Functional connectivity density aberrance in type 2 diabetes mellitus with and without mild cognitive impairment.

Purpose: The objective of this study was to investigate alterations in functional connectivity density (FCD) mapping and their impact on functional connectivity (FC) among individuals diagnosed with Type 2 diabetes mellitus (T2DM) across different cognitive states. Moreover, the study sought to explore the potential association between aberrant FCD/FC patterns and clinical or cognitive variables. Methods: A total of 211 participants were recruited for this study, consisting of 75 healthy controls (HCs), 89 T2DM patients with normal cognitive function (DMCN), and 47 T2DM patients with mild cognitive impairment (DMCI). The study employed FCD analysis to pinpoint brain regions exhibiting significant FCD alterations. Subsequently, these regions showing abnormal FCD served as seeds for FC analysis. Exploratory partial correlations were conducted to explore the relationship between clinical biochemical indicators, neuropsychological test scores, and altered FCD or FC. Results: The FCD analysis revealed an increased trend in global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD) within the bilateral supramarginal gyrus (SMG) among individuals with DMCN. Additionally, significant lFCD alterations were observed in the right inferior frontal gyrus and left precuneus when comparing DMCN to HCs and DMCI. Conclusion: When comparing individuals with T2DM and healthy controls (HCs), it was revealed that DMCN exhibited significant improvements in FCD. This suggests that the brain may employ specific compensatory mechanisms to maintain normal cognitive function at this stage. Our findings provide a novel perspective on the neural mechanisms involved in cognitive decline associated with T2DM.

Structural characteristics of amygdala subregions in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) patients often suffer from depressive symptoms, which seriously affect cooperation in treatment and nursing. The amygdala plays a significant role in depression. This study aims to explore the microstructural alterations of the amygdala in T2DM and to investigate the relationship between the alterations and depressive symptoms. Fifty T2DM and 50 healthy controls were included. Firstly, the volumes of subcortical regions and subregions of amygdala were calculated by FreeSurfer. Covariance analysis (ANCOVA) was conducted between the two groups with covariates of age, sex, and estimated total intracranial volume to explore the differences in volume of subcortical regions and subregions of amygdala. Furthermore, the structural covariance within the amygdala subregions was performed. Moreover, we investigate the correlation between depressive symptoms and the volume of subcortical regions and amygdala subregions in T2DM. We observed a reduction in the volume of the bilateral cortico-amygdaloid transition area, left basal nucleus, bilateral accessory basal nucleus, left anterior amygdaloid area of amygdala, the left thalamus and left hippocampus in T2DM. T2DM patients showed decreased structural covariance connectivity between left paralaminar nucleus and the right central nucleus. Moreover, there was a negative correlation between self-rating depression scale scores and the volume of the bilateral cortico-amygdaloid transition area in T2DM. This study reveals extensive structural alterations in the amygdala subregions of T2DM patients. The reduction in the volume of the bilateral cortico-amygdaloid transition area may be a promising imaging marker for early recognition of depressive symptoms in T2DM.

Detecting type 2 diabetes mellitus cognitive impairment using whole-brain functional connectivity.

Type 2 diabetes mellitus (T2DM) is closely linked to cognitive decline and alterations in brain structure and function. Resting-state functional magnetic resonance imaging (rs-fMRI) is used to diagnose neurodegenerative diseases, such as cognitive impairment (CI), Alzheimer's disease (AD), and vascular dementia (VaD). However, whether the functional connectivity (FC) of patients with T2DM and mild cognitive impairment (T2DM-MCI) is conducive to early diagnosis remains unclear. To answer this question, we analyzed the rs-fMRI data of 37 patients with T2DM and mild cognitive impairment (T2DM-MCI), 93 patients with T2DM but no cognitive impairment (T2DM-NCI), and 69 normal controls (NC). We achieved an accuracy of 87.91% in T2DM-MCI versus T2DM-NCI classification and 80% in T2DM-NCI versus NC classification using the XGBoost model. The thalamus, angular, caudate nucleus, and paracentral lobule contributed most to the classification outcome. Our findings provide valuable knowledge to classify and predict T2DM-related CI, can help with early clinical diagnosis of T2DM-MCI, and provide a basis for future studies.

White Matter Characteristics of Damage Along Fiber Tracts in Patients with Type 2 Diabetes Mellitus.

