Effect of apolipoprotein E (APOE) gene polymorphisms on the lipid profile of children being treated for acute lymphoblastic leukemia.

BACKGROUND: Medications used to treat acute lymphoblastic leukemia (ALL), such as L-asparaginase, can cause blood lipid disturbances. These can also be associated with polymorphisms of the lipoprotein lipase (LpL) and apolipoprotein E (APOE) genes. PROCEDURE: We aimed to investigate the association between lipid profile, certain LpL and APOE gene polymorphisms (rs268, rs328, rs1801177 and rs7412, rs429358 respectively) as well as the risk subgroup in 30 pediatric patients being treated for ALL, compared with 30 pediatric ALL survivors and 30 healthy controls. RESULTS: The only APOE gene polymorphism with significant allelic and genotypic heterogeneity was rs429358. Further analysis of this polymorphism showed that genotype (CC, CT, or TT) was significantly associated with (1) changes in the lipid profile at the end of consolidation (total cholesterol, LDL, apo-B100, and lipoprotein a) and during re-induction (total cholesterol and apo-B100), and (2) classification in the high risk-ALL subgroup (for CC genotype/C allele presence). CONCLUSIONS: Lipid abnormalities in children being treated for ALL may be associated with the APOE genotype, which is also possibly associated with risk stratification. Further research is needed to confirm the potential prognostic value of these findings.

Development and Validation of an Efficient and Safe Loud Music Exposure Paradigm.

PURPOSE: The purpose of this study was to develop a time-efficient music exposure and testing paradigm that safely creates temporary cochlear dysfunction that could be used in future temporary threshold shift (TTS) studies. METHOD: A 30-min audio compilation of pop rock music tracks was created. Adult volunteers with normal hearing were then exposed to this music material monaurally through headphones for 30 min at 97 dBA or 15 min at 100 dBA. Levels were measured from the ear of a manikin and are considered to provide an equivalent daily noise dose based on a 3-dB exchange. We assessed the changes in their hearing, by means of distortion product otoacoustic emission (DPOAE) testing, and standard and extended high-frequency pure-tone audiometry before and after exposure. There were 17 volunteers in total. In the first trial, eight volunteers (four females; Mdnage = 31 years [interquartile range, IQR = 4.25]) were included. Although TTS was observed in all eight participants for at least one frequency, a large variation in affected frequencies was observed. To address this issue, the audio material was further remastered to adjust levels across the different frequency bands. Fourteen adults (nine newly recruited and five from the first trial; seven females; Mdnage = 31 years [IQR = 5]) were exposed to the new material. RESULTS: All but two of 17 participants presented clinically significant TTS or decrease in DPOAE amplitude in at least one frequency. Statistically significant average TTS of 7.43 dB was observed at 6 kHz. There were statistically significant average DPOAE amplitude shifts of -2.55 dB at 4 kHz, -4.97 dB at 6 kHz, and -3.14 dB at 8 kHz. No participant presented permanent threshold shift. CONCLUSIONS: A monaural music paradigm was developed and shown to induce statistically significant TTS and DPOAE amplitude shifts, without evidence of permanent loss. This realistic and time-efficient paradigm may be considered a viable option for experimental studies of temporary music-induced hearing loss. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25016471.

Immunohistochemical Evidence Linking Interleukin-22 Tissue Expression Levels to FOXP3+ Cells and Neutrophil Densities in the Mycosis Fungoides Microenvironment.

