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Background: Folate and vitamin B12 are well-known as essential nutrients that play key roles in the normal functions of the brain. Inflammatory processes play at least some role in the pathology of AD. Effective nutritional intervention approaches for improving cognitive deficits that reduce the peripheral inflammatory cytokine levels have garnered special attention. Objective: The present study aimed to determine whether supplementation with folic acid and vitamin B12, alone and in combination improves cognitive performance via reducing levels of peripheral inflammatory cytokines. Methods: 240 participants with MCI were randomly assigned in equal proportion to four treatment groups: folic acid alone, vitamin B12 alone, folic acid plus vitamin B12 or control without treatment daily for 6 months. Cognition was measured with WAIS-RC. The levels of inflammatory cytokines were measured using ELISA. Changes in cognitive function or blood biomarkers were analyzed by repeatedmeasure analysis of variance or mixed-effects models. This trial has been registered with trial number ChiCTR-ROC-16008305. Results: Compared with control group, the folic acid plus vitamin B12 group had significantly greater improvements in serum folate, homocysteine, vitamin B12 and IL-6, TNF-α, MCP-1. The folic acid plus vitamin B12 supplementation significantly changed the Full Scale IQ (effect size d = 0.169; P = 0.024), verbal IQ (effect size d = 0.146; P = 0.033), Information (d = 0.172; P = 0.019) and Digit Span (d = 0.187; P = 0.009) scores. Post hoc Turkey tests found that folic acid and vitamin B12 supplementation was significantly more effective than folic acid alone for all endpoints. Conclusions: The combination of oral folic acid plus vitamin B12 in MCI elderly for six months can significantly improve cognitive performance and reduce the levels of inflammatory cytokines in human peripheral blood. The combination of folic acid and vitamin B12 was significantly superior to either folic acid or vitamin B12 alone.

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Spatiotemporal analysis is an important tool to monitor changes of tuberculosis (TB) epidemiology, identify high-risk regions and guide resource allocation. However, there are limited data on the contributing factors of TB incidence. This study aimed to investigate the spatiotemporal pattern of TB incidence and its associated factors in mainland China during 2005-2013. Global Moran's I test, Getis-Ord Gi index and heat maps were used to examine the spatial clustering and seasonal patterns. Generalized Linear Mixed Model was applied to identify factors associated with TB incidence. TB incidence presented high geographical variations with two main hot spots, while a generally consistent seasonal pattern was observed with a peak in late winter. Furthermore, we found province-level TB incidence increased with the proportion of the elderly but decreased with Gross Demographic Product per capita and the male:female ratio. Meteorological factors also influenced TB incidence. TB showed obvious spatial clustering in mainland China and both the demographic and socio-economic factors and meteorological measures were associated with TB incidence. These results provide the related information to identify the high-risk districts and the evidence for the government to develop corresponding control measures.

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In the dual-route language model, the dorsal pathway is known for sound-to-motor mapping, but the role of the ventral stream is controversial. With the goal of enhancing our understanding of language models, this study investigated the diffusion characteristics of candidate tracts in aphasic patients. We evaluated 14 subacute aphasic patients post-stroke and 11 healthy controls with language assessment and diffusion magnetic resonance imaging. Voxel-based lesion-symptom mapping found multiple linguistic associations for the ventral stream, while automated fiber quantification (AFQ) showed, via reduced fractional anisotropy (FA) and axial diffusivity with increased radial diffusivity (all corrected p < 0.05), that the integrity of both the left dorsal and ventral streams was compromised. The average diffusion metrics of each fascicle provided by AFQ also confirmed that voxels with significant FA-language correlations were located in the ventral tracts, including the left inferior fronto-occipital fascicle (IFOF) (comprehension: r = 0.839, p = 0.001; repetition: r = 0.845, p = 0.001; naming: r = 0.813, p = 0.002; aphasia quotient: r = 0.847, p = 0.001) and uncinate fascicle (naming: r = 0.948, p = 0.001). Furthermore, point-wise AFQ revealed that the segment of the left IFOF with the strongest correlations was its narrow stem. The temporal segment of the left inferior longitudinal fascicle was also found to correlate significantly with comprehension (r = 0.663, p = 0.03) and repetition (r = 0.742, p = 0.009). This preliminary study suggests that white matter integrity analysis of the ventral stream may have the potential to reveal aphasic severity and guide individualized rehabilitation. The left IFOF, specifically its narrow stem segment, associates with multiple aspects of language, indicating an important role in semantic processing and multimodal linguistic functions.

Background: Inflammation plays a significant role in the pathophysiology of cognitive impairment in previous studies. Neutrophil-lymphocyte ratio (NLR) is a reliable measure of systemic inflammation. Objective: The aim of this study was to investigate the association between NLR and mild cognitive impairment (MCI), and further to explore the diagnostic potential of the inflammatory markers NLR for the diagnosis of MCI in elderly Chinese individuals. Methods: 186 MCI subjects and 153 subjects with normal cognitive function were evaluated consecutively in this study. Neutrophil (NEUT) count and Lymphocyte (LYM) count were measured in fasting blood samples. The NLR was calculated by dividing the absolute NEUT count by the absolute LYM count. Multivariable logistic regression was used to evaluate the potential association between NLR and MCI. NLR for predicting MCI was analyzed using Receiver Operating Characteristic (ROC) curve analysis. Results: The NLR of MCI group was significantly higher than that of subjects with normal cognitive function (2.39 ± 0.55 vs. 1.94 ± 0.51, P < 0.001). Logistic regression analysis showed that higher NLR was an independent risk factor for MCI (OR: 4.549, 95% CI: 2.623-7.889, P < 0.001). ROC analysis suggested that the optimum NLR cut-off point for MCI was 2.07 with 73.66% sensitivity, 69.28% specificity, 74.48% Positive Predictive Values (PPV) and 68.36% negative predictive values (NPV). Subjects with NLR ≥ 2.07 showed higher risk relative to NLR < 2.07 (OR: 5.933, 95% CI: 3.467-10.155, P < 0.001). Conclusion: The elevated NLR is significantly associated with increased risk of MCI. In particular, NLR level higher than the threshold of 2.07 was significantly associated with the probability of MCI.

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