Alterations in gut microbiota contribute to cognitive deficits induced by chronic infection of Toxoplasma gondii.

Chronic infection with Toxoplasma gondii (T. gondii) emerges as a risk factor for neurodegenerative diseases in animals and humans. However, the underlying mechanisms are largely unknown. We aimed to investigate whether gut microbiota and its metabolites play a role in T. gondii-induced cognitive deficits. We found that T. gondii infection induced cognitive deficits in mice, which was characterized by synaptic ultrastructure impairment and neuroinflammation in the hippocampus. Moreover, the infection led to gut microbiota dysbiosis, barrier integrity impairment, and inflammation in the colon. Interestingly, broad-spectrum antibiotic ablation of gut microbiota attenuated the adverse effects of the parasitic infection on the cognitive function in mice; cognitive deficits and hippocampal pathological changes were transferred from the infected mice to control mice by fecal microbiota transplantation. In addition, the abundance of butyrate-producing bacteria and the production of serum butyrate were decreased in infected mice. Interestingly, dietary supplementation of butyrate ameliorated T. gondii-induced cognitive impairment in mice. Notably, compared to the healthy controls, decreased butyrate production was observed in the serum of human subjects with high levels of anti-T. gondii IgG. Overall, this study demonstrates that gut microbiota is a key regulator of T. gondii-induced cognitive impairment.

Ultrasensitive Photocathodic Biosensor Based on the Cu2O/PTB7-Th/PDA+ Composite with Enhanced Photoelectrochemical Performance for the Detection of MicroRNA-375-3p.

Herein, an ultrasensitive photocathodic biosensor was fabricated based on Cu2O/PTB7-Th/PDA+ photoactive materials with high photocarrier separation efficiency for the detection of microRNA-375-3p. Impressively, the photocathodic signal of the Cu2O material was significantly enhanced by using PTB7-Th as an energy level-matching photoactive material to enhance the bulk charge separation and N,N-bis (2-(trimethylammoniumiodide) propylene) perylene-3,4,9,10-tetracarboxydiimide (PDA+) as an interfacial charge transfer mediator to efficiently suppress charge recombination at the photoelectrode/electrolyte interface. Compared with the pristine Cu2O as a photocathode, the obtained Cu2O/PTB7-Th/PDA+ exhibited a 17 times higher photocathodic signal. As a proof of concept, a PEC biosensor was fabricated by using Cu2O/PTB7-Th/PDA+ as a photoactive material and a target-triggered 3D DNA walker integrated with the dumbbell hybridization chain reaction (DHCR) as a signal amplifier to achieve the sensitive detection of microRNA-375-3p with a detection limit of 0.3 fM. This work provided a method to increase the photocurrent signal and the sensitivity of PEC-sensing platforms for the detection of biomarkers and disease diagnosis.

Altered large-scale dynamic connectivity patterns in Alzheimer's disease and mild cognitive impairment patients: A machine learning study.

Alzheimer's disease (AD) is a common neurodegeneration disease associated with substantial disruptions in the brain network. However, most studies investigated static resting-state functional connections, while the alteration of dynamic functional connectivity in AD remains largely unknown. This study used group independent component analysis and the sliding-window method to estimate the subject-specific dynamic connectivity states in 1704 individuals from three data sets. Informative inherent states were identified by the multivariate pattern classification method, and classifiers were built to distinguish ADs from normal controls (NCs) and to classify mild cognitive impairment (MCI) patients with informative inherent states similar to ADs or not. In addition, MCI subgroups with heterogeneous functional states were examined in the context of different cognition decline trajectories. Five informative states were identified by feature selection, mainly involving functional connectivity belonging to the default mode network and working memory network. The classifiers discriminating AD and NC achieved the mean area under the receiver operating characteristic curve of 0.87 with leave-one-site-out cross-validation. Alterations in connectivity strength, fluctuation, and inter-synchronization were found in AD and MCIs. Moreover, individuals with MCI were clustered into two subgroups, which had different degrees of atrophy and different trajectories of cognition decline progression. The present study uncovered the alteration of dynamic functional connectivity in AD and highlighted that the dynamic states could be powerful features to discriminate patients from NCs. Furthermore, it demonstrated that these states help to identify MCIs with faster cognition decline and might contribute to the early prevention of AD.

