In-depth unveiling the interfacial adsorption mechanism of triazine derivatives as corrosion inhibitors for carbon steel in carbon dioxide saturated oilfield produced water.

In this work, two triazine derivatives (BTT-1 and BTT-2) were synthesized by the simple one-step condensation of three components and used as high-efficient corrosion inhibitors to deal with the corrosion issue of carbon steel (CS) in petroleum industry. Electrochemical tests indicate that both BTT-1 and BTT-2 present superior inhibition performance with the inhibition efficiency of 97.9 % and 98.4 % at a low concentration of 0.18 mM, respectively. Quantum chemical calculations reveal that compared to BTT-1 molecule with a butyl chain, the introduction of benzyl group endows BTT-2 molecule with more adsorption sites, which favors the adsorption of BTT-2 molecule on CS surface. Furthermore, the GFN-xTB calculations demonstrate that BTT-1 and BTT-2 could adsorb on CS surface through the formation of Fe-N and Fe-S bonds. Compared to BTT-1, BTT-2 exhibits stronger adsorption on CS surface by forming more and shorter bonds with a more negative adsorption energy, which accounts for the better inhibitive performance of BTT-2.

[Spatio-temporal distribution of pulmonary tuberculosis and influencing factors in Beijing, 2008-2018].

Objective: To understand the spatiotemporal distribution of pulmonary tuberculosis (TB) and influencing factors in Beijing from 2008 to 2018. Methods: The incidence data of pulmonary TB in Beijing from 2008 to 2018 were from Tuberculosis Information Management System of Chinese Disease Prevention and Control Information System. Software ArcGIS 10.2 was used to visualize the spatiotemporal distribution of pulmonary TB incidence. Getis's Gi* statistic was applied to analyze the spatial clustering of pulmonary TB incidence at street/township scale. Bayesian spatiotemporal model was applied to analyze factors affecting its spatiotemporal distribution, including urbanization rate, GDP per capita, number of hospital beds per thousand population, permanent migrant population and population density. Results: The reported pulmonary TB incidence showed a downward trend in the past 11 years in Beijing, from 58.64/100 000 to 30.43/100 000. The incidences were higher in Tongzhou, Changping and other newly developed urban districts, with the hot spots concentrated in local areas of these districts. The incidences of pulmonary TB were lower in Dongcheng, Xicheng and other old urban districts-with the cold spots also concentrated in these area. The risk for the incidence of pulmonary TB was associated with the urbanization rate and the permanent migrant population. For every 1% increase in the urbanization rate, the relative risk of pulmonary TB would increase by 1%. For every 10 000 person increase of permanent migrant population, the relative risk of pulmonary TB would increase by 0.6%. Conclusions: In Beijing, the current pulmonary TB prevention and control needs to be focused on the newly developed urban areas. Due to the accelerated process of urbanization, it is necessary to strengthen TB prevention and control in permanent migrant population to reduce the incidence of TB in Beijing.

[The diagnostic value of whole blood Epstein-Barr virus DNA load in lymphoproliferative diseases after allogeneic hematopoietic stem cell transplantation].

Objectives: To investigate the diagnostic value of whole blood quantitative PCR for DNA load of Epstein-Barr virus (EBV) in post-transplant lymphoproliferative disease (PTLD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: A total of 694 patients with hematologic diseases who underwent allo-HSCT at the Hematology Department of Peking University First Hospital from April 2004 to April 2019 were included, and their data were retrospectively analyzed. Results: ①Among the 694 cases, 29 cases (22 males and 7 females, with a median age of 22 (1-52) years) developed PTLD after allo-HSCT with a cumulative incidence of 4.2% and a median onset time of 2.1 (0.8-20.6) months. ② Univariate analysis showed that age<30 years, diagnosis with aplastic anemia, human leukocyte antigen (HLA) mismatch, use of antithymocyte globulin (ATG) in preconditioning regimens, and EBV reactivation were the risk factors for the occurrence of PTLD. Multivariate analysis showed that EBV reactivation was an independent risk factor for the occurrence of PTLD. ③Further analysis of EBV reactivation cases showed that the peak value of EBV-DNA load was significantly higher in the PTLD group than that in the non-PTLD group (P<0.001) and the incidence of PTLD increased with the increase of EBV-DNA load. Receiver operating characteristic (ROC) curve analysis indicated that PTLD was more likely to be diagnosed when the EBV-DNA load was >1.19×10(6) copies/ml (sensitivity 0.800 and specificity 0.768) . ④All patients with PTLD received rituximab-based treatment, with an overall response rate of 86.2% and an overall survival rate of 54.3%. Conclusion: The PTLD occurrence after allo-HSCT is highly correlated with EBV reactivation, and the higher the EBV-DNA load, the greater the risk of PTLD occurrence. The dynamic monitoring of EBV-DNA load plays an important role in predicting PTLD occurrence.

