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

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

Psychosis and help-seeking behaviour-A systematic review of the literature.

PURPOSE: Many people with psychosis do not seek help which delays access to recommended treatments. Duration of untreated psychosis is associated with poor healthcare outcomes and increased risk of relapse. The reasons why people delay accessing treatment remain unclear. This is the first systematic review to synthesise the literature examining professional and non-professional help-seeking in psychosis across clinical and subclinical populations. METHODS: We searched four databases (APA PsycINFO, APA PsycArticles, Medline and British Library EThOS) to generate a comprehensive account of the quantitative literature. Heterogeneity of measures precluded a meta-analysis. RESULTS: We identified 19 articles (including 9686 participants) that met criteria for the review. Help-seeking in psychosis is associated with being female, having a higher level of education, and experiencing more than one symptom. People with psychosis report stigma, poor mental health literacy and lack of family support as key barriers. Clinicians report childhood physical abuse, insecure attachment and severity of psychosis as additional barriers. We also found differences in preferred sources of help across cultures. There is currently no consensus on reliable help-seeking measures. CONCLUSIONS: This is the first systematic review to examine help-seeking behaviour in psychosis. Assertive and culturally sensitive engagement efforts should be targeted towards people with a history of early adversity, poor mental health literacy, limited social support and more severe psychosis.

Sensitivity to psychosocial influences at age 3 predicts mental health in middle childhood.

Children vary in how sensitive they are to experiences, with consequences for their developmental outcomes. In the current study, we investigated how behavioral sensitivity at age 3 years predicts mental health in middle childhood. Using a novel repeated measures design, we calculated child sensitivity to multiple psychological and social influences: parent praise, parent stress, child mood, and child sleep. We conceptualized sensitivity as the strength and direction of the relationship between psychosocial influences and child behavior, operationalized as toothbrushing time, at age 3 years. When children were 5-7 years old (n = 60), parents reported on children's internalizing and externalizing problems. Children who were more sensitive to their parents' praise at age 3 had fewer internalizing (r = -0.37, p = 0.016, pFDR = 0.042) and externalizing (r = -0.35, p = 0.021, pFDR = 0.042) problems in middle childhood. Higher average parent praise also marginally predicted fewer externalizing problems (r = -0.33, p = 0.006, pFDR = 0.057). Child sensitivity to mood predicted fewer internalizing (r = -0.32, p = 0.013, pFDR = 0.042) and externalizing (r = -0.38, p = 0.003, pFDR = 0.026) problems. By capturing variability in how children respond to daily fluctuations in their environment, we can contribute to the early prediction of mental health problems and improve access to early intervention services for children and families who need them most. RESEARCH HIGHLIGHTS: Children differ in how strongly their behavior depends on psychosocial factors including parent praise, child mood, child sleep, and parent stress. Children who are more sensitive to their parents' praise at age 3 have fewer internalizing and externalizing problems at age 5-7 years. Child sensitivity to mood also predicts fewer internalizing and externalizing problems.

Secure attachment imagery facilitates help-seeking and help-acceptance in psychosis.

OBJECTIVES: People with psychosis delay accessing recommended treatments, resulting in poor healthcare outcomes and increased risk of relapse. Means of improving help-seeking and help-acceptance could reduce duration of untreated psychosis (DUP). This study examined the role of attachment style in help-seeking and help-acceptance in psychosis. DESIGN: We used an experimental design to test the effect of attachment imagery priming on help-seeking and help-acceptance intentions, in a sample with self-reported psychosis. The independent variables were attachment imagery condition (secure vs. avoidant) and time (pre- vs. post-prime). The dependent variables were state paranoia, help-seeking intentions and help-acceptance intentions. METHODS: We used an online research platform to recruit people with psychosis (n = 61). Participants were randomly allocated to the secure or avoidant attachment priming condition. All completed measures of state paranoia, help-seeking, and help-acceptance, before and after priming. RESULTS: In comparison with the avoidant condition, secure attachment imagery resulted in reduced paranoia and increased help-seeking and acceptance intentions, all with large effect sizes. CONCLUSIONS: This is the first study to use an experimental design to assess the role of attachment style in help-seeking and help-acceptance in a clinical sample. Attachment style is causally linked to behavioural intentions that contribute to DUP. Clinicians should assess attachment and help-seeking and acceptance, highlight these in formulation, and prioritise in treatment planning. Interventions that enhance help-seeking and acceptance could improve access to recommended treatments and reduce DUP.

