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Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory marker associated with atherosclerotic and cardiovascular diseases. This study aimed to explore the association of Lp-PLA2 with carotid intima-media thickness (cIMT) in patients with acute ischemic stroke (AIS) and explore a threshold level to predict the risk of vulnerable plaques. This retrospective observational study included patients with AIS in the Neurology Department of our Hospital between January 2018 and December 2019. The study included 293 patients aged 65.29 ± 12.11 years, including 212 males, of whom 124 had carotid intima-media thickening (42.32%). Multivariable logistic regression showed that Lp-PLA2 level was an independent risk factor for cIMT (odds ratio [OR] = 1.004, 95% confidence interval [95% CI] 1.001-1.008, P = .008). Threshold effect analysis showed that the risk of vulnerable carotid plaque occurrence increased by 2% for every 1 ng/mL increase in Lp-PLA2 level with serum Lp-PLA2 levels between 157 and 279 ng/mL; this increase was statistically significant (OR = 1.02, 95% CI 1.01-1.03, P < .001). Serum Lp-PLA2 is an independent risk factor for increased cIMT in patients with AIS, and a threshold Lp-PLA2 level between 157 and 279 ng/mL showed a higher risk of carotid plaque rupture.
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The interaction of mining and the surface water or aquifer system in varying overburden strata conditions is one of the most critical aspects of sustainable mining practices, that can lead to water loss or water inrush into openings. This paper examined this phenomenon in a complex strata condition via a case study, and proposed a new mining design to minimize the impact of longwall mining on the overlaying aquifer. A range of factors have been identified contributing to the potential disturbance of the aquifer, including the extent of the water-rich area, the characteristics of overburden rock units, and the development height of the water-conducting fracture zone. In this study, the transient electromagnetic method and the high-density three-dimensional electrical method were used to identify two areas prone to water inrush danger in the working face. The vertical range of the water-rich abnormal area 1 is 45-60 m away from the roof, with an area of 3334 m2. The vertical range of the water-rich abnormal area 2 is 30-60 m away from the roof, with an area of approximately 2913 m2. The bedrock drilling method was used to determine that the thinnest part of the bedrock, with a thickness of approximately 60 m, and the thickest part, with a thickness of approximately 180 m. The maximum mining-induced height of the fracture zone was 42.64 m using empirical method, theoretical prediction based on the rock stratum group, field monitoring. In summary, the high risk area was determined, and the analysis shows that the size of the water prevention) pillar was 52.6 m, which was smaller than the safe water prevention pillar actually set in the mining range. The research conclusion provides important safety guidance significance for the mining of similar mines.
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Minas de Carbón , Agua Subterránea , Modelos Teóricos , Minería , Abastecimiento de Agua , AguaRESUMEN
The rock mass around deep roadways has obvious creep characteristics in high-stress environments. Meanwhile, the cyclic impact load induced by roof fracturing also causes dynamic damage to the surrounding rock, leading to long-term large deformation. This paper examined the rock mass deformation mechanism around deep roadways based on the theory of rock creep perturbation effect considering perturbation sensitive zone. This study proposed a long-term stability control guideline for deep roadways under dynamic load. An innovative support system was developed for deep roadways, with concrete-filled steel tubular support being recommended as the main supporting body. A case study was conducted to validate the proposed supporting system. Monitoring over one year in the case study mine showed that the overall convergence deformation of the roadway was 35 mm, indicating that the roadway's long-term large deformation induced by creep perturbation was effectively controlled by using the proposed bearing circle support system.
