Assessments and observations of infection prevention and control practices in US outpatient hemodialysis facilities, 2015-2018: important opportunities for improvement.

Infections cause substantial morbidity and mortality among patients receiving care in outpatient hemodialysis facilities. We describe comprehensive infection prevention assessments by US public health departments using standardized interview and observation tools. Results demonstrated how facility layouts can undermine infection prevention and that clinical practices often fall short of policies.

White matter tract integrity in isolated oral clefts: relationship to cognition and reading skills.

Children with isolated cleft of the lip and/or palate (iCL/P) have been shown to be at risk for impaired reading ability. Structural and functional neuroimaging studies have revealed subtle morphological and functional abnormalities correlated to cognition and reading ability. However, the integrity of white matter tracts and their potential relationship to reading performance in iCL/P is under-studied. The purpose of the present study was to evaluate white matter integrity related to cognition and reading skills among participants with and without iCL/P. Data from two cross-sectional, case/control studies with similar neuropsychological batteries and diffusion tensor imaging (DTI) protocols were combined. The final sample included 210 participants (ages 7 to 27 years). Group and sex differences in fractional anisotropy (FA) values were examined between participants with (n = 105) and without (n = 105) iCL/P. Potential associations between FA values and age, cognition, and reading skills were also evaluated separately by group and sex. Sex effects were prominent in association and projection fibers, and effects of cleft status were found in association fibers and cerebellar regions, with isolated associations to reading skills. Findings provide preliminary understanding of microstructural associations to cognitive and reading performance among children, adolescents, and young adults with iCL/P.

Circadian timing, melatonin and hippocampal volume in later-life adults.

Hippocampal atrophy is a prominent neurodegenerative feature of Alzheimer's disease and related dementias. Alterations in circadian rhythms can exacerbate cognitive aging and neurodegeneration. This study aimed to examine how dim light melatonin onset and melatonin levels are associated with hippocampal volume in cognitively healthy individuals. We studied data from 52 later-life adults (mean age ± SD = 70.0 ± 6.3 years). T1-weighted anatomical images from 3.0 T magnetic resonance imaging data were collected and processed using the BRAINSTools toolbox. Dim light melatonin onset was used to assess circadian timing. The area under the curve was calculated to quantify melatonin concentration levels 6 hr before bedtime, and 14-day wrist actigraphy data were used to assess habitual bedtime. Multiple linear regression modelling with hippocampal volume as the dependent variable was used to analyse the data adjusting for age and sex. The average dim light melatonin onset was 19:45 hours (SD = 84 min), and area under the curve of melatonin levels 6 hr before habitual bedtime was 38.4 pg ml-1 × hr (SD = 29.3). We found that later dim light melatonin onset time (b = 0.16, p = 0.005) and greater area under the curve of melatonin levels 6 hr before habitual bedtime (b = 0.05, p = 0.046) were associated with greater adjusted hippocampal volume. The time between dim light melatonin onset and the midpoint of sleep timing was not associated with hippocampal volume. The findings suggest that earlier circadian timing (dim light melatonin onset) and reduced melatonin may be associated with reduced hippocampal volume in older adults. Future research will help researchers utilize circadian rhythm information to delay brain aging.

Deception Cues During High-Risk Situations: 911 Homicide Calls.

During everyday interactions, cues tend to be weakly related to deception. However, there are theoretical reasons to suspect that such cues will be more prominent during high-risk interactions. The current study explored deception cues during one particular high-risk interaction-911 homicide calls placed by adults. In Sample 1, judges coded 911 homicide calls (n = 82) by Q-sorting 86 cues. Results indicated that deceptive callers tended to display emotional cues (e.g., self-dramatizing, moody, worried, emotional, nervous), appeared overwhelmed, and related narratives that lacked structure, clarity, and focus. Judges coded a separate sample of 911 calls (n = 64), and deception scores were computed using a template-matching approach based on the findings from Sample 1. Results indicated that deceptive 911 callers had higher deception scores than honest callers. The effect sizes yielded in this study highlight the relevance of deception cues during high-risk interactions and the usefulness of the person-centered Q-sort method.

