Search

Abstract Background Multi-family Therapy (MFT) is being increasingly used in specialist eating disorder services internationally. Despite evidence of its efficacy, little is understood about the treatment mechanisms and what specifically promotes change. This study aimed to understand clinician perspectives on how change occurs during MFT. Methods Clinicians with (a) 5 or more years’ experience facilitating MFT and (b) who had facilitated a minimum of two MFT groups were eligible for this study. Two individual interviews and four semi-structured focus groups were conducted online. Recordings were transcribed verbatim and analysed using reflexive thematic analysis. Results Twelve clinicians (five systemic/family psychotherapists, five clinical psychologists, and two consultant child and adolescent psychiatrists) from six different specialist services in the UK participated. Four main inter-connected themes describing how change is perceived to occur were generated; (1) Intensity and immediacy, (2) Flexibility, (3) New ideas and channels of learning and (4) Containment. Conclusions Current data matches closely with young person and parent experiences of MFT and intensive day treatment and how they perceive change to occur. Quantitative data are now needed to evaluate the impact of these factors on outcome. Plain English Summary Multi-family Therapy (MFT) is being increasingly used in specialist eating disorder services internationally. While there is evidence that it is helpful, little is understood about how the treatment works and what specifically promotes change. This study aimed to understand how clinician believe change to occur during MFT for young people and their family members. Clinicians with (a) five or more years’ experience facilitating MFT and (b) who had facilitated a minimum of two MFT groups were eligible for this study. Two individual interviews and four semi-structured focus groups were conducted online. Recordings were written out word-for-word and analysed using reflexive thematic analysis, a commonly used method for analysing this type of data. Twelve clinicians (five systemic/family psychotherapists, five clinical psychologists, and two consultant child and adolescent psychiatrists) from six different specialist services in the UK participated. Four related themes describing how change is perceived to occur were generated; (1) Intensity and immediacy, (2) Flexibility, (3) New ideas and channels of learning and (4) Containment. Current data matches closely with young person and parent experiences of MFT and intensive day treatment and how they perceive change to occur. These factors now need to be tested in future research.

Continued detection of Panton-Valentine leukocidin–positive Staphylococcus aureus in samples from a family with severe repeated skin infections and their pet cat suggests transmission between the family and the cat. Decolonizing the pet led to successful elimination of the bacteria from the household. Clinicians should consider pet cats as possible reinfection sources.

Abstract Systemic AL amyloidosis is one of the most frequently diagnosed forms of systemic amyloidosis. It arises from mutational changes in immunoglobulin light chains. To explore whether these mutations may affect the structure of the formed fibrils, we determine and compare the fibril structures from several patients with cardiac AL amyloidosis. All patients are affected by light chains that contain an IGLV3-19 gene segment, and the deposited fibrils differ by the mutations within this common germ line background. Using cryo-electron microscopy, we here find different fibril structures in each patient. These data establish that the mutations of amyloidogenic light chains contribute to defining the fibril architecture and hence the structure of the pathogenic agent.

Abstract Background Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse. Methods STORY follows 720 young people aged 16–25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings (‘Ōura ring’) unobtrusively measures individuals’ daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months. Discussion By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families.

Abstract Recent biological surveys of ancient inselbergs in southern Malawi and northern Mozambique have led to the discovery and description of many species new to science, and overlapping centres of endemism across multiple taxa. Combining these endemic taxa with data on geology and climate, we propose the ‘South East Africa Montane Archipelago’ (SEAMA) as a distinct ecoregion of global biological importance. The ecoregion encompasses 30 granitic inselbergs reaching > 1000 m above sea level, hosting the largest (Mt Mabu) and smallest (Mt Lico) mid-elevation rainforests in southern Africa, as well as biologically unique montane grasslands. Endemic taxa include 127 plants, 45 vertebrates (amphibians, reptiles, birds, mammals) and 45 invertebrate species (butterflies, freshwater crabs), and two endemic genera of plants and reptiles. Existing dated phylogenies of endemic animal lineages suggests this endemism arose from divergence events coinciding with repeated isolation of these mountains from the pan-African forests, together with the mountains’ great age and relative climatic stability. Since 2000, the SEAMA has lost 18% of its primary humid forest cover (up to 43% in some sites)—one of the highest deforestation rates in Africa. Urgently rectifying this situation, while addressing the resource needs of local communities, is a global priority for biodiversity conservation.

Abstract We study linear scalar perturbations of slowly accelerating Kerr-Newman-anti-de Sitter black holes using the method of isomonodromic deformations. The conformally coupled Klein-Gordon equation separates into two second-order ordinary differential equations with five singularities. Nevertheless, the angular equation can be transformed into a Heun equation, for which we provide an asymptotic expansion for the angular eigenvalues in the small acceleration and rotation limit. In the radial case, we recast the boundary value problem in terms of a set of initial conditions for the isomonodromic tau function of Fuchsian systems with five regular singular points. For the sake of illustration, we compute the quasi-normal modes frequencies.

Abstract Myeloproliferative neoplasms (MPNs) encompass a diverse group of hematologic disorders driven by mutations in JAK2, CALR, or MPL. The prevailing working model explaining how these driver mutations induce different disease phenotypes is based on the decisive influence of the cellular microenvironment and the acquisition of additional mutations. Here, we report increased levels of chromatin segregation errors in hematopoietic cells stably expressing CALRdel52 or JAK2V617F mutations. Our investigations employing murine 32DMPL and human erythroleukemic TF-1MPL cells demonstrate a link between CALRdel52 or JAK2V617F expression and a compromised spindle assembly checkpoint (SAC), a phenomenon contributing to error-prone mitosis. This defective SAC is associated with imbalances in the recruitment of SAC factors to mitotic kinetochores upon CALRdel52 or JAK2V617F expression. We show that JAK2 mutant CD34 + MPN patient-derived cells exhibit reduced expression of the master mitotic regulators PLK1, aurora kinase B, and PP2A catalytic subunit. Furthermore, the expression profile of mitotic regulators in CD34 + patient-derived cells allows to faithfully distinguish patients from healthy controls, as well as to differentiate primary and secondary myelofibrosis from essential thrombocythemia and polycythemia vera. Altogether, our data suggest alterations in mitotic regulation as a potential driver in the pathogenesis in MPN.

