Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

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Ferulic Acid Alleviates Changes in a Rat Model of Metabolic Syndrome Induced by High-Carbohydrate,High-Fat Diet

Metabolic syndrome is a cluster of metabolic abnormalities characterized by obesity, insulin resistance, hypertension and dyslipidemia. Ferulic acid (FA) is the major phenolic compound found in rice oil and various fruits and vegetables. In this study, we examined the beneficial effects of FA in minimizing insulin resistance, vascular dysfunction and remodeling in a rat model of high-carbohydrate, high-fat diet-induced metabolic changes, which is regarded as an analogue of metabolic syndrome (MS) in man. Male Sprague-Dawley rats were fed a high carbohydrate, high fat (HCHF) diet and 15% fructose in drinking water for 16 weeks, where control rats were fed with standard chow diet and tap water. FA (30 or 60 mg/kg) was orally administered to the HCHF and control rats during the last six weeks of the study. We observed that FA significantly improved insulin sensitivity and lipid profiles, and reduced elevated blood pressure, compared to untreated controls (p < 0.05). Moreover, FA also improved vascular function and prevented vascular remodeling of mesenteric arteries. The effects of FA in HCHF-induced MS may be realized through suppression of oxidative stress by down-regulation of p47phox, increased nitric oxide (NO) bioavailability with up-regulation of endothelial nitric oxide synthase (eNOS) and suppression of tumor necrosis factor-α (TNF-α). Our results suggest that supplementation of FA may have health benefits by minimizing the cardiovascular complications of MS and alleviating its symptoms.     

How distracting is distracting pain?

The study was to determine the effect of preexisting pain on the perception of a painful stimulus. We conducted a cross-section study at an urban ED using convenience sampling. Adult patients who had a 20-g IV catheter placed as part of their ED care were eligible for the study. Patients were excluded for the following reasons: more than one IV attempt, altered mental status, visual impairment, intoxication, or a physical abnormality at the IV site. Patients were asked to indicate on a 10-cm visual analog scale (VAS) the amount of pain they had at baseline immediately before IV placement. They were then asked to indicate on a separate VAS the amount of pain caused by the IV placement. Correlation between baseline pain and pain of the IV was assessed using Pearson's rho. One hundred patients were enrolled in the study. The pain of IV placement did not differ significantly by gender, race, who placed the IV, or the location of the IV. The correlation between baseline pain and pain of the IV placement was poor (rho =.14, confidence interval:-.06-.33). The response to a standardized painful stimulus among ED patients does not correlate highly with the severity of preexisting pain.     

The effect of timing of surgery for velopharyngeal dysfunction on speech

The timing of surgery for velopharyngeal dysfunction has been based on assumptions about the relation between age, speech development, and velopharyngeal dysfunction. Cleft palate teams often counsel parents to have an intervention for velopharyngeal dysfunction performed earlier rather than later, believing that earlier interventions result in more rapid or better normalization of speech. The objective of this retrospective chart review study is to determine whether the age at surgical intervention for velopharyngeal dysfunction has an effect on the subsequent length of speech therapy. Of 174 patients included in the study database, 36 had velopharyngeal dysfunction for which further velopharyngeal management was required. Of the 36 patients who received surgical velopharyngeal dysfunction management, 27 had verifiable speech therapy records. These 27 patients represent the study population. The outcome measure was the total length of subsequent speech therapy until speech normalization. The data suggest that there is no relation between the age at velopharyngeal dysfunction surgical management and the amount of speech therapy needed to achieve normalization of the speech impairments secondary to velopharyngeal dysfunction after that management. In conclusion, 1) the age at surgical velopharyngeal dysfunction management (pharyngeal flap or sphincter pharyngoplasty) does not have an effect on subsequent normalization of speech as measured by the duration of speech therapy necessary to achieve normalization of the speech impairments secondary to velopharyngeal dysfunction after that management, and 2) the age at surgical velopharyngeal dysfunction management does not affect the likelihood of subsequent surgical velopharyngeal dysfunction management procedures.     

