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Comparative Analysis of 3D Culture Methodologies in Prostate Cancer Cells
No full textThree-dimensional (3D) cell culture models are increasingly utilized in cancer research to better replicate in vivo tumor microenvironments. This study examines the effects of different 3D scaffolding materials, including Matrigel, GelTrex, and the plant-based GrowDex, on prostate cancer cell lines, with a particular emphasis on neuroendocrine prostate cancer (NEPC). Four cell lines (LNCaP, LASCPC-01, PC-3, and KUCaP13) were cultured in these scaffolds to evaluate spheroid formation, cell viability, and gene expression. The results revealed that while all scaffolds supported cell viability, spheroid formation varied significantly: Matrigel promoted the most robust spheroids, especially for LASCPC-01, whereas GrowDex exhibited limitations for certain cell lines. Gene expression analysis indicated a consistent reduction in androgen receptor (AR) expression in LNCaP cells across all scaffolds, suggesting a potential shift towards a neuroendocrine phenotype. However, the expression of neuroendocrine markers varied depending on the scaffold and culture method, with the mini-domes method in Matrigel leading to decreased expression of both castration-resistant prostate cancer (CRPC) and NEPC markers. These findings highlight the scaffold-dependent variability in 3D culture outcomes and emphasize the need for standardized methodologies to ensure consistency and relevance in prostate cancer research
Langerhans Cell Histiocytosis With Hypothalamic-pituitary and Bone Involvement: A Report of 2 Cases
No full textCase 1: A 31-year-old woman presented with secondary amenorrhea, polyuria, and polydipsia. Three years later, magnetic resonance imaging of the brain done for headaches found thickening of the pituitary infundibulum. Laboratory evaluation indicated central vasopressin deficiency, mild hyperprolactinemia, and central hypogonadism. Six months later, progression of the infundibular lesion was documented, now contacting the optic chiasm. Biopsy showed epithelioid histiocytes, chronic inflammation, and gliosis. On postoperative scan, a lesion in the parietal calvaria was identified, which was solitary on a bone scan. The patient received cytarabine for 12 months with resolution of infundibular and bone lesion on positron emission tomography-computed tomography scan 1 year later. Case 2: A 23-year-old man presented with polyuria, polydipsia, and unilateral tinnitus. Laboratory evaluation indicated vasopressin deficiency and central hypogonadism. External ear canal biopsy indicated an infiltrative lesion with eosinophils, small lymphocytes and histiocytes. Magnetic resonance of the brain revealed hypothalamic/infundibular and parietal and mastoid bone lesions; no other lesions were identified on positron emission tomography-computed tomography. Patient received cytarabine for 1 year with resolution of lesions, which was maintained during follow-up of 4 years. Although rare, Langerhans cell histiocytosis in adults should be considered in the appropriate clinical scenario. Multidisciplinary treatment is required
Longitudinal cognitive trajectories in sporadic early‐onset Alzheimer’s Disease: Findings from LEADS
No full textBackground:
Early Onset Alzheimer’s Disease (EOAD) is a rare condition that manifests prior to the age of 65, and affects approximately 5% of patients with Alzheimer’s disease. The Longitudinal Early‐Onset Alzheimer’s Disease Study (LEADS) is the largest prospectively‐evaluated cohort of participants with sporadic EOAD in the United States, initiated to better understand the features of this condition. The current analyses sought to examine longitudinal cognitive trajectories of patients with EOAD over time.
Method:
Data from 100 participants with amyloid‐positive EOAD, 30 participants with amyloid‐negative cognitive impairment (EOnonAD), and 65 cognitively normal age‐matched participants were compared. All had at least three study visits. Cognitive trajectories across a comprehensive cognitive battery across 24‐56 months were examined using mixed‐effects modeling, including the years of onset x diagnostic group interaction controlling for years since onset, education, sex, and the random effect of each participant.
Result:
Across all measures, clinical groups generally displayed declines over time, with performances for the EOAD group tending to approach the lower limit of performance ranges (Figure 1). Relatedly, significantly greater slopes of decline were seen over time for the EOAD group than the CN group across all cognitive domains evaluated (ps.05; Tables 1 and 2).