PURPOSE: The white matter (WM) of the brain of type 2 diabetes mellitus (T2DM) patients is susceptible to neurodegenerative processes, but the specific types and positions of microstructural lesions along the fiber tracts remain unclear. METHODS: In this study 61 T2DM patients and 61 healthy controls were recruited and underwent diffusion spectrum imaging (DSI). The results were reconstructed with diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). WM microstructural abnormalities were identified using tract-based spatial statistics (TBSS). Pointwise WM tract differences were detected through automatic fiber quantification (AFQ). The relationships between WM tract abnormalities and clinical characteristics were explored with partial correlation analysis. RESULTS: TBSS revealed widespread WM lesions in T2DM patients with decreased fractional anisotropy and axial diffusivity and an increased orientation dispersion index (ODI). The AFQ results showed microstructural abnormalities in T2DM patients in specific portions of the right superior longitudinal fasciculus (SLF), right arcuate fasciculus (ARC), left anterior thalamic radiation (ATR), and forceps major (FMA). In the right ARC of T2DM patients, an aberrant ODI was positively correlated with fasting insulin and insulin resistance, and an abnormal intracellular volume fraction was negatively correlated with fasting blood glucose. Additionally, negative associations were found between blood pressure and microstructural abnormalities in the right ARC, left ATR, and FMA in T2DM patients. CONCLUSION: Using AFQ, together with DTI and NODDI, various kinds of microstructural alterations in the right SLF, right ARC, left ATR, and FMA can be accurately identified and may be associated with insulin and glucose status and blood pressure in T2DM patients.

Altered cortical thickness, degree centrality, and functional connectivity in middle-age type 2 diabetes mellitus.

Purpose: This study aimed to investigate the changes in brain structure and function in middle-aged patients with type 2 diabetes mellitus (T2DM) using morphometry and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). Methods: A total of 44 middle-aged patients with T2DM and 45 matched healthy controls (HCs) were recruited. Surface-based morphometry (SBM) was used to evaluate the changes in brain morphology. Degree centrality (DC) and functional connectivity (FC) were used to evaluate the changes in brain function. Results: Compared with HCs, middle-aged patients with T2DM exhibited cortical thickness reductions in the left pars opercularis, left transverse temporal, and right superior temporal gyri. Decreased DC values were observed in the cuneus and precuneus in T2DM. Hub-based FC analysis of these regions revealed lower connectivity in the bilateral hippocampus and parahippocampal gyrus, left precuneus, as well as left frontal sup. Conclusion: Cortical thickness, degree centrality, as well as functional connectivity were found to have significant changes in middle-aged patients with T2DM. Our observations provide potential evidence from neuroimaging for analysis to examine diabetes-related brain damage.

Cortical gray matter microstructural alterations in patients with type 2 diabetes mellitus.

BACKGROUND AND PURPOSE: Neurodegenerative processes are widespread in the brains of type 2 diabetes mellitus (T2DM) patients; gaps remain to exist in the current knowledge of the associated gray matter (GM) microstructural alterations. METHODS: A cross-sectional study was conducted to investigate alterations in GM microarchitecture in T2DM patients by diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI). Seventy-eight T2DM patients and seventy-four age-, sex-, and education level-matched healthy controls (HCs) without cognitive impairment were recruited. Cortical macrostructure and GM microstructure were assessed by surface-based analysis and GM-based spatial statistics (GBSS), respectively. Machine learning models were trained to evaluate the diagnostic values of cortical intracellular volume fraction (ICVF) for the classification of T2DM versus HCs. RESULTS: There were no differences in cortical thickness or area between the groups. GBSS analysis revealed similar GM microstructural patterns of significantly decreased fractional anisotropy, increased mean diffusivity and radial diffusivity in T2DM patients involving the frontal and parietal lobes, and significantly lower ICVF values were observed in nearly all brain regions of T2DM patients. A support vector machine model with a linear kernel was trained to realize the T2DM versus HC classification and exhibited the highest performance among the trained models, achieving an accuracy of 74% and an area under the curve of 83%. CONCLUSIONS: NODDI may help to probe the widespread GM neuritic density loss in T2DM patients occurs before measurable macrostructural alterations. The cortical ICVF values may provide valuable diagnostic information regarding the early GM microstructural alterations in T2DM.

