Evaluating the Efficacy of Large Language Models in CPT Coding for Craniofacial Surgery: A Comparative Analysis.

BACKGROUND: The advent of Large Language Models (LLMs) like ChatGPT has introduced significant advancements in various surgical disciplines. These developments have led to an increased interest in the utilization of LLMs for Current Procedural Terminology (CPT) coding in surgery. With CPT coding being a complex and time-consuming process, often exacerbated by the scarcity of professional coders, there is a pressing need for innovative solutions to enhance coding efficiency and accuracy. METHODS: This observational study evaluated the effectiveness of 5 publicly available large language models-Perplexity.AI, Bard, BingAI, ChatGPT 3.5, and ChatGPT 4.0-in accurately identifying CPT codes for craniofacial procedures. A consistent query format was employed to test each model, ensuring the inclusion of detailed procedure components where necessary. The responses were classified as correct, partially correct, or incorrect based on their alignment with established CPT coding for the specified procedures. RESULTS: The results indicate that while there is no overall significant association between the type of AI model and the correctness of CPT code identification, there are notable differences in performance for simple and complex CPT codes among the models. Specifically, ChatGPT 4.0 showed higher accuracy for complex codes, whereas Perplexity.AI and Bard were more consistent with simple codes. DISCUSSION: The use of AI chatbots for CPT coding in craniofacial surgery presents a promising avenue for reducing the administrative burden and associated costs of manual coding. Despite the lower accuracy rates compared with specialized, trained algorithms, the accessibility and minimal training requirements of the AI chatbots make them attractive alternatives. The study also suggests that priming AI models with operative notes may enhance their accuracy, offering a resource-efficient strategy for improving CPT coding in clinical practice. CONCLUSIONS: This study highlights the feasibility and potential benefits of integrating LLMs into the CPT coding process for craniofacial surgery. The findings advocate for further refinement and training of AI models to improve their accuracy and practicality, suggesting a future where AI-assisted coding could become a standard component of surgical workflows, aligning with the ongoing digital transformation in health care.

Anti-HLA Class II Antibodies Are the Most Resistant to Desensitization in Crossmatch-positive Living-donor Kidney Transplantations: A Patient Series.

Background: In HLA-incompatible kidney transplantation, the efficacy of desensitization in terms of anti-HLA antibody kinetics is not well characterized. We present an overview of the course of anti-HLA antibodies throughout plasma exchange (PE) desensitization in a series of crossmatch-positive patients. Methods: All consecutive candidates in the Dutch HLA-incompatible kidney transplantation program between November 2012 and January 2022 were included. The eligibility criteria were a positive crossmatch with a living kidney donor and no options for compatible transplantation. Desensitization consisted of 5-10 PE with low-dose IVIg. Results: A total of 16 patient-donor pairs were included. Patients had median virtual panel-reactive antibody of 99.58%. Cumulative donor-specific anti-HLA antibody (cumDSA) mean fluorescence intensity (MFI) was 31 399 median, and immunodominant DSA (iDSA) MFI was 18 677 for class I and 21 893 for class II. Median anti-HLA antibody MFI response to desensitization was worse in class II as compared with class I (P < 0.001), particularly for HLA-DQ. Class I cumDSA MFI decreased 68% after 4 PE versus 53% in class II. The decrease between the fifth and the 10th PE sessions was modest with 21% in class I versus 9% in class II. Antibody-mediated rejection occurred in 85% of patients, with the iDSA directed to the same mismatched HLA as before desensitization, except for 3 patients, of whom 2 had vigorous rebound of antibodies to repeated mismatches (RMMs). Rebound was highest (86%) in RMM-DSA with prior grafts removed (transplantectomy n = 7), lower (39%) in non-RMM-DSA (n = 30), and lowest (11%) for RMM-DSA with in situ grafts (n = 5; P = 0.018 for RMM-DSA transplantectomy versus RMM-DSA graft in situ). With a median follow-up of 59 mo, 1 patient had died resulting in a death-censored graft survival of 73%. Conclusions: Patients with class II DSA, and particularly those directed against HLA-DQ locus, were difficult to desensitize.

The application of Global Burden of Animal Diseases methodology to aquatic animal production.

