Nevin Manimala

Tissue Cell. 2023 Sep 27;85:102226. doi: 10.1016/j.tice.2023.102226. Online ahead of print.

ABSTRACT

This study aimed to investigate the protective effect of melatonin against the acute toxicity of cisplatin in ocular tissues. The eyes of 40 rats were divided into 4 groups: Control group (10 rats), Melatonin (Mel) group (10 rats), Cisplatin (Cis) group (10 rats), Melatonin (Mel) + Cisplatin (Cis) group (10 rats). Retina, cornea, and ciliary body tissues were examined after hematoxylin-eosin staining of sections obtained from the eyes and were scored for disorganization and degeneration. Apoptotic cells were counted for the retina, cornea, and ciliary body with the TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) method. The total antioxidant status (TAS) / total oxidant status (TOS) of homogenized eye tissues were measured. While apoptotic cells were found to increase in the cornea of the Cisplatin (Cis) group, no difference was found regarding the retina and ciliary body cell count. An increased number of apoptotic cells in the cornea of the Cis group was found while there was a decrease in the group where Cisplatin and Melatonin were administered together (Mel+Cis group). There was no statistically significant difference amongst groups for TOS or TAS. Melatonin had a partial protective effect against histological damage.

PMID:37793209 | DOI:10.1016/j.tice.2023.102226

Clin Exp Dermatol. 2023 Oct 4:llad319. doi: 10.1093/ced/llad319. Online ahead of print.

ABSTRACT

BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-induced skin disorder characterized predominantly by IgA autoantibodies against endomysium, tissue transglutaminase (TG2/tTG), epidermal transglutaminase (TG3/eTG), and deamidated gliadin. To date, circulating autoantibody reactivity has not been systematically described.

OBJECTIVE: Characterization of serum reactivities in DH.

METHODS: This multicenter international study analyzed sera from 242 DH patients taken at the time of initial diagnosis. DH-specific IgA and IgG serum autoantibodies were analyzed by indirect immunofluorescence (IF) on monkey esophagus, and by enzyme-linked immune sorbent assay (ELISA) based on recombinant TG2/tTG, TG3/eTG, and deamidated gliadin (GAF3X).

RESULTS: IgA indirect IF microscopy on monkey esophagus revealed the highest reactivity (84.3%; specificity 100%) followed by IgA TG2/tTG ELISA (78.5%, 99.0%), IgA TG3/eTG ELISA (72.7%, 95.0%), and IgA GAF3X ELISA (69.0%, 98.5%).

CONCLUSION: Serum IgA and IgG autoantibodies against endomysium, TG2/tTG, TG3/eTG, and deamidated gliadin are highly prevalent in DH. Indirect IF microscopy on monkey esophagus (IgA) provides the highest diagnostic accuracy that can be further enhanced by 3.5% when combined with IgA TG2/tTG ELISA.

PMID:37793183 | DOI:10.1093/ced/llad319

J Clin Endocrinol Metab. 2023 Oct 4:dgad584. doi: 10.1210/clinem/dgad584. Online ahead of print.

ABSTRACT

CONTEXT: Volatile organic compounds (VOCs) are pervasive environmental pollutants that have been linked to various adverse health effects. However, the impact of ambient VOCs, whether individually or in mixtures, on diabetes remains uncertain and requires further investigation.

OBJECTIVE: This study investigates the effects of ambient VOCs exposure, whether single or mixed, on diabetes mellitus and glucose homeostasis in the general population.

METHODS: Urinary concentrations of VOCs metabolites were obtained from National Health and Nutrition Examination Survey. Survey-weighted logistic regression and generalized linear regression were used to explore the associations between individual VOC exposure and diabetes risk and glucose homeostasis indicators, respectively. Weighted quantile sum (WQS) regression models were applied to assess the combined effects of VOCs mixtures.

