Outcomes of Aural Rehabilitation Provided in Person or by Telehealth Among Deaf/Hard of Hearing Young Children with Cochlear Implants or Hearing Aids.

Background: Cochlear implants and hearing aids may facilitate the development of listening and spoken language (LSL) in deaf/hard of hearing young children, but they require aural rehabilitation therapy-often unavailable outside urban areas-for optimal outcomes. This trial assessed the relative effectiveness of LSL therapy delivered either in person or by interactive video. The hypothesis was that telehealth service delivery would be noninferior to in-person therapy. Methods: Most parents refused randomization of their children to telehealth or in-person conditions; therefore, randomization was impossible. In consultation with the funder (NIDCD), the study design was modified. Parents were allowed to select their preferred study condition, and the study team was blinded to group membership. Forty-two families were in the in-person group and 35 in telehealth (40 and 30, respectively, after attrition). Primary endpoints were total score, auditory comprehension, and expressive communication on the Preschool Language Scale, 5th edition. There were several secondary speech, hearing, and language outcome measures. Assessments occurred at baseline and at follow-up after 6 months of LSL therapy. Results: Propensity scores were used to create two matched groups. At baseline, groups did not differ on PLS-5 scores. Change from baseline to F/U on age-equivalents for all three scores was nearly identical for both groups, although the telehealth group was younger, on average, than the in-person group. Discussion: Telehealth was noninferior to in-person services for all primary endpoints. For secondary outcomes, neither group demonstrated a significant advantage. Magnitudes of estimated group differences were small, suggesting nonsignificant differences not predominantly because of sample size. The telehealth group showed greater improvement on 15/24 of secondary language outcome measures. The findings provide evidence that telehealth is equivalent to in-person care for providing LSL therapy to young children with cochlear implants and hearing aids.

Using Bibliometric Data to Define and Understand Publishing Network Equity in Anesthesiology.

BACKGROUND: Anesthesiology departments and professional organizations increasingly recognize the need to embrace diverse membership to effectively care for patients, to educate our trainees, and to contribute to innovative research. 1 Bibliometric analysis uses citation data to determine the patterns of interrelatedness within a scientific community. Social network analysis examines these patterns to elucidate the network's functional properties. Using these methodologies, an analysis of contemporary scholarly work was undertaken to outline network structure and function, with particular focus on the equity of node and graph-level connectivity patterns. METHODS: Using the Web of Science, this study examines bibliographic data from 6 anesthesiology-specific journals between January 1, 2017, and August 26, 2022. The final data represent 4453 articles, 19,916 independent authors, and 4436 institutions. Analysis of coauthorship was performed using R libraries software. Collaboration patterns were assessed at the node and graph level to analyze patterns of coauthorship. Influential authors and institutions were identified using centrality metrics; author influence was also cataloged by the number of publications and highly cited papers. Independent assessors reviewed influential author photographs to classify race and gender. The Gini coefficient was applied to examine dispersion of influence across nodes. Pearson correlations were used to investigate the relationship between centrality metrics, number of publications, and National Institutes of Health (NIH) funding. RESULTS: The modularity of the author network is significantly higher than would be predicted by chance (0.886 vs random network mean 0.340, P < .01), signifying strong community formation. The Gini coefficient indicates inequity across both author and institution centrality metrics, representing moderate to high disparity in node influence. Identifying the top 30 authors by centrality metrics, number of published and highly cited papers, 79.0% were categorized as male; 68.1% of authors were classified as White (non-Latino) and 24.6% Asian. CONCLUSIONS: The highly modular network structure indicates dense author communities. Extracommunity cooperation is limited, previously demonstrated to negatively impact novel scientific work. 2 , 3 Inequitable node influence is seen at both author and institution level, notably an imbalance of information transfer and disparity in connectivity patterns. There is an association between network influence, article publication (authors), and NIH funding (institutions). Female and minority authors are inequitably represented among the most influential authors. This baseline bibliometric analysis provides an opportunity to direct future network connections to more inclusively share information and integrate diverse perspectives, properties associated with increased academic productivity. 3 , 4.

