Research on the pathogenesis of Alzheimer's disease based on thalamocortical computational model.

Alpha rhythm slowing is an important electroencephalogram(EEG) feature associated with (AD). This study aims to understand the correlation between alpha band deceleration and molecular changes from the perspective of neural computing. Considering the effect of Aß amyloid deposition on the inhibitory changes in the thalamic, a thalamic cortical model coupled with Aß amyloid is established. The results show that Aß amyloid deposition may induce neurotoxicity in thalamic reticular nucleus neurons, which results in inhibitory changes in the thalamus and slows the alpha rhythm of EEG output from the thalamus. In order to understand the pathogenesis more intuitively, some numerical simulations are provided to illustrate the obtained theories. This research is helpful to understand the pathogenesis of AD, so as to provide theoretical basis for the intervention and control of the disease.

Blood Pressure Trajectories From Childhood to Youth and Arterial Stiffness in Adulthood: A 30-Year Longitudinal Follow-Up Study.

Background: This study aimed to identify the subgroups of individuals sharing similar blood pressure (BP) trajectories from childhood to youth and explore the associations of these trajectories with arterial stiffness in adulthood. Methods: A group-based trajectory model was used to identify BP trajectories among 2,082 individuals in the Hanzhong adolescent hypertension cohort by using BP values repeatedly measured at four visits from childhood (6-15 years) to youth (14-23 years). The brachial-ankle pulse wave velocity (baPWV) was examined 30 years after the baseline survey. Mixed linear regression models were used to examine the associations of these trajectories with adult baPWV. Results: Among the 2,082 individuals, three trajectory groups of systolic BP were identified as follows: the low-level group (n = 889), medium-level group (n = 1,021), and high-level group (n = 172). The baPWV in adulthood was higher in medium-level and high-level groups compared with the low-level group (1271.4 ± 224.7 cm/s, 1366.1 ± 249.8 cm/s vs. 1190.1 ± 220.3 cm/s, all p < 0.001). After adjustment for potential confounding factors, the association between baPWV and systolic BP trajectories was statistically significant (adjusted ß = 49.4 cm/s; p < 0.001 for the medium-level group and ß = 107.6 cm/s; p < 0.001 for the high-level group compared with the low-level group). Similar results were obtained for the association of baPWV with the trajectories of diastolic BP and mean arterial pressure (MAP), except for pulse pressure. Conclusion: Our investigation demonstrates different BP trajectories from childhood to youth and shows the trajectories of systolic BP, diastolic BP, and MAP are significant predictors of arterial stiffness in adulthood.

Association of Clinical Features of Colorectal Cancer with Circulating Tumor Cells and Systemic Inflammatory Markers.

Background: Circulating tumor cells (CTCs) in peripheral blood have been shown to reflect the prognosis of patients with colorectal cancer, and epithelial and mesenchymal markers further predict the likelihood of cancer dissemination. This study was conducted to identify possible association of clinical features of colorectal cancer with CTC counts, their subtypes, and systemic inflammatory markers. Methods: Blood samples of 316 colorectal cancer patients were used for CTC detection and subtyping with EpCAM, CK8/18/19, vimentin, and twist as biomarkers. The neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, C-reactive protein/albumin ratio, lymphocyte/monocyte ratio, and systemic immune-inflammation index (SII) were also measured. The relationship between clinical data and these markers or parameters was analyzed. Results: Total CTC counts were correlated with whether there was lymph node involvement but was not correlated with TNM staging. There was a difference in mesenchymal CTCs between patients with and without lymph node involvement (P < 0.05). Also, more patients with metastasis tested positive for mesenchymal CTCs (P < 0.05). Of the systemic inflammatory markers, platelet/lymphocyte ratio was positively correlated with CTC counts (P < 0.01), and lymphocyte/monocyte ratio was negatively correlated with CTC counts (P < 0.05). Conclusions: Colorectal cancer patients with the mesenchymal markers on their CTCs are more likely to have lymph node involvement or distant metastasis than those without these markers.

