Adapting a group-based, multimodal aphasia treatment for telehealth - co-design of M-MAT Tele.

Multi-Modality Aphasia Treatment (M-MAT) is an effective group intervention for post-stroke aphasia. M-MAT employs interactive card games and the modalities of gesture, drawing, reading, and writing to improve spoken language. However, there are challenges to implementation of group interventions such as M-MAT, particularly for those who cannot travel or live in rural areas. To maximise access to this effective treatment, we aimed to adapt M-MAT to telehealth format (M-MAT Tele). The Human-Centred Design Framework was utilized to guide the adaptation approach. We identified the intended context of use (outpatient/community rehabilitation) and the stakeholders (clinicians, people with aphasia, health service funders). People with aphasia and practising speech pathologists were invited to co-design M-MAT Tele in a series of iterative workshops, to ensure the end product was user-friendly and clinically feasible. The use of co-design allowed us to understand the hardware, software and other constraints and preferences of end users. In particular, clinicians (n = 3) required software compatible with a range of telehealth platforms and people with aphasia (n = 3) valued solutions with minimal technical demands and costs for participants. Co-design within the Human-Centred Design Framework led to a telehealth solution compatible with all major telehealth platforms, with minimal hardware or software requirements. Pilot testing is underway to confirm acceptability of M-MAT Tele to clinicians and people with aphasia, aiming to provide an effective, accessible tool for aphasia therapy in telehealth settings.

Physiological carry-over effects of variable precipitation are mediated by reproductive status in a long-lived ungulate.

In the age of global climate change, extreme climatic events are expected to increase in frequency and severity. Animals will be forced to cope with these novel stressors in their environment. Glucocorticoids (i.e. 'stress' hormones) facilitate an animal's ability to cope with their environment. To date, most studies involving glucocorticoids focus on the immediate physiological effects of an environmental stressor on an individual, few studies have investigated the long-term physiological impacts of such stressors. Here, we tested the hypothesis that previous exposure to an environmental stressor will impart lasting consequences to an individual's glucocorticoid levels. In semi-arid environments, variable rainfall drives forage availability for herbivores. Reduced seasonal precipitation can present an extreme environmental stressor potentially imparting long-term impacts on an individual's glucocorticoid levels. We examined the effects of rainfall and environmental characteristics (i.e. soil and vegetation attributes) during fawn-rearing (i.e. summer) on subsequent glucocorticoid levels of female white-tailed deer (Odocoileus virginianus) in autumn. We captured 124 adult (≥2.5-year-old) female deer via aerial net-gunning during autumn of 2015, 2016 and 2021 across four populations spanning a gradient of environmental characteristics and rainfall in the semi-arid environment of South Texas, USA. We found for every 1 cm decrease in summer rainfall, faecal glucocorticoid levels in autumn increased 6.9%, but only in lactating females. Glucocorticoid levels in non-lactating, female deer were relatively insensitive to environmental conditions. Our study demonstrates the long-lasting effects of environmental stressors on an individual's glucocorticoid levels. A better understanding of the long-term effects stressors impart on an individual's glucocorticoid levels will help to evaluate the totality of the cost of a stressor to an individual's welfare and predict the consequences of future climate scenarios.

Weather and leaf age separately contribute to temporal shifts in phyllosphere community structure and composition.

Microbial communities living on plant leaves can positively or negatively influence plant health and, by extension, can impact whole ecosystems. Most research into the leaf microbiome consists of snapshots, and little is known about how microbial communities change over time. Weather and host physiological characteristics change over time and are often collinear with other time-varying factors, such as substrate availability, making it difficult to separate the factors driving microbial community change. We leveraged repeated measures over the course of an entire year to isolate the relative importance of environmental, host physiological, and substrate age-related factors on the assembly, structure, and composition of leaf-associated fungal communities. We applied both culturing and sequencing approaches to investigate these communities, focusing on a foundational, widely-distributed plant of conservation concern: basin big sagebrush ( Artemisia tridentata subsp. tridentata ). We found that changes in alpha diversity were independently affected by the age of a community and the air temperature. Surprisingly, total fungal abundance and species richness were not positively correlated and responded differently, sometimes oppositely, to weather. With regard to beta diversity, communities were more similar to each other across similar leaf ages, air temperatures, leaf types, and δ 13 C stable isotope ratios. Nine different genera were differentially abundant with air temperature, δ 13 C, leaf type, and leaf age, and a set of 20 genera were continuously present across the year. Our findings highlight the necessity for longer-term, repeated sampling to parse drivers of temporal change in leaf microbial communities. Open Research Statement: All ITS DNA amplicon sequence raw data are deposited in the NCBI Sequence Read Archive (SRA), BioProject number PRJNA1107252, data will be released upon publication. All community data, metadata, taxonomic data, and R code necessary to reproduce these results are deposited in the GitHub repository archived on Zenodo: 10.5281/zenodo.11106439.

