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Cover page of The dose makes the poison: Non-linear behavioural response to CO<sub>2</sub>-induced aquatic acidification in zebrafish (Danio rerio).

The dose makes the poison: Non-linear behavioural response to CO2-induced aquatic acidification in zebrafish (Danio rerio).

(2021)

CO2-induced aquatic acidification is predicted to affect fish neuronal GABAA receptors leading to widespread behavioural alterations. However, the large variability in the magnitude and direction of behavioural responses suggests substantial species-specific CO2 threshold differences, life history and parental acclimation effects, experimental artifacts, or a combination of these factors. As an established model organism, zebrafish (Danio rerio) can be reared under stable conditions for multiple generations, which may help control for some of the variability observed in wild-caught fishes. Here, we used two standardized tests to investigate the effect of 1-week acclimatization to four pCO2 levels on zebrafish anxiety-like behaviour, exploratory behaviour, and locomotion. Fish acclimatized to 900 μatm CO2 demonstrated increased anxiety-like behaviour compared to control fish (~480 μatm), however, the behaviour of fish exposed to 2200 μatm CO2 was indistinguishable from that of controls. In addition, fish acclimatized to 4200 μatm CO2 had decreased anxiety-like behaviour; i.e. the opposite response than the 900 μatm CO2 treatment. On the other hand, exploratory behaviour did not differ among any of the pCO2 exposures that were tested. Thus, zebrafish behavioural responses to elevated pCO2 are not linear; with potential important implications for physiological, environmental, and aquatic acidification studies.

Cover page of Multilevel Barriers to HIV&nbsp;PrEP Uptake and Adherence Among Black and Hispanic/Latinx Transgender Women in Southern California.

Multilevel Barriers to HIV PrEP Uptake and Adherence Among Black and Hispanic/Latinx Transgender Women in Southern California.

(2021)

Black and Hispanic/Latinx transgender women in the United States (U.S.) are disproportionately affected by HIV. Pre-exposure prophylaxis (PrEP) reduces risk of HIV infection but PrEP uptake remains low among Black and Hispanic/Latinx transgender women. Between July 2018 and August 2019, we conducted individual interviews with 30 Black and Hispanic/Latinx transgender women who were prescribed PrEP through a PrEP demonstration project and 10 healthcare providers who provide PrEP services to transgender women in Los Angeles and San Diego, California. The interviews assessed general attitudes, experiences, and beliefs about PrEP as well as individual-, interpersonal-, community-, and structural-level barriers to PrEP uptake and adherence. PrEP adherence was assessed by collecting quantitative intracellular tenofovir-diphosphate (TFV-DP) levels in retrospect on batched, banked dried blood spot (DBS) samples. We utilized qualitative content analysis to identify themes from the interviews. Findings indicated the presence of individual-level barriers including cost concerns, mental health issues, substance use, and concerns about PrEP side effects including hormone interaction. Interpersonal-level barriers included the influence of intimate/romantic partners and the impact of patient-provider communication. Community-level barriers consisted of experiencing stigma and negative community opinions about PrEP use as well as having negative experiences in healthcare settings. Structural-level barriers included unreliable transportation, employment, and housing insecurity. Interventions aiming to increase PrEP uptake and adherence among Black and Hispanic/Latinx transgender women in the U.S. should employ a multilevel approach to addressing the needs of transgender women, especially the structural barriers that have greatly limited the use of PrEP.

The ketogenic diet raises brain oxygen levels, attenuates postictal hypoxia, and protects against learning impairments.

(2021)

Objectives

A prolonged vasoconstriction/hypoperfusion/hypoxic event follows self-terminating focal seizures. The ketogenic diet (KD) has demonstrated efficacy as a metabolic treatment for intractable epilepsy and other disorders but its effect on local brain oxygen levels is completely unknown. This study investigated the effects of the KD on tissue oxygenation in the hippocampus before and after electrically elicited (kindled) seizures and whether it could protect against a seizure-induced learning impairment. We also examined the effects of the ketone β-hydroxybutyrate (BHB) as a potential underlying mechanism.