Patients' Reflections on Treatment Decision After Surgery for Laryngeal Cancer.

Importance: Clinicians should understand how patients who were treated with laryngeal cancer surgery think about this later on and what factors may be related with regretting surgery. Objective: To assess variables associated with a positive attitude toward laryngeal cancer surgery. Design, Setting, and Participants: This combination of 2 cohorts, based on patient interviews and questionnaires, was studied in 16 hospitals in Germany. Participants scheduled for laryngeal cancer surgery were enrolled before surgery and followed up until 1 year after surgery. Data collection began on November 28, 2001, and ended on March 15, 2015. Statistical analysis was performed from August 21, 2023, to January 19, 2024. Main Outcomes and Measures: The attitude toward surgery was measured with the Psychosocial Adjustment After Laryngectomy Questionnaire (scores range from 0 to 100, with high scores representing a positive attitude toward the surgery) at 1 year after surgery. In multivariate regression analysis, the following variables were investigated: type of surgery, number of surgeries to the larynx, receipt of radiotherapy and chemotherapy, quality of life, speech intelligibility (objectively measured), age, sex, educational level, employment status, having a partner or not, counseling by patient association, and shared decision-making. Results: Patients (n = 780; mean [SD] age, 60.6 [10.4] years; 701 [90%] male) who had received counseling from the patient association reported a more positive attitude toward surgery (adjusted B = 8.8; 95% CI, 1.0-16.6). Among patients after total laryngectomy, those with a university degree had a less positive attitude toward their surgery (adjusted B = -50.8; 95% CI, -84.0 to -17.6); this result was not observed in patients after partial laryngectomy (adjusted B = -4.8; 95% CI, -15.1 to 5.4). Among patients after partial laryngectomy, the attitude toward surgery was most positive in those who had experienced shared decision-making (mean [SD] questionnaire score, 84 [20] in those without a wish and 83 [20] in those with a wish for shared decision-making). Those who had wished they could decide together with the physician but where this eventually was not experienced expressed the most regret toward surgery (mean [SD] score, 71 [22]). There was no association between attitudes toward surgery and type of surgery (total vs partial laryngectomy) and all other variables tested. Conclusion and Relevance: In this cohort study, most patients with head and neck cancer reported a positive attitude toward surgery, suggesting low levels of decision regret. Counseling by members of patient associations as well as individualized shared decision-making prior to surgery may have a positive impact on decision regret and is advisable in daily practice.

Quality of life in patients with hypoparathyroidism receiving standard treatment: an updated systematic review.

PURPOSE: Hypoparathyroidism is defined by hypocalcemia with inappropriately normal or low parathyroid hormone levels. The current standard treatment consists of lifelong calcium and/ or vitamin D supplementation. Even while on stable treatment regimens, hypoparathyroid patients might still suffer from symptoms that can negatively impact their quality of life. METHODS: A systematic literature review to identify the current knowledge regarding quality of life in patients with hypoparathyroidism receiving standard treatment was performed on November 1st, 2023. PubMed as well as Web of Science were searched. The systematic review is registered in PROSPERO (#CRD42023470924). RESULTS: After removal of duplicates, 398 studies remained for title and abstract screening, after which 30 were included for full-text screening. After exclusion of seven studies with five studies lacking a control population, one using a non-validated questionnaire, and one being a subsample of the larger included study, 23 studies were included in this systematic review. The majority of the included studies used a guideline-conform definition of hypoparathyroidism, and the SF-36 was the most often applied tool. Almost all studies (87%) reported statistically significantly lower scores in at least one quality of life domain compared to a norm population or controls. CONCLUSION: Patients with hypoparathyroidism receiving standard treatment report impairments in quality of life. The reasons for these impairments are probably multifaceted, making regular monitoring and the inclusion of various professionals necessary.

Cross-pollination in seed-blended refuge and selection for Vip3A resistance in a lepidopteran pest as detected by genomic monitoring.