Abstract Background Family therapy for anorexia nervosa (FT-AN) is the first line recommended treatment for child and adolescent anorexia nervosa. Despite evidence of its efficacy, little is understood about the treatment mechanisms. This study aimed to understand how young people who have received FT-AN perceive change to occur across treatment. Method Fifteen adolescents (age 12–18 years) completed individual semi-structured interviews online. Recordings were transcribed verbatim and analysed using reflexive thematic analysis. Results Four inter-connected themes describing the process of change during treatment were generated; (1) relationships as the vehicle for change, (2) an awakening, (3) through, not around – no way out, (4) the life beyond. Conclusions Current data match relatively closely with theoretical models of FT-AN and emphasise the importance of building trust with all family members, including the young person. Additionally, supporting the family to create a trusting context in which there is a sense that the only way out of the illness is by going through it (rather than avoiding it) is critical. Empirical investigation of each of the described mechanisms is needed.

BackgroundIn young adults, there is evidence that free arm movements do not help to compensate muscle fatigue-induced deteriorations in dynamic balance performance. However, the postural control system in youth is immature, and as a result, the use of arm movements may provide a compensatory “upper body strategy” to correct fatigue-related balance impairments. Thus, the purpose of the present study was to compare the effects of free vs. restricted arm movement on dynamic balance performance prior and following exercise-induced muscle fatigue.MethodsForty-three healthy youth (19 females; mean age: 12.8 ± 1.9 years) performed the Y Balance Test–Lower Quarter before and immediately after a fatiguing exercise (i.e., repetitive vertical bipedal box jumps until failure) using two different arm positions: free (move the arms freely) and restricted (keep the arms akimbo) arm movement.ResultsMuscle fatigue (p ≤ 0.033; 0.10 ≤ ηp2 ≤ 0.33) and restriction of arm movement (p ≤ 0.005; 0.17 ≤ ηp2 ≤ 0.46) resulted in significantly deteriorated dynamic balance performance. However, the interactions between the two did not reach the level of significance (p ≥ 0.091; 0.01 ≤ ηp2 ≤ 0.07).ConclusionOur findings indicate that the use of an “upper body strategy” (i.e., free arm position) has no compensatory effect on muscle fatigue-induced dynamic balance deteriorations in healthy youth.

Background: Checkpoint inhibitors are monoclonal antibodies with action against solid and hematologic neoplasia with increasing use, which is why there have been reports of adverse events including endocrine system compromise. We report the case of a patient treated with anti PD-1 who developed an endocrinopathy. Purpose: To present the case of a patient with an endocrinopathy (hypophysitis) with secondary adrenal compromise associated with the use of checkpoint inhibitor therapy in a clinic in the city of Medellín, Colombia. Case presentation: 75-year-old male patient with a history of poorly differentiated squamocellular carcinoma of the lung, without lymphovascular invasion, treated with nivolumab, who after 6 months of treatment seeks consultation due to abdominal pain and several emetic episodes. On physical examination, the patient was hypotensive, and hypotonic hyponatremia was documented with decreased morning and afternoon cortisol. A pituitary profile was requested, showing decreased ACTH, prolactin, and luteinizing hormone with a normal TSH. Additionally, a sella turcica MRI was performed without evidence of structural damage, which is why it was concluded to be hypophysitis with a secondary adrenal insufficiency. Discussion and conclusion: Checkpoint inhibitor therapy offers a great advance in cancer treatment, and its increasing use allows us to watch and describe its adverse effects, making it possible to understand its mechanisms and possible risk factors. This is the first case of hypophystis secondary to anti PD-1 alone without CTLA-4 reported in the country. It is important to consider the possible adverse effects that patients undergoing immunotherapy treatment may experience, and to have a high index of clinical suspicion to perform appropriate tests for early identification.

Probing the architecture of neuronal circuits and the principles that underlie their functional organization remains an important challenge of modern neurosciences. This holds true, in particular, for the inference of neuronal connectivity from large-scale extracellular recordings. Despite the popularity of this approach and a number of elaborate methods to reconstruct networks, the degree to which synaptic connections can be reconstructed from spike-train recordings alone remains controversial. Here, we provide a framework to probe and compare connectivity inference algorithms, using a combination of synthetic ground-truth and in vitro data sets, where the connectivity labels were obtained from simultaneous high-density microelectrode array (HD-MEA) and patch-clamp recordings. We find that reconstruction performance critically depends on the regularity of the recorded spontaneous activity, i.e., their dynamical regime, the type of connectivity, and the amount of available spike-train data. We therefore introduce an ensemble artificial neural network (eANN) to improve connectivity inference. We train the eANN on the validated outputs of six established inference algorithms and show how it improves network reconstruction accuracy and robustness. Overall, the eANN demonstrated strong performance across different dynamical regimes, worked well on smaller datasets, and improved the detection of synaptic connectivity, especially inhibitory connections. Results indicated that the eANN also improved the topological characterization of neuronal networks. The presented methodology contributes to advancing the performance of inference algorithms and facilitates our understanding of how neuronal activity relates to synaptic connectivity.

