Prediction of Learned Resistance or Helplessness by Hippocampal-Prefrontal Cortical Network Activity during Stress

The perception of control over a stressful experience may determine its impacts and generate resistance against future stressors. Although the medial prefrontal cortex (PFC) and the hippocampus (HPC) are implicated in the encoding of stressor controllability, the neural dynamics underlying this process are unknown. Here, we recorded HPC and PFC neural activities in male rats during the exposure to controllable, uncontrollable, or no shocks and investigated electrophysiological predictors of escape performance upon exposure to subsequent uncontrollable shocks. We were able to accurately discriminate stressed from nonstressed animals and predict resistant (R) or helpless (H) individuals based on hippocampal-cortical oscillatory dynamics. Remarkably, R animals exhibited an increase in theta power during CS, while H exhibited a decrease. Furthermore, R exhibited higher HPC to PFC θ synchronization during stress. Notably, HPC-PFC θ connectivity in the initial stress exposure showed strong correlations with escape performance evaluated days later. R rats also showed stronger θ coupling to both γ oscillations and neuronal firing in the PFC. Finally, we found that these distinct features of network dynamics collectively formed a pattern that accurately predicted learned resistance and was lacking in H individuals. Our findings suggest that hippocampal-prefrontal network θ activity supports cognitive mechanisms of stress coping, whose impairment may underlie vulnerability to stress-related disorders.SIGNIFICANCE STATEMENT The appraisal of adversities as controllable or uncontrollable is key in determining resilience or risk for stress-related disorders. Here, we performed the first electrophysiological investigation during controllable or uncontrollable stress. Pharmacological studies showed that the prefrontal cortex (PFC) and the hippocampus (HPC) encode stressor controllability, and here we identified the neural activity underlying this process. This “neural signature of stressor controllability” accurately predicted resistance to future stressors and was characterized by increased HPC-PFC oscillatory activity in the θ frequency (4–10 Hz). Our findings suggest a new role of frontal θ oscillations in adaptive stress coping, integrating its emotional and cognitive functions. We also endorse the potential of this biomarker to guide neurophysiologically-informed and rhythm-based stimulation therapies for depression.     

Hyperhomocysteinemia and the MTHFR C677T polymorphism promote steatosis and fibrosis in chronic hepatitis C patients

The factors and mechanisms implicated in the development of hepatitis C virus (HCV)-related steatosis are unknown. Hyperhomocysteinemia causes steatosis, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism induces hyperhomocysteinemia. We investigated the role of these factors in the development of HCV-related steatosis and in the progression of chronic hepatitis C (CHC). One hundred sixteen CHC patients were evaluated for HAI, fibrosis and steatosis grades, body mass index, HCV genotypes, HCV RNA levels, homocysteinemia, and the MTHFR C677T polymorphism. Hyperhomocysteinemia was associated with the TT genotype of MTHFR (r = 0.367; P = .001). Median values of homocysteine in the CC, CT, and TT genotypes of the MTHFR gene were 9.3, 12.2, and 18.6 micromol/L, respectively (P = .006). Steatosis correlated with the MTHFR polymorphism, homocysteinemia, HAI and fibrosis. Steatosis above 20% was significantly associated with fibrosis. Prevalence and high grade (>20%) of steatosis were 41% and 11% in CC, 61% and 49% in CT, and 79% and 64% in TT, respectively (P = .01). Relative risk of developing high levels of steatosis was 20 times higher for TT genotypes than CC genotypes. According to multivariate analysis, steatosis was independently associated with hyperhomocysteinemia (OR = 7.1), HAI (OR = 3.8), liver fibrosis (OR = 4.0), and HCV genotype 3 (OR = 4.6). On univariate analysis, fibrosis was associated with age, steatosis, MTHFR, homocysteinemia and HAI; however, on multivariate analysis, liver fibrosis was independently associated with age (P = .03), HAI (P = .0001), and steatosis (P = .007). In conclusion, a genetic background such as the MTHFR C677T polymorphism responsible for hyperhomocysteinemia plays a role in the development of higher degree of steatosis, which in turn accelerates the progression of liver fibrosis in CHC.     