The evolution of pest resistance to management tools reduces productivity and results in economic losses in agricultural systems. To slow its emergence and spread, monitoring and prevention practices are implemented in resistance management programs. Recent work suggests that genomic approaches can identify signs of emerging resistance to aid in resistance management. Here, we empirically examined the sensitivity of genomic monitoring for resistance management in transgenic Bt crops, a globally important agricultural innovation. Whole genome resequencing of wild North American Helicoverpa zea collected from non-expressing refuge and plants expressing Cry1Ab confirmed that resistance-associated signatures of selection were detectable after a single generation of exposure. Upon demonstrating its sensitivity, we applied genomic monitoring to wild H. zea that survived Vip3A exposure resulting from cross-pollination of refuge plants in seed-blended plots. Refuge seed interplanted with transgenic seed exposed H. zea to sublethal doses of Vip3A protein in corn ears and was associated with allele frequency divergence across the genome. Some of the greatest allele frequency divergence occurred in genomic regions adjacent to a previously described candidate gene for Vip3A resistance. Our work highlights the power of genomic monitoring to sensitively detect heritable changes associated with field exposure to Bt toxins and suggests that seed-blended refuge will likely hasten the evolution of resistance to Vip3A in lepidopteran pests.

Long-term health-related quality of life in head and neck cancer survivors: A large multinational study.

Head and neck cancer (HNC) patients suffer from a range of health-related quality of life (HRQoL) issues, but little is known about their long-term HRQoL. This study explored associations between treatment group and HRQoL at least 5 years' post-diagnosis in HNC survivors. In an international cross-sectional study, HNC survivors completed the European Organization for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (EORTC-QLQ-C30) and its HNC module (EORTC-QLQ-H&N35). Meaningful HRQoL differences were examined between five treatment groups: (a) surgery, (b) radiotherapy, (c) chemo-radiotherapy, (d) radiotherapy ± chemotherapy and neck dissection and (e) any other surgery (meaning any tumour surgery that is not a neck dissection) and radiotherapy ± chemotherapy. Twenty-six sites in 11 countries enrolled 1105 survivors. They had a median time since diagnosis of 8 years, a mean age of 66 years and 71% were male. After adjusting for age, sex, tumour site and UICC stage, there was evidence for meaningful differences (10 points or more) in HRQoL between treatment groups in seven domains (Fatigue, Mouth Pain, Swallowing, Senses, Opening Mouth, Dry Mouth and Sticky Saliva). Survivors who had single-modality treatment had better or equal HRQoL in every domain compared to survivors with multimodal treatment, with the largest differences for Dry Mouth and Sticky Saliva. For Global Quality of Life, Physical and Social Functioning, Constipation, Dyspnoea and Financial Difficulties, at least some treatment groups had better outcomes compared to a general population. Our data suggest that multimodal treatment is associated with worse HRQoL in the long-term compared to single modality.

Nurturing innovation, catalyzing change: Honoring the legacy of Dr. C. Barr Taylor in the eating disorders field.

This Virtual Issue of the International Journal of Eating Disorders honors the legacy of the late Dr. C. Barr Taylor in the eating disorders (EDs) field. For decades, Dr. Taylor led the way in not only conducting the research needed to achieve the ultimate goal of making affordable, accessible, and evidence-based care for EDs available to all, but also nurturing the next generation of scientific leaders and innovators. Articles included in this Virtual Issue are a selection of Dr. Taylor's published works in the Journal in the past decade, spanning original research, ideas worth researching, commentaries, and a systematic review. We hope this Virtual Issue will inspire the next generation of research in EDs, and equally, if not more importantly, the next generation of young investigators in the field. We urge the field to continue and build upon Dr. Taylor's vision-to increase access to targeted prevention and intervention for EDs in innovative and forward-thinking ways-while embracing his unique and powerful mentorship style to lift up early career investigators and create a community of leaders to address and solve our field's biggest challenges.

Does insecure attachment lead to psychosis via dissociation? A systematic review of the literature.

PURPOSE: Insecure attachment may constitute a vulnerability factor for psychosis, and dissociation may be a key mechanism in the development of auditory hallucinations specifically. While there is good evidence for the role of these processes in isolation, it is unclear whether dissociation accounts for the association between insecure attachment and psychosis. This systematic review takes a theory-driven approach to examine proposed causal relationships across the clinical and nonclinical literature. METHODS: We searched five databases (PubMeD, Web of Science, PsycINFO, CINAHL and ETHOS) for published and unpublished research examining attachment, dissociation and psychosis. Two independent reviewers extracted the data and assessed the quality of all included studies. RESULTS: We identified 242 potential articles and included 13 in the final review (2096 participants). We found that (1) disorganised attachment was consistently associated with dissociation and inconsistently associated with voices and paranoia, (2) dissociation was associated with voices and paranoia, and these links were stronger in clinical samples, and (3) dissociation played a role in the impact of insecure attachment on voice hearing and paranoia in clinical groups. CONCLUSIONS: This is the first review to synthesise the research examining attachment, dissociation, and psychosis. The evidence is consistent with proposed causal hypotheses and raises conceptual and measurement issues, for example, the need to clarify the relative contributions of different insecure attachment styles, and utilise behavioural/observational measures to strengthen study designs. Most importantly, we need experimental and longitudinal studies to confirm causal links and targets for treatment.

