Human iPSC-derived myelinating organoids and globoid cells to study Krabbe Disease.

Krabbe disease (Kd) is a lysosomal storage disorder (LSD) caused by the deficiency of the lysosomal galactosylceramidase (GALC) which cleaves the myelin enriched lipid galactosylceramide (GalCer). Accumulated GalCer is catabolized into the cytotoxic lipid psychosine that causes myelinating cells death and demyelination which recruits microglia/macrophages that fail to digest myelin debris and become globoid cells. Here, to understand the pathological mechanisms of Kd, we used induced pluripotent stem cells (iPSCs) from Kd patients to produce myelinating organoids and microglia. We show that Kd organoids have no obvious defects in neurogenesis, astrogenesis, and oligodendrogenesis but manifest early myelination defects. Specifically, Kd organoids showed shorter but a similar number of myelin internodes than Controls at the peak of myelination and a reduced number and shorter internodes at a later time point. Interestingly, myelin is affected in the absence of autophagy and mTOR pathway dysregulation, suggesting lack of lysosomal dysfunction which makes this organoid model a very valuable tool to study the early events that drive demyelination in Kd. Kd iPSC-derived microglia show a marginal rate of globoid cell formation under normal culture conditions that is drastically increased upon GalCer feeding. Under normal culture conditions, Kd microglia show a minor LAMP1 content decrease and a slight increase in the autophagy protein LC3B. Upon GalCer feeding, Kd cells show accumulation of autophagy proteins and strong LAMP1 reduction that at a later time point are reverted showing the compensatory capabilities of globoid cells. Altogether, this supports the value of our cultures as tools to study the mechanisms that drive globoid cell formation and the compensatory mechanism in play to overcome GalCer accumulation in Kd.

Arkansas crisis stabilization unit guests: Baseline characteristics from a longitudinal cohort study.

Crisis Stabilization Units (CSUs) are short-term residential facilities that provide care to people experiencing mental health crises, seeking to reduce reliance on local emergency departments and avoid unnecessary jail detention. Despite these intentions, there is little foundational literature to support research on CSU efficacy and a dearth of research on the sociodemographic characteristics and specific needs of CSU patients. Here, we recruited and surveyed 208 participants admitted to one of two focal Arkansas CSUs on their sociodemographic characteristics, justice-involvement, mental health, substance use, and health care utilization. Results revealed that participants were mostly unemployed (68.16%), low-income (72.34%), and experiencing insecure housing (33.33%). They reported extensive justice-involvement (85.57%), high rates of clinically significant mental illness symptom severity (77.00% for anxious symptoms; 78.33% for depressive symptoms; 79.40% for traumatic stress symptoms), and recent substance use (73.34%). Recent engagement with other medical services was common, though more participants reported visiting an emergency department (42.23%) than did receiving outpatient medical care (26.73%). While research on CSU patient outcomes is needed, our results indicate that CSUs have the potential to be an essential part of the health care continuum by serving a population with multiple, intersecting needs and addressing a deficit in community-based crisis care. Continued investigation of community-based crisis intervention services is critical to bridging the gap between vital behavioral health resources and the populations in need of them. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The positive dimension of schizotypy is associated with self-report measures of autobiographical memory and future thinking but not experimenter-scored indices.

ABSTRACTThe ability to remember our past and to imagine the future are critical to our sense of self. Previous research has indicated that they are disrupted in schizophrenia. However, it is unclear (i) whether this is found when examining experimenter-scored indices of content and/or participants' self-report of phenomenological characteristics, and (ii) how these abilities might be related to symptoms. This study sought to address these questions by taking a dimensional approach and measuring positive and negative schizotypal experiences in healthy people (n = 90). Participants were given cue words. For some, they remembered an event from the past and for others they generated an event in the future. No significant relationships were found with any aspect of schizotypy when participants' descriptions were scored by the experimenter according to a standardised episodic content measure. In contrast, several significant positive correlations were observed for past memory and future thinking when examining the positive dimension of schizotypy and participants' ratings, particularly to sensory characteristics of the experience and mental pre- or reliving. These results indicate enhanced subjective experiences of autobiographical memory and future thinking in those who report delusional and hallucinatory-like occurrences, which might be linked to mental imagery or metacognitive alterations.

