Energy Landscapes of Supramolecular Peptide-Drug Conjugates Directed by Linker Selection and Drug Topology.

Peptide-drug conjugates that self-assemble into supramolecular nanomaterials have promise for uses in drug delivery. These discrete molecular species offer high and precise drug loading, affording efficient carriers for various therapeutic agents. Their peptide modules, meanwhile, enable biological targeting and stimuli-responsive function while also ordering the assembled nanostructure. The often hydrophobic drug payload likewise acts as a directive for self-assembly in aqueous media. Though accessible synthetic methods have allowed for extensive exploration of the peptide design space, the specific contributions of the drug molecule and its linker to the resulting assembly have been less explored. Hydrophobic drugs frequently have planar domains, conjugated π-systems, and isolated polar groups, which in turn can lead to specific and directional self-interactions. These energies of interaction affect the free energy landscape of self-assembly and may impact the form and assembly process of the desired nanomaterial. Here, two model supramolecular peptide-drug conjugates (sPDCs) are explored, composed of the corticosteroid dexamethasone conjugated to a conserved peptide sequence via two different linker chemistries. The choice of linker, which alters the orientation, rotational freedom, and number of stereoisomers of the prodrug in the final sPDC, impacts the mechanism and energetic barrier of assembly as well as the nano/macroscale properties of the resultant supramolecular materials. Accordingly, this work demonstrates the nonzero energetic contributions of the drug and its linker to sPDC self-assembly, provides a quantitative exploration of the sPDC free energy landscape, and suggests design principles for the enhanced control of sPDC nanomaterials to inform future applications as therapeutic drug carriers.

Development of an observational tool to assess health coaching fidelity.

OBJECTIVE: This study describes the development of the Health Coaching Index (HCI), an observational tool for assessing fidelity to implementing health coaching practical skills. METHODS: Initial HCI items were developed, adapted following cognitive interviews, and refined during coding training. Participants (n = 42) were trainees who completed a National Board for Health and Wellness Coaching (NBHWC)-approved training program and coached a standardized patient. Interrater reliability for the HCI was determined by calculating interclass correlations from ten videos coded by three raters. Construct validity was evaluated from 42 recordings using Spearman's Rho between HCI and Roter Interaction Analysis System (RIAS) codes. RESULTS: The interclass correlation (ICC) for HCI total score was 0.81, considered an excellent level of inter-rater agreement. Some significant correlations between HCI and RIAS codes supported construct validity (e.g., patient activation: Rho = 0.32; empathy: Rho = 0.36). CONCLUSION: The HCI total score can reliably be used to assess fidelity to health coaching skills, and the HCI has construct validity similar to the RIAS as a measure of patient activation. PRACTICE IMPLICATIONS: Adoption and further study of the HCI tool will allow for a more consistent implementation of health coaching skills, and may facilitate more robust training of health coaches for clinical practice and research.

Proportion and Clinical Relevance of Intraspinal Air in Patients With Pneumomediastinum.

OBJECTIVE: The purposes of this study were to determine the incidence of pneumorrhachis among patients with pneumomediastinum, determine whether its proportion correlates with the extent of pneumomediastinum, and ascertain its clinical relevance. MATERIALS AND METHODS: The radiologic database was searched for CT reports between January 2009 and September 2013 containing the term "pneumomediastinum" or "mediastinal air." Scans were examined for pneumomediastinum, pneumorrhachis, pneumothorax, sternotomy, and distribution of pneumomediastinum. The age and sex of the patient and probable cause of the abnormality were recorded. Cases that might have had another cause were excluded. RESULTS: The search yielded 422 CT scans. Among these, 242 instances of pneumomediastinum in 241 patients were found. Fifteen of these patients had pneumorrhachis. One was excluded because of recent traumatic spinal penetration. There was no significant difference in age or sex between patients with and those without pneumorrhachis. After application of the exclusion criteria, there were 14 cases of pneumorrhachis, yielding a proportion of 5.8%. Pneumorrhachis was observed more frequently in cases of the most severe grade (grade C) of pneumomediastinum; however, that relationship was not statistically significant (11 cases [8.2%]; p = 0.304). Pneumorrhachis was found significantly more frequently in patients with distribution of air in all three mediastinal compartments (13 cases, 16.2%, p < 0.001). Pneumorrhachis was overrepresented among subjects with spontaneous compared with those with secondary pneumomediastinum, although the trend did not reach statistical significance. CONCLUSION: Pneumorrhachis was present in 5.8% of patients. It is significantly more common in patients with the broadest distributions of mediastinal air and nonsignificantly more common in association with spontaneous as opposed to secondary pneumomediastinum. Pneumorrhachis in patients with pneumomediastinum is a generally benign, self-resolving condition.