DNA Logic Gates Integrated on DNA Substrates in Molecular Computing.

Due to nucleic acid's programmability, it is possible to realize DNA structures with computing functions, and thus a new generation of molecular computers is evolving to solve biological and medical problems. Pioneered by Milan Stojanovic, Boolean DNA logic gates created the foundation for the development of DNA computers. Similar to electronic computers, the field is evolving towards integrating DNA logic gates and circuits by positioning them on substrates to increase circuit density and minimize gate distance and undesired crosstalk. In this minireview, we summarize recent developments in the integration of DNA logic gates into circuits localized on DNA substrates. This approach of all-DNA integrated circuits (DNA ICs) offers the advantages of biocompatibility, increased circuit response, increased circuit density, reduced unit concentration, facilitated circuit isolation, and facilitated cell uptake. DNA ICs can face similar challenges as their equivalent circuits operating in bulk solution (bulk circuits), and new physical challenges inherent in spatial localization. We discuss possible avenues to overcome these obstacles.

Adverse childhood experiences and trajectories of multimorbidity in individuals aged over 50: Evidence from the English Longitudinal Study of Ageing.

BACKGROUND: Adverse childhood experiences (ACE) are important for chronic diseases yet their association with multimorbidity remains understudied. Few studies consider the complexity of multimorbidity or observe multimorbidity development over time. OBJECTIVE: We investigated whether ACE were associated with multimorbidity at baseline and over a 12-year follow-up period. PARTICIPANTS AND SETTING: 5326 participants aged over 50 were obtained from the English Longitudinal Study of Ageing (ELSA). METHODS: An ACE summary score was derived using eight ACE items measuring abuse, social care, and household dysfunction. From repeated measurements of 29 chronic conditions over a 12-year period (2008-2019) we derived two multimorbidity measures: number of chronic diseases and number of chronic disease categories. We used multinomial logistic regression to assess associations between ACE and both measures. Mixed effects models were estimated to examine trajectories of multimorbidity by ACE over time. RESULTS: Graded associations between ACE and multimorbidity were observed. Compared to those without ACE, participants with ≥3 ACE had three times the risk of having ≥3 chronic diseases (RRR 3.06, 95 % CI 1.85-5.05) and falling into ≥3 chronic disease categories (RRR 2·93 95 % CI 1·74-4·95). Graded associations persisted during 12-year follow-up, though differences in multimorbidity between those with ≥3 ACE and those without ACE remained constant (B 0.02, 95 % CI 0·01-0·03, and B -0·01, 95 % CI -0·02-0·00, number of chronic conditions and chronic condition categories respectively). CONCLUSION: ACE are associated with multimorbidity risk and complexity, associations arising before the age of 50. Early intervention amongst those with ACE could attenuate this association.

Cognitive behavioural therapy for psychosis: The end of the line or time for a new approach?

PURPOSE: Following its introduction in the early 1990s, cognitive behavioural therapy for psychosis (CBTp) has been evaluated in a large number of clinical trials and is now established as a recommended treatment in the UK National Health Service and elsewhere in the world. Meta-analyses, however, indicate modest effects compared to treatment as usual or comparison therapies such as supportive counselling. Here, we seek to identify factors impacting the effectiveness of CBTp, and avenues for future psychotherapy research that may improve outcomes. METHOD: We outline two recent umbrella reviews and discuss factors likely to impact the effectiveness of CBTp. RESULTS: Modest effect sizes from meta-analyses mask heterogeneous outcomes, with some people benefiting and others possibly being harmed by therapy. Common factors such as the therapeutic alliance play an important role in determining outcomes but have been largely neglected by CBTp researchers. There is also the promise of improving outcomes by identifying and targeting the psychological mechanisms that either maintain psychotic symptoms (e.g. worry) or are causally implicated (e.g. trauma). CONCLUSIONS: It is unlikely that everyone with psychosis will be equally responsive to the same therapeutic protocols. We need a new, personalised psychotherapy approach to CBTp research and practice, and can learn from research for anxiety and depression examining predictors of therapeutic response to inform treatment decisions. Precision psychological therapies informed by a combination of individual characteristics, common factors and a focus on specific mechanisms will require new research strategies and are likely to lead to improved outcomes for people with psychosis.