Abstract Background A significant proportion of young people do not respond to the NICE recommended treatment for anorexia nervosa: Family Therapy. Whilst historically these young people would be admitted to inpatient services, which are associated with greater treatment cost, greater risk of relapse, and worse outcome, more recently evidence is building for the effectiveness of day programmes. One day programme that has been found to be effective is the Intensive Treatment Programme (ITP) of the Maudsley Centre for Child & Adolescent Eating Disorders in London, UK. However, to-date no studies have investigated how young people experience such a day programme. Method Anonymous feedback was completed via online survey by 51 young people over a 5-year period (2018–2023) on discharge from ITP. Results Four main themes were identified: (1) Support—young people expressed the importance of boundaries but also of feeling validated, and encouraged; (2) Uniqueness: an experience like no other—ITP was described as different to any other treatment received before (both outpatient and inpatient); (3) Relationships – young people valued connecting with others in a similar situation and reflected that relationships at home changed throughout treatment; (4) Self-development – learning skills, developing independence, and exploring an identity outside of the eating disorder was valued. Conclusions It is hoped that the reflections from these young people can help to inform clinicians working in DPs and those hoping to set up novel DPs about key aspects of treatment.

Abstract Systemic ATTR amyloidosis is an increasingly important protein misfolding disease that is provoked by the formation of amyloid fibrils from transthyretin protein. The pathological and clinical disease manifestations and the number of pathogenic mutational changes in transthyretin are highly diverse, raising the question whether the different mutations may lead to different fibril morphologies. Using cryo-electron microscopy, however, we show here that the fibril structure is remarkably similar in patients that are affected by different mutations. Our data suggest that the circumstances under which these fibrils are formed and deposited inside the body - and not only the fibril morphology - are crucial for defining the phenotypic variability in many patients.

Acquiring information on consumer preferences for the sensory properties of pomegranates is a cue for breeding programmes to set their quality targets and promote the consumption of this particularly healthy fruit. In this study, a total of 12 pomegranate varieties were evaluated, including commercial (Valenciana, Illina, Tastem, Rugalate, Wonderful, Mollar 49 y Mollar 45) and new varieties (Ref 102, Ref 383, H3/27, and D27/12). For the first time, consumers not only scored their acceptance of different pomegranate varieties but also described their sensory properties using CATA questions. This approach allowed us to identify the main drivers of liking, preference patterns, and the relationship between sensory and physico-chemical properties. Of all the sensory attributes, acidity intensity was revealed as the main driver of liking/disliking, and two different consumer preference patterns were identified: ‘low acid pomegranate lovers’ and ‘acid pomegranate lovers’. Seed properties like the intensity of woody flavour and seed/aril ratio were also key drivers for preferences. A relationship between sensory and physico-chemical properties was also established. Interestingly, sweetness perception correlated more strongly with low titratable acidity levels than with high total soluble solids levels, corroborating that acidity level is a key measurement for quality assessments. ‘H3/27’ was the most promising of the new varieties for having the well-appreciated internal properties of the ‘Mollar’ varieties and external and internal red colouration, which makes it much more appealing to consumers. This study shows that there is still room on the market for pomegranate varieties with very different sensory properties and highlights the need to develop sensory labels that help consumers make the right choices.

In 2012 and 2013, observational surveys from seismic vessels were conducted to evaluate the abundance and composition of floating marine debris (FMD) in the east of Tierra del Fuego (TDF), Argentina, and the Brazil/Malvinas Confluence zone (BMC), respectively. The mean abundance of FMD varied significantly between sampled ecosystems, with higher loads in TDF (mean abundance = 6.15 ± 8.84 items) when compared to BMC (3.31 ± 6.83 items). Plastics dominated the composition of FMD at both ecosystems (> 80%), followed by foamed plastics. Within the plastic category, bags were the most abundant item, followed by wrappers, and bottles, among others. According to its color, white/clear, and multicolor debris were the most abundant. The main presumed source of FMD was domestic activities, followed by fisheries-related, and construction. This is the first study demonstrating the utility of using seismic vessels as a platform for monitoring FMD in waters within the Argentine continental shelf and adjacent waters.

BackgroundPrompt access to evidence-based treatment for children and young people with eating disorders is important for outcomes, yet the gap in service provision remains pervasive. Record levels of young people are waiting for eating disorder treatment and access to care is limited. Guided self-help interventions that are brief and require minimal clinician support have the potential to meet the unprecedented demand for treatment quickly and effectively.ObjectiveTo examine the feasibility, acceptability and proof of concept of a novel, CBT guided self-help intervention for children and young people with threshold and subthreshold eating disorders.MethodsA single-arm, proof-of-concept pilot study of the CBT guided self-help intervention will be conducted. Children and young people (aged 11-19) with threshold and subthreshold eating disorders will receive a self-help intervention covering the core components of CBT, supported by 8 weekly guidance sessions delivered remotely. Clinical outcomes (eating-related psychopathology and associated impairment, changes in weight, depression, anxiety, and behavioural difficulties) will be assessed at baseline and post-intervention (12 weeks). Feasibility and acceptability of the intervention will be measured using various outcomes, including adherence to, and engagement with the intervention, rates of recruitment and retention, measure completion and treatment satisfaction. Qualitative data will also be collected for future intervention refinement.DiscussionIf the intervention is shown to produce clinical benefits in this pilot study, a fully powered randomised pilot study will be warranted with the ultimate goal of increasing access to psychological treatment for children and young people threshold and subthreshold eating disorders.Administrative informationThis study protocol (S1 File) adheres to the guidelines outlined in the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist for trial protocols [1, 2] which can be found in S1 Checklist. The numbers in parentheses in this protocol correspond to the item numbers in the SPIRIT checklist. The order of items has been modified to group similar items.

