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To evaluate the impact of receptive vocabulary versus years of education on neuropsychological performance of Black and White older adults. A community-based prospectively enrolled cohort ( = 1,007; 130 Black, 877 White) in the Emory Healthy Brain Study were administered the NIH Toolbox Picture Vocabulary Test and neuropsychological measures. Group differences were evaluated with age, sex, and education or age, sex, and Toolbox Vocabulary scores as covariates to determine whether performance differences between Black versus White participants were attenuated or eliminated. With vocabulary as a covariate, the main effect of race was no longer significant for the MoCA, Phonemic Fluency, Rey Auditory Verbal Learning Test, and Rey Complex Figure Test immediate and delayed recall. Although still significantly different between groups, the effect sizes for Animal Fluency, Trails B-A, Symbol Digit Modalities Test, and Rey Copy were attenuated, with the greatest reductions occurring for the Multilingual Naming Test and Judgment of Line Orientation. Findings support the value of using receptive vocabulary as a proxy for premorbid ability level when comparing the cognitive performance of Black and White older adults. The results extend investigations using measures of single word reading to encompass measures assessing word meaning.

Background Recent reports have demonstrated that among patients with subarachnoid hemorrhage (SAH) treated with hypertonic NaCl, resultant hyperchloremia has been associated with the development of acute kidney injury (AKI). We report a trial comparing the effect of two hypertonic solutions with different chloride contents on the resultant serum chloride concentrations in SAH patients, with a primary outcome aimed at limiting chloride elevation. Methods A low ChloridE hyperTonic solution for brain Edema (ACETatE) trial is a single-center, double-blinded, double-dummy, randomized pilot trial comparing bolus infusions of 23.4% NaCl and 16.4% NaCl/Na-acetate for the treatment of cerebral edema in patients with SAH. Randomization occurred when patients developed hyperchloremia (serum Cl − ≥ 109 mmol/L) and required hyperosmolar treatment. Results We enrolled 59 patients, of which 32 developed hyperchloremia and required hyperosmolar treatment. 15 patients were randomized to the 23.4% NaCl group, and 17 patients were randomized to the 16.4% NaCl/Na-acetate group. Although serum chloride levels increased similarly in both groups, the NaCl/Acetate group showed a significantly lower Cl − load at the end of the study period (978mEq vs. 2,464mEq, p < 0.01). Secondary outcome analysis revealed a reduced rate of AKI in the Na-acetate group (53.3% in the NaCl group vs. 11.8% in the Na-acetate group, p = 0.01). Both solutions had similar effects on ICP reduction, but NaCl/Acetate treatment had a more prominent effect on immediate post-infusion Na + concentrations (increase of 2.2 ± 2.8 vs. 1.4 ± 2.6, ( p < 0.01)). Proximal tubule renal biomarkers differed in concentration between the two groups. Conclusions Our pilot trial showed the feasibility and safety of replacing 23.4% NaCl infusions with 16.4% NaCl/Na-acetate infusions to treat cerebral edema in patients with SAH. The degree of hyperchloremia was similar in the two groups. 16.4% NaCl/Na-acetate infusions led to lower Cl − load and AKI rates than 23.4% NaCl infusions. Further multi-center studies are needed to corroborate these results. Trial registration clinicaltrials.gov # NCT03204955 , registered on 6/28/2017

Deposition of insoluble protein aggregates is a hallmark of neurodegenerative diseases. The universal presence of β-amyloid and tau in Alzheimer’s disease (AD) has facilitated advancement of the amyloid cascade and tau hypotheses that have dominated AD pathogenesis research and therapeutic development. However, the underlying etiology of the disease remains to be fully elucidated. Here we report a comprehensive study of the human brain-insoluble proteome in AD by mass spectrometry. We identify 4,216 proteins, among which 36 proteins accumulate in the disease, including U1-70K and other U1 small nuclear ribonucleoprotein (U1 snRNP) spliceosome components. Similar accumulations in mild cognitive impairment cases indicate that spliceosome changes occur in early stages of AD. Multiple U1 snRNP subunits form cytoplasmic tangle-like structures in AD but not in other examined neurodegenerative disorders, including Parkinson disease and frontotemporal lobar degeneration. Comparison of RNA from AD and control brains reveals dysregulated RNA processing with accumulation of unspliced RNA species in AD, including myc box-dependent-interacting protein 1, clusterin, and presenilin-1 . U1-70K knockdown or antisense oligonucleotide inhibition of U1 snRNP increases the protein level of amyloid precursor protein. Thus, our results demonstrate unique U1 snRNP pathology and implicate abnormal RNA splicing in AD pathogenesis.