Electrochemical [4 + 1] Tandem sp3(C-H) Double Amination for the Direct Synthesis of 3-Acyl-Functionalized Imidazo[1,5-a]pyridines.

3-Acyl imidazo[1,5-a]pyridines, featured pharmaceutical moieties that were prepared by a three-step reaction conventionally, could be obtained in one step by an electrochemical tandem sp3 (C-H) double amination of acetophenones with pyridine ethylamines using ammonium iodide as a redox mediator.

Child-to-adult body mass index trajectories and the risk of subclinical renal damage in middle age.

BACKGROUND: Although it is well established that obesity is a risk factor for chronic kidney disease, the impact of distinct long-term body mass index (BMI) developmental patterns on renal function in later life is poorly understood. METHODS: This study utilized data derived from the Hanzhong Adolescent Hypertension Cohort, a prospective cohort followed over 30 years. We used latent class growth mixture modeling method to identify the BMI trajectories of participants who had received BMI measurements at least three times from childhood (age: 6-15 years) to adulthood (age: 36-45 years). The modified Poisson regression model was used to identify potential associations between BMI trajectories and subclinical renal damage (SRD) in midlife. RESULTS: Within a total of 2162 individuals, we identified four distinct long-term BMI trajectories: stable normal (54.72%), moderately increasing overweight (32.42%), resolving (10.27%), and progressively increasing obese (2.59%). By the latest follow-up in 2017, a total of 257 (13.1%) individuals were diagnosed with SRD. Compared with the stable normal group, the moderately increasing overweight group and the progressively increasing obese group exhibited significantly a higher urinary albumin-to-creatinine ratio and a higher odd of existing SRD in 2017 (risk ratio [RR], 1.70 [95% confidence interval (CI), 1.33-2.19] and 4.35 [95% CI, 3.00-6.30], respectively). However, individuals who resolved their elevated BMI in early life had a similar risk for SRD as those who had never been obese or overweight (RR, 1.17 [95% CI, 0.77-1.79]). CONCLUSIONS: Child-to-adult BMI trajectories that worsen or persist at high levels were associated with an increased risk for SRD in midlife. Maintaining a normal BMI or reversing an elevated BMI in early life may be beneficial to renal function over the long term.

Effects of a Caregiver Training Program on Oral Hygiene of Alzheimer's Patients in Institutional Care.

OBJECTIVES: To investigate the effects of a caregiver training program on the oral hygiene of caregivers and patients with Alzheimer's disease (AD) and to identify program components and parameters for accurate assessment of outcomes. DESIGN: Single-blinded prospective cohort study. SETTING AND PARTICIPANTS: Patients with AD and caregivers in nursing homes in the Greater Zhengzhou Area, China. METHODS: Initially 168 AD patient/caregiver pairs were recruited and randomly assigned to control, limited training, and comprehensive training groups. The mini-mental state examination, global deterioration scale, and Katz activities of daily living scale were conducted for patients with AD. Information on participants' oral hygiene habits and general oral health was collected. The modified Quigley-Hein Plaque Index (PI) and Gingival Index (GI) were used to assess oral hygiene and gingival health. Intervention included (1) an educational video showing the role of dental plaque and the modified Bass technique; and (2) caregivers practicing toothbrushing on themselves and patients with AD under professional guidance. Changes in oral hygiene and correlations between patient PI/GI and caregiver PI/GI were analyzed. RESULTS: After 6 weeks, complete data for 146 AD patient/caregiver pairs were collected. Before enrollment, most patients with AD had very poor oral hygiene. Compared with controls and limited training, only comprehensive training was able to achieve steady reduction in PI and GI scores in patients with AD, which still fell short of desirable levels (PI: 2.46 ± 0.52, GI: 1.24 ± 0.24, week 6). PI and GI scores in caregivers saw steady improvement only through comprehensive training (PI: 1.41 ± 0.38, GI: 0.88 ± 0.19, week 6). Number of training sessions had the greatest influence on both patient PI and GI scores. CONCLUSIONS AND IMPLICATIONS: Comprehensive caregiver training on toothbrushing skills is effective in improving the oral hygiene of caregivers and patients with AD in nursing homes. Additional evidence is needed to establish the optimal program structure.

