Growth hormone augmentation in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis of randomized controlled trials.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis and metabolic dysregulation. Growth hormone (GH) augmentation has emerged as a potential therapeutic intervention for treating MASLD. This systematic review and meta-analysis aimed to evaluate the impact of GH augmentation on different parameters of MASLD. A systematic literature search identified randomized controlled trials investigating GH augmentation in MASLD patients. Search results were screened via Covidence and the Risk of Bias 2 tool was used to assess bias in randomized controlled trials. Statistical analysis utilized RevMan v5.3. We combined dichotomous outcomes employing odds ratios and continuous outcomes utilizing mean difference (MD), each with a 95% confidence interval (CI). Statistical significance was indicated by a P-value less than 0.05. Heterogeneity was evaluated using I2 tests. Our results showed that GH augmentation resulted in a significant reduction in both relative (MD: -46.26; 95% CI: -71.52, -21.00; P = 0.0003) and absolute (MD: -5.15; 95% CI: -7.93, -2.37; P = 0.0003) hepatic fat fraction. GH augmentation significantly reduced alanine aminotransferase (MD: -5.97; 95% CI: -10.31, -1.62; P = 0.007) and gamma-glutamyl transferase (MD: -16.18; 95% CI: -30.76, -1.59; P = 0.03) levels. No significant changes were observed in hemoglobin A1c, C-reactive protein, fasting serum glucose, BMI, triglycerides, and low-density lipoprotein cholesterol levels. Our meta-analysis highlights GH augmentation as a promising therapy for reducing liver steatosis and improving liver enzyme levels in MASLD patients. Further large-scale trials are warranted to examine the long-term effects, safety profiles, and potential impact on various measures.

No physiological costs of dual sequestration of chemically different plant toxins in the milkweed bug Spilostethus saxatilis (Heteroptera: Lygaeidae).

Many herbivorous insects not only cope with plant toxins but also sequester them as a defense against predators and parasitoids. Sequestration is a product of the evolutionary arms race between plants and herbivorous insects and has been hypothesized to incur physiological costs due to specific adaptations required. Contradictory evidence about these costs exists for insects sequestering only one class of toxin, but very little is known about the physiological implications for species sequestering structurally different classes of compounds. Spilostethus saxatilis is a milkweed bug belonging to the cardenolide-sequestering heteropteran subfamily Lygaeinae (Heteroptera: Lygaeidae) that has shifted to the colchicine-containing plant Colchicum autumnale, a resource of chemically unrelated alkaloids. Using feeding-assays on artificial diet and chemical analysis, we assessed whether S. saxatilis is still able to sequester cardenolides apart from colchicine and related metabolites (colchicoids), and tested the effect of (1) either a natural cardenolide concentration (using ouabain as a model compound) or a natural colchicine concentration, (2) an increased concentration of both toxins, and (3) seeds of either Asclepias syriaca (cardenolides) or C. autumnale (colchicoids) on a set of life-history traits. For comparison, we assessed the same life-history traits in the milkweed bug Oncopeltus fasciatus exposed to cardenolides only. Although cardenolides and colchicoids have different physiological targets (Na+/K+-ATPase vs tubulin) and thus require different resistance traits, chronic exposure and sequestration of both isolated toxins caused no physiological costs such as reduced growth, increased mortality, lower fertility, or shorter adult life span in S. saxatilis. Indeed, an increased performance was observed in O. fasciatus and an according trend was found in S. saxatilis when feeding on isolated ouabain and isolated colchicine, respectively. Positive effects were even more pronounced when insects were provided with natural toxic seeds (i.e. C. autumnale for S. saxatilis and A. syriaca for O. fasciatus), especially in O. fasciatus. Our findings suggest, that S. saxatilis can sequester two chemically unrelated classes of plant compounds at a cost-free level, and that colchicoids may even play a beneficial role in terms of fertility.

