Miracle-dz/UniFAR-FTUs huggingface dataset:
Alternative splicing of GluN1 gates glycine site–dependent nonionotropic signaling by NMDAR receptors

Significance N-methyl-D-aspartate receptors (NMDARs), which are critical in the brain, are increasingly being shown to signal without ion flux (i.e., “metabotropically”). What controls the metabotropic function of NMDARs is unknown. We discovered that a form of metabotropic signaling—glycine priming—is controlled by alternative splicing of the mRNA encoding one NMDAR subunit, GluN1. Our discovery was surprising because the spliced exon encodes a peptide cassette in the extracellular region of GluN1 far from the plasma membrane, and yet, metabotropic function requires signaling across the neuronal membrane. Moreover, we found that this metabotropic function of NMDARs is neuron cell–type specific: excitatory neurons show glycine priming, whereas inhibitory neurons do not. These findings have widespread implications for NMDARs in health and disease. N-methyl-D-aspartate (NMDA) receptors (NMDARs), a principal subtype of excitatory neurotransmitter receptor, are composed as tetrameric assemblies of two glycine-binding GluN1 subunits and two glutamate-binding GluN2 subunits. NMDARs can signal nonionotropically through binding of glycine alone to its cognate site on GluN1. A consequence of this signaling by glycine is that NMDARs are primed such that subsequent gating, produced by glycine and glutamate, drives receptor internalization. The GluN1 subunit contains eight alternatively spliced isoforms produced by including or excluding the N1 and the C1, C2, or C2’ polypeptide cassettes. Whether GluN1 alternative splicing affects nonionotropic signaling by NMDARs is a major outstanding question. Here, we discovered that glycine priming of recombinant NMDARs critically depends on GluN1 isoforms lacking the N1 cassette; glycine priming is blocked in splice variants containing N1. On the other hand, the C-terminal cassettes—C1, C2, or C2’—each permit glycine signaling. In wild-type mice, we found glycine-induced nonionotropic signaling at synaptic NMDARs in CA1 hippocampal pyramidal neurons. This nonionotropic signaling by glycine to synaptic NMDARs was prevented in mice we engineered, such that GluN1 obligatorily contained N1. We discovered in wild-type mice that, in contrast to pyramidal neurons, synaptic NMDARs in CA1 inhibitory interneurons were resistant to glycine priming. But we recapitulated glycine priming in inhibitory interneurons in mice engineered such that GluN1 obligatorily lacked the N1 cassette. Our findings reveal a previously unsuspected molecular function for alternative splicing of GluN1 in controlling nonionotropic signaling of NMDARs by activating the glycine site.
Investigation of the home-reablement program on rehabilitation outcomes for people with stroke

Abstract Background: Reablement is 1 approach to conduct rehabilitation in the community (ie, home environment), which aims to enhance an individual's functional ability to perform everyday activities that individuals perceive as important. We investigated the effects of a home-reablement program on different rehabilitation outcomes in people with stroke. Methods: A single-blind randomized clinical trial was conducted. Twenty-six people with stroke were randomly assigned to the home-reablement group or control group. For 6 weeks, participants in the home-reablement group received training for activities of daily living (ADL) that they perceived as important but difficult to perform. Participants in the control group received conventional rehabilitation in the hospital. Outcome measures included the Fugl–Meyer Assessment for the upper-extremity (FMA-UE) and the Stroke Impact Scale 3.0 (SIS 3.0) subscales. Results: No statistically significant differences between the 2 groups were noticed in the FMA-UE and the SIS 3.0 subscales (P = .226–1.000). Small effect size (success rate difference = 0.12–0.25) were noticed in the FMA-UE and the 5 SIS 3.0 subscales. The home-reablement group exhibited a greater proportion of participants with scores greater than the minimal detectable change in the FMA-UE and the 6 SIS 3.0 subscales (ie, strength, ADL/instrumental ADL, mobility, emotion, memory, and participation). Conclusions: People with stroke that underwent the 6-week home-reablement program showed potential for improving their motor function, ADL/instrumental ADL, emotion, memory, and activity participation.
Mean macular intercapillary area in eyes with diabetic macular oedema after anti‐vascular endothelial growth factor therapy and its association with treatment response