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OBJECTIVE: To assess the effects of metabolic syndrome (MetS) and its components on the survival and prognosis of patients with localized clear cell renal cell carcinoma (ccRCC). DESIGN AND METHODS: This retrospective cohort study in Chongqing, China, identified patients with localized ccRCC from two medical centers of Chongqing Medical University between January 1, 2011, and December 31, 2020. The Chinese Medical Association Diabetes Society criteria of 2004 were used to diagnose MetS. Univariate and multivariate Cox proportional hazards regression analyses were conducted to identify independent risk factors for ccRCC. The outcomes were overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS). RESULTS: In our cohort, 378 eligible patients with localized ccRCC were included (median age, 56; range, 30-85; 255 men [67.5%]), and 87 patients (23.0%) were diagnosed with MetS. The median follow-up time was 66 months (1-126 months). Kaplan-Meier and log-rank analyses showed shorter PFS (Pâ¯=â¯0.043) and CSS (Pâ¯=â¯0.009) in patients with MetS. Univariate and multivariate Cox regression analyses found that MetS and dyslipidemia were independent risk factors for CSS in patients with localized ccRCC (Pâ¯=â¯0.047; Pâ¯=â¯0.035). When we analyzed MetS separately, the 4 components of MetS (hypertension, hyperglycemia, overweight/obesity, and dyslipidemia) did not show significant differences in OS, PFS, and CSS. CONCLUSION: MetS and dyslipidemia are independent adverse prognostic factors for CSS in patients with localized ccRCC. It is suggested to assign comprehensive therapy and follow-up to this patient population.
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Carcinoma de Células Renales , Neoplasias Renales , Síndrome Metabólico , Masculino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Síndrome Metabólico/complicaciones , Estimación de Kaplan-Meier , Pronóstico , China/epidemiologíaRESUMEN
This study aims to determine whether APOE alleles would affect the functional outcome in acute ischemic stroke (AIS) and whether the relationship between inflammation and stroke-related disability varies according to APOE genotypes. We retrospectively collected the demographic and clinical data of AIS patients within one week of symptom-onset through medical records review. The primary outcome was dependence or death, defined as modified Rankin scale (mRS) score of 2-6, which was assessed at 3 months. Among 1929 enrolled patients, the prevalence of APOE ε4 carriers was 17.73% (342/1929). There were 394 AIS patients (394/1929, 20.43%) showed poor function outcome of 90-day mRS (2-6), of whom 147 (147/342, 42.98%) were APOE ε4 carriers and 247 (247/1587, 15.56%) were non-ε4 carriers. There was a significant increased probability of poor functional outcome after AIS among APOE ε4 carriers versus non-ε4 carriers (adjusted-OR 4.62, 95% CI 3.51 to 6.09, P < 0.001). Among ε4 carriers, high neutrophil-to-lymphocyte ratio (NLR) was significantly associated with stroke-related disability (Ptrend = 0.035); however, no significant association was observed among non-ε4 carriers. Our study showed that the APOE ε4 carriers had worse functional outcome after AIS as compared with non-ε4 carriers. APOE genotype may modify the relationship between NLR and 3-month stroke outcome.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Apolipoproteína E4/genética , Estudios Retrospectivos , Genotipo , Apolipoproteínas E/genética , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/epidemiología , Factores de RiesgoRESUMEN
Objective: This study aimed to develop a diagnostic model of multi-kinematic parameters for patients with amnestic mild cognitive impairment (aMCI). Method: In this cross-sectional study, 94 older adults were included (33 cognitively normal, CN; and 61 aMCI). We conducted neuropsychological battery tests, such as global cognition and cognitive domains, and collected gait parameters by an inertial-sensor gait analysis system. Multivariable regression models were used to identify the potential diagnostic variables for aMCI. Receiver operating characteristic (ROC) curves were applied to assess the diagnostic accuracy of kinematic parameters in discriminating aMCI from healthy subjects. Results: Multivariable regression showed that multi-kinematic parameters were the potential diagnostic variables for aMCI. The multi-kinematic parameter model, developed using Timed Up and Go (TUG) time, stride length, toe-off/heel stride angles, one-leg standing (OLS) time, and braking force, showed areas under ROC (AUC), 0.96 [95% confidence interval (CI), 0.905-0.857]; sensitivity, 0.90; and specificity, 0.91. In contrast, a single kinematic parameter's sensitivity was 0.26-0.95 and specificity was 0.21-0.90. Notably, the separating capacity of multi-kinematic parameters was highly similar to Montreal Cognitive Assessment (MoCA; AUC: 0.96 vs. 0.95). Compared to cognitive domain tests, the separating ability was comparable to Auditory Verbal Learning Test (AVLT) and Boston Naming Test (BNT; AUC: 0.96 vs. 0.97; AUC: 0.96 vs. 0.94). Conclusion: We developed one diagnostic model of multi-kinematic parameters for patients with aMCI in Foshan.