LncRNA NEAT1 regulates proliferation, apoptosis and invasion of liver cancer.

OBJECTIVE: The occurrence and progression of hepatocellular carcinoma (HCC) is a multi-step complex process and the exact molecular mechanisms remain to be elucidated. LncRNA NEAT1 is involved in tumorigenesis and progression. However, the role of LncRNA NEAT1 in HCC remains unclear. PATIENTS AND METHODS: The tumor tissues and adjacent tissues of HCC patients were collected and LncRNA NEAT1 expression was detected by Real time PCR. The hepatoma cell line HepG2 was cultured and transfected with lnc RNA NEAT1 siRNA or lnc RNA NEAT1 plasmid followed by analysis of LncRNA NEAT1 expression, cell proliferation by MTT assay, as well as Caspase 3 activity. In addition, cell apoptosis and cell cycle were assessed by flow cytometry and cell invasion was measured by transwell chambers. The expression of EGFR, Bax and Bcl-2 was detected by Western blot. RESULTS: LncRNA NEAT1 expression was significantly increased in HCC tissues compared with adjacent tissues (p < 0.05). Compared with the siRNA group, transfection of lncRNA NEAT1 siRNA into HepG2 cells significantly inhibited cell proliferation, increased Caspase 3 activity and apoptosis, reduced cell invasion, as well as arrested cell cycle (p < 0.05). Meanwhile, lncRNA NEAT1 siRNA also significantly decreased Bcl-2 and EGFR expression and increased Bax expression (p < 0.05). Transfection of lncRNA NEAT1 plasmid in hepatoma cells HepG2 reversed the above changes, compared with vector group, the differences were statistically significant (p < 0.05). CONCLUSIONS: LncRNA NEAT1 expression is increased in liver cancer tissues. Down-regulation of LncRNA NEAT1 can inhibit EGFR expression and promote hepatoma cell apoptosis, inhibit cell cycle, thus inhibiting tumor proliferation and invasion.

[Clinical outcome of allogeneic hematopoietic stem cell transplantation with FLAG sequential busulfan/cyclophosphamide conditioning regimen for refractory/relapsed acute myeloid leukemia].

Objective: To investigate the therapeutic effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with FLAG sequential busulfan/cyclophosphamide(Bu/Cy) conditioning regimen for refractory/relapsed acute myeloid leukemia. Methods: From February 2012 to June 2017, 21 patients with refractory/relapsed acute myeloid leukemia underwent allo-HSCT with FLAG sequential Bu/Cy conditioning regimen. Transplantation-related complications and clinical outcome were retrospectively analyzed. Results: After conditioning, no hepatic veno-occlusive disease (VOD) and grade Ⅲ hemorrhagic cystitis occurred. 76.2% (16/21) patients had fever with 4 septicemia. One patient died of septic shock before engraftment. Twenty patients achieved neutrophil engraftment with a median time of 13 days (range, 10 to 21 days). Seventeen patients achieved platelet engraftment with a median time of 18 days (range, 9 to 25 days). The cumulative incidence of acute graft-versus-host disease (aGVHD) was 39.5%, and 3 patients developed grade Ⅲ-Ⅳ aGVHD. Of 19 patients who survived more than 100 days after transplantation, 4 had local chronic graft-versus-host disease (cGVHD). Of 21 patients, the median survival time was 15 months (range, 0.5 to 67 months) post-transplantation. Transplantation-related mortality rate was 28.7%. Leukemia relapse occurred in 4 patients with a median time of 4 months (range, 3 to 8 months) after transplantation. The cumulative relapse rate at 1 year was 21.4%. The 1-year and 3-year overall survival (OS) rates were 60.7% and 54.9% respectively. Log-rank analysis revealed that bone marrow blasts ≥ 20% or extramedullary leukemia before transplantation, poor platelet engraftment and grade Ⅲ-Ⅳ aGVHD were significantly related to shortened OS (P<0.05). Conclusions: Allo-HSCT with FLAG sequential Bu/Cy conditioning regimen in patients with refractory/relapsed myeloid leukemia has acceptable transplantation-related risk and relapse rate. The 1-year and 3-year OS rates are comparable with those in remission patients.