A Multi-Informant Assessment of Food Security in Adolescents: Discordance in Self-Report and Parent-Proxy Report.

Food insecurity is associated with a multitude of negative outcomes among adolescents. Despite adolescents' burgeoning autonomy, much of the research has relied on parent-proxy report, with few studies directly comparing adolescents' and parents' perceptions of adolescent food security. In the present study, parent-adolescent dyads (N = 144) completed questionnaires measuring perceptions of adolescent food security. Adolescents (12-17 years) completed the Child Food Security Survey Module. Parents completed the Household Food Security Survey Module. Dyads demonstrated discordant perceptions of adolescent food security on categorical- and item-levels of analysis. Further research is needed to elucidate explanations for these discrepancies using longitudinal designs.

Circulating biomarkers of kidney angiomyolipoma and cysts in tuberous sclerosis complex patients.

Patients with tuberous sclerosis complex (TSC) develop multi-organ disease manifestations, with kidney angiomyolipomas (AML) and cysts being one of the most common and deadly. Early and regular AML/cyst detection and monitoring are vital to lower TSC patient morbidity and mortality. However, the current standard of care involves imaging-based methods that are not designed for rapid screening, posing challenges for early detection. To identify potential diagnostic screening biomarkers of AML/cysts, we performed global untargeted metabolomics in blood samples from 283 kidney AML/cyst-positive or -negative TSC patients using mass spectrometry. We identified 7 highly sensitive chemical features, including octanoic acid, that predict kidney AML/cysts in TSC patients. Patients with elevated octanoic acid have lower levels of very long-chain fatty acids (VLCFAs), suggesting that dysregulated peroxisome activity leads to overproduction of octanoic acid via VLCFA oxidation. These data highlight AML/cysts blood biomarkers for TSC patients and offers valuable metabolic insights into the disease.

The effectiveness of a protocol without routine radiographs for follow-up of adolescent idiopathic scoliosis patients (CURVE): a study protocol.

BACKGROUND AND PURPOSE: Current follow-up protocols for adolescent idiopathic scoliosis (AIS) are based on consensus and consist of regular full-spine radiographs to monitor curve progression and surgical complications. Consensus exists to avoid inappropriate use of radiographs in children. It is unknown whether a standard radiologic follow-up (S-FU) approach is necessary or if a patient-empowered follow-up (PE-FU) approach can reduce the number of radiographs without treatment consequences. METHODS AND ANALYSES: A nationwide multicenter pragmatic randomized preference trial was designed for 3 follow-up subgroups (pre-treatment, post-brace, post-surgery) to compare PE-FU and S-FU. 812 patients with AIS (age 10-18 years) will be included in the randomized trial or preference cohorts. Primary outcome is the proportion of radiographs with a treatment consequence for each subgroup. Secondary outcomes consist of the proportion of patients with delayed initiation of treatment due to non-routine radiographic follow-up, radiation exposure, societal costs, positive predictive value, and interrelation of clinical assessment, quality of life, and parameters for initiation of treatment during follow-up. Outcomes will be analyzed using linear mixed-effects models, adjusted for relevant baseline covariates, and are based on intention-to-treat principle. Study summary: (i) a national, multicenter pragmatic randomized trial addressing the optimal frequency of radiographic follow-up in patients with AIS; (ii) first study that includes patient-empowered follow-up; (iii) an inclusive study with 3 follow-up subgroups and few exclusion criteria representative for clinical reality; (iv) preference cohorts alongside to amplify generalizability; (v) first study conducting an economic evaluation comparing both follow-up approaches.

Generation of Oviductal Glycoprotein 1 Cre Mouse Model for the Study of Secretory Epithelial Cells of the Oviduct.

