Codesigning a Community Health Navigator program to assist patients to transition from hospital to community.

Background This study aimed to identify the potential roles for Community Health Navigators (CHNs) in addressing problems faced by patients on discharge from hospital to the community, and attitudes and factors which may influence their adoption. Methods Twenty-six qualitative interviews and an online codesign workshop were conducted with patients, nurses, general practice staff, health service managers, community health workers, general practitioners, medical specialists, and pharmacists in the Sydney Local Health District. Qualitative themes from the interviews and workshop transcripts were analysed inductively and subsequently grouped according to a socio-ecological model. Results CHNs could assist patients to navigate non-clinical problems experienced by patients on discharge through assessing needs, establishing trust, providing social and emotional support that is culturally and linguistically appropriate, engaging family and carers, supporting medication adherence, and helping to arrange and attend follow up health and other appointments. Important factors for the success of the CHNs in the performance and sustainability of their roles were the need to establish effective communication and trust with other healthcare team members, be accepted by patients, have access to information about referral and support services, receive formal recognition of their training and experience, and be supported by appropriate supervision. Conclusions This study was unique in exploring the potential role of CHNs in addressing problems faced by patients on discharge from Australian hospitals and the factors influencing their adoption. It informed training and supervision needs and further research to evaluate CHNs' effectiveness and the acceptance of their role within the healthcare team.

Freedom for some, but not for Mum: the reproductive injustice associated with pandemic 'Freedom Day' for perinatal women in the United Kingdom.

Introduction: Healthcare services for pregnant and postpartum ('perinatal') women were reconfigured significantly at the advent and for the duration of the SARS-CoV-2 pandemic, and despite the United Kingdom announcing 'Freedom Day' on 19 July 2021 (whereafter all legal lockdown-related restrictions were lifted), restrictions to maternity (antenatal, intrapartum, and postnatal) services remained. This study presents data from eight perinatal women about their experiences of psychosocial wellbeing and maternity care in the post-'Freedom Day' epoch. Methods: Semi-structured interviews were conducted virtually, with data recorded, transcribed, and analysed by hand. Grounded theory analysis was employed with the final theory assessing the reproductive injustice of the pandemic 'Freedom Day'. Results: Analysing iteratively and inductively led to four emergent themes: 'A Failing System, Failing Women'; 'Harm Caused by a State of Difference'; 'The Privileges (Not Rights) of Reproductive Autonomy, Agency, and Advocacy'; and 'Worried Women and Marginalised Mothers'. Together, these themes form the theory of 'Freedom for some, but not for Mum'. Discussion: Women experienced a lack of high-quality reliable information about the pandemic, vaccination against the virus, and the changes to, and decision-making surrounding, their perinatal care. Women recognised healthcare professionals and maternity services were stretched and that maternity services were failing but often reported hostility from staff and abandonment at times when they were unsure about how to navigate their care. The most singular injustice was the disparity between women having to accept continuing restrictions to their freedom whilst receiving maternity care and the (reckless) freedom being enacted by the general public.

Loss-of-function variants in JPH1 cause congenital myopathy with prominent facial and ocular involvement.

