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Frontiers in Aging Neuroscience 2024At least one-third of the identified risk alleles from Genome-Wide Association Studies (GWAS) of Alzheimer's disease (AD) are involved in lipid metabolism, lipid...
INTRODUCTION
At least one-third of the identified risk alleles from Genome-Wide Association Studies (GWAS) of Alzheimer's disease (AD) are involved in lipid metabolism, lipid transport, or direct lipid binding. In fact, a common genetic variant (ε4) in a cholesterol and phospholipid transporter, Apolipoprotein E (), is the primary genetic risk factor for late-onset AD. In addition to genetic variants, lipidomic studies have reported severe metabolic dysregulation in human autopsy brain tissue, cerebrospinal fluid, blood, and multiple mouse models of AD.
METHODS
We aimed to identify an overarching metabolic pathway in lipid metabolism by integrating analyses of lipidomics and transcriptomics from the Religious Order Study and Rush Memory Aging Project (ROSMAP) using differential analysis and network correlation analysis.
RESULTS
Coordinated differences in lipids were found to be dysregulated in association with both mild cognitive impairment (MCI) and carriers. Interestingly, these correlations were weakened when adjusting for education. Indeed, the cognitively non-impaired carriers have higher education levels in the ROSMAP cohort, suggesting that this lipid signature may be associated with a resilience phenotype. Network correlation analysis identified multiple differential lipids within a single module that are substrates and products in the Lands Cycle for acyl chain remodeling. In addition, our analyses identified multiple genes in the Lands Cycle acyl chain remodeling pathway, which were associated with cognitive decline independent of amyloid-β (Aβ) load and tau tangle pathologies.
DISCUSSION
Our studies highlight the critical differences in acyl chain remodeling in brain tissue from carriers and individual non-carriers with MCI. A coordinated lipid profile shift in dorsolateral prefrontal cortex from both carriers and MCI suggests differences in lipid metabolism occur early in disease stage and highlights lipid homeostasis as a tractable target for early disease modifying intervention.
PubMed: 38938596
DOI: 10.3389/fnagi.2024.1419253 -
Open Veterinary Journal May 2024The intramuscular (IM) administration of 7.5-10 mg/kg of alfaxalone produces anesthetic effects that enable endotracheal intubation with mild cardiorespiratory...
BACKGROUND
The intramuscular (IM) administration of 7.5-10 mg/kg of alfaxalone produces anesthetic effects that enable endotracheal intubation with mild cardiorespiratory depression in dogs. However, the effects of IM co-administration of medetomidine, butorphanol, and alfaxalone on cardiorespiratory function under inhalation anesthesia have not been studied.
AIM
To assess the cardiorespiratory function following the IM co-administration of 5 μg/kg of medetomidine, 0.3 mg/kg of butorphanol, and 2.5 mg/kg of alfaxalone (MBA) in dogs anesthetized with sevoflurane.
METHODS
Seven intact healthy Beagles (three males and four females, aged 3-6 years old and weighing 10.0-18.1 kg) anesthetized with a predetermined minimum alveolar concentration (MAC) of sevoflurane were included in this study. The baseline cardiorespiratory variable values were recorded using the thermodilution method with a pulmonary artery catheter after stabilization for 15 minutes at 1.3 times their individual sevoflurane MAC. The cardiorespiratory variables were measured again following the IM administration of MBA. Data are expressed as median [interquartile range] and compared with the corresponding baseline values using the Friedman test and Sheff's method. A < 0.05 was considered statistically significant.
RESULTS
The intramuscular administration of MBA transiently decreased the cardiac index [baseline: 3.46 (3.18-3.69), 5 minutes: 1.67 (1.57-1.75) l/minute/m : < 0.001], respiratory frequency, and arterial pH. In contrast, it increased the systemic vascular resistance index [baseline: 5,367 (3,589-6,617), 5 minutes:10,197 (9,955-15,005) dynes second/cm/m : = 0.0092], mean pulmonary arterial pressure, and arterial partial pressure of carbon dioxide.
CONCLUSION
The intramuscular administration of MBA in dogs anesthetized with sevoflurane transiently decreased cardiac output due to vasoconstriction. Although spontaneous breathing was maintained, MBA administration resulted in respiratory acidosis due to hypoventilation. Thus, it is important to administer MBA with caution to dogs with insufficient cardiovascular function. In addition, ventilatory support is recommended.
Topics: Animals; Sevoflurane; Butorphanol; Medetomidine; Dogs; Pregnanediones; Male; Female; Injections, Intramuscular; Anesthetics, Inhalation; Heart Rate; Blood Pressure
PubMed: 38938419
DOI: 10.5455/OVJ.2024.v14.i5.20 -
Frontiers in Medicine 2024Current estimates indicate that up to 50-75% of dementia cases are undiagnosed at an early stage when treatments are most effective. Conducting robust accurate cognitive...
