51886 research outputs found
Sort by
The use of transcranial direct current stimulation to facilitate motor skill reactivations of a choice reaction time task in adults
No full textMotor skill acquisition involves fast and slow learning phases, typically requiring extended practice. This study explored whether brief reactivations of a choice reaction time (CRT) task, combined with anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1), could yield performance improvements comparable to full-length practice. A total of 120 healthy adults were randomized into six groups varying in tDCS use (2 mA for 5 or 20 min) and practice duration (5 or 20 min). Reaction time (RT) and error rate were assessed across sessions. Across all groups, RT significantly improved from 423.5 ± 116.8 ms at pre-test to 357.9 ± 63.4 ms post-test (p < 0.001), of the first session. RTs at session 4 (377.8 ± 66.2 ms) remained significantly faster than baseline (p < 0.001), though slightly slower than immediate post-test in session 1 (p = 0.172). No significant between-group differences emerged in RT or error rate, though the brief reactivation + tDCS group achieved RTs similar to the full-practice group. When separated by sex, women showed slower reaction times initially and less improvement in reaction times with practice. These results suggest that brief, tDCS-enhanced reactivations can preserve behavioral improvements in learning, though their neurophysiological effects remain inconclusive
Pinto Bean Supplementation Modulates Gut Microbiota and Improves Markers of Gut Integrity in a Mouse Model of Estrogen Deficiency
No full textBackground: Emerging research suggests that changes in gut microbiota play a key role in menopause-related diseases by modulating gut health.
Objectives: This study investigated the effects of pinto bean (PB) supplementation on gut integrity in an estrogen-deficient mouse model.
Methods: Sixty 3-mo-old female C57BL/6J mice were injected with either sesame oil (vehicle) or vinylcyclohexene diepoxide (VCD, 160 mg/kg) for 30 d to induce estrogen deficiency. Mice were then randomly assigned to 2 dietary groups (n = 15/group): control (AIN-93M) or AIN-93M + 10% (wt/wt) PB for 16 wk. Ovarian failure was confirmed by uterine weight and serum follicle-stimulating hormone (FSH). Gut health was assessed by measuring tight junction proteins, β-glucuronidase activity, short-chain fatty acids (SCFAs), and 16S microbiota composition. PB was evaluated for its estrogenic effects by molecular docking analysis of the identified polyphenols against estrogen receptor (ER)-α and ER-β. Data were analyzed by 2-way analysis of variance, with estrogen status (VCD) and diet as factors followed by post hoc tests when significant (P < 0.05) interaction effect was observed.
Results: VCD significantly (PVCD < 0.05) reduced relative uterine weight (∼35%) and increased serum FSH (∼60%), confirming estrogen reduction. PB restored jejunal Cldn1 (Pdiet × VCD < 0.05) in VCD-treated mice and significantly increased (Pdiet=0.010) β-glucuronidase activity (∼25%). PB enriched some beneficial bacteria genera (i.e., Bifidobacterium, Bacteroides, Dubosiella, and Lactobacillus) and increased fecal acetic, propionic, n-butyric, and total SCFAs by 2-fold compared with those on the control diet. Molecular docking analysis identified sinapic and ferulic acid as phytoestrogens in PB with high binding affinity for ERs.
Conclusions: PB supplementation improves gut microbial diversity and integrity in estrogen deficiency, offering potential benefits for menopause-related gut health
Multicohort characterization of brain volume and cognitive decline in LATE‐NC cases with or without Alzheimer's disease pathology
No full textBackground:
Limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic change (LATE‐NC) is a research priority given its high prevalence in dementia cases with and without Alzheimer's disease pathology (AD). In the absence of LATE‐NC biomarkers, characterizing the clinical presentation of LATE‐NC would improve our ability to identify LATE‐NC cases during life. The present study evaluated the relationship of pathologically confirmed LATE‐NC with and without AD and medial temporal lobe (MTL) volume and longitudinal cognitive change.
Method:
Participants from the AD Sequencing Project Phenotype Harmonization Consortium age 70+ at death (n = 846) were examined using harmonized, longitudinal cognitive domain scores (memory, executive function, and language), neuropathology, and genetic data (Table 1). Post‐mortem neuropathology scores (AD+=intermediate to high AD likelihood; LATE‐NC+=TDP‐43 stage 1+) were used to categorize participants. Ante‐mortem 3T brain scans were segmented using a multi‐atlas label fusion method, MUSE. ANOVA and chi‐square analyses compared participant characteristics at the last cognitive visit across groups. Linear regression models assessed the effect of AD and LATE‐NC pathology on MTL subregional volume, adjusting for age, sex, education, time between last visit and autopsy, intracranial volume, and cohort. Linear mixed effects models assessed the effect of group on cognitive decline, additionally adjusting for age*time and race/ethnicity.
