Open Access Policy Deposits

This series is automatically populated with publications deposited by UC Davis School of Medicine Department of Neurology researchers in accordance with the University of California’s open access policies. For more information see Open Access Policy Deposits and the UC Publication Management System.

Sort By:

Show:

Long-term Neurological Outcomes in Adults with Traumatic Intracranial Hemorrhage Admitted to ICU versus Floor

(2015)

Introduction: The objective of this study was to compare long-term neurological outcomes in low-risk patients with traumatic intracranial hemorrhage (tICH) admitted to the ICU (intensive care unit) versus patients admitted to the floor.

Methods: This retrospective study was conducted at a Level 1 trauma center from October 1, 2008, to February 1, 2013. We defined low-risk patients as age less than 65 years, isolated head injury, normal admission mental status, and no shift or swelling on initial head CT (computed tomography). Clinical data were abstracted from a trauma registry and linked to a brain injury database. We compared the Extended Glasgow Outcome Scale (GOS-E) score at six months between patients admitted to the ICU and patients admitted to the floor. We did a risk-adjusted analysis of the influence of floor admission on a normal GOS-E.

Results: We identified 151 patients; 45 (30%) were admitted to the floor and 106 (70%) to the ICU. Twenty-three (51%; 95% CI [36-66%]) patients admitted to the floor and 55 (52%; 95% CI [42-62%]) patients admitted to the ICU had a normal GOS-E. On adjusted analysis; the odds ratio for floor admission was 0.77 (95% CI [0.36-1.64]) for a normal GOS-E at six months.

Conclusion: Long-term neurological outcomes in low-risk patients with tICH were not markedly different between patients admitted to the ICU and those admitted to the floor. However, we were unable to demonstrate non-inferiority on adjusted analysis. Future work aimed at a larger, prospective cohort may better evaluate the relative impacts of admission type on outcomes. [West J Emerg Med. 2015;16(2):284–290.]

2 supplemental files

The Importance of Racially and Ethnically Inclusive Gait Speed Reference Values in Individuals 90 Years and Older: LifeAfter90

(2024)

Background and purpose

Clinicians use reference values to contextualize physical performance scores, but data are sparse in individuals 90 years and older and racial/ethnic diversity is limited in existing studies. Gait speed provides valuable information about an individual's health status. Slow gait speed is associated with falls, cognitive decline, and mortality. Here, we report gait speed reference values in a racially/ethnically diverse oldest-old cohort.

Methods

LifeAfter90 is a multiethnic cohort study of individuals 90 years and older. Participants are long-term members of an integrated healthcare delivery system without a dementia diagnosis at enrollment. We assessed gait speed using the 4-m walk test and calculated means, standard deviations, and percentiles by age, sex, assistive device use, and device type. We used linear regression to compare means by sex, age, device use and type, living situation and arrangement, and race/ethnicity.

Results and discussion

The mean age of the 502 participants was 92.9 (range 90.1-102.8) years. Of these, 62.6% were women, 34.7% were college educated, 90.8% lived in a private residence, 20.9% self-reported as Asian, 22.5% as Black, 11.8% as Hispanic, 35.7% as White, and 9.2% as multiple, "other," or declined to state. The overall mean gait speed was 0.54 m/s (women = 0.51 m/s, men = 0.58 m/s). Mean gait speeds were 0.58 m/s, 0.53 m/s, and 0.48 m/s in the 90 to 91, 92 to 93, and 94+ age categories, respectively. In those without a device, mean gait speed was 0.63 m/s compared to 0.40 m/s in those with a device (cane = 0.44 m/s, walker = 0.37 m/s). Mean gait speed was significantly slower in women compared to men, age category 94+ compared to 90 to 91, participants with a device compared to those without, participants with a walker compared to a cane, and Black participants compared to Asian and White participants. However, differences by race/ethnicity were attenuated when chronic health conditions were considered.

Conclusions

Reference values developed from this multiethnic 90+ cohort will help clinicians interpret gait speed measures and tailor recommendations toward a 90+ population that is growing in number and in racial/ethnic diversity.

Cover page of Gender differences in the association between education and late‐life cognitive function in the LifeAfter90 Study: A multiethnic cohort of the oldest–old

Gender differences in the association between education and late‐life cognitive function in the LifeAfter90 Study: A multiethnic cohort of the oldest–old

(2024)

Introduction

Few studies have examined the relationship between education and cognition among the oldest-old.

Methods

Cognitive assessments were conducted biannually for 803 participants (62.6% women) of LifeAfter90, a longitudinal study of individuals ≥ 90 years old. Gender differences in associations between education (< high school, high school, some college, and ≥ college) and cognition (verbal episodic memory, semantic memory, and executive function) were examined at baseline and longitudinally using linear mixed models.

Results

Higher education levels were associated with better cognitive performance at baseline for both men and women. College completion was more strongly associated with better baseline executive function among women. Education-cognition associations for baseline verbal episodic memory and baseline semantic memory did not differ by gender. Education was not associated with a decline in any domain-specific cognitive scores, regardless of gender.