RESULTS: Out of 8468 participants, 1504 had diabetes mellitus. Eight VOCs metabolites showed positive associations with diabetes mellitus (OR ranged from 1.15 to 1.43, all P<0.05), insulin resistance (OR ranged from 1.02 to 1.06, P＜0.05), and other glucose homeostasis indicators (β ranged from 0.04 to 2.32, all P<0.05). Mixed-VOCs models revealed positive correlations between the WQS indices and diabetes risk (OR=1.52, 95% CI: 1.29-1.81), insulin resistance (OR=1.36, 95% CI=1.14-1.62), and other glucose homeostasis indicators (β ranged from 0.17 to 2.22, all P<0.05).

CONCLUSION: Urinary metabolites of ambient VOCs are significantly associated with an increased diabetes risk and impaired glucose homeostasis. Thus, primary prevention policies aimed at reducing ambient VOCs could attenuate diabetes burden.

PMID:37793167 | DOI:10.1210/clinem/dgad584

Oral Dis. 2023 Oct 4. doi: 10.1111/odi.14754. Online ahead of print.

ABSTRACT

OBJECTIVE: Opiorphin is a pentapeptide secreted in saliva and has a strong analgesic effect. Salivary opiorphin has been shown to increase in orofacial pain and may act as a pain reliever in pain caused by denture-related ulcers. The current study aimed to evaluate the salivary opiorphin levels in traumatic ulcers caused by ill-fitting dentures and demonstrate whether there is any correlation between trauma-related pain levels and salivary opiorphin levels.

MATERIALS AND METHODS: Twenty-two individuals with new full dentures and a complaint of pain due to ill-fitting were included in this study. Patients were asked to rate their level of pain on a visual analog scale (VAS). Then, saliva specimens were collected at the first visit with the complaint of pain and 7 days following the denture adjustment.

RESULTS: The average saliva opiorphin level before and after denture adjustment were 19.29 ± 5.44 and 15.78 ± 3.95 ng/mL, respectively. A dependent (paired) t-test determined that the mean salivary opiorphin level differed statistically significantly before and after the adjustment of the dentures.

CONCLUSIONS: The findings show that salivary opiorphin levels increase in pain associated with denture-related traumatic ulcers. Adjusting the dentures resulted in pain relief and a statistically significant reduction in opiorphin levels.

PMID:37793134 | DOI:10.1111/odi.14754

Neuro Oncol. 2023 Oct 4;25(Supplement_4):iv1-iv99. doi: 10.1093/neuonc/noad149.

ABSTRACT

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.83 per 100,000 population (malignant AAAIR=6.94 and non-malignant AAAIR=17.88). This overall rate was higher in females compared to males (27.85 versus 21.62 per 100,000) and non-Hispanic persons compared to Hispanic persons (25.24 versus 22.61 per 100,000). Gliomas accounted for 26.3% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (14.2% of all tumors and 50.9% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (40.8% of all tumors and 56.2% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.13 per 100,000 population. There were 86,030 deaths attributed to malignant brain and other CNS tumors between 2016 and 2020. This represents an average annual mortality rate of 4.42 per 100,000 population and an average of 17,206 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.7%, for a non-malignant brain and other CNS tumor the five-year relative survival rate was 91.8%.

PMID:37793125 | DOI:10.1093/neuonc/noad149

Epidemiology. 2023 Oct 2. doi: 10.1097/EDE.0000000000001680. Online ahead of print.

ABSTRACT

BACKGROUND: To meet regulatory approval, interventions must demonstrate efficacy against a primary outcome in randomized clinical trials. However, when there are multiple clinically relevant outcomes, selecting a single primary outcome is challenging. Incorporating data from multiple outcomes may increase statistical power in clinical trials. We examined methods for analyzing data on multiple endpoints, inspired by real-world trials of interventions against respiratory syncytial virus (RSV).

METHOD: We developed a novel permutation test representing a weighted average of individual outcome test statistics (wavP) to evaluate intervention efficacy in a multiple-endpoint analysis. We compared the power and type I error rate of this approach to the Bonferroni correction (bonfT) and the minP permutation test. We evaluated the different approaches using simulated data from three hypothetical trials varying the intervention efficacy, correlation, and incidence of the outcomes, as well as data from a real-world RSV clinical trial.

