Influence of food on the oral bioavailability of deramciclane from film-coated tablet in healthy male volunteers.

The effect of a high-fat meal on the oral bioavailability of deramciclane 30 mg tablet was evaluated in 18 healthy male volunteers in a randomised, single dose, two-way crossover study. The drug was administered following an overnight fast or a standardised high-fat breakfast. The plasma concentrations of deramciclane and N-desmethylderamciclane were determined by using a validated HPLC-MS -MS/MS method. An effect of food on the bioavailability was indicated if the 90% confidence interval (CI) for the ratio of geometric means of fed and fasted treatments was not contained in the equivalence limit of 0.8-1.25 for AUC and C(max). The ratios of the mean C(max) and AUC(0-infinity) values of deramciclane were 1.24 (90% CI 1.12-1.38) and 1.31 (90% CI 1.21-1.41) in fed versus fasted subjects, which overlapped but exceeded the equivalence limit. In contrast to the parent compound, the 90% CI of the mean ratios for AUC(0-infinity) and C(max) of N-desmethylderamciclane were within the predefined range. The 24 and 31% increase in C(max) and AUC(0-infinity) of deramciclane, respectively, under fed condition is modest and probably has no clinical significance since it is relatively small compared to the inter-individual variability of these parameters.     

Sex-Dependent Effects of the Intake of NOVA Classified Ultra-Processed Foods on Syndrome Metabolic Components in Brazilian Adults

Longitudinal studies evaluating the relationship between UPF consumption and the incidence of Metabolic Syndrome (MetS) and its components are still scarce. This study aimed to evaluate the effect of UPF consumption on the incidence of MetS and its components in adults. A prospective study was conducted with 896 participants from the 1978/79 Ribeirão Preto cohort, São Paulo, Brazil. UPF consumption was evaluated in %kcal and %g at ages 23–25 years. Incidence of MetS and its components were estimated at ages 37–39 years, according to the Joint Interim Statement criteria. Poisson regression was used to assess associations, and interactions with sex were investigated. UPF consumption had no association with MetS (%kcal Adjusted PR: 1.00; 95% CI: 0.99–1.01; %g Adjusted PR: 1.00; 95% CI: 0.99–1.01). However, women with higher UPF consumption, in %kcal and %g, had a higher risk of abdominal obesity (%kcal: p = 0.030; %g: p = 0.003); and women with higher UPF consumption, in %g, had a higher risk of low HDL-cholesterol (p = 0.041). For the other components of MetS, no significant associations were observed in either sex. These findings suggest evidence of no association between UPF consumption and MetS; however, consumption of UPF was associated with increased WC and low HDL-c, but only in women.     

Can Radiotherapy Empower the Host Immune System to Counterattack Neoplastic Cells? A Systematic Review on Tumor Microenvironment Radiomodulation

Despite the rising evidence in favor of immunotherapy (IT), the treatment of oncological patients affected by so-called “cold tumors” still represents an open issue. Cold tumors are characterized by an immunosuppressive (so-called cold) tumor microenvironment (TME), which favors host immune system suppression, cancer immune-escape, and a worse response to IT. However, the TME is not a static element, but dynamically mutates and can be changed. Radiotherapy (RT) can modulate a cold microenvironment, rendering it better at tumor killing by priming the quiescent host immune system, with a consequent increase in immunotherapy response. The combination of TME radiomodulation and IT could therefore be a strategy for those patients affected by cold tumors, with limited or no response to IT. Thus, this review aims to provide an easy, rapid, and practical overview of how RT could convert the cold TME and why cold tumor radiomodulation could represent an interesting strategy in combination with IT.     