A facile synthesis of FeS/Fe3C nanoparticles highly dispersed on in situ grown N-doped CNTs as cathode electrocatalysts for microbial fuel cells.

A novel composite of iron sulfide, iron carbide and nitrogen carbides (Nano-FeS/Fe3C@NCNTs) as a cathode electrocatalyst for microbial fuel cells (MFCs) is synthesized by a one-pot solid state reaction, which yields a unique configuration of FeS/Fe3C nanoparticles highly dispersed on in situ grown nitrogen-doped carbon nanotubes (NCNTs). The highly dispersed FeS/Fe3C nanoparticles possess large active sites, while the NCNTs provide an electronically conductive network. Consequently, the resultant Nano-FeS/Fe3C@NCNTs exhibit excellent electrocatalytic activity towards the oxygen reduction reaction (ORR), with a half-wave potential close to that of Pt/C (about 0.88 V vs. RHE), and enable MFCs to deliver a power density of 1.28 W m-2 after two weeks' operation, which is higher than that of MFCs with Pt/C as the cathode electrocatalyst (1.02 W m-2). Theoretical calculations and experimental data demonstrate that there is a synergistic effect between Fe3C and FeS in Nano-FeS/Fe3C@NCNTs. Fe3C presents a strong attraction and electron-donating tendency to oxygen molecules, serving as the main active component, while FeS reduces charge transfer resistance by transferring electrons to Fe3C, synergistically improving the kinetics of the ORR and power density of MFCs.

Impact of signs and symptoms on the prognosis of patients with HFmrEF.

BACKGROUND: Worsening of heart failure (HF) symptoms is the leading cause of medical contact and hospitalization of patients with mildly reduced ejection fraction (HFmrEF). The prognostic value of signs and symptoms for patients with HFmrEF is currently unclear. This study investigated the prognostic impact of signs and symptoms in HFmrEF patients. METHODS: A Cox proportional risk regression model analyzed the relationship between the number of signs/symptoms and outcomes in 1691 hospitalized HFmrEF patients. Ten significant signs and symptoms were included. Patients were divided into three groups (A: ≤2, B: 3-5, C: ≥6 signs/symptoms). Stratified analysis on male and female patients was performed. The primary endpoint was all-cause mortality, and the secondary outcome was a composite of cardiovascular death and heart failure readmission (CV events) post-discharge. RESULTS: After a median follow-up of 33 months, all-cause mortality occurred in 457 patients and CV events occurred in 977 patients. Incidence of all-cause mortality was 20.7%, 32.3%* and 49.4%*† in group A, B and C of male patients, (*P < 0.05 vs. A, †P < 0.05 vs. B) and 18.8%, 33.6% and 55.8%* in group A, B and C of female patients. Incidence of CV events was 64.8%, 70.1%* and 87.5%* in group A, B and C of male patients, 61.9%, 75.3%, and 86.1%* in group A, B and C of female patients. Multivariate Cox regression showed older age, renal insufficiency, higher number of signs and symptoms (≥ 3, hazard ratio [HR] 1.317, 95% confidence interval [CI] 1.070-1.621, P = 0.009; ≥6, HR 1.982, 95% CI 1.402-2.801, P < 0.001), myocardial infarction, stroke, faster heart rate on admission, and diabetes were independently associated with all-cause mortality(all P < 0.05). Similarly, higher number of signs and symptoms (≥ 3, HR 1.271, 95% CI 1.119-1.443, P < 0.001; ≥6, HR 1.955, 95% CI 1.524-2.508, P < 0.001), older age, renal insufficiency, atrial fibrillation, and diabetes were independently associated with cardiovascular events (all P < 0.05). CONCLUSIONS: Higher number of symptoms and signs is associated with increased risk of all-cause mortality and CV events in HFmrEF patients. Our results highlight the prognostic importance of careful inquiry on HF symptoms and related physical examination in HFmrEF patients.

Astragaloside IV attenuates high glucose-induced NF-κB-mediated inflammation through activation of PI3K/AKT-ERK-dependent Nrf2/ARE signaling pathway in glomerular mesangial cells.