Abstract Exposure to extreme temperatures can negatively affect animal reproduction, by disrupting the ability of individuals to produce any offspring (fertility), or the number of offspring produced by fertile individuals (fecundity). This has important ecological consequences, because reproduction is the ultimate measure of population fitness: a reduction in reproductive output lowers the population growth rate and increases the extinction risk. Despite this importance, there have been no large‐scale summaries of the evidence for effect of temperature on reproduction. We provide a systematic map of studies testing the relationship between temperature and animal reproduction. We systematically searched for published studies that statistically test for a direct link between temperature and animal reproduction, in terms of fertility, fecundity or indirect measures of reproductive potential (gamete and gonad traits). Overall, we collated a large and rich evidence base, with 1654 papers that met our inclusion criteria, encompassing 1191 species. The map revealed several important research gaps. Insects made up almost half of the dataset, but reptiles and amphibians were uncommon, as were non‐arthropod invertebrates. Fecundity was the most common reproductive trait examined, and relatively few studies measured fertility. It was uncommon for experimental studies to test exposure of different life stages, exposure to short‐term heat or cold shock, exposure to temperature fluctuations, or to independently assess male and female effects. Studies were most often published in journals focusing on entomology and pest control, ecology and evolution, aquaculture and fisheries science, and marine biology. Finally, while individuals were sampled from every continent, there was a strong sampling bias towards mid‐latitudes in the Northern Hemisphere, such that the tropics and polar regions are less well sampled. This map reveals a rich literature of studies testing the relationship between temperature and animal reproduction, but also uncovers substantial missing treatment of taxa, traits, and thermal regimes. This database will provide a valuable resource for future quantitative meta‐analyses, and direct future studies aiming to fill identified gaps.

Abstract Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene mutations lead to fragile X syndrome, cognitive disorders, and, in some individuals, scoliosis and craniofacial abnormalities. Four-month-old (mo) male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass. However, consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown. We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2- and 9-mo mice. The cancellous bone mass is higher only in females, whereas, cortical bone mass is higher in 2- and 9-mo males, but higher in 2- and lower in 9-mo female FMR1-knockout mice. Furthermore, male bones show higher biomechanical properties at 2mo, and females at both ages. Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro, without affecting osteoclasts in vivo/ex vivo. Thus, FMR1 is a novel osteoblast/osteocyte differentiation inhibitor, and its absence leads to age-, site- and sex-dependent higher bone mass/strength.

Abstract Background Hospitals with their high antimicrobial selection pressure represent the presumably most important reservoir of multidrug-resistant human pathogens. Antibiotics administered in the course of treatment are excreted and discharged into the wastewater system. Not only in patients, but also in the sewers, antimicrobial substances exert selection pressure on existing bacteria and promote the emergence and dissemination of multidrug-resistant clones. In previous studies, two main clusters were identified in all sections of the hospital wastewater network that was investigated, one K. pneumoniae ST147 cluster encoding NDM- and OXA-48 carbapenemases and one VIM-encoding P. aeruginosa ST823 cluster. In the current study, we investigated if NDM- and OXA-48-encoding K. pneumoniae and VIM-encoding P. aeruginosa isolates recovered between 2014 and 2021 from oncological patients belonged to those same clusters. Methods The 32 isolates were re-cultured, whole-genome sequenced, phenotypically tested for their antimicrobial susceptibility, and analyzed for clonality and resistance genes in silico. Results Among these strains, 25 belonged to the two clusters that had been predominant in the wastewater, while two others belonged to a sequence-type less prominently detected in the drains of the patient rooms. Conclusion Patients constantly exposed to antibiotics can, in interaction with their persistently antibiotic-exposed sanitary facilities, form a niche that might be supportive for the emergence, the development, the dissemination, and the maintenance of certain nosocomial pathogen populations in the hospital, due to antibiotic-induced selection pressure. Technical and infection control solutions might help preventing transmission of microorganisms from the wastewater system to the patient and vice versa, particularly concerning the shower and toilet drainage. However, a major driving force might also be antibiotic induced selection pressure and parallel antimicrobial stewardship efforts could be essential.

ABSTRACT Beta-lactam antibiotics are widely used to treat infections caused by the important human pathogen Staphylococcus aureus. Resistance to beta-lactams, as found in methicillin-resistant S. aureus, renders effective treatment difficult. The second messenger cyclic di-3′,5′-adenosine monophosphate (c-di-AMP) promotes beta-lactam resistance in clinical S. aureus isolates. C-di-AMP plays a crucial role in the regulation of cellular processes such as virulence, cell wall homeostasis, and resistance to beta-lactams in many bacterial species. In S. aureus, c-di-AMP synthesis is mediated by the diadenylate cyclase DacA, while its degradation is carried out by the phosphodiesterases GdpP and Pde2. In this work, we assessed the effect of altered c-di-AMP levels due to mutations in dacA, gdpP, or gdpP/pde2 on virulence determinants. We report that a previously described growth defect in bacteria producing high c-di-AMP levels is mainly attributable to smaller cell size. High c-di-AMP levels also led to decreased survival upon oxidative stress, reduced production of the antioxidant staphyloxanthin, increased oxacillin and fosfomycin resistance, and increased cell wall thickness. While resistance to ceftaroline was not affected, high c-di-AMP levels promoted tolerance to this antibiotic. In response to cell wall stress induced by antibiotics, the three-component regulatory system VraTSR mediates an increase in cell wall synthesis via the cell wall stress stimulon (CWSS). Increased c-di-AMP levels led to an activation of the CWSS. Upon deletion of vraR, resistance to oxacillin and fosfomycin as well as cell wall thickness diminished in the ΔgdpP mutant, indicating a contribution of the VraTSR system to the cell wall related phenotypes. IMPORTANCE Antibiotic resistance and tolerance are substantial healthcare-related problems, hampering effective treatment of bacterial infections. Mutations in the phosphodiesterase GdpP, which degrades cyclic di-3′, 5′-adenosine monophosphate (c-di-AMP), have recently been associated with resistance to beta-lactam antibiotics in clinical Staphylococcus aureus isolates. In this study, we show that high c-di-AMP levels decreased the cell size and increased the cell wall thickness in S. aureus mutant strains. As a consequence, an increase in resistance to cell wall targeting antibiotics, such as oxacillin and fosfomycin as well as in tolerance to ceftaroline, a cephalosporine used to treat methicillin-resistant S. aureus infections, was observed. These findings underline the importance of investigating the role of c-di-AMP in the development of tolerance and resistance to antibiotics in order to optimize treatment in the clinical setting.

