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“Frailty” is associated with worse outcomes in adult cardiology. There is limited data on the associations between frailty and outcomes in paediatric cardiology. We aimed to define the prevalence of frailty and identify associations between frailty and neurodevelopmental and quality-of-life outcomes in high-risk paediatric cardiac populations.
Study Design:
This cross-sectional study included patients 4–18 years seen in a neurodevelopmental programme between 6/2017 and 11/2022. Demographic and clinical data were obtained from medical records. As part of the routine care, physical therapy assessment and neurocognitive, psychosocial, adaptive functioning, and quality-of-life surveys were administered. Social determinants of health were assessed by insurance status and Childhood Opportunity Index. Frailty was defined as the abnormality in 3 of 5 categories: body composition, weakness, slowness, physical activity, and exhaustion. Chi-Square, Student t, and Wilcoxon Rank Sum tests were used to assess differences between frail and non-frail groups.
Results:
Of the 270 patients, 101 (37%) met the frailty criteria. Frailty was not associated with social determinants of health, cardiac diagnosis, genetic syndrome, number of cardiac surgeries, or history of clinical complications. Frail patients were more likely to be older (p = 0.004) and have neurocognitive (p = 0.024), emotional (p = 0.003), social (p < 0.001), motor (p < 0.001), and adaptive dysfunction (p < 0.001) and lower quality of life (p = 0.029).
Conclusion:
Frailty is common in school-aged patients with cardiac disease and is associated with adverse neurocognitive, psychosocial, motor, and adaptive outcomes and worse quality of life. Risk stratification for frailty may be a critical evaluation and screening element of high-risk cardiac patients in neurodevelopmental programmes.
The role of the gut microbiome in infant development has gained increasing interest in recent years. Most research on this topic has focused on the first three to four years of life because this is a critical period for developing gut-brain connections. Prior studies have identified associations between the composition and diversity of the gut microbiome in infancy and markers of temperament, including negative affect. However, the specific microbes affected, and the directionality of these associations have differed between studies, likely due to differences in the developmental period of focus and assessment approaches. In the current preregistered study, we examined connections between the gut microbiome, assessed at two time points in infancy (2 weeks and 18 months), and negative affect measured at 30 months of age in a longitudinal study of infants and their caregivers. We found that infants with higher gut microbiome diversity at 2 weeks showed more observed negative affect during a study visit at 30 months. We also found evidence for associations between specific genera of bacteria in infancy and negative affect. These results suggest associations between specific features of the gut microbiome and child behavior may differ based on timing of gut microbiome measurement.
Assessing children’s diets is currently challenging and burdensome. Abbreviated FFQ have the potential to assess dietary patterns in a rapid and standardised manner. Using nationally representative UK dietary intake and biomarker data, we developed an abbreviated FFQ to calculate dietary quality scores for pre-school and primary school-aged children. UK National Diet and Nutrition Survey (2008–2016) weekly consumption frequencies of 129 food groups from 4-d diaries were cross-sectionally analysed using principal component analysis. A 129-item score was derived, alongside a 12-item score based on foods with the six highest and six lowest coefficients. Participants included 1069 pre-schoolers and 2565 primary schoolchildren. The first principal component explained 3·4 and 3·0 % of the variation in the original diet variables for pre-school and primary school groups, respectively, and described a prudent diet pattern. Prudent diet scores were characterised by greater consumption of fruit, vegetables and tap water and lower consumption of crisps, manufactured coated chicken/turkey products, purchased chips and soft drinks for both age groups. Correlations between the 129-item and 12-item scores were 0·86 and 0·84 for pre-school and primary school-aged children, respectively. Bland–Altman mean differences between the scores were 0·00 sd; 95 % limits of agreement were −1·05 to 1·05 and −1·10 to 1·10 sd for pre-school and primary school-aged children, respectively. Correlations between dietary scores and nutritional biomarkers showed only minor attenuation for the 12-item compared with the 129-item scores, illustrating acceptable congruence between prudent diet scores. The two 12-item FFQ offer user-friendly tools to measure dietary quality among UK children.
