Bisphenol a Induces Autophagy Defects and AIF-Dependent Apoptosis via HO-1 and AMPK to Degenerate N2a Neurons.

Bisphenol A (BPA) is an environmental contaminant widely suspected to be a neurological toxicant. Epidemiological studies have demonstrated close links between BPA exposure, pathogenetic brain degeneration, and altered neurobehaviors, considering BPA a risk factor for cognitive dysfunction. However, the mechanisms of BPA resulting in neurodegeneration remain unclear. Herein, cultured N2a neurons were subjected to BPA treatment, and neurotoxicity was assessed using neuronal viability and differentiation assays. Signaling cascades related to cellular self-degradation were also evaluated. BPA decreased cell viability and axon outgrowth (e.g., by down-regulating MAP2 and GAP43), thus confirming its role as a neurotoxicant. BPA induced neurotoxicity by down-regulating Bcl-2 and initiating apoptosis and autophagy flux inhibition (featured by nuclear translocation of apoptosis-inducing factor (AIF), light chain 3B (LC3B) aggregation, and p62 accumulation). Both heme oxygenase (HO)-1 and AMP-activated protein kinase (AMPK) up-regulated/activated by BPA mediated the molecular signalings involved in apoptosis and autophagy. HO-1 inhibition or AIF silencing effectively reduced BPA-induced neuronal death. Although BPA elicited intracellular oxygen free radical production, ROS scavenger NAC exerted no effect against BPA insults. These results suggest that BPA induces N2a neurotoxicity characterized by AIF-dependent apoptosis and p62-related autophagy defects via HO-1 up-regulation and AMPK activation, thereby resulting in neuronal degeneration.

Acute glucose fluctuation impacts microglial activity, leading to inflammatory activation or self-degradation.

Diabetes mellitus is associated with an increased risk of Alzheimer's dementia and cognitive decline. The cause of neurodegeneration in chronic diabetic patients remains unclear. Changes in brain microglial activity due to glycemic fluctuations may be an etiological factor. Here, we examined the impact of acute ambient glucose fluctuations on BV-2 microglial activity. Biochemical parameters were assayed and showed that the shift from normal glucose (NG; 5.5 mM) to high glucose (HG; 25 mM) promoted cell growth and induced oxidative/inflammatory stress and microglial activation, as evidenced by increased MTT reduction, elevated pro-inflammatory factor secretion (i.e., TNF-α and oxygen free radicals), and upregulated expression of stress/inflammatory proteins (i.e., HSP70, HO-1, iNOS, and COX-2). Also, LPS-induced inflammation was enlarged by an NG-to-HG shift. In contrast, the HG-to-NG shift trapped microglia in a state of metabolic stress, which led to apoptosis and autophagy, as evidenced by decreased Bcl-2 and increased cleaved caspase-3, TUNEL staining, and LC3B-II expression. These stress episodes were primarily mediated through MAPKs, PI3K/Akt, and NF-κB cascades. Our study demonstrates that acute glucose fluctuation forms the stress that alters microglial activity (e.g., inflammatory activation or self-degradation), representing a novel pathogenic mechanism for the continued deterioration of neurological function in diabetic patients.

Traumatic Thoracic Burst Fracture Associated with Bronchial Rupture.

BACKGROUND: Rupture of, or injury to, the tracheobronchial tree is a rare occurrence in blunt chest trauma. CASE REPORT: We present a case of bronchial rupture caused by fragmented bone from a spinal burst fracture after blunt chest trauma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although tracheobronchial injury is infrequent, clinicians should be aware of this possible complication after blunt chest trauma. Bronchoscopy can help in the diagnosis.

Clinical Significance of Community- and Healthcare-Acquired Carbapenem-Resistant Enterobacteriaceae Isolates.

This study was conducted to investigate the clinical significance, manifestations, microbiological characteristics and outcomes of carbapenem-resistant Enterobacteriaceae (CRE) isolates, and compare the clinical features of community- and healthcare-acquired CRE isolates. A total of 78 patients were identified to have CRE. Klebsiella pneumoniae was the most common pathogens (n = 42, 53.8%), followed by Enterobacter cloacae (n = 24, 30.8%), and Escherichia coli (n = 11, 14.1%). Most of the patients acquired CRE from healthcare settings (n = 55, 70.5%), and other cases got CRE from community settings (n = 23, 29.5%). Nine cases (11.5%) were classified as CRE colonization. Among the remaining 69 cases of CRE infections, pneumonia (n = 28, 40.6%) was the most common type of infections, followed by urinary tract infection (n = 24, 34.8%), and intra-abdominal infection (n = 16, 23.2%). The patients acquired CRE from community settings were more likely to be elderly, female, and had more urinary tract infections than from healthcare settings. In contrast, the patients acquired CRE from healthcare settings had more intra-abdominal infections, intra-abdominal surgery, and presence of indwelling device than from community settings. In conclusion, community-acquired CRE are not rare, and their associated clinical presentations are different from healthcare-acquired CRE.

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery

BACKGROUND Stroke is the major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression. Recently, small trials have demonstrated that SSRIs might improve recovery after stroke, even in people who are not depressed. Systematic reviews and meta-analyses are the least biased way to bring together data from several trials. Given the promising effect of SSRIs on stroke recovery seen in small trials, a systematic review and meta-analysis is needed. OBJECTIVE To determine whether SSRIs improve recovery after stroke, and whether treatment with SSRIs was associated with adverse effects. METHODS Search methods: We searched the Cochrane Stroke Group Trials Register (August 2011), Cochrane Depression Anxiety and Neurosis Group Trials Register (November 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 8), MEDLINE (from 1948 to August 2011), EMBASE (from 1980 to August 2011), CINAHL (from 1982 to August 2011), AMED (Allied and Complementary Medicine) (from 1985 to August 2011), PsycINFO (from 1967 to August 2011) and PsycBITE (Pyschological Database for Brain Impairment Treatment Efficacy) (March 2012). To identify further published, unpublished and ongoing trials we searched trials registers, pharmaceutical websites, reference lists, contacted experts and performed citation tracking of included studies. Selection criteria: We included randomized controlled trials that recruited stroke survivors (ischaemic or haemorrhagic) at any time within the first year. The intervention was any SSRI, given at any dose, for any period. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. In order to be included, trials had to collect data on at least one of our primary (dependence and disability) or secondary (impairments, depression, ...