51886 research outputs found
Sort by
Branchiootorenal Spectrum Disorder
No full textClinical characteristics: Branchiootorenal spectrum disorder (BORSD) is characterized by second branchial arch anomalies (e.g., preauricular pits and branchial cleft sinuses or cysts) and malformations of the outer, middle, and inner ear associated with conductive, sensorineural, and/or mixed hearing impairment. Congenital anomalies of the kidney and urinary tract (CAKUT) include kidney agenesis, hypoplasia, and dysplasia as well as urinary tract anomalies such as ureteropelvic junction (UPJ) obstruction, calyceal cysts and/or diverticula, and/or vesicoureteral reflux (VUR). Glomerular pathology that includes proteinuria and glomerulosclerosis has been reported. Some individuals progress to end-stage kidney disease (ESKD) depending on the severity of the kidney involvement.
Diagnosis/testing: The clinical diagnosis of BORSD is established in an individual based on the presence of three or more major criteria OR two major criteria and two minor criteria OR one major criterion and a first-degree relative with BORSD. The molecular diagnosis of BORSD is established in a proband with suggestive findings and a heterozygous pathogenic variant in either EYA1 or SIX1 identified by molecular genetic testing.
Management:
Treatment of manifestations: Otologic considerations include canaloplasty to correct an atretic canal and/or excision of branchial cleft cysts/fistulae if they are infected, symptomatic, or cosmetically concerning. Audiologic considerations include hearing aids for individuals with mild-to-moderate sensorineural or mixed hearing loss and cochlear implantation (CI) for individuals with bilateral severe-to-profound hearing loss. All individuals with hearing loss should be enrolled in an appropriate educational program for the hearing impaired. CAKUT require (1) nephrologists to assess kidney function, control hypertension, manage proteinuria, and help in delaying progression of kidney disease when possible; and (2) urologists to perform corrective surgery (e.g., pyeloplasty) for UPJ obstruction and manage use of prophylactic antibiotics and/or surgical correction for VUR.
Surveillance: Routinely scheduled follow up with the treating otolaryngologist, audiologist, speech-language pathologist, nephrologist, and urologist.
Agents/circumstances to avoid: Individuals with hearing loss should avoid environmental exposures known to cause hearing loss. Individuals with CAKUT should use appropriate caution when taking medications (i.e., antibiotics and analgesics) that can impair kidney function and/or that require normal kidney physiology for their use.
Evaluation of relatives at risk: It is appropriate to evaluate apparently asymptomatic relatives at risk for BORSD to determine if treatable and/or possibly progressive otologic and/or kidney abnormalities are present. Evaluations can include molecular genetic testing if the BORSD-related genetic alteration in the family is known or comprehensive physical examination (to include hearing evaluation and kidney imaging and function studies) if the genetic alteration in the family is not known.
Genetic counseling.
BORSD is inherited in an autosomal dominant manner. Of individuals with a molecular diagnosis of BORSD, approximately 10%-20% have the disorder as the result of de novo EYA1 or SIX1 pathogenic variant. Each child of an individual with BORSD has a 50% chance of having BORSD. If the BORSD-related genetic alteration has been identified in an affected family member, prenatal and preimplantation genetic testing are possible. Intrafamilial variability makes it impossible to accurately predict which manifestations of BORSD may occur and how mild or severe they will be in a fetus found to have a familial BORSD-related genetic alteration
P-454. The Skip Phenomenon in Staphylococcus aureus Bacteremia: Prevalence in a Pediatric Tertiary Care Center
No full textBackground:
Bacteremia due to Staphylococcus aureus infections has been well-documented to exhibit fluctuating positivity in blood cultures, known as the “skip phenomenon” (SP). This phenomenon is defined as having at least one negative blood culture occurring between two positive cultures during a single episode of bacteremia while on adequate antibiotic therapy. However, data on its prevalence in pediatric patients remains scant. Current Infectious Diseases Society of America (IDSA) guidelines do not clearly define the number of negative culture sets needed to determine bacterial clearance. Common practice has been to obtain at least two serially negative blood cultures, but this is primarily based on adult data and observations. This study sought to assess the prevalence of the SP in pediatric patients with central lines and S. aureus bacteremia at a tertiary pediatric referral center.