The Emory Goizueta Alzheimer's Disease Research Center implemented targeted, community-based programs emphasizing health education and collaboration with community partners. This paper reports on their impact on research enrollment and the lessons learned. We analyzed attendance data from in-person events for new participants in the Uniform Data Set (UDS) cohort. Using regression modeling, we examined relationships among demographics and time to UDS enrollment. From 2016 to 2024, 194 adults enrolled in the UDS. They were mostly women (59%), evenly divided between African American (AA; 54%) and non-Hispanic White (NHW; 46%) individuals, and well-educated (median 16 years). Before consent, more AA participants attended events (82.7% vs. 42.0%; p < 0.0001) and a greater number of events (median 2, interquartile range [IQR]: 1-4 vs. 0, IQR: 0-2; p < 0.0001) than their NHW peers. Among all race-gender groups, the time to enrollment was shortest for AA men. Collaborative, community-based, structured outreach initiatives with focused content can influence research engagement. Despite higher dementia risk, older adults from understudied populations have low enrollment in aging and cognition studies, limiting the generalizability of knowledge about biomarkers and related mechanisms. Besides socioeconomic factors, disproportionate exclusion from screening criteria, less access to expert care, and fewer professional referrals are linked to lower research participation rates. Intentional recruitment activities that incorporate educational content and target community input about health challenges can enhance engagement and promote more representative cohorts, including understudied populations.

Constipation is the most common GI symptom in patients with diabetes mellitus (DM). Importantly, patients with constipation have lower health-related quality of life than those without constipation. Effective therapies for constipation are limited and there is a paucity of data evaluating the treatment of constipation in diabetics. Diabetic patients with chronic idiopathic constipation (CIC) as defined by Rome III criteria were recruited from outpatient clinics at a tertiary-care center and a Veterans Administration Hospital. Demographic data, baseline stool patterns, and a constipation-specific quality of life survey (Patient Assessment of Constipation Quality of Life (PAC-QOL)) were obtained. Baseline colonic transit time (CTT) was evaluated utilizing the wireless motility capsule. Patients were randomized in a double-blind fashion to 48 mcg per day lubiprostone or placebo for 8 weeks. The primary end point measured was the difference in number of spontaneous bowel movements (SBMs) per week vs. baseline for each group at each week after initiation of therapy. Secondary end points included changes in CTT after 4 weeks of therapy, PAC-QOL after 8 weeks of therapy, and changes from baseline in associated gastrointestinal (GI) symptoms as well as need for rescue medication at 2, 4, and 8 weeks. Seventy-six patients (mean age, 56.9±9.1 years, 62% females) were randomized. There were no significant differences between the two groups' baseline data or demographics. During the 8-week treatment period, patients in the lubiprostone group experienced an average of 1.83±0.80 (P=0.02) more SBMs per week than those in the placebo group as compared with baseline. The duration of CTT at Week 4 was shorter by an average of 13 h compared with baseline in the lubiprostone group, and was prolonged by an average of 7 h compared with baseline in the placebo group, leading to a treatment effect of 20.3±7.3 h (P=0.006). PAC-QOL improved in both the groups; however, there was no significant difference between the groups. There was no difference in associated GI symptoms and need for rescue medication between the two groups after 8 weeks. There were no serious adverse events reported during the study. This study suggests that lubiprostone is a safe and effective treatment for increasing weekly SBMs and decreasing CTT in patients with DM and CIC.

Background Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition that results from a ruptured cerebral vessel. Cerebral edema and vasospasm are common complications and frequently require treatment with hypertonic solutions, in particular hypertonic sodium chloride (NaCl). We have previously shown that hyperchloremia in patients with aSAH given hypertonic NaCl is associated with the development of acute kidney injury (AKI), which leads to higher morbidity and mortality. Our current trial aims to study the effect of two hypertonic solutions with different chloride content on serum chloride concentrations in patients with aSAH who are at risk for AKI. Methods A low ChloridE hyperTonic solution for brain Edema (ACETatE) is a single center, double-blinded, double-dummy pilot trial comparing bolus doses of 23.4% NaCl and 16.4% NaCl/Na-Acetate for the treatment of cerebral edema in patients with aSAH. All patients will be enrolled within 36 h following admission. Randomization will occur once patients who receive hypertonic treatment for cerebral edema develop hyperchloremia (serum Cl − concentration ≥ 109 mmol/L). Subsequent treatment will consist of either NaCl 23.4% or NaCl/Na-Acetate 16.4%. The primary outcome of this study will be the change in serum Cl − concentrations during treatment. Secondary outcomes will include incidence of AKI, mortality, changes in intracranial pressure, and extent of hypernatremia. Discussion In patients with aSAH, hyperchloremia is a known risk factor for subsequent development of AKI. The primary goal of this pilot study is to determine the effect of two hypertonic solutions with different Cl − content on serum Cl − concentrations in patients with aSAH who have already developed hyperchloremia. Data will be collected prospectively to determine the extent to which the choice of hypertonic saline solution affects subsequent serum Cl − concentrations and the occurrence of AKI. This approach will allow us to obtain preliminary data to design a large randomized trial assessing the effects of chloride-sparing hypertonic solutions on development of AKI in patients with SAH. This pilot study is the first to prospectively evaluate the relationship between hypertonic solution chloride content and its effect on serum electrolytes and renal function in aSAH patients at risk of AKI due to hyperchloremia. Trial registration Clinicaltrials.gov, NCT03204955 . Registered on 28 June 2017.

