目的:探讨中国社区糖尿病患者从家人或朋友获得直接支持和间接支持的现状,以及患者获得的直接支持与间接支持水平与其自我管理行为的相关关系。方法:研究对象的数据来自"北京市通州区社区诊断(2015)"专项调查,对符合要求的47...目的:探讨中国社区糖尿病患者从家人或朋友获得直接支持和间接支持的现状,以及患者获得的直接支持与间接支持水平与其自我管理行为的相关关系。方法:研究对象的数据来自"北京市通州区社区诊断(2015)"专项调查,对符合要求的474名社区糖尿病患者进行问卷调查、体格检查和糖化血红蛋白(glycated hemoglobin,Hb A1c)测量。应用糖尿病自我管理行为量表(the summary of diabetes self-care activities measure,SDSCA)对自我管理行为进行测量,应用糖尿病直接支持和间接支持量表(directive and nondirective support scale among patients with diabetes,DNSS-PD)对直接支持和间接支持水平进行测量,分析患者获得的直接支持与间接支持水平与其自我管理行为的相关关系。结果:共有452名患者纳入分析,患者获得的直接支持实际情况平均得分为2.53±1.07,27.6%患者获得的直接支持水平较高。患者获得的间接支持实际情况平均得分为3.13±1.12,50.8%患者获得的间接支持水平较高。患者SDSCA平均总得分为35.38±14.21,得分率为45.95%,仅20.6%患者自我管理的总体情况较好。直接支持水平高组患者的SDSCA平均总得分、饮食和运动维度得分、自我管理总体情况、饮食和运动维度自我管理情况显著优于直接支持水平低组。间接支持水平高组患者的SDSCA平均总得分,饮食、运动、血糖监测、足部护理、吸烟维度得分,自我管理总体情况,饮食、运动、血糖监测、足部护理以及吸烟维度自我管理情况均显著优于间接支持水平低组。性别(OR=2.729)、间接支持水平(OR=4.890)、年龄(OR=0.969)和体质指数(body msss index,BMI)(OR=0.819)是自我管理行为的重要影响因素。结论:社区糖尿病患者的自我管理情况不太理想,患者获得的间接支持水平高于直接支持水平,但均有待提升。间接支持和间接支持水平高均与糖尿病患者较好的自我管理行为相关,间接支持水平高与5个维度较好的自我管理行为均相关,直接支持水平高与较好的饮食和运动维度的自我管理行为相关。应对于社区男性老年肥胖的糖尿病患者的自我管理给予更多的关注和支持,特别是间接支持。展开更多
目的:探讨北京市通州区和顺义区747例2型糖尿病患者的生存质量现状及影响因素。方法:对纳入研究的747例2型糖尿病患者进行问卷调查和抽血实验室血生化检查。以糖化血红蛋白(hemoglobin A1c,HbA1c)作为血糖控制指标,以糖尿病患者特异性...目的:探讨北京市通州区和顺义区747例2型糖尿病患者的生存质量现状及影响因素。方法:对纳入研究的747例2型糖尿病患者进行问卷调查和抽血实验室血生化检查。以糖化血红蛋白(hemoglobin A1c,HbA1c)作为血糖控制指标,以糖尿病患者特异性生存质量量表(diabetes specific quality of life scale,DSQL)评分为患者生存质量指标,采用多元线性回归和结构方程模型(structural equation modeling,SEM)分析生存质量的影响因素。结果:调查747例患者,HbA1c平均水平(7.1±1.2)%,血糖控制达标率为35.1%(262/747)。血糖控制好和血糖控制差两组患者的病程、服药和使用胰岛素、吸烟情况及体重指数(body mass index,BMI)差异有统计学意义(P<0.05)。DSQL总分为(44.92±13.32)分,生理维度条目平均分最高,其次是心理维度。多元线性回归结果显示,家庭月收入、并发症、抑郁、病程时间、胰岛素、住院及自我效能是DSQL总分的影响因素(P<0.05)。SEM结果显示,血糖对于生存质量的生理维度(标准化效应值为0.166)、心理维度(0.076)及社会维度(0.124)存在影响,抑郁对于生存质量的生理维度(0.342)、心理维度(0.217)及治疗维度(0.050)存在影响,差异有统计学意义(P<0.05)。结论:北京市通州区和顺义区2型糖尿病患者HbA1c控制水平欠佳,生存质量尚可,仍有非常大的提升空间。应提高对男性、病程长、处于不服药状态、不使用胰岛素、吸烟、处于抑郁状态、糖尿病技能得分水平低的患者的关注和管理,同时应在临床治疗中提高对患者心理需求的重视,加强对患者及其家属的心理健康教育,采取相应的心理干预措施,以达到有效控制血糖的目的,从而提高患者的生活质量。展开更多
Post-translational protein modification, including phosphorylation, is generally quick and reversible, facilitating rapid biologic adjustments to altered cellular physiologic demands. In addition to protein phosphoryl...Post-translational protein modification, including phosphorylation, is generally quick and reversible, facilitating rapid biologic adjustments to altered cellular physiologic demands. In addition to protein phosphorylation, other post-translational modifications have been identified. Intracellular protein O-glycosylation, the addition of the simple sugar O-linked N-acetylglucosamine (O-G1cNAc) to serine/threonine residues, is a relatively recently identified post-translational modification that has added to the complexity by which protein function is regulated. Two intracellular enzymes, O-GlcNAc transferase and O-GlcNAcase, catalyze the addition and removal, respectively, of O-GlcNAc to serine and threonine side-chain hydroxyl groups. Numerous proteins, including enzymes, transcription factors, receptors and structural proteins have been shown to be modified by intracellular O-glycosylation. In this review, the mechanism and relevance of O-GlcNAc protein modification are discussed in the context of cell adhesion and several representative diseases.展开更多