To evaluate the changes in the mean macular intercapillary area (ICA) from sequential enface optical coherence tomography angiography (OCTA) images following intravitreal anti‐vascular endothelial growth factor (VEGF) therapy in initially treatment‐naïve eyes with diabetic macular oedema (DME).
Forty Years of Oxalobacter formigenes, a Gutsy Oxalate-Degrading Specialist

Oxalobacter formigenes, a unique anaerobic bacterium that relies solely on oxalate for growth, is a key oxalate-degrading bacterium in the mammalian intestinal tract. Degradation of oxalate in the gut by O. formigenes plays a critical role in preventing renal toxicity in animals that feed on oxalate-rich plants. ABSTRACT Oxalobacter formigenes, a unique anaerobic bacterium that relies solely on oxalate for growth, is a key oxalate-degrading bacterium in the mammalian intestinal tract. Degradation of oxalate in the gut by O. formigenes plays a critical role in preventing renal toxicity in animals that feed on oxalate-rich plants. The role of O. formigenes in reducing the risk of calcium oxalate kidney stone disease and oxalate nephropathy in humans is less clear, in part due to difficulties in culturing this organism and the lack of studies which have utilized diets in which the oxalate content is controlled. Herein, we review the literature on the 40th anniversary of the discovery of O. formigenes, with a focus on its biology, its role in gut oxalate metabolism and calcium oxalate kidney stone disease, and potential areas of future research. Results from ongoing clinical trials utilizing O. formigenes in healthy volunteers and in patients with primary hyperoxaluria type 1 (PH1), a rare but severe form of calcium oxalate kidney stone disease, are also discussed. Information has been consolidated on O. formigenes strains and best practices to culture this bacterium, which should serve as a good resource for researchers.
Zwanzig Jahre Levosimendan

Zusammenfassung Vasopressoren kommen besonders in kritischen, nicht selten lebensbedrohlichen Situationen der Anästhesie, Notfall- und Intensivmedizin zum Einsatz. Die Wahl der geeigneten Substanz sowie die Erkennung und Beherrschung möglicher Nebenwirkungen sind von großer Bedeutung. Im folgenden Beitrag sollen daher die klinisch wichtigsten Substanzen vorgestellt und deren pharmakologische Charakteristika beleuchtet werden.
Group Lifestyle Intervention With Mobile Health for Young Adults With Serious Mental Illness: A Randomized Controlled Trial.

OBJECTIVE Evidence-based lifestyle interventions tailored to young adults with serious mental illness are needed to reduce their cardiometabolic risk. This study evaluated the effectiveness of a group lifestyle intervention ("PeerFIT") enhanced with mobile health (mHealth) compared with one-on-one mHealth coaching (basic education supported by activity tracking [BEAT]) for young adults with serious mental illness who were overweight or obese. METHODS Participants were young adults ages 18-35 years with serious mental illness and a body mass index ≥25 kg/m2, who were randomly assigned to PeerFIT or BEAT. Research staff collected data at baseline and at 6 and 12 months. Main outcomes were clinically significant changes from baseline in weight (≥5% weight loss), cardiorespiratory fitness (CRF; increase of >50 m on the 6-minute walk test), and cardiovascular disease (CVD) risk reduction (clinically significant weight loss or CRF improvement). RESULTS Participants were 150 young adults with a mean ± SD body mass index of 37.1±7.4. Intent-to-treat analyses revealed no significant between-group difference for weight-loss, CRF, or CVD outcomes at 6 and 12 months. Participants in both conditions achieved clinically significant CVD risk reduction, weight loss, and CRF from baseline to 6 and 12 months, and all these improvements were statistically significant (p<0.01). CONCLUSION The PeerFIT group lifestyle intervention was not superior to one-on-one mHealth coaching in achieving clinically significant changes in weight, CRF, and CVD risk reduction. Although both interventions improved outcomes, low-intensity mHealth coaching may be a more scalable approach for addressing modifiable cardiometabolic risk factors among young adults with serious mental illness.
Intrinsic Innate Immune Responses Control Viral Growth and Protect against Neuronal Death in an Ex Vivo Model of West Nile Virus-Induced Central Nervous System Disease