The epithelial cell lining of the oviduct plays an important role in oocyte pickup, sperm migration, preimplantation embryo development, and embryo transport. The oviduct epithelial cell layer comprises ciliated and nonciliated secretory cells. The ciliary function has been shown to support gamete and embryo movement in the oviduct, yet secretory cell function has not been well characterized. Therefore, our goal was to generate a secretory cell-specific Cre recombinase mouse model to study the role of the oviductal secretory cells. A knock-in mouse model, Ovgp1Cre:eGFP, was created by expressing Cre from the endogenous Ovgp1 (oviductal glycoprotein 1) locus, with enhanced green fluorescent protein (eGFP) as a reporter. EGFP signals were strongly detected in the secretory epithelial cells of the oviducts at estrus in adult Ovgp1Cre:eGFP mice. Signals were also detected in the ovarian stroma, uterine stroma, vaginal epithelial cells, epididymal epithelial cells, and elongated spermatids. To validate recombinase activity, progesterone receptor (PGR) expression was ablated using the Ovgp1Cre:eGFP; Pgrf/f mouse model. Surprisingly, the deletion was restricted to the epithelial cells of the uterotubal junction (UTJ) region of Ovgp1Cre:eGFP; Pgrf/f oviducts. Deletion of Pgr in the epithelial cells of the UTJ region had no effect on female fecundity. In summary, we found that eGFP signals were likely specific to secretory epithelial cells in all regions of the oviduct. However, due to a potential target-specific Cre activity, validation of appropriate recombination and expression of the gene(s) of interest is absolutely required to confirm efficient deletion when generating conditional knockout mice using the Ovgp1Cre:eGFP line.

Rbpms2 promotes female fate upstream of the nutrient sensing Gator2 complex component Mios.

Reproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary biased. We previously showed the RNA binding protein (RNAbp), Rbpms2, is required for ovary fate in zebrafish. Here, we identified Rbpms2 targets in oocytes (Rbpms2-bound oocyte RNAs; rboRNAs). We identify Rbpms2 as a translational regulator of rboRNAs, which include testis factors and ribosome biogenesis factors. Further, genetic analyses indicate that Rbpms2 promotes nucleolar amplification via the mTorc1 signaling pathway, specifically through the mTorc1-activating Gap activity towards Rags 2 (Gator2) component, Missing oocyte (Mios). Cumulatively, our findings indicate that early gonocytes are in a dual poised, bipotential state in which Rbpms2 acts as a binary fate-switch. Specifically, Rbpms2 represses testis factors and promotes oocyte factors to promote oocyte progression through an essential Gator2-mediated checkpoint, thereby integrating regulation of sexual differentiation factors and nutritional availability pathways in zebrafish oogenesis.

High-Intensity Aphasia Intervention Is Minimally Fatiguing in Chronic Aphasia: An Analysis of Participant Self-Ratings From a Large Randomized Controlled Trial.

BACKGROUND: High-intensity therapy is recommended in current treatment guidelines for chronic poststroke aphasia. Yet, little is known about fatigue levels induced by treatment, which could interfere with rehabilitation outcomes. We analyzed fatigue experienced by people with chronic aphasia (>6 months) during high-dose interventions at 2 intensities. METHODS: A retrospective observational analysis was conducted on self-rated fatigue levels of people with chronic aphasia (N=173) collected during a previously published large randomized controlled trial of 2 treatments: constraint-induced aphasia therapy plus and multi-modality aphasia therapy. Interventions were administered at a higher intensity (30 hours over 2 weeks) or lower intensity (30 hours over 5 weeks). Participants rated their fatigue on an 11-point scale before and after each day of therapy. Data were analyzed using Bayesian ordinal multilevel models. Specifically, we considered changes in self-rated participant fatigue across a therapy day and over the intervention period. RESULTS: Data from 144 participants was analyzed. Participants were English speakers from Australia or New Zealand (mean age, 62 [range, 18-88] years) with 102 men and 42 women. Most had mild (n=115) or moderate (n=52) poststroke aphasia. Median ratings of the level of fatigue by people with aphasia were low (1 on a 0-10-point scale) at the beginning of the day. Ratings increased slightly (+1.0) each day after intervention, with marginally lower increases in the lower intensity schedule. There was no evidence of accumulating fatigue over the 2- or 5-week interventions. CONCLUSIONS: Findings suggest that intensive intervention was not associated with large increases in fatigue for people with chronic aphasia enrolled in the COMPARE trial (Constraint-Induced or Multimodality Personalised Aphasia Rehabilitation). Fatigue did not change across the course of the intervention. This study provides evidence that intensive treatment was minimally fatiguing for stroke survivors with chronic aphasia, suggesting that fatigue is not a barrier to high-intensity treatment.

DART.2: bidirectional synaptic pharmacology with thousandfold cellular specificity.

