Haaningmckay5594
rapies reach clinical applications, this information is critical to aid in the interpretation of the efficacy of new treatments.
To our knowledge, no study has investigated the effect of exposure to formaldehyde on cognition in the general population. Our objective was to examine the association between occupational exposure to formaldehyde and cognitive impairment in middle-aged and young-old adults (≥45 years).
In the French CONSTANCES cohort, cognitive function was assessed with a standardized battery of 7 cognitive tests to evaluate global cognitive function, episodic verbal memory, language abilities, and executive functions (e.g., Digit Symbol Substitution Test [DSST]). A global cognitive score was created using principal component analysis. Cognitive impairment was assessed in reference to norms of neuropsychological battery according to age, sex, and education. Lifetime exposure to formaldehyde was assessed using a French Job Exposure Matrix created in the framework of the Matgéné project. After performing multiple imputation, separate modified Poisson regression models were used to evaluate the association between cognitivghly exposed individuals (for DSST high past exposure aRR 1.23; 95% CI 1.11-1.36; high recent exposure aRR 1.24; 95% CI 1.13-1.35).
Our findings highlight the long-term detrimental effect of formaldehyde exposure on cognitive health in a relatively young population.
Our findings highlight the long-term detrimental effect of formaldehyde exposure on cognitive health in a relatively young population.
Experimental studies suggest that the balance between short and long β-amyloid (Aβ) species might modulate the toxic effects of Aβ in Alzheimer disease (AD), but clinical evidence is lacking. We studied whether Aβ
levels in CSF relate to risk of AD dementia and cognitive decline.
CSF Aβ
levels were measured in 656 individuals across 2 clinical cohorts the Swedish BioFINDER study and the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cox regression models were used to evaluate the association between baseline Aβ
levels and risk of AD dementia in AD biomarker-positive individuals (AD+; determined by CSF phosphorylated tau [P-tau]/Aβ
ratio) with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Linear mixed-effects models were used to evaluate the association between baseline Aβ
levels and cognitive decline as measured by the Mini-Mental State Examination (MMSE) in AD+ participants with SCD, MCI, or AD dementia.
In the BioFINDER cohort, high Aβ
levels were associated with slower decline in MMSE score (β = 0.30 points per SD,
= 0.001) and with lower risk of conversion to AD dementia (hazard ratio 0.83 per SD,
= 0.03). In the ADNI cohort, higher Aβ
levels were associated with less decline in MMSE score (β = 0.27,
= 0.01) but not risk of conversion to AD dementia (
= 0.66). Aβ
levels in both cohorts were significantly associated with both cognitive and clinical outcomes when further adjusted for CSF P-tau or CSF Aβ
levels.
Higher CSF Aβ
levels are associated with lower risk of AD-related changes in 2 independent clinical cohorts. These findings suggest that γ-secretase modulators could be effective as disease-altering therapy.
ClinicalTrials.gov Identifier NCT03174938.
ClinicalTrials.gov Identifier NCT03174938.
To study the relationship between the presence of cerebral microbleeds (CMBs) and acute hematoma characteristics among patients with primary intracerebral hemorrhage (ICH).
We pooled individual patient data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-2) trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation phase 3 trial (MISTIE III). We included subjects with a brain magnetic resonance imaging (MRI) scan. Exposure was the presence of a CMB. The co-primary outcomes were admission ICH volume and hematoma expansion. Mixed-effects linear and logistic regression models were used, with demographics and comorbidities considered fixed effects, and the study cohort treated as a random effect. Additional analyses assessed the relationship between CMB topography and number, and hematoma characteristics.
Of the 1,499 ICH patients enrolled in the parent trials, 466 (31.1%) were included in this analysis, and 231 (49.6%) patients had CMBs. In adjussentation and a lower rate of hematoma expansion on follow-up imaging.
Alzheimer's dementia is a complex clinical syndrome that can be defined broadly as an amnestic multidomain dementia. We previously reported human cortical proteins that are implicated in Alzheimer's dementia. To understand the pathologic correlates of these proteins for underlying disease mechanisms, we investigated cortical protein associations with common age-related neuropathologies.
Participants were community-dwelling older adults from two cohort studies of aging and dementia. All underwent detailed annual clinical evaluations, and brain autopsies were performed after death. We refer Alzheimer's disease (AD) to pathologically defined disease, and refer Alzheimer's dementia to the clinical syndrome. Indices for AD, cortical Lewy bodies, limbic predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC), hippocampal sclerosis, macroscopic infarcts, microinfarcts, cerebral amyloid angiopathy, atherosclerosis and arteriolosclerosis were quantified during uniform structured neuropatholotein was not associated with any of the neuropathologic indices investigated.
Cortical proteins implicated in Alzheimer's dementia do not necessarily work through AD pathogenesis; rather, non-AD neurodegenerative and vascular diseases, as well as other pathways are at play. Further, some proteins are pleiotrophic and associated with both neurodegenerative and cerebrovascular pathologies.