Brain Activities Responding to Acupuncture at ST36 (zusanli) in Healthy Subjects: A Systematic Review and Meta-Analysis of Task-Based fMRI Studies.

Purpose: Stomach 36 (ST36, zusanli) is one of the important acupoints in acupuncture. Despite clinical functional magnetic resonance imaging (fMRI) studies of ST36 acupuncture, the brain activities and the neural mechanism following acupuncture at ST36 remain unclear. Methods: Literature searches were conducted on online databases, including MEDLINE, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang database, WeiPu database, and China Biology Medicine, for task-based fMRI studies of acupuncture at ST36 in healthy subjects. Brain regions activated by ST36 acupuncture were systematically evaluated and subjected to seed-based d mapping meta-analysis. Subgroup analysis was conducted on control procedures, manual acupuncture, electrical acupuncture (EA), and acupuncture-specific activations. Meta-regression analysis was performed to explore the effects of needle retention time on brain activities following ST36 acupuncture stimulation. The activated brain regions were further decoded and mapped on large-scale functional networks to further decipher the clinical relevance of acupuncturing at ST36. Results: A total of sixteen studies, involving a total of 401 right-handed healthy participants, that satisfied the inclusion criteria were included in the present meta-analysis. Meta-analysis showed that acupuncturing on ST36 positively activates the opercular part of the right inferior frontal gyrus (IFG.R), left superior temporal gyrus (STG.L), and right median cingulate/paracingulate gyri (MCG.R) regions. Needle retention time in an acupuncture session positively correlates with the activation of the left olfactory cortex, as shown in meta-regression analysis. Subgroup analysis revealed that EA stimulation may be a source of heterogeneity in the pooled results. Functional network mappings showed that the activated areas were mapped to the auditory network and salience network. Further functional decoding analysis showed that acupuncture on ST36 was associated with pain, secondary somatosensory, sound and language processing, and mood regulation. Conclusion: Acupuncture at ST36 in healthy individuals positively activates the opercular part of IFG.R, STG.L, and MCG.R. The left olfactory cortex may exhibit positive needle retention time-dependent activities. Our findings may have clinical implications for acupuncture in analgesia, language processing, and mood disorders. Systematic Review Registration: https://inplasy.com/inplasy-2021-12-0035.

Convolutional Neural Networks for Classification of T2DM Cognitive Impairment Based on Whole Brain Structural Features.

Purpose: Cognitive impairment is generally found in individuals with type 2 diabetes mellitus (T2DM). Although they may not have visible symptoms of cognitive impairment in the early stages of the disorder, they are considered to be at high risk. Therefore, the classification of these patients is important for preventing the progression of cognitive impairment. Methods: In this study, a convolutional neural network was used to construct a model for classifying 107 T2DM patients with and without cognitive impairment based on T1-weighted structural MRI. The Montreal cognitive assessment score served as an index of the cognitive status of the patients. Results: The classifier could identify T2DM-related cognitive decline with a classification accuracy of 84.85% and achieved an area under the curve of 92.65%. Conclusions: The model can help clinicians analyze and predict cognitive impairment in patients and enable early treatment.

Estimating the Effect of a Bovine Viral Diarrhea Virus Control Program: An Empirical Study on the Performance of Dutch Dairy Herds.

More and more European countries have implemented a bovine viral diarrhea virus (BVDV) control program. The economic effects of such programs have been evaluated in simulations, but empirical studies are lacking, especially in the final stage of the program. We investigated the economic (gross margin) and production effects (milk yield, somatic cell count, and calving interval) of the herds obtaining BVDV-free certification based on longitudinal annual accounting and herd performance data from Dutch dairy herds between 2014 and 2019, the final stages of the Dutch national BVDV-free program. This study was designed as a case-control study: two types of case herds were defined for two analyses. The case herds in the first analysis are herds where the BVDV status changed from "BVDV not free" to "BVDV free" during the study period. The not-free status refers to a herd that participated in the BVDV-free program but had not yet obtained the BVDV-free certification. In the second analysis, the case herds started participating in the Dutch BVDV-free program during the study period and obtained the BVDV-free certification. Control herds in both analyses were BVDV-free during the entire study period. Potential bias between the covariates of the two herd groups was reduced by matching case and control herds using the propensity score matching method. To compare the differences between case and control herds before and after BVDV-free certification, we used the time-varying Difference-in-Differences estimation (DID) methodology. The results indicate that there was no significant change in milk yield, somatic cell count, calving interval, and gross margin upon BVDV-free certification. There are several possible explanations for the non-significant effects observed in our study, such as the final stage of the BVDV control program, not knowing the true BVDV infection situation in case herds and not knowing if control measures were implemented in case herds prior to participating in the BVDV-free program. In our study, the effects of BVDV-free certification might have been underestimated, given that the Dutch BVDV control program became mandatory during the study period, and some of the case herds might have never experienced any BVDV infection. The results of this study suggest that in the final stage of the BVDV control program, the program may no longer have a clear benefit to the herd performance of participating dairy herds. When designing national programs to eradicate BVDV, it is therefore important to include incentives for such farms to motivate them to join the program.