Effect of pulmonary vein isolation on atrial fibrillation recurrence after accessory pathway ablation in patients with Wolff-Parkinson-White syndrome.

BACKGROUND: Although successful ablation of the accessory pathway (AP) eliminates atrial fibrillation (AF) in some of patients with Wolff-Parkinson-White (WPW) syndrome and paroxysmal AF, in other patients it can recur. HYPOTHESIS: Whether adding pulmonary vein isolation (PVI) after successful AP ablation effectively prevents AF recurrence in patients with WPW syndrome is unknown. METHODS: We retrospectively studied 160 patients (102 men, 58 women; mean age, 46 ± 14 years) with WPW syndrome and paroxysmal AF who underwent AP ablation, namely 103 (64.4%) undergoing only AP ablation (AP group) and 57 (35.6%) undergoing AP ablation plus PVI (AP + PVI group). Advanced interatrial block (IAB) was defined as a P-wave duration of >120 ms and biphasic (±) morphology in the inferior leads, using 12-lead electrocardiography (ECG). RESULTS: During the mean follow-up period of 30.9 ± 9.2 months (range, 3-36 months), 22 patients (13.8%) developed AF recurrence. The recurrence rate did not differ in patients in the AP + PVI group and AP group (15.5% vs 10.5%, respectively; P = .373). Univariable and multivariable Cox regression analyses showed that PVI was not associated with the risk of AF recurrence (hazard ratio, 0.66; 95% confidence interval, 0.26-1.68; P = .380). In WPW patients with advanced IAB, the recurrence rate was lower in patients in the AP + PVI group vs the AP group (90% vs 33.3%, respectively; P = .032). CONCLUSIONS: PVI after successful AP ablation significantly reduced the AF recurrence rate in WPW patients with advanced IAB. Screening of a resting 12-lead ECG immediately after AP ablation helps identify patients in whom PVI is beneficial.

Contribution of CYP24A1 variants in coronary heart disease among the Chinese population.

BACKGROUND: Cytochrome P450 (CYPs) participate in the mechanisms of cardiovascular disease. The purpose of this research was to evaluate the contributions of CYP24A1 variants to coronary heart disease (CHD) among the Chinese Han population. METHODS: This study included 505 CHD cases and 508 controls. Four variants of CYP24A1 (rs2762934, rs1570669, rs6068816 and rs2296241) were chosen and genotyped by the Agena MassARRAY system among the Chinese population. The linkage between CYP24A1 variants and CHD risk were assessed by logistic regression to compute the odds ratio (OR) and 95% confidence interval (CI). Then, multifactor dimensionality reduction (MDR) was applied to analyze the interactions of CYP24A1 variants. RESULTS: The results of this study showed that CYP24A1 rs6068816 significantly enhanced CHD risk in multiple genetic models (allele: P = 0.014; codominant: P = 0.015; dominant: P = 0.043; recessive: P = 0.040; additive: P = 0.013), whereas rs2296241 was likely to protect individuals from CHD (codominant: P = 0.019; recessive: P = 0.013; additive: P = 0.033). Stratification analysis revealed that CYP24A1 polymorphisms had strong relationships with CHD risk that were dependent on age, sex, Gensini grade and smoking status (P <  0.05). Moreover, a four-locus model (rs2762934, rs1570669, rs6068816 and rs2296241) had significant impact on CHD risk in MDR analysis. CONCLUSION: It revealed that CYP24A1 variants were significantly linked with CHD susceptibility in the Chinese population.