Objectives Same day emergency care (SDEC) is a new model of care, which has emerged over the past 5 years, building on prior ambulatory care services. The National Health Service (NHS) England National Strategy for SDEC suggests SDEC can meet local health needs by providing alternatives to emergency department attendance or hospital admission, for people with an urgent healthcare need, beyond the limited scope of an urgent treatment centre. This review focuses on acute medical SDEC, as medical patients represent a significant proportion of emergency admissions. The planned scoping review aims to map the existing evidence base.Methods and analysis This is a protocol for a scoping review to be conducted in accordance with the format of the Joanna Briggs Institute (JBI) methodology for scoping reviews. The databases to be searched will include EMBASE, MEDLINE and CINAHL, via EBSCOhost. Sources of unpublished studies, policies and grey literature will include Google Scholar, the Cochrane Library, TRIP database, ProQuest Dissertations and Theses Open, and the Health Management Information Consortium. Papers relating to acute medicine adult patients attending NHS SDEC services in the UK will be included. International papers will be excluded, as will those over 5 years old, and those where full text is not available. The results of the search and study inclusion/exclusion process will be reported and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram. Data will be extracted from papers included in the scoping review by two reviewers, using a JBI data extraction tool. Any differences of opinion will be discussed until consensus is reached. If needed, a third reviewer will be asked to join the review team to achieve consensus. Data and themes extracted will be summarised and presented in tables. A narrative thematic summary will accompany the presented results, describing how the results relate to the review objective. Literature gaps will be identified and recommendations for future research made.Ethics and dissemination There is no requirement for ethical approval for this scoping review. On completion, it will be published in a peer-reviewed academic journal and presented at a conference.

Background: Despite dietitians being important members of the multidisciplinary team delivering family therapy for anorexia nervosa (FT-AN), their specific responsibilities and roles are unclear and their involvement in the treatment can be a contentious issue. Methodology: Clinicians (n = 20) experienced in the delivery of FT-AN who were working at a specialist child and adolescent eating disorder service responded to an online survey about their experience of including a dietitian in FT-AN and how they understand the role. Both categorical and open-ended questions were used. Reflexive thematic analysis was used to analyse the qualitative free-text responses of clinician perspectives on the role of the dietitian in FT-AN. Results: All clinicians agreed that dietetics had a role within FT-AN and most frequently sought dietetic involvement in the early phases of FT-AN. Reflexive thematic analysis of responses identified three main themes. These were (1) collaboration is key, (2) confidence as a core consideration and (3) case-by-case approach. These themes evidenced the role of the dietitian within FT-AN and highlighted both the benefits and concerns of this involvement. Conclusions: This study demonstrated that dietitians can take a core role as collaborators within therapy-led teams that facilitate joint working and sharing of expertise. However, dietetic input should be considered on a case-by-case basis, given its potential for creating an over-focus on nutrition and potentially diminishing parental confidence in feeding. When indicated for selected cases, nutritional counselling should be offered in joint sessions with the therapist rather than separately. The findings of the study were limited by the small sample size of participants recruited from a single centre and heterogeneity in the professional background of respondents. Although the integration of dietetics within the multidisciplinary team and the ability of dietitians to individualise patient care can enhance FT-AN treatment, potential benefits and disbenefits should be considered for each case.

Individuals with eating disorders (EDs) often encounter challenges related to body image, emotional, and sensory difficulties during nutritional rehabilitation. To address these challenges, a novel technology-enabled smart toy, Purrble, designed for immediate assistance in emotion regulation, is being explored. A mixed-method approach involving workshops, diaries, and focus groups was employed to examine the feasibility of Purrble as a therapeutic tool and its impact on participants’ daily routines, sensory experiences, and emotional states. The study results demonstrate the engagement and acceptability of this device. Qualitative analysis revealed that participants independently used and integrated Purrble into their emotional and sensory regulation practices. These pilot results support the potential for a shift in the delivery of adjunct therapeutic tools through technology, particularly for ED patients with complex presentations. Future research is necessary to further explore the psychological benefits of this intervention.

Este estudio propone un análisis multicriterio para priorizar las alternativas de equipos utilizados en el procesamiento de pruebas de RT-PCR para la detección del virus SARS-CoV-2 a través del hisopado nasofaríngeo. Se empleó el Proceso de Análisis Jerárquico (AHP) basado en la Evaluación de Tecnologías en Salud (ETES) para llevar a cabo este análisis. Para su desarrollo, primero se realizó una revisión bibliográfica para identificar los cinco criterios y doce subcriterios incluidos que facilitan la toma de decisiones en la compra de equipos para el procesamiento de pruebas RT-PCR; posteriormente se caracterizó el proceso de uso de la tecnología en una institución prestadora de salud. Los resultados obtenidos revelaron que la efectividad clínica y la seguridad fueron los criterios más relevantes en la selección de la tecnología propuesta. Para comprobar la utilidad de la herramienta multicriterio, se evaluaron dos equipos específicos.