Methods:
We conducted a retrospective review of pediatric admissions from January 2011 to February 2024 with a S. aureus associated central line infection. Data collected included antimicrobial resistance patterns, duration of bacteremia, absolute neutrophil count (ANC), and blood culture history.
Results:
Among 285 patients with S. aureus CLABSI, 19 (6.6%) exhibited the SP. Of these 19 cases, 13 (68%) were due to methicillin-resistant S. aureus (MRSA), although MRSA accounted for only 30% of the total cohort. 13/85 (15%) infections caused by MRSA demonstrated the SP versus 6/200 (3%) of MSSA infections. This means MRSA patients were approximately five times more likely to experience the SP compared to MSSA cases. Most notably, there was an increased average duration of positive cultures in the SP group (5.5 days) compared to those exhibiting no SP (2.2 days).
Conclusion:
Our findings support the practice of obtaining at least two consecutive negative blood cultures drawn at least 24 hours apart to confirm clearance of S. aureus bacteremia in pediatric patients. The skip phenomenon appears particularly common among patients with MRSA highlighting the need for vigilance when this organism is responsible
Integration of plasma and imaging data within the ADRC biofluid and imaging ecosystems
No full textBackground:
Data accessibility and interoperability across the U.S. Alzheimer's Disease Research Centers (ADRCs) provides necessary resources and data access to enable novel hypothesis testing without additional data collection and will allow end users to rapidly advance our understanding of multiple pathologies or multiple chronic conditions on disease progression within Alzheimer's disease and related diseases. The aim of the current study was to integrate plasma data from the National Centralized Repository for Alzheimer's Disease and Related Dementia's (NCRAD) with ADRC neuroimaging data from the SCAN initiative and National Alzheimer's Coordinating Center Uniform Data Set (NACC UDS) demographic data, all publicly available through the NACC Data Platform and Data Front Door. We provide sample descriptives and present the results of initial data explorations.
Method:
The NACC and NCRAD data request procedures were completed to gain access to the data. We focused on the subset of participants for whom Quanterix Simoa HD‐X Alzpath plasma pTau217 data was available (NCRAD). Amyloid pathology was defined based on centiloid values (cut‐off >= 20; SCAN initiative). Demographic information was available for all participants (NACC UDS). We integrated data using the NACC identifier and visit age where available. We used Spearman correlations to assess the association between plasma pTau217 and centiloid values and we used ROC analyses to assess amyloid classification performance.
Result:
Plasma pTau217 data was available for 927 participants (sample descriptives in Table 1). Figure 1 shows the distribution of plasma pTau217 levels across diagnostic groups. In the subset of participants for whom amyloid PET was available (n = 170, Table 1), the Spearman correlation between plasma pTau217 levels and centiloid values was 0.59. Quanterix pTau217 accurately classified amyloid status with a ROC AUC of .92 (95%CI 0.89–0.97; accuracy 85%; Figure 2). Tau PET was available for 135 participants with plasma pTau217 data and 114 participants with both plasma pTau217 and amyloid PET data.
Conclusion:
Combining the SCAN PET and NCRAD plasma results in a promising resource, already with 36% demographic diversity. Sample sizes will increase through ongoing efforts as part of the SCAN initiative and the ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI)
Use of non-prescription analgesic medications and survival among Black women with ovarian cancer
No full textBackground: Chronic inflammation and inflammatory-related exposures have been implicated in epithelial ovarian cancer (EOC) prognosis. However, no studies have evaluated whether analgesic medication use impacts survival in Black women with EOC, an understudied population with poor survival.