Kidney cancer in the Middle East and North Africa region: a 30-year analysis (1990-2019).

Kidney cancer, a type of urogenital cancer, imposes a high burden on patients. Despite this, no recent research has evaluated the burden of this type of cancer in the Middle East and North Africa (MENA) region. This study explored the burden of kidney cancer from 1990 to 2019 according to age, sex and socio-demographic index (SDI). The Global Burden of Disease (GBD) 2019 data was utilized to estimate the incidence, death, and disability-adjusted life-years (DALYs) caused by kidney cancer. These estimates were reported as counts and as age-standardised rates with 95% uncertainty intervals (UIs). The estimated age-standardised incidence, mortality, and DALY rates of kidney cancer in 2019 were 3.2 (2.8-3.6), 1.4 (1.2-1.6), and 37.2 (32.0-42.6) per 100,000, respectively. Over the period from 1990 to 2019, these rates have increased by 98.0%, 48.9%, and 37.7%, respectively. In 2019, the United Arab Emirates, Qatar, and Lebanon had the largest age-standardised incidence, mortality, and DALY rates. The smallest age-standardised incidence rates were seen in Yemen, Afghanistan, and the Syrian Arab Republic. Additionally, the smallest age-standardised mortality and DALY rates were observed in the Syrian Arab Republic, Yemen, and Morocco. The highest incidence rates were found among individuals aged 75-79 in both males and females. In 2019, the MENA/Global DALY ratio exceeded one for females aged 5-19 age and males aged 5-14, compared to 1990age groups in males. The burden of kidney cancer consistently rose with increasing SDI levels from 1990 to 2019. The increasing burden of kidney cancer highlights the urgent need for interventions aimed at improving early diagnosis and treatment in the region.

Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium.

Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.

Inflammatory myofibroblastic tumor in a patient with X-Linked hypophosphatemia: A case of Occam's razor or Hickam's dictum?

We present the case of a patient with X-Linked Hypophosphatemia (XLH) and an inflammatory myofibroblastic tumor (IMT) of the bladder which prompted further investigation into the possible relationship between XLH and IMT i.e. a case of Occam's Razor or Hickam's Dictum?

A substrate-interacting region of Parkin directs ubiquitination of the mitochondrial GTPase Miro1.

Mutations in the gene encoding for the E3 ubiquitin ligase Parkin have been linked to early-onset Parkinson's disease. Besides many other cellular roles, Parkin is involved in clearance of damaged mitochondria via mitophagy - a process of particular importance in dopaminergic neurons. Upon mitochondrial damage, Parkin accumulates at the outer mitochondrial membrane and is activated, leading to ubiquitination of many mitochondrial substrates and recruitment of mitophagy effectors. While the activation mechanisms of autoinhibited Parkin have been extensively studied, it remains unknown how Parkin recognises its substrates for ubiquitination, and no substrate interaction site in Parkin has been reported. Here, we identify a conserved region in the flexible linker between the Ubl and RING0 domains of Parkin, which is indispensable for Parkin interaction with the mitochondrial GTPase Miro1. Our results explain the preferential targeting and ubiquitination of Miro1 by Parkin and provide a biochemical explanation for the presence of Parkin at the mitochondrial membrane prior to activation induced by mitochondrial damage. Our findings are important for understanding mitochondrial homeostasis and may inspire new therapeutic avenues for Parkinson's disease.

Fundamentals and Translational Applications of Stem Cells and Biomaterials in Dental, Oral and Craniofacial Regenerative Medicine.