Conclusion:
In addition to worse cognition at baseline, sporadic EOAD participants displayed pronounced declines in cognition over 24‐56 months across all domains evaluated. Relative to the EOnonAD group, cognitive trajectories appear to be worse predominantly for executive and attentional processes, with variability across episodic memory tasks. This suggests that EOAD pathology is not solely directed at memory functioning. Future research will focus on comparing cognitive trajectories of EOAD and late‐onset AD, in an effort to understand similarities and differences in the types and rates of cognitive trajectories
Clinical Management Update of Oral Leukoplakia: A Review From the American Head and Neck Society Cancer Prevention Service
No full textBackground: Oral potentially malignant disorders (OPMDs) occur in up to 4%-5% of the population, of which oral leukoplakia (OL) is the most common subtype. Predicting high-risk OL remains a challenge. Early diagnosis and effective treatment are thought to be of paramount importance to improve outcomes.
Methods: We searched PubMed and Clinicaltrials.gov data for updates in the clinical management of OL from 2015 to current.
Results: Recent publication of large cohorts of patients with OL aids in counseling patients regarding risk of malignant transformation. Management for OL includes surveillance, excision, and laser surgery, as well as local and systemic approaches to chemoprevention. Several new entities show promise regarding candidate biomarkers, chemoprevention agents, and diagnostic adjuncts, though all require further validation.
Conclusion: This update serves to further inform clinical management of OL and provide impetus for future investigations
On-demand retrospective: The impact of model shift over 10 years
No full textLearn about the impact of a decade long shift in acquisition model to emphasize the on-demand acquisition of journal articles, AV materials, and books, which required changes in budget management, workflows, and stakeholder engagement. Presenters will share impact analysis of this change for both the library and its patrons
Effect of genetic and vascular risk factors on rates of cognitive decline in early-onset and late-onset Alzheimer’s disease
No full textBackground: Although previous studies have shown that cognitive decline in Alzheimer's disease (AD) is associated with various risk factors, they primarily focused on late-onset AD (LOAD).
Objective: We aim to evaluate the differential impact of risk factors on the cognitive decline between early-onset AD (EOAD, onset < 65 years) and LOAD (onset ≥ 65 years) and explore the longitudinal effect of Apolipoprotein E allele 4 (APOE ε4) on cortical atrophy in both cohorts.
Methods: Using data from 212 EOAD and 1101 LOAD participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI), we conducted multivariable mixed-effect models to evaluate the impact of APOE ε4, education, hypertension, diabetes, dyslipidemia, and body mass index on cognitive performance. Preprocessed MRI data were utilized for longitudinal parametric mapping.
Results: APOE ε4 carriers in both groups showed significantly accelerated declines in language, verbal memory, executive function, and general cognition. By controlling other significant risk factors, APOE ε4 carriers showed faster declines in language and verbal memory in both groups. Females exhibited accelerated declines in Language and verbal memory in the EOAD and LOAD cohorts respectively. LOAD individuals with hypertension showed faster declines while overweight and obese participants displayed slower declines in both cohorts across all domains except visuospatial. Notably, APOE ε4 status was associated with longitudinal cortical atrophy in the LOAD cohort but not in the EOAD cohort.
Conclusions: Known risk factors for AD were associated with cognitive decline in both EOAD and LOAD cohorts
Pharmacokinetics and Pharmacodynamics of an Antibody Targeting Pathological Tau for the Treatment of Alzheimer’s Disease: Nonclinical Studies in P301S Mice and Cynomolgus Macaques
Get PDFBackground:
VY‐TAU01 is a recombinant humanized IgG4 monoclonal antibody (mAb) directed against pathological tau for the treatment of patients with mild dementia or mild cognitive impairment due to Alzheimer’s disease (AD). Both VY‐TAU01 and its parental mouse IgG1 mAb Ab‐01 target an epitope in the C‐terminus of tau, bind pathological tau with high affinity and selectivity over wild‐type tau, block paired helical filament seed‐induced tau aggregates in vitro, and selectively stain tau tangles in AD and P301S mouse (C57/B6J‐Tg[Thy1‐MAPT*P301S]2541Godt) brain. Ab‐01 robustly inhibits seeding and propagation of pathological tau in a P301S mouse seeding model.
To support toxicology studies and the initiation of the first‐in‐human study, nonclinical studies have been conducted to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of Ab‐01 in P301S mice and the PK of VY‐TAU01 in cynomolgus macaques.