RESULTS: When the vaccine efficacy against different outcomes was similar, wavP yielded higher power than bonfT and minP; in some scenarios the improvement in power was substantial. In settings where vaccine efficacy was notably larger against one endpoint compared to the others, all three methods had similar power. We developed an R package, PERMEATE, to guide selection of the most appropriate method for analyzing multiple endpoints in clinical trials.

CONCLUSIONS: Analyzing multiple endpoints using a weighted permutation method can increase power while controlling the type I error rate compared to established methods under conditions mirroring real-world RSV clinical trials.

PMID:37793120 | DOI:10.1097/EDE.0000000000001680

Med Phys. 2023 Oct 4. doi: 10.1002/mp.16774. Online ahead of print.

ABSTRACT

BACKGROUND: Pulsed wave Doppler ultrasound is a useful modality for assessing vascular health as it quantifies blood flow characteristics. To facilitate accurate diagnosis, accuracy and consistency of this modality should be assessed through Doppler quality assurance (QA).

PURPOSE: The purpose of this study was to characterize the accuracy, reproducibility, and inter-scanner variability of ultrasound flow velocity measurements via a flow phantom, with a focus on the effect of systematic acquisition parameters on measured flow velocity accuracy.

METHODS: Using a manufacturer-calibrated flow phantom, pulsed wave measurements were acquired on five clinical systems (iU22, Philips) with three models of transducers, including both linear and curvilinear models. The peak and mean flow velocities were estimated by vendor-supplied spectral analysis tools. To investigate intra- and inter-scanner variability, measurements were repeated using each scanner-transducer pair under a standardized set of conditions. Inter-scanner variability was assessed using ANOVA. Flow velocity accuracy was investigated by mean absolute percentage error. The impacts of receive gain, measurement depth, and beam steering on measured flow velocity accuracy were examined by varying each parameter over its available range and comparing to the ground truth flow velocity.

RESULTS: Inter-scanner variability was statistically significant for peak flow measurements made using both linear and curvilinear transducers, though absolute differences in measured velocity were small. Inter-scanner variability was not statistically significant for mean flow velocity. Receive gain, measurement depth, and beam steering were all found to impact the accuracy of measured flow characteristics for linear transducers. Accuracy of the flow measurements made with the curvilinear transducer demonstrated high consistency to changes in receive gain at a constant depth, though were impacted by increasing the measurement depth.

CONCLUSIONS: Carefully and consistently selected acquisition and set-up parameters are essential in order to establish a reliable and meaningful QA program.

PMID:37793117 | DOI:10.1002/mp.16774

Epidemiology. 2023 Oct 2. doi: 10.1097/EDE.0000000000001683. Online ahead of print.

ABSTRACT

BACKGROUND: To our knowledge, no studies have explicitly studied the role of hypertensive disorders of pregnancy (HDP) in racial disparities in severe maternal morbidity (SMM).

METHODS: Using causal mediation models, we estimated the proportion of the non-Hispanic Black-White racial disparity in risk of SMM that is explained through the pathway of HDP. We linked 2006-2019 Georgia hospital discharge records with vital statistics birth and fetal death records for non-Hispanic Black and non-Hispanic White birthing persons. We used G-estimation of a structural nested mean model to decompose the absolute racial disparity in incidence of SMM into pathways operating through HDP.

RESULTS: Non-Hispanic Black birthing people experienced an excess 56 SMM events (95% CI: 52, 59) per 10,000 delivery hospitalizations compared to non-Hispanic White birthing people. If counterfactual disparity measure estimation assumptions hold, the estimated absolute disparity remaining after blocking the causal pathways through HDP was 41 SMM events per 10,000 deliveries (95% CI: 38, 44), suggesting that 26% (95% CI: 12, 40) of the absolute racial disparity would be eliminated if there was no contribution of HDP to SMM risk.