Methods

Male and female rats were given access to one of three diet protocols 2 weeks prior to the initiation of seizures: KD, caloric restricted standard chow, and ad libitum standard chow. Dorsal hippocampal oxygen levels were measured prior to initiation of diets as well as before and after a 10-day kindling paradigm. Male rats were then tested on a novel object recognition task to assess postictal learning impairments. In a separate cohort, BHB was administered 30 min prior to seizure elicitation to determine whether it influenced oxygen dynamics.

Results

The KD increased dorsal hippocampal oxygen levels, ameliorated postictal hypoxia, and prevented postictal learning impairments. Acute BHB administration did not alter oxygen levels before or after seizures.

Interpretation

The ketogenic diet raised brain oxygen levels and attenuated severe postictal hypoxia likely through a mechanism independent of ketosis and shows promise as a non-pharmacological treatment to prevent the postictal state.

Sex differences for phenotype in pathologically defined dementia with Lewy bodies.

(2021)

Introduction

Sex differences in dementia with Lewy bodies (DLB) have been reported in clinically defined cohorts; however, clinical diagnostic accuracy in DLB is suboptimal and phenotypic differences have not been assessed in pathologically confirmed participants.

Methods

Core DLB features were compared across 55 women and 156 men with pathologically defined DLB in the National Alzheimer's Coordinating Center. These analyses were repeated for 55 women and 55 men matched for age, education and tau burden.

Results

In the total sample, women died older, had fewer years of education, had higher tau burden but were less likely to be diagnosed with dementia and clinical DLB. In the matched sample, visual hallucinations continued to be less common in women, and fewer women met clinical DLB criteria.

Discussion

Sex impacts clinical manifestations of underlying pathologies in DLB. Despite similar underlying Lewy body pathology, women are less likely to manifest core DLB features and may be clinically underdiagnosed.

Cover page of Longitudinal Pooling &amp; Consistency Regularization to Model Disease Progression From MRIs.

Longitudinal Pooling & Consistency Regularization to Model Disease Progression From MRIs.

(2021)

Many neurological diseases are characterized by gradual deterioration of brain structure andfunction. Large longitudinal MRI datasets have revealed such deterioration, in part, by applying machine and deep learning to predict diagnosis. A popular approach is to apply Convolutional Neural Networks (CNN) to extract informative features from each visit of the longitudinal MRI and then use those features to classify each visit via Recurrent Neural Networks (RNNs). Such modeling neglects the progressive nature of the disease, which may result in clinically implausible classifications across visits. To avoid this issue, we propose to combine features across visits by coupling feature extraction with a novel longitudinal pooling layer and enforce consistency of the classification across visits in line with disease progression. We evaluate the proposed method on the longitudinal structural MRIs from three neuroimaging datasets: Alzheimer's Disease Neuroimaging Initiative (ADNI, N=404), a dataset composed of 274 normal controls and 329 patients with Alcohol Use Disorder (AUD), and 255 youths from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). In allthree experiments our method is superior to other widely used approaches for longitudinal classification thus making a unique contribution towards more accurate tracking of the impact of conditions on the brain. The code is available at https://github.com/ouyangjiahong/longitudinal-pooling.

Cover page of Broadband infrared photodetection using a narrow bandgap conjugated polymer.

Broadband infrared photodetection using a narrow bandgap conjugated polymer.

(2021)

Photodetection spanning the short-, mid-, and long-wave infrared (SWIR-LWIR) underpins modern science and technology. Devices using state-of-the-art narrow bandgap semiconductors require complex manufacturing, high costs, and cooling requirements that remain prohibitive for many applications. We report high-performance infrared photodetection from a donor-acceptor conjugated polymer with broadband SWIR-LWIR operation. Electronic correlations within the π-conjugated backbone promote a high-spin ground state, narrow bandgap, long-wavelength absorption, and intrinsic electrical conductivity. These previously unobserved attributes enabled the fabrication of a thin-film photoconductive detector from solution, which demonstrates specific detectivities greater than 2.10 × 109 Jones. These room temperature detectivities closely approach those of cooled epitaxial devices. This work provides a fundamentally new platform for broadly applicable, low-cost, ambient temperature infrared optoelectronics.