Normal Participants Research Articles

Bilateral meibomian gland morphological alterations in unilateral herpes simplex keratitis based on artificial intelligence analysis

AIM: To explore whether unilateral herpes simplex keratitis (HSK) can cause morphological changes of bilateral meibomian glands (MGs) based on artificial intelligence (AI) analytical system. METHODS: In the retrospective study, 29 patients with unilateral HSK and 29 participants matched in terms of age and sex were included as control group. Meibographic images of the upper eyelid using Keratograph 5M and assessed ocular surface parameters including tear meniscus height and tear break-up time. MG density and vagueness values were automatically analyzed and calculated using an AI analytical system. We compared the differences between the affected and the contralateral unaffected eyes in HSK patients, and the normal control eyes. We employed either the paired t-test or the Wilcoxon signed-rank test to compare significant difference between the affected and unaffected eyes in HSK patients or between the HSK group and control group. RESULTS: The MG density was 0.19±0.09 in the HSK-affected eye and 0.18±0.07 in contralateral unaffected eye, which had no significant difference (P=0.616). The MG density between the affected eye with HSK and the normal control group was statistically significant (P=0.028). There was a significant difference in MG density between the contralateral unaffected eye and the normal control group (P=0.012). However, no significant difference in vagueness value was observed between the eye with HSK and the control group or between HSK eye and contralateral eye. CONCLUSION: The MG density between the HSK-affected eye and the contralateral unaffected eye don't significantly differ, whereas there is a significant decrease in the HSK group compared to that of the normal participants. Unilateral HSV keratitis may suffer from bilateral changes of MG morphology indicating bilateral dry eye. Therefore, the fellow eye of patients with unilateral HSK should be considered a potential case of MG dysfunction, necessitating early treatment for bilateral dry eye in the clinic.

Lumipulse-Measured Cerebrospinal Fluid Biomarkers for the Early Detection of Alzheimer Disease.

CSF biomarkers of Aβ42 and phosphorylated tau (p-tau181) are used clinically for the detection of Alzheimer disease (AD) pathology during life. CSF biomarker validation studies have largely used clinical diagnoses and/or amyloid PET imaging as the reference standard. The few existing CSF-to-autopsy studies have been restricted to late-stage AD. This CSF-to-autopsy study investigated associations between CSF biomarkers of AD and AD neuropathologic changes among brain donors who had normal cognition at the time of lumbar puncture (LP). This was a retrospective study of brain donors from the National Alzheimer's Coordinating Center who had normal cognition at the time of LP and who had measurements of CSF Aβ42 and p-tau181 performed with Lumipulse assays. All brain donors were from Washington University Knight ADRC. Staging of AD neuropathologic change (ADNC) was made based on National Institute on Aging-Alzheimer's Association criteria. For this study, participants were divided into 2 categories: "AD-" (no AD/low ADNC) and "AD+" (intermediate/high ADNC). Accuracy of each biomarker for discriminating AD status was evaluated using area under the curve (AUC) statistics generated using predicted probabilities from binary logistic regressions that controlled for age, sex, APOE ε4, and interval between LP and death. The average age at LP was 79.3 years (SD = 5.6), and the average age at death was 87.1 years (SD = 6.5). Of the 49 brain donors, 24 (49%) were male and 47 (95.9%) were White. 20 (40.8%) had autopsy-confirmed AD. The average interval from LP until death was 7.76 years (SD = 4.31). CSF p-tau181/Aβ42 was the optimal predictor of AD, having excellent discrimination accuracy (AUC = 0.97, 95% CI 0.94-1.00, p = 0.003). CSF p-tau181 alone had the second-best discrimination accuracy (AUC = 0.92, 95% CI 0.84-1.00, p = 0.001), followed by CSF Aβ42 alone (AUC = 0.92, 95% CI 0.85-1.00, p = 0.007), while CSF t-tau had the numerically lowest discrimination accuracy (AUC = 0.87, 95% CI 0.76-0.97, p = 0.005). Effects remained after controlling for prevalent comorbid neuropathologies. CSF p-tau181/Aβ42 was strongly associated with CERAD ratings of neuritic amyloid plaque scores and Braak staging of NFTs. This study supports Lumipulse-measured CSF Aβ42 and p-tau181 and, particularly, the ratio of p-tau181 to Aβ42, for the early detection of AD pathophysiologic processes. This study provides Class II evidence that Lumipulse measures of p-tau181/Aβ42 in the CSF accurately discriminated cognitively normal participants with and without Alzheimer disease neuropathologic change.