Result:
Last memory, executive function, and language scores differed by post‐mortem pathology; AD‐LATE‐NC+ and AD‐LATE‐NC‐ groups differed only in memory scores. Longitudinally, all other groups, including AD‐LATE‐NC+, had a faster rate of decline in memory scores on average compared to the AD‐LATE‐NC‐ group (Figure 1; time x AD‐LATE‐NC+=‐0.20, CI [‐0.35, ‐0.06], p = 0.01). On average, only AD+ groups had a faster rate of decline in executive function and language scores compared to the AD‐LATE‐NC‐ group. All MTL subregional volumes were associated with both AD and LATE‐NC, except the superior temporal gyrus, which was associated with neither, and the hippocampus, which was associated with LATE‐NC but not AD pathology (Table 3).
Conclusion:
In a large, multicohort study, AD and LATE‐NC uniquely were associated with MTL volume and cognitive decline. Characterizing the clinical correlates of LATE‐NC is essential to identifying LATE‐NC during life and supporting future research into its pathogenesis
Psychiatric disorders converge on common pathways but diverge in cellular context, spatial distribution, and directionality of genetic effects
No full textPsychiatric conditions share common genes, but mechanisms that differentiate diagnoses remain unclear. We present a multidimensional framework for functional analysis of rare copy number variants (CNVs) across 6 diagnostic categories, including schizophrenia (SCZ), autism (ASD), bipolar disorder (BD), depression (MDD), PTSD, and ADHD (N = 574,965). Using gene-set burden analysis (GSBA), we tested duplication (DUP) and deletion (DEL) burden across 2,645 functional gene sets defined by the intersections of pathways, cell types, and cortical regions. While diagnoses converge on shared pathways, mixed-effects modeling revealed divergence of pathway effects by cell type, brain region, and gene dosage. Factor analysis identified latent dimensions aligned with clinical axes. A primary factor (F1) captured reciprocal dose-dependent effects of DUP and DEL in SCZ reflecting positive and negative effects in excitatory versus inhibitory neurons and association versus sensory cortex. SCZ and ASD were both strongly aligned with F1 but with opposing directionalities. Orthogonal factors highlighted neuronal versus non-neuronal effects in mood disorders (F2) and differential spatial distributions of DEL effects in ADHD and MDD (F3). High-impact CNVs at 16p11.2 and 22q11.2 were enriched for combinations of cell-type-specific genes involved in pathways consistent with our broader findings. These results reveal molecular and cellular mechanisms that are broadly shared across psychiatric traits but differ between diagnostic categories in context and directionality
Disparities in Chronic Stress Exposure and Appraisal and Later-Life Disability
No full textBackground and objectives: Influenced by the stress process theory, this study investigated the relationship between chronic stress (measured by exposure and appraisal) and the onset of a disability in later life among White, Black, U.S.-born Hispanic, and foreign-born Hispanic adults.
Research design and methods: Using nationally representative data from the Health and Retirement Study, I used Weibull accelerated failure time models to examine racial, ethnic, and nativity disparities in chronic stress exposure and appraisal and age of onset of disability during the following 8-10 years (i.e., incidence).
Results: Over time, earlier onset of disability was associated with higher levels of stress exposure (β = -0.04) and negative appraisals (β = -0.07). Appraising stress as more upsetting had a detrimental influence on later-life disability for Black adults (occurring 11% earlier), but a protective effect for foreign-born Hispanic adults (occurring 20% later) compared with White adults.
Discussion and implications: Overall, findings suggest it is important to acknowledge not just the exposure to chronic stressors, but how upsetting these chronic stressors make one feel to reduce racial, ethnic, and nativity disparities in disability
Quality indicators and patient outcome measures for palliative care in cancer patients: a systematic review
No full textIntroduction: With the exponential rise in global cancer incidence, the surge in demand for palliative care has outstripped capacity, limiting patients' access to quality and holistic palliative care, especially in low- and middle-income countries. Despite an upturn in research activity, evidence in palliative care remains limited, given its complexity as well as the shortage of standardised quality indicators (QIs) and patient outcome measures (POMs). The objective of this systematic review is to assess the QIs and POMs used to evaluate palliative care service on aggregated and individual levels.
Methods: We undertook a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines to determine the QIs and/or POMs of palliative care in patients with non-communicable diseases. A Web of Science, EMBASE, PubMed and SOCSCI search between 1 January 2013 and 31 Dec 2022 identified 41 articles. We appraised the quality of all studies using the mixed methods appraisal tool.
Results: 26.8% of studies focus on QIs, while 73.2% used POMs. >90% of palliative care research took place in high-income settings. Across domains of palliative care, the outcome of care is most studied, while the structure and process of palliative care are understudied. QIs and POMs identified often had overlapping themes. Due to the multidimensionality and intricacy of palliative care, evidence is limited, patchy and heterogenous in quality.