CONCLUSIONS: Our results are consistent with the hypothesis that intervening to prevent HDP is an important (yet incomplete) pathway for reducing the excess risk among NH Black pregnancies compared to NH White pregnancies.

PMID:37793115 | DOI:10.1097/EDE.0000000000001683

JCO Oncol Pract. 2023 Oct 4:OP2300147. doi: 10.1200/OP.23.00147. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the enrollment success rate of cancer clinical trials conducted in 2008-2019 and various factors lowering the enrollment success rate.

METHODS: This is a cross-sectional study with clinical trial information from the largest registration database ClinicalTrials.gov. Enrollment success rate was defined as actual enrollment greater or equal to 85% of the estimated enrollment goal. The association between trial characteristics and enrollment success was evaluated using the multivariable logistic regression.

RESULTS: A total of 4,004 trials in breast, lung, and colorectal cancers were included. The overall enrollment success rate was 49.1%. Compared with 2008-2010 (51.5%) and 2011-2013 (52.1%), the enrollment success rate is lower in 2014-2016 (46.5%) and 2017-2019 (36.4%). Regression analyses found trial activation year, phase I, phase I/phase II, and phase II (v phase III), sponsor agency of government (v industry), not requiring healthy volunteers, and estimated enrollment of 50-100, 100-200, 200, and >500 (v 0-50) were associated with a lower enrollment success rate (P < .05). However, trials with placebo comparator, ≥5 locations (v 1 location), and a higher number of secondary end points (eg, ≥5 v 0) were associated with a higher enrollment success rate (P < .05). The AUC for prediction of the final logistic regression models for all trials and specific trial groups ranged from 0.69 to 0.76.

CONCLUSION: This large-scale study supports a lower enrollment success rate over years in cancer clinical trials. Identified factors for enrollment success can be used to develop and improve recruitment strategies for future cancer trials.

PMID:37793091 | DOI:10.1200/OP.23.00147

Int J Dent Hyg. 2023 Oct 4. doi: 10.1111/idh.12771. Online ahead of print.

ABSTRACT

INTRODUCTION: The world’s population is in a demographic transition with a rising ageing population. Tooth loss is frequent among older people resulting in the replacement of natural teeth using complete or partial dentures. YouTube™ is the second most popular website in the world and is being increasingly used to access health care information. The aim of this study is to evaluate the usefulness and reliability of the information in YouTube™ videos regarding denture care.

METHODS: The YouTube™ website was used to systematically search for videos using the keyword ‘denture care’. Videos meeting the eligibility criteria were assessed separately by two independent researchers. The usefulness of the videos was assessed using the Global Quality Assessment Scale and a customized usefulness scoring scheme. Based on these scores, the usefulness of the videos was categorized as low, medium and high. A modified DISCERN tool (mDISCERN) was used for assessing reliability with scores ranging from 0 to 5. Other video characteristics like source/ownership of the videos, duration, views, likes, dislikes, number of days posted, like ratio, view ratio, interaction index and Video Power Index were also obtained. Statistical analysis was carried out using the Kruskal-Wallis test, Spearman correlation test and multiple linear regression analysis.

RESULTS: A total of 120 videos were included. Based on the usefulness score, the usefulness of 65.8% of videos were classified as low, 32.5% were medium and 1.6% had high usefulness. The mDISCERN score for 74.2% of videos was 2 or below 2 indicating that the majority of videos had low reliability. Video characteristics did not differ significantly according to the usefulness of videos. Videos uploaded by dentists or dental hygienists had significantly higher usefulness scores (p < 0.001) in comparison to videos uploaded by other sources. However, reliability scores did not differ based on the sources of the videos. Video reliability was found to have a significant (B = 2.08, p < 0.001) positive association with video usefulness.

CONCLUSION: YouTube™ cannot be recommended as the only source of information for denture care as most videos received low usefulness and reliability ratings in our study. Dentists and dental health professionals could take an active part in enhancing denture care-related content on YouTube™ and enable patients to have adequate and reliable knowledge of denture hygiene practices.

PMID:37793081 | DOI:10.1111/idh.12771