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Objectives: This study aimed to primarily examine the association between memory deficit and increased fall risk, second, explore the underlying neuroanatomical linkage of this association in the elderly with aMCI and mild AD. Methods: In this cross-sectional study, a total of 103 older adults were included (55 cognitively normal, CN; 48 cognitive impairment, CI, elderly with aMCI, and mild AD). Memory was assessed by the Auditory Verbal Learning Test (AVLT). Fall risk was evaluated by the Timed Up and Go (TUG) Test, heel strike angles, and stride speed, which were collected by an inertial-sensor-based wearable instrument (the JiBuEn™ gait analysis system). Brain volumes were full-automatic segmented and quantified using AccuBrain® v1.2 from three-dimensional T1-weighted (3D T1W) MR images. Multivariable regression analysis was used to examine the extent of the association between memory deficit and fall risk, the association of brain volumes with memory, and fall risk. Age, sex, education, BMI, and HAMD scores were adjusted. Sensitivity analysis was conducted. Results: Compared to CN, participants with aMCI and mild AD had poorer cognitive performance (p < 0.001), longer TUG time (p = 0.018), and smaller hippocampus and medial temporal volumes (p = 0.037 and 0.029). In the CI group, compared to good short delayed memory (SDM) performance (AVLT > 5), the elderly with bad SDM performance (AVLT ≤ 3) had longer TUG time, smaller heel strike angles, and slower stride speed. Multivariable regression analysis showed that elderly with poor memory had higher fall risk than relative good memory performance among cognitive impairment elderly. The TUG time increased by 2.1 s, 95% CI, 0.54â¼3.67; left heel strike angle reduced by 3.22°, 95% CI, -6.05 to -0.39; and stride speed reduced by 0.09 m/s, 95% CI, -0.19 to -0.00 for the poor memory elderly among the CI group, but not found the association in CN group. In addition, serious medial temporal atrophy (MTA), small volumes of the frontal lobe and occipital lobe were associated with long TUG time and small heel strike angles; small volumes of the temporal lobe, frontal lobe, and parietal lobe were associated with slow stride speed. Conclusion: Our findings suggested that memory deficit was associated with increased fall risk in the elderly with aMCI and mild AD. The association might be mediated by the atrophy of medial temporal, frontal, and parietal lobes. Additionally, increased fall risk, tested by TUG time, heel stride angles, and stride speed, might be objective and convenient kinematics markers for dynamic monitoring of both memory function and fall risk.
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BACKGROUND: We aim at describing the incidence, potential predisposing factors, and progression of major radiotherapy-related neurologic complications (RRNC) in nasopharyngeal carcinoma (NPC)-endemic regions, especially southern China. METHODS: We performed a multicenter longitudinal retrospective study with clinical follow-ups in 22,302 patients with post-radiotherapy NPC between January 2003 and June 2017 covering three major residential areas. Epidemiology, potential predisposing/protective factors, clinicopathologic progression, and survival conditions of each RRNC were separately recorded and analyzed on the basis of their related clinical, radiologic, and laboratory parameters. RESULTS: 949 new cases of RRNCs occurred among the 22,302 patients with post-radiotherapy NPC during 101,714 person years' follow-up, which is equal to an incidence density rate of 9.3 new cases per 1000 person year. Radiation-induced cranial nerve palsy showed the highest incidence (2.68%, 597/22,302) with the earliest onset (median latency, 4.45 years) as well. Patients benefited from intensity-modulated radiotherapy (IMRT) over conventional radiotherapy (CRT) in both overall survival (median survival 13.2 years for IMRT vs. 8.3 years for CRT) and RRNC-free survival (except for epilepsy and cranial nerve palsy). Causes of death varied substantially between patients with or without RRNCs. CONCLUSIONS: Our study indicates a non-negligible incidence of RRNC spectrum in southern China in the past ten years. IMRT is one of the most significant protectors against development and progression of RRNCs. IMPACT: Our findings support the hypothesis that patients with NPC with preexisting predispositions would receive long-term benefits from IMRT and other dose-related modulations (like hyperfractionation and dose conformation).