A retrospective analysis of the Svayampurna Upacara Therapy in addressing PCOD symptoms

Introduction: This study assesses the efficacy of Svayampurna Upacara therapy, a holistic energy-based treatment, in managing Polycystic Ovarian Syndrome (PCOS). Conducted retrospectively on 150 women treated from 1995 to 2024 at Niraamay Wellness Center in Maharashtra, the study included energy healing, yoga, and meditation counselling over 12 weeks. The therapy aims to balance Panch Tattva (five elements) and align Chakras to address the root causes of PCOS symptoms. Materials and Methods: The study was conducted on 150 women with PCOS, using Svayampurna Upacara therapy. Over 12 weeks, participants underwent energy healing, Yoga, and meditation counselling, focusing on balancing Panch Tattva and Chakra alignment. Outcomes were assessed using McNemar's Chi-square test. Results: The results showed significant improvements in menstrual cycle regularity and reduced dysmenorrhea severity. Body Mass Index (BMI) management was more effective in underweight and normal BMI participants, with modest changes observed in higher BMI individuals, likely due to Pruthvi and Jal Tattva imbalances. Additionally, there were notable improvements in hirsutism, hair shedding, acne severity, and emotional parameters, as measured by the Depression, Anxiety, and Stress Scale-10. Discussion: The study highlights the potential of Svayampurna Upacara therapy in stabilizing mood swings and enhancing emotional well-being by addressing Tattva imbalances. However, the findings underscore the need for further research with larger, controlled studies to validate these results and establish the treatment's clinical efficacy. Overall, Svayampurna Upacara therapy offers a comprehensive approach to managing PCOS, addressing both physical and emotional health through energy balancing techniques.

Active listening modulates the spatial hearing experience: a multicentric study.

Although flexible and portable virtual reality technologies have simplified measuring participants' perception of acoustic space, their clinical adoption remains limited, often lacking ecological fidelity. In clinical practice, participants are typically instructed to remain still when testing sound localization, whereas head movements are crucial in daily life. Additionally, assessing spatial hearing extends beyond measuring accuracy to include meta-cognitive evaluations like perceived effort and confidence, which are rarely adopted. Our study hypothesized that allowing head movement during sound localization, compared to a static head condition, would reduce perceived listening effort and enhance confidence in normal hearing participants. Conducted across three audiology and otology hospital services in Northern Italy, the study involved personnel inexperienced with our VR equipment. This also tested the feasibility and usability of our VR approach in clinical settings. Results showed that head movements reduced subjective effort but did not significantly affect perceived confidence. However, during the active condition, participants reporting higher confidence exhibited less head movement and explored the space less. Similarly, those with less head movement reported lower listening effort. These findings underscore the importance of allowing natural posture to capture the full extent of spatial hearing capabilities and the value of including metacognitive evaluations in assessing performance. Our use of affordable, off-the-shelf VR equipment effectively measured spatial hearing in clinical settings, providing a flexible alternative to current static systems. This approach highlights the potential for more dynamic and comprehensive assessments in clinical audiology.

The Relationship Between Dietary Intake and Anthropometric Indices Between Dietary Intake and Anthropometric Indices with Anxiety in Female Medical Students

Background: Vitamins play an important role in improving mental health. Healthy diets can significantly influence the development, progression, and treatment of mental health disorders. Objectives: This study aimed to investigate the correlation between dietary intake and anthropometric profiles with anxiety in female students of Zahedan University of Medical Sciences. Methods: This cross-sectional study evaluated 200 female medical students for daily intake of B vitamins, omega-3, anthropometric indices, and their correlation with anxiety. The Food Frequency Questionnaire and Bronze Anxiety Questionnaire were used to examine the relationship between dietary intake and anxiety. The associations between parameters were analyzed using Pearson’s correlation. Results: The findings revealed that the mean age of the female medical students was 22.60 ± 2.10 years, with a Body Mass Index (BMI) of 23.37 ± 4.01, a waist-to-hip ratio (WHpR) of 0.81 ± 0.11, a waist-to-height ratio (WHtR) of 10.55 ± 0.10, and an anxiety score of 44.83 ± 17.71. Positive correlations were observed between BMI (r = 0.89, P = 0.0001), WHpR (r = 0.86, P = 0.0001), and WHtR (r = 0.898, P = 0.0001) with anxiety. The mean anxiety scores were 23.84 ± 4.36, 38.59 ± 4.62, 61.44 ± 13.63, and 74.44 ± 5.96 in underweight, normal, overweight, and obese participants, respectively. A negative correlation was identified between the consumption of vitamins and omega-3 and anxiety scores (r = -0.63, P < 0.001). Conclusions: This study suggests that a higher intake of dietary B vitamins and omega-3 is associated with lower anxiety scores in Zahedan medical students.

