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Cytomegalovirus reactivation and acute and chronic complications in children with cerebral malaria: a prospective cohort study
Get PDFBackground: Virus co-infection or reactivation may modify the host response during cerebral malaria. Cytomegalovirus (CMV) DNAemia has been associated with increased morbidity and mortality in adults with sepsis; however, the impact of CMV DNAemia on adverse outcomes in children with cerebral malaria is unknown.
Methods: Clinical, physiological, and neurocognitive outcomes were compared in children aged 18 months to 12 years with cerebral malaria (N = 242) based on the presence or absence of CMV DNAemia 24 h after admission. The primary study outcome was subsequent in-hospital mortality. Secondary outcomes included the presence of acute kidney injury, neurocognitive impairment over a 2-year follow-up, and chronic kidney disease at the 1-year follow-up. Markers of platelet and endothelial cell activation and oxidative and nitrosative stress were measured to characterize the mechanisms by which CMV DNAemia might contribute to pathogenesis.
Results: CMV DNAemia was present in 33 children with cerebral malaria (13.6%) 24 h after admission. CMV DNAemia was not significantly associated with mortality in this study. Children with CMV-DNAemia had a higher prevalence of acute kidney injury than those without CMV-DNAemia (59.4% vs. 38.6%, p = 0.03). There was no difference in the prevalence of chronic kidney disease or long-term neurocognitive impairment based on the presence of DNAemia. CMV DNAemia was associated with elevated plasma levels of P-selectin, angiopoietin-1, asymmetric dimethylarginine, and platelet counts.
Conclusions: In children with cerebral malaria, CMV DNAemia is associated with acute kidney injury but not in-hospital mortality, chronic kidney disease, or long-term neurocognitive impairment
Association of Alzheimer’s disease polygenic risk score with concussion severity and recovery metrics
No full textBackground:
Shared genetic risk between Alzheimer’s disease (AD) and concussion may help explain the association between concussion and elevated risk for dementia. However, there has been little investigation into whether AD risk genes also associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) and APOE genotypes to investigate associations between AD genetic risk and concussion severity/recovery in the NCAA‐DoD Grand Alliance CARE Consortium (CARE) dataset.
Method:
There were 1,917 injuries in the dataset upon project initiation. After removing repeated injuries, related participants, and those without genetic/outcome data, we had 931 participants. Outcomes were number of days to return to play (RTP) as a recovery measure, and four severity measures (scores on SAC and BESS, SCAT symptom severity and total number of symptoms). We calculated PRS using a published score (de Rojas et al., 2021) and performed a linear regression (MLR) of RTP by PRS in normal (24 days) RTP subgroups. We then compared severity measures by PRS using MLR. Next, we used t‐tests to examine outcomes by APOE genotype in military and civilian subgroups. We also performed chi‐squared tests of RTP category (normal vs. long) by APOE genotype. Finally, we analyzed outcomes by PRS in European or African genetic ancestry subgroups using MLR.
Result:
Higher PRS was associated with longer injury to RTP interval in the normal RTP (<24 days) subgroup (estimate = 0.0412, SE = 0.182, p = 0.0237). 1 SD increase in PRS resulted in a 0.412 day (9.89 hours) increase to the interval. This may be clinically meaningful in the collegiate athlete environment. We did not identify any other significant differences.
Conclusion:
Our preliminary results provide limited evidence for an impact of AD PRS on concussion recovery, though the pattern was inconsistent and its clinical significance is uncertain. Future studies should attempt to replicate these findings in larger samples with longer follow‐up using PRS calculated from multiple/diverse populations, which will be especially relevant for diverse datasets like CARE
Dissociable spatial topography of cortical atrophy in early‐onset and late‐onset Alzheimer's disease: A head‐to‐head comparison of the LEADS and ADNI cohorts
No full textIntroduction: Early-onset and late-onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head-to-head comparison of cortical atrophy in EOAD and LOAD, using two large and well-characterized cohorts (LEADS and ADNI).
Methods: We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early-stage AD), along with cognitively unimpaired participants.
Results: After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD.
Discussion: Our findings point to the clinical utility of MRI-based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment.