Rat mandibular distraction osteogenesis: latency, rate, and rhythm determine the adaptive response

Distraction osteogenesis is a well-established technique of endogenous tissue engineering. The biomechanical factors thought to affect the quality of the distraction regenerate include the latency, rate, rhythm, and consolidation period. In an effort to understand the impact of these parameters on regenerate bone formation, this study was designed to decipher the most adaptive response in a rat model of mandibular distraction osteogenesis. Ninety-six adult Sprague-Dawley rats were divided into 16 subgroups (n = 6 per subgroup) based on variations in the distraction parameters (i.e., latency, rate, and rhythm). After a 28-day consolidation period, the mandibles were harvested, decalcified, and sectioned. A standardized histologic ranking system was used to evaluate the effect of each protocol on the adaptive response of the regenerate bone. In this study, we have demonstrated that the latency period dramatically affects the success of distraction osteogenesis. Furthermore, distraction rates up to 0.50 mm per day stimulated excellent regenerate bone formation, whereas greater distraction rates produced a fibrous union. Finally, higher frequency distraction (i.e., increased rhythm) appeared to accelerate regenerate bone formation. We believe that defining the critical parameters of this model will improve future analysis of gene expression during rat mandibular distraction osteogenesis and may facilitate the development of biologically based strategies designed to enhance regenerate bone formation.     

Estimated Brain Tissue Response Following Impacts Associated With and Without Diagnosed Concussion

Kinematic measurements of head impacts are sensitive to sports concussion, but not highly specific. One potential reason is these measures reflect input conditions only and may have varying degrees of correlation to regional brain tissue deformation. In this study, previously reported head impact data recorded in the field from high school and collegiate football players were analyzed using two finite element head models (FEHM). Forty-five impacts associated with immediately diagnosed concussion were simulated along with 532 control impacts without identified concussion obtained from the same players. For each simulation, intracranial response measures (max principal strain, strain rate, von Mises stress, and pressure) were obtained for the whole brain and within four regions of interest (ROI; cerebrum, cerebellum, brain stem, corpus callosum). All response measures were sensitive to diagnosed concussion; however, large inter-athlete variability was observed and sensitivity strength depended on measure, ROI, and FEHM. Interestingly, peak linear acceleration was more sensitive to diagnosed concussion than all intracranial response measures except pressure. These findings suggest FEHM may provide unique and potentially important information on brain injury mechanisms, but estimations of concussion risk based on individual intracranial response measures evaluated in this study did not improve upon those derived from input kinematics alone.     

A Randomized Controlled Trial of Sertraline for the Treatment of Depression in Persons With Traumatic Brain Injury

Ashman TA, Cantor JB, Gordon WA, Spielman L, Flanagan S, Ginsberg A, Engmann C, Egan M, Ambrose F, Greenwald B. A randomized controlled trial of sertraline for the treatment of depression in persons with traumatic brain injury.

Objective

To examine the efficacy of sertraline in the treatment of depression after traumatic brain injury (TBI).

Design

Double-blind, randomized controlled trial.

Setting

Research center at a major urban medical center.

Participants

Subjects were a referred and volunteer sample of 52 participants with TBI, a diagnosis of major depression disorder (MDD), and a score on the Hamilton Rating Scale for Depression (HAM-D) of 18 or greater. The majority of the sample was male (58%), had less than 14 years of education (73%), had incomes below $20,000 (82%), and were from minority backgrounds (75%). Approximately one third of the sample had mild brain injuries, and two thirds had moderate to severe brain injuries. The mean age was 47±11, and the mean time since injury was 17±14 years. One participant withdrew from the study because of side effects.

Intervention

Daily oral sertraline in doses starting at 25mg and increasing to therapeutic levels (up to 200mg) or placebo for 10 weeks.

Main Outcome Measures

The HAM-D, the Beck Anxiety Inventory, and the Life-3 quality of life (QOL).

Results

No statistically significant differences were found at baseline between drug and placebo groups on baseline measures of depression (24.8±7.3 vs 27.7±7.0), anxiety (16.4±12.3 vs 24.0±14.9), or QOL (2.96±1.0 vs 2.9±0.9). The income level of those receiving placebo was significantly lower than those participants receiving medication. Analyses of covariance revealed significant changes from preintervention to posttreatment for all 3 outcome measures (P<.001) but no group effects. Random-effects modeling did not find any significant difference in patterns of scores of the outcome measures between the placebo and medication groups.

Conclusions

Both groups showed improvements in mood, anxiety, and QOL, with 59% of the experimental group and 32% of the placebo group responding to the treatment, defined as a reduction of a person's HAM-D score by 50%.     

Mycobacterium bovis Infection in Humans and Cats in Same Household,Texas, USA, 2012

Mycobacterium bovis infection of cats is exceedingly rare in regions where bovine tuberculosis is not endemic. We describe the diagnosis and clinical management of pulmonary M. bovis infection in 2 indoor-housed cats and their association with at least 1 M. bovis–infected human in Texas, USA, in September 2012.