[A preliminary study on the outcome of lower-risk myelodysplastic syndrome by low-dose decitabine].

Objective: To assess the efficiency and safety of low-dose decitabine in patients with lower-risk myelodysplastic syndrome (MDS) to couple with the clinical significance of MDS-related gene mutations. Methods: This study was done in 4 institutions in Zhejiang Province. A total of 62 newly diagnosed patients with lower-risk MDS were assigned to two groups of decitabine (12 mg·m(-2)·d(-1) for 5 consecutive days) and best supportive care (BSC) . Their bone marrow samples were subject to examinations of MDS-related 15 gene mutations. The primary endpoints were the proportion of patients who achieved overall response (ORR) after at least two cycles and progression-free survival (PFS) , and their relevances to the gene mutations. Results: Of 62 enrolled patients, and 51 cases were included in the final analysis. 16 of 24 patients (66.7%) in decitabine group achieved ORR versus 8 of 27 (29.6%) in BSC group (χ(2)=6.996, P=0.008) ; PFS prolongation of decitabine versus BSC was statistically significant (not reached vs 13.7 months, P=0.037) . Among 51 patients, at least one gene mutation was identified in 20 patients (39.2%) , including 4 single SF3B1 mutation. PFS in cases with gene mutations (not including single SF3B1 mutation) was significantly shorter than of no gene mutation (9.2 months vs 18.5 months, P=0.008) , but not for ORR (37.5% vs 58.1%, P=0.181) . Among 16 patients with mutated genes, ORR in decitabine and BSC groups were 75% (6/8) and 0 (0/8) , respectively. The most adverse events in decitabine group were grade 3 to 4 neutropenia (45.8%) and grade 3 to 4 infections (33.3%) . Conclusion: This preliminary study showed that low-dose decitabine produced promising results with an acceptable safety in lower-risk MDS patients, especially for those with mutated genes. Further study targeting poor prognostic lower-risk MDS patients should be warranted.

Quantitative analysis of U251MG human glioma cells invasion in organotypic brain slice co-cultures.

OBJECTIVE: To develop an in vitro model under conditions that highly resemble the in vivo situation for searching new therapeutics targeting invasive glioma cells. MATERIALS AND METHODS: We generated organotypic brain slice "co-cultures" (OBSC) from mice and cultured the models on Millicell-CM membrane inserts. U251MG glioma cells expressing enhanced green fluorescent protein (EGFP) were established. After cultured the glioma cells to form spheroids, we implanted the spheroids onto brain slice surface. Then we evaluated the invasion area and cell density after U251MG cells were treated with the Na+-K+-2Cl- cotransporter 1 (NKCC1) inhibitor bumetanide by confocal laser microscopy. RESULTS: In the models, the organotypic morphology and neuronal viability were well preserved. The confocal results showed that the cell spheroid area and density of U251MG cells in bumetanide group were decreased compared to the control group in brain slices. Meanwhile, the phospho-NKCC1(p-NKCC1) protein level of U251MG cells in bumetanide-treated group was also lower than the control group. CONCLUSIONS: The OBSC model is a reliable and easy-to-perform in vitro method to quantify the glioma invasion ability.

Opening the band gap of graphene through silicon doping for the improved performance of graphene/GaAs heterojunction solar cells.

Graphene has attracted increasing interest due to its remarkable properties. However, the zero band gap of monolayered graphene limits it's further electronic and optoelectronic applications. Herein, we have synthesized monolayered silicon-doped graphene (SiG) with large surface area using a chemical vapor deposition method. Raman and X-ray photoelectron spectroscopy measurements demonstrate that the silicon atoms are doped into graphene lattice at a doping level of 2.7-4.5 at%. Electrical measurements based on a field effect transistor indicate that the band gap of graphene has been opened via silicon doping without a clear degradation in carrier mobility, and the work function of SiG, deduced from ultraviolet photoelectron spectroscopy, was 0.13-0.25 eV larger than that of graphene. Moreover, when compared with the graphene/GaAs heterostructure, SiG/GaAs exhibits an enhanced performance. The performance of 3.4% silicon doped SiG/GaAs solar cell has been improved by 33.7% on average, which was attributed to the increased barrier height and improved interface quality. Our results suggest that silicon doping can effectively engineer the band gap of monolayered graphene and SiG has great potential in optoelectronic device applications.