Methods: Leveraging data from the African American Cancer Epidemiology Study, we examined the association of pre-diagnostic analgesic medication use (aspirin, non-aspirin non-steroidal anti-inflammatory drugs [naNSAIDs], and acetaminophen) with survival among self-identified Black women diagnosed with EOC (N = 541) using multivariable Cox proportional hazards regression. Stratified analyses were conducted by comorbidities and histotype.
Results: Acetaminophen use was associated with a higher risk of mortality overall (HR = 1.40; 95% CI = 1.00-1.97) and for frequent and chronic use (≥30 days per month: HR = 1.62; 95% CI = 1.12-2.34; >5 years: HR = 1.57; 95% CI = 1.03-2.39). These associations were more pronounced among women with high-grade serous carcinoma (HGSC)/carcinosarcoma and those with comorbidities. Among women with comorbidities, naNSAID use was associated with a decreased risk of mortality (HR = 0.71; 95% CI = 0.51-0.99), but no association was observed among women without comorbidities (HR = 0.99; 95% CI = 0.56-1.75). No associations with survival were observed for aspirin.
Conclusion: Chronic use of acetaminophen negatively impacted survival among Black women with EOC, while naNSAID use conferred a survival advantage only among women with comorbidities
Collapsin Response Mediator Protein 2 (CRMP2) Modulates Induction of the Mitochondrial Permeability Transition Pore in a Knock-In Mouse Model of Alzheimer’s Disease
No full textHyperphosphorylated collapsin response mediator protein 2 (CRMP2) is elevated in the cerebral cortex of an APP-SAA knock-in mouse model of Alzheimer's disease and binds the adenine nucleotide translocase (ANT) in a phosphorylation-dependent manner. We propose that, in Alzheimer's disease (AD) mitochondria, dissociation of hyperphosphorylated CRMP2 from ANT promotes opening of the permeability transition pore (PTP). We showed that purified ANT, when reconstituted into giant liposomes, forms large calcium-dependent channels resembling the PTP, which are effectively blocked by recombinant, unphosphorylated CRMP2. In synaptic mitochondria isolated from the cortices of APP-SAA knock-in mice and control B6J hAbeta mice, we observed an increased susceptibility to permeability transition pore (PTP) induction in AD mitochondria, accompanied by reduced viability of cultured cortical neurons. Pre-treatment of AD mice with the CRMP2-binding small molecule (S)-lacosamide ((S)-LCM), which prevents CRMP2 hyperphosphorylation and restores its interaction with ANT, attenuated PTP induction and improved neuronal viability. Interestingly, direct application of (S)-LCM to isolated mitochondria failed to suppress PTP induction, indicating that its protective effect requires upstream cellular mechanisms. These findings support a phosphorylation-dependent role for CRMP2 in regulating PTP induction in AD mitochondria and highlight (S)-LCM as a promising therapeutic candidate for mitigating mitochondrial dysfunction and enhancing neuronal viability in AD
A validation of 3D imaging for non-invasive, tech-assisted diagnosis of caries and erosive tooth wear in primary teeth – an in vitro study
No full textThis in vitro study set out to assess the agreement of 3D-colored digital dental images in detecting occlusal caries and erosive tooth wear (ETW) in primary teeth, by comparing indirect digital assessments with conventional direct visual examinations. Extracted primary molars with varying degrees of caries severity and ETW were mounted on modeling wax, with the crowns exposed for the assessments. Then, two independent experiments were conducted. The first analyzed occlusal caries in 233 extracted primary molars using the International Caries Detection and Assessment System (ICDAS, scores 0–6), while the second evaluated ETW in 164 primary molars using the Basic Erosive Wear Examination (BEWE, scores 0–3). Direct visual examinations were performed under standardized lighting, dryness and magnification. For the indirect assessment, teeth were scanned using an intraoral scanner (TRIOS 4, 3Shape), and digital images were assessed via 3Shape Unite software. Agreement between methods was determined using kappa statistics and percent agreement. Substantial agreement was found for caries detection (Kappa = 0.64; 71% agreement) with the highest concordance at ICDAS scores 4–6 (> 90%) and the lowest at score 0 (36%). For ETW, substantial agreement was also observed Kappa = 0.58; 80% agreement), with highest concordance at BEWE score 2 (99%). The digital method tended to overestimate scores 0 and 1 and underestimate scores 2 and 3 in caries detection. 3D-colored digital images demonstrated substantial agreement with conventional visual methods for detecting both dental caries and ETW in primary teeth. These results highlight its promise as a practical and non-invasive adjunct in pediatric dental diagnostics, with potential to enhance early detection and support the integration of digital tools into routine and remote oral health care