The Global Burden of Animal Diseases (GBADs) programme's key objective â€" to provide a systematic approach to determine the burden of animal disease â€" is as relevant to aquatic as to terrestrial animal production systems. However, to date GBADs methods have mainly been applied to terrestrial animal production systems. The challenges in applying GBADs methods, notably the Animal Health Loss Envelope (AHLE), vary considerably by production system. The authors demonstrate how the AHLE can be calculated for rainbow trout production in England and Wales and acknowledge that its application to other systems (e.g. hatchery production, polyculture and no-feed mollusc production) is more complex. For example, in small scale tropical fish production the impact of suboptimal nutrition on production would need to be addressed. Recirculating aquaculture systems have inherent high levels of biosecurity and disease control, and thus low levels of disease. Removing the capital and running costs associated with biosecurity fundamentally changes the system and invalidates the AHLE calculation. Lack of data from many systems, notably small-scale tropical finfish farming, means that expert opinion will be needed to support the application of GBADs methods. While calculation of the AHLE is the focus of this article, it should be noted that attribution to causes and value chain modelling are needed to generate data on the wider societal impact of aquatic animal diseases (and possible interventions), which governments require to support decision-making about resource allocation.

Les principaux objectifs du programme " Impact mondial des maladies animales " (GBADs) visent à fournir une méthode systématique pour déterminer l'impact des maladies animales et sont pertinents aussi bien pour les systèmes de production d'animaux terrestres que pour les systèmes aquacoles. Néanmoins, à ce jour, les méthodes du GBADs ont surtout été appliquées aux systèmes de production d'animaux terrestres. Les difficultés d'application des méthodes du GBADs, en particulier le calcul de l'enveloppe des pertes sanitaires animales varient considérablement d'un système de production à l'autre. Les auteurs décrivent la méthode appliquée pour calculer l'enveloppe des pertes sanitaires animales dans les élevages de truites arc-en-ciel en Angleterre et au pays de Galles, méthode dont ils reconnaissent que l'application à d'autres systèmes (par exemple la production en écloserie, la polyculture et la production de mollusques sans intrants de fourrage) est plus complexe. Par exemple, dans la production de poissons tropicaux à petite échelle, l'impact d'une nutrition sous-optimale sur la production devrait être pris en compte. Les systèmes de recirculation fermée en aquaculture garantissent intrinsèquement des niveaux élevés de biosécurité et de contrôle sanitaire qui se traduisent par un niveau faible de maladies. La suppression des coûts d'investissement et de fonctionnement associés à la biosécurité modifie fondamentalement le système et invalide le calcul de l'enveloppe des pertes sanitaires animales. Compte tenu de l'absence de données disponibles concernant un grand nombre de systèmes, notamment les petits élevages de poissons tropicaux, il faudra recourir aux avis d'experts pour étayer l'application des méthodes du GBADs. Si l'article aborde essentiellement le calcul de l'enveloppe des pertes sanitaires animales, les auteurs signalent l'importance de rechercher les causes et de modéliser les chaînes de valeur afin de générer des données représentatives de l'impact sociétal au sens large des maladies affectant les animaux aquatiques (ainsi que des interventions envisageables), outils indispensables pour étayer les décisions gouvernementales concernant les ressources à allouer.

El objetivo principal del programa sobre el Impacto Global de las Enfermedades Animales (GBADs), a saber, proporcionar un enfoque sistemático para determinar el impacto de dichas enfermedades, es tan pertinente para los sistemas de producción de animales acuáticos como terrestres. Sin embargo, hasta la fecha, los métodos del GBADs se han aplicado principalmente a los sistemas de producción de animales terrestres. Las dificultades que plantea la aplicación de los métodos del GBADs, en particular la cartera de pérdidas en sanidad animal, varían considerablemente según el sistema de producción. Los autores demuestran cómo puede calcularse la cartera de pérdidas en sanidad animal para la producción de trucha arco iris en Inglaterra y Gales y reconocen que su aplicación en otros sistemas (por ejemplo, la producción en viveros, el policultivo y la producción de moluscos sin insumos alimentarios) es más compleja. Por ejemplo, en la producción de peces tropicales a pequeña escala habría que abordar el impacto de una nutrición subóptima en la producción. Los sistemas de recirculación en acuicultura conllevan altos niveles de bioseguridad y control de enfermedades y, por lo tanto, bajos niveles de enfermedad. Si se eliminan los costos de capital y de explotación asociados a la bioseguridad, el sistema cambia radicalmente e invalida el cálculo de la cartera de pérdidas en sanidad animal. La falta de datos de muchos sistemas, especialmente de la cría de peces tropicales a pequeña escala, implica que se necesitará la opinión de expertos para apoyar la aplicación de los métodos del GBADs. Aunque el presente artículo se centra en el cálculo de la cartera de pérdidas en sanidad animal, cabe señalar que la determinación de las causas y la modelización de la cadena de valor son necesarias para generar datos sobre el impacto social más amplio de las enfermedades de los animales acuáticos (y las posibles intervenciones), que los gobiernos necesitan para respaldar la toma de decisiones sobre la asignación de recursos.

[Open surgical management of recurrent pigmented villonodular synovitis: case report and literature review]. / Manejo quirúrgico abierto de la sinovitis villonodular pigmentada recurrente: reporte de caso y revisión de literatura.