Japan has not only suffered from dismal macroeconomic performance over the past two decades, but it has lost its edge in areas of its greatest competitive strength, such as electronics, especially information and communications technology (ICT) hardware Japanese electronics firms have declined by many standard measures of industrial performance, such as market share, exports, and profits.
This chapter deals with abnormal, spontaneous and reactive motor behavior as part of the clinical expression of some psychiatric disorders, including abnormal motility, locomotion, gestures, mimic, and speech. Here, the differentiation of the abnormal motor behavior motor dysfunction as an integral part of a psychiatric condition or as a side effect of its treatment is critical for the management but often remains difficult to differentiate. Iatrogenic movement disorders, as might be seen in the treatment of specific psychiatric disorders, for instance with neuroleptics, are discussed in Chapter 51. In this chapter, we focus on the signs and symptoms of movement disorders as an integral, genuine part of the clinical manifestation, sometimes even in prodromal states, in psychiatric diseases, such as in schizophrenia, catatonia, and stereotypies, as well as in major depressive disorders, attention deficit hyperactivity disorders, obsessive-compulsive disorders, and impulse control disorders. Psychogenic (functional or somatoform) motor behavioral abnormalities, the result of conversion, somatization and/or factious disorders (malingering), are described in Chapter 53.
Functional movement disorders are the most challenging movement disorders to diagnose and treat. Phenomenology and disease course are variable. This group of disorders includes tremor, dystonia, myoclonus, parkinsonism, speech and gait disturbances, and other movement disorders that are incongruent with patterns of pathophysiologic (organic) disease.
The translational science workforce requires preparation in both core skills for biomedical research and competencies for advancing progress along the translational pipeline. Delivering this content in a highly accessible manner will help expand and diversify the workforce.
Methods:
The NCATS Education Branch offers online case study-based courses in translational science for a general scientific audience. The branch updated its course in preclinical translational science with additional content aligned with the NCATS Translational Science Principles, which characterize effective approaches to advance translation. The updated course was offered in 2021 and 2022. The branch also revised the course evaluation to capture knowledge change aligned with the NCATS Translational Science Principles.
Results:
Of 106 students, 88 completed baseline or endpoint surveys, with 48 completing both. Most found the online format (n = 48; 91%) and case study approach (n = 48; 91%) effective. There was a statistically significant increase in knowledge related to the Translational Science Principles (p < 0.001). Survey items with the highest endpoint scores reflected the principles on creativity and innovation, efficiency, cross-disciplinary team science, and boundary-crossing collaborations. Findings highlighted the effectiveness of pairing a case study with lectures that offer generalizable strategies aligned with the translational science principles. Students reported the course helped them learn about the trajectory of a drug discovery and development initiative, where their own work fit in, and scientific and operational approaches to apply in their own work.
Conclusions:
This online case study-based course was effective in teaching generalizable principles for translational science to students with varied scientific backgrounds.
Here we present the first high-resolution continuous palaeoecological study from Greece covering the Mesolithic–Neolithic transition at Limni Zazari, a small lake in western Macedonia. We study how interactions between vegetation and climate might have affected the introduction of agriculture to Europe ca. 8500 years ago. We found that mixed deciduous oak woodlands established around the lake once moisture availability began to increase at ~10,300 cal yr BP. Between 8600 and 8000 cal yr BP, climate change, causing drier conditions, led to the decline of the woodlands and the expansion of steppe and grassland vegetation. Concurrently, in agreement with the archaeological record, pollen indicative of arable and pastoral farming indicate the onset of Neolithic farming. After 8000 cal yr BP the forest composition changed, with a major expansion of pine forests and increases in disturbance-adapted trees like Ostrya and Fagus. This change might be linked to changes in moisture availability, but it is likely that land use also facilitated these shifts. We conclude that the introduction of Neolithic farming was advantaged by climate-induced vegetation changes. While the vegetation structure around Zazari was very sensitive to changes in moisture, early anthropogenic disturbances led to changes in the vegetation composition that are still important today.