Precision pharmacology aims to manipulate specific cellular interactions within complex tissues. In this pursuit, we introduce DART.2 (drug acutely restricted by tethering), a second-generation cell-specific pharmacology technology. The core advance is optimized cellular specificity-up to 3,000-fold in 15 min-enabling the targeted delivery of even epileptogenic drugs without off-target effects. Additionally, we introduce brain-wide dosing methods as an alternative to local cannulation and tracer reagents for brain-wide dose quantification. We describe four pharmaceuticals-two that antagonize excitatory and inhibitory postsynaptic receptors, and two that allosterically potentiate these receptors. Their versatility is showcased across multiple mouse-brain regions, including cerebellum, striatum, visual cortex and retina. Finally, in the ventral tegmental area, we find that blocking inhibitory inputs to dopamine neurons accelerates locomotion, contrasting with previous optogenetic and pharmacological findings. Beyond enabling the bidirectional perturbation of chemical synapses, these reagents offer intersectional precision-between genetically defined postsynaptic cells and neurotransmitter-defined presynaptic partners.

Secondary Surgery Following Lapidus Bunionectomy.

While the Lapidus bunionectomy is a common procedure utilized to address hallux valgus, the incidence of secondary surgery is not well established. Our primary goal was to determine the incidence of revision surgery and hardware removal following the Lapidus bunionectomy in addition to the risk factors associated with each. A retrospective nested case-control study of adult patients who underwent a Lapidus bunionectomy for symptomatic hallux valgus over a nine-year period was performed. The incidence rates and 95% confidence intervals (CI) of secondary surgery in the three years following the procedure along with the estimated independent associations and odds ratios between baseline demographic, clinical, and radiographic characteristics were calculated. Of the original cohort of 2,540 patients, 127 were identified (5.0%; CI: 4.1%, 5.8%) who underwent revision surgery and 165 (6.5%; CI: 5.5%, 7.5%) who underwent hardware removal following Lapidus bunionectomy. Initially, the hallux valgus angle, intermetatarsal angle, and tibial sesamoid position were risk factors for revision surgery. However, in adjusted analyses for revision surgery, using a screw for third point of fixation emerged as the only independent risk factor (odds ratio [OR]=3.01; CI: 1.59, 5.69). In adjusted analyses for hardware removal, female sex (OR=2.33; CI: 1.08, 5.00) and third point of fixation (OR=2.92; CI: 1.82, 4.69) emerged as independent risk factors. While the overall risks associated with Lapidus bunionectomy are low and the need for revision surgery are low, this study helps to identify specific risk factors for secondary surgery and hardware removal to help in evaluation and discussion with patients. LEVEL OF EVIDENCE: : 4.

SNAPSHOT USA 2021: A third coordinated national camera trap survey of the United States.

SNAPSHOT USA is a multicontributor, long-term camera trap survey designed to survey mammals across the United States. Participants are recruited through community networks and directly through a website application (https://www.snapshot-usa.org/). The growing Snapshot dataset is useful, for example, for tracking wildlife population responses to land use, land cover, and climate changes across spatial and temporal scales. Here we present the SNAPSHOT USA 2021 dataset, the third national camera trap survey across the US. Data were collected across 109 camera trap arrays and included 1711 camera sites. The total effort equaled 71,519 camera trap nights and resulted in 172,507 sequences of animal observations. Sampling effort varied among camera trap arrays, with a minimum of 126 camera trap nights, a maximum of 3355 nights, a median 546 nights, and a mean 656 ± 431 nights. This third dataset comprises 51 camera trap arrays that were surveyed during 2019, 2020, and 2021, along with 71 camera trap arrays that were surveyed in 2020 and 2021. All raw data and accompanying metadata are stored on Wildlife Insights (https://www.wildlifeinsights.org/), and are publicly available upon acceptance of the data papers. SNAPSHOT USA aims to sample multiple ecoregions in the United States with adequate representation of each ecoregion according to its relative size. Currently, the relative density of camera trap arrays varies by an order of magnitude for the various ecoregions (0.22-5.9 arrays per 100,000 km2), emphasizing the need to increase sampling effort by further recruiting and retaining contributors. There are no copyright restrictions on these data. We request that authors cite this paper when using these data, or a subset of these data, for publication. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the US Government.

Mapping of susceptibility loci for Ebola virus pathogenesis in mice.