West Nile virus is the most common cause of epidemic encephalitis in the United States and can result in debilitating CNS disease. There are no effective vaccines or treatments for WNV-induced CNS disease in humans. ABSTRACT Recruitment of immune cells from the periphery is critical for controlling West Nile virus (WNV) growth in the central nervous system (CNS) and preventing subsequent WNV-induced CNS disease. Neuroinflammatory responses, including the release of proinflammatory cytokines and chemokines by CNS cells, influence the entry and function of peripheral immune cells that infiltrate the CNS. However, these same cytokines and chemokines contribute to tissue damage in other models of CNS injury. Rosiglitazone is a peroxisome proliferator-activated receptor gamma (PPARγ) agonist that inhibits neuroinflammation. We used rosiglitazone in WNV-infected ex vivo brain slice cultures (BSC) to investigate the role of neuroinflammation within the CNS in the absence of peripheral immune cells. Rosiglitazone treatment inhibited WNV-induced expression of proinflammatory chemokines and cytokines, interferon beta (IFN-β), and IFN-stimulated genes (ISG) and also decreased WNV-induced activation of microglia. These decreased neuroinflammatory responses were associated with activation of astrocytes, robust viral growth, increased activation of caspase 3, and increased neuronal loss. Rosiglitazone had a similar effect on in vivo WNV infection, causing increased viral growth, tissue damage, and disease severity in infected mice, even though the number of infiltrating peripheral immune cells was higher in rosiglitazone-treated, WNV-infected mice than in untreated, infected controls. These results indicate that local neuroinflammatory responses are capable of controlling viral growth within the CNS and limiting neuronal loss and may function to keep the virus in check prior to the infiltration of peripheral immune cells, limiting both virus- and immune-mediated neuronal damage. IMPORTANCE West Nile virus is the most common cause of epidemic encephalitis in the United States and can result in debilitating CNS disease. There are no effective vaccines or treatments for WNV-induced CNS disease in humans. The peripheral immune response is critical for protection against WNV CNS infections. We now demonstrate that intrinsic immune responses also control viral growth and limit neuronal loss. These findings have important implications for developing new therapies for WNV-induced CNS disease.
How relevant are in vitro culture models for study of tick-pathogen interactions?

ABSTRACT Although tick-borne infectious diseases threaten human and animal health worldwide, with constantly increasing incidence, little knowledge is available regarding vector–pathogen interactions and pathogen transmission. In vivo laboratory study of these subjects using live, intact ticks is expensive, labor-intensive, and challenging from the points of view of biosafety and ethics. Several in vitro models have been developed, including over 70 continuous cell lines derived from multiple tick species and a variety of tick organ culture systems, facilitating many research activities. However, some limitations have to be considered in the translation of the results from the in vitro environment to the in vivo situation of live, intact ticks, and vertebrate hosts. In this review, we describe the available in vitro models and selected results from their application to the study of tick-borne viruses, bacteria, and protozoa, where possible comparing these results to studies in live, intact ticks. Finally, we highlight the strengths and weaknesses of in vitro tick culture models and their essential role in tick-borne pathogen research.
Overview of clinical trial protocols for behavioral insomnia in infants.

OBJECTIVE to describe the overview of clinical trial protocols for behavioral insomnia in infants. METHODS an analytical study that reviewed protocols registered with the International Clinical Trials Registry Platform between August and September 2019, aiming to identify the interventions for behavioral insomnia in infants, the comparators, the main primary, secondary outcomes and their respective measurements. RESULTS eleven protocols registered between 2004 and 2018 were included. Nurses were the main coordinators of protocols (45.5%), with proposals using educational technologies, one-to-one and online follow-up consultations. The main outcome was improvement of infant and maternal sleep patterns. Secondary outcomes were anxiety, depression, and parental sexual satisfaction. To measure them, the following were used: sleep diary (54.5%), actigraphy (45.4%), and the Pittsburgh Sleep Quality Interview (36.3%) and Extended Brief Infant Sleep Questionnaire (27.2%) were used. CONCLUSION the protocols proposed interventions for independent sleep, aiming at quality of sleep for the whole family.
Knowledge and perceptions of COVID-19, prevalence of pre-existing conditions and access to essential resources in Somali IDP camps: a cross-sectional study

