bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensin II receptor blockade reduces salt sensitivity of blood pressure through restoration of renal nitric oxide synthesis in patients with diabetic nephropathy
Authors: Imanishi Masahito , Okada Noriyuki , Konishi Yoshio , Morikawa Takashi , Maeda Isseki , Kitabayashi Chizuko , Masada Masahiro , Shirahashi Nobuo , Wilcox Christopher S , Nishiyama Akira 
Published: August 2012

Introduction: We have previously demonstrated the increased salt sensitivity of blood pressure (BP) in diabetic patients with early nephropathy. Here, we examined the effects of an angiotensin II receptor blocker (ARB) on salt sensitivity and renal oxidative stress or nitric oxide (NO) in those patients. Patients and methods: Type 2 diabetic patients with ( n = 6) and without ( n = 6) microalbuminuria were studied on a high-salt diet for one week and on a salt-restricted diet for one week. The study was repeated in the patients with microalbuminuria during treatment with an ARB, valsartan (80 mg/day). Salt sensitivity was assessed from the BP/sodium excretion curve. Urinary excretion rates of NOx, 8-hydroxy-2-deoxyguanosine as a marker of oxidative stress, and plasma tetrahydrobiopterin as a cofactor for NO synthase were measured. Results: Compared with diabetic patients without microalbuminuria, patients with microalbuminuria showed greater salt sensitivity and lower urinary excretion of NOx. In the patients with microalbuminuria, treatment with valsartan reduced salt sensitivity in association with increased NOx excretion, reduced 8-hydroxy-2,-deoxyguanosine excretion, and increased plasma tetrahydrobiopterin levels. Conclusions: These data support the hypothesis that ARBs reduce the salt sensitivity of BP by decreasing renal oxidative stress and restoring NO activity in diabetic patients with microalbuminuria.
An observational study of the effect of metformin on B12 status and peripheral neuropathy
Authors: Chen Shihong , Lansdown Andrew J , Moat Stuart J , Ellis Richard , Goringe Andrew , Dunstan Frank DJ , Rees J Alan E 
Published: August 2012

Aims Metformin is associated with lowering of vitamin B12 levels. We hypothesise that holotranscobalamin (holoTC) and methylmalonic acid (MMA) are more sensitive indicators of B12 deficiency in patients receiving metformin therapy, and that these correlate with declining peripheral neurological function. Methods Patients with type 2 diabetes were recruited and divided into those receiving metformin for greater than 6 months and a non-metformin group. Baseline characteristics were measured in both groups including vitamin B12, holoTC and MMA concentrations. Neurological function was assessed using neurothesiometry, monofilament, Neuropathy Total Symptom Score-6 questionnaire and the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs questionnaire. Results In total, 202 patients were recruited: 152 in the metformin group and 50 in the non-metformin group. Vitamin B12 levels were lower in the metformin group (219.1±105.4 ng/L, 281.4±95.1 ng/L, p<0.001). HoloTC was significantly lower in the metformin group (54.8±30.5 pmol/L, 70.1±26.0 pmol/L, p=0.002). No significant difference in serum MMA was observed between the two groups (0.40±0.26 μmol/L, 0.35±0.22, p=0.23). No significant difference in neurological function was observed between the groups. Conclusion Although metformin therapy is associated with lower vitamin B12 status there does not appear to be any significant effect on peripheral neuropathy in those receiving metformin. We do not recommend changing current practice to routinely monitor or replace patients receiving metformin with vitamin B12 unless clinically indicated.
Activated Gs signaling in osteoblastic cells alters the hematopoietic stem cell niche in mice
Authors: Schepers Koen , Hsiao Edward C. , Garg Trit , Scott Mark J. , Passegué Emmanuelle 
Published: August 2012