Study of optimal scheme of spinal image-guided radiotherapy based on expression of caspase-3 in spinal cord neurons by orthogonal design.

The aim of the study was to optimize the biological safety scheme of spinal image-guided radiotherapy (IGRT) by determining the expression of caspase-3 in spinal cord neurons after IGRT. Thirty-six adult male beagles were assigned according to a random number table and subjected to IGRT to the 7th-12th canine thoracic vertebral bodies under a total dose of 80 Gy over 5 weeks. An immunohistochemical method was used to detect the expression of caspase-3 protein in spinal cord tissues, and real-time quantitative RT-PCR with SYBR Green I was used to detect the expression of caspase-3 mRNA in spinal cord tissues. Analysis of the orthogonal experiment results showed that caspase-3 expression in the spinal cord neurons was lowest when a single dose of 16 Gy was applied at a dose rate of 4 Gy/min, and field number of 9, with ray angle being equal. Thus, spinal IGRT showed high biological safety, and the best radiotherapy scheme for biological safety was single dose of 16 Gy at 4 Gy/min, with 9 fields and equal ray angle.

Sequence variations in the FAD2 gene in seeded pumpkins.

Seeded pumpkins are important economic crops; the seeds contain various unsaturated fatty acids, such as oleic acid and linoleic acid, which are crucial for human and animal nutrition. The fatty acid desaturase-2 (FAD2) gene encodes delta-12 desaturase, which converts oleic acid to linoleic acid. However, little is known about sequence variations in FAD2 in seeded pumpkins. Twenty-seven FAD2 clones from 27 accessions of Cucurbita moschata, Cucurbita maxima, Cucurbita pepo, and Cucurbita ficifolia were obtained (totally 1152 bp; a single gene without introns). More than 90% nucleotide identities were detected among the 27 FAD2 clones. Nucleotide substitution, rather than nucleotide insertion and deletion, led to sequence polymorphism in the 27 FAD2 clones. Furthermore, the 27 FAD2 selected clones all encoded the FAD2 enzyme (delta-12 desaturase) with amino acid sequence identities from 91.7 to 100% for 384 amino acids. The same main-function domain between 47 and 329 amino acids was identified. The four species clustered separately based on differences in the sequences that were identified using the unweighted pair group method with arithmetic mean. Geographic origin and species were found to be closely related to sequence variation in FAD2.

Involvement of miR-30c in resistance to doxorubicin by regulating YWHAZ in breast cancer cells.

MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated in cancer, which play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. The aim of this study was to investigate whether miR-30c mediated the resistance of breast cancer cells to the chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c was downregulated in the doxorubicin-resistant human breast cancer cell lines MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, we observed that transfection of an miR-30c mimic significantly suppressed the ability of MCF-7/ADR to resist doxorubicin. Moreover, the anti-apoptotic gene YWHAZ was confirmed as a target of miR-30c by luciferase reporter assay, and further studies indicated that the mechanism for miR-30c on the sensitivity of breast cancer cells involved YWHAZ and its downstream p38 mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings provided evidence that miR-30c was one of the important miRNAs in doxorubicin resistance by regulating YWHAZ in the breast cancer cell line MCF-7/ADR.

Involvement of miR-30c in resistance to doxorubicin by regulating YWHAZ in breast cancer cells

MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression implicated in cancer, which play crucial roles in diverse biological processes, such as development, differentiation, apoptosis, and proliferation. The aim of this study was to investigate whether miR-30c mediated the resistance of breast cancer cells to the chemotherapeutic agent doxorubicin (ADR) by targeting tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ). miR-30c was downregulated in the doxorubicin-resistant human breast cancer cell lines MCF-7/ADR and MDA-MB-231/ADR compared with their parental MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, we observed that transfection of an miR-30c mimic significantly suppressed the ability of MCF-7/ADR to resist doxorubicin. Moreover, the anti-apoptotic gene YWHAZ was confirmed as a target of miR-30c by luciferase reporter assay, and further studies indicated that the mechanism for miR-30c on the sensitivity of breast cancer cells involved YWHAZ and its downstream p38 mitogen-activated protein kinase (p38MAPK) pathway. Together, our findings provided evidence that miR-30c was one of the important miRNAs in doxorubicin resistance by regulating YWHAZ in the breast cancer cell line MCF-7/ADR.

Neuromuscular interfacing: a novel approach to EMG-driven multiple DOF physiological models.