INTRODUCTION: pigmented villonodular synovitis (PVNS) is a benign condition that affects the knee, leading to abnormal proliferation of the synovial membrane and the accumulation of hemosiderin in the joint cavity. Although it can be surgically treated, PVNS tends to have a high recurrence rate, potentially resulting in chronic joint damage. CASE REPORT: we present the case of a young woman who experienced localized pain in her right knee due to a recurrence of PVNS. Magnetic resonance imaging revealed multiple multilobulated cystic lesions affecting the entire joint, including the ligaments. The patient underwent open surgical resection with a favorable clinical outcome. Histopathological examinations confirmed the absence of malignancy. CONCLUSION: while arthroscopy is typically the preferred treatment for PVNS, this case highlights the tendency for recurrence associated with this approach. Open surgical resection, supported by benign histopathological findings in this case, suggests a favorable long-term prognosis.

INTRODUCCIÓN: la sinovitis villonodular pigmentada (SVNP) es una enfermedad benigna que afecta la articulación de la rodilla, que causa una proliferación anormal de la membrana sinovial y la acumulación de hemosiderina en la cavidad articular. A pesar de que es posible tratarla mediante cirugía, la SVNP tiende a tener una alta tasa de recurrencia, lo que puede resultar en daño articular crónico. REPORTE DEL CASO: se presenta el caso de una mujer joven que experimentó dolor localizado en la rodilla derecha debido a una recurrencia de SVNP. La resonancia magnética reveló múltiples lesiones quísticas multilobuladas que afectaban a toda la articulación, incluyendo los ligamentos. La paciente fue sometida a una resección quirúrgica abierta, con una evolución clínica favorable. Los exámenes histopatológicos confirmaron la ausencia de malignidad. CONCLUSIÓN: aunque la artroscopía se considera el tratamiento de elección para la SVNP, este caso ilustra la tendencia a la recurrencia asociada con este enfoque. La resección quirúrgica abierta, respaldada por los hallazgos histopatológicos benignos en este caso, sugiere un pronóstico favorable a largo plazo.

Clinical-grade whole genome sequencing-based haplarithmisis enables all forms of preimplantation genetic testing.

High-throughput sequencing technologies have increasingly led to discovery of disease-causing genetic variants, primarily in postnatal multi-cell DNA samples. However, applying these technologies to preimplantation genetic testing (PGT) in nuclear or mitochondrial DNA from single or few-cells biopsied from in vitro fertilised (IVF) embryos is challenging. PGT aims to select IVF embryos without genetic abnormalities. Although genotyping-by-sequencing (GBS)-based haplotyping methods enabled PGT for monogenic disorders (PGT-M), structural rearrangements (PGT-SR), and aneuploidies (PGT-A), they are labour intensive, only partially cover the genome and are troublesome for difficult loci and consanguineous couples. Here, we devise a simple, scalable and universal whole genome sequencing haplarithmisis-based approach enabling all forms of PGT in a single assay. In a comparison to state-of-the-art GBS-based PGT for nuclear DNA, shallow sequencing-based PGT, and PCR-based PGT for mitochondrial DNA, our approach alleviates technical limitations by decreasing whole genome amplification artifacts by 68.4%, increasing breadth of coverage by at least 4-fold, and reducing wet-lab turn-around-time by ~2.5-fold. Importantly, this method enables trio-based PGT-A for aneuploidy origin, an approach we coin PGT-AO, detects translocation breakpoints, and nuclear and mitochondrial single nucleotide variants and indels in base-resolution.

Human-wildlife conflict at high altitude: A case from Gaurishankar conservation area, Nepal.

Human-wildlife conflict studies of high-altitude areas are rare due to budget constraints and the challenging nature of research in these remote environments. This study investigates the prevalence and increasing trend of human-wildlife conflict (HWC) in the mountainous Gaurishankar Conservation Area (GCA) of Nepal, with a specific focus on leopard (Panthera pardus) and Himalayan black bear (Ursus thibetanus laniger). The study analyzes a decade of HWC reports and identifies goats as the livestock most targeted by leopards. The Dolakha district of GCA received the highest number of reports, highlighting the need for mitigation measures in the area. In GCA, livestock attacks accounted for 85% of compensation, with the remaining 15% for human injuries. We estimate that the number of reported wildlife attacks grew on average by 33% per year, with an additional increase of 57 reports per year following the implementation of a new compensation policy during BS 2076 (2019 AD). While bear attacks showed no significant change post-rule alteration, leopard attack reports surged from 1 to 60 annually, indicating improved compensation may have resulted in increased leopard-attack reporting rates. The findings emphasize the economic impact of HWC on local communities and suggest strategies such as increasing prey populations, promoting community education and awareness, enhancing alternative livelihood options, developing community-based insurance programs, and implementing secure enclosures (corrals) to minimize conflicts and foster harmonious coexistence. This research addresses a knowledge gap in HWC in high-altitude conservation areas like the GCA, providing valuable insights for conservation stakeholders and contributing to biodiversity conservation and the well-being of humans and wildlife.

