Screening for psychosis risk in primary mental health care services - Implementation, prevalence and recovery trajectories.

OBJECTIVES: Early interventions improve outcomes for people at high risk of psychosis and are likely to be cost saving. This group tends to seek help for emotional problems - depression and anxiety - via primary care services, where early detection methods are poor. We sought to determine prevalence rates of high risk for psychosis in UK primary care mental health services and clinical outcomes following routinely delivered psychological therapies. METHODS: We used a brief screen designed for settings with low base rates and significant time constraints to determine prevalence of high risk for psychosis in UK 'Talking Therapies' services. We examined socio-demographic characteristics, presenting problems and recovery trajectories for this group, compared with people not at risk of psychosis. RESULTS: A 2-item screen selected for specificity yielded a prevalence rate of 3% in primary care mental health services. People at elevated risk of psychosis were younger and more likely to report at least one long-term physical condition. This group presented with higher levels of depression, anxiety and trauma symptoms at assessment and were less likely to have recovered at the end of treatment, compared to people not at risk. CONCLUSIONS: Very brief screening tools can be implemented in busy health care settings. The 3% of referrals to UK primary care psychological therapies services at elevated risk of psychosis typically present with more severe symptoms and greater levels of comorbidity and may require augmented interventions to recover fully.

Neuromodulation with Ultrasound: Hypotheses on the Directionality of Effects and a Community Resource.

Low-intensity Transcranial Ultrasound Stimulation (TUS) is a promising non-invasive technique for deep-brain stimulation and focal neuromodulation. Research with animal models and computational modelling has raised the possibility that TUS can be biased towards enhancing or suppressing neural function. Here, we first conduct a systematic review of human TUS studies for perturbing neural function and alleviating brain disorders. We then collate a set of hypotheses on the directionality of TUS effects and conduct an initial meta-analysis on the human TUS study reported outcomes to date ( n = 32 studies, 37 experiments). We find that parameters such as the duty cycle show some predictability regarding whether the targeted area's function is likely to be enhanced or suppressed. Given that human TUS sample sizes are exponentially increasing, we recognize that results can stabilize or change as further studies are reported. Therefore, we conclude by establishing an Iowa-Newcastle (inTUS) resource for the systematic reporting of TUS parameters and outcomes to support further hypothesis testing for greater precision in brain stimulation and neuromodulation with TUS. Highlights: Systematic review of human TUS studies for enhancing or suppressing neural functionCollated set of hypotheses on using TUS to bias towards enhancement or suppressionMeta-analysis results identify parameters that may bias the directionality of effectsTUS resource established for systematic reporting of TUS parameters and outcomes.

Early follow-up colonoscopy after colorectal cancer resection detects significant pathology.

BACKGROUND: Colonoscopy is a key component of surveillance after colorectal cancer (CRC) resection. Surveillance intervals for colonoscopy vary across the world, with a limited evidence-base to support guidelines. OBJECTIVE: To evaluate the timing and outcome of colonoscopies after CRC resection. METHODS: Retrospective cohort study on prospectively collected data. Included adult patients under surveillance following CRC resection. Patients with organ transplant, inflammatory bowel disease or colon cancer syndromes were excluded. The outcomes of the first (up to) three follow-up colonoscopies were audited and classified for presence of advanced neoplasia (advanced adenoma or adenocarcinoma). RESULTS: 980 patients underwent at least one follow-up colonoscopy with a median time to first colonoscopy of 12.4 months. The findings included 2.7% CRC and 13.2% advanced adenoma. Older age, stage IV disease, and synchronous cancers at surgery were significantly associated with a finding of advanced neoplasia at first colonoscopy. 562 patients underwent a second colonoscopy (median of 35 months after the first surveillance colonoscopy) with findings of 1.8% CRC and 11.4% advanced adenoma. Advanced adenoma on prior colonoscopy was associated with finding advanced neoplasia at the second colonoscopy. 288 patients underwent a third colonoscopy (median of 37 months from the preceding colonoscopy), with similar outcomes of advanced neoplasia being associated with advanced adenoma at the previous colonoscopy. 43 (4.4%) patients developed CRC whilst on surveillance. CONCLUSIONS: Timely surveillance after CRC resection is important for detecting advanced neoplasia, and prolonged intervals between colonoscopies in the early years after surgery should be avoided.