Purpose: Non-adherence to recommended follow-up visits after an abnormal cytological finding is associated with poorer outcomes and higher health care costs. The purpose of this paper is to describe the challenges whe...Purpose: Non-adherence to recommended follow-up visits after an abnormal cytological finding is associated with poorer outcomes and higher health care costs. The purpose of this paper is to describe the challenges when examining reasons for non-adherence to cervical cancer screening follow-up and to discuss the recommendations to overcome those challenges. Methods: We conducted a telephone survey with two subgroups of women: 1) those which adhered to recommended follow-up care after an abnormal Pap test, and 2) those which did not adhere. Results: The follow-up accrual among non-adherent women lagged behind that of adherers. We were able to contact and conduct a survey with 51% of the adherers and 26% of the non-adherers. The challenges in studying non-adherent women were related to several distinct factors: 1) the definition of non-adherence, 2) the availability of alternate contact information, 3) the amount and type of financial incentives, and 4) the availability of staffing. We describe strategies employed to increase the accrual of non-adherent women. Discussion: This paper describes four recommendations that may play a role in understanding and reducing non-adherence to follow-up gynecological care.展开更多
Objective The aim of this study was to compare the long-term local control, overall survival, and late toxicities of positron emission tomography/computed tomography(PET/CT)-guided dose escalation radiotherapy versus ...Objective The aim of this study was to compare the long-term local control, overall survival, and late toxicities of positron emission tomography/computed tomography(PET/CT)-guided dose escalation radiotherapy versus conventional radiotherapy in the concurrent chemoradiotherapy treatment of locally advanced nasopharyngeal carcinoma(NPC).Methods A total of 48 patients with stage III–IVa NPC were recruited and randomly administered PET/CTguided dose escalation chemoradiotherapy(group A) or conventional chemoradiotherapy(group B). The dose-escalation radiotherapy was performed using the simultaneous modulated accelerated radiotherapy technique at prescribed doses of 77 gray(Gy) in 32 fractions(f) to the gross target volume(GTV): planning target volume(PTV) 1 received 64 Gy/32 f, while PTV2 received 54.4 Gy/32 f. Patients in group B received uniform-dose intensity-modulated radiotherapy, PTV1 received 70 Gy/35 f and PTV2 received 58 Gy/29 f. Concurrent chemotherapy consisted of cisplatin [20 mg/m2 intravenous(IV) on days 1–4] and docetaxel(75 mg/m2 IV on days 1 and 8) administered during treatment weeks 1 and 4. All patients received 2–4 cycles of adjuvant chemotherapy of the same dose and drug regimen.Results The use of fluorine-18-fluorodeoxyglucose(^(18)F-FDG) PET/CT significantly reduced the treatment volume delineation of the GTV in 83.3%(20/24) of patients. The 5-year local recurrence-free survival rates of the two groups were 100% and 79.2%, respectively(P = 0.019). The 5-year disease free survival(DFS) rates were 95.8% and 75.0%, respectively(P = 0.018). The 5-year local progression-free survival and DFS rates were significantly different. The 5-year overall survival(OS) rates were 95.8% and 79.2%, respectively. Differences in OS improvement were insignificant(P = 0.079). Late toxicities were similar in the two groups. The most common late toxicities of the two arms were grade 1–2 skin dystrophy, xerostomia, subcutaneous fibrosis, and hearing loss. There were no cases of grade 4 late toxicity.Conclusion The use of ^(18)F-FDG PET/CT-guided dose escalation radiotherapy is well tolerated and can reduce local recurrence rates for patients with locally advanced NPC compared to conventional chemoradiotherapy.展开更多