Confirming the Causal Role of Consistent Contexts in Developing a Walking Habit: A Randomized Comparison With Varied Contexts.

BACKGROUND: Physical activity interventions using habit development may help people increase and then maintain physical activity increases over time. Enacting behavior in consistent contexts is a central component of habit development, yet its causal role in habit development in health behaviors has not been confirmed. PURPOSE: This study tests the causal role of consistent context in habit development in health behavior, using a randomized control trial of a planning intervention to develop a walking habit in 127 insufficiently active, working, midlife adults in a real-world setting. METHODS: We compare participants who plan walking in consistent contexts with controls who plan walking in varied contexts and with controls not required to plan on a change in average daily steps (measured using an accelerometer) and inhabit automaticity during a 4-week intervention and at a 4-week follow-up. RESULTS: As expected, consistent and varied context planners increased walking during the intervention, but only consistent context planners developed (and maintained) habit automaticity. Counter to expectations, consistent context planners did not show walking maintenance. However, across conditions, participants who developed more habit automaticity during the intervention also maintained walking more (decreased less). Having a routine daily schedule moderated some effects. Notably, no-plan controls with greater routine developed more habit automaticity, mediated by walking in more consistent contexts. CONCLUSIONS: This study confirms the causal role of consistent contexts in developing a walking habit, in a real-world setting, with an important but challenging population for physical activity interventions and identifies a facilitating condition common for many: a routine schedule.

Developing an exercise habit may help people increase and then maintain physical activity. This study tests and confirms the role of exercising in consistent contexts as a cause of forming a daily walking habit. We use a randomized control trial of a 4-week planning intervention, with a follow-up 4 weeks after the intervention. Participants were 127 insufficiently active, working, midlife adults. We compared participants asked to plan their daily walks in consistent contexts from day-to-day, with participants asked to plan their walks in varied contexts and with participants not required to plan. As expected, consistent and varied context planners increased their daily walking steps (measured using an accelerometer) during the intervention compared to participants not required to plan. However, only consistent context planners developed (and then maintained) a daily walking habit, that is, where taking daily walks felt relatively automatic. Unexpectedly, consistent context planners did not show walking maintenance. However, across all participants, those who developed a stronger walking habit during the intervention maintained their walking more after the intervention ended. Lastly, having an existing routine daily schedule helped some participants. Those who were not asked to plan and had a more routine daily schedule also developed a daily walking habit.

Heterologous expression and purification of the phage lysin-like bacteriocin LysL from Lactococcus lactis LAC460.

The wild-type Lactococcus lactis strain LAC460 produces two bacteriocin-like phage lysins, LysL and LysP. This study aimed to produce and secrete LysL in various heterologous hosts and an in vitro cell-free expression system for further functional studies. Initially, the lysL gene from L. lactis LAC460 was cloned into Lactococcus cremoris NZ9000 and L. lactis N8 strains, with and without the usp45 signal sequence (SSusp45), under a nisin-inducible promoter. Active LysL was primarily produced intracellularly in recombinant L. lactis N8, with some secretion into the supernatant. Recombinant L. cremoris NZ9000 lysed upon nisin induction, indicating successful lysL expression. However, fusion with Usp45 signal peptide (SPUsp45-LysL) weakened LysL activity, likely due to incomplete signal peptide cleavage during secretion. Active LysL was also produced in vitro, and analysed in SDS-PAGE, giving a 42-kDa band. However, the yield of LysL protein was still low when produced from recombinant lactococci or by in vitro expression system. Therefore, His-tagged LysL was produced in Escherichia coli BL21(DE3). Western blot confirmed the intracellular production of about 44-kDa His-tagged LysL in E. coli. His-tagged active LysL was then purified by Ni-NTA affinity chromatography yielding sufficient 4.34 mg of protein to be used in future functional studies.

The Respiratory Effects of Chronic Exposure to Gas Faring Among Residents of Some Communities in the Niger Delta Region of Nigeria.