Advanced interatrial block predicts recurrence of atrial fibrillation after accessory pathway ablation in patients with Wolff-Parkinson-White syndrome.

BACKGROUND: Paroxysmal atrial fibrillation (AF) frequently occurs in patients with Wolff-Parkinson-White (WPW) syndrome. Although successful ablation of the accessory pathway (AP) eliminates paroxysmal AF in some patients, in other patients it can recur. HYPOTHESIS: We investigated the clinical utility of advanced interatrial block (IAB) for predicting the risk of AF recurrence in patients with verified paroxysmal AF and WPW syndrome after successful AP ablation. METHODS: This retrospective study included 103 patients (70 men, 33 women; mean age, 44 ± 16 years) with WPW syndrome who had paroxysmal AF. A resting 12-lead electrocardiogram was performed immediately after successful AP ablation to evaluate the presence of advanced IAB, which was defined as a P-wave duration of >120 ms and biphasic [±] morphology in the inferior leads. RESULTS: During the mean follow-up period of 30.9 ± 20.0 months (range, 2-71 months), 16 patients (15.5%) developed AF recurrence. Patients with advanced IAB had significantly reduced event-free survival from AF (P < .001). Cox regression analysis with adjustment for the left atrial diameter and CHA2 DS2 -VASc score identified advanced IAB (hazard ratio, 9.18; 95% confidence interval [CI], 2.30-36.72; P = .002) and age > 50 years (hazard ratio, 12.64; 95% CI, 1.33-119.75; P = .027) as independent predictors of AF recurrence. CONCLUSIONS: Advanced IAB was an independent predictor of AF recurrence after successful AP ablation in patients with WPW syndrome.

Association of Blood Pressure Trajectories in Early Life with Subclinical Renal Damage in Middle Age.

BACKGROUND: Although high BP is one of the most important factors affecting renal function, whether longitudinal BP trajectories in early life course are associated with renal function damage in later life is unclear. METHODS: To investigate the correlation between BP trajectories from childhood to adulthood and renal function in middle age, we used group-based trajectory models to identify BP trajectories in 2430 individuals (aged 6-15 years old at baseline) participating in the ongoing Hanzhong Adolescent Hypertension Cohort. We tested the association between these trajectories and subclinical renal damage in middle age, adjusting for several covariates. RESULTS: We identified four distinct systolic BP trajectories among 2430 subjects: low stable, moderate stable, high stable, and moderate increasing on the basis of systolic BP levels at baseline and during the 30-year follow-up period. The urinary albumin-to-creatinine ratio (uACR) was higher in moderate stable, high stable, and moderate increasing groups compared with the low stable group. A total of 228 individuals had subclinical renal disease by 2017. Compared with the low stable trajectory group, the other groups had increasingly greater odds of experiencing subclinical renal disease in middle age. These associations were not altered after adjustment for other covariates, except for in the moderate stable group. Analyzed results were similar for the mean arterial pressure and diastolic BP trajectory groups. CONCLUSIONS: Higher BP trajectories were correlated with higher of uACR levels and risk of subclinical renal disease in middle age. Identifying long-term BP trajectories from early age may assist in predicting individuals' renal function in later life.

Association Between CHADS2 Score and the Development of Interatrial Block.