The impact of electronic versus paper-based data capture on data collection logistics and on missing scores in thyroid cancer patients.

PURPOSE: The purpose of this study was to investigate the impact of the type of data capture on the time and help needed for collecting patient-reported outcomes as well as on the proportion of missing scores. METHODS: In a multinational prospective study, thyroid cancer patients from 17 countries completed a validated questionnaire measuring quality of life. Electronic data capture was compared to the paper-based approach using multivariate logistic regression. RESULTS: A total of 437 patients were included, of whom 13% used electronic data capture. The relation between data capture and time needed was modified by the emotional functioning of the patients. Those with clinical impairments in that respect needed more time to complete the questionnaire when they used electronic data capture compared to paper and pencil (ORadj 24.0; p = 0.006). This was not the case when patients had sub-threshold emotional problems (ORadj 1.9; p = 0.48). The odds of having the researcher reading the questions out (instead of the patient doing this themselves) (ORadj 0.1; p = 0.01) and of needing any help (ORadj 0.1; p = 0.01) were lower when electronic data capture was used. The proportion of missing scores was equivalent in both groups (ORadj 0.4, p = 0.42). CONCLUSIONS: The advantages of electronic data capture, such as real-time assessment and fewer data entry errors, may come at the price of more time required for data collection when the patients have mental health problems. As this is not uncommon in thyroid cancer, researchers need to choose the type of data capture wisely for their particular research question.

Early intervention in psychosis services: A systematic review and narrative synthesis of barriers and facilitators to seeking access.

BACKGROUND: The duration of untreated psychosis (DUP) continues to be a global priority. Early intervention services were established to reduce treatment delays but have had limited impact. This systematic review examines barriers and facilitators to seeking access to these services, to identify targets for service level change. METHODS: We conducted a systematic review of relevant databases (PsychINFO, MEDLINE, CINAHL, and PsychARTICLES) using pre-defined search terms for psychosis, early intervention, and barriers and facilitators. Given the majority of qualitative studies, a thematic synthesis rather than meta-analysis was indicated. RESULTS: The search yielded 10 studies. Mental health stigma and discrimination predict DUP, compounded by structural barriers which limit the impact of early intervention services on timely access to recommended treatments. Synthesis of the qualitative studies generated three themes: knowledge, relationships, and stigma. Lack of knowledge, absence of supportive relationships (social and professional), and self-stigma constitute significant barriers to seeking access to early intervention services. CONCLUSIONS: This is the first review of the barriers and facilitators to seeking access to early intervention services. The findings highlight public health and secondary care service targets to expedite access to recommended treatments and thereby reduce the DUP.

Automatic Prediction of Paediatric Cardiac Output From Echocardiograms Using Deep Learning Models.

Background: Cardiac output (CO) perturbations are common and cause significant morbidity and mortality. Accurate CO assessment is crucial for guiding treatment in anaesthesia and critical care, but measurement is difficult, even for experts. Artificial intelligence methods show promise as alternatives for accurate, rapid CO assessment. Methods: We reviewed paediatric echocardiograms with normal CO and a dilated cardiomyopathy patient group with reduced CO. Experts measured the left ventricular outflow tract diameter, velocity time integral, CO, and cardiac index (CI). EchoNet-Dynamic is a deep learning model for estimation of ejection fraction in adults. We modified this model to predict the left ventricular outflow tract diameter and retrained it on paediatric data. We developed a novel deep learning approach for velocity time integral estimation. The combined models enable automatic prediction of CO. We evaluated the models against expert measurements. Primary outcomes were root-mean-squared error, mean absolute error, mean average percentage error, and coefficient of determination (R2). Results: In a test set unused during training, CI was estimated with the root-mean-squared error of 0.389 L/min/m2, mean absolute error of 0.321 L/min/m2, mean average percentage error of 10.8%, and R2 of 0.755. The Bland-Altman analysis showed that the models estimated CI with a bias of +0.14 L/min/m2 and 95% limits of agreement -0.58 to 0.86 L/min/m2. Conclusions: Our model estimated CO with strong correlation to ground truth and a bias of 0.17 L/min, better than many CO measurements in paediatrics. Model pretraining enabled accurate estimation despite a small dataset. Potential uses include supporting clinicians in real-time bedside calculation of CO, identification of low-CO states, and treatment responses.

