Dementia is a global public health problem. The Mini-Mental State Examination (MMSE) is a proprietary instrument for detecting dementia, but many other tests are also available.
To evaluate the ...diagnostic performance of all cognitive tests for the detection of dementia.
Literature searches were performed on the list of dementia screening tests in MEDLINE, EMBASE, and PsychoINFO from the earliest available dates stated in the individual databases until September 1, 2014. Because Google Scholar searches literature with a combined ranking algorithm on citation counts and keywords in each article, our literature search was extended to Google Scholar with individual test names and dementia screening as a supplementary search.
Studies were eligible if participants were interviewed face to face with respective screening tests, and findings were compared with criterion standard diagnostic criteria for dementia. Bivariate random-effects models were used, and the area under the summary receiver-operating characteristic curve was used to present the overall performance.
Sensitivity, specificity, and positive and negative likelihood ratios were the main outcomes.
Eleven screening tests were identified among 149 studies with more than 49,000 participants. Most studies used the MMSE (n = 102) and included 10,263 patients with dementia. The combined sensitivity and specificity for detection of dementia were 0.81 (95% CI, 0.78-0.84) and 0.89 (95% CI, 0.87-0.91), respectively. Among the other 10 tests, the Mini-Cog test and Addenbrooke's Cognitive Examination-Revised (ACE-R) had the best diagnostic performances, which were comparable to that of the MMSE (Mini-Cog, 0.91 sensitivity and 0.86 specificity; ACE-R, 0.92 sensitivity and 0.89 specificity). Subgroup analysis revealed that only the Montreal Cognitive Assessment had comparable performance to the MMSE on detection of mild cognitive impairment with 0.89 sensitivity and 0.75 specificity.
Besides the MMSE, there are many other tests with comparable diagnostic performance for detecting dementia. The Mini-Cog test and the ACE-R are the best alternative screening tests for dementia, and the Montreal Cognitive Assessment is the best alternative for mild cognitive impairment.
Mechanical compliance has been demonstrated to be a key determinant of cell behavior, directing processes such as spreading, migration, and differentiation. Durotaxis, directional migration from ...softer to more stiff regions of a substrate, has been observed for a variety of cell types. Recent stiffness mapping experiments have shown that local changes in tissue stiffness in disease are often accompanied by an altered ECM composition in vivo. However, the importance of ECM composition in durotaxis has not yet been explored. To address this question, we have developed and characterized a polyacrylamide hydrogel culture platform featuring highly tunable gradients in mechanical stiffness. This feature, together with the ability to control ECM composition, allows us to isolate the effects of mechanical and biological signals on cell migratory behavior. Using this system, we have tracked vascular smooth muscle cell migration in vitro and quantitatively analyzed differences in cell migration as a function of ECM composition. Our results show that vascular smooth muscle cells undergo durotaxis on mechanical gradients coated with fibronectin but not on those coated with laminin. These findings indicate that the composition of the adhesion ligand is a critical determinant of a cell’s migratory response to mechanical gradients.
Screening for depression in older adults is recommended.
To evaluate the diagnostic accuracy of the Two-Question Screen for older adults and compare it with other screening instruments for ...depression.
We undertook a literature search for studies assessing the diagnostic performance of depression screening instruments in older adults. Combined diagnostic accuracy including sensitivity and specificity were the primary outcomes. Potential risks of bias and the quality of studies were also assessed.
A total of 46 506 participants from 132 studies were identified evaluating 16 screening instruments. The majority of studies (63/132) used various versions of the Geriatric Depression Scale (GDS) and 6 used the Two-Question Screen. The combined sensitivity and specificity for the Two-Question Screen were 91.8% (95% CI 85.2-95.6) and 67.7% (95% CI 58.1-76.0), respectively; the diagnostic performance area under the curve (AUC) was 90%. The Two-Question Screen showed comparable performance with other instruments, including clinician-rated scales. The One-Question Screen showed the lowest diagnostic performance with an AUC of 78%. In subgroup analysis, the Two-Question Screen also had good diagnostic performance in screening for major depressive disorder.
The Two-Question Screen is a simple and short instrument for depression screening. Its diagnostic performance is comparable with other instruments and, therefore, it would be favourable to use it for older adult screening programmes.
It is recommended that patients with acute upper gastrointestinal bleeding undergo endoscopy within 24 hours after gastroenterologic consultation. The role of endoscopy performed within time frames ...shorter than 24 hours has not been adequately defined.
To evaluate whether urgent endoscopy improves outcomes in patients predicted to be at high risk for further bleeding or death, we randomly assigned patients with overt signs of acute upper gastrointestinal bleeding and a Glasgow-Blatchford score of 12 or higher (scores range from 0 to 23, with higher scores indicating a higher risk of further bleeding or death) to undergo endoscopy within 6 hours (urgent-endoscopy group) or between 6 and 24 hours (early-endoscopy group) after gastroenterologic consultation. The primary end point was death from any cause within 30 days after randomization.