The steady-state pharmacokinetics of fixed-dose combination dolutegravir+rilpivirine in hemodialysis

Objective: Fixed dose combination (FDC) dolutegravir (DTG) plus rilpivirine (RPV) is an approved antiretroviral treatment regimen for people with HIV. The steady-state pharmacokinetics (PK) of FDC DTG+RPV in hemodialysis (HD) has not been previously studied. Design: We performed a single-center, prospective evaluation of the steady-state PK of FDC DTG +RPV in 4 adults without HIV either requiring HD and in 4 matched participants with normal renal function. Methods: All participants received FDC DTG(50mg)+RPV(25mg) daily for 10-14 days with food before undergoing an intensive 24-hour PK evaluation (performed between dialysis days for those requiring HD). Plasma drug and metabolite concentrations were measured using a validated UHPLC/MS/MS. Descriptive PK parameters were calculated. Results: The HD and normal renal function participants (each group with 2 men and 2 women) were of similar ages (range, 50-60 years) and body mass index (range, 18.5-34.5 kg/m2). No participant experienced serious or grade 3-4 adverse events; there were no study discontinuations. The AUC0-τ mean (SD) ratios of HD to normal renal function for DTG and RPV were 1.1 (0.4) and 1.1 (0.9), respectively. The mean (SD) Cmin for DTG and RPV in the HD group were 1033 (252) ng/mL and 49 (18) ng/mL, respectively. Conclusions: HD did not lead to clinically appreciable differential exposures to DTG and RPV. Exposures throughout the dosing interval were greater than the reported protein-binding adjusted IC90 efficacy values for DTG (64 ng/mL) and RPV (12 ng/mL) in all participants. These data suggest no dosing modifications are needed for the FDC DTG+RPV regimen in HD.

Quick-reference criteria for identifying multivariate cognitive change in older adults with mild cognitive impairment and dementia: An ADNI study.

To establish quick-reference criteria regarding the frequency of statistically rare changes in seven neuropsychological measures administered to older adults. Data from 935 older adults examined over a two-year interval were obtained from the Alzheimer's Disease Neuroimaging Initiative. The sample included 401 cognitively normal older adults whose scores were used to determine the natural distribution of change scores for seven cognitive measures and to set change score thresholds corresponding to the 5th percentile. The number of test scores that exceeded these thresholds were counted for the cognitively normal group, as well as 381 individuals with mild cognitive impairment (MCI) and 153 individuals with dementia. Regression analyses examined whether the number of change scores predicted diagnostic group membership beyond demographic covariates. Only 4.2% of cognitively normal participants obtained two or more change scores that fell below the 5th percentile of change scores, compared to 10.6% of the stable MCI participants and 38.6% of those who converted to dementia. After adjusting for age, gender, race/ethnicity, and premorbid estimates, the number of change scores below the 5th percentile significantly predicted diagnostic group membership. It was uncommon for older adults to have two or more change scores fall below the 5th percentile thresholds in a seven-test battery. Higher change counts may identify those showing atypical cognitive decline.

APOE ε4-associated heterogeneity of neuroimaging biomarkers across the Alzheimer's disease continuum.