Sensory processing challenges as a novel link between early caregiving experiences and mental health.

Early caregiving adversity (ECA) is associated with elevated psychological symptomatology. While neurobehavioral ECA research has focused on socioemotional and cognitive development, ECA may also increase risk for "low-level" sensory processing challenges. However, no prior work has compared how diverse ECA exposures differentially relate to sensory processing, or, critically, how this might influence psychological outcomes. We examined sensory processing challenges in 183 8-17-year-old youth with and without histories of institutional (orphanage) or foster caregiving, with a particular focus on sensory over-responsivity (SOR), a pattern of intensified responses to sensory stimuli that may negatively impact mental health. We further tested whether sensory processing challenges are linked to elevated internalizing and externalizing symptoms common in ECA-exposed youth. Relative to nonadopted comparison youth, both groups of ECA-exposed youth had elevated sensory processing challenges, including SOR, and also had heightened internalizing and externalizing symptoms. Additionally, we found significant indirect effects of ECA on internalizing and externalizing symptoms through both general sensory processing challenges and SOR, covarying for age and sex assigned at birth. These findings suggest multiple forms of ECA confer risk for sensory processing challenges that may contribute to mental health outcomes, and motivate continuing examination of these symptoms, with possible long-term implications for screening and treatment following ECA.

Understanding preferences of general educators for supporting classwide behavior.

Innovations, such as novel evidence-based practices, are not likely to diffuse to practice without explicit effort and design (Rogers, 2003). In an effort to understand how interventions should be designed to meet teacher preferences, the present study utilized a full-profile two-alternative forced-choice experiment to examine teacher preferences when selecting a classwide intervention to address student disruptive behavior. Attributes and levels for the experiment were derived in response to four characteristics from Rogers' diffusion of innovations theory. Results from 266 general education teachers of Grades K-5 indicated that nearly all theorized characteristics influenced teacher preference, with the exception of the observability of the intervention (i.e., receiving feedback from others). Specific findings of levels within attributes suggest that, for instance, short online video trainings are preferable to full-day workshops and specific details on adaptations for inclusivity are highly preferred. Given school psychologists' roles in consultation and behavior support, knowledge of teacher preferences may be utilized to support intervention uptake and more general dissemination efforts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Functional evidence supports adaptive plant chemical defense along a geographical cline.

Environmental clines in organismal defensive traits are usually attributed to stronger selection by enemies at lower latitudes or near the host's range center. Nonetheless, little functional evidence has supported this hypothesis, especially for coevolving plants and herbivores. We quantified cardenolide toxins in seeds of 24 populations of common milkweed (Asclepias syriaca) across 13 degrees of latitude, revealing a pattern of increasing cardenolide concentrations toward the host's range center. The unusual nitrogen-containing cardenolide labriformin was an exception and peaked at higher latitudes. Milkweed seeds are eaten by specialist lygaeid bugs that are even more tolerant of cardenolides than the monarch butterfly, concentrating most cardenolides (but not labriformin) from seeds into their bodies. Accordingly, whether cardenolides defend seeds against these specialist bugs is unclear. We demonstrate that Oncopeltus fasciatus (Lygaeidae) metabolized two major compounds (glycosylated aspecioside and labriformin) into distinct products that were sequestered without impairing growth. We next tested several isolated cardenolides in vitro on the physiological target of cardenolides (Na+/K+-ATPase); there was little variation among compounds in inhibition of an unadapted Na+/K+-ATPase, but tremendous variation in impacts on that of monarchs and Oncopeltus. Labriformin was the most inhibitive compound tested for both insects, but Oncopeltus had the greater advantage over monarchs in tolerating labriformin compared to other compounds. Three metabolized (and stored) cardenolides were less toxic than their parent compounds found in seeds. Our results suggest that a potent plant defense is evolving by natural selection along a geographical cline and targets specialist herbivores, but is met by insect tolerance, detoxification, and sequestration.