In healthcare and medical research, advisory boards are now commonplace, but most boards consist of a relatively homogenous, geographically collocated group, often demonstrating demographic imbalance. It is crucial to include individuals from diverse backgrounds on community advisory boards for healthcare and medical research to address ongoing health disparities and ensure studies are more culturally competent so that we can achieve more inclusive representation. We conducted purposeful recruitment to attract a demographically diverse group of community members across the United States (U.S.) to partner with the All of Us Research Program to inform our strategies including program recruitment, engagement, retention, and incentives. Recruitment of a diverse group of advisors and purposeful community building has created a psychologically safe environment where members openly share their opinions, thoughts, and perspectives to shape various aspects of this ambitious, nationwide research program.
This study investigates the level of knowledge and utilization of colorectal cancer (CRC) and prostate cancer (PCa) early detection measures (EDMs) over a period of 12 years in general practice from the patient’s perspective.
Background:
The role of general practitioners (GPs) in EDMs for CRC and PCa in Germany is not well-documented with comprehensive data.
Methods:
We conducted a patient-centric survey in the German federal state of Berlin-Brandenburg at a 12-year interval to examine the role of GPs in EDMs for CRC and PCa. In 2009, 55 GPs were tasked with informing 50 consecutive male patients, each aged over 35, about participating in a survey study (study phase 1/SP1). To evaluate changes over 12 years, a new survey involving 50 male patients from each of 150 GPs was conducted from October 2021 to March 2022 (SP2).
Findings:
We thoroughly reviewed the questionnaires of 890 patients, with 755 in SP1 and 135 in SP2. Patients showed greater awareness of recommendations regarding colonoscopy compared to prostate-specific antigen (PSA) testing. GPs were the most frequently reported source of information for both EDMs in our cohort. Comparing the two study phases, no significant difference in specific awareness of colonoscopy or PSA testing was found among men eligible for EDMs. However, there was a notable increase in the role of health insurance companies as a source of information about colonoscopy over time. Nearly 60% of included patients underwent colonoscopy and/or PSA testing as EDMs.
Conclusion:
The number of EDMs performed among study participants did not increase over time. Our study confirms that GPs remain the primary source of information about EDMs among the study participants.
There is growing interest in lifestyle interventions as stand-alone and add-on therapies in mental health care due to their potential benefits for both physical and mental health outcomes. We evaluated lifestyle interventions focusing on physical activity, diet, and sleep in adults with severe mental illness (SMI) and the evidence for their effectiveness. To this end, we conducted a meta-review and searched major electronic databases for articles published prior to 09/2022 and updated our search in 03/2024. We identified 89 relevant systematic reviews and assessed their quality using the SIGN checklist. Based on the findings of our meta-review and on clinical expertise of the authors, we formulated seven recommendations. In brief, evidence supports the application of lifestyle interventions that combine behavioural change techniques, dietary modification, and physical activity to reduce weight and improve cardiovascular health parameters in adults with SMI. Furthermore, physical activity should be used as an adjunct treatment to improve mental health in adults with SMI, including psychotic symptoms and cognition in adults with schizophrenia or depressive symptoms in adults with major depression. To ameliorate sleep quality, cognitive behavioural informed interventions can be considered. Additionally, we provide an overview of key gaps in the current literature. Future studies should integrate both mental and physical health outcomes to reflect the multi-faceted benefits of lifestyle interventions. Moreover, our meta-review highlighted a relative dearth of evidence relating to interventions in adults with bipolar disorder and to nutritional and sleep interventions. Future research could help establish lifestyle interventions as a core component of mental health care.
To evaluate the motor proficiency, identify risk factors for abnormal motor scores, and examine the relationship between motor proficiency and health-related quality of life in school-aged patients with CHD.