BackgroundDay programmes for adolescent anorexia nervosa (AN) can function as an alternative to inpatient admissions and/or an increase in outpatient treatment intensity. Processes of change during treatment for AN are currently poorly understood. This study aimed to explore how adolescents with AN and their parents understood the helpful and unhelpful factors and processes that impacted them during day programme treatment.MethodA critical realist paradigm was used to qualitatively explore the views of 16 participants. Participants were recruited from the Intensive Treatment Programme (ITP) at the Maudsley Center for Child and Adolescent Eating Disorders (MCCAED) at the end of treatment. Dyadic Interview Analysis (DIA) was used to compare and contrast the narratives of the seven adolescent–parent pairs after two inductive reflexive thematic analyses were conducted for the group of eight adolescents and the group of eight parents separately.ResultsEight subthemes across three themes were identified: 1) “Like me she didn't feel so alone anymore”—families connect with staff, peers, and each other; 2) “You have to eat because ITP say so”—the programme provides families with containment through its structure and authority; and 3) “I found that I was using the skills I learnt there like in multiple aspects of my life, not just around food”—families take in new ideas and generalize these into their lives. These interconnected themes generated hope and change. However, helpful elements individually could be unhelpful if one or more of the other factors were missing. For example, staff firmness, which participants often found helpful (theme two), could be experienced as harshness when adolescents did not feel related to as individuals (theme one).ConclusionThe findings can be conceptualized within recent descriptions regarding the therapeutic change, including epistemic trust and mentalization. Treatment characteristics, such as intensity and containment, as well as illness-specific factors and processes, such as control and collaboration, the role of peer support, and the potential for family members to experience the impact of the adolescent's AN and treatment non-response as traumatic, are equally important to consider.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a complex trait with an estimated prevalence of 25% globally. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation, and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes. Methods: Exome sequencing and genome comparisons were used to identify the likely causal variant. We extensively characterised the clinical phenotype and post-prandial metabolic responses of family members with the identified novel variant in comparison with healthy non-carriers and wild-type patients with NAFLD. Variant-expressing hepatocyte-like cells (HLCs) were derived from human-induced pluripotent stem cells generated from homozygous donor skin fibroblasts and restored to wild-type using CRISPR-Cas9. The phenotype was assessed using imaging, targeted RNA analysis, and molecular expression arrays. Results: We identified a rare causal variant c.1691T>C p.I564T (rs745447480) in MTTP, encoding microsomal triglyceride transfer protein (MTP), associated with progressive NAFLD, unrelated to metabolic syndrome and without characteristic features of abetalipoproteinaemia. HLCs derived from a homozygote donor had significantly lower MTP activity and lower lipoprotein ApoB secretion than wild-type cells, while having similar levels of MTP mRNA and protein. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators, and production of reactive oxygen species. Conclusions: We have identified and characterised a rare causal variant in MTTP, and homozygosity for MTTP p.I564T is associated with progressive NAFLD without any other manifestations of abetalipoproteinaemia. Our findings provide insights into mechanisms driving progressive NAFLD. Impact and Implications: A rare genetic variant in the gene MTTP has been identified as responsible for the development of severe non-alcoholic fatty liver disease in a four-generation family with no typical disease risk factors. A cell line culture created harbouring this variant gene was characterised to understand how this genetic variation leads to a defect in liver cells, which results in accumulation of fat and processes that promote disease. This is now a useful model for studying the disease pathways and to discover new ways to treat common types of fatty liver disease.

el artículo busca comprender la relación entre el Chocó y los procesos políticos nacionales en el marco de la pregunta por la configuración del Estado colombiano en las primeras décadas del siglo XX. En particular, el artículo se enfoca en los procesos electorales chocoanos en un contexto de reorganización del Partido Liberal y aumento de la participación de sectores populares de personas negras. A partir de la revisión de fuentes electorales, de una exhaustiva revisión del periódico local ABC. y partiendo de una crítica a las visiones del Estado como un “ente monolítico”, el artículo problematiza las ideas sobre la “marginalidad” del territorio. En cambio, el estudio de los procesos electorales chocoanos a principios del siglo XX muestra significativos niveles de articulación de las dinámicas políticas chocoanas con las del resto del país, aportando en la comprensión de la configuración del Estado colombiano desde una perspectiva partidista.

This study reports the cryo-EM structures of AA amyloid fibrils from two patients with vascular AA amyloidosis. The findings imply that different disease variants in systemic amyloidosis are associated with different fibril structures.

This manuscript reports the structure of a pathologically relevant wild type ATTR amyloid fibril from systemic non-hereditary transthyretin amyloidosis. The comparison of the wild type ATTR fibril with two previous published ex vivo V30M ATTR fibrils highlighted numerous similarities between these different reconstructions, pointing to a common underlying structure for ATTR fibrils despite coming from different mutants and patients.

Plain English summary This study investigated the experience of having a sibling with anorexia nervosa, and the sibling perspectives on the treatment they get. Four focus groups were held with siblings (11–19 year-olds) of adolescents with anorexia nervosa. Group discussions were written down word-for-word and analysed using thematic analysis. Four themes and eight sub-themes were identified. These illustrated siblings feel very affected by the way the family needs to change to support someone with anorexia nervosa. Feelings of ambivalence and acceptance were also evident. Siblings said they silenced their own emotions and needs so as not to trouble others, and distanced themselves from their families in order to cope. Siblings generally felt that services had not attended to their needs, and that they had not been appropriately included in treatment. Findings from this study point to ways siblings may be better supported, such as peer support groups.

Plain English Summary Multi-family therapy (MFT-BN) is a new treatment for adolescent bulimia nervosa. It involves a group of families (maximum nine) working together with a team of therapists over the course of 20 weeks. This study aimed to explore the experience of MFT-BN from the adolescents and parent/caregiver perspective, as this has not been explored before. Participants from two consecutive MFT-BN groups were invited to participate in either a focus group or individual interview. 8 parents, 1 older sibling, and 6 adolescents participated. Three themes were identified from what they said. Participants described overall shifts in their thoughts, emotions, behaviours, and relationships both individually and within their families, as a result of attending MFT-BN. Meeting other families with similar struggles and sharing experiences, skills and learning helped reduce isolation and promote change. There was also a sense from participants that some things did not, or could not, be spoken about in the group context and that more direct and challenging conversations might have been helpful at times. More research is needed to explore the experience of MFT-BN and its outcomes across a more diverse range of participants and treatment settings.