BACKGROUND: Weakness of facial, ocular and axial muscles is a common clinical presentation in congenital myopathies caused by pathogenic variants in genes encoding triad proteins. Abnormalities in triad structure and function resulting in disturbed excitation-contraction coupling and Ca2+ homeostasis can contribute to disease pathology. METHODS: We analysed exome and genome sequencing data from four unrelated individuals with congenital myopathy characterised by facial, ocular and bulbar involvement. We collected deep phenotypic data from the affected individuals. We analysed the RNA-sequencing (RNA-seq) data of F3-II.1 and performed gene expression outlier analysis in 129 samples. RESULTS: The four probands had a remarkably similar clinical presentation with prominent facial, ocular and bulbar features. Disease onset was in the neonatal period with hypotonia, poor feeding, cleft palate and talipes. Muscle weakness was generalised but prominent in the lower limbs with facial weakness also present. All patients had myopathic facies, bilateral ptosis, ophthalmoplegia and fatigability. Muscle biopsy on light microscopy showed type 1 myofiber predominance and ultrastructural analysis revealed slightly reduced triads, and structurally abnormal sarcoplasmic reticulum.DNA sequencing identified four unique homozygous loss-of-function variants in JPH1, encoding junctophilin-1 in the four families; one stop-gain (c.354C>A;p.Tyr118*) and three frameshift (c.373delG;p.Asp125Thrfs*30, c.1738delC;p.Leu580Trpfs*16 and c.1510delG;p. Glu504Serfs*3) variants. Muscle RNA-seq showed strong downregulation of JPH1 in the F3 proband. CONCLUSIONS: Junctophilin-1 is critical for the formation of skeletal muscle triad junctions by connecting the sarcoplasmic reticulum and T-tubules. Our findings suggest that loss of JPH1 results in a congenital myopathy with prominent facial, bulbar and ocular involvement.

An Integrated Transcriptomics and Genomics Approach Detects an X/Autosome Translocation in a Female with Duchenne Muscular Dystrophy.

Duchenne and Becker muscular dystrophies, caused by pathogenic variants in DMD, are the most common inherited neuromuscular conditions in childhood. These diseases follow an X-linked recessive inheritance pattern, and mainly males are affected. The most prevalent pathogenic variants in the DMD gene are copy number variants (CNVs), and most patients achieve their genetic diagnosis through Multiplex Ligation-dependent Probe Amplification (MLPA) or exome sequencing. Here, we investigated a female patient presenting with muscular dystrophy who remained genetically undiagnosed after MLPA and exome sequencing. RNA sequencing (RNAseq) from the patient's muscle biopsy identified an 85% reduction in DMD expression compared to 116 muscle samples included in the cohort. A de novo balanced translocation between chromosome 17 and the X chromosome (t(X;17)(p21.1;q23.2)) disrupting the DMD and BCAS3 genes was identified through trio whole genome sequencing (WGS). The combined analysis of RNAseq and WGS played a crucial role in the detection and characterisation of the disease-causing variant in this patient, who had been undiagnosed for over two decades. This case illustrates the diagnostic odyssey of female DMD patients with complex structural variants that are not detected by current panel or exome sequencing analysis.

Transcriptomic alterations in cortical astrocytes following the development of post-traumatic epilepsy.

Post-traumatic epilepsy (PTE) stands as one of the numerous debilitating consequences that follow traumatic brain injury (TBI). Despite its impact on many individuals, the current landscape offers only a limited array of reliable treatment options, and our understanding of the underlying mechanisms and susceptibility factors remains incomplete. Among the potential contributors to epileptogenesis, astrocytes, a type of glial cell, have garnered substantial attention as they are believed to promote hyperexcitability and the development of seizures in the brain following TBI. The current study evaluated the transcriptomic changes in cortical astrocytes derived from animals that developed seizures as a result of severe focal TBI. Using RNA-Seq and ingenuity pathway analysis (IPA), we unveil a distinct gene expression profile in astrocytes, including alterations in genes supporting inflammation, early response modifiers, and neuropeptide-amidating enzymes. The findings underscore the complex molecular dynamics in astrocytes during PTE development, offering insights into therapeutic targets and avenues for further exploration.

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene. The co-occurrence of predicted deleterious SRPK3/TTN variants was not seen among 76,702 healthy male individuals, and statistical modeling strongly supported digenic inheritance as the best-fitting model. Furthermore, double-mutant zebrafish (srpk3-/-; ttn.1+/-) replicated the myopathic phenotype and showed myofibrillar disorganization. Transcriptome data suggest that the interaction of srpk3 and ttn.1 in zebrafish occurs at a post-transcriptional level. We propose that digenic inheritance of deleterious changes impacting both the protein kinase SRPK3 and the giant muscle protein titin causes a skeletal myopathy and might serve as a model for other genetic diseases.

Community health navigator-assisted transition of care from hospital to community: protocol for a randomised controlled trial.

