A Large Naturalistic Study on the BRACHA: Confirmation of the Predictive Validity.

Aggression is a major challenge on child/adolescent inpatient psychiatric units. A screening instrument to accurately identify risk is urgently needed. To determine the predictive validity of the Brief Rating of Aggression by Children and Adolescents (BRACHA). Prospective cohort study. BRACHA is administered by clinical staff in the emergency department (ED) prior to inpatient psychiatric admission. A consecutive sample of 10,054 admitted patients from 2010-2021. No patients refused screening nor were excluded. BRACHA administered to patients in the ED prior to admission at Cincinnati Children's Hospital Medical Center (CCHMC). Patient behavioral outcomes measured by Overt Aggression Scale (OAS), categorizing aggression as verbal or physical, then as towards self, others, or objects. Female patients comprised 53.6% (n = 5,386) of the sample. Most patients were white (n = 6,556, 65.2%). Patients ranged in age from 4 to 18 years, with a mean age of 13.6 ± 3.1 years. A single biological parent (n = 5,317, 52.9%) was the predominant living arrangement among patients. The Area Under the Curve (AUC), as an assessment of predictive validity across all possible cut-offs of BRACHA scores ranged from 0.640 (aggression to self) to 0.758 (physical aggression towards others). Our findings support the BRACHA as a useful predictive instrument for aggression in inpatient psychiatric admissions from ED regardless of length of stay. Treating staff are then able to immediately classify risk level and inform care plans for all lengths of hospitalization. Applies to potential risk for aggression, except for self-aggression. Future data analyses will evaluate demographic factors to determine which improve predictive power of the BRACHA and can be used to create a BRACHA calculator. To our knowledge, this naturalistic outcomes study is one of the largest in psychiatry. The BRACHA will continue to be studied to evaluate risk for aggression on inpatient units and aim to assist in keeping unit staff and patients safe.

A novel peptide antagonist of the human growth hormone receptor.

Excess circulating human growth hormone (hGH) in vivo is linked to metabolic and growth disorders such as cancer, diabetes, and acromegaly. Consequently, there is considerable interest in developing antagonists of hGH action. Here, we present the design, synthesis, and characterization of a 16-residue peptide (site 1-binding helix [S1H]) that inhibits hGH-mediated STAT5 phosphorylation in cultured cells. S1H was designed as a direct sequence mimetic of the site 1 mini-helix (residues 36-51) of wild-type hGH and acts by inhibiting the interaction of hGH with the human growth hormone receptor (hGHR). In vitro studies indicated that S1H is stable in human serum and can adopt an α-helix in solution. Our results also show that S1H mitigates phosphorylation of STAT5 in cells co-treated with hGH, reducing intracellular STAT5 phosphorylation levels to those observed in untreated controls. Furthermore, S1H was found to attenuate the activity of the hGHR and the human prolactin receptor, suggesting that this peptide acts as an antagonist of both lactogenic and somatotrophic hGH actions. Finally, we used alanine scanning to determine how discrete amino acids within the S1H sequence contribute to its structural organization and biological activity. We observed a strong correlation between helical propensity and inhibitory effect, indicating that S1H-mediated antagonism of the hGHR is largely dependent on the ability for S1H to adopt an α-helix. Taken together, these results show that S1H not only acts as a novel peptide-based antagonist of the hGHR but can also be applied as a chemical tool to study the molecular nature of hGH-hGHR interactions.