Objective: To assess whether informant-reported apneas during sleep (witnessed apneas) in cognitively unimpaired (CU) elderly persons are associated with higher levels of brain tau. Methods: From the population-based Mayo Clinic Study of Aging, we identified 292 CU elderly aged >=65 years with both AV-1451 tau-PET and PiB-PET scans and whose bed partners and close relatives had completed a questionnaire that assessed whether participants had witnessed apneas during sleep. For this cross-sectional analysis, we selected the...

Objective: To develop evidence-informed, expert consensus research diagnostic criteria for Traumatic Encephalopathy Syndrome (TES), the clinical disorder associated with neuropathologically diagnosed Chronic Traumatic Encephalopathy (CTE). Methods: A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First NINDS Consensus Workshop to Define the Diagnostic Criteria for TES, April, 2019. Prior to consensus, panelists...

Objective: To identify novel genes involved in the etiology of intracranial aneurysms (IA) and / or subarachnoid hemorrhages (SAH) using whole exome sequencing. Methods. In the present study we performed whole exome sequencing in thirteen individuals from three families with an autosomal dominant IA/SAH inheritance pattern to look for candidate genes for disease. Additionally, we sequenced PCNT exon 38 in 161 sporadic IA/SAH patients in order to find additional carriers of potential pathogenic variants. Results....

Additional file 1: Supplementary Fig. 1. Systemic administration of the same dose of U-69,593 used in the rat study did not increase water consumption and urination in female mice. Mice were individually placed in metabolic chambers and received a single subcutaneous administration of U-69,593 at 0.56 mg/kg or vehicle-control. (A) Water consumption and (B) volume of urine, as outcome measurements of thirst and polyuria, respectively, were evaluated 120 minutes after treatment. Data are presented as...

Additional file 2: Supplementary Fig. 2. Representative images demonstrating the expression of Gi-DREADD-mCherry (red) in the ARC of female (A) and male (B) KORCRE heterozygous mice 4 weeks after stereotaxic administration of AAV8-hSyn-DIO-hM4D(Gi)-mCherry virus (100 nL) in the right ARC. Scale bars, 100 μm.

Abstract Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with...

Additional file 1: Figure S1. F-statistics of IV SNPs used in MR Analysis. Figure S2. A SNP effect on neutrophil count and CRS. Two-sample MR analyses performed using GWAS summary statistics for neutrophil count (exposure trait) and CRS (outcome trait). Primary analysis was performed using inverse-variance weighted two-sample MR. B SNP effect on lymphocyte count and CRS. Two-sample MR analyses performed using GWAS summary statistics for lymphocyte count (exposure trait) and CRS (outcome trait). Primary...

Intrapleural pressure during a forced vital capacity (VC) manoeuvre is often in excess of that required to generate maximal expiratory airflow. This excess pressure compresses alveolar gas (i.e., thoracic gas compression; TGC), resulting in underestimated forced expiratory flows (FEFs) at a given lung volume. It is unknown if TGC is influenced by sex; however, because men have larger lungs and stronger respiratory muscles, we hypothesized that men would have greater TGC. We examined TGC across...

Objective Localization of seizure onset zone in focal epilepsy patients is a crucial step prior to surgical planning. Noninvasively achieving this goal would have a tremendous impact on clinical management of intractable seizure. Methods In a total of 39 focal epilepsy patients, we recorded and extracted 138 seizures and 1,325 interictal epileptic discharges using high-density EEG. We have investigated a novel approach for directly imaging sources of seizures and interictal spikes from high density EEG...

Objective: We investigated different dimensions of subjective cognitive decline (SCD) to determine which was the best prognostic risk factor for incident mild cognitive impairment (MCI) among cognitively unimpaired (CU) participants. Methods: We included 1167 CU participants, aged 70-95 years from the Mayo Clinic Study of Aging based on 2 concurrent SCD scales (part of the Blessed memory test and the 39-item ECog, which included a validated 12-item derivative) and a single question assessing worry about...

Additional file 2: Supplementary Fig. 2. Representative images demonstrating the expression of Gi-DREADD-mCherry (red) in the ARC of female (A) and male (B) KORCRE heterozygous mice 4 weeks after stereotaxic administration of AAV8-hSyn-DIO-hM4D(Gi)-mCherry virus (100 nL) in the right ARC. Scale bars, 100 μm.

Abstract Background The migraine premonitory phase is characterized in part by increased thirst, urination and yawning. Imaging studies show that the hypothalamus is activated in the premonitory phase. Stress is a well know migraine initiation factor which was demonstrated to engage dynorphin/kappa opioid receptors (KOR) signaling in several brain regions, including the hypothalamus. This study proposes the exploration of the possible link between hypothalamic KOR and migraine premonitory symptoms in rodent models. Methods Rats were...

Additional file 1: Table S1. Search strategy. Table S2. Strategies followed to reduce the risk of bias. Table S3. List of fields covered for the collection of the data (data extraction template). Table S4. Reasons for excluding candidate records (inclusion stage in the study-selection flow). Table S5. Frequency of the hippocampal-sparing AD subtype – comparison of findings when using hippocampus versus entorhinal cortex for subtyping.

