actions toward improving the pathway into residency programs for URM students.

PMID:35726471 | DOI:10.1111/jphd.12520

J Public Health Dent. 2022 Mar;82 Suppl 1:114-122. doi: 10.1111/jphd.12516.

ABSTRACT

OBJECTIVES: The objective of this study was to assess the current efforts to move dental school curriculum beyond diversity and inclusion toward an anti-racism approach to racial equity.

METHODS: In this cross-sectional study, an electronic Qualtrics survey was sent to 67 Dental School Associate Deans/Deans of Academic Affairs and 15 Dental Public Health (DPH) Residency Program Directors. Survey topics included oral health equity, Critical Race Theory (CRT), racism and the physiologic impacts of racism on oral health. Descriptive statistics were used to demonstrate frequencies.

RESULTS: Overall response rate was 31.7% (DPH = 6, predoctoral Dental = 20). The majority of respondents that answered the question stated that the educational program offered instruction in oral health equity (96.2%), racism (75%), and the physiologic impacts of racism on oral health (83.3%). Only 17.4% of the respondents stated that the educational program offered instruction in CRT. The main barriers to providing the instruction was limited faculty trained in the topics to offer the instruction or there was limited time to offer additional content in the curriculum.

CONCLUSIONS: Findings demonstrate that oral health equity, racism and the physiologic impacts of racism are being discussed in dental education to some extent, but there is limited instruction in CRT. More robust efforts are needed to ensure dental students and DPH residents are competent in providing anti-racist and unbiased health care; there should be an incorporation of anti-racism standards in the Commission on Dental Accreditation (CODA)’s predoctoral and Advanced Education Program standards.

PMID:35726460 | DOI:10.1111/jphd.12516

J Public Health Dent. 2022 Mar;82 Suppl 1:89-102. doi: 10.1111/jphd.12522.

ABSTRACT

OBJECTIVES: Addressing inequities in oral health care requires identification of which populations are experiencing performance gaps and the extent of those gaps. This study used Dental Quality Alliance (DQA) measures to examine variations in quality by race and ethnicity.

METHODS: We used eligibility and claims data for 2018 for children aged <21 years for state Medicaid/CHIP programs available through the Transformed Medicaid Statistical Information System. For a subset of states with sufficient data quality, we calculated DQA measures of utilization of services, oral evaluation, and topical fluoride. The measures were stratified by race and ethnicity, age, sex, geographic location, and language. We used bivariate logistic regression to analyze relative disparities.

RESULTS: Variations in measure scores were noted between racial and ethnic groups. Measure scores were typically lower for non-Hispanic black and American Indian/Alaskan Native children and higher for non-Hispanic Asian and Hispanic children compared with non-Hispanic white children. There also was variation in the patterns of disparities between states. More than two-thirds of states had insufficient race and ethnicity data (>10% missing) to reliably report stratified measure scores.

CONCLUSIONS: Because disparities vary by state, each Medicaid/CHIP program should evaluate variations in care quality in the context of the population it serves. A critical first step is to improve collection of race and ethnicity. These measurements can be used to set improvement goals that not only raise quality of care for the population overall but also close gaps in performance between racial and ethnic groups.

PMID:35726463 | DOI:10.1111/jphd.12522

J Hypertens. 2022 Jun 21. doi: 10.1097/HJH.0000000000003172. Online ahead of print.

ABSTRACT

BACKGROUND: Little is known whether children’s sodium intake is affected by the national salt reduction programme in the United Kingdom (UK), particularly in relation to socioeconomic groups. We aimed to assess the trend of sodium intake among children from different socioeconomic backgrounds in the UK, from 2008-2009 to 2018-2019.

METHODS: Repeated cross-sectional analyses of data from the National Diet and Nutrition Survey in children aged 4-18 years. Sodium intake was estimated from a 4-day dietary record in years 2008-2009 to 2018-2019 and 24-h urine collection (2008-2009 to 2011-2012 only). Socioeconomic status was based on parental occupation and equivalized household income.

RESULTS: We included 6281 children (age 11.0 ± 4.3 years, 51.3% boys). In 2008-2009 to 2011-2012, the mean sodium intake was 2342.4 ± 60.0 mg/day as measured by 24-h urinary sodium excretion, and was 2053.1 ± 18.2 mg/day by dietary records. From 2008-2009 to 2018-2019, the sodium intake as assessed by dietary records decreased by 15, 9 and 12% in children from routine and manual occupation families, intermediate occupation families and higher managerial, administrative and professional occupation families, respectively. On the basis of dietary records, the sodium intake of children from families in routine and manual occupations was 109.6 ± 23.1 mg/day (P < 0.001) higher than those from higher managerial, administrative and professional occupation families in 2008-2009 to 2011-2012. Sodium intake measured by 24-h urine collection during the same period also showed a difference between occupation groups, but it was not statistically significant. The occupational differences in sodium intake became smaller over time and were no longer significant in 2016-2017 to 2018-2019. Similar findings were found for household income.

CONCLUSION: Sodium intake as assessed by dietary records decreased over the 10-year period from 2008-2009 to 2018-2019 in children from all socioeconomic groups, particularly in those from lower socioeconomic backgrounds. These findings suggest that the national salt reduction programme could potentially help reduce health inequality related to sodium intake in children.

PMID:35726456 | DOI:10.1097/HJH.0000000000003172