La evaluación de habilidades para la vida independiente de jóvenes en el sistema de protección: un enfoque multiinformante / Assessing Independent Life Skills of Youth in Child Protection: A MultiInformant Approach

Resultados:Los resultados confirman la estructura interna esperada para los instrumentos (tres factores de primer orden y un factor de segundo orden para PLANEA-S, modelo unidimensional para PLANEA-9-S y modelo bifactorial correlacionado para PLANEA-T-S). Los instrumentos mostraron niveles excelentes de fiabilidad (ω = .80-.97) y capacidad discriminativa. El personal informó de menor nivel de habilidades para la vida independiente que el grupo de jóvenes, pero no de autonomía en la vida diaria, lo cual estuvo mediado por el rol del informante adulto con respecto al joven.Conclusiones: Se concluye que la versión para educadores de los instrumentos PLANEA de evaluación de habilidades para la vida independiente amplía el campo de evaluación de este constructo en jóvenes en acogimiento desde una perspectiva multiinformante, lo que es clave para que los servicios de protección infantil puedan identificar y atender las necesidades individuales de estos jóvenes, seleccionando los apoyos necesarios en cada caso para la promoción de una transición exitosa desde el sistema de protección a la vida adulta.

Background:This study aimed to adapt and validate a staff version of the PLANEA Independent Life Skills Assessment tools, which were then used to explore the convergence between self-reported and staff views of independent living skills of young people in residential child care in Spain. Method: A sample of 422 care-experienced young people was evaluated by their residential or care workers (n = 219) using the staff version of PLANEA instruments. Psychometric analyses were carried out to study dimensionality and measuring properties of the instruments, while t-tests, Pearson correlations and Fisher’s z were used to study convergence between informants. Results: The results show that the internal structure of the instruments was confirmed for the staff versions (three first-order factors and one second-order factor model for PLANEA-S, unidimensional model for PLANEA-9-S, and two-factor correlated model for PLANEA-T-S). The instruments showed excellent reliability (ω = .80-.97) and discriminative capacity. Staff showed less optimistic views than young people about their independent living skills but not their autonomy to perform everyday life tasks. This was mediated by the role of the adult respondent towards the young person evaluated. Conclusions: As conclusions we can say that the validated staff version of the PLANEA Independent Life Skills Assessment tools expands the scope for assessing this construct in young people in care from a multi-informant perspective. This is key for child protection services to address young people’s individual needs and inform decision-making regarding the provision of support services that will promote a successful transition from care to adulthood for them.

Crossing Countries and Crossing Ages: The Difficult Transition to Adulthood of Unaccompanied Migrant Care Leavers.

The social changes experienced in many countries have prolonged the transition to adult life for young people. That being said, those who leave child care cannot afford this privilege, in that they do not benefit from the same support and resources, having to confront an accelerated transition which exposes them to increased risk of negative outcomes and social exclusion. Moreover, this transition might be even riskier for unaccompanied migrant care leavers, who are four times as vulnerable, given their status as young people in care, as adolescents, as migrants and being unaccompanied. This paper seeks to explore the profiles, needs, and experiences of unaccompanied young migrants in comparison with other care leavers. Data were collected by means of a semi-structured interview to explore their pre-care, in-care, and aftercare experiences. A highly specific profile of unaccompanied young migrants has been revealed that differs from the other care leavers in terms of worse educational, occupational, and economic outcomes, limited support networks, and more obstacles to accessing aftercare supports. Conversely, they also exhibited some strengths, such as having less pre-care, in care, and aftercare traumatic experiences, less psychological distress and fewer risky behaviors compared with other care leavers.

PLANEA Independent Life Skills Scale: Development and Validation.