Should I stay or should I go? An exploratory study comparing wheelchair-adapted rowing at home vs. in community gyms.

PURPOSE: Wheelchair users experience many barriers to physical activity as affordable and accessible exercise equipment options are limited. Thus, the home-based adapted rower (aROW) and gym-based aROW were developed. The objectives were to determine: 1) wheelchair users' preferences, perspectives, facilitators, and barriers to using the home-based versus the gym-based aROW, 2) perceived usability of the home and gym aROWs, and 3) recommendations to adapt the aROW further for home and community use. MATERIALS AND METHODS: In this two-phase exploratory mixed-methods study, participants completed one month of using a home aROW, followed by one month of using a community gym aROW. After each phase, participants completed a semi-structured interview and the System Usability Scale (SUS) questionnaire. Interview data were analyzed using conventional content analysis and effect size comparing SUS data was calculated. RESULTS AND CONCLUSIONS: Four categories were identified: what worked well, barriers to using the aROWs, what could be improved and important considerations. There was a large effect size in perceived usability between the aROWs with participants preferring the home aROW. Overall, rowing was enjoyable, and participants achieved positive physical outcomes. As preferences are individual, the home aROW provides wheelchair users with a potential choice between home or gym exercise.

Rowing is an enjoyable and effective form of aerobic exercise for wheelchair usersWheelchair users experience social, environment and financial barriers to engaging in exerciseThe home aROW provides a low-cost and accessible option for wheelchair-adapted aerobic exercise.

Cerebrovascular events after transcatheter aortic valve implantation.

Periprocedural stroke after transcatheter aortic valve implantation (TAVI) remains a significant issue, which is associated with high morbidity, and is increasingly important as intervention shifts to younger and lower-risk populations. Over the last decade of clinical experience with TAVI, the incidence of periprocedural stroke has stayed largely unchanged, although it is prone to underreporting due to variation in ascertainment methods. The aetiology of stroke in TAVI patients is multifactorial, and changing risk profiles, differing study populations, and frequent device iterations have made it difficult to discern consistent risk factors. The objective of this review is to analyse and clarify the contemporary published literature on the epidemiology and mechanisms of neurological events in TAVI patients and evaluate potential preventive measures. This summary aims to improve patient risk assessment and refine case selection for cerebral embolic protection devices, while also providing a foundation for designing future trials focused on stroke prevention.

Irreducible traumatic pure hip dislocation by the entrapment of the lateral rotator muscle group of the hip: A case report.

Introduction: Irreducibility is a rare complication of pure posterior hip dislocation requiring surgical intervention. Case presentation: We present a case of a 22-year-old female with posterior hip dislocation following a motor vehicle accident. Despite unsuccessful closed reduction attempts, open surgical reduction successfully released the incarcerated muscles and achieved reduction. Follow-up examinations showed excellent functional outcomes without complications. Clinical discussion: Irreducibility remains a rare complication of traumatic posterior hip dislocation. Three possible entities can cause soft tissue incarceration: labral buttonholing, intra-articular osteochondral bodies, and entrapment of the piriformis muscle. The posterior-lateral approach provides excellent exposure of the posterior hip structures, but it carries the risk of injury to the medial circumflex artery. After successfully reducing the dislocation, it is essential to perform a computed tomography (CT) scan to detect any osteochondral lesions, including femoral head impaction. Functional outcomes are better with early mobilization and prompt resumption of weight-bearing. However, femoral head osteonecrosis complicates 52.9 % of hip dislocations reduced beyond 6 h, whereas it occurs in only 4.8 % of dislocations reduced within this timeframe. Conclusion: This case underscores the importance of prompt recognition and appropriate surgical intervention for irreducible hip dislocations to prevent further complications and optimize patient outcomes.