Abstract
Adult hematopoiesis occurs primarily in the BM space where hematopoietic cells interact with stromal niche cells. Despite this close association, little is known about the specific roles of osteoblastic lineage cells (OBCs) in maintaining hematopoietic stem cells (HSCs), and how conditions affecting bone formation influence HSC function. Here we use a transgenic mouse model with the ColI(2.3) promoter driving a ligand-independent, constitutively active 5HT4 serotonin receptor (Rs1) to address how the massive increase in trabecular bone formation resulting from increased Gs signaling in OBCs impacts HSC function and blood production. Rs1 mice display fibrous dysplasia, BM aplasia, progressive loss of HSC numbers, and impaired megakaryocyte/erythrocyte development with defective recovery after hematopoietic injury. These hematopoietic defects develop without compensatory extramedullary hematopoiesis, and the loss of HSCs occurs despite a paradoxical expansion of stromal niche cells with putative HSC-supportive activity (ie, endothelial, mesenchymal, and osteoblastic cells). However, Rs1-expressing OBCs show decreased expression of key HSC-supportive factors and impaired ability to maintain HSCs. Our findings indicate that long-term activation of Gs signaling in OBCs leads to contextual changes in the BM niche that adversely affect HSC maintenance and blood homeostasis.
Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos
Authors: Yang Ying , García-Verdugo José Manuel , Soriano-Navarro Mario , Srinivasan R. Sathish , Scallan Joshua P. , Singh Manvendra K. , Epstein Jonathan A. , Oliver Guillermo 
Published: August 2012

Abstract
The lymphatic vasculature preserves tissue fluid balance by absorbing fluid and macromolecules and transporting them to the blood vessels for circulation. The stepwise process leading to the formation of the mammalian lymphatic vasculature starts by the expression of the gene Prox1 in a subpopulation of blood endothelial cells (BECs) on the cardinal vein (CV) at approximately E9.5. These Prox1-expressing lymphatic endothelial cells (LECs) will exit the CV to form lymph sacs, primitive structures from which the entire lymphatic network is derived. Until now, no conclusive information was available regarding the cellular processes by which these LEC progenitors exit the CV without compromising the vein's integrity. We determined that LECs leave the CV by an active budding mechanism. During this process, LEC progenitors are interconnected by VE-cadherin–expressing junctions. Surprisingly, we also found that Prox1-expressing LEC progenitors were present not only in the CV but also in the intersomitic vessels (ISVs). Furthermore, as LEC progenitors bud from the CV and ISVs into the surrounding mesenchyme, they begin expressing the lymphatic marker podoplanin, migrate away from the CV, and form the lymph sacs. Analyzing this process in Prox1-null embryos revealed that Prox1 activity is necessary for LEC progenitors to exit the CV.
BRAFV600E mutant protein is expressed in cells of variable maturation in Langerhans cell histiocytosis
Authors: Sahm Felix , Capper David , Preusser Matthias , Meyer Jochen , Stenzinger Albrecht , Lasitschka Felix , Berghoff Anna-Sophie , Habel Antje , Schneider Marion , Kulozik Andreas , Anagnostopoulos Ioannis , Müllauer Leonhard , Mechtersheimer Gunhild , von Deimling Andreas 
Published: August 2012

AbstractLangerhans cell histiocytosis (LCH) is a clinically and histologically heterogeneous disorder. Its classification as either reactive inflammatory or neoplastic has been a matter of debate. However, the recent finding of frequent BRAFV600E mutations in LCH argues for the latter. The exact cell type that harbors the mutation and is responsible for proliferation remains to be identified. We here apply a BRAFV600E mutation-specific antibody to detect the BRAF mutant cells in lesions from 89 patients with LCH. We found BRAFV600E mutations in 34 of 89 (38%) lesions. In lesions with the BRAFV600E mutation, the majority of cells coexpressing S-100 and CD1a harbored mutant BRAFV600E protein. These cells also expressed CD14 and CD36, whereas various fractions exhibited CD207. On the other hand, CD80 and CD86 expression was also present on BRAFV600E-positive cells. Thus, cells of variable maturation, exhibiting an immunohistochemical profile compatible either with myeloid cell or with dedifferentiated Langerhans cell antigens, carry the BRAFV600E mutation. In conclusion, we identify and characterize the neoplastic cells in LCH with BRAFV600E mutations by applying a mutation-specific marker and demonstrate feasibility for routine screening.
The role of the mycobacterial DNA-binding protein 1 (MDP1) from Mycobacterium bovis BCG in host cell interaction
Authors: Kunisch Ralph , Kamal Elisabeth , Lewin Astrid 
Published: August 2012

