Divergent Functional Diversification Patterns in the SEP/AGL6/AP1 MADS-box Transcription Factor Superclade

International audienceMembers of SEPALLATA (SEP) and APETALA1 (AP1)/SQUAMOSA (SQUA) MADS-box transcriptionfactor subfamilies play key roles in floral organ identity determination and floral meristem determinacyin the Rosid species Arabidopsis. Here, we present a functional characterization of the seven SEP/AGL6and four AP1/SQUA genes in the distant Asterid species Petunia x hybrida petunia. Based on the analysisof single and higher order mutants, we report that the petunia SEP1/SEP2/SEP3 orthologs together withAGL6 encode classical SEP floral organ identity and floral termination functions, with a master role forthe petunia SEP3 ortholog FLORAL BINDING PROTEIN 2 (FBP2). By contrast, the FBP9 subclademembers FBP9 and FBP23, for which no clear ortholog is present in Arabidopsis, play a major role indetermining floral meristem identity together with FBP4, while contributing only moderately to floralorgan identity. In turn, the four members of the petunia AP1/SQUA subfamily redundantly are requiredfor inflorescence meristem identity, and act as B-function repressors in the first floral whorl, togetherwith BEN/ROB genes. Overall, these data together with studies in other species suggest majordifferences in the functional diversification of the SEP/AGL6 and AP1/SQUA MADS-box subfamiliesduring angiosperm evolution

Mortality reduction in patients treated with long-term intensive lipid therapy: 25-year follow-up of the Familial Atherosclerosis Treatment Study—Observational Study

BackgroundCardiovascular disease (CVD) begins early in life and is associated with both the number of risk factors present and length of exposure to these risk factors including hyperlipidemia.ObjectivesThe clinical benefit of intensive lipid therapy over 25 years was investigated in the Familial Atherosclerosis Treatment Study-Observational Study.MethodsOf 175 coronary artery disease subjects with mean low-density lipoprotein cholesterol (LDL-C) of 191 mg/dL and mean age of 50 years, who completed the randomized and placebo-controlled Familial Atherosclerosis Treatment Study, 100 chose receiving lipid management by their physicians (usual care [UC]) and 75 elected to receive an intensive treatment [IT] for lipid management with lovastatin (40 mg/d), niacin (2.5 g/d), and colestipol (20 g/d) from 1989 to 2004, followed by double therapy with simvastatin (40-80 mg/d) and niacin from 2005 to 2006 and by triple therapy of ezetimibe 10 mg and simvastatin 40 to 80 mg/d plus niacin during 2007 to 2012. Deaths from CVD, non-CVD, and any cause were compared between UC and IT using Cox proportional hazards model.ResultsUC and IT groups were similar in risk factors with the exception that IT had more severe coronary artery disease. Mean LDL-C levels were 167 mg/dL from 1988 to 2004, 97 from 2005 to 2006, and 96 from 2007 to 2012 in surviving subjects receiving UC. IT lowered LDL-C to 119, 97, and 83 mg/dL in the 3 periods, respectively. Compared with UC, IT significantly reduced total mortality (11.1 vs 26.3 per 1000 person years [PY], hazard ratio [HR] = 0.45, 95% confidence interval [CI]: 0.26-0.77, P = .003) and CVD mortality (10.6 vs 27.7 per 1000 PY, HR = 0.34, 95% CI: 0.15-0.80, P = .009). The non-CVD mortality was also reduced but was not of statistical significance (6.8 vs 12.7 per 1000 PY, HR = 0.55, 95% CI: 0.27-1.14, P = .11).ConclusionsLong-term intensive lipid therapy significantly reduced total and cardiovascular mortality in Familial Atherosclerosis Treatment Study-Observational Study. These results support the importance of lifetime risk management to improve long-term outcome

Reducing Behavioral and Psychological Symptoms of Dementia in Acutely Ill Patients via Patient Engagement Specialists: A Pilot Feasibility Study

Behavioral and psychological symptoms of dementia (BPSD) are common in hospitalized persons living with dementia (PLWD). This pilot aimed to test the feasibility of an innovative model of care, PES-4-BPSD (a dementia unit staffed with Patient Engagement Specialists, PES). Non-randomized pilot feasibility trial was conducted, enrolling N  = 158 patients to the intervention unit ( n  = 79, a 10-bed dementia unit, staffed with nursing assistants, NAs, with mental health backgrounds, PES) and an enhanced control unit ( n  = 79, 40-bed medicine unit, staffed with NAs). All NAs/PES ( N  = 63) received dementia training, with completion rate of 82.5%. Overall, patients had ~1 NPI-Q (Neuropsychiatric Inventory Questionnaire) assessment/48 hr. 97% ( n  = 153) of PLWD exhibited at least one behavior. Average NPI-Q scores did not differ across intervention (5.36) and control (3.87) units ( p  = .23). Patients on the intervention unit had 88% ( p  = .002) shorter duration of constant observation. A dementia care unit staffed by PES is an innovative model requiring further research

Mortality reduction in patients treated with long-term intensive lipid therapy: 25-year follow-up of the Familial Atherosclerosis Treatment Study—Observational Study

BACKGROUND: Cardiovascular disease (CVD) begins early in life and is associated with both the number of risk factors present and length of exposure to these risk factors including hyperlipidemia. OBJECTIVES: The clinical benefit of intensive lipid therapy over 25 years was investigated in the Familial Atherosclerosis Treatment Study – Observational Study (FATS-OS). METHODS: Of 175 CAD subjects with mean LDL-C of 191 mg/dl and mean age of 50 years, who completed the randomized and placebo-controlled FATS, 100 choose receiving lipid management by their physicians (UC) and 75 elected to receive an intensive lipid therapy (IT) with lovastatin (40mg/day), niacin (2.5g/day) and colestipol (20g/day) from 1989 to 2004, followed by double therapy with simvastatin (40–80mg/day) and niacin from 2005 to 2006 and by triple therapy of ezetimibe 10 mg and simvastatin 40–80 mg/day plus niacin during 2007–2012. Death from CVD, non-CVD and any cause were compared between UC and IT using Cox proportional hazards model. RESULTS: UC and IT groups were similar in risk factors with the exception that IT had more sever CAD. Mean LDL-C levels were 167 mg/dl from 1988 to 2004, 97 from 2005 to 2006, and 96 from 2007 to 2012 in surviving subjects receiving UC. IT lowered LDL-C to 119 mg/dl, 97, and 83 in the 3 time periods. Compared to UC, IT significantly reduced total mortality (11.1 vs. 26.3 per 1,000 PY, HR=0.45, 95% CI: 0.26–0.77, p=0.003) and CVD mortality (10.6 vs. 27.7 per 1,000 PY, HR=0.34, 95% CI: 0.15–0.80, p=0.009). The non-CVD mortality was also reduced, but was not of statistical significance (6.8 vs. 12.7 per 1,000 PY, HR=0.55, 95% CI: 0.27–1.14, p=0.11). CONCLUSIONS: Long-term intensive lipid therapy significantly reduced total and cardiovascular mortality in FATS-OS. These results support the importance of lifetime risk management to improve long-term outcome