Prognostic implications of surrogate markers of atherosclerosis in low to intermediate risk patients with type 2 diabetes.

published_or_final_versio

Roles of the CHADS2 and CHA2DS2-VASc scores in post-myocardial infarction patients: Risk of new occurrence of atrial fibrillation and ischemic stroke

Background: Patients with myocardial infarction (MI) are at risk of the development of atrial fibrillation (AF) and ischemic stroke. We sought to evaluate the prognostic performance of the CHADS2 and CHA2DS2-VASc scores in predicting new AF and/or ischemic stroke in post-ST segment elevation MI (STEMI) patients. Six hundred and seven consecutive post-STEMI patients with no previously documented AF were studied.Methods and Results: After a follow-up of 63 months (3,184 patient-years), 83 (13.7%) patients developed new AF (2.8% per year). Patients with a high CHADS2 and/or CHA2DS2-VASc score were more likely to develop new AF. The annual incidence of new AF was 1.18%, 2.10%, 4.52%, and 7.03% in patients with CHADS2 of 0, 1, 2, and ≥ 3; and 0.39%, 1.72%, 1.83%, and 5.83% in patients with a CHA2DS2-VASc score of 1, 2, 3 and ≥ 4. The CHA2DS2-VASc score (C-statistic = 0.676) was superior to the CHADS2 (C-statistic = 0.632) for discriminating new AF. Ischemic stroke occurred in 29 patients (0.9% per year), the incidence increasing in line with the CHADS2 (0.41%, 1.02%, 1.11%, and 1.95% with score of 0, 1, 2, and ≥ 3) and CHA2DS2-VASc scores (0.39%, 0.49%, 1.02%, and 1.48% with score of 1, 2, 3 and ≥ 4). The C-statistic of the CHA2DS2-VASc score as a predictor of ischemic stroke was 0.601, superior to that of CHADS2 score (0.573). CHADS2 and CHA2DS2-VASc scores can identify post-STEMI patients at high risk of AF and stroke.Conclusions: The CHADS2 and CHA2DS2-VASc scores can identify post-STEMI patients at high risk of AF and ischemic stroke. This enables close surveillance and prompt anticoagulation for stroke prevention

Transmission dynamics of the etiological agent of SARS in Hong Kong: impact of public health interventions.

We present an analysis of the first 10 weeks of the severe acute respiratory syndrome (SARS) epidemic in Hong Kong. The epidemic to date has been characterized by two large clusters-initiated by two separate "super-spread" events (SSEs)-and by ongoing community transmission. By fitting a stochastic model to data on 1512 cases, including these clusters, we show that the etiological agent of SARS is moderately transmissible. Excluding SSEs, we estimate that 2.7 secondary infections were generated per case on average at the start of the epidemic, with a substantial contribution from hospital transmission. Transmission rates fell during the epidemic, primarily as a result of reductions in population contact rates and improved hospital infection control, but also because of more rapid hospital attendance by symptomatic individuals. As a result, the epidemic is now in decline, although continued vigilance is necessary for this to be maintained. Restrictions on longer range population movement are shown to be a potentially useful additional control measure in some contexts. We estimate that most currently infected persons are now hospitalized, which highlights the importance of control of nosocomial transmission

Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology

Drosophila Exo70 is Essential for Neurite Extension and Survival under Thermal Stress

The octomeric exocyst complex governs the final step of exocytosis in both plants and animals. Its roles, however, extend beyond exocytosis and include organelle biogenesis, ciliogenesis, cell migration, and cell growth. Exo70 is a conserved component of the exocyst whose function in Drosophila is unclear. In this study, we characterized two mutant alleles of Drosophila exo70. exo70 mutants exhibit reduced synaptic growth, locomotor activity, glutamate receptor density, and mEPSP amplitude. We found that presynaptic Exo70 is necessary for normal synaptic growth at the neuromuscular junction (NMJ). At the neuromuscular junction, exo70 genetically interacts with the small GTPase ralA to regulate synaptic growth. Loss of Exo70 leads to the blockage of JNK signaling-, activity-, and temperature-induced synaptic outgrowths. We showed that this phenotype is associated with an impairment of integral membrane protein transport to the cell surface at synaptic terminals. In octopaminergic motor neurons, Exo70 is detected in synaptic varicosities, as well as the regions of membrane extensions in response to activity stimulation. Strikingly, mild thermal stress causes severe neurite outgrowth defects and pharate adult lethality in exo70 mutants. exo70 mutants also display defective locomotor activity in response to starvation stress. These results demonstrated that Exo70 is an important regulator of induced synaptic growth and is crucial for an organism’s adaptation to environmental changes