Discussion

Education is associated with cognitive function among the oldest-old and varies by gender and cognitive domain at baseline but not over time.

Highlights

In the oldest-old, higher education was associated with better cognitive function. College completion was more strongly associated with executive function in women. Education was not associated with cognitive decline after age 90 regardless of gender. Improving education could decrease gaps in cognitive level among older individuals.

Large-scale sub-5-nm vertical transistors by van der Waals integration.

(2024)

Vertical field effect transistor (VFET), in which the semiconductor is sandwiched between source/drain electrodes and the channel length is simply determined by the semiconductor thickness, has demonstrated promising potential for short channel devices. However, despite extensive efforts over the past decade, scalable methods to fabricate ultra-short channel VFETs remain challenging. Here, we demonstrate a layer-by-layer transfer process of large-scale indium gallium zinc oxide (IGZO) semiconductor arrays and metal electrodes, and realize large-scale VFETs with ultra-short channel length and high device performance. Within this process, the oxide semiconductor could be pre-deposited on a sacrificial wafer, and then physically released and sandwiched between metals, maintaining the intrinsic properties of ultra-scaled vertical channel. Based on this lamination process, we realize 2 inch-scale VFETs with channel length down to 4 nm, on-current over 800 A/cm2, and highest on-off ratio up to 2 × 105, which is over two orders of magnitude higher compared to control samples without laminating process. Our study not only represents the optimization of VFETs performance and scalability at the same time, but also offers a method of transfer large-scale oxide arrays, providing interesting implication for ultra-thin vertical devices.

Cover page of Associations of Amyloid Burden, White Matter Hyperintensities, and Hippocampal Volume With Cognitive Trajectories in the 90+ Study

Associations of Amyloid Burden, White Matter Hyperintensities, and Hippocampal Volume With Cognitive Trajectories in the 90+ Study

(2024)

Background and objectives

Amyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old.

Methods

This was a longitudinal, observational community-based cohort study. We included participants with ¹⁸F-florbetapir PET and MRI data from the 90+ Study. Amyloid load was measured using the standardized uptake value ratio in the precuneus/posterior cingulate with eroded white matter mask as reference. WMH volume was log-transformed. All imaging measures were standardized using sample means and SDs. HV and log-WMH volume were normalized by total intracranial volume using the residual approach. Global cognitive performance was measured by the Mini-Mental State Examination (MMSE) and modified MMSE (3MS) tests, repeated every 6 months. We used linear mixed-effects models with random intercepts; random slopes; and interaction between time, time squared, and imaging variables to estimate the associations of imaging variables with cognitive level and cognitive decline. Models were adjusted for demographics, APOE genotype, and health behaviors.

Results

The sample included 192 participants. The mean age was 92.9 years, 125 (65.1%) were female, 71 (37.0%) achieved a degree beyond college, and the median follow-up time was 3.0 years. A higher amyloid load was associated with a lower cognitive level (β_MMSE = -0.82, 95% CI -1.17 to -0.46; β_3MS = -2.77, 95% CI -3.69 to -1.84). A 1-SD decrease in HV was associated with a 0.70-point decrease in the MMSE score (95% CI -1.14 to -0.27) and a 2.27-point decrease in the 3MS score (95% CI -3.40 to -1.14). Clear nonlinear cognitive trajectories were detected. A higher amyloid burden and smaller HV were associated with faster cognitive decline. WMH volume was not significantly associated with cognitive level or decline.

Discussion

Amyloid burden and hippocampal atrophy are associated with both cognitive level and cognitive decline in the oldest old. Our findings shed light on how different pathologies contributed to driving cognitive function in the oldest old.

Congenital myasthenic syndrome secondary to pathogenic variants in the SLC5A7 gene: report of two cases.

(2024)

BACKGROUND: Congenital Myasthenic Syndromes (CMS) are rare genetic diseases, which share as a common denominator muscle fatigability due to failure of neuromuscular transmission. A distinctive clinical feature of presynaptic CMS variants caused by defects of the synthesis of acetylcholine is the association with life-threatening episodes of apnea. One of these variants is caused by mutations in the SLC5A7 gene, which encodes the sodium-dependent HC-3 high-affinity choline transporter 1 (CHT1). To our knowledge there are no published cases of this CMS type in Latin America. CASE PRESENTATION: We present two cases of CHT1-CMS. Both patients were males presenting with repeated episodes of apnea, hypotonia, weakness, ptosis, mild ophthalmoparesis, and bulbar deficit. The first case also presented one isolated seizure, while the second case showed global developmental delay. Both cases, exhibited incomplete improvement with treatment with pyridostigmine. CONCLUSIONS: This report emphasizes the broad incidence of CMS with episodic apnea caused by mutations in the SLC5A7 gene and the frequent association of this condition with serious manifestations of central nervous system involvement.

Temporal progression of tau pathology and neuroinflammation in a rhesus monkey model of Alzheimer's disease

(2024)

Introduction

The understanding of the pathological events in Alzheimer's disease (AD) has advanced dramatically, but the successful translation from rodent models into efficient human therapies is still problematic.