Abstract Background Radically Open Dialectical Behaviour Therapy (RO DBT) is a novel transdiagnostic treatment that targets ‘maladaptive overcontrol’; a transdiagnostic cluster of traits associated with excessive emotional and behavioural inhibitory control. Outcomes are promising for adults with a range of psychiatric disorders. No study to date has explored the adolescent experience of RO DBT. Methods Of the 25 eligible adolescents who received RO DBT between March 2015 and April 2017, 15 (14–17 years) consented and completed a semi-structured interview about their experience of treatment within 1 month of discharge. Interviews were recorded and then transcribed manually. Free text responses were analysed using reflexive thematic analysis. Results The majority (n = 13) had a primary diagnosis of anorexia nervosa, although comorbidity was the norm, with 80.0% having two or more predicted comorbid psychiatric diagnoses. All had received some prior psychological treatment. Four themes were identified from analysis of transcripts: 1) Broadening Horizons, 2) Building Connections, 3) Flexibility, 4) Information Overload. Generally, RO DBT was perceived as helpful in both content and process. The focus on social and broader well-being, rather than specific mental health symptoms, was considered beneficial by many. Adolescents appreciated the group-based format of skills classes and reported benefiting from learning and practicing skills each week. The fourth theme, Information Overload, highlighted that for some, the amount of content felt overwhelming and that it was hard to remember and digest all the information, suggesting that adaptations, or simplifications, may be required to ensure accessibility for adolescents. Conclusions RO DBT is perceived as a relevant and beneficial new treatment for adolescents with maladaptive overcontrol. The broad treatment focus is perceived as unique and of particular benefit. It is reported to help with general and social functioning and foster cognitive and behavioural flexibility. Nevertheless, the amount and complexity of material was felt to be very large by some and may suggest the need for modified adolescent-specific materials.

Aim: The aim of this randomised, double-blind, placebo-controlled pilot clinical trial is to evaluate the capacity of a mouthwash to reduce SARS-CoV-2 viral load in the saliva of patients with COVID-19. Methods: Twenty-three symptomatic SARS-CoV-2-positive outpatients were selected and randomised into two groups and registered at NTC 04563689. Both groups rinsed and gargled for one minute with either distilled water (Placebo) or with 0.05% Cetylpyridinium chloride (CPC) plus 0.12% Chlorhexidine (CHX) mouthwash (PERIOAID Intensive CareÒ). Saliva samples were collected before the use of placebo or mouthwash and after 15 minutes and 1 and 2 hours of either of the above treatment. A saliva sample was also taken five days after regular use of placebo or mouthwash twice daily. The virus was detected by qRT-PCR. Results: A great heterogeneity in the viral load values was observed at baseline in both groups for nasopharyngeal and saliva samples. Most of the patients who used the mouthwash (8/12) had a significant decrease in baseline viral load after 15 min (greater than 99% reduction). This inhibitory effect was maintained for up to two hours in 10 of the 12 patients. At five days, SARS-CoV-2 RNA was detected in only 1 patient from the mouthwash group and in 5 from the placebo group. Conclusions: This study points out that a CPC mouthwash can reduce the viral load in saliva of COVID-positive patients. This finding may be important in transmission control of SARS-CoV-2. Nevertheless, the clinical relevance of CPC mouthwash-reduction on SARS-CoV-2 shedding in saliva requires further study

Ventilator-induced diaphragm dysfunction (VIDD) is a common sequela of intensive care unit (ICU) treatment requiring mechanical ventilation (MV) and neuromuscular blockade (NMBA). It is characterised by diaphragm weakness, prolonged respirator weaning and adverse outcomes. Dissociative glucocorticoids (e.g., vamorolone, VBP-15) and chaperone co-inducers (e.g., BGP-15) previously showed positive effects in an ICU-rat model. In limb muscle critical illness myopathy, preferential myosin loss prevails, while myofibrillar protein post-translational modifications are more dominant in VIDD. It is not known whether the marked decline in specific force (force normalised to cross-sectional area) is a pure consequence of altered contractility signaling or whether diaphragm weakness also has a structural correlate through sterical remodeling of myofibrillar cytoarchitecture, how quickly it develops, and to which extent VBP-15 or BGP-15 may specifically recover myofibrillar geometry. To address these questions, we performed label-free multiphoton Second Harmonic Generation (SHG) imaging followed by quantitative morphometry in single diaphragm muscle fibres from healthy rats subjected to five or 10 days of MV + NMBA to simulate ICU treatment without underlying confounding pathology (like sepsis). Rats received daily treatment of either Prednisolone, VBP-15, BGP-15 or none. Myosin-II SHG signal intensities, fibre diameters (FD) as well as the parameters of myofibrillar angular parallelism (cosine angle sum, CAS) and in-register of adjacent myofibrils (Vernier density, VD) were computed from SHG images. ICU treatment caused a decline in FD at day 10 as well as a significant decline in CAS and VD from day 5. Vamorolone effectively recovered FD at day 10, while BGP-15 was more effective at day 5. BGP-15 was more effective than VBP-15 in recovering CAS at day 10 although not to control levels. In-register VD levels were restored at day 10 by both compounds. Our study is the first to provide quantitative insights into VIDD-related myofibrillar remodeling unravelled by SHG imaging, suggesting that both VBP-15 and BGP-15 can effectively ameliorate the structure-related dysfunction in VIDD.

Male animals often show higher mutation rates than their female conspecifics. A hypothesis for this male bias is that competition over fertilization of female gametes leads to increased male investment into reproduction at the expense of maintenance and repair, resulting in a trade-off between male success in sperm competition and offspring quality. Here, we provide evidence for this hypothesis by harnessing the power of experimental evolution to study effects of sexual selection on the male germline in the seed beetle Callosobruchus maculatus. We first show that 50 generations of evolution under strong sexual selection, coupled with experimental removal of natural selection, resulted in males that are more successful in sperm competition. We then show that these males produce progeny of lower quality if engaging in sociosexual interactions prior to being challenged to surveil and repair experimentally induced damage in their germline and that the presence of male competitors alone can be enough to elicit this response. We identify 18 candidate genes that showed differential expression in response to the induced germline damage, with several of these previously implicated in processes associated with DNA repair and cellular maintenance. These genes also showed significant expression changes across sociosexual treatments of fathers and predicted the reduction in quality of their offspring, with expression of one gene also being strongly correlated to male sperm competition success. Sex differences in expression of the same 18 genes indicate a substantially higher female investment in germline maintenance. While more work is needed to detail the exact molecular underpinnings of our results, our findings provide rare experimental evidence for a trade-off between male success in sperm competition and germline maintenance. This suggests that sex differences in the relative strengths of sexual and natural selection are causally linked to male mutation bias. The tenet advocated here, that the allocation decisions of an individual can affect plasticity of its germline and the resulting genetic quality of subsequent generations, has several interesting implications for mate choice processes.