A total of 516 patients were enrolled. The 30-day mortality was 8.9% (23 of 258 patients) in the urgent-endoscopy group and 6.6% (17 of 258) in the early-endoscopy group (difference, 2.3 percentage points; 95% confidence interval CI, -2.3 to 6.9). Further bleeding within 30 days occurred in 28 patients (10.9%) in the urgent-endoscopy group and in 20 (7.8%) in the early-endoscopy group (difference, 3.1 percentage points; 95% CI, -1.9 to 8.1). Ulcers with active bleeding or visible vessels were found on initial endoscopy in 105 of the 158 patients (66.4%) with peptic ulcers in the urgent-endoscopy group and in 76 of 159 (47.8%) in the early-endoscopy group. Endoscopic hemostatic treatment was administered at initial endoscopy for 155 patients (60.1%) in the urgent-endoscopy group and for 125 (48.4%) in the early-endoscopy group.
In patients with acute upper gastrointestinal bleeding who were at high risk for further bleeding or death, endoscopy performed within 6 hours after gastroenterologic consultation was not associated with lower 30-day mortality than endoscopy performed between 6 and 24 hours after consultation. (Funded by the Health and Medical Fund of the Food and Health Bureau, Government of Hong Kong Special Administrative Region; ClinicalTrials.gov number, NCT01675856.).
Gut microbiota is believed to be a major determinant of health outcomes. We hypothesised that a novel oral microbiome formula (SIM01) can reduce the risk of adverse health outcomes in at-risk ...subjects during the coronavirus disease 2019 (COVID-19) pandemic. In this single-centre, double-blind, randomised, placebo-controlled trial, we recruited subjects aged ≥65 years or with type two diabetes mellitus. Eligible subjects were randomised in a 1:1 ratio to receive three months of SIM01 or placebo (vitamin C) within one week of the first COVID-19 vaccine dose. Both the researchers and participants were blinded to the groups allocated. The rate of adverse health outcomes was significantly lower in the SIM01 group than the placebo at one month (6 2.9% vs. 25 12.6,
< 0.001) and three months (0 vs. 5 3.1%,
= 0.025). At three months, more subjects who received SIM01 than the placebo reported better sleep quality (53 41.4% vs. 22 19.3%,
< 0.001), improved skin condition (18 14.1% vs. 8 7.0%,
= 0.043), and better mood (27 21.2% vs. 13 11.4%,
= 0.043). Subjects who received SIM01 showed a significant increase in beneficial Bifidobacteria and butyrate-producing bacteria in faecal samples and strengthened the microbial ecology network. SIM01 reduced adverse health outcomes and restored gut dysbiosis in elderly and diabetes patients during the COVID-19 pandemic.
The fabrication of functional small diameter blood vessel analogs has implications in vascular disease treatment. Current 3D models of the medial vessel layer lack micron-scale topographical cues ...that have shown promise in vitro by recapitulating native vascular smooth muscle cell (VSMC) behavior. A major obstacle to fabricating 3D scaffolds is maintaining adequate nutrient diffusion to cells. We have developed and characterized porous micro-patterned poly-caprolactone (PCL) scaffolds using a novel technique that integrates soft lithography, melt molding and particulate leaching of polylactic-
co-glycolic acid (PLGA) micro/nanoparticles. Scanning electron microscopy showed that PLGA-leached scaffolds have circular pores significantly smaller than the size scale of the grooved surface pattern (48
μm grooves; 5
μm deep; 12
μm spacing). Diffusion of media through PLGA-leached scaffolds was six-fold greater than through non-porous scaffolds, indicating successful introduction of through-pores into PCL by the PLGA leaching technique. VSMC alignment on micro-patterned PLGA-leached scaffolds was similar to that on micro-patterned non-porous scaffolds, indicating no loss in cellular organization on PLGA-leached scaffolds. In contrast, cells seeded on micro-patterned sodium bicarbonate-leached scaffolds remained un-aligned. The ability to micro-pattern cells on porous scaffolds may facilitate the transfer of micro-technology from simple 2D substrates to complex 3D architectures, allowing for tight control over cellular organization in fabricated tissues.
Literature on apraxia of speech (AOS) in Chinese speakers is sparse compared to the English literature. This study aims to examine the pitch variation skills of Cantonese adults with AOS poststroke ...in terms of perceptual tone accuracy, acoustic fundamental frequency (
) changes, and repetition durations on items with different syllable structures, lexical status, and tone syllables in various positions in a sequencing context.
Six Cantonese adults with AOS poststroke (AOS group), six adults without AOS poststroke (nAOS group), and six healthy controls (HC group) performed the tone sequencing task (TST), which was adapted from oral diadochokinetic tasks, with three different tone syllables. Tone accuracy,
values across 10 time points, and acoustic repetition durations were compared within and between the groups.
The AOS group produced significantly lower tone accuracy and different
changes on the three Cantonese tone syllables compared with the control groups and significantly longer repetition durations than the HC group. The AOS group showed more difficulty with the tone syllables with the consonant-vowel structure, while a priming effect was observed on the T2 (high-rising) syllables with lexical meanings. A unique lowering of
in the final syllable of the trisyllabic items was observed only in the AOS group.