Methods

To examine how tau pathology can develop in the primate brain, we injected 12 macaques with a dual tau mutation (P301L/S320F) into the entorhinal cortex (ERC). An investigation was performed using high-resolution microscopy, magnetic resonance imaging (MRI), positron emission tomography (PET), and fluid biomarkers to determine the temporal progression of the pathology 3 and 6 months after the injection.

Results

Using quantitative microscopy targeting markers for neurodegeneration and neuroinflammation, as well as fluid and imaging biomarkers, we detailed the progression of misfolded tau spreading and the consequential inflammatory response induced by glial cells.

Discussion

By combining the analysis of several in vivo biomarkers with extensive brain microscopy analysis, we described the initial steps of misfolded tau spreading and neuroinflammation in a monkey model highly translatable to AD patients.

Highlights

Dual tau mutation delivery in the entorhinal cortex induces progressive tau pathology in rhesus macaques. Exogenous human 4R-tau coaptates monkey 3R-tau during transneuronal spread, in a prion-like manner. Neuroinflammatory response is coordinated by microglia and astrocytes in response to tau pathology, with microglia targeting early tau pathology, while astrocytes engaged later in the progression, coincident with neuronal death. Monthly collection of CSF and plasma revealed a profile of changes in several AD core biomarkers, reflective of neurodegeneration and neuroinflammation as early as 1 month after injection.

High-density vertical sidewall MoS2 transistors through T-shape vertical lamination.

(2024)

Vertical transistors, in which the source and drain are aligned vertically and the current flow is normal to the wafer surface, have attracted considerable attention recently. However, the realization of high-density vertical transistors is challenging, and could be largely attributed to the incompatibility between vertical structures and conventional lateral fabrication processes. Here we report a T-shape lamination approach for realizing high-density vertical sidewall transistors, where lateral transistors could be pre-fabricated on planar substrates first and then laminated onto vertical substrates using T-shape stamps, hence overcoming the incompatibility between planar processes and vertical structures. Based on this technique, we vertically stacked 60 MoS2 transistors within a small vertical footprint, corresponding to a device density over 108 cm-2. Furthermore, we demonstrate two approaches for scalable fabrication of vertical sidewall transistor arrays, including simultaneous lamination onto multiple vertical substrates, as well as on the same vertical substrate using multi-cycle layer-by-layer laminations.

Site-specific regulation of RNA editing with ribose-modified nucleoside analogs in ADAR guide strands

(2024)

Adenosine Deaminases Acting on RNA (ADARs) are enzymes that catalyze the conversion of adenosine to inosine in RNA duplexes. These enzymes can be harnessed to correct disease-causing G-to-A mutations in the transcriptome because inosine is translated as guanosine. Guide RNAs (gRNAs) can be used to direct the ADAR reaction to specific sites. Chemical modification of ADAR guide strands is required to facilitate delivery, increase metabolic stability, and increase the efficiency and selectivity of the editing reaction. Here, we show the ADAR reaction is highly sensitive to ribose modifications (e.g. 4'-C-methylation and Locked Nucleic Acid (LNA) substitution) at specific positions within the guide strand. Our studies were enabled by the synthesis of RNA containing a new, ribose-modified nucleoside analog (4'-C-methyladenosine). Importantly, the ADAR reaction is potently inhibited by LNA or 4'-C-methylation at different positions in the ADAR guide. While LNA at guide strand positions -1 and -2 block the ADAR reaction, 4'-C-methylation only inhibits at the -2 position. These effects are rationalized using high-resolution structures of ADAR-RNA complexes. This work sheds additional light on the mechanism of ADAR deamination and aids in the design of highly selective ADAR guide strands for therapeutic editing using chemically modified RNA.

Measurement invariance of a neuropsychological battery across urban and rural older adults in Costa Rica

(2024)

This study evaluated the measurement invariance of a neuropsychological battery across rural and urban older adults from Costa Rica. Rural and urban older adults (N = 295) from the Epidemiology and Development of Alzheimer's Disease (EDAD) study in Costa Rica were assessed. The baseline factor model for the EDAD neuropsychological measures was identified with nine neuropsychological measures and three cognitive constructs: Verbal Memory, Spatial Reasoning, and Cognitive Flexibility. Measurement and structural invariance were established, and, then, group comparisons of the latent cognitive factors were conducted to explore regional disparities. The findings showed that most of the neuropsychological tests in EDAD can be directly compared across the groups, allowing for cognitive constructs comparisons. The rural sample showed a disadvantage in the Spatial Reasoning and Cognitive Flexibility abilities. When age and education were included in the models, differences between the regions disappeared. Having more years of education was associated with higher cognitive abilities, with a larger effect for the rural group. Norms for Costa Rican older adults should consider age and education adjustments. This study contributes to the growing area of measurement invariance in neuropsychological assessment as it highlights the importance of examining the comparability of assessment measures across different cultural groups.

Department of Neurology, UC Davis School of Medicine