Objectives This study examined knowledge and perceptions of COVID-19, prevalence of pre-existing conditions and access to essential resources among residents of internally displaced person (IDP) camps in Somalia, where overcrowded settlements with weakened infrastructure, inadequate water, sanitation, and hygiene facilities, and limited access to health services make this vulnerable population particularly susceptible to a COVID-19 outbreak. Design A descriptive, cross-sectional survey. Setting Twelve IDP camps across six areas of the Lower Shabelle region in Somalia. Participants 401 adult Somali IDP camp residents. Results The majority of participants were female (86%) and had received no formal education (89%). While 58% reported being in ‘good’ health, half of the participants reported having one or more pre-existing conditions. Though 77% of respondents reported taking at least one COVID-19 preventative public health measure, respondents reported a lack of access to adequate sanitation, an inability to practice social distancing and nearly universal inability to receive a COVID-19 screening exam. Questions assessing knowledge surrounding COVID-19 prevention and treatment yielded answers of ‘I don’t know’ for roughly 50% of responses. The majority of participants were not familiar with basic information about the virus or confident that they could receive medical services if infected. 185 (47%) respondents indicated that camp living conditions needed to change to prevent the spread of COVID-19. Conclusion This study highlights low levels of COVID-19 knowledge and limited access to essential prevention and treatment resources among individuals living in Somali IDP camps. A massive influx of additional resources is required to adequately address COVID-19 in Somalia, starting with codesigning interventions to educate those individuals most vulnerable to infection.
Associations Between Children’s Physical Activity, Pain and Injuries

Our aim in this study was to investigate the relationships between physical activity (PA), pain, and injury among children. Secondarily, we examined whether these relationships differed between children with normal versus excessive weight or obesity. This was a cross-sectional study of 102 children (57 girls) aged 8–12 years old. We assessed the prevalence of moderate and vigorous PA using accelerometry over a seven-day period. We examined the associations between moderate PA, vigorous PA, pain presence, and injury presence using generalized estimating equations with a logit link and binomial distribution. We adjusted the obtained models for potential confounders and explored the moderating effect of weight status. We found no association between moderate PA and pain, but time spent in vigorous PA was associated with pain. Neither moderate or vigorous PA were associated with injury, and there was no moderating effect of weight status in these relationships. In summary, we found that objectively measured vigorous PA is associated with pain among 8–12 year old children. While these results should be replicated in longitudinal studies, they suggest that an association between vigorous PA and pain should be considered when developing PA interventions for children.
Validation of persuasive audiovisual communication to reduce salt consumption by people with heart failure *

* Extracted from the thesis: “Comunicação persuasiva para motivar a intenção de reduzir o consumo de sal em pessoas com insuficiência cardíaca”, Programa de Pós-Graduação em Enfermagem, Universidade Federal da Paraíba, 2019. 1 Universidade Federal da Paraíba, Programa de Pós-Graduação em Enfermagem, João Pessoa, PB, Brazil. 2 Universidade Federal de Campina Grande, Campina Grande, PB, Brazil. 3 Universidade Federal de Campina Grande, Campus Cuité, Cuité, PB, Brazil. 4 Universidade Federal da Paraíba, Departamento de Enfermagem Clínica, João Pessoa, PB, Brazil. 5 Universidade Federal da Paraíba, Escola Técnica de Saúde, João Pessoa, PB, Brazil. ABSTRACT Objective: To build and validate persuasive audiovisual communication content to reduce salt consumption in the diet of people with heart failure. Method: Methodological study, of a technological method, based on the Theory of Planned Behavior, in which the stages of pre-production, production and post-production were followed. Content validation was carried out with specialists in the field of health and communication. Results: Based on the survey of beliefs related to salt reduction, the video contains 42 screens with three minutes and eleven seconds in duration and has animations and motivational arguments with the aim of positively influencing behavioral intention and modeling negative beliefs in positive ones. In content validation, the judges unanimously agreed with the evaluation criteria for the target audience, language, harmony, figures, narration and persuasion strategy. The Content Validity Index was satisfactory with a 97% agreement. Conclusion: Persuasive audiovisual communication was considered valid in terms of content, becoming a tool to enhance the reduction of salt consumption in the care of people with heart failure.
Hygro-thermo-mechanical performance of wheelchair cushion technologies in the prevention of pressure ulcers and moisture-associated skin damages