Associations between neurofilament light-chain protein, brain structure, and chronic kidney disease.

BACKGROUND: Neurofilament light-chain (NfL) protein is a blood-based marker of neuroaxonal injury. We sought to (1) compare plasma NfL levels in children with chronic kidney disease (CKD) and healthy peers, (2) characterize the relationship between NfL level and kidney function, and (3) evaluate NfL as a predictor of abnormal brain structure in CKD. METHODS: Sixteen children with CKD due to congenital kidney anomalies and 23 typically developing peers were included. Plasma NfL was quantified using single-molecule array immunoassay. Participants underwent structural magnetic resonance imaging. Multiple linear regression models were used to evaluate the association between plasma NfL levels, kidney function, and brain structure. RESULTS: An age × group interaction was identified whereby NfL levels increased with age in the CKD group only (estimate = 0.65; confidence interval (CI) = 0.08-1.22; p = 0.026). Decreased kidney function was associated with higher NfL levels (estimate = -0.10; CI = -0.16 to -0.04; p = 0.003). Lower cerebellar gray matter volume predicted increased plasma NfL levels (estimate = -0.00024; CI = -0.00039 to 0.00009; p = 0.004) within the CKD group. CONCLUSIONS: Children with CKD show accelerated age-related increases in NfL levels. NfL level is associated with lower kidney function and abnormal brain structure in CKD. IMPACT: NfL is a component of the neuronal cytoskeleton providing structural axonal support. Elevated NfL has been described in relation to gray and white matter brain volume loss. We have previously described the abnormal cerebellar gray matter in CKD. We explored the relationship between NfL, CKD, and brain volume. There is an accelerated, age-related increase in NfL level in CKD. Within the CKD sample, NfL level is associated with abnormal kidney function and brain structure. Decreased kidney function may be linked to abnormal neuronal integrity in pediatric CKD.

Global and Regional White Matter Fractional Anisotropy in Children with Chronic Kidney Disease.

OBJECTIVE: To investigate the associations between neurocognition and white matter integrity in children with chronic kidney disease (CKD). STUDY DESIGN: This cross-sectional study included 17 boys (age 6-16 years) with a diagnosis of mild to moderate (stages 1-3, nondialysis/nontransplant) CKD because of congenital anomalies of the kidney and urinary tract and 20 typically developing community controls. Participants underwent 3T neuroimaging and diffusion-weighted magnetic resonance imaging to assess white matter fractional anisotropy. Multivariable linear regression models were used to evaluate the impact of each group (controls vs CKD) on white matter fractional anisotropy, adjusting for age. Associations between white matter fractional anisotropy and neurocognitive abilities within the CKD group were also evaluated using regression models that were adjusted for age. The false discovery rate was used to account for multiple comparisons; wherein false discovery values <0.10 were considered significant. RESULTS: Global white matter fractional anisotropy was reduced in patients with CKD relative to controls (standardized estimate = -0.38, 95% CI -0.69:-0.07), driven by reductions within the body of the corpus callosum (standardized estimate = -0.44, 95% CI -0.75:-0.13), cerebral peduncle (SE = -0.37, 95% CI -0.67:-0.07), cingulum (hippocampus) (standardized estimate = -0.45, 95% CI -0.75:-0.14), and posterior limb of the internal capsule (standardized estimate = -0.46, 95% CI -0.76:-0.15). Medical variables and neurocognitive abilities were not significantly associated with white matter fractional anisotropy. CONCLUSIONS: White matter development is vulnerable in children with CKD because of congenital causes, even prior to the need for dialysis or transplantation.

Attention capture by episodic long-term memory.