An investigation of a novel milk allergy-friendly food supplement program.

Introduction: Compared to households not managing food allergy, households managing food allergy are faced with greater direct and indirect costs. To address these cost burdens, we developed and piloted a milk allergy-friendly food supplement program for lower- and middle-income households managing a dairy allergy in a child age <6 years. Herein, we aimed to evaluate to the impact of this program on food costs, food security, and caregiver mental health using a longitudinal design. Methods: Participants living in or near the city of Winnipeg, in Manitoba, Canada were recruited from January to February 2022 via social media, word-of-mouth, and a database maintained by the principal investigator. Consenting participants took part in a 6-month allergen-friendly food supplement program that provided them with biweekly deliveries of allergen-friendly foods free of charge. To evaluate the impact of the program on food costs, food security, and well-being, participants completed a series of questionnaires at baseline, mid-point, and at the end of the program. Changes in these variables were assessed via a series of Friedman tests. Results: The final sample was comprised of 8 households. Relative to baseline, participants reported higher total direct food costs at midpoint (+5.6%) and endpoint (+13.5%), but these changes did not reach statistical significance. In contrast, total indirect food costs decreased over the course of the study relative to baseline (midpoint = -28.2%; endpoint = -18.5%), but the changes were not found to be statistically significant. Participants did, however, report a statistically significant decrease in costs related to lost time from work or school as a result of their child's food allergy at endpoint relative to baseline (-100%). Few changes in food security, caregiver well-being, or child food allergy quality of life were noted. Discussion: The provision of allergen-friendly foods helped keep grocery costs below the pace of inflation. Participants also reported reduced costs associated with missed time from work or school as a result of their child's food allergy. Despite these encouraging findings, a relatively high proportion of the current sample reported experiencing food insecurity throughout the study period, suggesting that additional financial support for families is needed.

HCV prevalence and phylogenetic characteristics in a cross-sectional, community study of young people who inject drugs in New York City: Opportunity for and threats to HCV elimination.

Background and Aims: In the United States, the opioid epidemic has led many young people who use opioids to initiate injection drug use, putting them at risk for hepatitis C virus (HCV) infection. However, community surveys to monitor HCV prevalence among young people who inject drugs (YPWID) are rare. Methods: As part of Staying Safe (Ssafe), a trial to evaluate an HCV-prevention intervention, a community-recruited sample of 439 young people who use opioids (ages 18-30) in New York City (NYC) were screened from 2018 to 2021. Screening procedures included a brief verbal questionnaire, a visual check for injection marks, onsite urine drug testing, rapid HCV antibody (Ab) testing, and dried blood spot (DBS) collection. DBS specimens were sent to a laboratory for HCV RNA testing and phylogenetic analysis to identify genetic linkages among HCV RNA-positive specimens. Multivariable logistic regression was used to assess associations between HCV status (Ab and RNA) and demographics and drug use patterns. Results: Among the 330 participants who reported injecting drugs (past 6 months), 33% (n = 110) tested HCV Ab-positive, 58% of whom (n = 64) had HCV RNA-positive DBS specimens, indicating active infection. In multivariable analysis, visible injection marks (AOR = 3.02; p < 0.001), older age (AOR = 1.38; p < 0.05), and female gender (AOR = 1.69; p = 0.052) were associated with HCV Ab-positive status. Visible injection marks were also associated with HCV RNA-positive status (AOR = 5.24; p < 0.01). Twenty-five percent of RNA-positive specimens (14/57) were genetically linked. Conclusion: The relatively low prevalence of active infection suggests the potential impact of treatment-as-prevention in reducing HCV prevalence among YPWID. Targeted community serosurveys could help identify actively infected YPWID for treatment, thereby reducing HCV incidence and future transmissions.