Study design:
Patients ≥ 4 years old referred to the cardiac neurodevelopmental program between June 2017 and April 2020 were included. Motor skills were evaluated by therapist-administered Bruininks-Oseretsky Test of Motor Proficiency Second-Edition Short Form and parent-reported Adaptive Behavior Assessment System and Patient-Reported Outcomes Measurement Inventory System Physical Functioning questionnaires. Neuropsychological status and health-related quality of life were assessed using a battery of validated questionnaires. Demographic, clinical, and educational variables were collected from electronic medical records. General linear modelling was used for multivariable analysis.
Results:
The median motor proficiency score was the 10th percentile, and the cohort (n = 272; mean age: 9.1 years) scored well below normative values on all administered neuropsychological questionnaires. In the final multivariable model, worse motor proficiency score was associated with family income, presence of a genetic syndrome, developmental delay recognised in infancy, abnormal neuroimaging, history of heart transplant, and executive dysfunction, and presence of an individualised education plan (p < 0.03 for all predictors). Worse motor proficiency correlated with reduced health-related quality of life. Parent-reported adaptive behaviour (p < 0.001) and physical functioning (p < 0.001) had a strong association with motor proficiency scores.
Conclusion:
This study highlights the need for continued motor screening for school-aged patients with CHD. Clinical factors, neuropsychological screening results, and health-related quality of life were associated with worse motor proficiency.
The hippocampal formation represents a key region in the pathophysiology of schizophrenia. Aerobic exercise poses a promising add-on treatment to potentially counteract structural impairments of the hippocampal formation and associated symptomatic burden. However, current evidence regarding exercise effects on the hippocampal formation in schizophrenia is largely heterogeneous. Therefore, we conducted a systematic review and meta-analysis to assess the impact of aerobic exercise on total hippocampal formation volume. Additionally, we used data from a recent multicenter randomized-controlled trial to examine the effects of aerobic exercise on hippocampal formation subfield volumes and their respective clinical implications.
Methods
The meta-analysis comprised six studies that investigated the influence of aerobic exercise on total hippocampal formation volume compared to a control condition with a total of 186 people with schizophrenia (100 male, 86 female), while original data from 29 patients (20 male, 9 female) was considered to explore effects of six months of aerobic exercise on hippocampal formation subfield volumes.
Results
Our meta-analysis did not demonstrate a significant effect of aerobic exercise on total hippocampal formation volume in people with schizophrenia (g = 0.33 [−0.12 to 0.77]), p = 0.15), but our original data suggested significant volume increases in certain hippocampal subfields, namely the cornu ammonis and dentate gyrus.
Conclusions
Driven by the necessity of better understanding the pathophysiology of schizophrenia, the present work underlines the importance to focus on hippocampal formation subfields and to characterize subgroups of patients that show neuroplastic responses to aerobic exercise accompanied by corresponding clinical improvements.
22q11.2 deletion syndrome (22q11.2DS) is associated with cognitive impairments and an increased risk of psychopathology. Most of the research has been conducted in children and adolescents, although the majority of affected individuals live well into adulthood. Hence, limited data are available on functional outcomes in adults.
Aims
To provide more insight in cognitive and adaptive abilities, and daily life functioning (marital status, living situation and work situation) in adults with 22q11.2DS.
Method
This retrospective study included 250 Dutch-speaking adults (16–69 years) with 22q11.2DS from three sites in The Netherlands and Belgium. Data on full-scale IQ (FSIQ) scores (assessed with the Wechsler Adult Intelligence Scale), adaptive functioning (assessed with the Vineland Adaptive Behavior Scale II), and functional outcomes including marital status, living and work situation were systematically collected from clinical files. In addition, we examined predictors of adaptive functioning.
Results
The majority of individuals in our adult sample demonstrated a low level of adaptive functioning (65%). In contrast to previous findings in children and adolescents, the majority functioned at an intellectual disability level (56%). Male sex, lower FSIQ and autism spectrum disorder were predictors of lower adaptive functioning (P = 0.016, P < 0.001 and P = 0.16, respectively).
Conclusions
These results suggest that low levels of cognitive and adaptive functioning are common in adults with 22q11.2DS. Future longitudinal and multicentre studies including older patients (>40 years) are needed to further investigate cognitive and adaptive trajectories and their interactions with physical and psychiatric comorbidities.