INTRODUCTION: The objective of this parallel group, randomised controlled trial is to evaluate a community health navigator (CHN) intervention provided to patients aged over 40 years and living with chronic health conditions to transition from hospital inpatient care to their homes. Unplanned hospital readmissions are costly for the health system and negatively impact patients. METHODS AND ANALYSIS: Patients are randomised post hospital discharge to the CHN intervention or usual care. A comparison of outcomes between intervention and control groups will use multivariate regression techniques that adjust for age, sex and any independent variables that are significantly different between the two groups, using multiple imputation for missing values. Time-to-event analysis will examine the relationship between seeing a CHN following discharge from the index hospitalisation and reduced rehospitalisations in the subsequent 60 days and 6 months. Secondary outcomes include medication adherence, health literacy, quality of life, experience of healthcare and health service use (including the cost of care). We will also conduct a qualitative assessment of the implementation of the navigator role from the viewpoint of stakeholders including patients, health professionals and the navigators themselves. ETHICS APPROVAL: Ethics approval was obtained from the Research Ethics and Governance Office, Sydney Local Health District, on 21 January 2022 (Protocol no. X21-0438 and 2021/ETH12171). The findings of the trial will be disseminated through peer-reviewed journals and national and international conference presentations. Data will be deposited in an institutional data repository at the end of the trial. This is subject to Ethics Committee approval, and the metadata will be made available on request. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN 12622000659707). ARTICLE SUMMARY: The objective of this trial is to evaluate a CHN intervention provided to patients aged over 40 years and living with chronic health conditions to transition from hospital inpatient care to their homes.

Loss-of-function variants in JPH1 cause congenital myopathy with prominent facial involvement.

Background: Weakness of facial, ocular, and axial muscles is a common clinical presentation in congenital myopathies caused by pathogenic variants in genes encoding triad proteins. Abnormalities in triad structure and function resulting in disturbed excitation-contraction coupling and Ca 2+ homeostasis can contribute to disease pathology. Methods: We analysed exome and genome sequencing data from three unrelated individuals with congenital myopathy characterised by striking facial, ocular, and bulbar involvement. We collected deep phenotypic data from the affected individuals. We analysed the RNA-seq data of one proband and performed gene expression outlier analysis in 129 samples. Results: The three probands had remarkably similar clinical presentation with prominent facial, ocular, and bulbar features. Disease onset was in the neonatal period with hypotonia, poor feeding, cleft palate and talipes. Muscle weakness was generalised but most prominent in the lower limbs with facial weakness also present. All patients had myopathic facies, bilateral ptosis, ophthalmoplegia and fatiguability. While muscle biopsy on light microscopy did not show any obvious morphological abnormalities, ultrastructural analysis showed slightly reduced triads, and structurally abnormal sarcoplasmic reticulum. DNA sequencing identified three unique homozygous loss of function variants in JPH1 , encoding junctophilin-1 in the three families; a stop-gain (c.354C>A; p.Tyr118*) and two frameshift (c.373del p.Asp125Thrfs*30 and c.1738del; p.Leu580Trpfs*16) variants. Muscle RNA-seq showed strong downregulation of JPH1 in the F3 proband. Conclusions: Junctophilin-1 is critical to the formation of skeletal muscle triad junctions by connecting the sarcoplasmic reticulum and T-tubules. Our findings suggest that loss of JPH1 results in a congenital myopathy with prominent facial, bulbar and ocular involvement. Key message: This study identified novel homozygous loss-of-function variants in the JPH1 gene, linking them to a unique form of congenital myopathy characterised by severe facial and ocular symptoms. Our research sheds light on the critical impact on junctophilin-1 function in skeletal muscle triad junction formation and the consequences of its disruption resulting in a myopathic phenotype. What is already known on this topic: Previous studies have shown that pathogenic variants in genes encoding triad proteins lead to various myopathic phenotypes, with clinical presentations often involving muscle weakness and myopathic facies. The triad structure is essential for excitation-contraction (EC) coupling and calcium homeostasis and is a key element in muscle physiology. What this study adds and how this study might affect research practice or policy: This study establishes that homozygous loss-of-function mutations in JPH1 cause a congenital myopathy predominantly affecting facial and ocular muscles. This study also provides clinical insights that may aid the clinicians in diagnosing similar genetically unresolved cases.

