51886 research outputs found
Sort by
Engaging Patients in User centered Design for Passive Detection of Dementia and Participation in Brain Health Research in Primary Care
No full textMost older adults who have or who are at‐risk of developing dementia rely solely on primary care (PC). PC is the ideal setting to establish guidelines and workflows for detection and diagnostic assessment for dementia, and to facilitate access to pharmacologic and nonpharmacological treatment and research. Indiana University (IU) and IU Health (IUH) are testing using a machine learning algorithm (MLA) to passively detect PC patients who have undetected cognitive impairment or who are at risk of developing dementia in the next 1‐3 years. The feasibility and acceptability of implementing this intervention into clinical use requires engagement from patients and providers to create both the message and the mode by which high risk patients will be engaged in their diagnostic and care journey. The IU/ IUH Brain Health Navigator (BHN) is a PC‐based nurse navigator who conducts evidence‐based assessments for addressable and pathophysiologic causes of cognitive impairment, provides recommendations to the PCP for next steps, answers patient and family questions, and facilitates access to participation in research. This study will test the feasibility and acceptability of using a MLA to (1) detect PC patients who are at high risk of having undetected dementia or developing dementia; (2) engage these high‐risk patients to have a visit with the PC‐based BHN, and (3) increase the number of patients who agree to be contacted for brain health research. To date 20 patients are scheduled to participate in the user‐centered design session and ten diverse clinics have been approached to participate in the pilot
Palliative Care Knowledge and Attitudes of Nursing Home Staff: Baseline Data From the UPLIFT Trial
No full textPalliative care and hospice are known to improve quality of care within nursing homes. However, such care is underutilized in long term care settings. One known barrier is staff knowledge and attitudes. To evaluate the palliative care knowledge, attitudes, and practices among nursing home staff, we surveyed (n = 242) frontline nursing home staff in 16 facilities located in two states, n = 8 in Maryland and n = 8 in Indiana, using a validated survey instrument. The survey contains domains including family communication, provider communication, planning/intervention, and bereavement, and utilizes patient vignettes. Participating nursing home communities were eligible if they: had >40 long stay residents with cognitive impairment and did not have an active in-house palliative care program. Surveys were collected in person by research staff. Survey completion varied across facilities (from n = 6 to n = 23). Participating nursing home staff had an average age of 43 years old, 92% female, and 49% were Black/African American. The most common job categories for nursing home staff completing the survey were certified nursing assistants (44%), followed by nurses including LPNs (20%, and RNs (8%). With higher scores indicating greater knowledge/better attitudes (possible range 1-4 on each item), we found that participating staff had: M = 3.1 (SD = 0.6) on the Family Communication subscale; M = 2.9 (SD = 0.8) on the Provider Coordination subscale; M = 2.7 (SD = 0.9) on the Planning/Intervention subscale; and M = 2.4 (SD = 0.6) on the Bereavement subscale. Overall, palliative care knowledge scores for physical symptoms were higher than psychological symptoms, which were both higher than knowledge of end of life
Digital droplet PCR is an accurate and precise method to measure DNA copy number
No full textDNA copy number research is impeded by limited methodology to determine true DNA copy numbers accurately and precisely. Human alpha defensin 1-3 (DEFA1A3) is a multiallelic gene with DNA copy numbers generally ranging from 2 to 12 copies per diploid genome. In this study, we developed a digital droplet PCR (ddPCR) protocol using DEFA1A3 as a model locus. We compared these results to DNA copy numbers determined by pulsed field gel electrophoresis (PFGE), which is considered a gold standard in CNV identification, on 40 DNA samples from a clinical study cohort. Taqman real-time quantitative PCR (qPCR) was also compared, being the other major available low cost, high-throughput system. The copy number measurements of 40 genomic samples were highly concordant between ddPCR and PFGE, while copy number by qPCR correlated only weakly with PFGE copy number. In conclusion, ddPCR is a low-cost, high-throughput technique with accurate resolution of CNV at both low and high DNA copy numbers. This makes it an ideal model to adapt for CNV testing in clinical practice
Contusive spinal cord injury causes Nav1.8 dysfunction to upregulate small sensory neuron excitability