Regenerative dental medicine continuously expands to improve treatments for prevalent clinical problems in dental and oral medicine. Stem cell based translational opportunities include regenerative therapies for tooth restoration, root canal therapy, and inflammatory processes (e.g., periodontitis). The potential of regenerative approaches relies on the biological properties of dental stem cells. These and other multipotent somatic mesenchymal stem cell (MSC) types can in principle be applied as either autologous or allogeneic sources in dental procedures. Dental stem cells have distinct developmental origins and biological markers that determine their translational utility. Dental regenerative medicine is supported by mechanistic knowledge of the molecular pathways that regulate dental stem cell growth and differentiation. Cell fate determination and lineage progression of dental stem cells is regulated by multiple cell signaling pathways (e.g., WNTs, BMPs) and epigenetic mechanisms, including DNA modifications, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs). This review also considers a broad range of novel approaches in which stem cells are applied in combination with biopolymers, ceramics, and composite materials, as well as small molecules (agonistic or anti-agonistic ligands) and natural compounds. Materials that mimic the microenvironment of the stem cell niche are also presented. Promising concepts in bone and dental tissue engineering continue to drive innovation in dental and non-dental restorative procedures.

A MicroRNA Approach to Evaluating Elevated Prostate Cancer Risk in Cancer-Free Men.

Objective criteria are required for prostate cancer (PCa) risk assessment, treatment decisions, evaluation of therapy, and initial indications of recurrence. Circulating microRNAs were utilized as biomarkers to distinguish PCa patients from cancer-free subjects or those encountering benign prostate hyperplasia. A panel of 60 microRNAs was developed with established roles in PCa initiation, progression, metastasis, and recurrence. Utilizing the FirePlex® platform for microRNA analysis, we demonstrated the efficacy and reproducibility of a rapid, high-throughput, serum-based assay for PCa biomarkers that circumvents the requirement for extraction and fractionation of patient specimens supporting feasibility for expanded clinical research and diagnostic applications.

Joint-specific regulation of homeobox D10 expression in rheumatoid arthritis fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is a systemic immune-mediated disease characterized by joint inflammation and destruction. The disease typically affects small joints in the hands and feet, later progressing to involve larger joints such as the knees, shoulders, and hips. While the reasons for these joint-specific differences are unclear, distinct epigenetic patterns associated with joint location have been reported. In this study, we evaluated the unique epigenetic landscapes of fibroblast-like synoviocytes (FLS) from hip and knee synovium in RA patients, focusing on the expression and regulation of Homeobox (HOX) transcription factors. These highly conserved genes play a critical role in embryonic development and are known to maintain distinct expression patterns in various adult tissues. We found that several HOX genes, especially HOXD10, were differentially expressed in knee FLS compared with hip FLS. Epigenetic differences in chromatin accessibility and histone marks were observed in HOXD10 promoter between knee and hip FLS. Histone modification, particularly histone acetylation, was identified as an important regulator of HOXD10 expression. To understand the mechanism of differential HOXD10 expression, we inhibited histone deacetylases (HDACs) with small molecules and siRNA. We found that HDAC1 blockade or deficiency normalized the joint-specific HOXD10 expression patterns. These observations suggest that epigenetic differences, specifically histone acetylation related to increased HDAC1 expression, play a crucial role in joint-specific HOXD10 expression. Understanding these mechanisms could provide insights into the regional aspects of RA and potentially lead to therapeutic strategies targeting specific patterns of joint involvement during the course of disease.

Impact of chickpea hummus on postprandial blood glucose, insulin and gut hormones in healthy humans combined with mechanistic studies of food structure, rheology and digestion kinetics.