Inflammation is a key contributor to diabetic kidney disease pathogenesis, including reactive oxidation stress (ROS)-mediated nuclear factor-κB (NF-κB) signaling pathway. In this study, we examined the effect of Astragaloside IV (AS-IV) on anti-inflammatory and anti-oxidative properties under high glucose (HG) condition and the potential mechanism in glomerular mesangial cells (GMCs). We showed that AS-IV concentration-dependently reduced GMCs proliferation, restrained ROS release and hydrogen peroxide content, and suppressed pro-inflammatory cytokines as well as pro-fibrotic factors expression, which were associated with the inhibition of NF-κB and nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling activation. Accordingly, both NF-κB overexpression by using RNA plasmid and Nrf2 gene silencing by using RNA interference weakened the ability of AS-IV to ameliorate HG-induced oxidative stress, inflammation, and cell proliferation. Furthermore, phosphatidylinositide 3-kinases (PI3K)/serine/threonine protein kinase (Akt) and extracellular regulated protein kinases (ERK) signaling pathway regulated the process of AS-IV-induced Nrf2 activation and antioxidant capacity, which evidenced by using PI3K inhibitor LY294002 or ERK inhibitor PD98059 that largely abolished the AS-IV efficacy. Taken together, these results indicated that AS-IV protected against HG-induced GMCs damage by inhibiting ROS/NF-kB-induced increases of inflammatory cytokines, fibrosis biomarkers, and cell proliferation via up-regulation of Nrf2-dependent antioxidant enzyme expression, which were mediated by PI3K/Akt and ERK signaling pathway activation.

Role of cGAS-STING signaling pathway in cardiometabolic diseases. / cGAS-STINGé€šè·¯åœ¨ä»£è°¢æ€§å¿ƒè¡€ç®¡ç–¾ç— ä¸­çš„ä½œç”¨.

Cardiometabolic disease is a common clinical syndrome with exact causal relationship between the aberrant of glucose/lipid metabolism and cardiovascular disfunction, but its pathogenesis is unclear. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway regulates the activation of innate immunity by sensing intracellular double stranded DNA. Metabolic risk factors drive the activation of cGAS-STING pathway through mitochondrial DNA, nuclear DNA and endoplasmic reticulum stress. In addition, the activation of the cGAS-STING pathway triggers chronic sterile inflammation, excessive activation of autophagy, senescence and apoptosis in related cells of cardiovascular system. These changes induced by cGAS-STING pathway might be implicated in the onset and deterioration of cardiometabolic disease. Therefore, the targeting intervention of cGAS-STING signaling pathway may emerge as a novel treatment for cardiometabolic disease.

CD44/ERM/F-actin complex mediates targeted nuclear degranulation and excessive neutrophil extracellular trap formation during sepsis.

Neutrophils release neutrophil extracellular traps (NETs) to capture and kill pathogens, but excessive NET release can damage the surrounding tissues. Myeloperoxidase (MPO) and neutrophil elastase (NE) are thought to be important in promoting histone depolymerization and DNA breakage in the nucleus. However, the detailed path by which MPO and NE enter the nucleus is unknown. In the present study, we observed that delayed fusion of azurophilic granules with the nuclear membrane 15-20 min after extracellular degranulation in activated neutrophils. In a subsequent experiment, we further demonstrated that this fusion leads to MPO entry into the nucleus and promotes nuclear histone depolymerization and DNA breakage, a process called 'targeted nuclear degranulation'. This process can be effectively inhibited by dexamethasone and accompanied by the continuous low levels of MPO in the nucleus after PMA stimulation. Meanwhile, we found that 'targeted nuclear degranulation' is dependent on the CD44 translocation and subsequent redistribution of CD44 / ERM (Ezrin/Radixin/Moesin) / F-actin complexes, which guides the movement of azurophilic granules towards the nucleus. Application of ERM phosphorylation inhibitors and importin activity inhibitors significantly reduced the complexes formation and redistribution. Taken together, these findings indicate for the first time that delayed 'targeted nuclear degranulation' after neutrophil activation is a key mechanism of NET formation. CD44/ERM/F-actin complex mediates this process, which providing targets with promising prospects for the precise regulation of NET formation.

Development of a multi-scene universal multiple wavelet-FFT algorithm (MW-FFTA) for denoising motion artifacts in OCT-angiography in vivo imaging.