No full textChronic neuropathic pain associated with spinal cord injury (SCI) poses a significant medical challenge. Studies have shown that moderate thoracic (T10) SCI can substantially enhance the excitability of small diameter dorsal root ganglion (DRG) neurons, suggesting that pain resulting from SCI may arise from pathological alternations in peripheral neurons. However, the molecular mechanisms underlying these changes remain unclear. Here we show that contusive SCI significantly increases transient and resurgent sodium currents mainly through Nav1.8 in rat small DRG neurons. Additionally, SCI increases the proportion of small DRG neurons that produce tetrodotoxin-resistant resurgent currents. The SCI-induced increase of Nav1.8 currents can be reversed by ZL0177, a small peptidomimetic of the critical residues in fibroblast growth factor homologous factors 4 (FHF4) that binds to the C-terminal tail of sodium channels. ZL0177 not only decreases the transient and resurgent currents of Nav1.8 and Nav1.9 but also reduces the proportion of the neurons that generate Nav1.8 resurgent currents. We further show that ZL0177 greatly attenuates the hyperexcitability of small DRG neurons induced by SCI. Taken together, our results indicate Nav1.8 dysfunction following SCI plays a critical role in enhancing excitability of nociceptive neurons. Furthermore, the binding site of FHFs at the C-terminal tail of Nav1.8 and Nav1.9 can serve as a promising therapeutic target for the treatment of SCI pain. KEY POINTS: Traumatic spinal cord injury (SCI) often leads to chronic pain conditions. Recent clinical and experimental studies indicate that the pain induced by SCI may be attributed to abnormal peripheral neuron inputs; however, the molecular mechanisms underlying these changes remain unclear. Here we studied sodium currents and action potential firing in rat small DRG neurons following contusive SCI. Contusive SCI significantly increased Nav1.8 transient and resurgent sodium currents in the rat small DRG neurons. ZL0177, a peptidomimetic inhibitor of fibroblast growth factor homologous factor (FHF) binding to the C-terminus of sodium channels not only decreased Nav1.8/Nav1.9 currents, but also greatly attenuated the hyperexcitability of small DRG neurons induced by SCI. Thus, targeting FHF modulation of Nav1.8/Nav1.9 may serve as a promising treatment strategy for SCI pain
The Clinical View of Sepsis-Associated AKI: How Basic Science Can Help Solve This Problem
No full textThe global health impact of sepsis is difficult to understate. As a complication of sepsis, the development of sepsis-associated acute kidney injury (SA-AKI) significantly increases the risk of mortality. Although several epidemiological risk factors for SA-AKI are known, the heterogeneity of this syndrome-across patients, pathogens, and treatment responses-has hindered therapeutic innovation and contributed to persistently poor outcomes. Precision medicine offers a promising framework to address this complexity, yet a substantial translational gap remains between mechanistic insights from preclinical models and the therapeutic strategies used in clinical practice. To bridge this gap, researchers should consider aligning preclinical models with human sepsis and embrace SA-AKI heterogeneity to identify treatable, mechanistically informed subtypes (endotypes). These efforts could enable the development of personalized therapies aimed at reducing the burden of SA-AKI
Plasma proteomic Alzheimer's risk score: Biological age clock and pseudotime trajectory
No full textIntroduction: Alzheimer's disease (AD) involves progressive cognitive decline. Plasma proteomics data may provide insights into disease risk and mechanisms.
Methods: Plasma proteomics data (N = 498) by the SomaScan 7k platform from the Indiana AD Research Center was used to calculate proteomics-based Alzheimer's risk scores: organ-specific aging clocks and pseudotime trajectory. The Alzheimer's risk scores were investigated for associations with plasma- and imaging-based biomarkers for AD and diagnosis and evaluated for classification performance for diagnosis and biomarker positivity status.
Results: Cognition-optimized brain and liver age acceleration showed significant associations with AD diagnosis and biomarkers. Pseudotime showed a molecular trajectory from cognitively normal to AD individuals, in association with plasma and imaging biomarkers. Previously known plasma biomarkers yielded better classification performance with inclusion of proteomics-based Alzheimer's risk scores.
Discussion: The findings highlight proteomics-derived biological aging clocks and pseudotime trajectory as potential biomarkers to complement current biomarker frameworks and identify disease mechanisms.
Highlights: Plasma proteomic aging clocks and pseudotime provide potential markers for Alzheimer's disease (AD) risk. Cognition-optimized brain aging and pseudotime link to diagnosis and AD biomarkers. Brain aging clock and pseudotime improve the diagnosis classification performance. Pseudotime outperformed established plasma biomarkers for diagnosis classification
Cervical HPV 18 detection is associated with high-grade cervical dysplasia in Kenyan and Ugandan women living with HIV
No full textObjectives: Cervical cancer, caused by "high-risk" (HR) HPV, is the most common malignancy and the leading cause of cancer deaths among women living in Kenya and Uganda. Women living with HIV (WLWH) are at a high risk for HR-HPV infection. This longitudinal, observational cohort analysis was conducted to identify factors that are important among WLWH in prediction of cervical intraepithelial neoplasia grades 2 or 3 (CIN2/3).
Methods: Data of this analysis was based on a study of HPV natural history and cervical cancer among Kenyan and Ugandan WLWH. Demographic, behavioral and biological data were collected; HR-HPV DNA testing of cervical swabs was performed (Roche Cobas Assay); all WLWH underwent cervical biopsy on two occasions.