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

(a) Immunoblotting analysis of IRβ in the hippocampus and frontal cortex of 18-month old wildtype and APN-KO mice. (b) Densitometric analysis of the ratio of IRβ. Mean ± S.E.M.; ***p < 0.001, n.s. statistically not significant; Scale bar: 100 μm. (JPG 30 kb

The fractional amplitude of low-frequency fluctuations signals related to amyloid uptake in high-risk populations—A pilot fMRI study

BackgroundPatients with type 2 diabetes mellitus (T2DM) and subjective cognitive decline (SCD) have a higher risk to develop Alzheimer's Disease (AD). Resting-state-functional magnetic resonance imaging (rs-fMRI) was used to document neurological involvement in the two groups from the aspect of brain dysfunction. Accumulation of amyloid-β (Aβ) starts decades ago before the onset of clinical symptoms and may already have been associated with brain function in high-risk populations. However, this study aims to compare the patterns of fractional amplitude of low-frequency fluctuations (fALFF) maps between cognitively normal high-risk groups (SCD and T2DM) and healthy elderly and evaluate the association between regional amyloid deposition and local fALFF signals in certain cortical regions.Materials and methodsA total of 18 T2DM, 11 SCD, and 18 healthy elderlies were included in this study. The differences in the fALFF maps were compared between HC and high-risk groups. Regional amyloid deposition and local fALFF signals were obtained and further correlated in two high-risk groups.ResultsCompared to HC, the altered fALFF signals of regions were shown in SCD such as the left posterior cerebellum, left putamen, and cingulate gyrus. The T2DM group illustrated altered neural activity in the superior temporal gyrus, supplementary motor area, and precentral gyrus. The correlation between fALFF signals and amyloid deposition was negative in the left anterior cingulate cortex for both groups. In the T2DM group, a positive correlation was shown in the right occipital lobe and left mesial temporal lobe.ConclusionThe altered fALFF signals were demonstrated in high-risk groups compared to HC. Very early amyloid deposition in SCD and T2DM groups was observed to affect the neural activity mainly involved in the default mode network (DMN)

The Aqueous Extract of Rhizome of Gastrodia elata

This study aims to investigate the neuroprotective effect of the rhizome of Gastrodia elata (GE) aqueous extract on beta-amyloid(Aβ)-induced toxicity in vivo and in vitro. Transgenic Drosophila mutants with Aβ-induced neurodegeneration in pan-neuron and ommatidia were used to determine the efficacy of GE. The antiapoptotic and antioxidative mechanisms of GE were also studied in Aβ-treated pheochromocytoma (PC12) cells. In vivo studies demonstrated that GE (5 mg/g Drosophila media)-treated Drosophila possessed a longer lifespan, better locomotor function, and less-degenerated ommatidia when compared with the Aβ-expressing control (all P<0.05). In vitro studies illustrated that GE increased the cell viability of Aβ-treated PC12 cells in dose-dependent manner, probably through attenuation of Aβ-induced oxidative and apoptotic stress. GE also significantly upregulated the enzymatic activities of catalase, superoxide dismutase, and glutathione peroxidase, leading to the decrease of reactive oxidation species production and apoptotic marker caspase-3 activity. In conclusion, our current data presented the first evidence that the aqueous extract of GE was capable of reducing the Aβ-induced neurodegeneration in Drosophila, possibly through inhibition of apoptosis and reduction of oxidative stress. GE aqueous extract could be developed as a promising herbal agent for neuroprotection and novel adjuvant therapies for Alzheimer’s disease