A recurrent neural circuit in Drosophila deblurs visual inputs.

A critical goal of vision is to detect changes in light intensity, even when these changes are blurred by the spatial resolution of the eye and the motion of the animal. Here we describe a recurrent neural circuit in Drosophila that compensates for blur and thereby selectively enhances the perceived contrast of moving edges. Using in vivo, two-photon voltage imaging, we measured the temporal response properties of L1 and L2, two cell types that receive direct synaptic input from photoreceptors. These neurons have biphasic responses to brief flashes of light, a hallmark of cells that encode changes in stimulus intensity. However, the second phase was often much larger than the first, creating an unusual temporal filter. Genetic dissection revealed that recurrent neural circuitry strongly shapes the second phase of the response, informing the structure of a dynamical model. By applying this model to moving natural images, we demonstrate that rather than veridically representing stimulus changes, this temporal processing strategy systematically enhances them, amplifying and sharpening responses. Comparing the measured responses of L2 to model predictions across both artificial and natural stimuli revealed that L2 tunes its properties as the model predicts in order to deblur images. Since this strategy is tunable to behavioral context, generalizable to any time-varying sensory input, and implementable with a common circuit motif, we propose that it could be broadly used to selectively enhance sharp and salient changes.

The importance of early recognition of extraintestinal manifestations of digestive tract dysfunction following gastrointestinal surgery.

We report a case of a 47-year-old male who presented with altered mental status. A review of his records revealed a weight loss of 20 lbs over the past 6 years, a recent hospitalization for idiopathic polyneuropathy with failure to thrive, and prior surgeries for peptic ulcer disease and small bowel obstruction. He was alert but had retrograde amnesia and peripheral neuropathy. A diagnosis was made, and the patient improved with treatment but was unfortunately left with irreversible neurological deficits. We discuss the importance of recognizing the extraintestinal manifestations of gastrointestinal dysfunction following gastrointestinal surgery.

Optimization and Validation of the DESIGNER dMRI preprocessing pipeline in white matter aging.

Various diffusion MRI (dMRI) preprocessing pipelines are currently available to yield more accurate diffusion parameters. Here, we evaluated accuracy and robustness of the optimized Diffusion parameter EStImation with Gibbs and NoisE Removal (DESIGNER) pipeline in a large clinical dMRI dataset and using ground truth phantoms. DESIGNER has been modified to improve denoising and target Gibbs ringing for partial Fourier acquisitions. We compared the revisited DESIGNER (Dv2) (including denoising, Gibbs removal, correction for motion, EPI distortion, and eddy currents) against the original DESIGNER (Dv1) pipeline, minimal preprocessing (including correction for motion, EPI distortion, and eddy currents only), and no preprocessing on a large clinical dMRI dataset of 524 control subjects with ages between 25 and 75 years old. We evaluated the effect of specific processing steps on age correlations in white matter with DTI and DKI metrics. We also evaluated the added effect of minimal Gaussian smoothing to deal with noise and to reduce outliers in parameter maps compared to DESIGNER (Dv2)'s noise removal method. Moreover, DESIGNER (Dv2)'s updated noise and Gibbs removal methods were assessed using ground truth dMRI phantom to evaluate accuracy. Results show age correlation in white matter with DTI and DKI metrics were affected by the preprocessing pipeline, causing systematic differences in absolute parameter values and loss or gain of statistical significance. Both in clinical dMRI and ground truth phantoms, DESIGNER (Dv2) pipeline resulted in the smallest number of outlier voxels and improved accuracy in DTI and DKI metrics as noise was reduced and Gibbs removal was improved. Thus, DESIGNER (Dv2) provides more accurate and robust DTI and DKI parameter maps as compared to no preprocessing or minimal preprocessing.

Mapping tissue microstructure of brain white matter in vivo in health and disease using diffusion MRI.

Diffusion magnetic resonance imaging offers unique in vivo sensitivity to tissue microstructure in brain white matter, which undergoes significant changes during development and is compromised in virtually every neurological disorder. Yet, the challenge is to develop biomarkers that are specific to micrometer-scale cellular features in a human MRI scan of a few minutes. Here we quantify the sensitivity and specificity of a multicompartment diffusion modeling framework to the density, orientation and integrity of axons. We demonstrate that using a machine learning based estimator, our biophysical model captures the morphological changes of axons in early development, acute ischemia and multiple sclerosis (total N=821). The methodology of microstructure mapping is widely applicable in clinical settings and in large imaging consortium data to study development, aging and pathology.