Method:
The PK of Ab‐01 in the P301S mouse after 5 weekly intravenous or intraperitoneal doses at 10 to 120 mg/kg and VY‐TAU01 in cynomolgus macaques after a single intravenous high or mid dose was evaluated with validated ELISAs using their target epitope peptide. The PD of Ab‐01 in the P301S mouse was also evaluated using an ELISA to quantify unbound p‐tau levels.
Result:
Ab‐01 and VY‐TAU01 PK profiles in serum and cerebrospinal fluid (CSF) were characterized by a distribution phase followed by a typical elimination phase without evidence of substantial target‐mediated disposition in the respective compartments. Serum and CSF concentrations increased with increasing dose levels in an approximately dose proportional manner, and their half‐lives were approximately 9 to 13 days. CSF concentrations were 0.1 ‐ 0.2% of serum concentrations.
PD effects of Ab‐01 in the P301S mouse were robust, with up to ∼90% lowering of unbound p‐tau. Additional PD as well as PK/PD modeling results will also be presented.
Conclusion:
The PK of Ab‐01 in the P301S mouse and VY‐TAU01 in the cynomolgus macaque, and CSF to serum ratios were typical of murine IgG1 and human IgG4 administered to these respective species. The PD of Ab‐01 in the P301S mouse demonstrated robust lowering of unbound p‐tau. These results support VY‐TAU01’s continued development and advancement into the clinic
Empowering Families: The Role of Provider Coaching in Indiana Early Intervention
No full textIUIIn 2022, Indiana’s early intervention program, First Steps, provided services to over 27,000 children ages 0-3. Throughout a comprehensive needs assessment, First Steps identified a need for more culturally inclusive educational materials to ensure early intervention therapists are providing culturally appropriate care. The goal of this capstone project was to provide education to early intervention providers regarding cultural humility in home visiting. This project consisted of a cultural presentation informing providers about typical household routines in Haitian, Burmese, and Latino/Hispanic cultures, as well as the creation of several cultural handouts. A pre- and post-survey approach was used to gather data regarding provider comfort, confidence, and use of Family Guided Routines Based Intervention (FGRBI) in early intervention home visits. Quantitative results of these surveys found that providers reported increases in all the previously mentioned categories. Many providers also provided qualitative evidence of increased knowledge due to the cultural presentation and handouts.Occupational Therap
An Ethnographic Study of Black Teenagers, Gun Violence, and the Youth Control Complex in Indianapolis
No full textIUIThe violent gun-related death of teenager David Lowery in 2020, alongside troubling statistical trends, catalyzed this research on teen gun violence in Indianapolis. While Black teenagers are not inherently more violent than their white counterparts, they often live in racially segregated neighborhoods that foster isolation, economic hardship, and higher crime rates. Structural inequities, combined with historical disinvestment, leave these communities vulnerable to cycles of violence. This study employs community-based participatory research (CBPR) principles and multi-modal ethnography, centering teenage voices—including a teenage co-researcher and video producer—to explore the lived realities of youth impacted by gun-related offenses. Data collection began with semi-structured interviews of ten young people charged with gun-related crimes as teenagers by the Marion County Prosecutor's Office. These youth described peer influence, social media portrayals, and fear as motivations for carrying firearms. To address gun violence, teenagers recommended increased community activities, mentoring, and counseling, alongside improvements to their neighborhoods, such as repairing abandoned homes and fostering deeper relationships with youth. Many expressed feelings of entrapment within their environments, highlighting the need for safe spaces that instill hope and provide tangible opportunities for change. The research team created a short film based on interview data and screened it with youth workers and stakeholders within the youth control complex to gather feedback and spur discourse. The significance of incorporating a teenage co-researcher is amplified through storytelling, demonstrating how participatory approaches shift narratives around expertise and youth agency. This project revealed four critical recommendations: (1) Reconsider who is an expert as research is designed and carried out: (2) Dismantle the youth control complex and focus resources no developing relationship sand connections with families; (3) Foster discussion and conversation for an educated civil society; (4) Critique the failure of local elected officials and public policy to support families and build thriving neighborhoods. This study contributes to conversations on violence prevention, racial justice, and youth advocacy, emphasizing how rethinking expertise and prioritizing youth-led initiatives can generate systemic solutions to gun violence rather than merely treating symptoms