Ginsenosides enhance P2X7-dependent cytokine secretion from LPS-primed rodent macrophages

The activation of P2X7 is a well-known stimulus for the NLRP3-caspase 1 inflammasome and subsequent rapid IL-1β secretion from monocytes and macrophages. Here we show that positive allosteric modulators of P2X7, ginsenosides, can enhance the release of three important cytokines, IL-1β, IL-6 and TNF-α from LPS-primed rodent macrophages using the J774 mouse macrophage cell line and primary rat peritoneal macrophages. We compared the immediate P2X7 responses in un-primed and LPS-primed macrophages and found no difference in calcium response amplitude or kinetics. These results suggest that under inflammatory conditions positive allosteric modulators are capable of increasing cytokine secretion at lower concentrations of ATP, thus boosting the initial pro-inflammatory signal. This may be important in the control of intracellular infections

Insufficient Control of Blood Pressure and Incident Diabetes

Incidence of type 2 diabetes might be associated with preexisting hypertension. There is no information on whether incident diabetes is predicted by blood pressure control. We evaluated the hazard of diabetes in relation to blood pressure control in treated hypertensive patients.Nondiabetic, otherwise healthy, hypertensive patients (N = 1,754, mean +/- SD age 52 +/- 11 years, 43\% women) participated in a network over 3.4 +/- 1 years of follow-up. Blood pressure was considered uncontrolled if systolic was >or=140 mmHg and/or diastolic was >or=90 mmHg at the last outpatient visit. Diabetes was defined according to American Diabetes Association guidelines.Uncontrolled blood pressure despite antihypertensive treatment was found in 712 patients (41\%). At baseline, patients with uncontrolled blood pressure were slightly younger than patients with controlled blood pressure (51 +/- 11 vs. 53 +/- 12 years, P < 0.001), with no differences in sex distribution, BMI, duration of hypertension, baseline blood pressure, fasting glucose, serum creatinine and potassium, lipid profile, or prevalence of metabolic syndrome. During follow-up, 109 subjects developed diabetes. Incidence of diabetes was significantly higher in patients with uncontrolled (8\%) than in those with controlled blood pressure (4\%, odds ratio 2.08, P < 0.0001). In Cox regression analysis controlling for baseline systolic blood pressure and BMI, family history of diabetes, and physical activity, uncontrolled blood pressure doubled the risk of incident diabetes (hazard ratio [HR] 2.10, P < 0.001), independently of significant effects of age (HR 1.02 per year, P = 0.03) and baseline fasting glucose (HR 1.10 per mg/dl, P < 0.001).In a large sample of treated nondiabetic hypertensive subjects, uncontrolled blood pressure is associated with twofold increased risk of incident diabetes independently of age, BMI, baseline blood pressure, or fasting glucose

Heart rate variability and target organ damage in hypertensive patients

Background: We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD). Methods: A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index. Results: Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors. Conclusions: Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD

Treatment efficacy with electrochemotherapy: A multi-institutional prospective observational study on 376 patients with superficial tumors

BACKGROUND: Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened. METHODS: This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire). RESULTS: We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p < 0.001; wound bleeding, p < 0.001; healing, p = 0.002; and aesthetics, p < 0.001). Skin toxicity (grade 653, 7.8%) was lower in patients with tumors <2 cm (p 640.001). One-year LPFS was 73.7% (95%CI 68.4-78.3). CONCLUSIONS: ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs

The Large-Scale Polarization Explorer (LSPE)