AbstractBackgroundMycobacterium tuberculosisdiffers from most pathogens in its ability to multiply inside monocytes and to persist during long periods of time within granuloma in a status of latency. A class of proteins called mycobacterial histone-like proteins has been associated with regulation of replication and latency, but their precise role in the infection process has yet to be uncovered. Our study aimed at defining the impact of the histone-like protein MDP1 fromM. bovisBCG (mycobacterial DNA-binding protein 1, corresponding to Rv2986c fromM. tuberculosis) on early steps of infection.ResultsPreviously, a BCG (Bacillus Calmette Guérin) strain had been generated by antisense-technique exhibiting reduced MDP1 expression. This strain was now used to analyse the impact of reduced amount of MDP1 on the interaction with human blood monocytes, macrophage lines and PBMC (peripheral blood mononuclear cells). MDP1 was revealed to be required for growth at acidic pH and for intracellular replication in human blood monocytes. Down-regulation of MDP1 resulted in reduced secretion of the cytokine IL-1β by infected human PBMC. In addition, a reduction of MDP1 expression had a major impact on the formation of fused multi-nucleated macrophages. In monocyte preparations from human blood as well as in human and mouse macrophage cell lines, both the percentage of multi-nucleated cells and the number of nuclei per cell were much enhanced when the monocytes were infected with BCG expressing less MDP1.ConclusionMDP1 fromM. bovisBCG affects the growth at acidic pH and the intracellular replication in human monocytes. It furthermore affects cytokine secretion by host cells, and the formation of fused multi-nucleated macrophages. Our results suggest an important role of MDP1 in persistent infection.
Health-related quality of life and all-cause mortality in patients with diabetes on dialysis
Authors: Østhus Tone Britt Hortemo , von der Lippe Nanna , Ribu Lis , Rustøen Tone , Leivestad Torbjørn , Dammen Toril , Os Ingrid 
Published: August 2012

Abstract

Background
This study tests the hypotheses that health-related quality of life (HRQOL) in prevalent dialysis patients with diabetes is lower than in dialysis patients without diabetes, and is at least as poor as diabetic patients with another severe complication, i.e. foot ulcers. This study also explores the mortality risk associated with diabetes in dialysis patients.

Methods
HRQOL was assessed using the Short Form-36 Health Survey (SF-36), in a cross-sectional study of 301 prevalent dialysis patients (26% with diabetes), and compared with diabetic patients not on dialysis (n = 221), diabetic patients with foot ulcers (n = 127), and a sample of the general population (n = 5903). Mortality risk was assessed using a Kaplan-Meier plot and Cox proportional hazards analysis.

Results
Self-assessed vitality, general and mental health, and physical function were significantly lower in dialysis patients with diabetes than in those without. Vitality (p = 0.011) and general health (p <0.001) was impaired in diabetic patients receiving dialysis compared to diabetic patients with foot ulcers, but other subscales did not differ. Diabetes was a significant predictor for mortality in dialysis patients, with a hazard ratio (HR) of 1.6 (95% CI 1.0-2.5) after adjustment for age, dialysis vintage and coronary artery disease. Mental aspects of HRQOL were an independent predictor of mortality in diabetic patients receiving dialysis after adjusting for age and dialysis vintage (HR 2.2, 95% CI 1.0-5.0).

Conclusions
Physical aspects of HRQOL were perceived very low in dialysis patients with diabetes, and lower than in other dialysis patients and diabetic patients without dialysis. Mental aspects predicted mortality in dialysis patients with diabetes. Increased awareness and measures to assist physical function impairment may be particularly important in diabetes patients on dialysis.
Oxidative stress markers are associated to vascular recurrence in non-cardioembolic stroke patients non-treated with statins
Authors: Brea David , Roquer Jaume , Serena Joaquín , Segura Tomás , Castillo José 
Published: August 2012

Abstract

Background
Since atherogenesis is related to oxidative stress, our objective was to study the association of oxidative stress markers with the vascular recurrence in non-cardioembolic stroke.

Methods
Atherosclerotic and oxidative stress markers were evaluated on admission, in 477 patients suffering from a first non-cardioembolic stroke. Patients were followed at 6 and 12 months after inclusion, recording cardiovascular events. As markers of endothelial oxidative stress we used oxidized LDL, Cu/Zn superoxide dismutase and 8-OH deoxiguanosine. 136 patients were being treated with statins at the moment of serum samples acquisition.

Results
Patients who suffered vascular recurrence or vascular-origin death had higher levels of 8-OHDG (40.06±24.70vs33.11±15.18;p=0.003). We also found associations between vascular recurrence or vascular origin death and Cu/ZnSOD (OR,1.02; 95%CI,1.00-1.03;p=0.0001) and 8-OHDG (OR,1.12;95%CI,1.08-1.16;p<0.0001) in a subgroup of 333 patients that were not in treatment with statins on admission. We also found associations between 8-OHDG and intima media thickness (IMT) (OR,1.13;95%CI,1.09-1.16;p<0.0001), presence of ipsilatieral stenosis≥50% (OR,1.03;95%CI1.00-1.05;p=0.007) and other atherosclerotic plaque characteristics.