Anemia: uma avaliação em pacientes portadores de HIV/AIDS / Anemia: an assessment in patients with HIV/AIDS / Anemia: an assessment in patients with HIV/AIDS

Introdução: Doenças hematológicas são comumente associadas ao descontrole da replicação do HIV e à consequente depleção dos linfócitos T-helper e, especial atenção merece a anemia, que é a alteração hematológica mais frequente. Objetivo: Avaliar a prevalência de anemia e relação com os dados antropométricos de portadores de HIV/AIDS que fazem tratamento em uma Casa de Assistência a pessoas com AIDS do município de Aracaju-SE. Método: Estudo observacional descritivo transversal, composto por 120 indivíduos de ambos os sexos, na faixa etária de 26 a 61 anos, no qual foi avaliada a frequência de anemia e sua associação com algumas características sociodemográficas, clínicas e antropométricas. Resultados: Foi evidenciado predomínio do sexo masculino (54,8%), com média de idade próxima aos 40 anos. A frequência de anemia foi elevada, em 50,8% da amostra. Porém, dentre as variáveis analisadas, a anemia manifestou-se independentemente da faixa etária, do gênero, do tempo de descoberta da doença ou do tipo de fármaco utilizado no tratamento da infecção estudada. Já em relação aos dados antropométricos, a anemia prevaleceu nos pacientes que apresentaram maior índice de massa corporal, maior AMBc e associação entre menor somatório de dobras cutâneas e a ocorrência da anemia. Conclusão: A alta prevalência de anemia na amostra analisada é uma informação preocupante, visto que esse distúrbio tem sido associado à piora da condição clínica e está relacionada ao risco aumentado de óbitos em pacientes infectados pelo HIV/AIDS.

De novo copy number variants are associated with congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a common birth defect with significant morbidity and mortality. Although the aetiology of CDH remains poorly understood, studies from animal models and patients with CDH suggest that genetic factors play an important role in the development of CDH. Chromosomal anomalies have been reported in CDH. METHODS: In this study, the authors investigated the frequency of chromosomal anomalies and copy number variants (CNVs) in 256 parent-child trios of CDH using clinical conventional cytogenetic and microarray analysis. The authors also selected a set of CDH related training genes to prioritise the genes in those segmental aneuploidies and identified the genes and gene sets that may contribute to the aetiology of CDH. RESULTS: The authors identified chromosomal anomalies in 16 patients (6.3%) of the series including three aneuploidies, two unbalanced translocation, and 11 patients with de novo CNVs ranging in size from 95 kb to 104.6 Mb. The authors prioritised the genes in the CNV segments and identified KCNA2, LMNA, CACNA1S, MYOG, HLX, LBR, AGT, GATA4, SOX7, HYLS1, FOXC1, FOXF2, PDGFA, FGF6, COL4A1, COL4A2, HOMER2, BNC1, BID, and TBX1 as genes that may be involved in diaphragm development. Gene enrichment analysis identified the most relevant gene ontology categories as those involved in tissue development (p=4.4×10(-11)) or regulation of multicellular organismal processes (p=2.8×10(-10)) and 'receptor binding' (p=8.7×10(-14)) and 'DNA binding transcription factor activity' (p=4.4×10(-10)). CONCLUSIONS: The present findings support the role of chromosomal anomalies in CDH and provide a set of candidate genes including FOXC1, FOXF2, PDGFA, FGF6, COL4A1, COL4A2, SOX7, BNC1, BID, and TBX1 for further analysis in CDH.