The efficacy of electroencephalography neurofeedback for enhancing episodic memory in healthy and clinical participants: A systematic qualitative review and meta-analysis.

Several studies have examined whether electroencephalography neurofeedback (EEG-NF), a self-regulatory technique where an individual receives real-time feedback on a pattern of brain activity that is theoretically linked to a target behaviour, can enhance episodic memory. The aim of this research was to i) provide a qualitative overview of the literature, and ii) conduct a meta-analysis of appropriately controlled studies to determine whether EEG-NF can enhance episodic memory. The literature search returned 46 studies, with 21 studies (44 effect sizes) meeting the inclusion criteria for the meta-analysis. The qualitative overview revealed that, across EEG-NF studies on both healthy and clinical populations, procedures and protocols vary considerably and many studies were insufficiently powered with inadequate design features. The meta-analysis, conducted on studies with an active control, revealed a small-size, significant positive effect of EEG-NF on episodic memory performance (g = 0.31, p = 0.003), moderated by memory modality and EEG-NF self-regulation success. These results are discussed with a view towards optimising EEG-NF training and subsequent benefits to episodic memory.

Adolescent exposure to sucrose increases cocaine-mediated behaviours in adulthood via Smad3.

Adolescence, a critical period of developmental period, is marked by neurobiological changes influenced by environmental factors. Here, we show how exposure to sucrose, which is ubiquitously available in modern diets, results in changes in behavioural response to cocaine as an adult. Rats were given daily access to either 10% sucrose or water during the adolescent period (PND28-42). Following this period, rats are left undisturbed until they reach adulthood. In adulthood, rats were tested for (i) acquisition of a low dose of cocaine, (ii) progressive ratio (PR) test, and (iii) resistance to punished cocaine taking. Sucrose exposure resulted in significant alterations in all behavioural measures. To determine the neurobiological mechanisms leading to such behavioural adaptations, we find that adolescent sucrose exposure results in an upregulation of the transcription factor Smad3 in the nucleus accumbens (NAc) when compared with water-exposed controls. Transiently blocking the active form of this transcription factor (HSV-dnSmad3) during adolescence mitigated the enhanced cocaine vulnerability-like behaviours observed in adulthood. These findings suggest that prior exposure to sucrose during adolescence can heighten the reinforcing effects of cocaine. Furthermore, they identify the TGF-beta pathway and Smad3 as playing a key role in mediating enduring and long-lasting adaptations that contribute to sucrose-induced susceptibility to cocaine. Taken together, these results have important implications for development and suggest that adolescent sucrose exposure may persistently enhance the susceptibility to substance abuse.

Pollinator identity and behavior affect pollination in kiwifruit (Actinidia chinensis Planch.).

Many crop plants rely on insect pollination, particularly insect-pollinated crops which are functionally dioecious. These crops require insects to move pollen between separate plants which are functionally male or female. While honey bees are typically considered the most important crop pollinator species, many other insects are known to visit crops but the pollination contribution of the full diversity of these flower visitors is poorly understood. In this study, we examine the role of diverse insect pollinators for two kiwifruit cultivars as model systems for dioecious crops: Actinidia chinensis var. deliciosa 'Hayward' (a green-fleshed variety) and A. chinensis var. chinensis 'Zesy002' (a gold-fleshed variety). In our round-the-clock insect surveys, we identified that psychodid flies and mosquitoes were the second and third most frequent floral visitors after honey bees (Apis mellifera L), but further work is required to investigate their pollination efficiency. Measures of single-visit pollen deposition identified that several insects, including the bees Leioproctus spp. and Bombus spp. and the flies Helophilus hochstetteri and Eristalis tenax, deposited a similar amount of pollen on flowers as honey bees (Apis mellifera). Due to their long foraging period and high pollen deposition, we recommend the development of strategies to boost populations of Bombus spp., Eristalis tenax and other hover flies, and unmanaged bees for use as synergistic pollinators alongside honey bees.