BACKGROUND: Emerging data indicate that the cellular microenvironment and interleukins (IL) play a crucial role in mycosis fungoides (MF). We aimed to explore the potential association between the composition of the cellular microenvironment and the expression of IL-22 and IL-17A in MF skin lesions. METHODS: The study encompassed 16 cases of MF of different stages, for which sufficient skin tissue for immunohistochemistry and frozen tissue for reverse transcription-polymerase chain reaction, both taken from the same lesion, were available. Histological evaluation of eosinophils, neutrophils, CD20+, CD4+, CD8+, FOXP3+, CD56+, and CD1a+ cells was conducted. Additionally, mRNA expression levels of IL-22 and IL-17 mRNA were quantified using reverse transcription-quantitative polymerase chain reaction. SPSS version 28 (IBM Corp., Armonk, NY) was utilized for statistical analysis. RESULTS: Among the cases examined, three were in the patch stage, eight in the plaque stage, and five in the transformation to high-grade large cell lymphoma (t-LCL). B-lymphocytes, neutrophils, and eosinophils were primarily observed in t-LCL cases. IL-22 levels displayed a significant association with IL-17A levels (Pearson's r = 0.961, p < 0.001), FOXP3+ cells (Pearson's r = 0.851, p < 0.001), and neutrophil density (Pearson's r = 0.586, p = 0.014). No correlation was detected between IL-17A levels and the evaluated subtypes of microenvironmental cells. CONCLUSION: The microenvironment of MF lesions with t-LCL is noticeably different from early MF in terms of cellular composition. Histopathological identification of the cellular microenvironment may serve as an indicator of IL-22 tissue levels. These results implicate certain types of cells in IL-22 expression in the MF microenvironment and may contribute to advancing our knowledge on the pathogenesis and progression of the disease.

Federated benchmarking of medical artificial intelligence with MedPerf.

Medical artificial intelligence (AI) has tremendous potential to advance healthcare by supporting and contributing to the evidence-based practice of medicine, personalizing patient treatment, reducing costs, and improving both healthcare provider and patient experience. Unlocking this potential requires systematic, quantitative evaluation of the performance of medical AI models on large-scale, heterogeneous data capturing diverse patient populations. Here, to meet this need, we introduce MedPerf, an open platform for benchmarking AI models in the medical domain. MedPerf focuses on enabling federated evaluation of AI models, by securely distributing them to different facilities, such as healthcare organizations. This process of bringing the model to the data empowers each facility to assess and verify the performance of AI models in an efficient and human-supervised process, while prioritizing privacy. We describe the current challenges healthcare and AI communities face, the need for an open platform, the design philosophy of MedPerf, its current implementation status and real-world deployment, our roadmap and, importantly, the use of MedPerf with multiple international institutions within cloud-based technology and on-premises scenarios. Finally, we welcome new contributions by researchers and organizations to further strengthen MedPerf as an open benchmarking platform.

Dysregulation of Plasma miR-146a and miR-155 Expression Profile in Mycosis Fungoides Is Associated with rs2910164 and rs767649 Polymorphisms.

Diagnosis of Mycosis Fungoides (MF) may be challenging, due to its polymorphic nature. The use of miRNAs as biomarkers to assist in diagnosis has been investigated, mainly in skin lesion biopsies. The purpose of this study is to evaluate the plasma levels of miR-146a and miR-155 in MF patients and to investigate their association with SNPs of their genes. Plasma miRNAs were quantified by RT-qPCR. Genomic DNA was used for SNPs' genotyping by Sanger sequencing. Plasma levels of miR-146a and miR-155 were significantly higher in patients vs. controls, in early MF patients vs. controls, and in advanced vs. early MF patients. Both miRNAs' levels were significantly higher in stage IIB vs. early-stage patients. miR-155 plasma levels were significantly higher in patients with skin tumors or erythroderma. CC genotype (rs2910164 C>G) was significantly more frequent in healthy controls and associated with lower MF risk and lower miR-146a levels. The AA genotype (rs767649 T>A) was significantly more frequent in patients and correlated with increased MF risk and increased miR-155 levels. The combination of GG+AA was only detected in patients and was correlated with higher MF susceptibility. Increased mir-146a and mir-155 plasma levels in MF is an important finding to establish putative noninvasive biomarkers. The presence of SNPs is closely associated with miRs' expression, and possibly with disease susceptibility.

Investigating the dynamic linkages among carbon dioxide emissions, economic growth, and renewable and non-renewable energy consumption: evidence from developing countries.