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Neoplasias Nasofaríngeas , Traumatismos por Radiación , Radioterapia de Intensidad Modulada , China/epidemiología , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/epidemiología , Neoplasias Nasofaríngeas/radioterapia , Traumatismos por Radiación/epidemiología , Traumatismos por Radiación/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Estudios RetrospectivosRESUMEN
This paper presents an experimental study to assess the behaviour of coal samples under tensile loadings to better understand the failure mechanisms and the interactions with the coal characteristics. A set of Brazilian splitting tests were carried out using disk specimens obtained from Tashan Coal Mine in China. The digital speckle correlation method and acoustic emission (AE) were used to capture the deformation localisation and AE characteristics of each specimen during the loading process. The precursor characteristics of AE and the failure mechanism are discussed. It was found that the entire loading process mainly consists of compaction, elastic and post-peak dropping stage without an obvious yielding stage. Two kinds of deformation localisation were observed: central symmetry and axis symmetry. The corresponding AE evolution patterns have different phases, including gradual rise, step rise, transient rise and steady rise. During the subcritical failure stage, AE counts demonstrate a "rapidly increasing + flatten" intermittent feature. The results provide a reference for a better understanding of the damage process of the brittle coal material and its application in ground control design.
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The global market demand for natural astaxanthin is rapidly increasing owing to its safety, the potential health benefits, and the diverse applications in food and pharmaceutical industries. The major native producers of natural astaxanthin on industrial scale are the alga Haematococcus pluvialis and the yeast Xanthopyllomyces dendrorhous. However, the natural production via these native producers is facing challenges of limited yield and high cost of cultivation and extraction. Alternatively, astaxanthin production via metabolically engineered non-native microbial cell factories such as Escherichia coli, Saccharomyces cerevisiae and Yarrowia lipolytica is another promising strategy to overcome these limitations. In this review we summarize the recent scientific and biotechnological progresses on astaxanthin biosynthetic pathways, transcriptional regulations, the interrelation with lipid metabolism, engineering strategies as well as fermentation process control in major native and non-native astaxanthin producers. These progresses illuminate the prospects of producing astaxanthin by microbial cell factories on industrial scale.
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OBJECTIVE: The association between peptic ulcer disease (PUD) and chronic urticaria (CU) is rarely examined in individuals without Helicobacter pylori infection. The study aimed to investigate the association between Helicobacter pylori-negative PUD and CU. METHODS: Patients without Helicobacter pylori infection were retrospectively enrolled from those who visited the clinic or were admitted to the ward of the dermatological department with recent gastroscopy and Helicobacter pylori testing in a tertiary hospital between 2015 and 2019. After categorizing them as patients with and without PUD, we used propensity score matching to identify a cohort of PUD and a control cohort at a ratio of 1:2. CU was determined by examining medical records of the two cohorts, and logistic regression analyses were used to evaluate the association between PUD and CU with or without adjusting for covariates. RESULTS: We included 40 patients with PUD as the PUD cohort and 80 patients without PUD as the control cohort, between which there were no significant differences in patient characteristics, including age, sex, and several comorbidities (P all >0.05). Among the PUD cohort, 25.00% (10/40) of them were with CU, which was significantly higher than that in the control cohort 8.75% (7/80, P = 0.016). Results of logistic regression analyses showed PUD was significantly associated with increased risk of CU (odds ratio (OR) 3.48, 95% confidence interval (CI) 1.21-9.99, P = 0.021), which was consistent with that after adjusted for potential confounding factors (OR 3.77, 95% CI 1.24-11.45, P = 0.019). CONCLUSION: Helicobacter pylori-negative PUD is associated with increased risk of CU.