Mitochondria-derived peptides in liver disease: Emerging regulators of hepatic metabolism and therapeutic targets
No full textMitochondria-derived peptides (MDPs) are bioactive molecules encoded by small open reading frames within mitochondrial DNA (mtDNA). Humanin, the first MDP to be discovered, functions as a cytoprotective factor, protecting cells from stress-induced apoptosis. Subsequent discoveries expanded this family to include Mitochondrial Open-reading-frame of the Twelve S rRNA-c (MOTS-c), a key regulator of metabolic homeostasis and stress adaptation, and the Small Humanin-Like Peptides (SHLP1-6), which modulate mitochondrial bioenergetics and insulin sensitivity. MDPs play critical roles in liver homeostasis by maintaining mitochondrial function and metabolic balance. Intracellularly, they modulate mitochondrial activity, oxidative stress, and apoptosis, promoting hepatocyte survival. Extracellularly, they act in autocrine, paracrine, or endocrine manners, engaging receptors or signaling pathways to regulate nuclear gene expression and metabolic adaptation. Emerging evidence highlights their relevance in metabolic dysfunction-associated steatotic liver disease (MASLD). Humanin exerts hepatoprotective effects by inhibiting apoptosis and modulating lipid metabolism. MOTS-c activates AMPK, regulates nuclear gene expression, suppresses fibrotic and inflammatory signaling, and restores mitochondrial function in MASLD and fibrosis models. SHLPs, particularly SHLP2, enhance mitochondrial function and insulin sensitivity, supporting glucose homeostasis and mitigating oxidative stress. Collectively, MDPs establish a novel paradigm in mitochondrial signaling, extending mtDNA function beyond energy production. This review summarizes current insights into MDP biology and highlights its emerging therapeutic potential in chronic liver disease
Indiana Emergency Medical Services Workforce July 1 - November 1, 2024 Student Data Report
No full textThis report presents findings from the Indiana EMS Student Pulse Check survey for July 1 through November 1, 2024, capturing responses from 58 EMS trainees who completed Indiana‑based training programs. Respondents primarily completed EMT programs, with many holding EMT or firefighter certifications and reporting limited prior ambulance experience. The average training cost was approximately 25. Participants indicated high comfort with common EMS scenarios, though discomfort remained higher for emotionally complex events such as pediatric deaths. Employment expectations showed strong interest in full‑time work, particularly within fire departments and hospital‑based ambulance services. Key factors influencing employment decisions included cost of living, commute time, safety, and benefit packages—especially health insurance and paid time off. Additional priorities included flexible scheduling, adequate time off, and professional development opportunities. Geographic analysis showed that fewer than half of respondents completed training in their home county, with some traveling from neighboring states
Hearing and Speech Perception are Associated with A/T/N Biomarkers of Alzheimer's Disease
No full textBackground
Hearing loss is linked to dementia, yet its relationship with Alzheimer's disease (AD) biomarkers remains unclear. This study examines associations between performance on auditory and speech perception measures with neuroimaging measures of neurodegeneration (N; cortical volume), amyloid (A), and tau (T) to aid early AD detection.
Method:
121 participants from the Indiana Alzheimer's Disease Research Center underwent auditory testing and neuroimaging. Auditory assessments included CUNY sentences, Speech‐in‐Noise (QuickSiN), and Letter Number Sequencing (LNS). Neuroimaging measures included MRI‐based cortical volume extracted with Freesurfer v6 (N), cortical Centiloid value from amyloid PET (A), and bilateral mean meta‐temporal tau standardized uptake value ratio from tau PET (T). A one‐way ANCOVA was used to compare differences in auditory tests between diagnostic groups, while partial Pearson correlations were used to assess associations of auditory tests with A/T/N biomarkers, covaried for age, sex, and total intracranial volume (N only).