Conclusions
Specific oxidative stress markers were found to be markers of atherosclerosis plaque types and vascular recurrence in non-statins treated patients at admission.
Prognostic factors for different outcomes in patients with metastatic spinal cord compression from cancer of unknown primary
Authors: Douglas Sarah , Huttenlocher Stefan , Bajrovic Amira , Rudat Volker , Schild Steven E , Rades Dirk 
Published: August 2012

Abstract

Background
Patients with cancer of unknown primary account for 10% of patients with metastatic spinal cord compression (MSCC). This retrospective study was performed to identify prognostic factors for functional outcome, local control of MSCC, and survival in 175 of such patients treated with radiotherapy alone.

Methods
Investigated were nine potential prognostic factors including age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), number of involved vertebrae, pre-radiotherapy ambulatory status, other bone metastases, visceral metastases, time developing motor deficits before radiotherapy, and the radiation schedule.

Results
On multivariate analysis, better functional outcome was associated with absence of visceral metastases (estimate: 0.72; 95%-confidence interval [CI]: 0.07-1.36; p = 0.030) and a slower (>7 days) development of motor deficits (estimate: 1.93; 95%-CI: 1.18-2.68; p < 0.001). Improved local control of MSCC was associated with absence of visceral metastases (risk ratio [RR]: 10.26; 95%-CI: 2.11-74.73; p = 0.004). Improved survival was associated with favorable ECOG-PS (RR: 2.12; 95%-CI: 1.40-3.29; p < 0.001), being ambulatory prior to radiotherapy (RR: 1.98; 95%-CI: 1.40-2.81; p < 0.001), absence of visceral metastases (RR: 2.74; 95%-CI: 1.93-3.91; p < 0.001), and slower development of motor deficits (RR: 1.27; 95%-CI: 1.07-1.51; p = 0.007). Absence of other bone metastases showed a trend (RR: 1.38; 95%-CI: 0.98-1.95; p = 0.07).

Conclusions
This study identified additional independent prognostic factors for functional outcome, local control of MSCC, and survival after radiotherapy of MSCC from cancer of unknown primary. These prognostic factors can help select the best treatment regimen for each individual patient.
Effect of the pringle maneuver on tumor recurrence of hepatocellular carcinoma after curative resection (EPTRH): a randomized, prospective, controlled multicenter trial
Authors: Xiaobin Feng , Shuguo Zheng , Jian Zhou , Yudong Qiu , Lijian Liang , Kuansheng Ma , Xiaowu Li , Feng Xia , Dong Yi , Shuguang Wang , Ping Bie , Jiahong Dong 
Published: August 2012

Abstract

Background
Hepatic resection is currently still the best choice of therapeutic strategies for liver cancer, but the long-term survival rate after surgery is unsatisfactory. Most patients develop intra- and/or extrahepatic recurrence. The reasons for this high recurrence rate are not entirely clear. Recent studies have indicated that ischemia-reperfusion injury to the liver may be a significant factor promoting tumor recurrence and metastasis in animal models. If this is also true in humans, the effects of the Pringle maneuver, which has been widely used in hepatectomy for the past century, should be examined. To date, there are no reported data or randomized controlled studies examining the relationship between use of the Pringle maneuver and local tumor recurrence. We hypothesize that the long-term prognosis of patients with liver cancer could be worsened by use of the Pringle maneuver due to an increase in the rate of tumor recurrence in the liver remnant. We designed a multicenter, prospective, randomized surgical trial to test this hypothesis.

Methods
At least 498 eligible patients from five participating centers will be enrolled and randomized into either the Pringle group or the non-Pringle group in a ratio of 1:1 using a permuted-blocks randomization protocol. After the completion of surgical intervention, patients will be included in a 3-year follow-up program.

Discussion
This multicenter surgical trial will examine whether the Pringle maneuver has a negative effect on the long-term outcome of hepatocellular carcinoma patients. The trial will also provide information about prognostic differences, safety, advantages and disadvantages between Pringle and non-Pringle surgical procedures. Ultimately, the results will increase the available information about the effects of ischemia-reperfusion injury on tumor recurrence, which will be of immense benefit to general surgery.