A positively tuned voltage indicator for extended electrical recordings in the brain.

Genetically encoded voltage indicators (GEVIs) enable optical recording of electrical signals in the brain, providing subthreshold sensitivity and temporal resolution not possible with calcium indicators. However, one- and two-photon voltage imaging over prolonged periods with the same GEVI has not yet been demonstrated. Here, we report engineering of ASAP family GEVIs to enhance photostability by inversion of the fluorescence-voltage relationship. Two of the resulting GEVIs, ASAP4b and ASAP4e, respond to 100-mV depolarizations with ≥180% fluorescence increases, compared with the 50% fluorescence decrease of the parental ASAP3. With standard microscopy equipment, ASAP4e enables single-trial detection of spikes in mice over the course of minutes. Unlike GEVIs previously used for one-photon voltage recordings, ASAP4b and ASAP4e also perform well under two-photon illumination. By imaging voltage and calcium simultaneously, we show that ASAP4b and ASAP4e can identify place cells and detect voltage spikes with better temporal resolution than commonly used calcium indicators. Thus, ASAP4b and ASAP4e extend the capabilities of voltage imaging to standard one- and two-photon microscopes while improving the duration of voltage recordings.

The effect of weight loss on whole-body and tissue-specific insulin sensitivity and hepatic lipid content and composition: SWEET substudy.

OBJECTIVE: This study (1) investigated the effect of weight loss on whole-body and tissue-specific insulin sensitivity and on intrahepatic lipid (IHL) content and composition and (2) investigated the association between weight-loss-induced changes in insulin sensitivity and IHL content in individuals with overweight or obesity. METHODS: In this secondary analysis of the European SWEET project, 50 adults (age 18-65 years) with overweight or obesity (BMI ≥ 25 kg/m2 ) followed a low-energy diet (LED) for 2 months. At baseline and after the LED, body composition (dual-energy x-ray absorptiometry), IHL content and composition (proton magnetic resonance spectroscopy), whole-body insulin sensitivity (Matsuda index), muscle insulin sensitivity index (MISI), and hepatic insulin resistance index (HIRI) were determined (7-point oral glucose tolerance test). RESULTS: The LED reduced body weight (p < 0.001). This was accompanied by increased Matsuda index and reduced HIRI (both p < 0.001) but no change in MISI (p = 0.260). Weight loss decreased IHL content (mean [SEM], 3.9% [0.7%] vs. 1.6% [0.5%], p < 0.001) and the hepatic saturated fatty acid fraction (41.0% [1.5%] vs. 36.6% [1.9%], p = 0.039). The reduced IHL content was associated with an improvement in HIRI (r = 0.402, p = 0.025). CONCLUSIONS: Weight loss decreased IHL content and the hepatic saturated fatty acid fraction. The decrease in IHL content was associated with weight-loss-induced improvement in hepatic insulin sensitivity in individuals with overweight or obesity.

Visual processing in the fly, from photoreceptors to behavior.

Originally a genetic model organism, the experimental use of Drosophila melanogaster has grown to include quantitative behavioral analyses, sophisticated perturbations of neuronal function, and detailed sensory physiology. A highlight of these developments can be seen in the context of vision, where pioneering studies have uncovered fundamental and generalizable principles of sensory processing. Here we begin with an overview of vision-guided behaviors and common methods for probing visual circuits. We then outline the anatomy and physiology of brain regions involved in visual processing, beginning at the sensory periphery and ending with descending motor control. Areas of focus include contrast and motion detection in the optic lobe, circuits for visual feature selectivity, computations in support of spatial navigation, and contextual associative learning. Finally, we look to the future of fly visual neuroscience and discuss promising topics for further study.

Influence of glycan structure on the colonization of Streptococcus pneumoniae on human respiratory epithelial cells.

Virtually all living cells are encased in glycans. They perform key cellular functions such as immunomodulation and cell-cell recognition. Yet, how their composition and configuration affect their functions remains enigmatic. Here, we constructed isogenic capsule-switch mutants harboring 84 types of capsular polysaccharides (CPSs) in Streptococcus pneumoniae. This collection enables us to systematically measure the affinity of structurally related CPSs to primary human nasal and bronchial epithelial cells. Contrary to the paradigm, the surface charge does not appreciably affect epithelial cell binding. Factors that affect adhesion to respiratory cells include the number of rhamnose residues and the presence of human-like glycomotifs in CPS. Besides, pneumococcal colonization stimulated the production of interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractantprotein-1 (MCP-1) in nasal epithelial cells, which also appears to be dependent on the serotype. Together, our results reveal glycomotifs of surface polysaccharides that are likely to be important for colonization and survival in the human airway.

Visual and motor signatures of locomotion dynamically shape a population code for feature detection in Drosophila.

Natural vision is dynamic: as an animal moves, its visual input changes dramatically. How can the visual system reliably extract local features from an input dominated by self-generated signals? In Drosophila, diverse local visual features are represented by a group of projection neurons with distinct tuning properties. Here, we describe a connectome-based volumetric imaging strategy to measure visually evoked neural activity across this population. We show that local visual features are jointly represented across the population, and a shared gain factor improves trial-to-trial coding fidelity. A subset of these neurons, tuned to small objects, is modulated by two independent signals associated with self-movement, a motor-related signal, and a visual motion signal associated with rotation of the animal. These two inputs adjust the sensitivity of these feature detectors across the locomotor cycle, selectively reducing their gain during saccades and restoring it during intersaccadic intervals. This work reveals a strategy for reliable feature detection during locomotion.

Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy.

Genetically encoded voltage indicators are emerging tools for monitoring voltage dynamics with cell-type specificity. However, current indicators enable a narrow range of applications due to poor performance under two-photon microscopy, a method of choice for deep-tissue recording. To improve indicators, we developed a multiparameter high-throughput platform to optimize voltage indicators for two-photon microscopy. Using this system, we identified JEDI-2P, an indicator that is faster, brighter, and more sensitive and photostable than its predecessors. We demonstrate that JEDI-2P can report light-evoked responses in axonal termini of Drosophila interneurons and the dendrites and somata of amacrine cells of isolated mouse retina. JEDI-2P can also optically record the voltage dynamics of individual cortical neurons in awake behaving mice for more than 30 min using both resonant-scanning and ULoVE random-access microscopy. Finally, ULoVE recording of JEDI-2P can robustly detect spikes at depths exceeding 400 µm and report voltage correlations in pairs of neurons.

Barriers and facilitators to opioid agonist treatment (OAT) engagement among individuals released from federal incarceration into the community in Ontario, Canada.

INTRODUCTION: Correctional populations with opioid use disorder experience increased health risks during community transition periods. Opioid Agonist Treatment (OAT) can reduce these risks, but retention is a key challenge. This study addresses a knowledge gap by describing facilitators and barriers to OAT engagement among federal correctional populations released into the community in Ontario, Canada. METHODS: This article describes results from a longitudinal mixed-methods study examining OAT transition experiences among thirty-five individuals released from federal incarceration in Ontario, Canada. Assessments were completed within one year of participants' release. Data were thematically analyzed. RESULTS: The majority (77%) of participants remained engaged in OAT, however, 69% had their release suspended and 49% returned to custody. Key facilitators for OAT engagement included flexibility, positive staff rapport, and structure. Fragmented OAT transitions, financial OAT coverage, balancing reintegration requirements, logistical challenges, and inaccessibility of 'take-home' OAT medications were common barriers. CONCLUSIONS: Post-incarceration transition periods are critical for OAT retention, yet individuals in Ontario experience barriers to OAT engagement that contribute to treatment disruptions and related risks such as relapse and/or re-incarceration. Additional measures to support community OAT transitions are required, including improved discharge planning, amendments to OAT and financial coverage policies, and an expansion of OAT options.

Opioid agonist treatment (OAT) experiences and release plans among federally incarcerated individuals with opioid use disorder (OUD) in Ontario, Canada: a mixed-methods study.

BACKGROUND: Incarcerated populations experience an elevated prevalence of opioid use disorder (OUD). Federal correctional institutions in Canada have increasingly treated OUD among correctional populations via opioid agonist treatment (OAT) - an evidence based pharmacotherapy that works to reduce drug use and related health harms. However, there is limited evidence regarding incarcerated individuals' experiences with institutional-based OAT, as well potential OAT-related community release prospects. This information is important for optimal treatment retention and improved health. To address this knowledge gap, we conducted a longitudinal follow-up study examining OAT-related experiences among federally incarcerated individuals before and after community release. This article focuses on the baseline (pre-release) data. METHODS: This mixed-methods study examined OAT-related experiences and release prospects among n = 46 individuals scheduled for community release, recruited from seven federal prisons located in Ontario, Canada. Participants underwent a comprehensive interviewer-administered on-site assessment, including quantitative and qualitative items. Assessment data was furthermore linked to administrative correctional data. Data were analyzed using thematic qualitative and descriptive quantitative approaches. RESULTS: Participants had complex histories with opioid use including related negative health outcomes. Experiences with institutional OAT were divergent and provision was not standardized; those with OAT engagement pre-admission did not experience many challenges, whereas those initiating OAT during incarceration experienced barriers such as treatment waitlists and adverse process experiences. Most participants expressed a preference for buprenorphine-naloxone over methadone, but described difficulties accessing it. Participants were keen to transition into community-based treatment, yet envisaged prospective barriers and facilitators concerning successful reintegration and treatment continuity. CONCLUSIONS: Major barriers towards the current administration of OAT in federal correctional systems in Canada exist, including extensive waitlists, non-standardized practices, and challenges accessing preferred OAT formulations; this contributes to sub-optimal treatment. Eliminating waitlists, standardizing OAT provision, providing additional OAT options, and more comprehensive release planning may be essential for treatment retention and positive outcomes.

Rising through the pandemic: a scoping review of quality improvement in public health during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic generated a growing interest in and need for evidence-based tools to facilitate the implementation of emergency management strategies within public health practice. Quality improvement (QI) is a key framework and philosophy to guide organizational emergency response efforts; however, the nature and extent to which it has been used in public health settings during the COVID-19 pandemic remains unclear. METHODS: We conducted a scoping review of literature published January 2020 - February 2021 and focused on the topic of QI at public health agencies during the COVID-19 pandemic. The search was conducted using four bibliographic databases, in addition to a supplementary grey literature search through custom Google search engines and targeted website search methods. Of the 1,878 peer-reviewed articles assessed, 15 records met the inclusion criteria. An additional 11 relevant records were identified during the grey literature search, for a total of 26 records included in the scoping review. RESULTS: Records were organized into five topics: 1) collaborative problem solving and analysis with stakeholders; 2) supporting learning and capacity building in QI; 3) learning from past emergencies; 4) implementing QI methods during COVID-19; and 5) evaluating performance using frameworks/indicators. CONCLUSIONS: The literature indicates that QI-oriented activities are occurring at the organizational and program levels to enhance COVID-19 response. To optimize the benefits that QI approaches and methodologies may offer, it is important for public health agencies to focus on both widespread integration of QI as part of an organization's management philosophy and culture, as well as project level activities at all stages of the emergency management cycle.

The association of changes in body mass index and metabolic parameters between adults with overweight or obesity and their children in a family-based randomized trial (DiOGenes).

BACKGROUND: Family-based approaches have been reported to be effective in improving overweight or obesity in children. OBJECTIVES: To investigate the relationship of changes in body mass index and metabolic parameters between adults with overweight or obesity and their children during a weight-maintenance family-based dietary intervention. METHODS: In a multicentre randomized controlled trial, families with at least one parent with overweight or obesity and one healthy child aged between 5 and 18 years, of which the parents completed an 8-week weight-loss phase successfully, were randomized into five different dietary intervention groups to achieve weight maintenance for 6 months. Anthropometric parameters and body composition were measured and blood samples were collected before and after the dietary intervention. Data were analysed using Pearson correlation coefficient analyses and multiple linear regression analysis adjusted for diet group, centre, child's sex and age. RESULTS: A positive association was found between the change in body mass index (BMI) of the mother and change in BMI-for-age Z-score of first and second child (std ß = 0.248, p = 0.000; std ß = 0.326, p = 0.000, respectively). The change in BMI of the father was only significantly associated with the change in BMI-for-age Z-score of first child (std ß = 0.186, p = 0.031). No consistent pattern of associations between parents and children was found for homeostatic model assessment for insulin resistance, fasting glucose and fasting insulin. CONCLUSION: This study supports the inclusion of parents into family-based dietary approaches for weight management of their children regardless of the child's weight status in eight different countries throughout Europe.