Novel Process Methods for the Whole Cottonseed: Effect on the Digestibility, Productivity, Fat Profile, and Milk Gossypol Levels in Lactating Dairy Cows.

In this study, we aimed to determine the effect of mixed-process methods on the ruminal degradability of whole cottonseed (WCS) both in situ and in vitro, and the effect on the production performance of dairy cows. Eight WCS process methods were tested on the ruminal digestibility, including crush-alkali 1 (CA1), crush-alkali 2 (CA2), crush-alkali 3 (CA3), alkali 1-crush (A1C), alkali 2-crush (A2C), alkali 3-crush (A3C), crush-only (CO), and non-processed. Alkali 1, 2, and 3 indicate the supplementation of alkali to WCS at the dose of 4% on dry matter (DM) base as followed: 4% NaOH, 2% NaOH + 2% CaO, and 2% NaOH + 2% CaCl2 alkaline, respectively. Among all treatments, CA2 showed the highest WCS ruminal degradation in situ and the highest intestinal digestibility of WCS in vitro. Furthermore, an animal experiment was conducted for 60 days on 30 Holstein dairy cows, using a diet without WCS (CON group), a diet containing 8% non-processed WCS (NP group), and a diet containing 8% CA2-treated WCS (CA2 group). The results indicated that the dry matter intake, 4% fat-corrected milk production, milk protein, milk fat, and content of short-chain saturated fatty acid of milk in the CA2 group were significantly higher (P < 0.05) than CON group. Furthermore, DMI, the CLA was significantly greater (P < 0.05) in the CA2 group than the other groups. Additionally, the free gossypol concentration in serum or milk was under safety level in the three groups. Overall, crush and alkalization (NaOH: CaO = 1:1) treatment could improve the utilization of WCS in dairy farms.

The effect of new bovine viral diarrhea virus introduction on somatic cell count, calving interval, culling, and calf mortality of dairy herds in the Dutch bovine viral diarrhea virus-free program.

Bovine viral diarrhea virus (BVDV) infection has a major effect on the health of cows and consequently on herd performance. Many countries have implemented control or eradication programs to mitigate BVDV infection and its negative effects. These negative effects of BVDV infection on dairy herds are well documented, but there is much less information about the effects of new introduction of BVDV on dairy herds already participating in a BVDV control program. The objective of our study was to investigate the effect of a new BVDV introduction in BVDV-free herds participating in the Dutch BVDV-free program on herd performance. Longitudinal herd-level surveillance data were combined with herd information data to create 4 unique data sets, including a monthly test-day somatic cell count (SCC) data set, annual calving interval (CIV) and culling risk (CR) data sets, and a quarterly calf mortality rate (CMR) data set. Each database contained 2 types of herds: herds that remained BVDV free during the whole study period (defined as free herds), and herds that lost their BVDV-free status during the study period (defined as breakdown herds). The date of losing the BVDV-free status was defined as breakdown date. To compare breakdown herds with free herds, a random breakdown date was artificially generated for free herds by simple random sampling from the distribution of the breakdown month of the breakdown herds. The SCC and CIV before and after a new introduction of BVDV were compared through linear mixed-effects models with a Gaussian distribution, and the CR and CMR were modeled using a negative binomial distribution in generalized linear mixed-effects models. The explanatory variables for all models included herd type, BVDV status, year, and a random herd effect. Herd size was included as an explanatory variable in the SCC, CIV, and CMR model. Season was included as an explanatory variable in the SCC and CMR model. Results showed that free herds have lower SCC, CR, CMR, and shorter CIV than the breakdown herds. Within the breakdown herds, the new BVDV introduction affected the SCC and CMR. In the year after BVDV introduction, the SCC was higher than that in the year before BVDV introduction, with a factor of 1.011 [2.5th to 97.5th percentile (95% PCTL): 1.002, 1.020]. Compared with the year before BVDV breakdown, the CMR in the year of breakdown and the year after breakdown was higher, with factors of 1.170 (95% PCTL: 1.120; 1.218) and 1.096 (95% PCTL: 1.048; 1.153), respectively. This study reveals that a new introduction of BVDV had a negative but on average relatively small effect on herd performance in herds participating in a BVDV control program.