BACKGROUND: This study presents the pattern of respiratory effects seen among residents chronically exposed to gas flaring in some communities in the Niger Delta Region, Nigeria. The other health challenges associated with this chronic exposure to gas were also evaluated in the study. METHODS: A total of three hundred and eighty-six 386 adult residents in Ibeno, Niger Delta Region who have been residents for at least two years. Four hundred and fourteen (414) age, sex, and height-matched control unexposed residents in Etinan were recruited for a cross-sectional survey study comparing their respiratory symptoms and other related health challenges. Past and current smokers were excluded from the study in both groups. The study was conducted using a questionnaire as the investigative tool. Both descriptive and inferential statistics were used to analyze the data. RESULTS: Most of the respondents in both exposed and control communities were aged 18-30 years, with a height range of 161-170 cm. Both exposed and control subjects experienced similar symptoms suggestive of respiratory disorders, however, the prevalence was significantly higher among exposed subjects than controls: Cough 57(14.8%) vs. 39(10.1%); breathlessness 58(15%) vs. 28(7.3); wheezing 22(5.7) vs. 12(3.1). The respondents from the exposed community were mostly traders and fishermen while the controls were predominantly farmers. CONCLUSION: There is substantial evidence from the data presented that prolonged exposure to air pollution from gas flaring has significant respiratory and other health implications on residents in these communities reflected as increased frequency of symptoms of cough, chest pain, difficulty in breathing, wheezing, chest tightness, Skin and eye irritation. There is therefore an urgent need for intensified efforts and commitment by the government to speed up the implementation of policies regarding the reduction of flaring of natural gas associated with oil production and the adoption of measures to mitigate the effect of the exposure on human health.

CONTEXTE: Cette étude présente les effets respiratoires observés chez les résidents chroniquement exposés au torchage de gaz dans certaines communautés de la région du delta du Niger, au Nigeria. Les autres problèmes de santé associés à cette exposition chronique au gaz ont également été évalués dans cette étude. MÉTHODES: Un total de 386 résidents adultes d'Ibeno, dans la région du delta du Niger, ayant résidé pendant au moins deux ans, ont été inclus dans l'étude. Quatre cent quatorze (414) résidents non exposés, appariés en fonction de l'âge, du sexe et de la taille, à Etinan ont été recrutés pour une étude transversale comparant leurs symptômes respiratoires et d'autres problèmes de santé associés. Les fumeurs passés et actuels ont été exclus de l'étude dans les deux groupes. L'étude a été menée à l'aide d'un questionnaire comme outil d'investigation. Des statistiques descriptives et inférentielles ont été utilisées pour analyser les données. RÉSULTATS: La plupart des répondants dans les communautés exposées et témoins avaient entre 18 et 30 ans, avec une taille allant de 161 à 170 cm. Les sujets exposés et témoins ont présenté des symptômes similaires suggérant des troubles respiratoires, cependant, la prévalence était significativement plus élevée chez les sujets exposés que chez les témoins : Toux - 57 (14,8 %) contre 39 (10,1 %) ; essoufflement 58 (15 %) contre 28 (7,3 %) ; sifflement 22 (5,7 %) contre 12 (3,1 %). Les répondants de la communauté exposée étaient principalement des commerçants et des pêcheurs, tandis que les témoins étaient principalement des agriculteurs. CONCLUSION: Les données présentées fournissent des preuves substantielles que l'exposition prolongée à la pollution de l'air due au torchage de gaz a des implications respiratoires et autres sur la santé des résidents de ces communautés, se traduisant par une fréquence accrue des symptômes de toux, douleur thoracique, difficulté à respirer, sifflement, oppression thoracique, irritation de la peau et des yeux. Il est donc urgent d'intensifier les efforts et l'engagement du gouvernement pour accélérer la mise en œuvre des politiques visant à réduire le torchage du gaz naturel associé à la production de pétrole et à adopter des mesures pour atténuer les effets de l'exposition sur la santé humaine. MOTS CLÉS: Effet respiratoire, Exposition chronique, Torchage de gaz, Delta du Niger.

Verrucous Carcinoma of the Foot: A Single Canadian Center Experience on Diagnosis, Management, and Outcomes.

INTRODUCTION: Verrucous carcinoma (VC) was first described in 1948 by Dr. Ackerman. It is a low-grade cutaneous squamous carcinoma that usually develops in the oral cavity, the anogenital region, and the plantar surface of the foot. Clinically, there is low suspicion for malignancy given the slow growth of VC lesions and their wart-like appearance. Diagnosis can be difficult because of the benign histological appearance with well-differentiated cells and absence of dysplasia. Surgical excision is the only satisfactory form of treatment for plantar VC; however, this becomes difficult given its benign clinical appearance and the pathologic misinterpretation of the lesion as a benign hyperplasia. While there are case reports and retrospective studies of patients with plantar VC in the literature, we present the largest case series of plantar VC within North America, with recurrence despite negative margins. METHODS: We report on all the plantar VC excised between 2014-2023. We report six cases of VC, their treatment, and their outcomes. RESULTS: Six patients obtained a diagnosis of plantar VC by incisional biopsy. All patients underwent excision of their lesions and had negative margins reported on the final pathology. All patients developed nonhealing wounds at the site of their lesion excision; therefore, biopsies were performed to confirm a recurrence. All patients had a recurrence of VC at the initial site. All patients underwent re-excision of the lesions. Despite negative margins again on final pathology, all patients had a subsequent second recurrence. Ultimately, all patients underwent an amputation as definitive management. Each patient had an average of 3 operations. There were 4 different surgeons and different pathologists reporting their findings. CONCLUSIONS: Our experience with plantar VC suggests that an aggressive approach to surgical management is needed. Furthermore, management is optimized with the combined expertise of an experienced dermatopathologist and surgeon. Despite negative margins and repeated excisions, VC lesions recur and invade local tissues to the extent that only amputation of the involved foot has resulted in cure.