STING-Dependent Signaling in Microglia or Peripheral Immune Cells Orchestrates the Early Inflammatory Response and Influences Brain Injury Outcome.

While originally identified as an antiviral pathway, recent work has implicated that cyclic GMP-AMP-synthase-Stimulator of Interferon Genes (cGAS-STING) signaling is playing a critical role in the neuroinflammatory response to traumatic brain injury (TBI). STING activation results in a robust inflammatory response characterized by the production of inflammatory cytokines called interferons, as well as hundreds of interferon stimulated genes (ISGs). Global knock-out (KO) mice inhibiting this pathway display neuroprotection with evidence that this pathway is active days after injury; yet, the early neuroinflammatory events stimulated by STING signaling remain understudied. Furthermore, the source of STING signaling during brain injury is unknown. Using a murine controlled cortical impact (CCI) model of TBI, we investigated the peripheral immune and microglial response to injury utilizing male chimeric and conditional STING KO animals, respectively. We demonstrate that peripheral and microglial STING signaling contribute to negative outcomes in cortical lesion volume, cell death, and functional outcomes postinjury. A reduction in overall peripheral immune cell and neutrophil infiltration at the injury site is STING dependent in these models at 24 h. Transcriptomic analysis at 2 h, when STING is active, reveals that microglia drive an early, distinct transcriptional program to elicit proinflammatory genes including interleukin 1-ß (IL-1ß), which is lost in conditional knock-out mice. The upregulation of alternative innate immune pathways also occurs after injury in these animals, which supports a complex relationship between brain-resident and peripheral immune cells to coordinate the proinflammatory response and immune cell influx to damaged tissue after injury.

Data from a national survey of United States primary care physicians on genetic risk scores for common disease prevention.

Genetic risk scores (GRS) are an emerging and rapidly evolving genomic medicine innovation that may contribute to more precise risk stratification for disease prevention. Inclusion of GRS in routine medical care is imminent, and understanding how physicians perceive and intend to utilize GRS in practice is an important first step in facilitating uptake. This dataset was derived from an electronic survey and comprises one of the first, largest, and broadest samples of United States primary care physician perceptions on the clinical decision-making, benefits, barriers, and utility of GRS to date. The dataset is nearly complete (<1% missing data) and contains responses from 369 PCPs spanning 58 column variables. The public repository includes minimally filtered, de-identified data, all underlying survey versions and items, a data dictionary, and associated analytic files.

The identification and measurement of postpartum anxiety in England: A Delphi survey.

Postpartum anxiety has negative consequences for both mother and infant, so effective identification and measurement is vital to enable intervention. Despite NICE recommendations to prioritise the measurement of postpartum anxiety in mothers, current clinical measurement in England remains both fragmented and flawed. The Postpartum Specific Anxiety Scale [PSAS] offers an alternative, as it measures maternal-focused anxieties which can enable specifically targeted interventions. However, it is only currently used as a research tool and may require modification for clinical use. To inform modification of the PSAS, nineteen stakeholders from a variety of organisations participated in a two-round Delphi consensus survey to measure its clinical relevance and potential for effective identification of clinical anxiety. Descriptive analyses revealed all subscales of the PSAS scored highly across all domains, excluding Practical Infant Care Anxieties. Analyses also indicated good consensus between stakeholders across specific items, suggesting that the some items on the PSAS are relevant and effective at identifying clinical postpartum anxiety. Participants also expressed a need for a shorter version of the PSAS for clinical use, and that additional items may need including. Future research must now adapt the existing PSAS based on the results of this study and pilot the adapted measure in a clinical population.

The GenoVA study: Equitable implementation of a pragmatic randomized trial of polygenic-risk scoring in primary care.