This research paper examines the causal relationships among carbon dioxide emissions, economic growth, and renewable and non-renewable energy consumption, for a panel of 68 developing countries over the period 1990 - 2014. We use the multivariate panel cointegration framework and apply a battery of conventional (Pedroni 1999, 2004; and Kao 1999) as well as newly developed methodologies accounting for heterogeneity and cross-sectional correlation (Westerlund's ECM panel cointegration (2007) and panel bootstrap cointegration (2007) tests). The pooled mean group (PMG), mean group (MG), and dynamic fixed effects (DFE) methodologies were further applied to trace out the short-run dynamics. The results support evidence of significant dynamic linkages among the involved variables and reveal possible differences in the magnitude of the impacts from renewable and non-renewable energy consumption on environmental quality. The issue of distinguishing by source and determining the magnitude of the detected effects could provide valuable information for a sustainable economic and environmental development, substantially helping policy makers to designate more efficient policy measures.

The association between smoking and psychopathology adjusted for body mass index and gender.

OBJECTIVE: This study examined the correlation between smoking habits and psychopathology status, as well as the impact of confounders such as body mass index and gender. METHOD: A total of 134 non-smokers and 152 smokers were enrolled in this study. We measured psychopathology features using Symptom Checklist 90-Revised. We ran logistic regression models testing the smoking-psychopathology association, controlling for body mass index and gender. RESULTS: Smoking was positively correlated with depression, interpersonal sensitivity, hostility, somatization, paranoid ideation and psychoticism (P<0.05). Adjusting for body mass index and gender, the results remained largely unchanged, with a slight independent effect of body mass index. CONCLUSIONS: Our data suggest that smoking is a stronger predictor of psychopathology than body mass index and gender.

The Association Between Obesity and Hostility: The Mediating Role of Plasma Lipids.

OBJECTIVE: Recent research indicates an association between obesity and psychopathology status, the nature of which remains unclear. We evaluated the mediating role of biochemical disturbances in this association among a treatment-seeking sample of obese individuals. METHOD: The study enrolled 143 consecutive overweight and obese individuals (mean age 35±9 y) and 143 normal-weight controls (mean age 34±9 y), matched by age and sex. We measured psychopathology features using the Symptom Checklist 90-Revised (SCL-90-R), a standardized self-evaluation rating scale, and biochemical parameters (plasma cholesterol, triglyceride, and fasting glucose levels) of all participants. Nonlinear regression models were used to estimate the associations among obesity, psychopathology, and biochemical factors. RESULTS: Obesity was associated positively and significantly (P<0.05) with all of the SCL-90-R subscales, with the exception of anxiety and phobic anxiety, as well as with levels of plasma glucose, cholesterol (P<0.01), and triglycerides (P<0.001). Tests for mediation showed that obesity was significantly associated, for the mediators of plasma cholesterol [parameter estimate=-0.033, P<0.05] and triglycerides (parameter estimate=-0.059, P<0.05), only with hostility (parameter estimate=-0.024, P<0.05 and parameter estimate=-0.041, P<0.05, respectively). CONCLUSIONS: Our data suggest that biological substrates that are critically related to obesity, such as dyslipidemia, may mediate, at least in part, the association between obesity and hostility.

The Association between Obesity and Symptoms of Psychopathology and its Relationship with Sedentary Behavior and Mediterranean Diet.

BACKGROUND: Recent research indicates an association between obesity and symptoms of psychopathology, the nature of which remains obscure. This study examined the confounding role of behavioral factors on this association. METHOD: One hundred and forty-two overweight/obese subjects who sought treatment for obesity, of both genders (51 males and 91 females), 18 to 64 years old and 139 normal-weight controls of both genders (41 males and 98 females), 18 to 63 years old, were enrolled in this study. We measured psychopathology features, using the Symptom Checklist 90-Revised (SCL-90-R), dietary habits, using the MedDietScore (MDS) questionnaire, and physical activity, using the International Physical Activity Questionnaire (IPAQ). A series of regression models were used to estimate the mediation of dietary patterns and physical activity on the obesity-psychopathology association. RESULTS: The associations between obesity and depression (ß=0.32/ß=0.15), obsession-compulsion (ß=0.03/ß=-0.13), anxiety (ß=-0.25/ß=-0.12), interpersonal sensitivity (ß=0.08/ß=-0.04) and psychoticism (ß=-0.01/ ß=0.025) are accounted for by sedentary behavior and Mediterranean diet. CONCLUSIONS: Our data suggest that modifiable behavioral factors such as sedentary time and dietary patterns positively affect the association between obesity and symptoms of psychopathology.