Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for BrafV600E‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (TyrCreERT2/+; BrafLSL‐V600E/+; Ptenflox/flox) to Sirt5?/? knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5?/? mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor. 相似文献
Background: Little is known of stroke outcomes in low- and middle-income countries with limited formal stroke rehabilitation services and of homebased-stroke services delivered within the primary health care (PHC) context by community health workers (CHWs).
Objectives: To describe and analyze the outcomes of patients with stroke from a rural PHC setting in the Western Cape, South Africa.
Methods: In a longitudinal survey, 93 stroke patients, referred to home and community-based care services (HCBC) between June 2015 and December 2017, were assessed at baseline, one month and three months. Changes in function (Barthel Index (BI)), caregiver strain (Caregiver Strain Index (CSI)), impact of environmental factors and satisfaction with stroke care were measured.
Results: HCBC was delayed, fragmented and brief (median session duration 20 minutes (IQR 15.0–30.0)). Although function improved significantly, dependence remained high: median BI score changed from 40.0 (IQR 15.0–70.0) to 62.5 (IQR 30.0–81.25) (p = .019). A third (33.0% (30/91)) of caregivers initially experienced strain and the median CSI score remained 3.0 (IQR 0.0–7.0) (p = .672). Overall, patient and caregiver satisfaction with HCBC was low with only 46.9% (31/66) of caregivers and 17.4% (12/69) of patients satisfied with all aspects of care. Only 47.6% of assistive product needs were met. Environmental factors negatively impacted on patient function and caregiving.
Conclusions: Clinical practice pathways and referral guidelines should be developed for the HCBC platform. Specific training of CHWs, focusing on how to educate, support and train family caregivers, provide assistive devices and refer to health services is needed. 相似文献
Background: Large randomized trials show that in appropriately selected patients with left ventricular dysfunction, implantable cardioverter-defibrillators (ICDs) can improve overall survival at 2–5 years. Since direct implementation of the criteria used in the MADIT II and SCD-HeFT will lead to a marked rise in ICD implants, there is a growing fear that increased use of ICDs may cause a dramatic burden to health care systems. The ICD has traditionally been seen as an expensive form of treatment, which is difficult to accept at the first look. This is mainly due to the nonlinear character of the ICD investment, characterized by high initial expenditure, followed by a deferred pay-off in terms of clinical benefits. Cost-effectiveness analysis may help provide a different perspective on the problem of ICD cost, as may estimation of the daily cost of ICD treatment, assuming a time horizon of 5–7 years—a particularly interesting subject for further registry studies. Methods and Results: Based on real expenditure data from 2002 to 2005, as recorded in the Search-MI Registry-Italian Sub-study of patients implanted on MADIT II indications, we estimated the daily costs associated with the device and leads. Over a 5–7 year time horizon, the average daily cost was estimated to be €4.60–€6.70. Translation of these figures into U.S. market conditions suggests a daily cost of around $7.90–$11.40. Conclusions: These findings appear useful to help evaluate the affordability of ICD in comparison with other therapeutic options in a context of limited available economic resources. 相似文献
AIM/BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown aetiology. Up to 10% of patients with typical features of PBC will have additional features of autoimmune hepatitis (AIH). A subset, however, have no such features but go on to develop a 'sequential' AIH overlap syndrome. Objectives: Describe our experience with eight patients who developed AIH after the diagnosis of PBC was made. METHODS: We reviewed the charts of all PBC patients over a 9-year period (from 1996 to 2005). Only PBC patients with no features of AIH were included. RESULTS: There were 1476 patients with PBC. Of these, eight patients developed features of AIH overlap syndrome based on biochemical and histological parameters. Treatment included prednisone and azathioprine for 24 or more months. The majority of patients remained on ursodeoxycholic acid (UDCA) throughout treatment. Response to therapy was defined by improvement in enzymes, and was rapid for all patients. One patient was able to discontinue treatment with prednisone and azathioprine, while seven have continued on therapy to date. CONCLUSIONS: A 'sequential' overlap syndrome of AIH with PBC can occur. Treatment with prednisone and azathioprine may lead to a rapid improvement in aminotransferase levels. 相似文献
Cutaneous plasmacytosis is a rare disorder characterized by a benign proliferation of mature plasma cells that appears as multiple dark-brown to purplish skin lesions, often associated with polyclonal hypergammaglobulinaemia. We present the case of a 55-year-old Caucasian man who suffered from a cutaneous plasmacytosis associated with two different carcinomas. Cutaneous plasmacytosis seems to be a reactive process because most cases reported are not associated with any apparent underlying disease. Nevertheless, because few reported cases were associated with malignancies, screening of additional neoplasms would be justified. 相似文献