Chronic health conditions and disability are prevalent among community users of a digital mental health service: a scoping survey.

Objectives: Digital interventions can offer accessible and scalable treatment for chronic conditions, though often focus separately on physical or mental health. People accessing digital health services may live with multiple conditions or experience overlapping symptoms. This study aimed to describe the breadth and characteristics of chronic health conditions and self-reported disability among routine users of a digital mental health service, and to examine related motivations to engage with digital mental health interventions.Methods: A cross-sectional survey of adults registered with a digital mental health service in the Australian community (THIS WAY UP) was conducted. Participant demography, chronic health conditions, self-reported disability and motivations for accessing digital treatment were collected and analyzed descriptively.Results: 366 participants responded (77% female, mean age 50 ± 15 years). 71.6% of participants (242/338) reported ≥1 chronic health condition and one-third reported multimorbidity (112/338, 33.1%). Chronic pain, musculoskeletal and connective tissue disorders were most common. 26.9% of respondents (90/334) reported a disability, most commonly physical disabilities. 95% of those with chronic conditions reported negative mental health effects and 46% reported heightened interest in digital mental health treatments because of their condition. Primary motivations for digital service use were receiving a recommendation from a health professional and service accessibility.Discussion: People who access digital mental health services in routine care report high rates of heterogenous chronic illness and related disability. There is interest in accessible digital treatments to support mental health at scale among people who live with varied chronic conditions and disabilities.

Heterogenous chronic health conditions and disability are prevalent among people who engage with digital mental health interventions in the community.Approximately three-quarters of people (72%) who access digital mental health interventions have at least one chronic condition, and approx. one quarter (27%) have a disability.The accessibility of digital mental health treatments appealed to people with chronic conditions and/or disabilities.Digital mental health services may have a role to play in supporting mental health and wellbeing at scale among people with varied, disabling chronic conditions.

Leveraging distributed brain signal at rest to predict internalizing symptoms in youth.

BACKGROUND: The prevalence of internalizing psychopathology rises precipitously from early to mid-adolescence, yet the underlying neural phenotypes that give rise to depression and anxiety during this developmental period remain unclear. METHODS: Youth from the Adolescent Brain and Cognitive DevelopmentSM Study (ages 9-10 years at baseline) with a resting-state fMRI scan and mental health data were eligible for inclusion. Internalizing subscale scores from the Brief Problem Monitor - Youth Form were combined across two years of follow-up to generate a cumulative measure of internalizing symptoms. The total sample (n = 6521) was split into a large discovery dataset and a smaller validation dataset. Brain-behavior associations of resting-state functional connectivity (RSFC) with internalizing symptoms were estimated in the discovery dataset. The weighted contributions of each functional connection were aggregated using multivariate statistics to generate a polyneuro risk score (PNRS). The predictive power of the PNRS was evaluated in the validation dataset. RESULTS: The PNRS explained 10.73% of the observed variance in internalizing symptom scores in the validation dataset. Model performance peaked when the top 2% functional connections identified in the discovery dataset (ranked by absolute ß-weight) were retained. The RSFC networks that were implicated most prominently were the default mode, dorsal attention, and cingulo-parietal networks. These findings were significant (p < 1*10-6) as accounted for by permutation testing (n = 7000). CONCLUSIONS: These results suggest that the neural phenotype associated with internalizing symptoms during adolescence is functionally distributed. The PNRS approach is a novel method for capturing relationships between RSFC and behavior.

(1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterol.