Trial registration

http://www.clinicaltrials.gov NCT00725335
Social, psychological, and environmental-structural factors determine consistent condom use among rural-to-urban migrant female sex workers in Shanghai China
Authors: Ye Xiuxia , Shang Meili , Shen Tian , Pei Bei , Jiang Xueqin , Cai Yong 
Published: August 2012

Abstract

Background
To determine potential social, psychological, and environmental-structural factors that may result in motivating female sex workers (FSWs), who are rural-to-urban migrants, and their paying partners in Shanghai, China to promote consistent condom use (CCU).

Methods
A cross-sectional study was conducted in five districts of Shanghai, including three suburbs and two downtown locales. We adopted a cluster randomized sampling method to obtain 20 geographic sites, which consisted of 1 or more communities/villages proximal to a location where FSWs were accessible. Five hundred four FSWs from 132 Xitou Fang (shampoo wash rooms), massage parlors, and hair salons who explicitly provided sexual services were enrolled in the study. Each participant completed a questionnaire survey and interview aimed to collect information on the perceptions and behaviors of individuals associated with a risk for human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/AIDS),self-efficacy at negotiating safe sex,and the physical, social, and policy environment of the establishments where they worked.

Results
The percentage of FSWs who reported consistent condom use with their paying partners was 63.3%. Controlling for socio-demographic characteristics in multivariate analyses, environmental-structural support (OR, 3.96; CI, 2.52–6.22) for condom use was the most significant positive predictor of CCU among FSWs and their regular paying partners. A high perception of susceptibility and risk of HIV/AIDS (OR, 1.96; CI, 1.25–3.01), a high perception of benefits on condom use to protect themselves (OR, 2.06; CI, 1.32–3.22), and high safe sex self-efficacy (OR, 2.52; CI, 1.64–3.85) also play important roles on CCU based on multivariate analyses.

Conclusions
Environmental-structural factor support for condom use, in addition to social, psychological, and individual cognitive factors are significant predictors of CCU among FSWs, which should be assessed and addressed in research and interventions related to HIV/AIDS prevention among FSWs in China.
Perinatal and early life factors associated with symptoms of depression in Brazilian children
Authors: Pereira Thaís S , Silva Antônio A , Alves Maria T , Simões Vanda M , Batista Rosângela F , Rodriguez Juliana D , Figueiredo Felipe P , Lamy-Filho Fernando , Barbieri Marco A , Bettiol Heloisa 
Published: August 2012

Abstract

Background
Few studies have been conducted on the association between perinatal and early life factors with childhood depression and results are conflicting. Our aim was to estimate the prevalence and perinatal and early life factors associated with symptoms of depression in children aged 7 to 11 years from two Brazilian birth cohorts.

Methods
The study was conducted on 1444 children whose data were collected at birth and at school age, in 1994 and 2004/2005 in Ribeirao Preto, where they were aged 10–11 years and in 1997/98 and 2005/06 in São Luís, where children were aged 7–9 years. Depressive symptoms were investigated with the Child Depression Inventory(CDI), categorized as yes (score ≥ 20) and no (score < 20). Adjusted and non-adjusted prevalence ratios (PR) were estimated by Poisson regression with robust estimation of the standard errors.

Results
The prevalence of depressive symptoms was 3.9% (95%CI = 2.5-5.4) in Ribeirão Preto and 13.7% (95%CI = 11.0-16.4) in São Luís. In the adjusted analysis, in Ribeirão Preto, low birth weight (PR = 3.98; 95%CI = 1.72-9.23), skilled and semi-skilled manual occupation (PR = 5.30; 95%CI = 1.14-24.76) and unskilled manual occupation and unemployment (PR = 6.65; 95%CI = 1.16-38.03) of the household head were risk factors for depressive symptoms. In São Luís, maternal schooling of 0–4 years (PR = 2.39; 95%CI = 1.31-4.34) and of 5 to 8 years (PR = 1.80; 95%CI = 1.08-3.01), and paternal age <20 years (PR = 1.92; 95%CI = 1.02-3.61), were independent risk factors for depressive symptoms.

Conclusions
The prevalence of depressive symptoms was much higher in the less developed city, São Luís, than in the more developed city, Ribeirão Preto, and than those reported in several international studies. Low socioeconomic level was associated with depressive symptoms in both cohorts. Low paternal age was a risk factor for depressive symptoms in the less developed city, São Luís, whereas low birth weight was a risk factor for depressive symptoms in the more developed city, Ribeirão Preto.