Cortical proteins implicated in Alzheimer's dementia do not necessarily work through AD pathogenesis; rather, non-AD neurodegenerative and vascular diseases, as well as other pathways are at play. Further, some proteins are pleiotrophic and associated with both neurodegenerative and cerebrovascular pathologies.An immunocompetent 47-year-old man presented with a five-month history of progressive lower limb weakness, back pain, sphincter dysfunction, and intermittent fever, suggesting myelopathy in a chronic deteriorating course. A comprehensive analysis comprising of blood tests, neuroimaging, CSF profiling, molecular analysis, and histopathology was performed. Notably, enhanced spinal cord MRI revealed longitudinally extensive intradural-extramedullary lesions involving the cervical, thoracic, and lumbosacral spinal cord, with homogeneous enhancement and spinal cord compression. Serum TPHA and RPR tests were positive. CSF profiling showed pleocytosis, significant protein elevations, hypoglycorrhachia, and positive TPHA test. 18F-FDG-PET/CT indicated slightly increased intraspinal FDG uptake. Spinal cord biopsy further showed small round blue cells in poorly differentiated tissues. Immunostaining was positive for NKX2.2, CD56, CD99, Synaptophysin, and Ki67 (50%). Molecular analysis detected a novel MALAT-CYSLTR1 fusion protein and variants in oncogenic genes including PTCH1, TERT, CREBBP, SPEN, and STK11 The diagnosis of intraspinal extraosseous Ewing's sarcoma (ES) was confirmed. Briefly, our case details the diagnosis of a patient with intradural-extramedullary ES and highlights the value of spinal cord biopsy in progressive myelopathy of unknown causes.Coronavirus RNA-dependent RNA polymerases produce subgenomic RNAs (sgRNAs) that encode viral structural and accessory proteins. User-friendly bioinformatic tools to detect and quantify sgRNA production are urgently needed to study the growing number of next-generation sequencing (NGS) data of SARS-CoV-2. We introduced sgDI-tector to identify and quantify sgRNA in SARS-CoV-2 NGS data. sgDI-tector allowed detection of sgRNA without initial knowledge of the transcription-regulatory sequences. We produced NGS data and successfully detected the nested set of sgRNAs with the ranking M > ORF3a > N>ORF6 > ORF7a > ORF8 > S > E>ORF7b. We also compared the level of sgRNA production with other types of viral RNA products such as defective interfering viral genomes.Aspergillus fumigatus is a ubiquitous mold associated with the development of pulmonary diseases that include invasive pulmonary aspergillosis (IPA), an often fatal opportunistic infection. FIBCD1 is a transmembrane endocytic membrane receptor widely expressed on human epithelium. Although FIBCD1 was previously shown to bind chitin, modulate fungal colonization of the gut, and inhibit intestinal inflammation, the role of FIBCD1 in the context of lung fungal infection remains unknown. In this study, we observed that mortality, fungal burden, and tissue histopathology were decreased in the absence of FIBCD1 in murine IPA. Quantitative RT-PCR analyses demonstrated decreased inflammatory cytokines in the lungs of neutrophil-depleted FIBCD1-/- mice with IPA, when compared with wild-type controls. In contrast, inflammatory cytokines were increased in immune-competent FIBCD1-/- mice after fungal aspiration, suggesting that the presence of neutrophils is associated with cytokine modulation. In contrast to the clear IPA phenotype, FIBCD1-/- mice with systemic infection or bleomycin-induced lung injury exhibited similar morbidity and mortality when compared with their wild-type counterparts. Thus, our study identifies a detrimental role of FIBCD1 in IPA.
Antibody response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is impaired in kidney transplant recipients. Emerging variants, such as B.1.617.2 (
), are of particular concern because of their higher transmissibility and partial immune escape. Little is known about protection against these variants in immunocompromised patients.
In this prospective two-center study, antispike 1 IgG and surrogate neutralizing antibodies were measured in 173 kidney transplant recipients and 166 healthy controls with different vaccination schedules. In addition, different SARS-CoV-2 epitope antibodies from 135 vaccinated kidney transplant recipients were compared with antibodies in 25 matched healthy controls after second vaccination. Selleckchem GSK3 inhibitor In 36 kidney transplant recipients with seroconversion, neutralization against B.1.1.7 (
), B.1.351 (
), and B.1.617.2 (
) was determined on VeroE6 cells and compared with neutralization in 25 healthy controls.
Kidney transplant recipients had significantSeroconverted kidney transplant recipients show impaired neutralization against emerging variants of concern after standard two-dose vaccination.
Observational study to assess the SARS-CoV-2 specific immune response in kidney transplant recipients (COVID-19 related immune response), DRKS00024668.
Observational study to assess the SARS-CoV-2 specific immune response in kidney transplant recipients (COVID-19 related immune response), DRKS00024668.The arcuate nucleus (ArcN) is an integrative hub for the regulation of energy balance, reproduction, and arterial pressure (AP), all of which are influenced by Angiotensin II (AngII); however, the cellular mechanisms and downstream neurocircuitry are unclear. Here, we show that ArcN AngII increases AP in female rats via two phases, both of which are mediated via activation of AngII type 1 receptors (AT1aRs) initial vasopressin-induced vasoconstriction, followed by slowly developing increases in sympathetic nerve activity (SNA) and heart rate (HR). In male rats, ArcN AngII evoked a similarly slow increase in SNA, but the initial pressor response was variable. In females, the effects of ArcN AngII varied during the estrous cycle, with significant increases in SNA, HR, and AP occurring during diestrus and estrus, but only increased AP during proestrus. Pregnancy markedly increased the expression of AT1aR in the ArcN with parallel substantial AngII-induced increases in SNA and MAP. In both sexes, the sympathoexcitation relied on suppression of tonic ArcN sympathoinhibitory neuropeptide Y (NPY) inputs, and activation of proopiomelanocortin (POMC) projections, to the paraventricular nucleus (PVN).
