The Montreal Cognitive Assessment: Norms and Reliable Change Indices for Standard and MoCA-22 Administrations.

OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is among the most frequently administered cognitive screening tests, yet demographically diverse normative data are needed for repeated administrations. METHOD: Data were obtained from 18,410 participants using the National Alzheimer's Coordinating Center Uniform Data Set. We developed regression-based norms using Tobit regression to account for ceiling effects, explored test-retest reliability of total scores and by domain stratified by age and diagnosis with Cronbach's alpha, and reported the cumulative change frequencies for individuals with serial MoCA administrations to gage expected change. RESULTS: Strong ceiling effects and negative skew were observed at the total score, domain, and item levels for the cognitively normal group, and performances became more normally distributed as the degree of cognitive impairment increased. In regression models, years of education was associated with higher MoCA scores, whereas older age, male sex, Black and American Indian or Alaska Native race, and Hispanic ethnicity were associated with lower predicted scores. Temporal stability was adequate and good at the total score level for the cognitively normal and cognitive disorders groups, respectively, but fell short of reliability standards at the domain level. CONCLUSIONS: MoCA total scores are adequately reproducible among those with cognitive diagnoses, but domain scores are unstable. Robust regression-based norms should be used to adjust for demographic performance differences, and the limited reliability, along with the ceiling effects and negative skew, should be considered when interpreting MoCA scores.

Classification statistics of the Montreal Cognitive Assessment (MoCA): Are we interpreting the MoCA correctly?

OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is a common cognitive screener for detecting mild cognitive impairment (MCI). However, previously suggested cutoff scores of 26/30 and above is often criticized and lacks racial diversity. The purpose of this study is to investigate the potential influence of race on MoCA classification cutoff score accuracy. METHOD: Data were obtained from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set and yielded 4,758 total participants. Participants were predominately White (82.8%) and female (61.7%) with a mean age of 69.3 years (SD = 10.3) and education level of 16.3 years (SD = 2.6). Based on NACC's classification, participants were either cognitively normal (n = 3,650) or MCI (n = 1,108). RESULTS: Sensitivity and specificity analyses revealed that when using the cutoff score of ≤26/30, the MoCA correctly classified 73.2% of White cognitively normal participants and 83.1% of White MCI participants. In contrast, this criterion correctly classified 40.5% of Black cognitively normal participants and 90.8% of Black MCI participants. Our sample was highly educated; therefore, we did not observe significant differences in scores when accounting for education across race. Classification statistics are presented. CONCLUSIONS: Black participants were misclassified at a higher rate than White participants when applying the ≤26/30 cutoff score. We suggest cutoff scores of ≤25/30 be applied to White persons and ≤22/30 for Black persons. These findings highlight the need for racially stratified population-based norms given the high misclassification of Black participants without such adjustment.

SARS-CoV-2 Vaccine Booster Elicits Robust Prolonged Maternal Antibody Responses and Passive Transfer Via The Placenta And Breastmilk.

Background: Infection during pregnancy can result in adverse outcomes for both pregnant persons and offspring. Maternal vaccination is an effective mechanism to protect both mother and neonate into post-partum. However, our understanding of passive transfer of antibodies elicited by maternal SARS-CoV-2 mRNA vaccination during pregnancy remains incomplete. Objective: We aimed to evaluate the antibody responses engendered by maternal SARS-CoV-2 vaccination following initial and booster doses in maternal circulation and breastmilk to better understand passive immunization of the newborn. Study Design: We collected longitudinal blood samples from 121 pregnant women who received SARS-CoV-2 mRNA vaccines spanning from early gestation to delivery followed by collection of blood samples and breastmilk between delivery and 12 months post-partum. During the study, 70% of the participants also received a booster post-partum. Paired maternal plasma, breastmilk, umbilical cord plasma, and newborn plasma samples were tested via enzyme-linked immunosorbent assays (ELISA) to evaluate SARS-CoV-2 specific IgG antibody levels. Results: Vaccine-elicited maternal antibodies were detected in both cord blood and newborn blood, albeit at lower levels than maternal circulation, demonstrating transplacental passive immunization. Booster vaccination significantly increased spike specific IgG antibody titers in maternal plasma and breastmilk. Finally, SARS-CoV-2 specific IgG antibodies in newborn blood correlated negatively with days post initial maternal vaccine dose. Conclusion: Vaccine-induced maternal SARS-CoV-2 antibodies were passively transferred to the offspring in utero via the placenta and after birth via breastfeeding. Maternal booster vaccination, regardless of gestational age at maternal vaccination, significantly increased antibody levels in breastmilk and maternal plasma, indicating the importance of this additional dose to maximize passive protection against SARS-CoV-2 infection for neonates and infants until vaccination eligibility.