This paper presents a novel approach that involves first identifying and verifying the available superficial muscles that can be recorded by surface electromyography (EMG) signals, and then developing a musculoskeletal model based on these findings, which have specifically independent DOFs for movement. Such independently controlled multiple DOF EMG-driven models have not been previously developed and a two DOF model for the masticatory system was achieved by implementing independent antagonist muscle combinations for vertical and lateral movements of the jaw. The model has six channels of EMG signals from the bilateral temporalis, masseter and digastric muscles to predict the motion of the mandible. This can be used in a neuromuscular interface to manipulate a jaw exoskeleton for rehabilitation. For a range of different complexities of jaw movements, the presented model is able to consistently identify movements with 0.28 - 0.46 average normalized RMSE. The results demonstrate the feasibility of the approach at determining complex multiple DOF movements and its applicability to any joint system.

Methylenetetrahydrofolate reductase genotypes and haplotypes associated with susceptibility to colorectal cancer in an eastern Chinese Han population.

Methylenetetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and is involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, C677T and A1298C have been associated with several diseases, including cancer. We made a case-control study to analyze a possible association of MTHFR gene polymorphisms C677T and A1298C with risk for colorectal cancer in an eastern Chinese Han population of 137 patients with a confirmed histopathological diagnosis of CRC and 145 age- and gender-matched controls with no history of cancer. DNA was isolated from peripheral blood samples and the genotypes were determined by PCR-RFLP. The concentrations of folate in plasma were measured by chemiluminescence immunoassay. The MTHFR 677TT genotype had a protective effect against colorectal cancer, with an odds ratio (OR) = 0.467 (95% confidence interval (CI) = 0.225-0.966). The 1298CC genotype was significantly correlated with a reduced risk of colorectal cancer (OR = 0.192; 95%CI = 0.040-0.916). Compared with the MTHFR 677CC and MTHFR 1298 AA genotypes, for individuals who carried both MTHFR 677CC and 1298CC genotypes, the OR of colorectal cancer was 0.103 (95%CI = 0.012-0.900); among individuals who carried both MTHFR 677TT and 1298AC genotypes, the OR for risk of colorectal cancer was 0.169 (95%CI = 0.044-0.654). MTHFR 677TT+CT genotypes had a significantly lower plasma folate concentration than those with the MTHFR 677CC genotype. MTHFR 1298AC+CC genotypes had a lower plasma folate concentration than those with the MTHFR 1298AA genotype (P < 0.05). In conclusion, subjects with the MTHFR 677TT and MTHFR 1298CC genotypes appeared to have a significantly lower risk for colorectal cancer. MTHFR haplotypes 677CC/1298CC and 677TT/1298AC were less common in cases than in controls. These haplotypes, when compared to the most common haplotype 677CC/1298AA, were associated with a decreased risk for colorectal cancer. We conclude that plasma folate level is influenced by MTHFR genotypes.

Diagnostic radiograph based 3D bone reconstruction framework: application to the femur.

Three dimensional (3D) visualization of anatomy plays an important role in image guided orthopedic surgery and ultimately motivates minimally invasive procedures. However, direct 3D imaging modalities such as Computed Tomography (CT) are restricted to a minority of complex orthopedic procedures. Thus the diagnostics and planning of many interventions still rely on two dimensional (2D) radiographic images, where the surgeon has to mentally visualize the anatomy of interest. The purpose of this paper is to apply and validate a bi-planar 3D reconstruction methodology driven by prominent bony anatomy edges and contours identified on orthogonal radiographs. The results obtained through the proposed methodology are benchmarked against 3D CT scan data to assess the accuracy of reconstruction. The human femur has been used as the anatomy of interest throughout the paper. The novelty of this methodology is that it not only involves the outer contours of the bony anatomy in the reconstruction but also several key interior edges identifiable on radiographic images. Hence, this framework is not simply limited to long bones, but is generally applicable to a multitude of other bony anatomies as illustrated in the results section.

Midlife overweight and obesity increase late-life dementia risk: a population-based twin study.