Integrated workflows and interfaces for data-driven semi-empirical electronic structure calculations.

Modern software engineering of electronic structure codes has seen a paradigm shift from monolithic workflows toward object-based modularity. Software objectivity allows for greater flexibility in the application of electronic structure calculations, with particular benefits when integrated with approaches for data-driven analysis. Here, we discuss different approaches to create deep modular interfaces that connect big-data workflows and electronic structure codes and explore the diversity of use cases that they can enable. We present two such interface approaches for the semi-empirical electronic structure package, DFTB+. In one case, DFTB+ is applied as a library and provides data to an external workflow; in another, DFTB+receives data via external bindings and processes the information subsequently within an internal workflow. We provide a general framework to enable data exchange workflows for embedding new machine-learning-based Hamiltonians within DFTB+ or enabling deep integration of DFTB+ in multiscale embedding workflows. These modular interfaces demonstrate opportunities in emergent software and workflows to accelerate scientific discovery by harnessing existing software capabilities.

Nanosized Chevrel phases for dendrite-free zinc-ion based energy storage: unraveling the phase transformations.

The nanoscale form of the Chevrel phase, Mo6S8, is demonstrated to be a highly efficient zinc-free anode in aqueous zinc ion hybrid supercapacitors (ZIHSCs). The unique morphological characteristics of the material when its dimensions approach the nanoscale result in fast zinc intercalation kinetics that surpass the ion transport rate reported for some of the most promising materials, such as TiS2 and TiSe2. In situ Raman spectroscopy, post-mortem X-ray diffraction, Hard X-ray photoelectron spectroscopy, and density functional theory (DFT) calculations were combined to understand the overall mechanism of the zinc ion (de)intercalation process. The previously unknown formation of the sulfur-deficient Zn2.9Mo15S19 (Zn1.6Mo6S7.6) phase is identified, leading to a re-evaluation of the mechanism of the (de)intercalation process. A full cell comprised of an activated carbon (YEC-8A) positive electrode delivers a cell capacity of 38 mA h g-1 and an energy density of 43.8 W h kg-1 at a specific current density of 0.2 A g-1. The excellent cycling stability of the device is demonstrated for up to 8000 cycles at 3 A g-1 with a coulombic efficiency close to 100%. Post-mortem microscopic studies reveal the absence of dendrite formation at the nanosized Mo6S8 anode, in stark contrast to the state-of-the-art zinc electrode.

Supramolecular architectures in multicomponent crystals of imidazole-based drugs and trithiocyanuric acid.

The structures of three multicomponent crystals formed with imidazole-based drugs, namely metronidazole, ketoconazole and miconazole, in conjunction with trithiocyanuric acid are characterized. Each of the obtained adducts represents a different category of crystalline molecular forms: a cocrystal, a salt and a cocrystal of salt. The structural analysis revealed that in all cases, the N-H...N hydrogen bond is responsible for the formation of acid-base pairs, regardless of whether proton transfer occurs or not, and these molecular pairs are combined to form unique supramolecular motifs by centrosymmetric N-H...S interactions between acid molecules. The complex intermolecular forces acting in characteristic patterns are discussed from the geometric and energetic perspectives, involving Hirshfeld surface analysis, pairwise energy estimation, and natural bond orbital calculations.

Estimating an EQ-5D-Y-3L Value Set for Brazil.