Consonant Age of Acquisition Reveals Nonlinear Effects in Nonword Repetition Performance.

Recent work has shown significant sublexical effects of long-term memory in nonword repetition (NWR) using a dichotomous consonant age of acquisition (CAoA) variable (Moore, 2018; Moore, Fiez, and Tompkins, 2017). Performance consistently decreased when stimuli comprised consonants acquired later versus earlier in speech development. To address potential confounds related to stimulus design and linearity, the purpose of this study was to test whether performance decreases as the CAoA value of stimuli increases in various linguistic tasks using a continuous CAoA variable. Thirty-one college students completed NWR and other linguistic tasks in which the stimuli varied in average CAoA values. Data were analyzed using multilevel modeling. After accounting for phonotactic probability, CAoA was a statistically significant predictor of performance across the models reported. The relationship was more complex in some of the models in which CAoA showed a statistically significant nonlinear relationship with the outcome measure. Results from this study support previous work showing that CAoA affects performance on NWR and other linguistic tasks that vary in their memory, auditory perceptual, and articulatory demands. Importantly, this line of work was extended here by demonstrating that the CAoA effect is robust across novel stimulus sets and study designs, and may be more complex than previously understood when using a dichotomous CAoA variable. Quadratic results suggest that the CAoA variable has a differential effect on performance for low to moderate CAoA values, but for higher CAoA values the effect is similarly negative. The nonlinear relationship between CAoA and measures of speed and accuracy on some of the tasks warrants further study into the complex relationship between various predictive factors that contribute to language performance.

The 14-3-3 Protein Homolog ArtA Regulates Development and Secondary Metabolism in the Opportunistic Plant Pathogen Aspergillus flavus.

The opportunistic plant-pathogenic fungus Aspergillus flavus produces carcinogenic mycotoxins termed aflatoxins (AF). Aflatoxin contamination of agriculturally important crops, such as maize, peanut, sorghum, and tree nuts, is responsible for serious adverse health and economic impacts worldwide. In order to identify possible genetic targets to reduce AF contamination, we have characterized the artA gene, encoding a putative 14-3-3 homolog in A. flavus The artA deletion mutant presents a slight decrease in vegetative growth and alterations in morphological development and secondary metabolism. Specifically, artA affects conidiation, and this effect is influenced by the type of substrate and culture condition. In addition, normal levels of artA are required for sclerotial development. Importantly, artA negatively regulates AF production as well as the concomitant expression of genes in the AF gene cluster. An increase in AF is also observed in seeds infected with the A. flavus strain lacking artA Furthermore, the expression of other secondary metabolite genes is also artA dependent, including genes in the cyclopiazonic acid (CPA) and ustiloxin gene clusters, in this agriculturally important fungus.IMPORTANCE In the current study, artA, which encodes a 14-3-3 homolog, was characterized in the agriculturally and medically important fungus Aspergillus flavus, specifically, its possible role governing sporulation, formation of resistant structures, and secondary metabolism. The highly conserved artA is necessary for normal fungal morphogenesis in an environment-dependent manner, affecting the balance between production of conidiophores and the formation of resistant structures that are necessary for the dissemination and survival of this opportunistic pathogen. This study reports a 14-3-3 protein affecting secondary metabolism in filamentous fungi. Importantly, artA regulates the biosynthesis of the potent carcinogenic compound aflatoxin B1 (AFB1) as well as the production of other secondary metabolites.

Effects of obesity on patient experience in the emergency department.