While the role of apolipoprotein E (APOE) ε4 in Alzheimer's disease (AD) susceptibility has been studied extensively, much less is known about the differences in disease presentation in APOE ε4 carriers versus non-carriers. To help elucidate these differences, we performed a broad analysis comparing the regional levels of six different neuroimaging biomarkers in the brains of APOE ε4 carriers versus non-carriers who participated in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We observed significant APOE ε4-associated heterogeneity in regional amyloid beta deposition, tau accumulation, glucose uptake, brain volume, cerebral blood flow, and white matter hyperintensities within each AD diagnostic group. We also observed important APOE ε4-associated differences in cognitively unimpaired individuals who converted to mild cognitive impairment/AD versus those who did not convert. This observed heterogeneity in neuroimaging biomarkers between APOE ε4 carriers versus non-carriers may have important implications regarding the prevention, diagnosis, and treatment of AD in different subpopulations. An extensive study was performed on the apolipoprotein E (APOE) ε4-associated heterogeneity in neuroimaging biomarkers from the Alzheimer's Disease Neuroimaging Initiative. Robust APOE ε4-associated increases in amyloid beta (Aβ) deposition throughout the brain, in every diagnostic group, were observed. APOE ε4-associated increases in tau pathology, decreases in glucose uptake, and increases in brain atrophy, which expand in regional scope and magnitude with disease progression, were observed. Significant sex- and age-related differences in APOE ε4-associated neuroimaging biomarker heterogeneity, with overall increases in pathological presentation in female APOE ε4 carriers, were observed. Regional differences in Aβ deposition, tau accumulation, glucose uptake, ventricle size, and white matter hyperintensities were observed in cognitively normal participants who converted to mild cognitive impairment/Alzheimer's disease, which may hold potential predictive value.

Age-Related Differences in the Association between Life's Essential 8 and Cognition in Cognitively Normal Adults: The CABLE Study.

This study investigated the relationship between Life's Essential 8 (LE8), a recently updated lifestyle-related health factor, and cognition across multiple life stages. We enrolled 1098 cognitively normal participants from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study. We investigated the interactions between age and LE8 on cognition. Multiple linear regression models were utilized to explore the relationship between the LE8 total scores and its two subscales scores with cognition in the total sample, as well as in the mid-age (≤65 years) and the late-age (>65 years) subgroups. In addition, mediation analyses were performed to explore the biologically plausible pathways between LE8 and cognition. There was a significant interaction effect between age and LE8 total scores on MOCA score (P = 0.030). The mid-age subgroup showed a positive correlation between LE8 total scores and CM-MMSE (β = 0.110, P = 0.005) and MOCA (β = 0.112, P = 0.005) scores. However, no significant associations were found in the late-age subgroup. In the mid-age subgroup, CSF p-tau partially mediated the relationship between LE8 total scores and its two subscales and cognition, with a mediation proportion ranging from 6% to 12%. Our findings revealed that the association of the LE8 total scores with MOCA and CM-MMSE scores were significant in mid-age adults rather than late-age adults, indicating that the association might be age-specific and emphasizing the importance of lifestyle interventions in mid-life.

Associations among healthy lifestyle characteristics, neuroinflammation, and cerebrospinal fluid core biomarkers of Alzheimer's disease in cognitively intact adults: The CABLE study.

The occurrence of Alzheimer's disease (AD) can be partially prevented through healthy lifestyles, but the mechanisms associated with AD pathology are unclear. To explore associations among healthy lifestyle characteristics (HLCs), cerebrospinal fluid (CSF) soluble TREM2 (sTREM2), and AD biomarkers. From the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study, 924 cognitively normal participants were enrolled in this cross-sectional analysis. We defined the following 11 HLCs: appropriate frequencies of coffee and tea consumption, sufficient frequencies of fish and fruit intake, non-social isolation, adequate sleep, regular physical activity, no depression, never smoking, non-hazardous drinking, and well-maintained blood pressure. We categorized participants according to the number of HLCs reported by participants into favorable, intermediate, and unfavorable lifestyle groups. Multiple linear regression was used to investigate the relationship among HLCs, CSF sTREM2, and AD biomarkers. Mediation effects were tested using a causal mediation analysis having 10,000 bootstrap iterations. Included subjects were with a mean age of 61.8 ± 10.2 years, of which 41.8% were female. Sufficient fish intake (β = -0.164, p = 0.017) and well-maintained blood pressure (β = -0.232, p = 0.006) were significantly correlated with lower CSF sTREM2 levels. A larger number of HLCs were associated with lower CSF T-tau (p = 0.001), P-tau (p = 0.012), and sTREM2 (p = 0.040) levels. CSF sTREM2 partially mediated the association between the number of HLCs and CSF tau pathology (mediating proportion T-tau: 22.4%; P-tau: 25.0%). HLCs might impact the pathological processes of AD by regulating neuroinflammation.

Cerebello-Cerebral Resting-State Functional Connectivity in Poststroke Aphasia.