The specific risks and mental health needs of women in forensic services and the relevance of gender-responsive treatment include gender differences in criminological and psychiatric characteristics; gender-sensitive risk assessment; and gender-sensitive management. Some recommendations are provided for practitioners working with women in forensic services.
The design of gear boxes is a complex challenge characterized by conflicting requirements and seemingly circular dependencies. Existing tools support engineers but focus on a single predefined design, often leading to costly iterative processes and non-optimal solutions. Solution Space Engineering (SSE) alleviates this by generating multiple designs represented by solution spaces. For this, a particular model structure is needed, and thus restructuring existing models, e.g., from industry standards. The application of solution spaces to a two-stage gear box is presented.
Plant growth requires the integration of internal and external cues, perceived and transduced into a developmental programme of cell division, elongation and wall thickening. Mechanical forces contribute to this regulation, and thigmomorphogenesis typically includes reducing stem height, increasing stem diameter, and a canonical transcriptomic response. We present data on a bZIP transcription factor involved in this process in grasses. Brachypodium distachyon SECONDARY WALL INTERACTING bZIP (SWIZ) protein translocated into the nucleus following mechanostimulation. Classical touch-responsive genes were upregulated in B. distachyon roots following touch, including significant induction of the glycoside hydrolase 17 family, which may be unique to grass thigmomorphogenesis. SWIZ protein binding to an E-box variant in exons and introns was associated with immediate activation followed by repression of gene expression. SWIZ overexpression resulted in plants with reduced stem and root elongation. These data further define plant touch-responsive transcriptomics and physiology, offering insights into grass mechanotranduction dynamics.
Early-life adversity as neglect or low socioeconomic status is associated with negative physical/mental health outcomes and plays an important role in health trajectories through life. The early-life environment has been shown to be encoded as changes in epigenetic markers that are retained for many years.
We investigated the effect of maternal major financial problems (MFP) and material deprivation (MD) on their children’s epigenome in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Epigenetic aging, measured with epigenetic clocks, was weakly accelerated with increased MFP. In subsequent EWAS, MFP, and MD showed strong, independent programing effects on children’s genomes. MFP in the period from birth to age seven was associated with genome-wide epigenetic modifications on children’s genome visible at age 7 and partially remaining at age 15.
These results support the hypothesis that physiological processes at least partially explain associations between early-life adversity and health problems later in life. Both maternal stressors (MFP/MD) had similar effects on biological pathways, providing preliminary evidence for the mechanisms underlying the effects of low socioeconomic status in early life and disease outcomes later in life. Understanding these associations is essential to explain disease susceptibility, overall life trajectories and the transition from health to disease.
Preliminary work suggests anxiety moderates the relationship between irritability and bullying. As anxiety increases, the link between irritability and perpetration decreases. We hypothesize that any moderation effect of anxiety is driven by social anxiety symptoms. We sought to explicate the moderating effect of anxiety, while clarifying relations to other aggressive behaviors.
Methods:
A sample of adolescents (n = 169, mean = 12.42 years of age) were assessed using clinician rated assessments of anxiety, parent reports of irritability and bullying behaviors (perpetration, generalized aggression, and victimization). Correlations assessed zero-order relations between variables, and regression-based moderation analyses were used to test interactions. Johnson–Neyman methods were used to represent significant interactions.
Results:
Irritability was significantly related to bullying (r = .403, p < .001). Social, but not generalized, anxiety symptoms significantly moderated the effect of irritability on bully perpetration (t(160) = −2.94, b = −.01, p = .0038, ΔR2 = .0229, F(1, 160) = 8.635). As social anxiety symptoms increase, the link between irritability and perpetration decreases.
Conclusions:
Understanding how psychopathology interacts with social behaviors is of great importance. Higher social anxiety is linked to reduced relations between irritability and bullying; however, the link between irritability and other aggression remains positive. Comprehensively assessing how treatment of psychopathology impacts social behaviors may improve future intervention.