The treatment of metastatic renal cell carcinoma(RCC)and urothelial carcinoma(UC)remains a major challenge.Past research has implicated the immune system in tumor surveillance of both malignancies,leading to the appli...The treatment of metastatic renal cell carcinoma(RCC)and urothelial carcinoma(UC)remains a major challenge.Past research has implicated the immune system in tumor surveillance of both malignancies,leading to the application of immunotherapy agents for both cancers.Among them,the most promising agents are the checkpoint blockade drugs,such as antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),programmed death receptor 1(PD-1),and PD-1 ligand(PD-L1).In normal physiology,these immune checkpoints act as inhibitory signals to fine-tune the duration and strength of immune reactions,which is pivotal for maintaining self-tolerance.However,tumor cells also utilize immune checkpoint pathways to evade anti-tumor immune response,leading to disease progression and metastasis.Thus,there has been intense preclinical and clinical effort focused on the application of checkpoint inhibitors in metastatic RCC and UC.To date,nivolumab(anti-PD-1)and atezolizumab(anti-PD-L1)have been approved for the treatment of metastatic RCC and UC,respectively.Despite these successes,challenges remain in how to further improve response rates to immunotherapy and how to select patients that will benefit from this approach.In this report,we review existing data and research on immunotherapy in metastatic RCC and UC.展开更多
Background: States in the United States have primary public health authority. This is the case with cervical cancer, and yet little is known about state policy issues affecting the comprehensive public health response...Background: States in the United States have primary public health authority. This is the case with cervical cancer, and yet little is known about state policy issues affecting the comprehensive public health response. This study identifies and explores state policy issues affecting cervical cancer efforts in the United States. Methods: Key informant interviews were conducted with a purposeful sample of 15 professionals affiliated with cervical cancer prevention and treatment from national, state and local levels;across sectors: public, private and non-profit;and aspects of the work: screening, treatment and vaccine;program implementation, research, coalition work, and policy. Results: Identified policy issues were administrative and implementation oriented (“small p” policy issues). While participants recognized the importance of laws for vaccine or no cost screening access, the key policy issues preventing successful cervical cancer efforts involved 1) health system complexity;2) general lack of state level policy, program and funding coordination;and 3) social and organizational cultural issues affecting the adoption of national recommendations and reinforcing program inertia. Conclusions: Understanding state policy issues in cervical cancer is critical for public health success. Dramatic reduction or even elimination of cervical cancer in the United States depends upon the policy work in the “little p” policy areas such as planning and health system organization to affect change. This will require greater leadership and coordination of state efforts across myriad programs. It will require health system improvements, and also the adoption of new practice and program behaviors to capitalize on available technology to reach underserved women.展开更多