The effect of bovine viral diarrhea virus introduction on milk production of Dutch dairy herds.

Dairy cows are negatively affected by the introduction of bovine viral diarrhea virus (BVDV), and consequently, produce less milk. Existing literature on potential milk production losses is based on relatively outdated data and hardly evaluates milk production loss in relation to a new BVDV infection in a surveillance system. This study determined the annual and quarterly loss in milk production of BVDV introduction in 3,126 dairy herds participating in the Dutch BVDV-free program between 2007 and 2017. Among these herds, 640 were "breakdown-herds" that obtained and subsequently lost their BVDV-free status during the study period, and 2,486 herds obtained and retained their BVDV-free status during the study period. Milk yields before and after BVDV introduction were compared through annual and quarterly linear mixed models. The fixed variables for both models included herd type (breakdown-herd or free-herd), bovine viral diarrhea status (on an annual and quarterly basis), year, season, and a random herd effect. The dependent variable was the average daily milk yield on the test day. To define the possible BVDV-introduction dates, 4 scenarios were developed. In the default scenario, the date of breakdown (i.e., loss of the BVDV-free status) was assumed as the BVDV-introduction date. For the other 3 scenarios, the BVDV-introduction dates were set at 4, 6, and 9 mo before the date of breakdown, based on the estimated birth date of a persistently infected calf. In the default scenario, the loss in milk yield due to BVDV introduction occurred mainly in the first year after breakdown, with a reduction in yield of 0.08 kg/cow per day compared with the last year before breakdown. For the other 3 scenarios, the greatest yield reduction occurred in the second year after BVDV introduction, with a loss of 0.09, 0.09, and 0.1 kg/cow per day, respectively. For the first 4 quarters after BVDV introduction in the default scenario, milk yield loss was 0.14, 0.09, 0.02, and 0.08 kg/cow per day, respectively. These quarterly results indicated that milk yield loss was greatest in the first quarter after BVDV introduction. Overall, BVDV introduction had a negative, but on average a relatively small, effect on milk yield for herds participating in the BVDV-free program. This study will enable dairy farmers and policymakers to have a clearer understanding of the quantitative milk production effect of BVDV on dairy farms in a control program.

The prevalence of occult HBV infection in immunized children with HBsAg-positive parents: a hospital-based analysis.

BACKGROUND AND OBJECT: The risk of occult HBV infection (OBI) in children whose mothers are HBV carriers has received more widespread attention, but there were few reports to focus on the children with HBsAg-positive parents. In this study, we aimed to investigate the prevalence of OBI in immunized children with HBsAg-positive parents. METHODS: HBV-vaccinated Chinese hospitalized children with HBsAg-positive parents were analyzed in our investigation. Eligible subjects were tested using a standard nested PCR for all HBV genes, and analyzed by direct sequencing. RESULTS: There were 327 HBsAg-negative children included in the study out of about 9800 involved HBV-vaccinated hospitalized children. The positive rate of OBI was 3.1% (10/327) in the eligible children and 14.1% (46/327) with HBV DNA detectable. No significant differences were found between one and at least two regions positive groups (p > 0.05). The proportions of HBV DNA detectable in children with HBV father-carriers and mother-carriers were similar. The risk factors for HBV DNA-positive children could be male, anti-HBs levels, and anti-HBc positive. CONCLUSION: There are 3.1% of OBIs and 14.1% of suspected OBI in vaccinated children with HBsAg-positive parents. The potential risk of suspected OBI in children with HBsAg-positive father should not be ignored. Anti-HBc positivity may be a useful seromarker for suspected OBI screening in vaccinated children. To prevent HBV breakthrough infection, accurate and convenient method is needed to detect OBI timely and exhaustively.