Interatrial block (IAB) is associated with a multitude of medical conditions. The aim of this retrospective study was to investigate whether CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) score is positively associated with the development of IAB. A total of 1072 patients (men, 555; women, 517; mean age, 61 ± 14 years) were included in the study. P-wave duration was measured manually using a caliper. IAB was defined as a P-wave duration of ≥ 120 ms on a 12-lead electrocardiogram. CHADS2 scores were calculated retrospectively. Among the 1072 patients, the prevalence of IAB was 36.1% (387/1072). In multivariate analysis, increased CHADS2 score (odds ratio [OR], 1.810; 95% confidence interval [CI], 1.577-2.077; P < 0.001), coronary artery disease (OR, 1.536; 95% CI, 1.065-2.216; P = 0.022), and increased left atrial diameter (OR, 1.039; 95% CI, 1.008-1.071; P = 0.013) were independently associated with IAB. The percentages of patients with IAB among those with a CHADS2 score of 0, 1, 2, 3, 4, 5, and 6 were 20.6%, 33.0%, 45.0%, 55.9%, 61.9%, 77.8%, and 100%, respectively (P < 0.001). There was a greater percentage of patients with a CHADS2 score of ≥ 2 with IAB compared with a CHADS2 score of < 2 (26.5% vsrsus 52.0%; P < 0.001). In receiver operating curve (ROC) analysis, CHADS2 score (area under the curve, 0.670; 95% CI, 0.636-0.704; P < 0.001) was predictive of IAB. In conclusion, CHADS2 score was significantly associated with the development of IAB in this study population.

Association between urinary sodium excretion and uric acid, and its interaction on the risk of prehypertension among Chinese young adults.

High uric acid (UA) level and high salt intake are reportedly associated with cardiovascular disease. This study investigated the association between UA and urinary sodium excretion, as well as its interaction on the risk of prehypertension. A total of 1869 participants without hypertension were recruited from a previously established cohort in Shaanxi Province, China. The participants were classified as normotensive or prehypertensive on the basis of their blood pressure. Increasing quartiles of sodium excretion were associated with high urinary UA/creatinine levels in prehypertensive participants. Estimated sodium excretion positively correlated with urinary UA/creatinine excretions in the prehypertensive group. In addition, the multivariate-adjusted odds ratios for prehypertension compared with normotension were 1.68 (1.27-2.22) for sodium excretion and 1.71 (1.21-2.42) for serum UA. Increasing sodium excretion and serum UA were associated with higher risk of prehypertension. Compared with the lowest quartiles, the highest sodium excretion and serum UA quartiles entailed 3.48 times greater risk of prehypertension. Sodium excretion is associated with urinary UA excretion in prehypertensive participants. The present study shows that high levels of salt intake and serum UA simultaneously are associated with a higher risk of prehypertension.

Usefulness of a Low Resting Heart Rate to Predict Recurrence of Atrial Fibrillation After Catheter Ablation in People ≥65 Years of Age.

A low resting heart rate (RHR) is associated with an increased risk of atrial fibrillation (AF), and this is common in older people. Whether a low RHR in older people can predict recurrence of AF after catheter ablation is unclear. A total of 329 consecutive patients ≥65 years of age with paroxysmal AF who underwent index circumferential pulmonary vein isolation were prospectively enrolled. A 10-second standard resting 12-lead electrocardiogram in sinus rhythm was recorded to measure the RR interval, P-wave duration, and PR interval. The RHR was calculated based on the mean RR interval. During a mean follow-up period of 17.0 ± 8.3 months (range, 3 to 32 months), 96 (29.2%) patients developed recurrence of AF. The AF recurrence rate was 46.2%, 32.3%, and 25.4% in patients with an RHR <50, 50 to 59, and ≥60 beats/min, respectively (log-rank test, p = 0.009). Cox regression analysis with adjustment for P-wave duration and the CHADS2 score showed that an RHR <50 beats/min (hazard ratio [HR] 1.92, 95% confidence interval [CI] 1.12 to 3.28, p = 0.017), advanced interatrial block (HR 1.82, 95% CI 1.09 to 3.04, p = 0.022), and left atrial diameter (HR 1.05, 95% CI 1.00 to 1.09, p = 0.029) were independent predictors of recurrence of AF after catheter ablation. In conclusion, in people ≥65 years of age, an RHR <50 beats/min is an independent predictor of AF recurrence in patients who have undergone catheter ablation for paroxysmal AF.