Morphological characteristics of pollen from triploid watermelon and its fate on stigmas in a hybrid crop production system.

Hybrid crop production is more reliant on pollinators compared to open-pollinated crops because they require cross-pollination between a male-fertile and a male-sterile line. Little is known about how stigma receipt of pollen from male-sterile genotypes affects reproduction in hybrids. Non-viable and non-compatible pollen cannot fertilise plant ovules, but may still interfere with pollination success. Here we used seedless watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai) as a model hybrid plant, to evaluate the morphology, physiology, and movement of pollen from inter-planted genotypes (diploids and triploids). We found that pollen from triploids ('Exclamation' and 'Royal Armada') and diploids ('SP-6', 'Summer Flavor 800', and 'Tiger') was visually distinguishable. Pollen in triploids had more deformities (42.4-46%), tetrads (43-44%), and abnormal growth of callose plugs in pollen tubes. The amount of pollen in triploids to germinate on stigmas was low (8 ± 3%), and few pollen grains produced pollen tubes (6.5 ± 2%). Still, contrary to previous reports our results suggest that some viable pollen grains are produced by triploid watermelons. However, whilst honey bees can collect and deposit pollen from triploids onto stigmas, its effect on hybrid watermelon reproduction is likely to be minimal due to its low germination rate.

Crisis stabilization units for jail diversion: A preliminary assessment of patient characteristics and outcomes.

Crisis stabilization units (CSUs), which offer a range of short-term psychiatric and psychological services, are one of several treatment programs that may create "alternative to arrest" options for law enforcement. Here, we examined the characteristics of the population who was referred to a newly established CSU in its first year of operation and examined the impact of the CSU on regional jail bookings. Administrative medical records and regional jail booking data were merged to form our study sample. Adults who had at least one jail booking and/or one CSU admission during our study period were included. We found that from September 1, 2018 to August 30, 2019, 458 people were admitted into the CSU. Approximately one-third (33.8%) had a jail booking during the study period. In the 3 months following CSU admission, 4.1% had an increase in jail bookings, 11.1% had a decrease, and 66.2% had no change. CSU patients self-reported high depressive and posttraumatic stress disorder symptoms, while also reporting low quality of life scores overall. We conclude that CSUs may be promising components of jail diversion efforts, providing critical services to populations experiencing significant mental health symptoms and who are at risk for incarceration. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

An Economic Analysis of the Cost of a Regional Crisis Stabilization Unit.

Crisis stabilization units (CSUs) are one type of "alternative to arrest" program used for jail diversion. We aimed to estimate the economic costs of starting and operating a CSU in Arkansas. We estimated the economic costs of the Pulaski County Regional CSU (PCRCSU) located in Little Rock, Arkansas, from September 1, 2018, to August 31, 2019. We collected data through interviews about start-up and ongoing management costs. We calculated total annual economic cost, average admission cost, and average 24 hr admission cost. There were 536 admissions to the CSU during the study period. The average length of stay was 60.27 hr. The total annual cost of the PCRCSU was $1,636,831 and average per admission cost was $3,054. Our results provide valuable economic data to government stakeholders who are considering establishing a CSU.

The impact of web-based and face-to-face simulation education programs on nurses' response to patient deterioration: A multi-site interrupted time series study.

BACKGROUND: Nurses' response to patient deterioration in acute hospital wards is a priority issue. Simulation education programs improve nurses' knowledge and confidence, but the translation into better care is largely unknown for both web based (WB) and face to face (F2F) simulation programs. AIM: To measure the impact of simulation education on nurses' response to patient deterioration in acute medical ward settings, and to compare the impact of WB and F2F versions. DESIGN: An interrupted time series, non-randomised trial across four medical wards in Victoria, Australia. Wards were allocated to either web-based or face-to-face versions of the same simulation program, FIRST2ACT. Interrupted time series measurement for six fortnights both before and after the intervention were used to measure and compare responses to deterioration. Responses to patient deterioration were extracted from medical records and grouped into outcomes for escalation (e.g. initiation of clinical review), assessment and observation (e.g. increased recording of vital signs, conscious state and pain scores) and clinical interventions (e.g. oxygen administration). RESULTS: 126 nurses (89%) participated across the four wards. 946 patient records (506 in the F2F; 440 in the WB group) were included in analyses. There were significant and sustained improvements between pre and post samples in outcomes for escalation (13.0% to 28.8%; p = 0.000) and assessment and observation (conscious state recorded increased from 91.1% to 100%; p = 0.000, and pain score recorded increased from 97.8% to 99.8%; p = 0.000). There were no differences between the web-based and face-to-face groups except in appropriate oxygen application which increased by 7.7% in the F2F group and decreased by 11.8% in the WB group (p = 0.046). CONCLUSIONS: There was a significant improvement in nurses' response to patient deterioration following both versions of simulation, indicating that both have a role to play in supporting nurses' response to patient deterioration.