OBJECTIVE: The relation of overweight to dementia is controversial. We aimed to examine the association of midlife overweight and obesity with dementia, Alzheimer disease (AD), and vascular dementia (VaD) in late life, and to verify the hypothesis that genetic and early-life environmental factors contribute to the observed association. METHODS: From the Swedish Twin Registry, 8,534 twin individuals aged ≥65 (mean age 74.4) were assessed to detect dementia cases (DSM-IV criteria). Height and weight at midlife (mean age 43.4) were available in the Registry. Data were analyzed as follows: 1) unmatched case-control analysis for all twins using generalized estimating equation (GEE) models and 2) cotwin matched case-control approach for dementia-discordant twin pairs by conditional logistic regression taking into account lifespan vascular disorders and diabetes. RESULTS: Among all participants, dementia was diagnosed in 350 subjects, and 114 persons had questionable dementia. Overweight (body mass index [BMI] >25-30) and obesity (BMI >30) at midlife were present in 2,541 (29.8%) individuals. In fully adjusted GEE models, compared with normal BMI (20-25), overweight and obesity at midlife were related to dementia with odds ratios (ORs) (95% CIs) of 1.71 (1.30-2.25) and 3.88 (2.12-7.11), respectively. Conditional logistic regression analysis in 137 dementia-discordant twin pairs led to an attenuated midlife BMI-dementia association. The difference in ORs from the GEE and the matched case-control analysis was statistically significant (p = 0.019). CONCLUSIONS: Both overweight and obesity at midlife independently increase the risk of dementia, AD, and VaD. Genetic and early-life environmental factors may contribute to the midlife high adiposity-dementia association.

A multicenter, retrospective study of acute kidney injury in adult patients with nonmyeloablative hematopoietic SCT.

Acute kidney injury (AKI) is a common early complication in patients with hematopoietic SCT (HSCT). However, there are limited data about the incidence and risk factors of AKI in patients with nonmyeloablative HSCT. We conducted a multicenter, retrospective cohort study of 62 patients from three institutions who were treated with similar protocols for nonmyeloablative HSCT. AKI was classified according to the Acute Kidney Injury Network criteria. It was shown that 29% of the patients developed AKI in the first 100 days after nonmyeloablative HSCT. The risk factor at baseline for AKI was incomplete HLA-matched transplant (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.1-13.0). Complications such as acute GVHD, veno-occlusive disease of liver and sepsis were also associated with the development of AKI (OR 12.1; 95% CI 2.4-62.4). AKI was significantly associated with mortality (OR=4.7; 95% CI 1.9-11.5). We concluded that AKI is a very common complication in patients with nonmyeloablative HSCT, which is associated with incomplete HLA-matched transplant and complications, and has an important impact on the patients' first year of survival.

Uncontrolled diabetes increases the risk of Alzheimer's disease: a population-based cohort study.

AIMS/HYPOTHESIS: Diabetes has been related to Alzheimer's disease with inconsistent findings. We aimed to clarify the association of diabetes with different dementing disorders taking into account glycaemic control, and to explore the link between glucose dysregulation and neurodegeneration. METHODS: A dementia-free cohort (n = 1,248) aged >or=75 years was longitudinally examined to detect dementia, Alzheimer's disease and vascular dementia (VaD) cases (Diagnostic and Statistical Manual of Mental Disorders, revised third edition [DSM-III-R] criteria). The Alzheimer's disease diagnoses were subdivided into Alzheimer's disease with stroke and Alzheimer's disease without hypertension, heart disease and stroke. Diabetes was ascertained based on medical history, or hypoglycaemic medication use, or a random blood glucose level >or=11.0 mmol/l, which included undiagnosed diabetes when neither a history of diabetes nor hypoglycaemic drugs use was present. Uncontrolled diabetes was classified as a random blood glucose level >or=11.0 mmol/l in diabetic patients. Borderline diabetes was defined as a random blood glucose level of 7.8-11.0 mmol/l in diabetes-free individuals. Cox models were used to estimate HRs. RESULTS: During the 9 year follow-up, 420 individuals developed dementia, including 47 with VaD and 320 with Alzheimer's disease (of the 320 Alzheimer's disease cases, 78 had previous, temporally unrelated stroke, and 137 had no major vascular comorbidities). Overall diabetes was only related to VaD (HR 3.21, 95% CI 1.20-8.63). Undiagnosed diabetes led to an HR of 3.29 (95% CI 1.20-9.01) for Alzheimer's disease. Diabetic patients with random blood glucose levels <7.8 mmol/l showed no increased dementia risk. Uncontrolled and borderline diabetes were further associated with Alzheimer's disease without vascular comorbidities. CONCLUSIONS/INTERPRETATION: Uncontrolled diabetes increases the risk of Alzheimer's disease and VaD. Our findings suggest a direct link between glucose dysregulation and neurodegeneration.