Improved efficacy of 10-Day sequential treatment for Helicobacter pylori eradication in children: a randomized trial

BACKGROUND & AIMS: The currently recommended first-line eradication treatment of Helicobacter pylori in children is usually successful in about 75%. Recently, in adults, a novel 10-day sequential treatment has achieved an eradication rate of 95%. The aim of the study was to assess the H pylori eradication rate of the sequential treatment regimen compared with conventional triple therapy in children. METHODS: Seventy-eight consecutive children with H pylori infection were randomized to receive either sequential treatment (omeprazole plus amoxicillin for 5 days, followed by omeprazole plus clarithromycin plus tinidazole for another 5 days) (n = 38; 15 boys [39.5%]; median age, 11.0 years [range, 3.3-16 years]) or triple therapy (omeprazole, amoxicillin, and metronidazole) for 1 week (n = 37; 15 boys [40.5%]; median age, 9.9 years [range, 4.3-16 years]). H pylori infection was based on 2 out of 3 positive tests results: 13C-urea breath test, rapid urease test, and histologic analysis. Eradication was assessed by 13C-urea breath test 8 weeks after therapy. RESULTS: Seventy-four patients completed the study. H pylori eradication was achieved in 36 children receiving sequential treatment (97.3%; 95% confidence interval, 86.2-99.5) and 28 children receiving triple therapy (75.7%; 95% confidence interval, 59.8-86.7) (P < .02). Compliance with therapy was good (>95%) in all. CONCLUSIONS: Our study shows, for the first time in children, that 10-day sequential treatment achieves a higher eradication rate than standard triple therapy, which is consistent with the results of adult studies.     

Ozonized autohemotransfusion does not affect arterial vasodilation in patients with peripheral arterial disease

Ozonized autohemotransfusion has been used as a complementary therapy in patients with peripheral arterial disease (PAD). To determine whether ozone therapy could acutely modify artery vasodilatory capacity, a flow-mediated dilation test was performed at the brachial artery level before and after an ozonized autohemotransfusion in 16 patients with PAD, mean (± SD) age 55±1.8 years, and 14 healthy volunteers matched for age, sex and body mass index. Before ozonized autohemotransfusion, the mean baseline diameter of the brachial artery was higher in PAD patients than in healthy subjects (4.6±0.54 mm versus 3.6±0.54 mm, P<0.001) while mean flow-mediated brachial artery dilation and percentage of increase in flow were significantly lower in PAD patients than in controls (6.3±6.1% versus 11.8±2.4%, P<0.02; 433±61% versus 580±46%, P<0.02, respectively). No significant changes were observed after ozonized autohemotransfusion, indicating that ozonized autohemotransfusion does not modify endothelium-dependent ischemia-induced vascular reactivity.     

A nutraceutical extract from Inula viscosa leaves: UHPLC-HR-MS/MS based polyphenol profile,and antioxidant and cytotoxic activities

Nowadays, advanced extraction techniques and highly sensitive metabolic profiling methods are effectively employed to get new information on plant chemical constituents. Among them wild medicinal plants or their parts, with large and ancient use in folk medicine, are investigated for their potential functional use and cultivation. In this context, Inula viscosa leaves engaged our attention. A simple experimental design, based on Soxhlet extraction and chromatographic fractionation, allowed us to obtain the investigated polyphenol fraction (IvE). UHPLC-HRMS analyses revealed shikimoyl depsides of caffeic acid and unusual dihydrobenzofuran lignans as main secondary metabolites. These compounds, together with cinchonain-type phenols, and hydroxycinnamoyl flavonol glycosides, are reported for the first time in inula. Overall, forty-three secondary metabolites were identified. The extract exerted a remarkable antiradical activity towards DPPH^• and ABTS^+•. Furthermore, it was able to inhibit cell viability and mitochondrial redox activity of neuroblastoma, hepatoblastoma and colon carcinoma cells, whereas it did not affect cell density of HaCaT cells immortalized human keratinocytes. As detected by the oxidant-sensing probe 2′,7′-dichlorodihydrofluorescein diacetate, the inhibitory responses seemed to be related to IvE-induced increase of intracellular reactive oxygen species (ROS). The obtained results highlighted that inula leaves, nowadays even undervalued and unexplored, could be considered a renewable source of nutraceutical compounds.     