We searched for long period variation in V-band, It-band and RXTE X-ray light curves of the High Mass X-ray Binaries (HMXBs) LS 1698 / RX J1037.5-5647, HD 110432 / 1H 1249-637 and HD 161103 / RX J1744.7-2713 in an a...We searched for long period variation in V-band, It-band and RXTE X-ray light curves of the High Mass X-ray Binaries (HMXBs) LS 1698 / RX J1037.5-5647, HD 110432 / 1H 1249-637 and HD 161103 / RX J1744.7-2713 in an attempt to discover orbitally induced variation. Data were obtained primarily from the ASAS database and were supplemented by shorter term observations made with the 24- and 40-inch ANU telescopes and one of the robotic PROMPT telescopes. Fourier periodograms suggested the existence of long period variation in the V-band light curves of all three HMXBs, however folding the data at those periods did not reveal convincing periodic variation. At this point we cannot rule out the existence of long term V-band variation for these three sources and hints of longer term variation may be seen in the higher precision PROMPT data. Long term V-band observations, on the order of several years, taken at a frequency of at least once per week and with a precision of 0.01 mag, therefore still have a chance of revealing long term variation in these three HMXBs.展开更多
The Wnt/β-catenin signaling pathway appears to be particularly important for bone homeostasis,whereas nuclear accumulation ofβ-catenin requires the activation of Rac1,a member of the Rho small GTPase family.The aim ...The Wnt/β-catenin signaling pathway appears to be particularly important for bone homeostasis,whereas nuclear accumulation ofβ-catenin requires the activation of Rac1,a member of the Rho small GTPase family.The aim of the present study was to investigate the role of RhoA/Rho kinase(Rock)-mediated Wnt/β-catenin signaling in the regulation of aging-associated bone loss.We find that Lrp5/6-dependent and Lrp5/6-independent RhoA/Rock activation by Wnt3a activates Jak1/2 to directly phosphorylate Gsk3βat Tyr216,resulting in Gsk3βactivation and subsequentβ-catenin destabilization.In line with these molecular events,RhoA loss-or gain-of-function in mouse embryonic limb bud ectoderms interacts genetically with Dkk1 gain-of-function to rescue the severe limb truncation phenotypes or to phenocopy the deletion ofβ-catenin,respectively.Likewise,RhoA loss-of-function in pre-osteoblasts robustly increases bone formation while gain-of-function decreases it.Importantly,high RhoA/Rock activity closely correlates with Jak and Gsk3βactivities but inversely correlates withβ-catenin signaling activity in bone marrow mesenchymal stromal cells from elderly male humans and mice,whereas systemic inhibition of Rock therefore activates theβ-catenin signaling to antagonize aging-associated bone loss.Taken together,these results identify RhoA/Rock-dependent Gsk3βactivation and subsequentβ-catenin destabilization as a hitherto uncharacterized mechanism controlling limb outgrowth and bone homeostasis.展开更多
文摘目的:探讨中国社区糖尿病患者从家人或朋友获得直接支持和间接支持的现状,以及患者获得的直接支持与间接支持水平与其自我管理行为的相关关系。方法:研究对象的数据来自"北京市通州区社区诊断(2015)"专项调查,对符合要求的474名社区糖尿病患者进行问卷调查、体格检查和糖化血红蛋白(glycated hemoglobin,Hb A1c)测量。应用糖尿病自我管理行为量表(the summary of diabetes self-care activities measure,SDSCA)对自我管理行为进行测量,应用糖尿病直接支持和间接支持量表(directive and nondirective support scale among patients with diabetes,DNSS-PD)对直接支持和间接支持水平进行测量,分析患者获得的直接支持与间接支持水平与其自我管理行为的相关关系。结果:共有452名患者纳入分析,患者获得的直接支持实际情况平均得分为2.53±1.07,27.6%患者获得的直接支持水平较高。患者获得的间接支持实际情况平均得分为3.13±1.12,50.8%患者获得的间接支持水平较高。患者SDSCA平均总得分为35.38±14.21,得分率为45.95%,仅20.6%患者自我管理的总体情况较好。直接支持水平高组患者的SDSCA平均总得分、饮食和运动维度得分、自我管理总体情况、饮食和运动维度自我管理情况显著优于直接支持水平低组。间接支持水平高组患者的SDSCA平均总得分,饮食、运动、血糖监测、足部护理、吸烟维度得分,自我管理总体情况,饮食、运动、血糖监测、足部护理以及吸烟维度自我管理情况均显著优于间接支持水平低组。性别(OR=2.729)、间接支持水平(OR=4.890)、年龄(OR=0.969)和体质指数(body msss index,BMI)(OR=0.819)是自我管理行为的重要影响因素。结论:社区糖尿病患者的自我管理情况不太理想,患者获得的间接支持水平高于直接支持水平,但均有待提升。间接支持和间接支持水平高均与糖尿病患者较好的自我管理行为相关,间接支持水平高与5个维度较好的自我管理行为均相关,直接支持水平高与较好的饮食和运动维度的自我管理行为相关。应对于社区男性老年肥胖的糖尿病患者的自我管理给予更多的关注和支持,特别是间接支持。