The discovery of a novel sphingolipid subclass, the (1-deoxy)sphingolipids, which lack the 1-hydroxy group, attracted considerable attention in the last decade, mainly due to their involvement in disease. They differed in their physico-chemical properties from the canonical (or 1-hydroxy) sphingolipids and they were more toxic when accumulated in cells, inducing neurodegeneration and other dysfunctions. (1-Deoxy)ceramides, (1-deoxy)dihydroceramides, and (1- deoxymethyl)dihydroceramides, the latter two containing a saturated sphingoid chain, have been studied in this work using differential scanning calorimetry, confocal fluorescence and atomic force microscopy, to evaluate their behavior in bilayers composed of mixtures of three or four lipids. When compared to canonical ceramides (Cer), a C16:0 (1-deoxy)Cer shows a lower miscibility in mixtures of the kind C16:0 sphingomyelin/cholesterol/XCer, where XCer is any (1-deoxy)ceramide, giving rise to the coexistence of a liquid-ordered phase and a gel phase. The latter resembles, in terms of thermotropic behavior and nanomechanical resistance, the gel phase of the C16:0 sphingomyelin/cholesterol/C16:0 Cer mixture [Busto et al., Biophys. J. 2014, 106, 621-630]. Differences are seen between the various C16:0 XCer under study in terms of nanomechanical resistance, bilayer thickness and bilayer topography. When examined in a more fluid environment (bilayers based on C24:1 SM), segregated gel phases are still present. Probably related to such lateral separation, XCer preserve the capacity for membrane permeation, but their effects are significantly lower than those of canonical ceramides. Moreover, C24:1 XCer show significantly lower membrane permeation capacity than their C16:0 counterparts. The above data may be relevant in the pathogenesis of certain sphingolipid-related diseases, including certain neuropathies, diabetes, and glycogen storage diseases.

Prediction of the Intra-T Lymphocyte Tacrolimus Concentration after Kidney Transplantation with Population Pharmacokinetic Modeling.

The intracellular tacrolimus concentration in CD3+ T lymphocytes is proposed to be a better representative of the active component of tacrolimus than the whole blood concentration. However, intracellular measurements are complicated. Therefore, the aim of this study was to describe the relationship between intracellular and whole blood tacrolimus concentrations in a population pharmacokinetic model. Twenty-eight de novo kidney transplant recipients, treated with a once-daily oral extended-release tacrolimus formulation, were followed during the first-month post-transplantation. Additional whole blood and intracellular tacrolimus concentrations were measured at day 6 ± 1 (pre-dose, 4 and 8 hours post-dose) and day 14 ± 3 (pre-dose) post-transplantation. Pharmacokinetic analysis was performed using nonlinear mixed effects modeling software (NONMEM). The ratio between intracellular (n = 109) and whole blood (n = 248) concentrations was best described by a two-compartment whole blood model with an additional intracellular compartment without mass transfer from the central compartment. The ratio remained stable over time. Prednisolone dose influenced the absorption rate of tacrolimus, while hemoglobin, CYP3A4*22 allele carrier, and CYP3A5 expresser status were associated with the oral clearance of tacrolimus (P-value < 0.001). Furthermore, the intracellular tacrolimus concentrations were correlated with the intracellular production of interleukin-2 (P-value 0.015). The intracellular tacrolimus concentration can be predicted from a measured whole blood concentration using this model, without the need for repeated intracellular measurements. This knowledge is particularly important when the intracellular concentration is ready to be implemented into clinical practice, to overcome the complexities of cell isolation and analytical methods.

Identifying trajectories of change in sleep disturbance during psychological treatment for depression.

BACKGROUND: Sleep disturbance may impact response to psychological treatment for depression. Understanding how sleep disturbance changes during the course of psychological treatment, and identifying the risk factors for sleep disturbance response may inform clinical decision-making. METHOD: This analysis included 18,915 patients receiving high-intensity psychological therapy for depression from one of eight London-based Improving Access to Psychological Therapies (IAPT) services between 2011 and 2020. Distinct trajectories of change in sleep disturbance were identified using growth mixture modelling. The study also investigated associations between identified trajectory classes, pre-treatment patient characteristics, and eventual treatment outcomes from combined PHQ-9 and GAD-7 metrics used by the services. RESULTS: Six distinct trajectories of sleep disturbance were identified: two demonstrated improvement, while one showed initial deterioration and the other three groups displayed only limited change in sleep disturbance, each with varying baseline sleep disturbance. Associations with trajectory class membership were found based on: gender, ethnicity, unemployment status, antidepressant medication use, long-term health condition status, severity of depressive symptom, and functional impairment. Groups that showed improvement in sleep had the best eventual outcomes from depression treatment, followed by groups that consistently slept well. LIMITATION: Single item on sleep disturbance used, no data on treatment adherence. CONCLUSIONS: These findings reveal heterogeneity in the course of sleep disturbance during psychological treatment for depression. Closer monitoring of changes in sleep disturbance during treatment might inform treatment planning. This includes decisions about when to incorporate sleep management interventions, and whether to change or augment therapy with interventions to reduce sleep disturbance.