Polygenic risk scores (PRSs) hold promise for disease risk assessment and prevention. The Genomic Medicine at Veterans Affairs (GenoVA) Study is addressing three main challenges to the clinical implementation of PRSs in preventive care: defining and determining their clinical utility, implementing them in time-constrained primary care settings, and countering their potential to exacerbate healthcare disparities. The study processes used to test patients, report their PRS results to them and their primary care providers (PCPs), and promote the use of those results in clinical decision-making are modeled on common practices in primary care. The following diseases were chosen for their prevalence and familiarity to PCPs: coronary artery disease; type 2 diabetes; atrial fibrillation; and breast, colorectal, and prostate cancers. A randomized clinical trial (RCT) design and primary outcome of time-to-new-diagnosis of a target disease bring methodological rigor to the question of the clinical utility of PRS implementation. The study's pragmatic RCT design enhances its relevance to how PRS might reasonably be implemented in primary care. Steps the study has taken to promote health equity include the thoughtful handling of genetic ancestry in PRS construction and reporting and enhanced recruitment strategies to address underrepresentation in research participation. To date, enhanced recruitment efforts have been both necessary and successful: participants of underrepresented race and ethnicity groups have been less likely to enroll in the study than expected but ultimately achieved proportional representation through targeted efforts. The GenoVA Study experience to date offers insights for evaluating the clinical utility of equitable PRS implementation in adult primary care.

Design Strategies for Luminescent Titanocenes: Improving the Photoluminescence and Photostability of Arylethynyltitanocenes.

Complexes that undergo ligand-to-metal charge transfer (LMCT) to d0 metals are of interest as possible photocatalysts. Cp2Ti(C2Ph)2 (where C2Ph = phenylethynyl) was reported to be weakly emissive in room-temperature (RT) fluid solution from its phenylethynyl-to-Ti 3LMCT state but readily photodecomposes. Coordination of CuX between the alkyne ligands to give Cp2Ti(C2Ph)2CuX (X = Cl, Br) has been shown to significantly increase the photostability, but such complexes are not emissive in RT solution. Herein, we investigate whether inhibition of alkyne-Ti-alkyne bond compression might be responsible for the increased photostability of the CuX complexes by investigating the decomposition of a structurally constrained analogue, Cp2Ti(OBET) (OBET = o-bis(ethynyl)tolane). To investigate the mechanism of nonradiative decay from the 3LMCT states in Cp2Ti(C2Ph)2CuX, the photophysical properties were investigated both upon deuteration and upon rigidifying in a poly(methyl methacrylate) film. These investigations suggested that inhibition of structural rearrangement may play a dominant role in increasing emission lifetimes and quantum yields. The bulkier Cp*2Ti(C2Ph)2CuBr was prepared and is emissive at 693 nm in RT THF solution with a photoluminescent quantum yield of 1.3 × 10-3 (τ = 0.18 µs). Time-dependent density functional theory (TDDFT) calculations suggest that emission occurs from a 3LMCT state dominated by Cp*-to-Ti charge transfer.

Dissemination and implementation of clinical practice guidelines: a longitudinal, mixed-methods evaluation of the Canadian Task Force on Preventive Health Care's knowledge translation efforts.

BACKGROUND: The Canadian Task Force on Preventive Health Care (task force) develops evidence-based preventive health care guidelines and knowledge translation (KT) tools to facilitate guideline dissemination and implementation. We aimed to determine practitioners' awareness of task force guidelines and KT tools and explore barriers and facilitators to their use. METHODS: The task force's KT team completed annual evaluations using surveys and interviews with primary care providers in Canada from 2014 to 2020, to assess practitioners' awareness and determinants of use of task force guidelines and tools. We transcribed interviews verbatim and double-coded them using a framework analysis approach. RESULTS: A total of 1284 primary care practitioners completed surveys and 183 participated in interviews. On average, 79.9% of participants were aware of the task force's 7 cancer screening guidelines, 36.2% were aware of the other 6 screening guidelines and 18.6% were aware of the 3 lifestyle or prevention guidelines. Participants identified 13 barriers and 7 facilitators to guideline and KT tool implementation; these were consistent over time. Participants identified strategies at the public and patient, provider and health systems levels to improve uptake of guidelines. INTERPRETATION: Canadian primary care practitioners were more aware of task force cancer screening guidelines than its other preventive health guidelines. Over the 6-year period, participants consistently reported barriers to guideline uptake, including misalignment with patient preferences and other provincial or specialty guideline organizations. Further evaluations will assess tailored strategies to address the barriers identified.