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BACKGROUND: Stroke affects 3-4% of adults and kills numerous people each year. Recovering blood flow with minimal reperfusion-induced injury is crucial. However, the mechanisms underlying reperfusion-induced injury, particularly inflammation, are not well understood. Here, we investigated the function of miR-19a/b-3p/SIRT1/FoxO3/SPHK1 axis in ischemia/reperfusion (I/R). METHODS: MCAO (middle cerebral artery occlusion) reperfusion rat model was used as the in vivo model of I/R. Cultured neuronal cells subjected to OGD/R (oxygen glucose deprivation/reperfusion) were used as the in vitro model of I/R. MTT assay was used to assess cell viability and TUNEL staining was used to measure cell apoptosis. H&E staining was employed to examine cell morphology. qRT-PCR and western blot were performed to determine levels of miR-19a/b-3p, SIRT1, FoxO3, SPHK1, NF-κB p65, and cytokines like TNF-α, IL-6, and IL-1ß. EMSA and ChIP were performed to validate the interaction of FoxO3 with SPHK1 promoter. Dual luciferase assay and RIP were used to verify the binding of miR-19a/b-3p with SIRT1 mRNA. RESULTS: miR-19a/b-3p, FoxO3, SPHK1, NF-κB p65, and cytokines were elevated while SIRT1 was reduced in brain tissues following MCAO/reperfusion or in cells upon OGD/R. Knockdown of SPHK1 or FoxO3 suppressed I/R-induced inflammation and cell death. Furthermore, knockdown of FoxO3 reversed the effects of SIRT1 knockdown. Inhibition of the miR-19a/b-3p suppressed inflammation and this suppression was blocked by SIRT1 knockdown. FoxO3 bound SPHK1 promoter and activated its transcription. miR-19a/b-3p directly targeted SIRT1 mRNA. CONCLUSION: miR-19a/b-3p promotes inflammatory responses during I/R via targeting SIRT1/FoxO3/SPHK1 axis.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteína Forkhead Box O3/metabolismo , Inflamación/metabolismo , MicroARNs/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Daño por Reperfusión/metabolismo , Sirtuina 1/metabolismo , Animales , Apoptosis , Muerte Celular , Línea Celular , Modelos Animales de Enfermedad , Técnicas de Silenciamiento del Gen , Humanos , Infarto de la Arteria Cerebral Media , Masculino , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/patologíaRESUMEN
BACKGROUND: Approximately 75% of Chinese hypertensive patients have elevated homocysteine (Hcy). Its implication in risk assessment and prevention of the first stroke remains an important clinical and public health question. METHODS: This study was based on a community cohort recruited from 2016 to 2018 in the rural China. To maximize cost efficiency, we used a nested case-control design, including 3,533 first stroke cases and 3,533 controls matched for age ±1 years, sex, and village. Individual associations of tHcy and traditional risk factors with the first stroke were examined, and their population-attributable risks (PARs) were estimated. RESULTS: There was a significant dose-response association between first stroke and total Hcy (tHcy) levels, with adjusted odds ratios of 1.11 (95% CI: 0.97, 1.26) for tHcy 10-15 µmol/L and 1.44 (1.22, 1.69) for tHcy ≥ 15 µmol/L, all compared to tHcy < 10 µmol/L. A similar trend was found for ischemic and hemorrhagic stroke. tHcy and systolic blood pressure (SBP) were independently and additively associated with the risk of first stroke (tHcy: 1.06 [1.02, 1.1]; SBP: 1.13 [1.1, 1.16]; P-interaction, 0.889). Among the ten main risk factors examined, the top two contributors to the first stroke were SBP and tHcy, with PARs of 25.73 and 11.24%, respectively. CONCLUSIONS: Elevated tHcy is the second most important contributor and acts additively with SBP to increase the risk of the first stroke. This finding underscores the importance of screening and treating elevated tHcy along with traditional risk factors to further reduce the burden of the first stroke in the high-risk populations.