Results: Of 114 WLWH enrolled, the median age was 38.2 years. All WLWH were receiving ART during the study. CIN2/3 was found in 13 (11.4 %) WLWH; HPV 16 was detected in 10 (8.8 %); HPV 18 in 11 (9.6 %), and Non-16/18 HR-HPV in 62 (54.4 %). Aflatoxin exposure was not associated with CIN2/3 in this analysis. A multivariable logistic regression found that cervical detection of HPV 18 was significantly associated with CIN2/3 (OR = 6.36, 95 % CI = 1.36-29.75, p = 0.019), after adjusting for the effects of HIV viral load, CD4 counts, and Non-16/18 HR-HPV detection.
Conclusions: CIN2/3 was detected in 11.4% of WLWH; HPV 18 detection in cervical swabs was strongly associated with CIN2/3. Larger studies among WLWH are needed to determine optimal approaches for screening and treatment to prevent cervical cancer
Neonatal outcomes among pregnant women with COVID-19: a systematic scoping review and meta-analysis
No full textBackground: Current findings on the neonatal outcomes among pregnant women infected with COVID-19 remain inconclusive. The purpose of this systematic scoping review and meta-analysis was to summarize the literature regarding this topic and provide an overview of the methodologies and results present in current research.
Methods: PubMed was searched up to December 2022 to identify observational studies that reported neonatal outcomes among children delivered by mothers diagnosed with COVID-19 during pregnancy. Outcomes of interest included vertical transmission to neonates, neonatal intensive care unit (NICU) admission, and neonatal death. Qualitative analysis and meta-analysis were applied to summarize and synthesize the results.
Results: Out of an initial selection of 13,387 studies, 187 were included in this systematic scoping review. There was high heterogeneity in the epidemiologic study design, sample size, and outcomes of interest. Most studies focused on neonatal outcomes from birth to day 14 rather than the full neonatal period. Conflicting conclusions were drawn regarding outcomes among neonates delivered by COVID-19-positive mothers. Results of meta-analysis revealed that maternal COVID-19 infection was moderately associated with the risk of vertical transmission to neonates (Incidence Rate [IR], 2.66%; 95%CI, 2.11-3.35%), neonatal intensive care unit admission (IR, 16.43%; 95%CI, 14.59-18.45%), and neonatal death (IR, 1.29%; 95%CI, 0.95-1.74%), and these risks seemed to be increased with the severity of maternal COVID-19.
Conclusions: This review identified heterogeneity in the epidemiologic studies. Maternal COVID-19 infection was associated with the risk of adverse neonatal outcomes and these risks seemed to be increased with the severity of maternal COVID-19
Lower amyloid and small vessel disease in unimpaired older adults with Down syndrome
No full textBackground:
The revised Alzheimer's Association Research Framework presumes that all adults with Down syndrome (DS) are on the Alzheimer's disease (AD) continuum, developing AD at a median age of 54 years old after lifelong overproduction of amyloid precursor protein. However, some older adults with DS “escape” AD biomarker development or cognitive impairment, even in the context of genetically determined AD risk. We explored whether older adults with DS without a clinical diagnosis or with lower‐than‐expected amyloid differed in their tau and cerebrovascular disease burden.
Method:
Adults with DS (n = 259; 45±10 yrs, 43% women, 75% Cognitively‐Stable/12% MCI‐DS/13%AD‐DS) from the Alzheimer's Biomarker Consortium‐Down syndrome (ABC‐DS) underwent vascular MRI (white matter hyperintensity (WMH), enlarged perivascular space (PVS), infarcts, microbleeds), amyloid PET, and tau PET. Adults with DS who were Cognitively‐Stable above the age of 54 years old (i.e., greater‐than‐expected cognition for their age) were categorized separately from all others. All biomarkers were fit against left‐null piecewise regression models with age, adjusting for site; the lower 5th percentile of age‐trajectory residuals (i.e., less‐than‐expected for their age) for amyloid were categorized separately from the upper 95th percentile. Participants with better‐than‐expected cognition and amyloid were compared in terms of demographic characteristics as well as tau and cerebrovascular residuals.
Result:
Older Cognitively‐Stable adults were older by definition (15 [10, 19], p = 2E‐9), had lower age‐residuals for amyloid (‐27 [‐44, ‐9], p = 0.003), and temporal (‐0.3 [‐0.6, ‐0.01], p = 0.04), parietal (‐1.4 [‐2.5, ‐0.2], p = 0.02), and occipital WMH (‐0.8 [‐1.5, ‐0.06], p = 0.03). Individuals in the 5th percentile of age‐residuals for amyloid were older (11 [5, 17], p = 0.0003), had lower age‐residuals for tau in early Braak tau (‐0.2 [‐0.4, ‐0.1], p = 0.0002), middle Braak (‐0.3 [‐0.4, ‐0.1], p = 0.0002), late Braak (‐0.2 [‐0.4, ‐0.06], p = 0.007), as well as deep microbleeds (‐1.0 [‐0.2, ‐0.04], p = 0.002).
Conclusion:
Older adults with DS who remain cognitively‐stable had lower amyloid and posterior WMH, while those that maintain low amyloid at older ages had lower tau and microbleeds. Future work will investigate protective factors that may contribute to biomarker and clinical variability, even in the context of genetically determined AD risk