Discussion: There is an overall lack of standardisation of QIs and POMs, as well as variability in evidence of palliative care research. We recommend that stakeholders collaborate to develop a standardised repository of metrics for monitoring and evaluating palliative care services at both individual and system levels, with a particular focus on structural and process indicators. Incorporating validated, patient-centred measures and selecting key items as quality indicators will enable meaningful tracking of changes, guiding resource allocation and driving improvements in patient-centred care. Furthermore, exploring alternative research designs is essential to enhance feasibility, uphold ethical integrity and strengthen the robustness of future studies
Synthesizing Stable Matrices from the HS-5 Bone Marrow Stromal Cell Line
No full textBACKGROUND:
Our lab is focused on investigating the physical and biochemical mechanisms through which the bone marrow extracellular matrix (ECM) regulates musculoskeletal and hematopoietic homeostasis. Previously, we showed that primary cells from young and aging bone produce matrices which recapitulate aging-related remodeling of the bone marrow microenvironment. Among these changes is a significant depletion of CCN matricellular proteins. However, isolating the impact of CCNs from the variety of aging-associated changes requires producing ECMs from immortalized bone marrow stromal cell lines, in which individual CCNs may be deleted without disturbing other matrix components. However, matrices produced by immortalized stromal lines are highly susceptible to damage by decellularization.
METHODS:
A 9-day matrix production protocol was performed with HS-5 bone marrow stromal cells maintained on a variety of commercially available substrates/surfaces. Briefly, the procedure consisted of ascorbic acid induction on day 5 and decellularization on day 8, followed by ECM collection and analysis/imaging with Coomassie Blue stain. Substrates evaluated included tissue culture plastic (TCP), Cell-Tak, Collagen, PDL, CellBind, Silane, Supra, UpCell; with and without fibronectin coating.
RESULTS:
While HS-5 cells readily produced matrix on several substrates, plates coated with Collagen I, further supplemented with fibronectin, most consistently supported the preparation of a well-anchored matrix, which remained intact following decellularization.
CONCLUSION AND POTENTIAL IMPACT:
Producing stable ECMs from HS-5 bone stromal cells will allow our lab to specifically modify and study proteins of interest, including CCN1 and CCN2, which have been suggested to play important roles related to the aging-associated remodeling of the bone marrow niche. When coated with fibronectin, UpCell (Corning) supported stable matrix anchoring, while also allowing for detachment from the culture surface, suggesting potential applications in manufacturing of orthobiologic implants
Proliferative proteome induced by HPV 16E6 and NFX1-123 partnership in longitudinal keratinocyte cultures
No full textHuman papillomaviruses (HPVs) cause cervical, anogenital, and oropharyngeal cancers. Despite the availability of preventive HPV vaccines, their poor uptake leaves individuals at risk for these cancers, many of which remain common globally and others that are increasing domestically. The HPV 16 E6 (16E6) protein plays a significant role in inducing and maintaining cellular transformation of its infected host cell; however, 16E6 itself has no enzymatic activity and executes its functions through partnerships with host proteins. Previously, we demonstrated that 16E6 binds to the host protein NFX1-123, and NFX1-123 expression is increased in HPV 16-positive cervical cancer cell lines and primary cancers compared to normal tissues. In this study, we quantify growth patterns of 16E6-expressing keratinocytes with endogenous or overexpressed NFX1-123 (16E6/vec and 16E6/FN123, respectively) levels and interrogate proteome expression changes early and late in longitudinal growth cultures. Early-passage 16E6/vec and 16E6/FN123 cells showed similar growth rates; however, late-passage 16E6/FN123 cells had accelerated growth, greater population doublings, increased telomerase activity, and a dysplastic phenotype when compared to 16E6/vec cells. Matching this, mass spectrometry revealed only 22 differentially expressed proteins at early passage; meanwhile, late-passaged cells had 827 differentially expressed proteins among 16E6/FN123 and 16E6/vec cells. In that, DNA maintenance and repair, proteins, namely, MCM2 and MCM4, were highly expressed in the 16E6/FN123 compared to 16E6/vec cells. These findings indicate that the 16E6 and NFX1-123 partnership, especially with sustained higher levels of NFX1-123, alters the longitudinal cellular environment in a manner that may initiate a preneoplastic phenotype.
Importance: The high-risk HPV 16E6 protein plays a significant role in inducing and maintaining cellular transformation of its infected host cell; however, 16E6 has no enzymatic activity and carries out most of its functions through partnerships with host endogenous proteins, one being NFX1-123. That NFX1-123 expression is increased in HPV 16-positive cervical cancer and primary cancers compared to normal tissues, and NFX1-123 binds directly to 16E6. This study leverages proteomics to reinforce the synergistic actions of HPV16E6 and NFX1-123 and identifies cellular pathways impacted by this protein partnership over time. These findings encourage further investigation of NFX1-123 as a potential therapeutic target of HPV 16-positive tissues
Therapeutic Factors of U.S. Veterans Exhibiting Art Therapy Artwork in a Gallery: Multi-Year Qualitative Study
No full textThe art therapy gallery exhibition empowered clients to share their experiences publicly. A multi-year, grant-funded qualitative study utilizing a post-exhibition survey question identified the impact of an art therapy gallery exhibition for veterans. Ethical considerations included autonomy, loss of confidentiality, maleficence, and beneficence. Over two exhibitions, 17 veterans participated, and nine completed the post-exhibition survey question. The overall return rate was 60.8%. Content and thematic analyses were used to identify and code themes in the first exhibition, and comparative analysis was used with the second round of data. The findings revealed themes of vulnerability, empowerment, connectedness, and validation. These preliminary findings support publicly exhibiting artwork created in art therapy groups to target clinical treatment needs often seen in veteran populations