The AOS group showed degraded pitch variation skills. The effects of the three linguistic elements were discussed. Future investigations are called for to adapt the TST in other tonal languages to determine if degraded pitch variation skills are present in other tonal language speakers with AOS.
To successfully develop a functional tissue-engineered vascular patch, recapitulating the hierarchical structure of vessel is critical to mimic mechanical properties. Here, we use a cell sheet ...engineering strategy with micropatterning technique to control structural organization of bovine aortic vascular smooth muscle cell (VSMC) sheets. Actin filament staining and image analysis showed clear cellular alignment of VSMC sheets cultured on patterned substrates. Viability of harvested VSMC sheets was confirmed by Live/Dead® cell viability assay after 24 and 48 h of transfer. VSMC sheets stacked to generate bilayer VSMC patches exhibited strong inter-layer bonding as shown by lap shear test. Uniaxial tensile testing of monolayer VSMC sheets and bilayer VSMC patches displayed nonlinear, anisotropic stress-stretch response similar to the biomechanical characteristic of a native arterial wall. Collagen content and structure were characterized to determine the effects of patterning and stacking on extracellular matrix of VSMC sheets. Using finite-element modeling to simulate uniaxial tensile testing of bilayer VSMC patches, we found the stress-stretch response of bilayer patterned VSMC patches under uniaxial tension to be predicted using an anisotropic hyperelastic constitutive model. Thus, our cell sheet harvesting system combined with biomechanical modeling is a promising approach to generate building blocks for tissue-engineered vascular patches with structure and mechanical behavior mimicking native tissue.
Digital drawing tests have been proposed for cognitive screening over the past decade. However, the diagnostic performance is still to clarify. The objective of this study was to evaluate the ...diagnostic performance among different types of digital and paper-and-pencil drawing tests in the screening of mild cognitive impairment (MCI) and dementia. Diagnostic studies evaluating digital or paper-and-pencil drawing tests for the screening of MCI or dementia were identified from OVID databases, included Embase, MEDLINE, CINAHL, and PsycINFO. Studies evaluated any type of drawing tests for the screening of MCI or dementia and compared with healthy controls. This study was performed according to PRISMA and the guidelines proposed by the Cochrane Diagnostic Test Accuracy Working Group. A bivariate random-effects model was used to compare the diagnostic performance of these drawing tests and presented with a summary receiver-operating characteristic curve. The primary outcome was the diagnostic performance of clock drawing test (CDT). Other types of drawing tests were the secondary outcomes. A total of 90 studies with 22,567 participants were included. In the screening of MCI, the pooled sensitivity and specificity of the digital CDT was 0.86 (95% CI = 0.75 to 0.92) and 0.92 (95% CI = 0.69 to 0.98), respectively. For the paper-and-pencil CDT, the pooled sensitivity and specificity of brief scoring method was 0.63 (95% CI = 0.49 to 0.75) and 0.77 (95% CI = 0.68 to 0.84), and detailed scoring method was 0.63 (95% CI = 0.56 to 0.71) and 0.72 (95% CI = 0.65 to 0.78). In the screening of dementia, the pooled sensitivity and specificity of the digital CDT was 0.83 (95% CI = 0.72 to 0.90) and 0.87 (95% CI = 0.79 to 0.92). The performances of the digital and paper-and-pencil pentagon drawing tests were comparable in the screening of dementia. The digital CDT demonstrated better diagnostic performance than paper-and-pencil CDT for MCI. Other types of digital drawing tests showed comparable performance with paper-and-pencil formats. Therefore, digital drawing tests can be used as an alternative tool for the screening of MCI and dementia.
Magnetic resonance imaging (MRI), a non‐invasive, non‐radiative technique, is thought to lead to cellular or even molecular resolution if optimized targeted MR contrast agents are introduced. This ...would allow diagnosing progressive diseases in early stages. Here, it is shown that the high binding affinity of poly(ethylene glycol)‐gallol (PEG‐gallol) allows freeze drying and re‐dispersion of 9 ± 2‐nm iron oxide cores individually stabilized with ≈9‐nm‐thick stealth coatings, yielding particle stability for at least 20 months. Particle size, stability, and magnetic properties of PEGylated particles are compared to Feridex, a commercially available untargeted negative MR contrast agent. Biotin‐PEG(3400)‐gallol/methoxy‐PEG(550)‐gallol stabilized nanoparticles are further functionalized with biotinylated human anti‐VCAM‐1 antibodies using the biotin–neutravidin linkage. Binding kinetics and excellent specificity of these nanoparticles are demonstrated using quartz crystal microbalance with dissipation monitoring (QCM‐D). These MR contrast agents can be functionalized with any biotinylated ligand at controlled ligand surface density, rendering them a versatile research tool.
Using quartz crystal microbalance ith dissipation monitoring it is shown that 9 ± 2‐nm iron oxide cores individually stabilized with biotin‐PEG(3400)‐gallol/methoxy‐PEG(550)‐gallol can be targeted with high binding affinity and excellent specificity toward recombinant VCAM‐1 chimera. Highly potent targeted magnetic resonance imaging contrast agents are demonstrated (see image).
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