Self-reporting of psychoneurophysical (PNP) symptoms in adults with four chronic diseases: a protocol for a scoping review.

BACKGROUND: Patient self-reporting of health-specific information, including symptoms, allows healthcare providers to provide more timely, personalized, and patient-centered care to meet their needs. It is critical to acknowledge that symptom reporting draws from the individual's unique sociocultural background influencing how one perceives health and illness. This scoping review will explore whether racial groups with 4 chronic diseases (cardiovascular diseases, respiratory diseases, cancers, and diabetes) differ in self-reporting of psychoneurophysical (PNP) symptoms. The PNP symptoms of interest include depressive symptoms, fatigue, anxiety, pain, cognitive impairment, sleep impairment, mood impairment, irritability, and shortness of breath. METHODS: Four databases will be searched by a biomedical librarian: CINAHL Plus (EBSCOhost), Embase (Elsevier), PubMed (NLM), Web of Science: Core Collection (Clarivate Analytics), and limited to publications written in the English language. Two independent reviewers will screen the records' title, abstract, and then full text and extract the data from included articles using Covidence. A third reviewer will be used for resolving disagreements. Included articles must comprise adult patients with at least one of the specified chronic diseases who self-report at least one of the specified PNP symptoms. Studies that used clinician-administered questionnaires or obtained symptom responses from primary caregiver or patient designee will be excluded. Articles on patient-reported functionality or perceived quality of life will also be excluded from the review. Two reviewers will independently extract data (e.g., demographics, study design, racial group, chronic disease, measure/scale used for self-report) from each included article using Covidence and Microsoft Excel for data cleaning and analyses. DISCUSSION: This scoping review may potentially identify the relevant and practical implications related to clinical decision-making and health outcomes for patients experiencing the psychoneurophysical symptoms included in this study. The authors will present how the results can be utilized in clinical practice, health policy, and research planning. SYSTEMATIC REVIEW REGISTRATION: The protocol was registered on Open Science Framework (OSF) at: https://osf.io/ps7aw.

A mosaic activating mutation in AKT1 associated with the Proteus syndrome.

BACKGROUND: The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state. METHODS: We performed exome sequencing of DNA from biopsy samples obtained from patients with the Proteus syndrome and compared the resultant DNA sequences with those of unaffected tissues obtained from the same patients. We confirmed and extended an observed association, using a custom restriction-enzyme assay to analyze the DNA in 158 samples from 29 patients with the Proteus syndrome. We then assayed activation of the AKT protein in affected tissues, using phosphorylation-specific antibodies on Western blots. RESULTS: Of 29 patients with the Proteus syndrome, 26 had a somatic activating mutation (c.49G→A, p.Glu17Lys) in the oncogene AKT1, encoding the AKT1 kinase, an enzyme known to mediate processes such as cell proliferation and apoptosis. Tissues and cell lines from patients with the Proteus syndrome harbored admixtures of mutant alleles that ranged from 1% to approximately 50%. Mutant cell lines showed greater AKT phosphorylation than did control cell lines. A pair of single-cell clones that were established from the same starting culture and differed with respect to their mutation status had different levels of AKT phosphorylation. CONCLUSIONS: The Proteus syndrome is caused by a somatic activating mutation in AKT1, proving the hypothesis of somatic mosaicism and implicating activation of the PI3K-AKT pathway in the characteristic clinical findings of overgrowth and tumor susceptibility in this disorder. (Funded by the Intramural Research Program of the National Human Genome Research Institute.).