Reweighted ℓ1 referenceless PRF shift thermometry

Temperature estimation in proton resonance frequency (PRF) shift MR thermometry requires a reference, or pretreatment, phase image that is subtracted from image phase during thermal treatment to yield a phase difference image proportional to temperature change. Referenceless thermometry methods derive a reference phase image from the treatment image itself by assuming that in the absence of a hot spot, the image phase can be accurately represented in a smooth (usually low order polynomial) basis. By masking the hot spot out of a least squares (?₂) regression, the reference phase image's coefficients on the polynomial basis are estimated and a reference image is derived by evaluating the polynomial inside the hot spot area. Referenceless methods are therefore insensitive to motion and bulk main field shifts, however, currently these methods require user interaction or sophisticated tracking to ensure that the hot spot is masked out of the polynomial regression. This article introduces an approach to reference PRF shift thermometry that uses reweighted ?₁ regression, a form of robust regression, to obtain background phase coefficients without hot spot tracking and masking. The method is compared to conventional referenceless thermometry, and demonstrated experimentally in monitoring HIFU heating in a phantom and canine prostate, as well as in a healthy human liver. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

The emergence of coryneform bacteria as a cause of nosocomial infections in compromised hosts

Corynebacterium species that are normally abundant on the skin and mucous membranes rarely cause infections and are susceptible to most antibiotics. The report in 1976 of four cases of sepsis at the National Institutes of Health caused by a hitherto undescribed Corynebacterium that is highly antibiotic resistant, but uniformly susceptible to vancomycin, alerted the medically oriented scientific community to the emergence of these organisms as a possible new cause of nosocomial infections. Although we have always performed antibiotic susceptibility tests on all microorganisms recovered from normally sterile body fluids, our first recovery of these organisms was in August 1977. Since then we have recovered 52 such strains from 39 patients, most frequently from the rectum, followed by the groin, blood, lesions and urine in order of predominance. Characterization by API 50 L strips revealed that most, but not all strains resemble the JK group of Riley et al. [1]. Cell wall studies and DNA base ratios further confirmed their status as corynebacteria. Hospital acquisition has been proved; cross infection between patients is the most likely mode of spread. Their recognition is necessary for optimal preventive and therapeutic care of patients with compromised host defenses.     

Baroreflex sensitivity in the elderly with silent myocardial ischemia

In order to assess high-pressure barocepture sensitivity and parasympathetic function in elderly patients with silent myocardial ischemia, we selected 45 inpatients in our geriatric unit for a prospective cohort study of patients with coronary heart disease. All patients were over 65 years of age (37 men and 8 women) and had coronary heart disease, documented by an angiographic study and electrocardiographic evidence of myocardial ischemia during exercise stress testing, performed according to the Bruce protocol. The subjects were divided in three subgroups: group 1 (22 patients) with electrocardiographic and echocardiographic history of myocardial infarction but no angina chest pain during exercise testing; group 2 (13 patients) with no exercise induced chest pain; and group 3 (10 patients) with exercise-induced chest pain. Baroceptor sensitivity was assessed in all subjects, by evaluating heart rate changes expressed in RR interval on the basis of changes in the mean arterial pressure during intravenous infusion of stepwise doses (50-100 and 150 mug) of phenylephrine hydrochloride. Heart rate changes were also evaluated during overshoot of the Valsalva maneuver (Valsalva max.), providing an index of parasympathetic activity. Our results showed that group two patients (only silent ischemia) had significantly (P>0.001) greater baroceptor sensitivity than the other two groups (group 2; 15.2+/-1.9 ms/mmHg; group 1: 10.0+/-1.7 ms/mmHg; and group 3: 9.8+/-1.7 ms/mmHg). Group two also showed a significant positive correlation (r=0.58; P<0.05) between baroceptor sensitivity and end-diastolic pressure and a significant inverse correlation (r=-0.672; P<0.05) between baroceptor sensitivity and the ejection fraction. Group 2 patients had a significantly longer RR interval than group 1 (P<0.05) and group 3 (P<0.05); a significant positive correlation (r=0.620; P<0.05) between Valsalva max. and end-diastolic pressure; and a significant inverse correlation (r=0.694; P<0.05) between Valsalva max. and the ejection fraction. Valsalva max. and baroceptor sensitivity correlated significantly in all three groups (group 1, r=0.707; P<0.001; group 2, r=0.94; P<0.001; and group 3; r=0.833; P<0.05). In conclusion our data suggest that elderly patients with silent ischemia appear to have an increased capacity for evoking parasympathetic reflexes that could inhibit pain perception.