BACKGROUND: The aim of this study was to develop and validate the PLANEA Independent Life Skills Scale, an instrument created according to the Planea Program framework for training independent living skills in young people in residential care. METHOD: A sample of 1,098 young people took part, 60% were women and 37% were living in residential child care, with a mean age of 17.69 years ( SD = 2.25). Psychometric analyses were carried out within the frameworks of Classical Test Theory and Item Response Theory models. RESULTS: The new instrument demonstrated three first-order factors (Self-Care and Wellbeing, Daily Arrangements and Organizational Skills, and Employment and Accommodation) and one second-order factor (Independent Life Skills), with excellent test score reliability, including a short version, PLANEA-9 (ω = .86 - .94). Clear evidence was found of validity in relation to other variables, such as general self-efficacy ( r = .519), and discriminative capacity. CONCLUSIONS: The PLANEA Independent Life Skills Scale was shown to be a reliable valid instrument for assessing this construct in young people.

PLANEA Independent Life Skills Scale: Development and Validation / Escala PLANEA de Habilidades Para la Vida Independiente: Desarrollo y Validación

Background: The aim of this study was to develop and validate the PLANEA Independent Life Skills Scale, an instrument created according to the Planea Program framework for training independent living skills in young people in residential care. Method: A sample of 1,098 young people took part, 60% were women and 37% were living in residential child care, with a mean age of 17.69 years (SD = 2.25). Psychometric analyses were carried out within the frameworks of Classical Test Theory and Item Response Theory models. Results: The new instrument demonstrated three fi rst-order factors (Self-Care and Wellbeing, Daily Arrangements and Organizational Skills, and Employment and Accommodation) and one second-order factor (Independent Life Skills), with excellent test score reliability, including a short version, PLANEA-9 (ω = .86 - .94). Clear evidence was found of validity in relation to other variables, such as general self-effi cacy (r = .519), and discriminative capacity. Conclusions: The PLANEA Independent Life Skills Scale was shown to be a reliable valid instrument for assessing this construct in young people. (AU)

Antecedentes: el objetivo del estudio fue el desarrolloy validación de la Escala PLANEA de Habilidades para la Vida Independiente, un instrumento creado a partir del Programa Planea de desarrollo de habilidades para la vida independiente en jóvenes en acogimiento residencial. Método: participaron 1.098 jóvenes, de los cuales el 60% eran mujeres y el 37% vivían en acogimiento residencial, con una media de edad de 17,69 años (DT = 2,25). Los análisis psicométricos se realizaron en el marco de los modelos de la Teoría Clásica de los Tests y la Teoría de Respuesta al Ítem. Resultados: el nuevo instrumento quedó conformado por tres factores de primer orden (Autocuidado y bienestar, Gestiones y organización diaria, y Trabajo e Independencia) y un factor de segundo orden (Habilidades para la vida independiente), con excelente fiabilidad, incluida una versión corta, PLANEA-9 (ω = ,86 - ,94). Se encontró evidencia clara de validez en relación con otras variables, como autoeficacia (r = ,519), así como buena capacidad discriminativa. Conclusiones: la Escala PLANEA de Habilidades para la Vida Independiente mostró ser un instrumento válido y fiable para evaluar este constructo en población juvenil. (AU)

Working memory moderates the association between early institutional care and separation anxiety symptoms in late childhood and adolescence.

Adverse caregiving, for example, previous institutionalization (PI), is often associated with emotion dysregulation that increases anxiety risk. However, the concept of developmental multifinality predicts heterogeneity in anxiety outcomes. Despite this well-known heterogeneity, more work is needed to identify sources of this heterogeneity and how these sources interact with environmental risk to influence mental health. Here, working memory (WM) was examined during late childhood/adolescence as an intra-individual factor to mitigate the risk for separation anxiety, which is particularly susceptible to caregiving adversities. A modified "object-in-place" task was administered to 110 youths (10-17 years old), with or without a history of PI. The PI youths had elevated separation anxiety scores, which were anticorrelated with morning cortisol levels, yet there were no group differences in WM. PI youths showed significant heterogeneity in separation anxiety symptoms and morning cortisol levels, and WM moderated the link between caregiving and separation anxiety and mediated the association between separation anxiety and morning cortisol in PI youth. Findings suggest that (a) institutional care exerts divergent developmental consequences on separation anxiety versus WM, (b) WM interacts with adversity-related emotion dysregulation, and (c) WM may be a therapeutic target for separation anxiety following early caregiving adversity.