Association Between Pretreatment Sleep Disturbance and Radiation Therapy-Induced Pain in 573 Women With Breast Cancer.

CONTEXT: Pain can be a debilitating side effect of radiation therapy (RT). Data from the general population have shown that sleep disturbance can influence pain incidence and severity; however, less is known about this relationship in patients with breast cancer receiving RT. OBJECTIVES: This secondary analysis examined the association of pretreatment moderate/severe levels of sleep disturbance with subsequent RT-induced pain after adjusting for pre-RT pain. METHODS: We report on 573 female patients with breast cancer undergoing RT from a previously completed Phase II clinical trial for radiation dermatitis. Sleep disturbance, total pain, and pain subdomains-sensory pain, affective pain, and perceived pain intensity were assessed at pre-RT and post-RT. At pre-RT, patients were dichotomized into two groups: those with moderate/severe sleep disturbance (N = 85) vs. those with no/mild sleep disturbance (control; N = 488). RESULTS: At pre-RT, women with moderate/severe sleep disturbance were younger, less likely to be married, more likely to have had mastectomy and chemotherapy, and more likely to have depression/anxiety disorder and fatigue than the control group (all Ps < 0.05). Generalized estimating equations model, after controlling for pre-RT pain and other covariates (e.g., trial treatment condition and covariates that were significantly correlated with post-RT pain), showed that women with moderate/severe sleep disturbance at pre-RT vs. control group had significantly higher mean post-RT total pain as well as sensory, affective, and perceived pain (effect size = 0.62, 0.60, 0.69, and 0.52, respectively; all Ps < 0.05). CONCLUSION: These findings suggest that moderate/severe disturbed sleep before RT is associated with increased pain from pre-to-post-RT in patients with breast cancer.

Neural evidence that disengaging memory retrieval is modulated by stimulus valence and rumination.

To remember information from our personal past we need to be in a cognitive state where we treat stimuli as cues for memory retrieval. In this study we considered whether participants could exert control and disengage from a memory state when it was no longer required for the task at hand. In particular, we examined whether this ability was affected by the valence of the stimuli and participant's rumination scores. After a study phase participants completed test blocks where the task switched every two trials between a memory task (retrieving information from the study phase) and a perceptual task. Even though there was no episodic memory requirement in the perceptual task, a well-established event-related potential (ERP) index of memory retrieval was present for both trials when the stimuli were negative valenced pictures but not for neutral pictures. Furthermore, there was a positive correlation between the magnitude of this ERP memory index in the perceptual task and rumination scores but only for neutral stimuli and not negative. Thus, in this study participants generally had difficultly suppressing memory retrieval when negative stimuli were presented. However, for neutral stimuli only ruminators were more susceptible to memory intrusions.

Evaluating the taxa that provide shared pollination services across multiple crops and regions.