Introduction: The influence of the cerebellum in poststroke aphasia recovery is poorly understood. Despite the right cerebellum being identified as a critical region involved in both language and cognitive functions, little is known about functional connections between the cerebellum and bilateral cortical hemispheres following stroke. This study investigated the relationship between chronic poststroke naming deficits and cerebello-cerebral resting-state functional connectivity (FC). Methods: Twenty-five cognitively normal participants and 42 participants with chronic poststroke aphasia underwent resting-state functional magnetic resonance imaging. Participants with aphasia also underwent language assessment. We conducted regions of interest (ROI)-to-ROI analyses to investigate the FC between the right cerebellar Crus I/II (seed ROI; Cereb1r/Cereb2r) and bilateral cortical language regions and compared these results to cognitively normal controls. Single-subject connectivity parameters were extracted and used as independent variables in a stepwise multiple linear regression model associating Boston Naming Test (BNT) score with FC measures. Results: FC analyses demonstrated correlations between the right cerebellar Crus I/II and both left and right cortical regions for both cognitively normal controls and stroke participants. Additionally, aphasia severity and lesion load had an effect on the cerebello-cerebral network connectivity in participants with aphasia. In a stepwise multiple linear regression, controlling for aphasia severity, time poststroke and lesion load, FC between the right Cereb2-left Cereb1 (standardized beta [std B]= -0.255, p < 0.004), right Cereb2-right anterior MTG (std B = 0.259, p < 0.004), and the right Cereb2-left anterior STG (std B = -0.208, p < 0.018) were significant predictors of BNT score. The overall model fit was R2 = 0.786 (p = 0.001). Conclusion: Functional connections between the right cerebellum and residual bilateral cerebral hemisphere regions may play a role in predicting naming ability in poststroke aphasia.

Relationships between abdominal adipose tissue and neuroinflammation with diffusion basis spectrum imaging in midlife obesity.

This study investigated how obesity, BMI ≥ 30 kg/m2, abdominal adiposity, and systemic inflammation relate to neuroinflammation using diffusion basis spectrum imaging. We analyzed data from 98 cognitively normal midlife participants (meanage: 49.4 [SD 6.2] years; 34 males [34.7%]; 56 with obesity [57.1%]). Participants underwent brain and abdominal magnetic resonance imaging (MRI), blood tests, and amyloid positron emission tomography (PET) imaging. Abdominal visceral and subcutaneous adipose tissue (VAT and SAT, respectively) was segmented, and Centiloids were calculated. Diffusion basis spectrum imaging parameter maps were created using an in-house script, and tract-based spatial statistics assessed white matter differences in high versus low BMI values, VAT, SAT, insulin resistance, systemic inflammation, and Centiloids, with age and sex as covariates. Obesity, high VAT, and high SAT were linked to lower axial diffusivity, reduced fiber fraction, and increased restricted fraction in white matter. Obesity was additionally associated with higher hindered fraction and lower fractional anisotropy. Also, individuals with high C-reactive protein showed lower axial diffusivity. Higher restricted fraction correlated with continuous BMI and SAT particularly in male individuals, whereas VAT effects were similar in male and female individuals. The findings suggest that, at midlife, obesity and abdominal fat are associated with reduced brain axonal density and increased inflammation, with visceral fat playing a significant role in both sexes.

Age-related decline in blood-brain barrier function is more pronounced in males than females in parietal and temporal regions.

The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8-92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60 s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.

The Effect of Prism Presentation Order on Near Vertical Fusional Vergence Ranges of Normal Young Adults.

Fusional vergence ranges (FVR) quantify the oculomotor system's ability to overcome heterophoria, playing a critical role in diagnosis and treatment.This study investigated the effect of prism order on near vertical FVR using the smooth and step methods. Normal participants were randomly assigned to either the smooth or step testing method and to Base-Up (BU, infravergence) first or Base Down (BD, supravergence) first prism type. After an hour, they crossed over tothe alternative testing method and prism-type. The mean of two consecutive measurements of break and recovery values for one eye in each of the 16 experimental conditions were compared using the Friedman test with post-hoc Bonferroni correction, and non-parametric Bland and Altman analysis. The mean break/recovery values of 27 participants (mean age: 22.5±2.0, range: 20-29, 20female) when BU or BD were measured first were BU: 4.20±1.15Δ/3.07±1.04Δand BD: 4.20±1.21Δ/3.00±0.96Δfor step, and BU: 4.31±0.98Δ/2.97±0.85Δand BD: 4.15±1.14Δ/2.70±0.87Δfor smooth methods, respectively. When measured second, they were BU: 3.74±1.02Δ/2.63±0.93Δand BD: 3.85±1.09Δ/2.64±1.06Δfor step, BU: 3.91±0.99Δ/2.73±0.93Δand BD: 3.81±1.04Δ/2.54±1.04Δ for smooth, respectively. The Friedman test found a significant effect of prism order on break values of the smooth (p<0.001) and step (p<0.02) methods, and recovery values of the step method (p<0.005), but post-hoc tests showed no significant differences. Mean differences were below 0.50Δindicating clinical insignificance. Unlike horizontal FVR, prism order does not affect near vertical FVR using the smooth and step. This simplifies clinical assessment and suggests that horizontal and vertical fusion systems may be treated as separate entities.