Highlights: Early-onset Alzheimer's disease (EOAD) and late-onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns. EOAD patients showed prominent atrophy in widespread neocortical regions. LOAD patients showed prominent atrophy in the anterior medial temporal lobe. Regional atrophy was correlated with the severity of global cognitive impairment. Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia
Deciphering genetic regulation at single-cell resolution in gastric cancer
Get PDFUnderstanding cell-type-specific genetic regulation in gastric cancer is essential for uncovering disease susceptibility. By performing single-cell eQTL mapping in gastric tissues, Bian et al.1 identified previously uncharacterized regulatory genetic mechanisms, risk genes, and co-localization signals associated with gastric cancer susceptibility, providing insights into its pathogenesis and potential therapeutic approaches
Examining Psychological Moderators of the Relationships between Financial Toxicity and Symptoms in Patients with Cancer
No full textIUIFinancial toxicity, which includes both the objective financial burden and subjective financial distress related to cancer treatment, has been linked to decrements in patient well-being. Drawing on the Transactional Model of Stress and Coping, this study examines relationships between cancer-related financial toxicity and changes in physical and psychological symptoms over time. Additionally, perceived injustice and acceptance-based coping were examined as potential moderators of these relationships. Patients (N=200) with early-stage solid tumors and at least mild financial toxicity were recruited from Indiana hospitals. Patients were undergoing cancer treatment or had completed treatment within the past 6 months. Assessments were completed at baseline and two months later and included self-report measures of financial toxicity, perceived injustice, acceptance-based coping, and symptoms (anxiety, depressive symptoms, fatigue, sleep disturbance, and pain).
I used path analysis to evaluate direct and moderated relationships between financial toxicity and symptoms while adjusting for theoretically relevant demographic and medical covariates. Results showed that higher financial toxicity was significantly correlated with increased depressive symptoms over time (B=-0.19, p<.01) but was not associated with changes in pain, fatigue, sleep disturbance, or anxiety. Contrary to hypotheses, perceived injustice and acceptance-based coping did not moderate these relationships. However, perceived injustice was significantly associated with heightened anxiety (B=2.16, p<.01), depressive symptoms (B=2.41, p<.01), and sleep disturbance (B=1.27, p=.02), and acceptance-based coping was linked to reduced depressive symptoms (B=-1.19, p=.03).
Findings contribute to limited longitudinal findings on the detrimental effect of financial toxicity on mental health. Other symptoms were relatively stable over time, and limited variance may have contributed to null findings. Limitations include the primarily non-Hispanic White sample, short follow-up duration, and potential self-report biases. Despite these limitations, results underscore the prevalence of financial toxicity and the need to develop and evaluate interventions that jointly address financial and mental well-being. Next steps also include examining mechanisms linking financial toxicity to mental health outcomes
A scoping review of librarian involvement in competency-based medical education
No full textObjective: A scoping review was undertaken to understand the extent of literature on librarian involvement in competency-based medical education (CBME).
Methods: We followed Joanna Briggs Institute methodology and PRISMA-ScR reporting guidelines. A search of peer-reviewed literature was conducted on December 31, 2022, in Medline, Embase, ERIC, CINAHL Complete, SCOPUS, LISS, LLIS, and LISTA. Studies were included if they described librarian involvement in the planning, delivery, or assessment of CBME in an LCME-accredited medical school and were published in English. Outcomes included characteristics of the inventions (duration, librarian role, content covered) and of the outcomes and measures (level on Kirkpatrick Model of Training Evaluation, direction of findings, measure used).
Results: Fifty studies were included of 11,051 screened: 46 empirical studies or program evaluations and four literature reviews. Studies were published in eight journals with two-thirds published after 2010. Duration of the intervention ranged from 30 minutes to a semester long. Librarians served as collaborators, leaders, curriculum designers, and evaluators. Studies primarily covered asking clinical questions and finding information and most often assessed reaction or learning outcomes.