To empirically expand the existing subtypes of mild cognitive impairment (MCI) by incorporating information on neuropsychiatric and functional features, and to assess whether cerebrovascular disease (CVD) risk factors are associated with any of these subgroups. Latent class analysis using 1,655 patients with MCI. Participants in the Uniform Data Set (UDS) from 29 National Institutes of Health–supported Alzheimer's Disease Centers. Patients with a consensus diagnosis of MCI from each center and with a Mini-Mental State Examination score of 22 or greater. UDS cognitive battery, Neuropsychiatric Inventory Questionnaire, and Functional Assessment Questionnaire administered at initial visit. Seven empirically based subgroups of MCI were identified: 1) minimally impaired (relative frequency, 12%); 2) amnestic only (16%); 3) amnestic with functional and neuropsychiatric features (16%); 4) amnestic multidomain (12%); 5) amnestic multidomain with functional and neuropsychiatric features (12%); 6) functional and neuropsychiatric features (15%); and 7) executive function and language impairments (18%). Two of these subgroups with functional and neuropsychiatric features were at least 3.8 times more likely than the minimally impaired subgroup to have a Rosen-Hachinski score of 4 or greater, an indicator of probable CVD. Findings suggest that there are several distinct phenotypes of MCI characterized by prominent cognitive features, prominent functional features, and neuropsychiatric features or a combination of all three. Subgroups with functional and neuropsychiatric features are significantly more likely to have CVD, which suggests that there may be distinct differences in disease etiology from the other phenotypes.

Rights and permissions Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Exploring the potential of the platelet membrane proteome as a source of peripheral biomarkers for Alzheimer’s disease [RAW_REF_TEXT] Laura E. Donovan1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Eric B. Dammer2, [/RAW_REF_TEXT] [RAW_REF_TEXT] Duc M. Duong3, [/RAW_REF_TEXT] [RAW_REF_TEXT] John J. Hanfelt4, [/RAW_REF_TEXT] [RAW_REF_TEXT] Allan I. Levey1, [/RAW_REF_TEXT] [RAW_REF_TEXT] Nicholas T. Seyfried 1,3 & [/RAW_REF_TEXT] [RAW_REF_TEXT] James J. Lah 1 [/RAW_REF_TEXT] Alzheimer's Research & Therapy volume 13, Article number: 102 (2021) Cite this article [RAW_REF_TEXT] 1 Altmetric [/RAW_REF_TEXT] [RAW_REF_TEXT] Metrics details [/RAW_REF_TEXT] The Original Article was published on 13 June 2013 Correction to: Table 1 Participants Full size table Table 2 DAVID analysis of changes in proteins associated with platelet-specific secretion Full size table Table 3 Overlap of AD platelet membrane protein changes with previously proposed mechanistic and diagnostic biomarkers Full size table Correction Open Access Published:18 May 2021 [/RAW_REF_TEXT] Correction to:

Oromandibular dystonia (OMD) causes involuntary movements of masticatory and lingual muscles impairing eating, speaking, and swallowing. Treatment options are limited. The objective of this study was to determine the safety and efficacy of abobotulinumtoxinA (aboBoNTA) in OMD. A dose-finding study (phase 1) followed by a single session, prospective, single-blind trial (phase 2) was carried out. OMD subjects were evaluated at baseline, 6 and 12 weeks. Muscles injected were tailored to individual symptoms using EMG guidance, but the aboBoNTA dose for each muscle was pre-specified based on phase 1 results. Evaluations were Global Dystonia Rating Scale (GDS), Unified Dystonia Rating Scale (UDRS), Clinical Global Impression (CGI) improvement and severity, and quality of life (OMDQ-25). Adverse events were monitored. The lowest dosage in phase 1 resulted in adverse effects in two of three patients and thus was used in phase 2. In phase 2, adverse effects were observed in 50% of subjects including dysphagia, voice change, and soft palate weakness. Most were mild. Significant improvement was seen in quality of life (OMDQ-25), speech (BFMq21), and change in GDS, UDRS, CGI severity assessed by the unblinded investigator, but not in blinded video ratings. We conclude that aboBoNTA therapy in this study was associated with improved quality of life and was generally well tolerated in OMD, but occurrence of dysphagia dictated the importance of using low genioglossus dosing. Face to face assessment appears to be more sensitive than video assessment for change in OMD severity. Consideration of the disability in OMD places constraints on traditional placebo-control trial design. Development of novel trial designs is warranted.

When the data are sparse but not exceedingly so, we face a trade-off between bias and precision that makes the usual choice between conducting either a fully unconditional inference or a fully conditional inference unduly restrictive. We propose a method to relax the conditional inference that relies upon commonly available computer outputs. In the rectangular array asymptotic setting, the relaxed conditional maximum likelihood estimator has smaller bias than the unconditional estimator and smaller mean square error than the conditional estimator.