OBJECTIVE: The study aims to determine if obesity (body mass index ≥30.0 kg/m(2) ) adversely affects the patients' ED experience in terms of flow variables and rates of assistance, investigation and procedure. METHODS: This was a prospective, analytical, observational study in a large tertiary referral ED. Consecutive patients, presenting during data collection periods, were enrolled after they had received ≥3 h of care. Height and weight data were collected from the patient; demographics, presenting complaint, triage category, time to be seen and modes of arrival and disposition from the Emergency Department Information System, and investigations from the electronic pathology and radiology records. Data on a wide range of procedures and management variables were collected directly from the ED staff using a specifically designed survey instrument. RESULTS: Seven hundred and eleven patients were enrolled (mean age 64.3 ± 18.6 years, 375 [52.7%] male). One hundred and ninety-one (26.9%, 95% confidence interval 23.7-30.3) patients were obese. Obese patients were significantly younger than non-obese patients (median 63 vs 70 years, P < 0.001). They had significantly more intravenous cannulation attempts, liver function tests (69.1% vs 60.2%), cardiac enzyme tests (40.8% vs 30.0%) and abdominal X-rays (17.8% vs 8.7%) (P < 0.05). There were no differences between the groups in time to be seen, monitoring, other procedures, assistance required, place of disposition or ED length of stay (P > 0.05). Obese patients had a lower death rate in the ED or hospital than non-obese patients (1.6% vs 7.5%, P < 0.01). CONCLUSION: In this single-centre study, obesity did not appear to adversely affect ED treatment. The observed differences in some investigation rates might relate to suspected morbidities and difficulties in physical examination.

Uranyl nitrate-induced proximal tubule alterations in rabbits: a quantitative analysis.

Naturally occurring uranium in drinking water is a significant health concern in several areas of North America. Because the kidney is a known target organ to examine the effects of uranium or its compounds, the objective of this study was to determine whether kidney repair occurs after exposure to, and withdrawal of, uranyl nitrate (UN). This work, part of a larger study to establish safe levels of uranium in drinking water supplies, examined the ultrastructural changes in proximal tubule cells of New Zealand white rabbits following subchronic exposure to UN in water and for 91 days after exposure ended. The rabbit was chosen as the experimental animal because of its high sensitivity to uranium. Animals were exposed to 24 or 600 mg UN per liter (UN/L) in drinking water for 91 days, with no recovery or recovery periods of 45 or 91 days. Ultrastructural changes, quantified by a stereological image analysis system based on point counting, were observed in renal proximal tubules (PTs). Each electron micrograph was statistically considered an experimental unit. The severity of lesions was directly proportional to the dose. Animals exposed to 600 mg UN/L had the most severe lesions; nevertheless, alterations were remarkable in animals exposed to the low dose. At both recovery periods, the lesions were significantly more severe than those in animals of the no-recovery group, which may result from the kidney's ability to store uranium. The PT cells had increased lysosomal and vacuolar mass as well as variations in mitochondrial mass. In addition, there was epithelial cell degeneration with a focal loss of brush borders, thickening and splitting of tubular basement membrane, and occasionally cell necrosis. Interstitial fibrosis of the renal cortex persisted as the recovery period increased in the animals of UN-dosed groups. Alterations may be due to disturbed fluid transport across the PT and other cells and decreased cell respiration resulting from damaged cell constituents. Cell damage caused by UN in drinking water persisted throughout the 91-day recovery period. By eventually determining the no observable effect level for the kidney by UN, this study may assist in devising a model to ascertain the safe levels of uranium in water.

"mdx" mouse myopathy: histopathological, morphometric and histochemical observations on young mice.

Histopathological examination of tibialis anterior (TA) and lateral gastrocnemius (LG) muscles from "mdx" mice sometimes revealed lesions of calcification and the close proximity of degenerative lesions with regenerative changes. Morphometric examinations showed that the TA was more severely affected than the LG in mice of all age groups. The soleus muscle was less severely affected than the TA in very young mice, but appeared to be affected almost as severely as the TA in older mice. Type 1 myofibres were more acid-labile in the mdx mice than in control mice and all three major fibre types degenerated and subsequently regenerated in young mdx mice. The aetiological significance of the above findings is unknown at present.