"It's so Cute I Could Crush It!": Understanding Neural Mechanisms of Cute Aggression.

The urge people get to squeeze or bite cute things, albeit without desire to cause harm, is known as "cute aggression." Using electrophysiology (ERP), we measured components related to emotional salience and reward processing. Participants aged 18-40 years (n = 54) saw four sets of images: cute babies, less cute babies, cute (baby) animals, and less cute (adult) animals. On measures of cute aggression, feeling overwhelmed by positive emotions, approachability, appraisal of cuteness, and feelings of caretaking, participants rated more cute animals significantly higher than less cute animals. There were significant correlations between participants' self-report of behaviors related to cute aggression and ratings of cute aggression in the current study. N200: A significant effect of "cuteness" was observed for animals such that a larger N200 was elicited after more versus less cute animals. A significant correlation between N200 amplitude and the tendency to express positive emotions in a dimorphous manner (e.g., crying when happy) was observed. RewP: For animals and babies separately, we subtracted the less cute condition from the more cute condition. A significant correlation was observed between RewP amplitude to cute animals and ratings of cute aggression toward cute animals. RewP amplitude was used in mediation models. Mediation Models: Using PROCESS (Hayes, 2018), mediation models were run. For both animals and babies, the relationship between appraisal and cute aggression was significantly mediated by feeling overwhelmed. For cute animals, the relationship between N200 amplitude and cute aggression was significantly mediated by feeling overwhelmed. For cute animals, there was significant serial mediation for RewP amplitude through caretaking, to feeling overwhelmed, to cute aggression, and RewP amplitude through appraisal, to feeling overwhelmed, to cute aggression. Our results indicate that feelings of cute aggression relate to feeling overwhelmed and feelings of caretaking. In terms of neural mechanisms, cute aggression is related to both reward processing and emotional salience.

Repetitive behaviors in autism are linked to imbalance of corticostriatal connectivity: a functional connectivity MRI study.

The neural underpinnings of repetitive behaviors (RBs) in autism spectrum disorders (ASDs), ranging from cognitive to motor characteristics, remain unknown. We assessed RB symptomatology in 50 ASD and 52 typically developing (TD) children and adolescents (ages 8-17 years), examining intrinsic functional connectivity (iFC) of corticostriatal circuitry, which is important for reward-based learning and integration of emotional, cognitive and motor processing, and considered impaired in ASDs. Connectivity analyses were performed for three functionally distinct striatal seeds (limbic, frontoparietal and motor). Functional connectivity with cortical regions of interest was assessed for corticostriatal circuit connectivity indices and ratios, testing the balance of connectivity between circuits. Results showed corticostriatal overconnectivity of limbic and frontoparietal seeds, but underconnectivity of motor seeds. Correlations with RBs were found for connectivity between the striatal motor seeds and cortical motor clusters from the whole-brain analysis, and for frontoparietal/limbic and motor/limbic connectivity ratios. Division of ASD participants into high (n = 17) and low RB subgroups (n = 19) showed reduced frontoparietal/limbic and motor/limbic circuit ratios for high RB compared to low RB and TD groups in the right hemisphere. Results suggest an association between RBs and an imbalance of corticostriatal iFC in ASD, being increased for limbic, but reduced for frontoparietal and motor circuits.

N-ω-chloroacetyl-l-ornithine, a new competitive inhibitor of ornithine decarboxylase, induces selective growth inhibition and cytotoxicity on human cancer cells versus normal cells.