Result:
The sample (age=71.90±6.6; 63.9% female) included 49 cognitively normal older adults, 40 with subjective cognitive decline, 23 with mild cognitive impairment (MCI) due to AD, 7 with MCI due to other conditions, and 2 with AD. Significant diagnostic differences were observed in SNR loss on QuickSiN (p = .006) and CUNY subtests, including AV words (p <.001), AV sentences (p = .037), and A words (p = .002).
Cortical amyloid correlated with SNR loss (r=.231, p = .045) and CUNY subscores, including auditory (Au) words (r=‐.272, p = .018) and word gain (r=‐.250, p = .031). LNS raw scores correlated with cortical volume (r=‐.311, p = .008). Associations were found between cortical volume and CUNY audiovisual (AV) words (r=.254, p = .023), A words (r=.395, p < .001), and sentence gain (r=‐.261, p = .020), but not with SNR loss. Meta‐temporal tau SUVR was associated with CUNY A words (r=‐.294, p = .021), A sent (r=‐.276, p = .031), word gain (r=.303, p = .016), and LNS raw scores (r=‐.276, p = .036), but not with SNR measures.
Conclusion:
Findings suggest that auditory and speech perception tests are associated with neuroimaging biomarkers of AD, supporting the potential utility of hearing assessments as early screening tools for AD‐related pathology. Further research with larger sample sizes is warranted to strengthen these findings and explore their clinical implications
National Compliance With Community Input on Nonprofit Hospital Community Benefit Activities
No full textImportance: In exchange for tax exemptions valued at $37.4 billion, the Patient Protection and Affordable Care Act (ACA) requires all nonprofit hospitals to conduct a triennial community health needs assessment (CHNA) and develop an implementation strategy (IS). As part of these community benefit (CB) activities, hospitals must solicit and account for input from the community in the form of written comments, which may improve hospital investments in population health.
Objective: To examine nonprofit hospital compliance with the community input requirement and the approaches hospitals have used to solicit and account for written comments from the community.
Design, setting, and participants: This cross-sectional study used data from CHNAs and ISs completed by nonprofit hospitals between 2018 and 2021. CHNAs and ISs were downloaded from hospital websites in 2022. A 20% stratified random sample was drawn from all 3087 US nonprofit hospitals. Data extraction and content analysis was performed from July 2024 to March 2025, and statistical analysis was performed from March to June 2025.
Exposure: ACA community input requirement in CB activities.
Main outcomes and measures: Hospitals were considered compliant with the community input requirement if they described the following in their CHNA or IS: (1) how written comments on the most recent CHNA and/or IS were solicited, (2) at least 1 written comment received, and (3) how this information was taken into account in the current CHNA and/or IS. Bivariate analyses using χ2 tests to compare the organizational characteristics of compliant vs noncompliant hospitals.
Results: The final study sample included 543 nonprofit hospitals, and 57 hospitals (10.5%) were compliant with the community input requirement. Among compliant hospitals, 27 (47.4%) used paper surveys, 20 (35.1%) used web-based surveys, 13 (22.8%) used in-person surveys at community outreach events, and 2 (3.5%) used telephone-based surveys to solicit community input. None of the characteristics assessed in the bivariate analysis were significantly different between compliant vs noncompliant hospitals.
Conclusions and relevance: This cross-sectional study of a nationally representative sample of nonprofit hospitals found low hospital compliance with the Internal Revenue Service community input requirement in CB documents. This finding raises questions about whether the needs and strategies identified and addressed through CB activities reflect community priorities. To ensure that CB activities address community needs as intended under the ACA, policy changes are needed to improve nonprofit hospital compliance, transparency, and accountability