INTRODUCTION: The EQ-5D-Y-3L is a generic measure of health-related quality of life in children and adolescents. Although the Brazilian-Portuguese EQ-5D-Y-3L version is available, there is no value set for it, hampering its use in economic evaluations. This study aimed to elicit a Brazilian EQ-5D-Y-3L value set based on preferences of the general adult population. METHODS: Two independent samples of adults participated in an online discrete choice experiment (DCE) survey and a composite time trade-off (cTTO) face-to-face interview. The framing was "considering your views for a 10-year-old child". DCE data were analyzed using a mixed-logit model. The 243 DCE predicted values were mapped into the observed 28 cTTO values using linear and non-linear mapping approaches with and without intercept. Mapping approaches' performance was assessed to estimate the most valid method to rescale DCE predicted values using the model fit (R2), Akaike Information Criteria (AIC), root mean squared error (RMSE), and mean absolute error (MAE). RESULTS: A representative sample of 1376 Brazilian adults participated (DCE, 1152; cTTO, 211). The linear mapping without intercept (R2 = 96%; AIC, - 44; RMSE, 0.0803; MAE, - 0.0479) outperformed the non-linear without intercept (R2 = 98%; AIC, - 63; RMSE, 0.1385; MAE, - 0.1320). Utilities ranged from 1 (full health) to - 0.0059 (the worst health state). Highest weights were assigned to having pain or discomfort (pain/discomfort), followed by walking about (mobility), looking after myself (self-care), doing usual activities (usual activities), and feeling worried, sad, or unhappy (anxiety/depression). CONCLUSION: This study elicited the Brazilian EQ-5D-Y-3L value set using a mixed-logit DCE model with a power parameter based on a linear mapping without intercept, which can be used to estimate the quality-adjusted life-years for economic evaluations of health technologies targeting the Brazilian youth population.

A familiar face and person processing area in the human temporal pole.

How does the brain process the faces of familiar people? Neuropsychological studies have argued for an area of the temporal pole (TP) linking faces with person identities, but magnetic susceptibility artifacts in this region have hampered its study with fMRI. Using data acquisition and analysis methods optimized to overcome this artifact, we identify a familiar face response in TP, reliably observed in individual brains. This area responds strongly to visual images of familiar faces over unfamiliar faces, objects, and scenes. However, TP did not just respond to images of faces, but also to a variety of high-level social cognitive tasks, including semantic, episodic, and theory of mind tasks. The response profile of TP contrasted with a nearby region of the perirhinal cortex that responded specifically to faces, but not to social cognition tasks. TP was functionally connected with a distributed network in the association cortex associated with social cognition, while PR was functionally connected with face-preferring areas of the ventral visual cortex. This work identifies a missing link in the human face processing system that specifically processes familiar faces, and is well placed to integrate visual information about faces with higher-order conceptual information about other people. The results suggest that separate streams for person and face processing reach anterior temporal areas positioned at the top of the cortical hierarchy.

Engineered mini-G proteins block the internalization of cognate GPCRs and disrupt downstream intracellular signaling.

Mini-G proteins are engineered, thermostable variants of Gα subunits designed to stabilize G protein-coupled receptors (GPCRs) in their active conformations. Because of their small size and ease of use, they are popular tools for assessing GPCR behaviors in cells, both as reporters of receptor coupling to Gα subtypes and for cellular assays to quantify compartmentalized signaling at various subcellular locations. Here, we report that overexpression of mini-G proteins with their cognate GPCRs disrupted GPCR endocytic trafficking and associated intracellular signaling. In cells expressing the Gαs-coupled GPCR glucagon-like peptide 1 receptor (GLP-1R), coexpression of mini-Gs, a mini-G protein derived from Gαs, blocked ß-arrestin 2 recruitment and receptor internalization and disrupted endosomal GLP-1R signaling. These effects did not involve changes in receptor phosphorylation or lipid nanodomain segregation. Moreover, we found that mini-G proteins derived from Gαi and Gαq also inhibited the internalization of GPCRs that couple to them. Finally, we developed an alternative intracellular signaling assay for GLP-1R using a nanobody specific for active Gαs:GPCR complexes (Nb37) that did not affect GLP-1R internalization. Our results have important implications for designing methods to assess intracellular GPCR signaling.

Redox-Switchable Aromaticity in a Helically Extended Indeno[2,1-c]fluorene.