文摘目的:探讨北京市通州区和顺义区747例2型糖尿病患者的生存质量现状及影响因素。方法:对纳入研究的747例2型糖尿病患者进行问卷调查和抽血实验室血生化检查。以糖化血红蛋白(hemoglobin A1c,HbA1c)作为血糖控制指标,以糖尿病患者特异性生存质量量表(diabetes specific quality of life scale,DSQL)评分为患者生存质量指标,采用多元线性回归和结构方程模型(structural equation modeling,SEM)分析生存质量的影响因素。结果:调查747例患者,HbA1c平均水平(7.1±1.2)%,血糖控制达标率为35.1%(262/747)。血糖控制好和血糖控制差两组患者的病程、服药和使用胰岛素、吸烟情况及体重指数(body mass index,BMI)差异有统计学意义(P<0.05)。DSQL总分为(44.92±13.32)分,生理维度条目平均分最高,其次是心理维度。多元线性回归结果显示,家庭月收入、并发症、抑郁、病程时间、胰岛素、住院及自我效能是DSQL总分的影响因素(P<0.05)。SEM结果显示,血糖对于生存质量的生理维度(标准化效应值为0.166)、心理维度(0.076)及社会维度(0.124)存在影响,抑郁对于生存质量的生理维度(0.342)、心理维度(0.217)及治疗维度(0.050)存在影响,差异有统计学意义(P<0.05)。结论:北京市通州区和顺义区2型糖尿病患者HbA1c控制水平欠佳,生存质量尚可,仍有非常大的提升空间。应提高对男性、病程长、处于不服药状态、不使用胰岛素、吸烟、处于抑郁状态、糖尿病技能得分水平低的患者的关注和管理,同时应在临床治疗中提高对患者心理需求的重视,加强对患者及其家属的心理健康教育,采取相应的心理干预措施,以达到有效控制血糖的目的,从而提高患者的生活质量。
基金supported by NIH RO1 (No. AI49427) to Dr David S.Rubenstein
文摘Post-translational protein modification, including phosphorylation, is generally quick and reversible, facilitating rapid biologic adjustments to altered cellular physiologic demands. In addition to protein phosphorylation, other post-translational modifications have been identified. Intracellular protein O-glycosylation, the addition of the simple sugar O-linked N-acetylglucosamine (O-G1cNAc) to serine/threonine residues, is a relatively recently identified post-translational modification that has added to the complexity by which protein function is regulated. Two intracellular enzymes, O-GlcNAc transferase and O-GlcNAcase, catalyze the addition and removal, respectively, of O-GlcNAc to serine and threonine side-chain hydroxyl groups. Numerous proteins, including enzymes, transcription factors, receptors and structural proteins have been shown to be modified by intracellular O-glycosylation. In this review, the mechanism and relevance of O-GlcNAc protein modification are discussed in the context of cell adhesion and several representative diseases.
文摘Purpose: Non-adherence to recommended follow-up visits after an abnormal cytological finding is associated with poorer outcomes and higher health care costs. The purpose of this paper is to describe the challenges when examining reasons for non-adherence to cervical cancer screening follow-up and to discuss the recommendations to overcome those challenges. Methods: We conducted a telephone survey with two subgroups of women: 1) those which adhered to recommended follow-up care after an abnormal Pap test, and 2) those which did not adhere. Results: The follow-up accrual among non-adherent women lagged behind that of adherers. We were able to contact and conduct a survey with 51% of the adherers and 26% of the non-adherers. The challenges in studying non-adherent women were related to several distinct factors: 1) the definition of non-adherence, 2) the availability of alternate contact information, 3) the amount and type of financial incentives, and 4) the availability of staffing. We describe strategies employed to increase the accrual of non-adherent women. Discussion: This paper describes four recommendations that may play a role in understanding and reducing non-adherence to follow-up gynecological care.