Optical coherence tomography angiography (OCTA) images suffer from inevitable micromotion (breathing, heartbeat, and blinking) noise. These image artifacts can severely disturb the visibility of results and reduce accuracy of vessel morphological and functional metrics quantization. Herein, we propose a multiple wavelet-FFT algorithm (MW-FFTA) comprising multiple integrated processes combined with wavelet-FFT and minimum reconstruction that can be used to effectively attenuate motion artifacts and significantly improve the precision of quantitative information. We verified the fidelity of image information and reliability of MW-FFTA by the image quality evaluation. The efficiency and robustness of MW-FFTA was validated by the vessel parameters on multi-scene in vivo OCTA imaging. Compared with previous algorithms, our method provides better visual and quantitative results. Therefore, the MW-FFTA possesses the potential capacity to improve the diagnosis of clinical diseases with OCTA.

Association of the cumulative triglyceride-glucose index with major adverse cardiovascular events in patients with type 2 diabetes.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and is associated with major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). However, the long-term effect of the TyG index on the incidence of MACEs remains unclear. We aimed to investigate the association between the cumulative TyG index and the risk of MACEs in patients with T2DM. METHODS: This post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial assessed patients' (T2DM > 3 months) cumulative TyG index and MACE data from the study database. Five fasting blood glucose and triglyceride measurements, at baseline and the first four visits, were taken from 5695 participants who had not experienced MACEs. Cumulative exposure to the TyG index was calculated as the weighted sum of the mean TyG index value for each time interval (value × time). Multivariable-adjusted Cox proportional hazard models and restricted cubic spline analysis were used to determine the association between the cumulative TyG index and MACEs. The incremental predictive value of the cumulative TyG index was further assessed. RESULTS: Over a median follow-up of 5.09 years, 673 (11.82%) MACEs occurred, including 256 (4.50%) cardiovascular disease (CVD) deaths, 288 (5.06%) non-fatal myocardial infarctions (MIs), and 197 (3.46%) strokes. The risk of developing MACEs increased with the cumulative TyG index quartile. After adjusting for multiple potential confounders, the hazard ratios for the very high cumulative TyG index group versus the low group were 1.59 (95% confidence interval [CI], 1.17-2.16), 1.97 (95% CI 1.19-3.26), and 1.66 (95% CI 1.02-2.70) for overall MACEs, CVD death, and non-fatal MI, respectively. Restricted cubic spline analysis also showed a cumulative increase in the risk of MACEs with an increase in the magnitude of the cumulative TyG index. The addition of the cumulative TyG index to a conventional risk model for MACEs improved the C-statistics, net reclassification improvement value, and integrated discrimination improvement value. CONCLUSIONS: In patients with T2DM, the cumulative TyG index independently predicts the incidence of MACEs, and monitoring the long-term TyG index may assist with optimized-for-risk stratification and outcome prediction for MACEs. Trial registration URL: http://www. CLINICALTRIALS: gov . Unique identifier: NCT00000620.

Giant and Controllable Photoplasticity and Photoelasticity in Compound Semiconductors.

We show that the wide-band gap compound semiconductors ZnO, ZnS, and CdS feature large photoplastic and photoelastic effects that are mediated by point defects. We measure the mechanical properties of ceramics and single crystals using nanoindentation, and we find that elasticity and plasticity vary strongly with moderate illumination. For instance, the elastic stiffness of ZnO can increase by greater than 40% due to blue illumination of intensity 1.4 mW/cm^{2}. Above-band-gap illumination (e.g., uv light) has the strongest effect, and the relative effect of subband gap illumination varies between samples-a clear sign of defect-mediated processes. We show giant optomechanical effects can be tuned by materials processing, and that processing dependence can be understood within a framework of point defect equilibrium. The photoplastic effect can be understood by a long-established theory of charged dislocation motion. The photoelastic effect requires a new theoretical framework which we present using density functional theory to study the effect of point defect ionization on local lattice structure and elastic tensors. Our results update the longstanding but lesser-studied field of semiconductor optomechanics, and suggest interesting applications.

Prediction of Alzheimer's disease using multi-variants from a Chinese genome-wide association study.