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OBJECTIVE: The association between plasma magnesium and risk of incident cancer remains inconclusive in previous studies. We aimed to investigate the prospective relationship of baseline plasma magnesium concentrations with the risk of incident cancer and to examine possible effect modifiers. METHODS: A nested case-control study with 228 incident cancer cases and 228 matched controls was conducted using data from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, controlled trial, conducted from May 2008 to August 2013. Study outcomes included incident cancer and its subtypes. RESULTS: When plasma magnesium concentrations were assessed as quartiles, a significantly higher incident risk of total cancer was found in participants in quartile 1 (<0.76 mmol/L; odds ratio [OR] = 2.70; 95% CI: 1.33-5.49) and quartile 4 (≥0.89 mmol/L; OR = 2.05; 95% CI: 1.12-3.76), compared with those in quartile 3 (0.83 to <0.89 mmol/L). In cancer site-specific analyses, similar trends were found for gastrointestinal cancer, esophageal cancer, gastric cancer, breast cancer, lung cancer, and other cancers. Furthermore, none of the variables, including age, sex, current smoking status, current alcohol intake, BMI, systolic blood pressure, and total cholesterol levels at baseline significantly modified the association between plasma magnesium and cancer risk. CONCLUSIONS: Both low and high plasma magnesium concentrations were significantly associated with an increased incident risk of cancer, compared with the reference concentrations of 0.83 to <0.89 mmol/L among hypertensive adults.
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Hipertensión/sangre , Magnesio/sangre , Neoplasias/epidemiología , Estudios de Casos y Controles , China/epidemiología , Método Doble Ciego , Femenino , Humanos , Hipertensión/complicaciones , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias/etiología , Oportunidad Relativa , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Valores de Referencia , Factores de RiesgoRESUMEN
STUDY OBJECTIVES: To investigate the extent to which sleep quality associated with plasma Aß levels in amnestic mild cognitive impairment (aMCI) elderly. METHODS: A total of 172 cognitively normal (NC) elderly and 133 aMCI elderly were included in this study. For the evaluation of sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used. Levels of plasma Aß were determined by the sandwich enzyme-linked immunosorbent assay technique. Multivariable linear regression analysis was applied to evaluate associations between sleep quality and plasma Aß levels after adjusting potential confounders. RESULTS: Compared to NC subjects, participants with aMCI had a higher global PSQI score (8.72 ± 3.87 vs. 7.10 ± 3.07, p < 0.001). The global PSQI score was positively associated with plasma Aß42 level in the aMCI group (ß = 0.063, 95% CI 0.001-0.125, and p = 0.049) but not in the NC group (p > 0.05). Additionally, a higher global PSQI score was associated with a higher plasma Aß42/Aß40 ratio in both NC (ß = 0.010, 95% CI 0.003-0.016, and p = 0.003) and aMCI groups (ß = 0.012, 95% CI 0.005-0.018, and p < 0.001). The association between global PSQI score and plasma Aß42/Aß40 ratio was stronger in individuals with aMCI relative to the NC subjects (ß = 0.076 vs. 0.030, p for interaction = 0.023). CONCLUSION: Poor sleep quality was associated with plasma Aß42 and Aß42/Aß40 ratio, with a stronger effect among individuals with aMCI. A better understanding of the role of sleep in plasma Aß levels in aMCI patients could lead to effective sleep-based intervention against the risk of Alzheimer's disease.