Conclusions: A solid base of literature on librarian involvement in CBME exists; however, few studies measure user behavior or use validated outcomes measures. When librarians are communicating their value to stakeholders, having evidence for the contributions of librarians is essential. Existing publications may not capture the extent of work done in this area. Additional research is needed to quantify the impact of librarian involvement in competency-based medical education
The TREM2 Dependent and Independent Effects of Ozone on Immune Cell Trafficking in the Lung-Brain Axis
No full textIUIAir pollution remains a major health threat, responsible for 8.1 million deaths globally and ranking as the second leading cause of death in 2021. Ozone (O3), one of the six main pollutants defined by the Clean Air Act of 1970, has been linked to various health issues, including respiratory and cardiovascular diseases, as well as cognitive decline. Because O3 is confined to the respiratory tract after inhalation and unable to reach the brain directly, its toxicity to distant organs is thought to arise from a cascade of byproducts generated in the lungs. This suggests the pulmonary immune response may contribute to O3-induced effects on the central nervous system (CNS), a concept known as the Lung-Brain Axis. O3 reacts in the lungs, producing reactive oxygen species (ROS) that trigger oxidative stress and inflammation. These ROS can spread throughout the body, leading to widespread oxidative stress and damage. The CNS is particularly vulnerable to oxidative stress, which is closely associated with neuroinflammation. Recent studies have highlighted the role of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) as a key immune signaling hub, particularly in Alzheimer's Disease (AD) due to its implications in AD pathology and neuroinflammation. However, little research has explored TREM2's role in other myeloid cells or its involvement in the Lung-Brain Axis. This study investigates TREM2 and its adapter protein, DAP12, in O3-driven immune cell trafficking across the Lung-Brain Axis. The findings show that O3 exposure alters immune cell dynamics in the lungs and lymph nodes and that Trem2-deficient mice exhibit transcriptional changes in both pulmonary and neuroimmune responses. These results highlight the complex interplay of TREM2-dependent and independent pathways in O3-induced immune responses, shedding light on how peripheral immune activity can influence the neuroimmune environment and linking environmental factors to CNS health and disease
Pharmacokinetic, Safety, and Pharmacodynamic Profiles of Saroglitazar Magnesium in Cholestatic Cirrhosis With Hepatic Impairment and Participants With Renal Impairment
No full textSaroglitazar magnesium, a dual PPAR α/γ agonist, currently in Phase III for treating primary biliary cholangitis (PBC), was evaluated for its pharmacokinetic (PK) profile, safety, and pharmacodynamics in participants with cholestatic liver disease (CLD) across different levels of hepatic impairment (HI) and participants with severe renal impairment (RI). Three PK studies comparing saroglitazar with healthy controls were conducted: Study 1 involved daily oral doses of 1 or 2 mg for 4 weeks in 12 PBC cirrhosis participants with mild or moderate HI; Study 2 assessed single-dose PK (2 or 4 mg) in eight non-cirrhotic CLD participants; Study 3 evaluated single-dose PK (2 mg) in eight participants with severe RI. On day 1, saroglitazar exposure increased by 14.6-42% in mild HI vs. normal, but by day 28, levels were similar, indicating no accumulation. In moderate HI, exposure was significantly increased by 50.4-85% on days 1 and 28, with 34-46% lower clearance despite a similar half-life. The moderate HI group had a 59% higher exposure than the non-cirrhotic group. Saroglitazar (1 and 2 mg) reduced alkaline phosphatase (ALP) levels by 17-40% after 4 weeks in participants with abnormal baseline ALP. Single-dose PK in non-cirrhotic CLD (2 and 4 mg) and severe RI (2 mg) was comparable to matched controls without significant safety issues. Overall, saroglitazar (1 and 2 mg) was safe and well-tolerated in cholestatic cirrhosis with mild HI and participants with severe RI without major PK changes. Moderate HI increased exposure and decreased clearance without any safety concerns
Peripheral metabolism informs on future cognitive decline and development of Alzheimer’s disease in population at risk
No full textBackground:
Peripheral metabolic health status can reflect and/or contribute to the risk of Alzheimer’s disease (AD). Peripheral metabolic health status can be indicated by metabolic health markers, such as inflammatory biomarker glycoprotein acetyls (GlycA) and specific components of lipoproteins (e.g., triacylglycerol of high‐density lipoprotein). However, it is unclear if the relationship between peripheral metabolism and AD‐related markers is heterogenous among diverse populations and throughout the disease progression.
Methods:
Utilizing Alzheimer’s Disease Neuroimaging Initiative data, we determined whether baseline plasma GlycA can inform on cognitive and brain structural changes among sub‐populations with different diagnosis status. Furthermore, correlation analyses were performed between blood metabolomics and cerebrospinal fluid (CSF) proteomics data in sub‐populations with different diagnosis status or different mild cognitive impairment (MCI)/AD outcomes in 3 years.
Results:
GlycA was elevated in AD patients compared to cognitively normal participants. Baseline GlycA level was associated with executive function decline at 3‐9 year follow‐up in participants diagnosed with late mild cognitive impairment (LMCI) at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. In addition, peripheral metabolomics signatures of CSF proteomics were well‐distinguished between cognitive normal participants and AD patients. Moreover, different peripheral‐central metabolic connection was also observed in MCI‐AD converters vs. MCI‐MCI non‐converters across 3 years follow up.
Conclusion:
Peripheral inflammation was linked to future cognitive decline and brain structural atrophy for population at risk. In addition, peripheral metabolomics‐CSF proteomics correlation reveals distinguishing peripheral‐central connection patterns in AD patients as well as MCI participant soon to develop AD in 3 years. Findings here point to peripheral systemic inflammation and metabolic health in general as risk factors in AD development, pointing to therapeutic intervention related to periphery metabolic health for patients at risk
Networking Name Tag
No full textName Tag Design used as a part of the Kismet Connections activity done at the 2025 Indiana Libraries and Literacy Symposium