Previous genome-wide association studies have identified dozens of susceptibility loci for sporadic Alzheimer's disease, but few of these loci have been validated in longitudinal cohorts. Establishing predictive models of Alzheimer's disease based on these novel variants is clinically important for verifying whether they have pathological functions and provide a useful tool for screening of disease risk. In the current study, we performed a two-stage genome-wide association study of 3913 patients with Alzheimer's disease and 7593 controls and identified four novel variants (rs3777215, rs6859823, rs234434, and rs2255835; Pcombined = 3.07 × 10-19, 2.49 × 10-23, 1.35 × 10-67, and 4.81 × 10-9, respectively) as well as nine variants in the apolipoprotein E region with genome-wide significance (P < 5.0 × 10-8). Literature mining suggested that these novel single nucleotide polymorphisms are related to amyloid precursor protein transport and metabolism, antioxidation, and neurogenesis. Based on their possible roles in the development of Alzheimer's disease, we used different combinations of these variants and the apolipoprotein E status and successively built 11 predictive models. The predictive models include relatively few single nucleotide polymorphisms useful for clinical practice, in which the maximum number was 13 and the minimum was only four. These predictive models were all significant and their peak of area under the curve reached 0.73 both in the first and second stages. Finally, these models were validated using a separate longitudinal cohort of 5474 individuals. The results showed that individuals carrying risk variants included in the models had a shorter latency and higher incidence of Alzheimer's disease, suggesting that our models can predict Alzheimer's disease onset in a population with genetic susceptibility. The effectiveness of the models for predicting Alzheimer's disease onset confirmed the contributions of these identified variants to disease pathogenesis. In conclusion, this is the first study to validate genome-wide association study-based predictive models for evaluating the risk of Alzheimer's disease onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants, and particularly for young individuals seeking genetic consultation.

ß-Glucan ameliorates anxiety-like behavior in mice chronically infected with the Toxoplasma gondii Wh6 strain.

Chronic Toxoplasma gondii (T. gondii) infection has been revealed to be a risk factor for neuropsychiatric diseases, including anxiety. However, there is no intervention strategy. The present study aimed to investigate the protective effect of ß-glucan on T. gondii Wh6 strain-induced anxiety-like behavior in mice. The anxiety mouse model was established by infection with 10 cysts of the T. gondii Wh6 strain. ß-Glucan was intraperitoneally administered 2 weeks before infection. Open field and elevated plus maze tests were performed to assess anxiety-like behavior. In the open field test, Wh6-infected mice spent less time in the central zone and had fewer entries into the central zone. In the elevated plus maze test, the infection reduced the frequency and time of head entries in the open arms. These results showed that Wh6 causes anxiety-like behavior in mice. Interestingly, the administration of ß-glucan significantly ameliorated anxiety-like behavioral performance. The present study shows that ß-glucan can alleviate the anxiety-like behavior induced by chronic T. gondii infection in mice, which indicates that ß-glucan may be a potential drug candidate for treating T. gondii-related mental disorders, including anxiety.

Recent advances in neutrophil chemotaxis abnormalities during sepsis.

Sepsis remains one of the leading causes of death globally, in spite of advanced developments in intensive care and better understandings of pathophysiology related to sepsis. There is no special treatment or drug available for sepsis, currently. Under normal circumstances, neutrophil is a major player in acute infection control. However, during sepsis, the migration abilities and antimicrobial functions of neutrophils are impaired, resulting in a dysregulated immune response. Recent studies have indeed demonstrated that blocking or reversing neutrophil migration and impaired antibacterial function can improve the outcomes in septic animal models. This article systemically synthesized information regarding related factors and signaling involved in the functions of neutrophils in sepsis. This review also discussed the possibility that neutrophils be used as a marker for specific diagnosis and/or prediction of the outcomes of sepsis.

Grab-AD: Generalizability and reproducibility of altered brain activity and diagnostic classification in Alzheimer's Disease.