Slowing the rate of carbohydrate digestion leads to low postprandial glucose and insulin responses, which are associated with reduced risk of type 2 diabetes. There is increasing evidence that food structure plays a crucial role in influencing the bioaccessibility and digestion kinetics of macronutrients. The aims of this study were to compare the effects of two hummus meals, with different degrees of cell wall integrity, on postprandial metabolic responses in relation to the microstructural and rheological characteristics of the meals. A randomised crossover trial in 15 healthy participants was designed to compare the acute effect of 27 g of starch, provided as hummus made from either intact chickpea cells (ICC) or ruptured chickpea cells (RCC), on postprandial metabolic responses. In vitro starch digestibility, microstructural and rheological experiments were also conducted to evaluate differences between the two chickpea hummus meals. Blood insulin and GIP concentrations were significantly lower (P < 0.02, P < 0.03) after the consumption of the ICC meal than the meal containing RCC. In vitro starch digestion for 90 min was slower in ICC than in RCC. Microscopic examination of hummus samples digested in vitro for 90 min revealed more intact chickpea cells in ICC compared to the RCC sample. Rheological experiments showed that fracture for ICC hummus samples occurred at smaller strains compared to RCC samples. However, the storage modulus for ICC was higher than RCC, which may be explained by the presence of intact cells in ICC. Food structure can affect the rate and extent of starch bioaccessibility and digestion and may explain the difference in the time course of metabolic responses between meals. The rheological properties were measured on the two types of meals before ingestion, showing significant differences that may point to different breakdown mechanisms during subsequent digestion. This trial was registered at clinicaltrial.gov as NCT03424187.

Effects of 2 months of methylphenidate on energy expenditure in individuals with obesity: A randomized, double-blind, placebo-controlled pilot study.

Methylphenidate (MPH) has been previously shown to increase resting energy expenditure (REE) in individuals of normal weight; however, the effects on individuals living with obesity are currently unknown. Ten individuals living with obesity were randomly assigned to undergo 60 days of MPH administration with a daily dose of 0.5 mg/kg body weight or a placebo control. REE was measured before and after the 60-day intervention. There was a trend toward significance for group × time interaction on REE (p = 0.082) with a large effect size (η2 = 0.331), with MPH administration increasing REE compared to a decrease in placebo control. Preliminary findings from this pilot study show that MPH has the potential to counter the adaptive thermogenic process commonly seen in weight loss. This is a unique finding among pharmacotherapies, as no approved obesity drugs measurably impact REE.

Joint-specific rheumatoid arthritis fibroblast-like synoviocyte regulation identified by integration of chromatin access and transcriptional activity.

The mechanisms responsible for the distribution and severity of joint involvement in rheumatoid arthritis (RA) are not known. To explore whether site-specific fibroblast-like synoviocyte (FLS) biology might be associated with location-specific synovitis and explain the predilection for hand (wrist/metacarpal phalangeal joints) involvement in RA, we generated transcriptomic and chromatin accessibility data from FLS to identify the transcription factors and pathways. Networks were constructed by integration of chromatin accessibility and gene expression data. Analysis revealed joint-specific patterns of FLS phenotype, with proliferative, migratory, proinflammatory, and matrix-degrading characteristics observed in resting FLS derived from the hand joints compared with hip or knee. TNF stimulation amplified these differences, with greater enrichment of proinflammatory and proliferative genes in hand FLS compared with hip and knee FLS. Hand FLS also had the greatest expression of markers associated with an "activated" state relative to the "resting" state, with the greatest cytokine and MMP expression in TNF-stimulated hand FLS. Predicted differences in proliferation and migration were biologically validated with hand FLS exhibiting greater migration and cell growth than hip or knee FLS. Distinctive joint-specific FLS biology associated with a more aggressive inflammatory response might contribute to the distribution and severity of joint involvement in RA.

Reporting completeness of nutrition and diet-related randomised controlled trials protocols.