INTRODUCTION
Current estimates indicate that up to 50-75% of dementia cases are undiagnosed at an early stage when treatments are most effective. Conducting robust accurate cognitive assessments can be time-consuming for providers and difficult to incorporate into a time-limited Primary Care Provider (PCP) visit. We wanted to compare PCP visits with and without using the self-administered SAGE to determine differences in identification rates of new cognitive disorders.
METHODS
Three hundred patients aged 65-89 without diagnosed cognitive disorders completing a non-acute office visit were enrolled (ClinicalTrials.gov identifier: NCT04063371). Two PCP offices conducted routine visits for 100 consecutive eligible patients each. One office used the SAGE in an additional 100 subjects and asked available informants about cognitive changes over the previous year. Chart reviews were conducted 60 days later. One-way analysis of variance and Fisher exact tests were used to compare the groups and outcomes.
RESULTS
When SAGE was utilized, the PCP documented the detection of new cognitive conditions/concerns six times (9% versus 1.5%) as often ( = 0.003). The detection rate was nearly 4-fold for those with cognitively impaired SAGE scores ( = 0.034). Patients having impaired SAGE score and informant concerns were 15-fold as likely to have new cognitive conditions/concerns documented ( = 0.0007). Among providers using SAGE, 86% would recommend SAGE to colleagues.
DISCUSSION
SAGE was easily incorporated into PCP visits and significantly increased identification of new cognitive conditions/concerns leading to new diagnoses, treatment, or management changes. The detection rate increased 15-fold for those with impaired SAGE scores combined with informant reports.
PubMed: 38938387
DOI: 10.3389/fmed.2024.1353104 -
JACC. Advances Oct 2023In recent decades, adults living with congenital heart disease (ACHD) have improved their survival, thus increasing their predisposition to the onset of cardiometabolic...
BACKGROUND
In recent decades, adults living with congenital heart disease (ACHD) have improved their survival, thus increasing their predisposition to the onset of cardiometabolic risk factors and chronic health conditions.
OBJECTIVES
The purpose of this study was to describe cardiometabolic risk profiles in the ACHD population and their relationship to congenital heart disease (CHD) lesion complexity.
METHODS
We performed a cross-sectional study from ACHD in a third-tier referral center in Mexico City. The association between cardiometabolic risk factors and CHD complexity was estimated using logistic regression models.
RESULTS
Our study cohort included 1,171 ACHD patients (median age: 31 [IQR: 23.2-42.7] years, male 63.6%). Cardiac diagnosis was classified as mild (44.9%), moderate (37.8%), and severe (17.2%) CHD complexity. Low high-density lipoprotein cholesterol (55%) was the most common cardiometabolic risk factor; followed by insulin resistance (54.5%) and prediabetes (52.4%). Patients with mild and moderate CHD had a higher prevalence of obesity and metabolic syndrome, while patients with severe CHD had a higher prevalence of hyperuricemia and subclinical hypothyroidism. In the logistic regression analysis, the severity of CHD was associated with higher odds of hyperuricemia (moderate CHD, OR: 1.87; 95% CI: 1.20-2.93; = 0.010; severe CHD, OR: 2.75; 95% CI: 1.64-4.62; < 0.001) and lower risks of metabolic syndrome (OR: 0.61; 95% CI: 0.41-0.91; = 0.010), prediabetes (OR: 0.58; 95% CI: 0.42-0.81; < 0.001), and arterial hypertension (OR: 0.49; 95% CI: 0.33-0.74; < 0.001) compared with mild CHD complexity.
CONCLUSIONS
We observed high rates of cardiometabolic risk factors in Mexican ACHD patients and these risk profiles varied by CHD lesion complexity. These results highlight the need for ongoing metabolic health surveillance in the ACHD population.
PubMed: 38938341
DOI: 10.1016/j.jacadv.2023.100596 -
Case Reports in Obstetrics and... 2024Primary extragonadal germ cell tumors (EGCTs) are a very rare clinical encounter most commonly reported in males. Among females, the placenta, pelvis, uterus, brain, and...