Everyday behavior depends upon the operation of concurrent cognitive processes. In visual search, studies that examine memory-attention interactions have indicated that long-term memory facilitates search for a target (e.g., contextual cueing), but the potential for memories to capture attention and decrease search efficiency has not been investigated. To address this gap in the literature, five experiments were conducted to examine whether task-irrelevant encoded objects might capture attention. In each experiment, participants encoded scene-object pairs. Then, in a visual search task, 6-object search displays were presented and participants were told to make a single saccade to targets defined by shape (e.g., diamond among differently colored circles; Experiments 1, 4, and 5) or by color (e.g., blue shape among differently shaped gray objects; Experiments 2 and 3). Sometimes, one of the distractors was from the encoded set, and occasionally the scene that had been paired with that object was presented prior to the search display. Results indicated that eye movements were made, in error, more often to encoded distractors than to baseline distractors, and that this effect was greatest when the corresponding scene was presented prior to search. When capture did occur, participants looked longer at encoded distractors if scenes had been presented, an effect that we attribute to the representational match between a retrieved associate and the identity of the encoded distractor in the search display. In addition, the presence of a scene resulted in slower saccade deployment when participants made first saccades to targets, as instructed. Experiments 4 and 5 suggest that this slowdown may be due to the relatively rare and therefore, surprising, appearance of visual stimulus information prior to search. Collectively, results suggest that information encoded into episodic memory can capture attention, which is consistent with the recent proposal that selection history can guide attentional selection.

Angiotensin II Type 2 Receptor-Expressing Neurons in the Central Amygdala Influence Fear-Related Behavior.

BACKGROUND: The renin-angiotensin system has been implicated in posttraumatic stress disorder; however, the mechanisms responsible for this connection and the therapeutic potential of targeting the renin-angiotensin system in posttraumatic stress disorder remain unknown. Using an angiotensin receptor bacterial artificial chromosome (BAC) and enhanced green fluorescent protein (eGFP) reporter mouse, combined with neuroanatomical, pharmacological, and behavioral approaches, we examined the role of angiotensin II type 2 receptor (AT2R) in fear-related behavior. METHODS: Dual immunohistochemistry with retrograde labeling was used to characterize AT2R-eGFP+ cells in the amygdala of the AT2R-eGFP-BAC reporter mouse. Pavlovian fear conditioning and behavioral pharmacological analyses were used to demonstrate the effects of AT2R activation on fear memory in male C57BL/6 mice. RESULTS: AT2R-eGFP+ neurons in the amygdala were predominantly expressed in the medial amygdala and the medial division of the central amygdala (CeM), with little AT2R-eGFP expression in the basolateral amygdala or lateral division of the central amygdala. Characterization of AT2R-eGFP+ neurons in the CeM demonstrated distinct localization to gamma-aminobutyric acidergic projection neurons. Mice receiving acute intra-central amygdala injections of the selective AT2R agonist compound 21 prior to tests for cued or contextual fear expression displayed less freezing. Retrograde labeling of AT2R-eGFP+ neurons projecting to the periaqueductal gray revealed AT2R-eGFP+ neuronal projections from the CeM to the periaqueductal gray, a key brain structure mediating fear-related freezing. CONCLUSIONS: These findings suggest that CeM AT2R-expressing neurons can modulate central amygdala outputs that play a role in fear expression, providing new evidence for a novel angiotensinergic circuit in the regulation of fear.

A peripheral immune response to remembering trauma contributes to the maintenance of fear memory in mice.

Alterations in peripheral immune markers are observed in individuals with post-traumatic stress disorder (PTSD). PTSD is characterized in part by impaired extinction of fear memory for a traumatic experience. We hypothesized that fear memory extinction is regulated by immune signaling stimulated when fear memory is retrieved. The relationship between fear memory and the peripheral immune response was tested using auditory Pavlovian fear conditioning in mice. Memory for the association was quantified by the amount of conditioned freezing exhibited in response to the conditioned stimulus (CS), extinction and time-dependent changes in circulating inflammatory cytokines. Brief extinction training with 12 CS rapidly and acutely increased circulating levels of the cytokine interleukin-6 (IL-6), downstream IL-6 signaling, other IL-6 related pro-inflammatory cytokines. Transgenic manipulations or neutralizing antibodies that inhibit IL-6 activity did not affect conditioned freezing during the acquisition of fear conditioning or extinction but significantly reduced conditioned freezing 24 h after extinction training with 12 CS. Conversely, conditioned freezing after extinction training was unchanged by IL-6 inhibition when 40 CS were used during the extinction training session. In addition to effectively diminishing conditioned freezing, extinction training with 40 CS also diminished the subsequent IL-6 response to the CS. These data demonstrate that IL-6 released following fear memory retrieval contributes to the maintenance of that fear memory and that this effect is extinction dependent. These findings extend the current understanding for the role of the immune system in PTSD and suggest that IL-6 and other IL-6 related pro-inflammatory cytokines may contribute to the persistence of fear memory in PTSD where fear memory extinction is impaired.