Severity of bulimia: Relationship with depression and other psychopathology

There were 53 women (35 bulimics and 18 normal controls) who were compared on the Minnesota Multiphasic Personality inventory, the Symptom Checklist-90R, and the Beck Depression Inventory. The bulimics were separated into two groups, high (N = 18) and low (N = 17) frequency purgers, based upon a median split self-monitored purging data. Bulimics who purged less than 3 times per week (M = 1.71) were classified as low frequency purgers, and those who purged more than 3 times per week (M = 9.94) were classified as high frequency purgers. Comparisons of the three groups showed that both groups of bulimics differed from normals on measures of depression, but on other measres, i. e., anxiety interpersonal sensitivity and sociopathic trait, only the high frequency purgers differed from normals. Correlational analyses indicated that these same variables, and especially depression, were positively correlated with purging, suggesting that severity of bulimia may be associated with additional psychopathology. These findings were discussed in terms of the existing literature concerning the psychopathology of bulimia.     

Skeletal muscle ventricles as left atrial-aortic pumps: short-term studies.

In 5 dogs, skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle and placed in the left hemithorax. After a 3-week vascular delay period, SMVs were electrically preconditioned with 2-Hz stimulation for 6 weeks. At a second operation, SMVs were connected between the left atrium and thoracic aorta by afferent and efferent aortic root homografts, and stimulated to contract in a 1:2 diastolic mode. At a mean left atrial pressure of 12.4 +/- 1.3 mm Hg and a burst stimulation frequency of 33 Hz, SMV stroke volume was initially 43% of that of the native left ventricle, achieving a flow equivalent to 21% of cardiac output (194 +/- 38 versus 902 +/- 85 mL/min). At 50-Hz stimulation, this figure rose to 27% (246 +/- 41 mL/min; p less than 0.05). Skeletal muscle ventricle power output (the product of stroke work and contraction rate) at 33 Hz was 0.016 +/- 0.003 W, increasing to 0.024 +/- 0.004 W at 50 Hz (p less than 0.05), corresponding to 14% and 22%, respectively, of left ventricular power output (0.11 +/- 0.012 W). After 4 hours of continuous pumping, four of the SMVs were still generating flows of more than 70% of starting values and more than 60% of initial power output. This study demonstrates that SMVs can function in the systemic circulation at physiologic left atrial preloads.     

Aqueductal stenosis 9 years after mumps meningoencephalitis: treatment by endoscopic third ventriculostomy

Introduction Hydrocephalus due to aqueductal stenosis following mumps meningoencephalitis is a rare condition, reported only in 16 cases in the literature. The pathogenetic role of the mumps virus in inducing aqueductal stenosis has been demonstrated experimentally in animal models and clinically proven in a few cases. Although obstructive in nature, the post-infectious etiology raises the question as to whether third ventriculostomy is the appropriate treatment.Patient We report a case of hydrocephalus due to pure aqueductal stenosis occurring in an 11-year-old boy who suffered from mumps meningoencephalitis 9 years previously. The boy was successfully treated by endoscopic third ventriculostomy.Conclusions The present case offers further evidence of the purely obstructive nature of the hydrocephalus induced by paramyxovirus meningoencephalitis, even if it did occur several years after the infectious disease. The pathogenesis of mumps-induced hydrocephalus and the rationale of treatment are discussed, and the literature is reviewed.     

“The Challenge Facing Renal Artery Revascularization: What Have we Not Proven and Why we Must?”

Endovascular renal artery stent therapy for atherosclerotic renal artery stenosis (RAS) is associated with excellent acute technical success, low complication rates and acceptable long-term patency. However, the clinical benefits to patients of renal artery stenting remain uncertain.

To facilitate debate regarding the treatment of RAS, we need to understand the epidemiology, basic physiology and clinical consequences of renal artery stenosis. We must attempt to determine which patients are likely to benefit from renal artery stenting, assess the nuances of the percutaneous procedure and review the current literature pertaining to renal artery stenting.