BACKGROUND AND AIMS: There is a need to consolidate reporting guidance for nutrition randomised controlled trial (RCT) protocols. The reporting completeness in nutrition RCT protocols and study characteristics associated with adherence to SPIRIT and TIDieR reporting guidelines are unknown. We, therefore, assessed reporting completeness and its potential predictors in a random sample of published nutrition and diet-related RCT protocols. METHODS: We conducted a meta-research study of 200 nutrition and diet-related RCT protocols published in 2019 and 2021 (aiming to consider periods before and after the start of the COVID pandemic). Data extraction included bibliometric information, general study characteristics, compliance with 122 questions corresponding to items and subitems in the SPIRIT and TIDieR checklists combined, and mention to these reporting guidelines in the publications. We calculated the proportion of protocols reporting each item and the frequency of items reported for each protocol. We investigated associations between selected publication aspects and reporting completeness using linear regression analysis. RESULTS: The majority of protocols included adults and elderly as their study population (n = 73; 36.5%), supplementation as intervention (n = 96; 48.0%), placebo as comparator (n = 89; 44.5%), and evaluated clinical status as the outcome (n = 80; 40.0%). Most protocols described a parallel RCT (n = 188; 94.0%) with a superiority framework (n = 141; 70.5%). Overall reporting completeness was 52.0% (SD = 10.8%). Adherence to SPIRIT items ranged from 0% (n = 0) (data collection methods) to 98.5% (n = 197) (eligibility criteria). Adherence to TIDieR items ranged from 5.5% (n = 11) (materials used in the intervention) to 98.5% (n = 197) (description of the intervention). The multivariable regression analysis suggests that a higher number of authors [ß = 0.53 (95%CI: 0.28-0.78)], most recent published protocols [ß = 3.19 (95%CI: 0.24-6.14)], request of reporting guideline checklist during the submission process by the journal [ß = 6.50 (95%CI: 2.56-10.43)] and mention of SPIRIT by the authors [ß = 5.15 (95%CI: 2.44-7.86)] are related to higher reporting completeness scores. CONCLUSIONS: Reporting completeness in a random sample of 200 diet or nutrition-related RCT protocols was low. Number of authors, year of publication, self-reported adherence to SPIRIT, and journals' endorsement of reporting guidelines seem to be positively associated with reporting completeness in nutrition and diet-related RCT protocols.

Calcified Nodule in Percutaneous Coronary Intervention: Therapeutic Challenges.

Calcified nodules (CNs) are among the most challenging lesions to treat in contemporary percutaneous coronary intervention. CNs may be divided into 2 subtypes, eruptive and noneruptive, which have distinct histopathological and prognostic features. An eruptive CN is a biologically active lesion with a disrupted fibrous cap and possibly adherent thrombus, whereas a noneruptive CN has an intact fibrous cap and no adherent thrombus. The use of intravascular imaging may allow differentiation between the 2 subtypes, thus potentially guiding treatment strategy. Compared with noneruptive CNs, eruptive CNs are more likely to be deformable, resulting in better stent expansion, but are paradoxically associated with worse clinical outcomes, in part because of their frequent initial presentation as an acute coronary syndrome and subsequent reprotrusion of the CN into the vessel lumen through the stent struts. Pending the results of ongoing studies, a tailored therapeutic approach based on the distinct features of the different CNs may be of value.

Higher Dietary Polyphenol Intake Is Associated With Lower Blood Inflammatory Markers.