Longitudinal Analysis of Respiratory Function of Different Types of Limb Girdle Muscular Dystrophies Reveals Independent Trajectories.

Background and Objectives: The prevalence and progression of respiratory muscle dysfunction in patients with limb girdle muscular dystrophies (LGMDs) has been only partially described to date. Most reports include cross-sectional data on a limited number of patients making it difficult to gain a wider perspective on respiratory involvement throughout the course of the disease and to compare the most prevalent LGMD subtypes. Methods: We reviewed the results of spirometry studies collected longitudinally in our cohort of patients in routine clinical visits from 2002 to 2020 along with additional clinical and genetic data. A linear mixed model was used to investigate the factors associated with the progression of respiratory dysfunction. Results: We followed up 156 patients with 5 different forms of LGMDs for a median of 8 years (range 1-25 years). Of them, 53 patients had pathogenic variants in the Capn3 gene, 47 patients in the Dysf gene, 24 patients in the Fkrp gene, 19 in the Ano5 gene, and 13 in one of the sarcoglycan genes (SCG). At baseline, 58 patients (37.1%) had a forced vital capacity percentage predicted (FVCpp) below 80%, while 14 patients (8.9%) had peak cough flow (PCF) values below 270 L/min. As a subgroup, FKRP was the group with a higher number of patients having FVC <80% and/or PCF <270 L/min at initial assessment (66%). We observed a progressive decline in FVCpp and PCF measurements over time, being age, use of wheelchair, and LGMD subtype independent factors associated with this decline. Fkrp and sarcoglycan patients had a quicker decline in their FVC (Kaplan-Meier curve, F test, p < 0.001 and p = 0.02, respectively). Only 7 of the 58 patients with low FVCpp values reported symptoms of respiratory dysfunction, which are commonly reported by patients with FVCpp below 50%-60%. The number of patients ventilated increased from 2 to 8 during follow-up. Discussion: Respiratory dysfunction is a frequent complication of patients with LGMDs that needs to be carefully studied and has direct implications in the care offered in daily clinics. Respiratory dysfunction is associated with disease progression because it is especially seen in patients who are full-time wheelchair users, being more frequent in patients with mutations in the Fkrp and sarcoglycan genes.

Broadening the Spectrum of SLC22A5 Phenotype: Primary Carnitine Deficiency Presenting with Focal Myoclonus.

Primary carnitine deficiency (PCD) is caused by pathogenic variants of the SLC22A5 gene, which encodes a transmembrane protein that functions as a high affinity carnitine transporter. Carnitine is essential for the transport of acyl-CoA, produced from fatty acids, into the mitochondria where they are oxidised to produce energy. We present the case history of an 8-year-old boy who presented with fever, lethargy, focal rhythmic (3 Hz) left wrist twitching, and severe encephalopathy. MRI brain showed basal ganglia involvement. Metabolic investigations revealed low serum carnitine; whole genome sequencing confirmed compound heterozygous SLC22A5 mutations. With carnitine replacement, intensive care support, and neurorehabilitation, he made a remarkable recovery, regaining independent breathing, speech, mobility, and hand use. Seizure presentation in PCD is rare and presentation with sustained focal myoclonus has not been previously reported. This case expands the known phenotype of PCD. Prompt carnitine replacement is imperative.

A Mobile Application Adjunct to Augment Cognitive-Behavioral Group Therapy for Adolescents with Social Anxiety: Feasibility and Acceptability Results from the Wiring Adolescents with Social Anxiety via Behavioral Interventions Pilot Trial.