The LSPE is a balloon-borne mission aimed at measuring the polarization of the Cosmic Microwave Background (CMB) at large angular scales, and in particular to constrain the curl component of CMB polarization (B-modes) produced by tensor perturbations generated during cosmic inflation, in the very early universe. Its primary target is to improve the limit on the ratio of tensor to scalar perturbations amplitudes down to r = 0.03, at 99.7% confidence. A second target is to produce wide maps of foreground polarization generated in our Galaxy by synchrotron emission and interstellar dust emission. These will be important to map Galactic magnetic fields and to study the properties of ionized gas and of diffuse interstellar dust in our Galaxy. The mission is optimized for large angular scales, with coarse angular resolution (around 1.5 degrees FWHM), and wide sky coverage (25% of the sky). The payload will fly in a circumpolar long duration balloon mission during the polar night. Using the Earth as a giant solar shield, the instrument will spin in azimuth, observing a large fraction of the northern sky. The payload will host two instruments. An array of coherent polarimeters using cryogenic HEMT amplifiers will survey the sky at 43 and 90 GHz. An array of bolometric polarimeters, using large throughput multi-mode bolometers and rotating Half Wave Plates (HWP), will survey the same sky region in three bands at 95, 145 and 245 GHz. The wide frequency coverage will allow optimal control of the polarized foregrounds, with comparable angular resolution at all frequencies.Comment: In press. Copyright 2012 Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibite

Current treatment goals are achieved by the majority of patients with atopic dermatitis treated with tralokinumab: results from a multicentric, multinational, retrospective, cohort study

Background: Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab in a real-world setting are scarce. Research design and methods: A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts. Results: A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (&lt;65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumabtreated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16. Conclusions: This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients

The possible role of chromosome X variability in hypertensive familiarity

Familiarity participates in the pathogenesis of hypertension, although only recently, whole genome studies have proposed regions of the human genome possibly involved in the transmission of the hypertensive phenotype. Although studies have mainly focused on autosome, hitherto the influence of sex on familial transmission of hypertension has not been considered. We analysed the database of the Campania Salute Network of Hypertension center of the Federico II University Hospital of Naples (Italy), using dichotomous variables for paternal and maternal familiarity and gender (male and female) of 12 504 hypertensive patients (6868 males and 5636 females) and 6352 controls (3484 males and 2868 females), totaling 18 856 subjects. In the hypertensive group, familiarity was present in 75% of cases with odds of 3.77 and in only 26% of the normotensives with odds of 0.94. The odds ratio (OR) indicated that familiarity increases the risk of developing hypertension by 2.91 (95% confidence interval (CI)=2.67–3.17, P<0.001) times. Additionally, maternal familiarity was 37% (OR=3.01, 95% CI=2.66–3.41, P<0.001), paternal familiarity was 21% (OR=2.31, 95% CI=2.01–2.68, P<0.001) and the double familiarity was 17% (OR=3.45, 95% CI=2.87–4.01, P<0.001), thus suggesting a plausible association between maternal familiarity and development of hypertension; this finding was observed both in male and in female patients, although the phenomenon was larger in males. Given the dominance of maternal transmission in males, by genome-wide analysis of the X chromosome, we found two regions that were differently distributed in male hypertensives with maternal hypertension. Our data highlight the importance of genetic variants in the X chromosome to the maternal transmission of the hypertensive phenotype

LHC phenomenology of dark matter with a color-octet partner

Colored dark sectors where the dark matter particle is accompanied by colored partners have recently attracted theoretical and phenomenological interest. We explore the possibility that the dark sector consists of the dark matter particle and a color-octet partner, where the interaction with the Standard Model is governed by an effective operator involving gluons. The resulting interactions resemble the color analogues of electric and magnetic dipole moments. Although many phenomenological features of this kind of model only depend on the group representation of the partner under SU(3)c, we point out that interesting collider signatures such as R-hadrons are indeed controlled by the interaction operator between the dark and visible sector. We perform a study of the current constraints and future reach of LHC searches, where the complementarity between different possible signals is highlighted and exploited

Nanoscale transient polarization gratings

We present the generation of transient polarization gratings at the nanoscale, achieved using a tailored accelerator configuration of the FERMI free electron laser. We demonstrate the capabilities of such a transient polarization grating by comparing its induced dynamics with the ones triggered by a more conventional intensity grating on a thin film ferrimagnetic alloy. While the signal of the intensity grating is dominated by the thermoelastic response of the system, such a contribution is suppressed in the case of the polarization grating. This exposes helicity-dependent magnetization dynamics that have so-far remained hidden under the large thermally driven response. We anticipate nanoscale transient polarization gratings to become useful for the study of any physical, chemical and biological systems possessing chiral symmetry