Isolation and Identification of Individual Intestinal Bacteria Associated with Waist Circumference Increase

Abstract Background: The bacterial flora of the gastrointestinal tract (GIT) of humans, there are differences in the composition of the flora which are influenced by age, diet, cultural conditions, and the use of antibiotics. Since the origin of obesity is multifactorial and complex, resulting from the interaction between genetic/epigenetic, environmental, and socio-psychological determinants, in addition to the bacterial composition of the intestinal flora could be a third element involved in the development of excess weight. Therefore intestinal flora plays an intermediary role in the metabolism and inflammation and is involved in the pathogenesis of diabetes type 2 and obesity. Objectives: This study aimed to draw the relationship between identified intestinal bacterial types on increasing the waist circumference among study participants. Materials and Methods: This study included the collection of 180 samples from participants (20–60 years) during the period from December 2022 to June 2023. Body mass index and waist circumference were calculated for study participants and intestinal bacteria was microbiologically and biochemically identified. Results: Results obtained showed that the intestinal flora of obese participants is significantly (P &lt; 0.001) different from that of thin and normal participants. This flora was characterized by the presence of high levels of Gram’s negative at the percentage (80.6% in obese), and Gram’s positive at the percentage (19.4% in obese), with higher body mass index and waist circumference than those participants, with lower body mass index and waist circumference. Conclusion: This study showed a significant relationship between intestinal bacteria and diabetic patients with increased body mass index and waist circumference, leading to probable useful tools for developing strategies to prevent obesity.

Machine learning based on event-related oscillations of working memory differentiates between preclinical Alzheimer’s disease and normal aging

ObjectiveTo apply machine learning approaches on EEG event-related oscillations (ERO) to discriminate preclinical Alzheimer’s disease (AD) from age- and sex-matched controls. MethodsTwenty-two cognitively normal preclinical AD participants with elevated amyloid and 21 cognitively normal controls without elevated amyloid completed n-back working memory tasks (n = 0, 1, 2). The absolute and relative power of ERO was extracted using the discrete wavelet transform in the delta, theta, alpha, and beta bands. Four machine learning methods were employed, and classification performance was assessed using three metrics. ResultsThe low-frequency bands produced higher discriminative performances compared to high-frequency bands. The 2-back task yielded the best classification capability among the three tasks. The highest area under the curve value (0.86) was achieved in the 2-back delta band nontarget condition data. The highest accuracy (80.47%) was obtained in the 2-back delta and theta bands nontarget data. The highest F1 score (0.82) was in the 2-back theta band nontarget data. The support vector machine achieved the highest performance among tested classifiers. ConclusionThis study demonstrates the promise of using machine learning on EEG ERO from working memory tasks to detect preclinical AD. SignificanceEEG ERO may reveal pathophysiological differences in the earliest stage of AD when no cognitive impairments are apparent.

Latent change-on-change between amyloid accumulation and cognitive decline.

While the influence of cross-sectional β-amyloid (Aβ) on longitudinal changes in cognition is well established, longitudinal change-on-change between Aβ and cognition is less explored. A series of bivariate latent change score models (LCSM) examined the relationship between changes in 11C-Pittsburgh Compound-B (PiB) positron emission tomography (PET) and the Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) while adjusting for covariates, including cross-sectional medial temporal lobe (MTL) tau-PET burden. We selected 352 clinically normal older participants with up to 9 years of PiB-PET and PACC-5 data from the Harvard Aging Brain Study (HABS). Aβ accumulation was associated with subsequent cognitive decline beyond the effects of cross-sectional Aβ burden. Within this model including covariates such as age, sex, and apolipoprotein ε4 (APOEε4) status, we found no evidence supporting previously published associations between cross-sectional tau-PET and cognitive intercept/slope. Short-term Aβ changes are significantly associated with cognitive decline in clinically normal older adults and may eclipse the effect of cross-sectional Aβ and MTL tau. Aβ accumulation is associated with subsequent cognitive decline. High Aβ burden is not the sole metric signaling impending cognitive decline. Contrary to prior work, MTL tau-PET and cognition were not associated in our models. Models of bivariate latent Aβ and cognitive change may eclipse theeffects of MTL tau.