INTRODUCTION
Primary extragonadal germ cell tumors (EGCTs) are a very rare clinical encounter most commonly reported in males. Among females, the placenta, pelvis, uterus, brain, and mediastinum are the most common extragonadal sites and predominantly display nondysgerminoma histology. In this report, we present a case of a primary cervical dysgerminoma in a young female patient. . An 18-year-old nulligravid woman presented with a 12-month history of vaginal bleeding and discharge. Routine blood tests and serum levels of tumor markers were within normal limits. The chest X-ray was normal. A high-resolution pelvic MRI showed a well-defined lobulated cervicovaginal mass measuring 8 × 6 × 5 cm expanding into the vaginal canal with mild homogenous contrast enhancement. An incisional biopsy was performed vaginally under anesthesia, and histologic findings were consistent with dysgerminoma. A repeat follow-up pelvic MRI was done and showed a reduction in the size of the mass by more than 70%. The patient was treated with 4 cycles of bleomycin, etoposide, and cisplatin chemotherapy. Additional external pelvic beam radiation treatment was administered for a partial response. After 3 months of radiotherapy, a contrast abdominopelvic CT scan showed a recurrent cervicovaginal mass with extension to the pelvic sidewalls. The patient was initiated with ifosfamide, paclitaxel, and cisplatin (ITP) as second-line chemotherapy for a recurrent germ cell tumor but later died from hydronephrosis, chronic anemia, and sepsis.
CONCLUSION
The uterine cervix is a very unusual site for primary dysgerminoma and can have a very aggressive clinical course. A high index of suspicion and an exhaustive workup are necessary to reach a diagnosis, particularly in a young patient presenting with a cervical lesion.
PubMed: 38938322
DOI: 10.1155/2024/6465387 -
Journal of Preventive Medicine and... Jun 2024This study was conducted to measure financial toxicity (FT) among patients with cancer in Vietnam using the COmprehensive Score for financial Toxicity (COST) and to...
OBJECTIVES
This study was conducted to measure financial toxicity (FT) among patients with cancer in Vietnam using the COmprehensive Score for financial Toxicity (COST) and to describe the cost management strategies employed by these patients.
METHODS
This comprehensive cross-sectional study enrolled 634 patients from 2 specialized oncology hospitals in Vietnam. Using COST cutoff scores, FT was classified as none/mild (≥26), moderate (14-25), or severe (≤13). Cost management strategies, or coping mechanisms, were classified into 4 groups: lifestyle changes, financial resource strategies, treatment modifications, and support seeking.
RESULTS
The prevalence of FT was 91.8%, with 51.7% of participants demonstrating severe and 40.1% exhibiting moderate FT. Severe FT was significantly associated with female sex, low education level, unstable employment, low household economic status, and advanced cancer stage. The most common coping strategies were as follows: among lifestyle changes, reducing spending on basic items and leisure activities (78.7%) and cutting back on essential household expenses (66.4%); among financial resource strategies, borrowing money from relatives or friends (49.1%) and withdrawing funds from retirement or savings accounts (32.1%); within treatment modifications, switching treatment facilities or doctors due to cost concerns (9.3%); and within support seeking, obtaining help from welfare or community organizations (18.8%). All strategies were significantly more likely to be used by patients with severe FT.
CONCLUSIONS
FT was highly prevalent among patients with cancer. Most patients relied on lifestyle adjustments and coping strategies, underscoring the need for improved financial support systems to alleviate the economic burden associated with cancer care.
PubMed: 38938045
DOI: 10.3961/jpmph.24.090 -
Aging Cell Jun 2024Elevated plasma total homocysteine (tHcy) is associated with the development of Alzheimer's disease and other forms of dementia. In this study, we report the...
Elevated plasma total homocysteine (tHcy) is associated with the development of Alzheimer's disease and other forms of dementia. In this study, we report the relationship between tHcy and epigenetic age in older adults with mild cognitive impairment from the VITACOG study. Epigenetic age and rate of aging (ROA) were assessed using various epigenetic clocks, including those developed by Horvath and Hannum, DNAmPhenoAge, and with a focus on Index, a new principal component-based epigenetic clock that, like DNAmPhenoAge, is trained to predict an individual's "PhenoAge." We identified significant associations between tHcy levels and ROA, suggesting that hyperhomocysteinemic individuals were aging at a faster rate. Moreover, Index revealed a normalization of accelerated epigenetic aging in these individuals following treatment with tHcy-lowering B-vitamins. Our results indicate that elevated tHcy is a risk factor for accelerated epigenetic aging, and this can be ameliorated with B-vitamins. These findings have broad relevance for the sizable proportion of the worldwide population with elevated tHcy.
PubMed: 38937999
DOI: 10.1111/acel.14255 -
ESC Heart Failure Jun 2024Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there...
AIMS
Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti-inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF).
METHODS AND RESULTS
We present the rationale and design of the ARCHER Trial, an international multicentre, double-blind, randomized, placebo-controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow-up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs-troponin, NT-proBNP, markers of inflammation and endothelial function during the 12-week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper.
CONCLUSIONS
The ongoing ARCHER Trial is an international, multicentre, double-blind, randomized, placebo-controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025.