Alzheimer's disease (AD) is associated with disruptions in brain activity and networks. However, there is substantial inconsistency among studies that have investigated functional brain alterations in AD; such contradictions have hindered efforts to elucidate the core disease mechanisms. In this study, we aim to comprehensively characterize AD-associated functional brain alterations using one of the world's largest resting-state functional MRI (fMRI) biobank for the disorder. The biobank includes fMRI data from six neuroimaging centers, with a total of 252 AD patients, 221 mild cognitive impairment (MCI) patients and 215 healthy comparison individuals. Meta-analytic techniques were used to unveil reliable differences in brain function among the three groups. Relative to the healthy comparison group, AD was associated with significantly reduced functional connectivity and local activity in the default-mode network, basal ganglia and cingulate gyrus, along with increased connectivity or local activity in the prefrontal lobe and hippocampus (p < .05, Bonferroni corrected). Moreover, these functional alterations were significantly correlated with the degree of cognitive impairment (AD and MCI groups) and amyloid-ß burden. Machine learning models were trained to recognize key fMRI features to predict individual diagnostic status and clinical score. Leave-one-site-out cross-validation established that diagnostic status (mean area under the receiver operating characteristic curve: 0.85) and clinical score (mean correlation coefficient between predicted and actual Mini-Mental State Examination scores: 0.56, p < .0001) could be predicted with high accuracy. Collectively, our findings highlight the potential for a reproducible and generalizable functional brain imaging biomarker to aid the early diagnosis of AD and track its progression.

LRRC52-AS1 is associated with clinical progression and regulates cell migration and invasion in papillary thyroid cancer.

The incidence of thyroid cancer has increased in recent decades. The potential molecular mechanisms of papillary thyroid cancer (PTC) are still to be uncovered. In recent years, a number of studies reported that LRRC super family members are up-regulated in cancer cells. Cancer cells can experience a feature change from an epithelial to a mesenchymal phenotype, which is called epithelial-mesenchymal transition (EMT) during cancer progression. We found that LRRC52-AS1 is highly expressed in PTC cell lines rather than normal tissues and this observation was consistent with The Cancer Genome Atlas (TCGA) cohort. In a word, LRRC52-AS1 is associated with clinical progression in papillary thyroid cancer. In vitro experiments showed that knocking down LRRC52-AS1 significantly decreased the migration and invasion of the PTC cell lines (BCPAP and TPC). Meanwhile, LRRC52-AS1 may influence the progress of papillary thyroid cancer via mesenchymal markers N-cadherin, vimentin and TAZ. The LRRC52-AS1 gene is up-regulated in papillary thyroid cancer, and knockdown of LRRC52-AS1 could restrain cellular migration, and invasion in vitro. This study indicated that LRRC52-AS1 is a gene associated with PTC and might become a potential therapeutic target in PTC.

Ginsenoside Ameliorates Cognitive Dysfunction in Type 2 Diabetic Goto-Kakizaki Rats.

BACKGROUND Ginsenoside is the major bioactive component of ginseng, which has been proven to be a neuroprotective drug. The aim of this study was to evaluate the therapeutic effect of ginsenoside in a diabetic Goto-Kakizaki (GK) rat model. MATERIAL AND METHODS Twenty GK rats were randomly divided into a diabetic model (DM) group (n=10) and a ginsenoside + DM group (n=10); Wistar rats with the same age and body weight were used as the control (CON) group (n=10). Food and water intake, body weight, and blood fasting plasma glucose were measured. The Morris water maze test was used to detect learning and memory functions of the rats. Superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in the hippocampus were analyzed after ginsenoside treatment. RESULTS The blood glucose, body weight, Morris correlation index, SOD, MDA, and other test results were increased in the diabetic rats. Ginsenoside ameliorated diabetic cognitive decline. CONCLUSIONS The possible mechanism was related to inhibiting brain oxidative/nitrosative damage and affecting the expression of the cytokines IL-1ß, IL-6, and TNF-α.

Caregiver burden, sleep quality, depression, and anxiety in dementia caregivers: a comparison of frontotemporal lobar degeneration, dementia with Lewy bodies, and Alzheimer's disease.

ABSTRACTBackground:Very few recent studies are available that compare caregiver burden, sleep quality, and stress in caregivers of different types of dementia. We aimed to investigate caregiver burden, sleep quality, and stress in caregivers of patients with frontotemporal lobar degeneration and dementia with Lewy bodies, as compared with caregivers of patients with Alzheimer's disease. METHODS: This study was carried out from March 2011 to January 2014. In total, 492 dyads of patient and caregiver (frontotemporal lobar degeneration, n = 131; dementia with Lewy bodies, n = 36; Alzheimer's disease, n = 325) participated in this study. We compared patients with respect to the Neuropsychiatric Inventory and caregivers with respect to the Zarit Caregiver Burden Interview, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9, and Generalized Anxiety Disorder scale. RESULTS: Frontotemporal lobar degeneration and dementia with Lewy bodies patients presented significantly more neuropsychiatric symptoms compared to Alzheimer's disease patients. Caregivers of frontotemporal lobar degeneration and dementia with Lewy bodies patients experienced significantly more burden compared to Alzheimer's disease caregivers. Furthermore, among caregivers of both frontotemporal lobar degeneration and dementia with Lewy bodies patients burden was predicted by the neuropsychiatric symptoms, PHQ-9 scores, and GAD-7 scores. CONCLUSIONS: The frequency and severity of behavioral disturbances in patient and caregiver stress accounted for the increased caregiver burden, which suggests that frontotemporal lobar degeneration and dementia with Lewy bodies caregivers should receive more support than is currently available.