Contexte: Les perturbations du débit cardiaque sont fréquentes et associées à des taux élevés de morbidité et de mortalité. Une évaluation juste du débit cardiaque est essentielle pour orienter le choix du traitement anesthésique et des soins critiques. Or, il est difficile de mesurer le débit cardiaque, même pour les experts. Les méthodes fondées sur l'intelligence artificielle semblent toutefois prometteuses pour évaluer le débit cardiaque avec exactitude et rapidité. Méthodologie: Nous avons analysé des échocardiogrammes pédiatriques chez des personnes dont le débit cardiaque est normal ainsi que chez des patients qui étaient atteints d'une cardiomyopathie dilatée et dont le débit cardiaque était réduit. Des experts ont mesuré le diamètre de la voie d'éjection ventriculaire gauche, l'intégrale de la vitesse par rapport au temps (IVT), le débit cardiaque et l'index cardiaque. L'outil EchoNet-Dynamic est un modèle d'apprentissage profond qui donne une estimation de la fraction d'éjection chez les adultes. Nous avons modifié ce modèle afin qu'il puisse prédire le diamètre de la voie d'éjection ventriculaire gauche et l'avons entraîné à l'aide de données pédiatriques. Nous avons également mis au point une nouvelle approche d'apprentissage profond pour l'estimation des valeurs d'IVT. La combinaison de ces modèles a permis de prédire de façon automatique le débit cardiaque, et nous avons évalué les résultats obtenus par rapport à ceux des experts. Les principaux critères d'évaluation étaient l'erreur moyenne quadratique (EMQ), l'erreur moyenne absolue (EMA), le pourcentage d'erreur moyen (PEM) ainsi que le coefficient de détermination (R2). Résultats: Dans un ensemble d'essais n'ayant pas été utilisé au cours de l'entraînement du modèle, l'index cardiaque a été estimé avec une EMQ de 0,389 L/min/m2, une EMA de 0,321 L/min/m2, un PEM de 10,8 % et un R2 de 0,755. Selon l'analyse de Bland-Altman, le biais pour les estimations de l'index cardiaque était de + 0,14 L/min/m2, et les limites de concordance à 95 % étaient de ­0,58 à 0,86 L/min/m2. Conclusions: Les estimations générées par le modèle pour le débit cardiaque montraient une forte corrélation avec les valeurs de référence et un biais à 0,17 L/min, ce qui est mieux que bien des mesures du débit cardiaque utilisées en pédiatrie. Malgré un petit ensemble de données, le modèle entraîné a permis de produire une estimation juste. Les utilisations potentielles comprennent l'aide aux cliniciens dans le calcul du débit cardiaque en temps réel et au chevet du patient, le dépistage d'un faible débit cardiaque et l'évaluation de la réponse au traitement.

Assessing Squarates as Amine-Reactive Probes.

Probes that covalently label protein targets facilitate the identification of ligand-binding sites. Lysine residues are prevalent in the proteome, making them attractive substrates for covalent probes. However, identifying electrophiles that undergo amine-specific, regioselective reactions with binding site lysine residues is challenging. Squarates can engage in two sequential conjugate addition-elimination reactions with amines. Nitrogen donation reduces the second reaction rate, making the mono squaramide a mild electrophile. We postulated that this mild electrophilicity would demand a longer residence time near the amine, affording higher selectivity for binding site lysines. Therefore, we compared the kinetics of squarate and monosquaramide amine substitution to alternative amine bioconjugation handles. The data revealed that N-hydroxy succinimidyl esters react 4 orders of magnitude faster, consistent with their labeling promiscuity. Squarate reactivity can be tuned by a substitution pattern. Electron-withdrawing groups on the vinylogous ester or amide increase reaction rates. Dithionosquarates react more rapidly than squarates, while vinylogous thioester analogs, dithiosquarates, react more slowly. We assessed squarate selectively using the UDP-sugar processing enzyme GlfT2 from Mycobacterium tuberculosis, which possesses 21 surface-exposed lysines. The reaction predominately modified one lysine proximal to a binding site to afford covalent inhibition. These findings demonstrate the selectivity of squaric esters and squaramides, which is a critical feature for affinity-based chemoproteomic probes.