Many pollinator species visit multiple crops in multiple regions, yet we know little about their pollination service provisioning at local and regional scales. We investigated the floral visitors (n = 13,200), their effectiveness (n = 1718 single visits) and response to landscape composition across three crops avocado, mango and macadamia within a single growing region (1 year), a single crop (3 years) and across different growing regions in multiple years. In total, eight wild visitor groups were shared across all three crops. The network was dominated by three pollinators, two bees (Apis mellifera and Tetragonula spp.) and a fly, Stomorhina discolor. The visitation network for the three crops was relatively generalised but with the addition of pollen deposition data, specialisation increased. Sixteen managed and wild taxa were consistently present across three years in avocado, yet their contribution to annual network structure varied. Node specialisation (d') analyses indicated many individual orchard sites across each of the networks were significantly more specialised compared to that predicted by null models, suggesting the presence of site-specific factors driving these patterns. Identifying the taxa shared across multiple crops, regions and years will facilitate the development of specific pollinator management strategies to optimize crop pollination services in horticultural systems.

A protocol for a randomised controlled, double-blind feasibility trial investigating fluoxetine treatment in improving memory and learning impairments in patients with mesial temporal lobe epilepsy: Fluoxetine, Learning and Memory in Epilepsy (FLAME trial).

BACKGROUND: People with temporal lobe epilepsy (TLE) report significant problems with learning and memory. There are no effective therapies for combatting these problems in people with TLE, resulting in an unmet therapeutic need. The lack of treatment is, in part, due to a poor understanding of the neurobiology underlying these memory deficits. We know that hippocampal neurogenesis, a process believed to be important in learning and memory formation, is permanently reduced in chronic TLE, and this may go some way to explain the learning and memory impairments seen in people with TLE.The common anti-depressant drug fluoxetine has been shown to stimulate neurogenesis both in the healthy brain and in neurological diseases where neurogenesis is impaired. In an animal model of TLE, administration of fluoxetine was found to restore neurogenesis and improve learning on a complex spatial navigational task. We now want to test this effect in humans by investigating whether administration of fluoxetine to people with TLE can improve learning and memory. METHODS: This is a single-centre randomised controlled, double-blind feasibility trial. We plan to recruit 20 participants with a diagnosis of TLE and uni-lateral hippocampal sclerosis, confirmed by 3T MRI. Eligible participants will undergo baseline assessments of learning and memory prior to being randomised to either 20 mg/day fluoxetine or matching placebo for 60 days. Follow-up assessments will be conducted after 60 days of trial medication and then again at 60 days after cessation of trial medication. Feasibility will be assessed on measures of recruitment, retention and adherence against pre-determined criteria. DISCUSSION: This trial is designed to determine the feasibility of conducting a double-blind randomised controlled trial of fluoxetine for the treatment of learning and memory impairments in people with TLE. Data collected in this trial will inform the design and utility of any future efficacy trial involving fluoxetine for the treatment of learning and memory in people with TLE. TRIAL REGISTRATION: EudraCT 2014-005088-34, registered on May 18, 2015.

Netted crop covers reduce honeybee foraging activity and colony strength in a mass flowering crop.

The widespread use of protective covers in horticulture represents a novel landscape-level change, presenting the challenges for crop pollination. Honeybees (Apis mellifera L) are pollinators of many crops, but their behavior can be affected by conditions under covers. To determine how netting crop covers can affect honeybee foraging dynamics, colony health, and pollination services, we assessed the performance of 52 nucleus honeybee colonies in five covered and six uncovered kiwifruit orchards. Colony strength was estimated pre- and postintroduction, and the foraging of individual bees (including pollen, nectar, and naïve foragers) was monitored in a subset of the hives fitted with RFID readers. Simultaneously, we evaluated pollination effectiveness by measuring flower visitation rates and the number of seeds produced after single honeybee visits. Honeybee colonies under cover exhibited both an acute loss of foragers and changes in the behavior of successful foragers. Under cover, bees were roughly three times less likely to return after their first trip outside the hive. Consequently, the number of adult bees in hives declined at a faster rate in these orchards, with colonies losing on average 1,057 ± 274 of their bees in under two weeks. Bees that did forage under cover completed fewer trips provisioning their colony, failing to reenter after a few short-duration trips. These effects are likely to have implications for colony health and productivity. We also found that bee density (bees/thousand flowers) and visitation rates to flowers were lower under cover; however, we did not detect a resultant change in pollination. Our findings highlight the need for environment-specific management techniques for pollinators. Improving honeybee orientation under covers and increasing our understanding of the effects of covers on bee nutrition and brood rearing should be primary objectives for maintaining colonies and potentially improving pollination in these systems.