Molecular switches have received major attention to enable the reversible modulation of various molecular properties and have been extensively used as trigger elements in diverse fields, including molecular machines, responsive materials, and photopharmacology. Antiaromaticity is a fascinating property that has attracted not only significant fundamental interest but is also increasingly relevant in different applications, in particular organic (opto)electronics. However, designing systems in which (anti)aromaticity can be judiciously and reversibly switched ON and OFF remains challenging. Herein, we report a helicene featuring an indenofluorene-bridged bisthioxanthylidene as a novel switch wherein a simultaneous two-electron (electro)chemical redox process allows highly reversible modulation of its (anti)aromatic character. Specifically, the two thioxanthylidene rotors, attached to the initially aromatic indenofluorene scaffold via overcrowded alkenes, adopt an anti-folded structure, which upon oxidation convert to singly bonded, twisted conformations. This is not only associated with significant (chir)optical changes but importantly also results in formation of the fully conjugated, formally antiaromatic as-indacene motif in the helical core of the switch. This process proceeds without the buildup of radical cation intermediates and thus enables highly reversible switching of molecular geometry, aromaticity, absorbance, and chiral expression under ambient conditions, as evidenced by NMR, UV-vis, CD, and (spectro)electrochemical analyses, supported by DFT calculations. We expect this concept to be extendable to a wide range of robust antiaromatic-aromatic switches and to provide a basis for modulation of the structure and properties of these fascinating inherently chiral polycyclic π-scaffolds.

Complications unveiled: A detailed case report on mesh migration post-incisional hernia repair.

INTRODUCTION AND IMPORTANCE: Repairing incisional abdominal wall hernia with nonabsorbable meshes is one of the most common procedures in general surgery. Mesh migration into the intestine is rare but a serious complication. It can occur months or even years after surgery and often presents with vague abdominal pain, making diagnosis tricky. CASE PRESENTATION: We report a rare case of a 52-year-old female presenting a small bowel obstruction secondary to mesh migration from the abdominal wall into the intestine, 10 years after repeated surgical repair of a ventral incisional hernia. At surgery, a mesh was migrated into a small bowl. The patient had a small bowel resection. The postoperative course was simple and the patient was discharged after 5 days. CASE DISCUSSION: Incisional hernia repair with mesh is one of the most commonly performed surgical procedures worldwide. Many complications have been linked to the use of mesh; among the most frequently reported are seromas, hematomas, and infections. Mesh migration remains an uncommon event after incisional hernia repair, and even rarer when considering complete migration within the intestinal lumen. The exact cause of this complication remains unknown. Multiple hypotheses have been proposed for mesh migration. Abdominal pain, intermittent or persistent intestinal obstruction, mass formation, and viscus perforation represent the most common clinical manifestation. Total removal of the mesh via laparoscopy or laparotomy is recommended, along with either partial or entire resection of the organ. CONCLUSION: Mesh migration is a an uncommon possible complication in case of incisional hernia mesh repair and it requires often surgical intervention.

Multigenerational inheritance drives symbiotic interactions of the bacterium Bacillus subtilis with its plant host.

Bacillus subtilis is a beneficial bacterium that supports plant growth and protects plants from bacterial, fungal, and viral infections. Using a simplified system of B. subtilis and Arabidopsis thaliana interactions, we studied the fitness and transcriptome of bacteria detached from the root over generations of growth in LB medium. We found that bacteria previously associated with the root or exposed to its secretions had greater stress tolerance and were more competitive in root colonization than bacteria not previously exposed to the root. Furthermore, our transcriptome results provide evidence that plant secretions induce a microbial stress response and fundamentally alter signaling by the cyclic nucleotide c-di-AMP, a signature maintained by their descendants. The changes in cellular physiology due to exposure to plant exudates were multigenerational, as they allowed not only the bacterial cells that colonized a new plant but also their descendants to have an advance over naive competitors of the same species, while the overall plasticity of gene expression and rapid adaptation were maintained. These changes were hereditary but not permanent. Our work demonstrates a bacterial memory manifested by multigenerational reversible adaptation to plant hosts in the form of activation of the stressosome, which confers an advantage to symbiotic bacteria during competition.