Caregiver burden and prevalence of depression, anxiety and sleep disturbances in Alzheimer's disease caregivers in China.

AIMS AND OBJECTIVES: To evaluate caregiver burden and factors that influence this burden among caregivers and patients with Alzheimer's disease in China. BACKGROUND: Long-term care can reduce the quality of life for caregivers and result in both mental and physical exhaustion. However, little is known about caregiver burden and associated factors in China. DESIGN: The study had a quantitative cross-sectional design. METHODS: A total of 309 caregivers and their patients were included in the study. The patients' cognitive, psychological and functional status and their caregivers' burden, sleep quality and mental state were evaluated. Descriptive analyses, single-factor regression and stepwise factor regression were used to determine the effects of various factors on caregiver burden. RESULTS: Older females and spouses still play an important role in providing family care for those with dementia. Most of the caregivers were the sole full-time caregiver and had little time for themselves. Sleepiness was a common physical problem for caregivers, and some of them had moderate to severe depression and anxiety. A lower functional status of the patient was associated with higher caregiver burden. Poorer physical status compared with before caregiving began, lower life satisfaction, and higher degrees of depression and anxiety were associated with higher caregiver burden. CONCLUSION: Depression, anxiety and sleep problems are the main challenges that are faced by family caregivers of patients with Alzheimer's disease. Caregivers' functional status, lower life satisfaction, depression and anxiety influenced caregiver burden. Caregiver burden was related to the severity of the patient's dementia and the personal factors of the caregivers. RELEVANCE TO CLINICAL PRACTICE: To provide information about caregivers' current status while caring for patients with Alzheimer's disease and to understand caregiver burden and its related factors. Professionals who work with Alzheimer's disease should pay more attention to caregiver burden, especially those with mental and physical problems.

Resveratrol Improves Cognitive Impairment by Regulating Apoptosis and Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats.

AIMS: To investigate the effects of resveratrol on cognitive impairment in streptozotocin (STZ)-induced diabetic rats and to explore the mechanisms of that phenomenon. METHODS: Sixty healthy male Sprague Dawley rats were randomly divided into four groups: normal control group (Con group, n = 15), Res group (normal Sprague Dawley rats treated with resveratrol, n = 15), diabetes mellitus group (DM group, n = 15) and DM + Res group (diabetic rats treat with resveratrol, n = 15). Streptozotocin (STZ) was injected intraperitoneally to establish the diabetic model. One week after diabetic model induction, the animals in the Res group and the DM + Res group received resveratrol intraperitoneally once a day for consecutive 4 weeks. The Morris water maze test was applied to assess the effect of resveratrol on learning and memory. To explore the mechanisms of resveratrol on cognition, we detected the protein expression levels of Caspase-3, Bcl-2, Bax, NMDAR1 (N-Methyl-d-Aspartate receptor) and BDNF (Brain Derived Neurotrophic Factor) via western blotting analysis. RESULTS: Resveratrol has no obvious effect on normal SD rats. Compared to Con group, cognitive ability was significantly impaired with increased expression of Caspase-3, Bax and down-regulation of Bcl-2, NMDAR1 and BDNF in diabetic rats. By contrast, resveratrol treatment improved the cognitive decline. Evidently, resveratrol treatment reversed diabetes-induced changes of protein expression. CONCLUSIONS: Resveratrol significantly ameliorates cognitive decline in STZ-induced diabetic model rats. The potential mechanism underlying the protective effect could be attributed to the inhibition of hippocampal apoptosis through the Bcl-2, Bax and Caspase-3 signaling pathways and improvement of synaptic dysfunction. BDNF may also play an indispensable role in this mechanism.