Pre-retrieval event-related potentials predict source memory during task switching.

Neural activity preceding memory probes differs according to retrieval goals. These divergences have been linked to retrieval orientations, which are content-specific memory states that bias retrieval towards specific contents. Here, participants were cued to retrieve either spatial location or encoding operations. On the first trial of each memory task ('switch' trials), preparatory ERPs preceding correct source memory judgments differed according to retrieval goal, but this effect was absent preceding memory errors. Initiating appropriate retrieval orientations therefore predicted criterial recollection. Preparatory ERPs on the second trial of each memory task (i.e. 'stay' trials) also differed according to retrieval goal, but the polarity of this effect was reversed from that observed on switch trials and the effect did not predict memory accuracy. This was interpreted as a correlate of retrieval orientation maintenance, with initiation and maintenance forming dissociable components of these goal-directed memory states. More generally, these findings highlight the importance of pre-retrieval processes in episodic memory.

High delusional ideation is associated with false pictorial memory.

BACKGROUND AND OBJECTIVES: To assess the relationship between false memories and schizotypal experiences in healthy volunteers. Previous research has examined a number of schizotypal dimensions and experiences and found a variety of results. Our aim was to determine the specificity of these associations by giving participants a schizotypy measure which tapped positive, negative and disorganised dimensions (O-LIFE) and another which focused on delusional ideation (PDI). METHODS: A new memory task was used consisting of images of everyday items, separated into categories. At test participants were presented with pictures which had been seen in the study phase, related lures (additional items from the same categories but which were new) and new items which were not from these categories. RESULTS: Positive correlations were found between scores on the positive dimension of schizotypy/delusional ideation and proportion of false memories. Moreover, these participants also had a greater tendency to respond with the highest confidence old response, regardless of the status of the item. No significant correlations were found with the other dimensions of schizotypy. LIMITATIONS: The confidence finding differs somewhat from previous research, which has found more confidence in memory errors and less confidence in correct responses in schizophrenia. It is unclear the reason(s) for this discrepancy. CONCLUSIONS: Increased false memory is associated with the positive dimension of schizotypy and delusional ideation and not the disorganised or negative dimensions. Furthermore, our results suggest that those high in positive schizotypy/delusional ideation require less evidence before they are willing to call an item old.

A Novel, Fast, Reliable, and Data-Driven Method for Simultaneous Single-Trial Mining and Amplitude-Latency Estimation Based on Proximity Graphs and Network Analysis.

Both amplitude and latency of single-trial EEG/MEG recordings provide valuable information regarding functionality of the human brain. In this article, we provided a data-driven graph and network-based framework for mining information from multi-trial event-related brain recordings. In the first part, we provide the general outline of the proposed methodological approach. In the second part, we provide a more detailed illustration, and present the obtained results on every step of the algorithmic procedure. To justify the proposed framework instead of presenting the analytic data mining and graph-based steps, we address the problem of response variability, a prerequisite to reliable estimates for both the amplitude and latency on specific N/P components linked to the nature of the stimuli. The major question addressed in this study is the selection of representative single-trials with the aim of uncovering a less noisey averaged waveform elicited from the stimuli. This graph and network-based algorithmic procedure increases the signal-to-noise (SNR) of the brain response, a key pre-processing step to reveal significant and reliable amplitude and latency at a specific time after the onset of the stimulus and with the right polarity (N or P). We demonstrated the whole approach using electroencephalography (EEG) auditory mismatch negativity (MMN) recordings from 42 young healthy controls. The method is novel, fast and data-driven succeeding first to reveal the true waveform elicited by MMN on different conditions (frequency, intensity, duration, etc.). The proposed graph-oriented algorithmic pipeline increased the SNR of the characteristic waveforms and the reliability of amplitude and latency within the adopted cohort. We also demonstrated how different EEG reference schemes (REST vs. average) can influence amplitude-latency estimation. Simulation results revealed robust amplitude-latency estimations under different SNR and amplitude-latency variations with the proposed algorithm.