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Objectives: To characterize gait disorders in patients with amnestic mild cognitive impairment (aMCIs) and determine the association between the performance of the gait function and cognition. Methodology: In this study, we enrolled 38 patients with aMCI and 30 cognitively normal individuals normal controls (NC). Neuropsychological assessments included tests of memory, executive function, language, and attention. Using an inertial-sensor-based wearable instrument, we collected the gait data dynamically for at least 1 h/day for 2 weeks. The gait parameters included walking velocity, stride length, stride time, cadence, and stride time variability. Results: The aMCI patients had reduced walking velocity and stride length and increased stride time variability compared with the NCs. The total number of steps, stride time, and cadence did not differ between the two groups. For all the subjects, walking velocity and stride length was positively associated with memory and executive function. Stride time variability was negatively correlated with the cognitive domains including memory, executive function and attention. Conclusion: This study suggested that cognitive impairment-related gait disorders occur (reduced gait speed, gait length, and gait stability) in daily life walking among the aMCI patients. A sensor-based wearable device for gait measurement may be an alternative and convenient tool for screening cognitive impairment.
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OBJECTIVE: It was recently found that structural changes in the substantia nigra (SN) and motor symptoms become more prominent in Parkinson's disease (PD) patients with striatal silent lacunar infarction (SSLI) than in those without SSLI. Hyperhomocysteinemia (HHCY) was an independent risk factor for SSLI in PD patients. In this follow-up study, we investigated the relationship between HHCY and structural changes of the SN in PD patients. METHODS: A total of 72 untreated early PD patients without SSLI, divided into control and HHCY groups, were enrolled in this study. All participants underwent conventional MRI and diffusion kurtosis imaging (DKI) twice; at baseline and at the 2-year visit. The differences of the following variables between the two groups were analyzed: mean kurtosis (MK) values of the SN, the severity of disease, daily dosage of levodopa, and the variation of these indexes from baseline to 2-year visit. Logistic regression analysis was used to identify the relationship between HHCY and structural changes of the SN in PD patients. RESULTS: 1.All variables mentioned above showed significant differences between the two groups. 2. The variation in MK values of the SN were positively correlated with the variation in the severity of disease. 3. HHCY was an independent risk factor for the variation in MK values of the SN in PD patients. CONCLUSION: HHCY is associated with the structural changes of the SN in PD patients. As PD progresses, motor symptoms become aggravated with increased structural changes to the SN, especially in patients with HHCY.
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Progresión de la Enfermedad , Hiperhomocisteinemia , Enfermedad de Parkinson , Accidente Vascular Cerebral Lacunar , Sustancia Negra/patología , Anciano , Femenino , Estudios de Seguimiento , Humanos , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/complicaciones , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Índice de Severidad de la Enfermedad , Accidente Vascular Cerebral Lacunar/sangre , Accidente Vascular Cerebral Lacunar/etiología , Accidente Vascular Cerebral Lacunar/patología , Sustancia Negra/diagnóstico por imagenRESUMEN
OBJECTIVE: To assess the association of CYP2C19 gene polymorphisms with the incidence of ischemic stroke among patients receiving clopidogrel therapy following coronary stenting for coronary artery disease. METHODS: Clinical data of patients receiving clopidogrel therapy after coronary stenting were retrospectively studied. For a case-control study, 137 patients with acute cerebral infarction and 122 non-stroke patients were selected. Based on the variants of the CYP2C19 gene detected by a DNA microarray assay, the patients were further divided into the wild-type group(CYP2C19*1/*1) and mutant group(defined by the presence of at least one loss-of-function allele, including CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3). The incidences of ischemic stroke in the two groups were compared through a chi-square analysis. The influence of CYP2C19 gene polymorphisms and clopidogrel therapy on the incidence of ischemic stroke was analyzed through multivariable logistic regression. RESULTS: A total of 259 patients were enrolled. The case and control groups showed no difference in terms of gender and age. There were 123 cases (47.5%) in the CYP2C19 wild-type group and 136 cases (52.5%) in the mutant group. The incidence of ischemic stroke of mutant group was significantly higher than that of wild-type group (59.9% vs. 44.3%, X2=6.398, P=0.042). Multivariate analysis revealed that loss-of-function polymorphisms of the CYP2C19 gene carried a 1.13 times greater risk for ischemic stroke compared to wild-type genotype (OR=2.13, 95%CI: 1.23-3.71). CONCLUSION: The efficacy of clopidogrel for the prevention of ischemic stroke in post-coronary stent patients may be reduced by the insufficiency of the CYP2C19 gene. The dosage of clopidogrel therapy should be adjusted based on its polymorphisms.
