Yo jyo hen shi ko, a novel Chinese herbal, prevents nonalcoholic steatohepatitis in ob/ob mice fed a high fat or methionine-choline-deficient diet.

BACKGROUND: Oxidative stress plays a role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Yo jyo hen shi ko (YHK) is a complex compound purported to reduce reactive oxygen species (ROS) by blocking the propagation of radical-induced reactions. The aim of this study was to evaluate the role of the effect of YHK in experimental NASH. METHODS: NASH was induced in male ob/ob mice by a high-fat (HF) diet or methionine/choline-deficient (MCD) diet for 4 weeks. YHK-treated animals received YHK solution orally (20 mg/kg/day) in both experimental diets (n=6; each group) while control animals received only vehicle. RESULTS: The MCD and HF groups developed moderate diffuse macrosteatosis, hepatocellular ballooning, and a diffuse inflammatory infiltrate. With the addition of YHK, there was a marked reduction in macrosteatosis in both groups. This was associated with decreased lipoperoxide and reduced glutathione-GSH concentrations as well as reduced serum aminotransferases and improved histological markers of inflammation. These changes were also associated with weight loss in the MCD+YHK group and diminished weight gain in the HF+YHK group. CONCLUSION: YHK therapy blunts the development of macrosteatosis in these models of NASH and significantly reduces markers of oxidative stress. YHK also diminishes weight gain in this obesity prone model. Our findings warrant further study on the mechanisms involved with these effects.     

Participant report of therapist-delivered active ingredients in a telephone-delivered brief motivational intervention predicts taking steps towards change

Objective: Given the widespread potential for disseminating Motivational Interviewing (MI) through technology, the question of whether MI active ingredients are present when not delivered in person is critical to assure high treatment quality. The Participant Rating Form (PRF) was developed and used to evaluate therapist-delivered active ingredients in phone-delivered MI with hazardous drinking Emergency Department patients. Method: A factor analysis of all PRFs completed after receiving one call (n?=?256) was conducted. Multiple regression analysis was used to examine whether PRF factors predicted a measure of motivation to change – taking steps – at the second call (n?=?214). Results: The majority of participants were male (65%), with a mean age of 32 years and with an average alcohol ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) score of 20.5 (SD?=?7.1). Results of the factor analysis for the PRF revealed Relational (working collaboration) and Technical (MI behaviours) factors. After controlling for demographics, alcohol severity and baseline readiness, the technical factor predicted self-report of increased taking steps towards change while the relational factor did not explain any additional variance. Conclusions: Our study adds to the growing literature investigating patient perspectives of therapist skill as a source of information to better understand MI active ingredients. The PRF is a feasible instrument for measuring the patient’s experience of phone-based MI. Results indicate that MI active ingredients of change (relational and technical components) were present in the telephone intervention as hypothesized. Clinical Trial Registration # 01326169.     

LPS-induced impairment of Na+/K+-ATPase activity: ameliorative effect of tannic acid in mice

Metabolic Brain Disease - Acetylcholine is an excitatory neurotransmitter that modulates synaptic plasticity and communication, and it is essential for learning and memory processes. This...     

Factors influencing patient delay before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: The Stent for life initiative in Portugal

Introduction and Aims

Shorter patient delays are associated with a better prognosis for patients diagnosed with ST-segment elevation myocardial infarction (STEMI). This study aimed to identify predictors of patient delay in the Portuguese population.

Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy

The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N-methyl-d-aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser⁸⁴⁵ in the Ctx and GluR1-Ser⁸³¹ in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS.     

Impact of anterior occlusal conditions in the mixed dentition on oral health–related quality-of-life item levels:: A multivariate analysis

ObjectivesTo evaluate the impact of anterior occlusal conditions in the mixed dentition on item-level analysis of oral health–related quality of life (OHRQoL).Materials and MethodsA population-based cross-sectional study of 787 children aged 8 to 10 years was conducted. The Child Perceptions Questionnaire (CPQ_8-10) was used to evaluate OHRQoL, and the analysis of item levels was performed on CPQ_8-10 domains. Anterior occlusal characteristics were diagnosed according to the Dental Aesthetic Index criteria. Individual analyses were performed relating the outcome as independent variables. The variables with P < .20 in the individual analyses were tested in multiple logistic regression models, and those with P < .10 remained in the model. The adjusted odds ratio (OR) was estimated with a 95% confidence interval (CI).ResultsNo associations were found with regard to anterior occlusal characteristics (P < .001) after the variables of the previous determinants were adjusted for multivariate analysis. However, the following variables were significantly associated with negative impact on OHRQoL item levels: sex, in oral symptoms (OR = 1.42; CI, 1.07–1.89) and emotional well-being (OR = 1.34; CI, 1.00–1.79); race, in oral symptoms (OR = 1.48; CI, 1.10–1.98), emotional well-being (OR = 1.54; CI, 1.14–2.06), and social well-being (OR = 1.34; CI, 1.00–1.80); and family income in functional limitation (OR = 1.46; CI, 1.06–2.02), emotional well-being (OR = 1.71; CI, 1.21–2.42), and social well-being (OR = 1.59; CI, 1.14–2.21).ConclusionsAnterior occlusal conditions did not affect the levels of OHRQoL items.     

Risk factors for transient dysfunction of gas exchange after cardiac surgery

Objective

A retrospective cohort study was preformed aiming to verify the presence of transient dysfunction of gas exchange in the postoperative period of cardiac surgery and determine if this disorder is linked to cardiorespiratory events.

Methods

We included 942 consecutive patients undergoing cardiac surgery and cardiac procedures who were referred to the Intensive Care Unit between June 2007 and November 2011.

Results

Fifteen patients had acute respiratory distress syndrome (2%), 199 (27.75%) had mild transient dysfunction of gas exchange, 402 (56.1%) had moderate transient dysfunction of gas exchange, and 39 (5.4%) had severe transient dysfunction of gas exchange. Hypertension and cardiogenic shock were associated with the emergence of moderate transient dysfunction of gas exchange postoperatively (P=0.02 and P=0.019, respectively) and were risk factors for this dysfunction (P=0.0023 and P=0.0017, respectively). Diabetes mellitus was also a risk factor for transient dysfunction of gas exchange (P=0.03). Pneumonia was present in 8.9% of cases and correlated with the presence of moderate transient dysfunction of gas exchange (P=0.001). Severe transient dysfunction of gas exchange was associated with patients who had renal replacement therapy (P=0.0005), hemotherapy (P=0.0001), enteral nutrition (P=0.0012), or cardiac arrhythmia (P=0.0451).

Conclusion

Preoperative hypertension and cardiogenic shock were associated with the occurrence of postoperative transient dysfunction of gas exchange. The preoperative risk factors included hypertension, cardiogenic shock, and diabetes. Postoperatively, pneumonia, ventilator-associated pneumonia, renal replacement therapy, hemotherapy, and cardiac arrhythmia were associated with the appearance of some degree of transient dysfunction of gas exchange, which was a risk factor for reintubation, pneumonia, ventilator-associated pneumonia, and renal replacement therapy in the postoperative period of cardiac surgery and cardiac procedures.     

Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder

Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala–calcarine (P=0.01) and amygdala–thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala–ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.