Objective: Cognitive-Behavioral Group Therapy (CBGT) is an established treatment for Social Anxiety (SA). However, diagnostic recovery rate is only 20.5% in CBGT, and up to 50% of patients remain symptomatic posttreatment. Using videocalls to deliver digital CBGT (dCBGT) is feasible, cost-effective, and efficacious. Yet, the impact of dCBGT on social functioning remains limited, as dCBGT does not offer opportunities for monitoring cognition and behavior in social situations. Wiring Adolescents with Social Anxiety via Behavioral Interventions (WASABI), a clinician-assisted application that uses ecological momentary assessments (EMAs), cognitive bias tests, and clinical self-reports, was investigated as an adjunct to dCBGT. Methods: A prospective, parallel arm, double-blind randomized controlled trial was employed in 24 SA adolescents randomly assigned to dCBGT versus dCBGT plus WASABI. Results: Study completion rates (83%) and exit survey data indicated that WASABI is feasible and acceptable. Engagement with EMAs varied from four to 244 EMAs completed per person. Cognitive bias tests and clinical self-reports were completed at least weekly by 53% and 69% of participants, respectively. While standard tests did not reveal statistically significant differences between dCBGT plus WASABI and dCBGT alone, effect sizes were greater for dCBGT plus WASABI on symptom severity, social skills, and functioning. Conclusions: Despite the small sample, preliminary results suggest that WASABI is feasible, acceptable, and may be an effective augmentation tool for treating SA in teenagers.

Activating hidden signals by mimicking cryptic sites in a synthetic extracellular matrix.

Cryptic sites are short signaling peptides buried within the native extracellular matrix (ECM). Enzymatic cleavage of an ECM protein reveals these hidden peptide sequences, which interact with surface receptors to control cell behavior. Materials that mimic this dynamic interplay between cells and their surroundings via cryptic sites could enable application of this endogenous signaling phenomenon in synthetic ECM hydrogels. We demonstrate that depsipeptides ("switch peptides") can undergo enzyme-triggered changes in their primary sequence, with proof-of-principle studies showing how trypsin-triggered primary sequence rearrangement forms the bioadhesive pentapeptide YIGSR. We then engineered cryptic site-mimetic synthetic ECM hydrogels that experienced a cell-initiated gain of bioactivity. Responding to the endothelial cell surface enzyme aminopeptidase N, the inert matrix transformed into an adhesive synthetic ECM capable of supporting endothelial cell growth. This modular system enables dynamic reciprocity in synthetic ECMs, reproducing the natural symbiosis between cells and their matrix through inclusion of tunable hidden signals.

The role of political devotion in sharing partisan misinformation and resistance to fact-checking.

Online misinformation is disproportionality created and spread by people with extreme political attitudes, especially among the far-right. There is a debate in the literature about why people spread misinformation and what should be done about it. According to the purely cognitive account, people largely spread misinformation because they are lazy, not biased. According to a motivational account, people are also motivated to believe and spread misinformation for ideological and partisan reasons. To better understand the psychological and neurocognitive processes that underlie misinformation sharing among the far-right, we conducted a cross-cultural experiment with conservatives and far-right partisans in the Unites States and Spain (N = 1,609) and a neuroimaging study with far-right partisans in Spain (N = 36). Far-right partisans in Spain and U.S. Republicans who highly identify with Trump were more likely to share misinformation than center-right voters and other Republicans, especially when the misinformation was related to sacred values (e.g., immigration). Sacred values predicted misinformation sharing above and beyond familiarity, attitude strength, and salience of the issue. Moreover, far-right partisans were unresponsive to fact-checking and accuracy nudges. At a neural level, this group showed increased activity in brain regions implicated in mentalizing and norm compliance in response to posts with sacred values. These results suggest that the two components of political devotion-identity fusion and sacred values-play a key role in misinformation sharing, highlighting the identity-affirming dimension of misinformation sharing. We discuss the need for motivational and identity-based interventions to help curb misinformation for high-risk partisan groups. (PsycInfo Database Record (c) 2023 APA, all rights reserved).