Additional file 1: Table S1. Search strategy. Table S2. Strategies followed to reduce the risk of bias. Table S3. List of fields covered for the collection of the data (data extraction template). Table S4. Reasons for excluding candidate records (inclusion stage in the study-selection flow). Table S5. Frequency of the hippocampal-sparing AD subtype – comparison of findings when using hippocampus versus entorhinal cortex for subtyping.

Objective: To assess US physicians’ attitudes towards using shared decision-making (SDM) to achieve cost containment. Design: Cross-sectional mailed survey. Setting: US medical practice. Participants: 3897 physicians were randomly selected from the AMA Physician Masterfile. Of these, 2556 completed the survey. Main outcome measures: Level of enthusiasm for “Promoting better conversations with patients as a means of lowering healthcare costs”; degree of agreement with “Decision support tools that show costs would be helpful in my practice”...

Objective: Research in animals has shown that chronic stress exacerbates tau pathology. In humans, psychological stress has been associated with higher risk of Alzheimer’s disease (AD) clinical syndrome. The objective of this cross-sectional study was to assess the hypothesis that stress coping ability (assessed via the “Brief Resilience Scale” [BRS]) is associated with tau burden and to evaluate whether these associations differed by sex and amyloid status (A+/A-) in cognitively unimpaired older adults (CU). Methods:...

The “number sense” describes the intuitive ability to quantify without counting. Single neuron recordings in non-human primates and functional imaging in humans suggest the intraparietal sulcus is an important neuroanatomical locus of numerical estimation. Other lines of inquiry implicate the IPS in numerous other functions, including attention and decision making. Here we provide a direct test of whether IPS has functional specificity for numerosity judgments. We used muscimol to reversibly and independently inactivate the ventral...

The highly polymorphic human leukocyte antigen (HLA) class I molecules present peptide antigens to CD8+ T cells, inducing immunity against infections and cancers. Quality control mediated by peptide loading complex (PLC) components is expected to ensure the cell surface expression of stable peptide-HLA class I complexes. This is exemplified by HLA-B*08:01 in primary human lymphocytes, with both expression level and half-life at the high end of the measured HLA-B expression and stability hierarchies. Conversely, low...

Objective: To review the role of the acute hypertensive response in patients with intracerebral hemorrhage, current treatment options and areas for further research. Methods: Systematic review of the literature to assess 1) Frequency of acute hypertensive response in intracerebral hemorrhage 2) Consequences of acute hypertensive response in clinical outcomes 3) Acute hypertensive response and secondary brain injury: hematoma expansion and perihematomal edema 4) Vascular autoregulation, safety data side effects of acute antihypertensive treatment, and 5)...

Objective: To revise the 1999 Airlie House consensus guidelines for the design and implementation of preclinical therapeutic studies and clinical trials in amyotrophic lateral sclerosis (ALS). Methods: A consensus committee comprising 140 key members of the international ALS community (ALS researchers, clinicians, patient representatives, research funding representatives, industry and regulatory agencies) addressed nine areas of need within ALS research: 1. Pre-clinical studies; 2. Biological and phenotypic heterogeneity; 3. Outcome measures; 4. Disease-modifying and symptomatic interventions;...

Objective: To evaluate the association of cognitive declines in the domains of memory, language, and executive function with brain gray matter (GM) volume in old age. Methods: Prospective study of 1,846 participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent 3T brain MRI scans in 2011-2013. Participants were categorized by cognitive domain performance trajectory over the prior 20 years (cut-point to define decline: 20th percentile). Associations between GM volume and cognitive declines were...

Pre-emptive recognition of the ethical implications of study design and algorithm choices in artificial intelligence (AI) research is an important but challenging process. AI applications have begun to transition from a promising future to clinical reality in neurology. As the clinical management of neurology is often concerned with discrete, often unpredictable, and highly consequential events linked to multimodal data streams over long timescales, forthcoming advances in AI have great potential to transform care for patients....

Senescent cells have detrimental effects across tissues with aging but may have beneficial effects on tissue repair, specifically on skin wound healing. However, the potential role of senescent cells in fracture healing has not been defined. Here, we performed an in silico analysis of public mRNAseq data and found that senescence and senescence-associated secretory phenotype (SASP) markers increased during fracture healing. We next directly established that the expression of senescence biomarkers increased markedly during murine...

Abstract Neuropathology and neuroimaging studies have identified several subtypes of Alzheimer’s disease (AD): hippocampal sparing AD, typical AD, and limbic predominant AD. An unresolved question is whether hippocampal sparing AD cases can present with neurofibrillary tangles (NFT) in association cortices while completely sparing the hippocampus. To address that question, we conducted a systematic review and performed original analyses on tau positron emission tomography (PET) data. We searched EMBASE, PubMed, and Web of Science databases until...

Article full text The Role of Microbiome-Based Therapeutics in Clostridioides difficile Infection: Durable, Long-Term Results of RBX2660 | SpringerLink
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