Variables Associated with Coronavirus Disease 2019 Vaccine Hesitancy Amongst Patients with Neurological Disorders.

INTRODUCTION: Given that the success of vaccines against coronavirus disease 2019 (COVID-19) relies on herd immunity, identifying patients at risk for vaccine hesitancy is imperative-particularly for those at high risk for severe COVID-19 (i.e., minorities and patients with neurological disorders). METHODS: Among patients from a large neuroscience institute in Hawaii, vaccine hesitancy was investigated in relation to over 30 sociodemographic variables and medical comorbidities, via a telephone quality improvement survey conducted between 23 January 2021 and 13 February 2021. RESULTS: Vaccine willingness (n = 363) was 81.3%. Univariate analysis identified that the odds of vaccine acceptance reduced for patients who do not regard COVID-19 as a severe illness, are of younger age, have a lower Charlson Comorbidity Index, use illicit drugs, or carry Medicaid insurance. Multivariable logistic regression identified the best predictors of vaccine hesitancy to be: social media use to obtain COVID-19 information, concerns regarding vaccine safety, self-perception of a preexisting medical condition contraindicated with vaccination, not having received the annual influenza vaccine, having some high school education only, being a current smoker, and not having a prior cerebrovascular accident. Unique amongst males, a conservative political view strongly predicted vaccine hesitancy. Specifically for Asians, a higher body mass index, while for Native Hawaiians and other Pacific Islanders (NHPI), a positive depression screen, both reduced the odds of vaccine acceptance. CONCLUSION: Upon identifying the variables associated with vaccine hesitancy amongst patients with neurological disorders, our clinic is now able to efficiently provide ancillary COVID-19 education to sub-populations at risk for vaccine hesitancy. While our results may be limited to the sub-population of patients with neurological disorders, the findings nonetheless provide valuable insight to understanding vaccine hesitancy.

Evaluation of students' perceived clinical competence and learning needs following an online virtual simulation education programme with debriefing during the COVID-19 pandemic.

AIMS AND OBJECTIVES: This study aimed to evaluate the effect of a virtual simulation education programme with debriefing in undergraduate nursing students. Perceived clinical competence and learning needs of students in a simulation environment were also measured. BACKGROUND: Evidence showed virtual simulation education programmes provided better knowledge acquisition. However, these studies to date did not incorporate virtual simulation in the combination of a debriefing model in nursing students. DESIGN: A one-group pre-test and post-test design. METHODS: 188 final year undergraduate nursing students participated in the study. Linear mixed model analysis was conducted to evaluate the effect of the programme. RESULTS: Students have perceived a significant improvement in clinical competence and nursing process. Self-efficacy has also boosted. Communication and critical thinking were applied better in the traditional clinical environment. CONCLUSION: Perceived clinical competence of Chinese nursing students has significant improvements by using virtual simulation combining a debriefing model during the COVID-19 period. Virtual simulation met students' learning needs. Future studies should include a control group for comparison and long-term measurement. RELEVANCE TO CLINICAL PRACTICE: The study provided an innovative clinical learning pedagogy to serve as a potential alternative with traditional clinical practicum during the COVID-19 period as this is substantially limited.

Rubric-based debriefing to enhance nursing students' critical thinking via simulation.