基金Supported by grants from the National Natural Science Foundation of China(No.81071831)Jiangsu Provincial Health Bureau issues(No.H201021)+1 种基金Xuzhou City Science and Technology Bureau issues(No.XF10C082)Jiangsu Province Natural Science Foundation of China(No.BK20131131)
文摘Objective The aim of this study was to compare the long-term local control, overall survival, and late toxicities of positron emission tomography/computed tomography(PET/CT)-guided dose escalation radiotherapy versus conventional radiotherapy in the concurrent chemoradiotherapy treatment of locally advanced nasopharyngeal carcinoma(NPC).Methods A total of 48 patients with stage III–IVa NPC were recruited and randomly administered PET/CTguided dose escalation chemoradiotherapy(group A) or conventional chemoradiotherapy(group B). The dose-escalation radiotherapy was performed using the simultaneous modulated accelerated radiotherapy technique at prescribed doses of 77 gray(Gy) in 32 fractions(f) to the gross target volume(GTV): planning target volume(PTV) 1 received 64 Gy/32 f, while PTV2 received 54.4 Gy/32 f. Patients in group B received uniform-dose intensity-modulated radiotherapy, PTV1 received 70 Gy/35 f and PTV2 received 58 Gy/29 f. Concurrent chemotherapy consisted of cisplatin [20 mg/m2 intravenous(IV) on days 1–4] and docetaxel(75 mg/m2 IV on days 1 and 8) administered during treatment weeks 1 and 4. All patients received 2–4 cycles of adjuvant chemotherapy of the same dose and drug regimen.Results The use of fluorine-18-fluorodeoxyglucose(^(18)F-FDG) PET/CT significantly reduced the treatment volume delineation of the GTV in 83.3%(20/24) of patients. The 5-year local recurrence-free survival rates of the two groups were 100% and 79.2%, respectively(P = 0.019). The 5-year disease free survival(DFS) rates were 95.8% and 75.0%, respectively(P = 0.018). The 5-year local progression-free survival and DFS rates were significantly different. The 5-year overall survival(OS) rates were 95.8% and 79.2%, respectively. Differences in OS improvement were insignificant(P = 0.079). Late toxicities were similar in the two groups. The most common late toxicities of the two arms were grade 1–2 skin dystrophy, xerostomia, subcutaneous fibrosis, and hearing loss. There were no cases of grade 4 late toxicity.Conclusion The use of ^(18)F-FDG PET/CT-guided dose escalation radiotherapy is well tolerated and can reduce local recurrence rates for patients with locally advanced NPC compared to conventional chemoradiotherapy.
文摘The treatment of metastatic renal cell carcinoma(RCC)and urothelial carcinoma(UC)remains a major challenge.Past research has implicated the immune system in tumor surveillance of both malignancies,leading to the application of immunotherapy agents for both cancers.Among them,the most promising agents are the checkpoint blockade drugs,such as antibodies targeting the cytotoxic T-lymphocyte-associated antigen 4(CTLA-4),programmed death receptor 1(PD-1),and PD-1 ligand(PD-L1).In normal physiology,these immune checkpoints act as inhibitory signals to fine-tune the duration and strength of immune reactions,which is pivotal for maintaining self-tolerance.However,tumor cells also utilize immune checkpoint pathways to evade anti-tumor immune response,leading to disease progression and metastasis.Thus,there has been intense preclinical and clinical effort focused on the application of checkpoint inhibitors in metastatic RCC and UC.To date,nivolumab(anti-PD-1)and atezolizumab(anti-PD-L1)have been approved for the treatment of metastatic RCC and UC,respectively.Despite these successes,challenges remain in how to further improve response rates to immunotherapy and how to select patients that will benefit from this approach.In this report,we review existing data and research on immunotherapy in metastatic RCC and UC.