Ebola virus (EBOV), a major global health concern, causes severe, often fatal EBOV disease (EVD) in humans. Host genetic variation plays a critical role, yet the identity of host susceptibility loci in mammals remains unknown. Using genetic reference populations, we generate an F2 mapping cohort to identify host susceptibility loci that regulate EVD. While disease-resistant mice display minimal pathogenesis, susceptible mice display severe liver pathology consistent with EVD-like disease and transcriptional signatures associated with inflammatory and liver metabolic processes. A significant quantitative trait locus (QTL) for virus RNA load in blood is identified in chromosome (chr)8, and a severe clinical disease and mortality QTL is mapped to chr7, which includes the Trim5 locus. Using knockout mice, we validate the Trim5 locus as one potential driver of liver failure and mortality after infection. The identification of susceptibility loci provides insight into molecular genetic mechanisms regulating EVD progression and severity, potentially informing therapeutics and vaccination strategies.

Developing consensus-based clinical competencies to guide stroke clinicians in the implementation of psychological care in aphasia rehabilitation.

Background People with aphasia experience depression and anxiety associated with negative outcomes across a range of time post-stroke. Stroke clinicians are well-positioned to facilitate low-intensity psychotherapeutic interventions after aphasia (e.g. mood screening, behavioural activation, problem-solving therapy, relaxation therapy); however, they self-report a lack of knowledge, skills and confidence to do so. The Theoretical Domains Framework (TDF) provides a lens through which to view and target clinician behaviours and training needs in this area of practice. The aim of this study was to develop and gain consensus on items for a rating scale of clinical competencies in facilitating individual-based, low-intensity psychotherapeutic interventions for people with aphasia. Methods An e-Delphi methodology using focus groups and survey rounds was used to gain consensus on clinical competencies considered important. Results Eight stroke clinicians (speech pathologists and psychologists), two people with aphasia and three family members participated in one of four focus groups. Four themes were derived from the data: (1) Communication support, (2) Assessment and therapy structure, (3) Interpersonal skills, and (4) Needs of the significant other (family or friend). Themes informed an initial list of 23 self-rated and observer-rated competency items. Following two rounds of e-Delphi surveys, 11 stroke clinicians (six speech pathologists and five psychologists) reached consensus (80-100%) for 19 competencies. Conclusions The Psychological Care in Aphasia Rehabilitation Competency scale offers a preliminary list of items to guide and train clinicians to implement low-intensity psychotherapeutic interventions for people with aphasia.

Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that causes severe and often lethal respiratory illness in humans. The MERS-CoV spike (S) protein is the viral fusogen and the target of neutralizing antibodies, and has therefore been the focus of vaccine design efforts. Currently there are no licensed vaccines against MERS-CoV and only a few candidates have advanced to Phase I clinical trials. Here we developed MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including a licensed vaccine for SARS-CoV-2. Two-component protein nanoparticles displaying MERS-CoV S-derived antigens induced robust neutralizing antibody responses and protected mice against challenge with mouse-adapted MERS-CoV. Electron microscopy polyclonal epitope mapping and serum competition assays revealed the specificities of the dominant antibody responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle vaccine elicited antibodies targeting multiple non-overlapping epitopes in the RBD, whereas anti-NTD antibodies elicited by the S-2P- and NTD-based immunogens converged on a single antigenic site. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.

The Costs of Caring: Quantifying Compassion Fatigue and Compassion Satisfaction in Burn Therapists.

Recovery from a severe burn injury requires early and aggressive therapy, which is often painful and distressing to the patient. Burn therapists who guide these interventions may be prone to experiencing secondary trauma and compassion fatigue through repeated exposure to difficult situations. At the same time, therapists may gain a sense of purpose and altruism from their work, fostering compassion satisfaction. Despite being well documented in other health professions, compassion fatigue and compassion satisfaction have not been sufficiently explored among burn therapists. This study aimed to quantify and characterize burn therapists' compassion fatigue and satisfaction using the Professional Quality of Life scale and to answer the question of what job-related factors may impact these outcomes. A total of 143 burn therapists participated in this study. Results revealed compassion fatigue subsale scores of burnout and secondary traumatic stress in the low or moderate range and compassion satisfaction scores in the moderate or high ranges for all participants. This study presents new knowledge for the field of burn care in its quantification of professional quality of life in burn therapists. While burn therapists experienced moderate-to-high levels of compassion satisfaction in their work, burnout and stress also approached moderate levels. Years of practice was a significant predictor of compassion. Although the reasons for this are not clear, it may be related to increased competence or confidence in practice and may suggest a need for different support strategies for practitioners at each stage of their burn therapy career.

Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.