BACKGROUND: Evidence suggests a link between polyphenol intake and reduced incidence of several chronic diseases. This could arise through associations between polyphenol intake and reduced systemic oxidative stress and subsequent inflammation. However, confirming this association is difficult, as few large cohorts allow for comprehensive assessments of both polyphenol intake and markers of systemic inflammation. OBJECTIVES: To address this, polyphenol intake was assessed in the UK-based Airwave cohort using 7-d diet diaries and data from Phenol-Explorer to test for associations between polyphenol intake and blood biomarkers of inflammation. METHODS: Participants included 9008 males and females aged 17-74 y (median age: 42 y) whose data was included in a cross-sectional analysis. Phenol-Explorer was used to estimate individuals' polyphenol intake from diet data describing the consumption of 4104 unique food items. C-reactive protein (CRP) and fibrinogen were used as blood biomarkers of inflammation. RESULTS: There were 448 polyphenols found in reported diet items. Median total polyphenol intake was 1536 mg/d (1058-2092 mg/d). Phenolic acids and flavonoids were the main types of polyphenols, and nonalcoholic beverages, vegetables, and fruit were the primary sources. Variation in energy-adjusted polyphenol intake was explained by age, sex, salary, body mass index, education level, smoking, and alcohol consumption. Linear regressions showed inverse associations between total daily intake and both CRP (ß: -0.00702; P < 0.001) and fibrinogen (ß: -0.00221; P = 0.038). Associations with specific polyphenol compound groups were also found. Logistic regressions using total polyphenol intake quartiles showed stepwise reductions in the odds of elevated CRP with higher intake (6%, 23%, and 24% compared with quartile 1; P = 0.003), alongside 3% and 7% lower odds per unit of polyphenol consumption equivalent to 1 cup of tea or coffee per day. CONCLUSIONS: This study describes polyphenol intake in a large, contemporary UK cohort. We observed associations between higher intake and lower CRP and fibrinogen. This contributes to evidence supporting the health benefits of dietary polyphenols.

Plaque Ruptures Are Related to High Plaque Stress and Strain Conditions: Direct Verification by Using In Vivo OCT Rupture Data and FSI Models.

BACKGROUND: While it has been hypothesized that high plaque stress and strain may be related to plaque rupture, its direct verification using in vivo coronary plaque rupture data and full 3-dimensional fluid-structure interaction models is lacking in the current literature due to difficulty in obtaining in vivo plaque rupture imaging data from patients with acute coronary syndrome. This case-control study aims to use high-resolution optical coherence tomography-verified in vivo plaque rupture data and 3-dimensional fluid-structure interaction models to seek direct evidence for the high plaque stress/strain hypothesis. METHODS: In vivo coronary plaque optical coherence tomography data (5 ruptured plaques, 5 no-rupture plaques) were acquired from patients using a protocol approved by the local institutional review board with informed consent obtained. The ruptured caps were reconstructed to their prerupture morphology using neighboring plaque cap and vessel geometries. Optical coherence tomography-based 3-dimensional fluid-structure interaction models were constructed to obtain plaque stress, strain, and flow shear stress data for comparative analysis. The rank-sum test in the nonparametric test was used for statistical analysis. RESULTS: Our results showed that the average maximum cap stress and strain values of ruptured plaques were 142% (457.70 versus 189.22 kPa; P=0.0278) and 48% (0.2267 versus 0.1527 kPa; P=0.0476) higher than that for no-rupture plaques, respectively. The mean values of maximum flow shear stresses for ruptured and no-rupture plaques were 145.02 dyn/cm2 and 81.92 dyn/cm2 (P=0.1111), respectively. However, the flow shear stress difference was not statistically significant. CONCLUSIONS: This preliminary case-control study showed that the ruptured plaque group had higher mean maximum stress and strain values. Due to our small study size, larger scale studies are needed to further validate our findings.

Prolonged HPA axis dysregulation in postpartum depression associated with adverse early life experiences: A cross-species translational study.

Childhood and adolescent stress increase the risk of postpartum depression (PPD), often providing an increased probability of treatment refractoriness. Nevertheless, the mechanisms linking childhood/adolescent stress to PPD remain unclear. Our study investigated the longitudinal effects of adolescent stress on the hypothalamic-pituitary-adrenal (HPA) axis and postpartum behaviors in mice and humans. Adolescent social isolation prolonged glucocorticoid elevation, leading to long-lasting postpartum behavioral changes in female mice. These changes were unresponsive to current PPD treatments but improved with post-delivery glucocorticoid receptor antagonist treatment. Childhood/adolescent stress significantly impacted HPA axis dysregulation and PPD in human females. Repurposing glucocorticoid receptor antagonists for some cases of treatment-resistant PPD may be considered.