文摘Background: States in the United States have primary public health authority. This is the case with cervical cancer, and yet little is known about state policy issues affecting the comprehensive public health response. This study identifies and explores state policy issues affecting cervical cancer efforts in the United States. Methods: Key informant interviews were conducted with a purposeful sample of 15 professionals affiliated with cervical cancer prevention and treatment from national, state and local levels;across sectors: public, private and non-profit;and aspects of the work: screening, treatment and vaccine;program implementation, research, coalition work, and policy. Results: Identified policy issues were administrative and implementation oriented (“small p” policy issues). While participants recognized the importance of laws for vaccine or no cost screening access, the key policy issues preventing successful cervical cancer efforts involved 1) health system complexity;2) general lack of state level policy, program and funding coordination;and 3) social and organizational cultural issues affecting the adoption of national recommendations and reinforcing program inertia. Conclusions: Understanding state policy issues in cervical cancer is critical for public health success. Dramatic reduction or even elimination of cervical cancer in the United States depends upon the policy work in the “little p” policy areas such as planning and health system organization to affect change. This will require greater leadership and coordination of state efforts across myriad programs. It will require health system improvements, and also the adoption of new practice and program behaviors to capitalize on available technology to reach underserved women.
文摘We searched for long period variation in V-band, It-band and RXTE X-ray light curves of the High Mass X-ray Binaries (HMXBs) LS 1698 / RX J1037.5-5647, HD 110432 / 1H 1249-637 and HD 161103 / RX J1744.7-2713 in an attempt to discover orbitally induced variation. Data were obtained primarily from the ASAS database and were supplemented by shorter term observations made with the 24- and 40-inch ANU telescopes and one of the robotic PROMPT telescopes. Fourier periodograms suggested the existence of long period variation in the V-band light curves of all three HMXBs, however folding the data at those periods did not reveal convincing periodic variation. At this point we cannot rule out the existence of long term V-band variation for these three sources and hints of longer term variation may be seen in the higher precision PROMPT data. Long term V-band observations, on the order of several years, taken at a frequency of at least once per week and with a precision of 0.01 mag, therefore still have a chance of revealing long term variation in these three HMXBs.
基金We are grateful to X. D. Xi, T. Wu, H. Hu, and Z. Z. Kang for helpful discussions, and P. Liu for technical help with western blot analysis. This work was supported by the National Natural Science Foundation of China (Nos. 20873122, 21222307, and 21003106), Fok Ying Tung Education Foundation (No. 131015), the Science & Technology Department of Zhejiang Province (Nos. 2008C11125 and R12B030002), and the Fundamental Research Funds for the Central Universities (No. 2014XZZX003-02).
基金This work was supported by 973 Program(No.2018YFC1004404)National Natural Science Foundation of China(Nos.31071292,31271561,31571493,81741043,31871395,and 31801207).
文摘The Wnt/β-catenin signaling pathway appears to be particularly important for bone homeostasis,whereas nuclear accumulation ofβ-catenin requires the activation of Rac1,a member of the Rho small GTPase family.The aim of the present study was to investigate the role of RhoA/Rho kinase(Rock)-mediated Wnt/β-catenin signaling in the regulation of aging-associated bone loss.We find that Lrp5/6-dependent and Lrp5/6-independent RhoA/Rock activation by Wnt3a activates Jak1/2 to directly phosphorylate Gsk3βat Tyr216,resulting in Gsk3βactivation and subsequentβ-catenin destabilization.In line with these molecular events,RhoA loss-or gain-of-function in mouse embryonic limb bud ectoderms interacts genetically with Dkk1 gain-of-function to rescue the severe limb truncation phenotypes or to phenocopy the deletion ofβ-catenin,respectively.Likewise,RhoA loss-of-function in pre-osteoblasts robustly increases bone formation while gain-of-function decreases it.Importantly,high RhoA/Rock activity closely correlates with Jak and Gsk3βactivities but inversely correlates withβ-catenin signaling activity in bone marrow mesenchymal stromal cells from elderly male humans and mice,whereas systemic inhibition of Rock therefore activates theβ-catenin signaling to antagonize aging-associated bone loss.Taken together,these results identify RhoA/Rock-dependent Gsk3βactivation and subsequentβ-catenin destabilization as a hitherto uncharacterized mechanism controlling limb outgrowth and bone homeostasis.