Handball players are at a high risk of suffering a sport-related injury. Recent studies in various adult populations (e.g., US Army soldiers/warrior athletes, and military members) showed that poor scores in the upper quarter Y-balance test (YBT-UQ) are related to an increased risk of injury. Yet, it is unclear whether this also applies to adolescent handball players. Thus, the present study aims to determine if pre-season YBT-UQ performance is associated with sport-related injuries during the competitive season in adolescent handball players. One hundred and thirty-three adolescent handball players (age: 15.4 ± 1.7 years; m = 99, f = 42) who competed in the second highest league in the Rhine-Ruhr region, Germany, during the 2021/2022 season participated in the study. Before the competitive season, the players performed the YBT-UQ to assess upper extremity mobility and stability of the throwing and non-throwing arm. Over the 8-month competitive season, the coaches monitored the occurrence of sports-related injuries once a week, using an injury report form from the legal accident insurance. Fifty-seven players (43%) incurred a sport-related injury during the competitive season, of which 27 (47%) had upper body injuries, and 30 (53%) were lower body injuries. The YBT-UQ performance of the throwing and non-throwing arm did not significantly differ between injured and non-injured players. Further, Cox proportional hazard survival regression model analyses revealed that only the presence of an inferolateral reach asymmetry score ≥7.75% arm length was associated with a moderate increase in the risk (hazard ratio = 2.18, 95% confidence interval = 1.02–4.68, p = 0.045) of lower but not upper or whole-body injuries. Our findings suggest that the YBT-UQ has limited value as a field-based screening tool to assess the risk of sport-related injuries in adolescent handball players.

Myeloproliferative neoplasms (MPN) are rare hematologic disorders characterized by clonal hematopoiesis. Familial clustering is observed in a subset of cases, with a notable proportion exhibiting heterozygous germline mutations in DNA double-strand break repair genes (e.g., BRCA1). We investigated the therapeutic potential of targeting BRCA1 haploinsufficiency alongside the JAK2V617F driver mutation. We assessed the efficacy of combining the PARP inhibitor olaparib with interferon-alpha (IFNα) in CRISPR/Cas9-engineered Brca1+/− Jak2V617F-positive 32D cells. Olaparib treatment induced a higher number of DNA double-strand breaks, as demonstrated by γH2AX analysis through Western blot (p = 0.024), flow cytometry (p = 0.013), and confocal microscopy (p = 0.071). RAD51 foci formation was impaired in Brca1+/− cells compared to Brca1+/+ cells, indicating impaired homologous recombination repair due to Brca1 haploinsufficiency. Importantly, olaparib enhanced apoptosis while diminishing cell proliferation and viability in Brca1+/− cells compared to Brca1+/+ cells. These effects were further potentiated by IFNα. Olaparib induced interferon-stimulated genes and increased endogenous production of IFNα in Brca1+/− cells. These responses were abrogated by STING inhibition. In conclusion, our findings suggest that the combination of olaparib and IFNα presents a promising therapeutic strategy for MPN patients by exploiting the synthetic lethality between germline BRCA1 mutations and the JAK2V617F MPN driver mutation.

Future aviation concepts should be both CO2-neutral and without other emissions. One approach to reaching both targets is based on sustainably produced synthetic liquid fuels, which may allow very clean, lean premixed prevaporized (LPP) combustion. For that, fuels are needed with much longer ignition delay times and a lower flashback propensity than current jet fuels. We describe an experimental setup to investigate the flashback stability of liquid fuels in a multi-fuel burner. In this work, the measurement procedure and the determination of the experimentally obtained accuracy are in focus with regard to prevaporized and preheated iso-propanol/air flames in an equivalence ratio range of 0.85 to 1.05 involving three preheating levels (573, 673, and 773 K). As the determination of the accurate unburnt gas temperature just ahead of the flame is of strong importance for flashback but not directly possible, a model is implemented to determine it from the measurable quantities. Even with this indirect method, and also regarding the hysteresis of the experimental preheating temperature, it is found that the relevant quantities, namely, measured temperatures, mass flows, and values derived from them, can be determined with accuracy in the range below 1.7%.

In a prepurchase situation, consumers base their choice decision on external fruit characteristics, from which they infer internal characteristics. This study investigates consumer preference for pomegranate appearance using a choice-based conjoint analysis with 320 participants. We created 27 images of pomegranates that differed in varietal characteristics: colour (yellow, bicoloured, and red), shape (round, oval, and flattened), and calyx shape (open, semi-open, and closed). Colour was by far the most important factor for consumers, followed by fruit shape and calyx shape. Two preference profiles were identified. Most consumers liked bicolour and red pomegranates equally, and rejected yellow ones, while a smaller group concentrated their choice on bicolour pomegranates. In terms of fruit and calyx shape, oval and flattened fruit and open calyx were the most preferred by both consumer groups. Barriers and drivers for consumption were also investigated. There is still plenty of room to increase pomegranate consumption. Greater availability of pomegranates and ready-to-eat arils in grocery shops, obtaining new unseeded/easier-to-peel varieties, and providing a sensory label would help to overcome current barriers. Marketing campaigns should focus on a pomegranate’s health benefits and its versatility in consumption.