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Isquemia Encefálica/prevención & control , Citocromo P-450 CYP2C19/genética , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Polimorfismo Genético , Stents/efectos adversos , Accidente Cerebrovascular/prevención & control , Ticlopidina/análogos & derivados , Clopidogrel , Genotipo , Humanos , Ticlopidina/uso terapéuticoRESUMEN
BACKGROUND: Obesity is a risk factor for many diseases. However, the potential association between adiposity and cognitive decline in hypertensive patients is inconclusive. We performed a secondary data analysis of the CSPPT (China Stroke Primary Prevention Trial) to examine whether adiposity is correlated with longitudinal cognitive performance in hypertensive adults. METHODS AND RESULTS: The analysis included 16 791 patients in the CSPPT who received at least 2 cognitive assessments by the Mini-Mental State Examination (MMSE) during the follow-up (median, 4.5 years; interquartile range, 4.2-4.8 years). Outcomes included changes in MMSE scores and cognitive impairment (defined as MMSE score less than education-specific cutoff point). A marked reduction in MMSE scores at the final (compared with at the 1-year) follow-up was apparent in both men (n=4838; mean [SD] score, 0.41 [3.62]) and women (n=7190; mean [SD] score, 1.07 [4.61]; both P<0.001). Analysis using a mixed-effects model revealed an association between higher body mass index with less MMSE decline, even after controlling for demographics and comorbidities (men, ß=0.0134 [SE, 0.0036]; women, ß=0.0133 [SE, 0.0034]; both P<0.001). A total of 1037 men (15.3%) and 3317 women (33.1%) developed cognitive impairment. In multivariable Cox regression analyses, being obese in men (11.3% versus 18.0%; hazard ratio, 0.75; 95% confidence interval, 0.60-0.94) and women (30.1% versus 36.5%; hazard ratio, 0.82; 95% confidence interval, 0.74-0.91) was a protective factor against cognitive impairment compared with normal body mass index. CONCLUSIONS: Higher adiposity is independently associated with slower cognitive decline in Chinese hypertensive adults. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885 CSPPT.
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Adiposidad , Presión Sanguínea , Trastornos del Conocimiento/psicología , Cognición , Hipertensión/fisiopatología , Obesidad/fisiopatología , Anciano , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Índice de Masa Corporal , Distribución de Chi-Cuadrado , China/epidemiología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Modelos Lineales , Estudios Longitudinales , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Análisis Multivariante , Dinámicas no Lineales , Obesidad/diagnóstico , Obesidad/epidemiología , Prevención Primaria/métodos , Modelos de Riesgos Proporcionales , Factores Protectores , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Factores de Tiempo , Circunferencia de la CinturaRESUMEN
OBJECTIVE: Striatal silent lacunar infarction (SSLI) is associated with structural changes to the substantia nigra (SN), detectable by diffusion kurtosis imaging (DKI). In this follow-up study, we investigated the effects of SSLI on the SN and movement disorders in patients with Parkinson's disease (PD). METHODS: A total of 60 untreated patients with early-stage PD, divided into control and SSLI groups, were enrolled in this study. All participants underwent conventional MRI and DKI twice; at baseline and after a 1-year period. We analyzed the differences of the following variables between the two groups: mean kurtosis (MK) values of the SN, the severity of disease, daily dosage of levodopa, and the variation of these indexes from baseline to 1-year visit. Logistic regression analysis was used to identify the major risk factors for SSLI in PD patients. RESULTS: 1. All variables showed significant differences between the two groups. 2. The variation in MK values of the SN had a positive correlation with the variation in the severity of disease. 3. Hypertension and hyperhomocysteinemia were independent factors for SSLI in patients with PD. CONCLUSION: As PD progresses, movement disorders become more prominent, with increased structural changes to the SN, especially in patients with SSLI. Furthermore, PD patients with hypertension and hyperhomocysteinemia are more likely to have SSLI.