Introduction: Debriefing plays a vital role in effective simulation-based learning by providing feedback to students to foster their development of critical thinking in the learning. Objectives: We evaluated the effects of rubric-based debriefing on students' critical thinking, level of confidence in performing tasks and communication. Method: This is a quasi-experimental study. Final year nursing undergraduates (n=204) of a local university participated in the study. In the intervention group, students performed two 20 min simulation sessions individually with simulated patients followed by a 15 min individual rubric-based debriefing between the two sessions and had a 5 min of that at the end. In the control group, students performed the same simulation sessions followed by a 20 min individual rubric-based debriefing at the end. The primary outcome was comparing the critical thinking of students between two groups, which was assessed by The Northeastern Illinois University Critical Thinking Rubric. The qualitative data were collected by an open-ended question. Results: Based on generalised estimating equation models, the intervention effect over time was found to be statistically significant (ß=2.06, 95% CI 1.04 to 3.08) in enhancing students' critical thinking. No statistically significant differences were reported in the self-perceived confidence levels between the intervention group and control group. Qualitative data reflected positive feedback from students on simulation activities. Conclusions: This is the first study to provide evidence that a rubric-based debriefing enhances students' critical thinking in simulation learning.

A rational review on the effects of sweeteners and sweetness enhancers on appetite, food reward and metabolic/adiposity outcomes in adults.

Numerous strategies have been investigated to overcome the excessive weight gain that accompanies a chronic positive energy balance. Most approaches focus on a reduction of energy intake and the improvement of lifestyle habits. The use of high intensity artificial sweeteners, also known as non-caloric sweeteners (NCS), as sugar substitutes in foods and beverages, is rapidly developing. NCS are commonly defined as molecules with a sweetness profile of 30 times higher or more that of sucrose, scarcely contributing to the individual's net energy intake as they are hardly metabolized. The purpose of this review is first, to assess the impact of NCS on eating behaviour, including subjective appetite, food intake, food reward and sensory stimulation; and secondly, to assess the metabolic impact of NCS on body weight regulation, glucose homeostasis and gut health. The evidence reviewed suggests that while some sweeteners have the potential to increase subjective appetite, these effects do not translate in changes in food intake. This is supported by a large body of empirical evidence advocating that the use of NCS facilitates weight management when used alongside other weight management strategies. On the other hand, although NCS are very unlikely to impair insulin metabolism and glycaemic control, some studies suggest that NCS could have putatively undesirable effects, through various indirect mechanisms, on body weight, glycemia, adipogenesis and the gut microbiota; however there is insufficient evidence to determine the degree of such effects. Overall, the available data suggests that NCS can be used to facilitate a reduction in dietary energy content without significant negative effects on food intake behaviour or body metabolism, which would support their potential role in the prevention of obesity as a complementary strategy to other weight management approaches. More research is needed to determine the impact of NCS on metabolic health, in particular gut microbiota.

Exploring the role of simulation to foster interprofessional teamwork among medical and nursing students: A mixed-method pilot investigation in Hong Kong.

Effective teamwork is a critical component of maintaining patient safety. However, there is lack of clarity on the best teaching approach to interprofessional teamwork training in medical and nursing curricula. This study aimed to compare the effects of blended classroom plus clinical simulation versus clinical simulation alone on teamwork attitudes, perceptions and performance in medical and nursing students in Hong Kong. This was a pilot study with a mixed-method research design, with both quantitative and qualitative evaluations. Students who studied medicine or nursing courses at a university in Hong Kong were invited to this study. They were assigned into two groups: clinical simulation alone versus blended classroom plus clinical simulation. The primary outcome was attitudinal change related to teamwork behaviours, which was measured using the Human Factors Attitude Survey. The secondary outcomes were perceptions of team-based learning and teamwork performance, which were accessed by the Team-Based Learning Student Assessment Instrument and Ottawa Global Rating Scale, respectively. Four focus group interviews were conducted after the training sessions. Conventional content analysis using inductive coding was performed with the qualitative data. Forty-six students participated in this study. There was a significant increase in the participants' positive attitudes on teamwork for both groups (intervention: MD = 5.36 and control: MD = 3.6, p <.05); however, there was no significant difference on increasing positive attitudes between the groups (estimate = 1.76, 95% CI [-8.59, 5.06], p = .61). Qualitative analysis identified four themes: (1) reconsidering professional roles in managing patients; (2) embodying the experience to share responsibility and complement each other's skills; (3) realizing the importance of trust and communication; and (4) engaging to achieve the mission within a limited time. This pilot study found that a blended classroom did not further improve teamwork attitudes, perceptions and performance in medical and nursing students compared with clinical simulation alone. Qualitative findings showed that students had reconsidered their professional roles in managing patients and realized the importance of teamwork in caring patients.