Impact of Monocular Retinal Lesions on Blob Size in Adult Human V1.

We studied the attributes of cytochrome c oxidase (CytOx)-rich blobs and ocular dominance columns (OD) in human V1 associated with monocular retinal lesions. Interblob distance, blob cross-sectional area, OD width, and OD arrangement pattern were analyzed in CytOx-reacted tangential sections of flat-mounted V1 preparations. Monocular deprivation induces differential expression of CytOx in the corresponding ODs in V1. We were thereby able to identify the V1 regions associated with the lesioned area in the retina, assign which OD was associated with each eye, and assign the corresponding blob in Layer III as deprived or nondeprived of visual input. We found that nondeprived blobs are more conspicuously stained than blobs outside the lesioned area. Notably, we found a selective expansion of blobs associated with the nonlesioned eye, whereas blobs associated with the deprived eye showed no significant change in size. Blob size in the latter condition was similar to the one observed in normal participants. These effects were present throughout the representation of the lesion in V1, suggesting that the underlying plasticity mechanisms do not depend on eccentricity. Retinal lesion caused no change in interblob distance, which was comparable to the normal brain (i.e., participants with no retinal lesion). This indicates that blob center is a stable hallmark of cortical organization. Finally, the width of ODs associated with the nonlesioned eye tended to be larger compared with ODs of the lesioned eye. However, this effect did not reach statistical significance. The stability of ODs thereby contrasts with blob plasticity, suggesting that the retinal lesion-triggered imbalance in the thalamocortical projection to Layer IVc has a limited impact on OD CytOx reactivity. On the other hand, we argue that ocular imbalance supports intracortical lateral competition that increases CytOx reactivity in the periblob region associated with the nonlesioned eye, accounting for the blob expansion we observe.

No agreement between expected phoropter Risley prism and prism bar fusional vergences in a prospective cross-sectional study of African school children.

Purpose: To determine the agreement between phoropter Risley prism and prism bar fusional vergence amplitudes in a normative group of school-aged children, aged 8 to 17 years. Method: This prospective cross-sectional study utilized multistage sampling to recruit participants with normal binocular vision. Horizontal fusional vergence amplitudes were measured at distance and near using the phoropter with Risley prisms and the prism bar. Result: The study included 422 normal participants (48.1% male, 51.9% female) with a mean age of 12.39 ± 1.94 years. There were significant differences in the base-in break, base-in recovery, base-out blur, base-out break, and base-out recovery at distance and near between phoropter Risley prism and prism bar fusional vergences (p < 0.05); amplitudes for phoropter Risley prism were higher than that for prism bar. Their mean differences were clinically meaningful except for base-in recovery at distance; however, there was no level of agreement on Bland Altman analysis. Conclusion: Fusional vergence amplitudes measured with the phoropter Risley prism and prism bar should not be considered interchangeable in African schoolchildren.

Impact of statin use in head and neck cancer: a nested case-control study.

Dyslipidemia and statin use are associated with an increased risk of various cancers. However, the association in head and neck cancer (HNC) remains unclear. Therefore, this study aimed to investigate the impact of dyslipidemia and statin use on the development of HNC. Using data from the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2019, we compared two groups HNC patients (n = 1006) and matched control participants (n = 4024) after propensity score overlap weighted balancing. The odds ratios (ORs) for HNC development according to dyslipidemia and statin use duration were assessed using propensity score overlap-weighted multivariable logistic regression. Individuals with untreated dyslipidemia had significantly lower odds of developing HNC than those of normal participants (OR 0.70, 95% confidence interval [CI] 0.59-0.82). Conversely, patients with dyslipidemia who received statin therapy (< 60days) showed a nearly two-fold increase in the odds of HNC (OR 1.94, 95% CI 1.29-2.90). Long-term statin use (≥ 60days) aligned the odds with those of normal participants (OR 0.89, 95% CI 0.76-1.04). The adverse effect of short-term statin use on HNC development requires further study, and long-term statin use for dyslipidemia treatment does not increase the odds of HNC.