Eye movements are captured by a perceptually simple conditioned stimulus in the absence of explicit contingency knowledge.

Past reports suggest that threatening materials can impact the efficiency of goal-directed behavior. However, questions remain about whether a conditional stimulus (CS) can capture attention as previous results may have been influenced by voluntary prioritization of a to-be-ignored CS. In 2 experiments, eye tracking was used to evaluate whether neutral, perceptually simple materials capture attention when they take on aversive properties via probabilistic fear conditioning with strict methods in place to eliminate voluntary CS prioritization. During training, participants attempted to fixate search targets (i.e., horizontally or vertically oriented rectangles) as quickly as possible to avoid shock. In reality, shock administration was related to rectangle orientation so that 1 rectangle (CS+) predicted shock more often than the other (CS-). Subsequently rectangles became distractors and were to be ignored. At this point, participants were instructed to fixate a new target and incidences of CS capture were examined. Results showed that saccades were made more quickly to the CS+ than the CS- as training progressed, and that oculomotor capture by irrelevant rectangles occurred more often for the CS+ than the CS-. An independent physiological index (skin conductance response) confirmed that contingencies had been learned, as SCR magnitude was greater for CS+ than CS- trials early in the test phase. These effects were documented despite the absence of explicit contingency knowledge, assessed using a postexperimental questionnaire. Collectively, these outcomes indicate that a CS can capture attention despite being task-irrelevant, and that these effects do not depend on conscious awareness of learned contingencies. (PsycINFO Database Record

Eye Movements Index Implicit Memory Expression in Fear Conditioning.

The role of contingency awareness in simple associative learning experiments with human participants is currently debated. Since prior work suggests that eye movements can index mnemonic processes that occur without awareness, we used eye tracking to better understand the role of awareness in learning aversive Pavlovian conditioning. A complex real-world scene containing four embedded household items was presented to participants while skin conductance, eye movements, and pupil size were recorded. One item embedded in the scene served as the conditional stimulus (CS). One exemplar of that item (e.g. a white pot) was paired with shock 100 percent of the time (CS+) while a second exemplar (e.g. a gray pot) was never paired with shock (CS-). The remaining items were paired with shock on half of the trials. Participants rated their expectation of receiving a shock during each trial, and these expectancy ratings were used to identify when (i.e. on what trial) each participant became aware of the programmed contingencies. Disproportionate viewing of the CS was found both before and after explicit contingency awareness, and patterns of viewing distinguished the CS+ from the CS-. These observations are consistent with "dual process" models of fear conditioning, as they indicate that learning can be expressed in patterns of viewing prior to explicit contingency awareness.

Functionally distinct amygdala subregions identified using DTI and high-resolution fMRI.

Although the amygdala is often directly linked with fear and emotion, amygdala neurons are activated by a wide variety of emotional and non-emotional stimuli. Different subregions within the amygdala may be engaged preferentially by different aspects of emotional and non-emotional tasks. To test this hypothesis, we measured and compared the effects of novelty and fear on amygdala activity. We used high-resolution blood oxygenation level-dependent (BOLD) imaging and streamline tractography to subdivide the amygdala into three distinct functional subunits. We identified a laterobasal subregion connected with the visual cortex that responds generally to visual stimuli, a non-projecting region that responds to salient visual stimuli, and a centromedial subregion connected with the diencephalon that responds only when a visual stimulus predicts an aversive outcome. We provide anatomical and functional support for a model of amygdala function where information enters through the laterobasal subregion, is processed by intrinsic circuits in the interspersed tissue, and is then passed to the centromedial subregion, where activation leads to behavioral output.