Endoscopic duodenal-jejunal bypass liner treatment of moderate obstructive sleep apnoea-A pilot study.

We aimed to assess the extent to which people with type 2 diabetes or pre-diabetes, obesity (BMI 30-45 kg/m2) and moderate obstructive sleep apnoea (OSA) requiring continuous positive airway pressure ventilation (CPAP) were able to discontinue CPAP following EndoBarrier-related weight loss. We assessed sleep and metabolic parameters before, during and after EndoBarrier in 12 participants with moderate OSA requiring CPAP (75% female, 8/12 [66%] type 2 diabetes, 4/12 [34%] prediabetes, mean ± SD age 52.6 ± 9.7 years, BMI 37.4 ± 3.5 kg/m2, median duration of OSA while on CPAP 9.0 [7.0-15.0] months). With EndoBarrier in-situ, mean ± SD Apnoea Hypopnoea Index (AHI) fell by 9.1 ± 5.0 events/h from 18.9 ± 3.8 to 9.7 ± 3.0 events/h (p < .001) with an associated reduction in symptoms of daytime sleepiness (mean Epworth Sleepiness Score) such that all the 12 participants no longer required CPAP according to National Institute for Health and Care Excellence criteria. After EndoBarrier removal, 10/12 (83%) patients attended follow-up and at 12 months after removal, AHI remained below 15 in 5/10 (50%) patients but in other five the AHI rose above 15 such that restarting CPAP was recommended as justified by their symptoms. Rather than restart CPAP, two patients lost the regained weight and their AHI dropped below 15 again. Thus, 7/10 (70%) of patients were able to remain off CPAP 12 or more months after EndoBarrier removal. These results demonstrate major benefit of EndoBarrier in moderate OSA, allowing all patients to discontinue CPAP during treatment, and with maintenance of improvement at follow-up in 70%. They confirm previously demonstrated metabolic improvements in diabetes and obesity.

Voices of experience: insights from Dutch parents on periviability guidelines and personalisation.

OBJECTIVE: To investigate the perspectives of experienced parents regarding guidelines and personalisation for managing imminent extremely premature births (22-26 weeks gestational age (GA)) . The study examined four scenarios: no guideline, a guideline based on GA, a guideline based on GA plus other factors and a guideline based on a calculated prognosis. DESIGN: Nineteen semistructured qualitative interviews were conducted with Dutch parents who experienced (imminent) extremely premature births between 23+5 and 26+2 weeks of gestation. Diversity was aimed for through purposive sampling from a database created prior to this study. Four of the parents opted for palliative care. Among the parents who chose intensive care, in nine cases the infant(s) survived. RESULTS: All participants acknowledged the necessity of having a periviability guideline because it would provide valuable decision-making support, and counterbalance decisions solely based on parental instincts to save their infant. Parents preferred guidelines that considered multiple prognostic factors beyond GA alone, without overwhelming parents with information, because more information would not necessarily make the decision easier for parents. Personalisation was defined by parents mainly as 'being seen and heard' and associated with building relationships with healthcare professionals and effective communication between them and professionals. CONCLUSIONS: The results underscore the importance of having a periviability guideline including multiple prognostic factors to assist parents in making decisions at the limit of viability, and the importance of a personalised care approach to meet parental needs in the context of imminent extremely preterm birth.

Voices of experience: what Dutch parents teach us about values and intuition in periviable decisions.

OBJECTIVE: When extremely premature birth at the limits of viability is imminent, shared decision-making with parents regarding the infant's treatment is widely recommended. Aligning decisions with parental values can be challenging. So, this study aims to get insight into (1) what values parents considered important in their decision, (2) whether their decision was based on intuition and/or rational analysis and (3) parental suggestions on how to help explore and articulate values during prenatal counselling. DESIGN: A qualitative study was performed among Dutch parents who experienced (imminent) extremely premature birth. Diversity was aimed for through purposive sampling. Semistructured interviews were conducted until saturation was achieved. Transcripts were coded and themes were derived from the data. RESULTS: Nineteen interviews were performed. Results show what parents considered important in their decision, such as the infants' future, family life and 'giving a chance'. Most parents made their decision more intuitively rather than rationally, for others both coexisted. Particularly fathers and parents who opted for palliative comfort care experienced the decision as rational. Parents would have liked to explore values, but found it challenging. They suggested strategies and conditions to help explore and articulate their values during counselling, such as a multidisciplinary approach. CONCLUSIONS: Various considerations and underlying values were found to be important. Parents recognise the influence of emotions and intuition in decision-making and struggle to articulate their values, emphasising the need for guidance. Healthcare providers should engage in open, personalised discussions to facilitate value exploration, enabling informed decisions aligned with parental values.