PubMed: 38937900
DOI: 10.1002/ehf2.14889 -
Porcine Health Management Jun 2024Ear and tail lesions are prevalent indicators of impaired welfare observed in pig production with different multifactorial causes. Understanding the progression of ear...
BACKGROUND
Ear and tail lesions are prevalent indicators of impaired welfare observed in pig production with different multifactorial causes. Understanding the progression of ear and tail lesions over time is important to implement preventative strategies on commercial pig farms. Therefore, this case study aimed to provide a detailed account of patterns of ear and tail lesions in pigs on a single commercial farm during the grower-finisher period.
CASE PRESENTATION
A total of 1,676 12-week old pigs (n = 773 females and n = 903 males, all tail docked) were followed from arrival to the grower facilities until transferred to the finisher stage on a commercial pig farm in Ireland. Pigs were individually weighed and inspected for the severity of fresh ear and tail lesions (score 0-4) on transfer to the first grower (24.9 ± 5.33 kg, 12 weeks of age, n = 1,676 pigs), second grower (33.3 ± 7.04 kg, 14 weeks of age, n = 1,641 pigs), and finisher stage (60.2 ± 7.74 kg, 18 weeks of age, n = 1,626 pigs). Due to the low number of pigs with high scores, ear lesions were classified as no (score 0), mild (score 1), moderate (score 2) and severe (score ≥ 3) and tail lesions were classified as no (score 0), mild (score 1), and moderate-to-severe (score ≥ 2). Ear lesions were more prevalent than tail lesions at each inspection. There were approx. 19% of pigs with ear lesions at all three inspections but no pigs presented with tail lesions at all three inspections. When considering the specific severity categories, we observed 32 different ear lesion score combinations and 15 different tail lesion score combinations across the three inspections.
CONCLUSION
The high number of observed patterns of ear and tail lesions suggest large individual variability in lesion progression. Ear lesions were more of an issue than tail lesions and little is known about this health and welfare problem indicating that further research into causes and management strategies is needed.
PubMed: 38937857
DOI: 10.1186/s40813-024-00374-w -
Alzheimer's Research & Therapy Jun 2024Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer's... (Meta-Analysis)
Meta-Analysis Review
The cognitive effect of non-invasive brain stimulation combined with cognitive training in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.
BACKGROUND
Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, data from clinical trials or meta-analysis involving NIBS combined with CT have shown controversial results. The aim of this systematic review and meta-analysis was to evaluate short-term and long-term effects of NIBS combined with CT on improving global cognition and other specific cognitive domains in patients with AD and MCI.
METHODS
This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases including PubMed, Web of Science, EBSCO, Cochrane Library and Embase were searched up from inception to 20 November 2023. The PEDro scale and the Cochrane's risk of bias assessment were used to evaluate risk of bias and methodological quality of included studies. All statistical analyses were conducted with Review Manager 5.3.
RESULTS
We included 15 studies with 685 patients. The PEDro scale was used to assess methodological quality with a mean score of 7.9. The results of meta-analysis showed that NIBS combined with CT was effective on improving global cognition in AD and MCI (SMD = 0.52, 95% CI (0.18, 0.87), p = 0.003), especially for patients accepting repetitive transcranial magnetic stimulation (rTMS) combined with CT (SMD = 0.46, 95% CI (0.14, 0.78), p = 0.005). AD could achieve global cognition improvement from NIBS combined with CT group (SMD = 0.77, 95% CI (0.19, 1.35), p = 0.01). Transcranial direct current stimulation (tDCS) combined with CT could improve language function in AD and MCI (SMD = 0.29, 95% CI (0.03, 0.55), p = 0.03). At evaluation follow-up, rTMS combined with CT exhibited larger therapeutic responses to AD and MCI in global cognition (SMD = 0.55, 95% CI (0.09, 1.02), p = 0.02). AD could achieve global cognition (SMD = 0.40, 95% CI (0.03, 0.77), p = 0.03) and attention/working memory (SMD = 0.72, 95% CI (0.23, 1.20), p = 0.004) improvement after evaluation follow-up from NIBS combined with CT group.
CONCLUSIONS
Overall, NIBS combined with CT, particularly rTMS combined with CT, has both short-term and follow-up effects on improving global cognition, mainly in patients with AD. tDCS combined with CT has advantages on improving language function in AD and MCI. Future more studies need evaluate cognitive effects of NIBS combined with CT on other specific cognitive domain in patients with cognitive deterioration.
Topics: Humans; Cognitive Dysfunction; Alzheimer Disease; Transcranial Magnetic Stimulation; Transcranial Direct Current Stimulation; Cognitive Behavioral Therapy; Cognition; Combined Modality Therapy; Cognitive Training
PubMed: 38937842
DOI: 10.1186/s13195-024-01505-9