Many cancer cells have high expression of ornithine decarboxylase (ODC) and there is a concerted effort to seek new inhibitors of this enzyme. The aim of the study was to initially characterize the inhibition properties, then to evaluate the cytotoxicity/antiproliferative cell based activity of N-ω-chloroacetyl-l-ornithine (NCAO) on three human cancer cell lines. Results showed NCAO to be a reversible competitive ODC inhibitor (Ki = 59 µM) with cytotoxic and antiproliferative effects, which were concentration- and time-dependent. The EC50,72h of NCAO was 15.8, 17.5 and 10.1 µM for HeLa, MCF-7 and HepG2 cells, respectively. NCAO at 500 µM completely inhibited growth of all cancer cells at 48 h treatment, with almost no effect on normal cells. Putrescine reversed NCAO effects on MCF-7 and HeLa cells, indicating that this antiproliferative activity is due to ODC inhibition.

Effect of exendin (exenatide)--GLP 1 receptor agonist on the thyroid and parathyroid gland in a rat model.

Exenatide or Exendin-4 is a 39-amino acid agonist of the glucagon like peptide (GLP-1) receptor approved for the adjunctive treatment for type 2 diabetes. Recent reports suggest that GLP-1 agonists may also have distant effects including C-cell thyroid hyperplasia. The aim of this study was to evaluate the effect of exendin-4 on the thyroid and parathyroid cells in a rat model. Rat thyroids were stained for calcitonin, H&E and for carcinoembryonic antigen (CEA). Thyroid C-cell hyperplasia was graded on H&E stained slides using cell size and secretory granule numbers, morphological features of the parathyroid glands and the serum calcium concentrations of the rats were also evaluated. Counts of stained cells/high power field and intensity of staining were recorded by two pathologists. Data were analyzed by ANOVA/post-tests. C cell hypertrophy was elevated in exenatide-treated vs. untreated animals (22.5 ± 8.7 vs. 10.5 ± 2.7 cells/HPF). CEA staining failed to show effects by exendin. Calcitonin staining was significantly elevated in exenatide treated controls (P<0.001). Parathyroid glands were histologically normal in both groups, and serum calcium levels were within normal range in all animals. In summary, exenatide was associated with C cell hyperplasia and increased calcitonin staining of thyroids, but was unrelated to CEA levels. These data raise important concerns about the effects of exenatide which, given its wide clinical use, should be clarified with urgency.

Treatment with omega-3 fatty acids but not exendin-4 improves hepatic steatosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the Western world. The aim of this study was to evaluate the biochemical and histological effects of omega-3 fatty acid and exendin-4 treatment on NAFLD in an animal model. METHODS: Sixty-three 8-week-old outbred Sprague-Dawley male rats were used for this study. Three animals were used as procedure controls, and 30 rats were fed a methionine and choline deficient (MCD) diet and 30 were fed a regular chow diet. In each group of 30 animals, 10 served as controls, 10 received exendin-4, and 10 received omega-3 fatty acids. After 75 days of treatment, the animals were euthanized, the tissues and serum were harvested, and the livers were formalin-fixed for histology. RESULTS: The MCD diet was exceptionally efficient at producing fatty livers. The MCD control animals had a liver steatosis score of 38+/-6.7 (of 50 possible); treatment with exendin-4 was not associated with a significant reduction of steatosis (44+/-5.16, P=0.07) and the omega-3 fatty acid treatment was associated with a significant decrease in the liver steatosis score (15.6+/-13.46, P<0.001) compared with both the controls and the exendin-4 groups. The omega-3 fatty acid treatment increased serum aspartate aminotransferase significantly, whereas exendin-4 had no effect. CONCLUSION: In an animal model of NAFLD, the omega-3 fatty acid therapy was associated with significant improvement in hepatic steatosis compared with exendin-4. These data suggest that omega-3 fatty acid supplements may have a potential therapeutic role in patients with NAFLD.