ABSTRACT This study aims at investigating the effects of three different wheelchair cushion technologies at the patient–wheelchair interface. To this end, eight participants were recruited to remain in an unrelieved seated position on a wheelchair successively equipped with three different cushions (foam, air-cell-based and gel), for a duration of 45 min. Interface pressure, temperature (measured with infrared thermography) and relative humidity were measured at the seat interface, at different timestamps. Experimental results show that foam cushion is significantly more efficient in reducing contact peak pressure (p < .01), while the gel cushion displays higher heat evacuation capabilities. In terms of relative humidity, no significant difference is observed among the three technologies (p > .29): all of them evacuate around only 10% of the total humidity compared to the reference situation (i.e., without cushion). Besides, a complementary numerical simulation corresponding to the steady state of the patient-wheelchair structure clearly highlights the temperature volume field at the underside of the seat, which acts like a thermal barrier and contributes to heat accumulation. Besides, an air flow at the underside of the chair in motion is shown to significantly reduce heat accumulation.
What is the median volume of intracerebral hemorrhage and is it changing?

Objectives Population-level estimates of the median intracerebral hemorrhage (ICH) volume would allow for the evaluation of clinical trial external validity and determination of temporal trends. We previously reported the median ICH volume in 1988. However, differences in risk factor management, neuroimaging, and demographics may have affected ICH volumes. The goal of this study is to determine the median volume of ICH within a population-based cross-sectional study, including whether it has changed over time. Methods The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was a population-based study of ICH among residents of the Greater Cincinnati/Northern Kentucky region from 2008 through 2012. This study utilizes those data and compares with ICH cases from the same region in 1988. Initial computed tomography images of the head were reviewed, and ICH volumes were calculated using consistent methodology. Results From 2008 through 2012, we identified 1117 cases of ICH. The median volume of ICH was 14.0 mL and was lower in black (11.6) than in white (15.5) patients. Median volumes of lobar and deep ICH were 28.8 mL and 9.8 mL, respectively. Median ICH volume changed significantly from 1988 to 2008–2012, with age-and-race-adjusted volume decreasing from 18.3 mL to 13.76 mL (p = 0.025). Conclusions Median volume of ICH was 13.76 mL, and this should be considered in clinical trial design. Median ICH volume has apparently decreased from 1988 to 2008–2012.
Basis of Image Analysis for Evaluating Cell Biomaterial Interaction Using Brightfield Microscopy

Medical imaging is a growing field that has stemmed from the need to conduct noninvasive diagnosis, monitoring, and analysis of biological systems. With the developments and advances in the medical field and the new techniques that are used in the intervention of diseases, very soon the prevalence of implanted biomedical devices will be even more significant. The implanted materials in a biological system are used in diverse fields, which require lengthy evaluation and validation processes. However, currently the evaluation of the toxicity of biomaterials has not been fully automated yet. Moreover, image analysis is an integral part of biomaterial research, but it is not within the core capacities of a significant portion of biomaterial scientists, which results in the use of predominantly ready-made tools. The detailed image analysis can be conducted once all the relevant parameters including the inherent characteristics of image acquisition techniques are considered. Herein, we cover the currently used image analysis-based techniques for assessment of biomaterial/cell interaction with a specific focus on unstained brightfield microscopy acquired mostly in but not limited to microfluidic systems, which serve as multiparametric sensing platforms for noninvasive experimental measurements. We present the major imaging acquisition techniques that enable point-of-care testing when incorporated with microfluidic cells, discuss the constraints enforced by the geometry of the system and the material that is analyzed, and the challenges that rise in the image analysis when unstained cell imaging is employed. Emerging techniques such as utilization of machine learning and cell-specific pattern recognition algorithms and potential future directions are discussed. Automation and optimization of biomaterial assessment can facilitate the discovery of novel biomaterials together with making the validation of biomedical innovations cheaper and faster.