A functional alternative splicing mutation in human tryptophan hydroxylase-2

The brain serotonergic system has an essential role in the physiological functions of the central nervous system and dysregulation of serotonin (5-HT) homeostasis has been implicated in many neuropsychiatric disorders. The tryptophan hydroxylase-2 (TPH2) gene is the rate-limiting enzyme in brain 5-HT synthesis, and thus is an ideal candidate gene for understanding the role of dysregulation of brain serotonergic homeostasis. Here, we characterized a common, but functional single-nucleotide polymorphism (SNP rs1386493) in the TPH2 gene, which decreases efficiency of normal RNA splicing, resulting in a truncated TPH2 protein (TPH2-TR) by alternative splicing. TPH2-TR, which lacks TPH2 enzyme activity, dominant-negatively affects full-length TPH2 function, causing reduced 5-HT production. The predicted mRNA for TPH2-TR is present in postmortem brain of rs1386493 carriers. The rs13864923 variant does not appear to be overrepresented in either global or multiplex depression cohorts. However, in combination with other gene variants linked to 5-HT homeostasis, this variant may exhibit important epistatic influences

ACR appropriateness criteria stage i breast cancer: Initial workup and surveillance for local recurrence and distant metastases in asymptomatic women

© 2014 American College of Radiology. Women newly diagnosed with stage 1 breast cancer have an early-stage disease that can be effectively treated. Evidence provides little justification for performing imaging to exclude metastasis in asymptomatic women with stage I breast cancer. No differences have been found in survival or quality of life in women regardless of whether they underwent initial workup for metastatic disease. These women generally prefer intensive follow-up to detect an early recurrence. However, survival rates do not differ between women who obtain intensive screening and surveillance, with imaging and laboratory studies, and women who undergo testing only as a result of development of symptoms or findings on clinical examinations. In addition, quality of life is similar for women who undergo intensive surveillance compared with those who do not. American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines state that annual mammography is the only imaging examination that should be performed to detect a localized breast recurrence in asymptomatic patients. Additional imaging may be needed if the patient has locoregional symptoms. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review by the panel include extensive analysis of current medical literature from peer-reviewed journals and application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. When evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment

ACR Appropriateness Criteria Evaluation of the Symptomatic Male Breast

Most male breast problems are benign, and men with typical symptoms of gynecomastia or pseudogynecomastia do not usually need imaging. When a differentiation between benign disease and breast cancer cannot be made on the basis of clinical findings or when the clinical findings are suspicious for breast cancer, imaging is indicated. Mammography is useful in both identifying cancer and obviating the need for biopsy in patients for whom a benign mammographic impression confirms the clinical impression. However, because of the relationship of breast cancer to increasing age, age-based protocols that do not include mammography have been developed. For men with an indeterminate palpable mass, begin with ultrasound if the patient is <25 years of age, because breast cancer is highly unlikely. Mammography should be performed if ultrasound is suspicious. For men ≥25 years of age or having a highly concerning physical examination, usually begin with mammography; ultrasound is useful if mammography is inconclusive or suspicious. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals, and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment

ACR Appropriateness Criteria Stage I Breast Cancer: Initial Workup and Surveillance for Local Recurrence and Distant Metastases in Asymptomatic Women

© 2014 American College of Radiology Women newly diagnosed with stage 1 breast cancer have an early-stage disease that can be effectively treated. Evidence provides little justification for performing imaging to exclude metastasis in asymptomatic women with stage I breast cancer. No differences have been found in survival or quality of life in women regardless of whether they underwent initial workup for metastatic disease. These women generally prefer intensive follow-up to detect an early recurrence. However, survival rates do not differ between women who obtain intensive screening and surveillance, with imaging and laboratory studies, and women who undergo testing only as a result of development of symptoms or findings on clinical examinations. In addition, quality of life is similar for women who undergo intensive surveillance compared with those who do not. American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines state that annual mammography is the only imaging examination that should be performed to detect a localized breast recurrence in asymptomatic patients. Additional imaging may be needed if the patient has locoregional symptoms. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review by the panel include extensive analysis of current medical literature from peer-reviewed journals and application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. When evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment