Mapping of hormones and cortisol responses in patients after Lyme neuroborreliosis

<p>Abstract</p> <p>Background</p> <p>Persistent symptoms after treatment for neuroborreliosis are common for reasons mainly unknown. These symptoms are often unspecific and could be caused by dysfunctions in endocrine systems, an issue that has not been previously addressed systematically. We therefore mapped hormone levels in patients with previous confirmed Lyme neuroborreliosis of different outcomes and compared them with a healthy control group.</p> <p>Methods</p> <p>Twenty patients of a retrospective cohort of patients treated for definite Lyme neuroborreliosis were recruited 2.3 to 3.7 years (median 2.7) after diagnosis, together with 23 healthy controls. Lyme neuroborreliosis patients were stratified into two groups according to a symptom/sign score. All participants underwent anthropometric and physiological investigation as well as an extensive biochemical endocrine investigation including a short high-dose adrenocorticotropic hormone stimulation (Synacthen^®) test. In addition to hormonal status, we also examined electrolytes, 25-hydroxy-vitamin D and interleukin-6.</p> <p>Results</p> <p>Eight patients (40%) had pronounced symptoms 2-3 years after treatment. This group had a higher cortisol response to synacthen as compared with both controls and the Lyme neuroborreliosis patients without remaining symptoms (p < 0.001 for both comparisons). No other significant differences in the various baseline biochemical parameters, anthropometric or physiological data could be detected across groups.</p> <p>Conclusions</p> <p>Apart from a positive association between the occurrence of long-lasting complaints after Lyme neuroborreliosis and cortisol response to synacthen, no corticotropic insufficiency or other serious hormonal dysfunction was found to be associated with remaining symptoms after treatment for Lyme neuroborreliosis.</p

The effect of excess weight on circulating inflammatory cytokines in drug-naïve first-episode psychosis individuals

Background: Low-grade inflammation has been repeatedly associated with both excess weight and psychosis. However, no previous studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode psychosis (FEP). Objectives: The aim of this study is to analyze the effect of BMI on basal serum cytokine levels in FEP patients and control subjects, separating the total sample into two groups: normal-weight and overweight individuals. Methods: This is a prospective and open-label study. We selected 75 FEP patients and 75 healthy controls with similar characteristics to patients according to the following variables: sex, age, and cannabis and tobacco consumption. Both controls and patients were separated into two groups according to their BMI: subjects with a BMI under 25 were considered as normal weight and those with a BMI equal to or more than 25 were considered as overweight. Serum levels of 21 cytokines/chemokines were measured at baseline using the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. We compared the basal serum levels of the 21 cytokines between control and patient groups according to their BMI. Results: In the normal-weight group, IL-8 was the only cytokine that was higher in patients than in the control group (p = 0.001), whereas in the overweight group, serum levels of two pro-inflammatory cytokines (IL-6, p = 0.000; IL-1?, p = 0.003), two chemokines (IL-8, p = 0.001; MIP-1?, p = 0.001), four Th-1 and Th-2 cytokines (IL-13, p = 0.009; IL-2, p = 0.001; IL-7, p = 0.001; IL-12p70, p = 0.010), and one Type-3 cytokine (IL-23, p = 0.010) were higher in patients than in controls. Conclusions: Most differences in the basal serum cytokine levels between patients and healthy volunteers were found in the overweight group. These findings suggest that excess weight can alter the homeostasis of the immune system and therefore may have an additive pro-inflammatory effect on the one produced by psychosis in the central nervous system.Funding: The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support from MINECO SAF2013-46292-R, Instituto de Salud Carlos III, and Fundación Marqués de Valdecilla. No pharmaceutical company has participated in the study concept and design, data collection, analysis and interpretation of the results, and drafting of the manuscript. We thank the Valdecilla Biobank for blood sampling handling and storage. We also wish to thank the participants and their families for enrolling in this study. The study, designed and directed by B C-F, conformed to international standards for research ethics and was approved by the local institutional review board

Monitoring and prevalence rates of metabolic syndrome in military veterans with serious mental illness

Background: Cardiovascular disease is the leading cause of mortality among patients with serious mental illness (SMI) and the prevalence of metabolic syndrome-a constellation of cardiovascular risk factors-is significantly higher in these patients than in the general population. Metabolic monitoring among patients using second generation antipsychotics (SGAs)-a risk factor for metabolic syndrome-has been shown to be inadequate despite the release of several guidelines. However, patients with SMI have several factors independent of medication use that predispose them to a higher prevalence of metabolic syndrome. Our study therefore examines monitoring and prevalence of metabolic syndrome in patients with SMI, including those not using SGAs. Methods and Findings: We retrospectively identified all patients treated at a Veterans Affairs Medical Center with diagnoses of schizophrenia, schizoaffective disorder or bipolar disorder during 2005-2006 and obtained demographic and clinical data. Incomplete monitoring of metabolic syndrome was defined as being unable to determine the status of at least one of the syndrome components. Of the 1,401 patients included (bipolar disorder: 822; schizophrenia: 222; and schizoaffective disorder: 357), 21.4% were incompletely monitored. Only 54.8% of patients who were not prescribed SGAs and did not have previous diagnoses of hypertension or hypercholesterolemia were monitored for all metabolic syndrome components compared to 92.4% of patients who had all three of these characteristics. Among patients monitored for metabolic syndrome completely, age-adjusted prevalence of the syndrome was 48.4%, with no significant difference between the three psychiatric groups. Conclusions: Only one half of patients with SMI not using SGAs or previously diagnosed with hypertension and hypercholesterolemia were completely monitored for metabolic syndrome components compared to greater than 90% of those with these characteristics. With the high prevalence of metabolic syndrome seen in this population, there appears to be a need to intensify efforts to reduce this monitoring gap

Proposal for an Extended Run of T2K to 20×102120\times10^{21} POT

68 pages, 31 figures68 pages, 31 figures68 pages, 31 figuresRecent measurements by the T2K neutrino oscillation experiment indicate that CP violation in neutrino mixing may be observed in the future by long-baseline neutrino oscillation experiments. We propose an extension to the currently approved T2K running from 7.8\times 10^{21}~\mbox{POT} to 20\times 10^{21}~\mbox{POT}, aiming at initial observation of CP violation with 3$\,\sigma$ or higher significance for the case of maximum CP violation. The program also contains a measurement of mixing parameters, $\theta_{23}$ and $\Delta m^2_{32}$, with a precision of 1.7$^\circ$ or better and 1%, respectively. With accelerator and beamline upgrades, as well as analysis improvements, this program would occur before the next generation of long-baseline neutrino oscillation experiments that are expected to start operation in 2026

Measurement of the single pi(0) production rate in neutral current neutrino interactions on water

The single π0 production rate in neutral current neutrino interactions on water in a neutrino beam with a peak neutrino energy of 0.6 GeV has been measured using the PØD, one of the subdetectors of the T2K near detector. The production rate was measured for data taking periods when the PØD contained water (2.64×10(20) protons-on-target) and also periods without water (3.49×10(20) protons-on-target). A measurement of the neutral current single π0 production rate on water is made using appropriate subtraction of the production rate with water in from the rate with water out of the target region. The subtraction analysis yields 106 ± 41 ± 69 signal events where the uncertainties are statistical (stat.) and systematic (sys.) respectively. This is consistent with the prediction of 157 events from the nominal simulation. The measured to expected ratio is 0.68 ± 0.26 (stat) ± 0.44 (sys) ± 0.12 (flux). The nominal simulation uses a flux integrated cross section of 7.63×10(−39)cm(2) per nucleon with an average neutrino interaction energy of 1.3 GeV

First Measurement of the Muon Neutrino Charged Current Single Pion Production Cross Section on Water with the T2K Near Detector

The T2K off-axis near detector, ND280, is used to make the first differential cross section measurements of muon neutrino charged current single positive pion production on a water target at energies ${\sim}0.8$ GeV. The differential measurements are presented as a function of muon and pion kinematics, in the restricted phase-space defined by $p_{\pi^+}>200$MeV/c, $p_{\mu^-}>200$MeV/c, $\cos \theta_{\pi^+}>0.3$ and $\cos \theta_{\mu^-}>0.3$. The total flux integrated $\nu_\mu$ charged current single positive pion production cross section on water in the restricted phase-space is measured to be $\langle\sigma\rangle_\phi=4.25\pm0.48 (\mathrm{stat})\pm1.56 (\mathrm{syst})\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}$. The total cross section is consistent with the NEUT prediction ($5.03\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}$) and 2$\sigma$ lower than the GENIE prediction ($7.68\times10^{-40} \mathrm{cm}^{2}/\mathrm{nucleon}$). The differential cross sections are in good agreement with the NEUT generator. The GENIE simulation reproduces well the shapes of the distributions, but over-estimates the overall cross section normalization

Supramolecular nanosubstrate-mediated delivery for reprogramming and transdifferentiation of mammalian cells

Supramolecular nanosubstrate-mediated delivery (SNSMD) leverages the power of molecular self-assembly and a nanostructured substrate platform for the low toxicity, highly efficient co-delivery of biological factors encapsulated in a nanovector. Human fibroblasts are successfully reprogrammed into induced pluripotent stems and transdifferentiated into induced neuronal-like cells

Supramolecular nanosubstrate-mediated delivery for reprogramming and transdifferentiation of mammalian cells

Supramolecular nanosubstrate-mediated delivery (SNSMD) leverages the power of molecular self-assembly and a nanostructured substrate platform for the low toxicity, highly efficient co-delivery of biological factors encapsulated in a nanovector. Human fibroblasts are successfully reprogrammed into induced pluripotent stems and transdifferentiated into induced neuronal-like cells

Relative risk of diabetes, dyslipidaemia, hypertension and the metabolic syndrome in people with severe mental illnesses: Systematic review and metaanalysis

<p>Abstract</p> <p>Background</p> <p>Severe mental illnesses (SMI) may be independently associated with cardiovascular risk factors and the metabolic syndrome. We aimed to systematically assess studies that compared diabetes, dyslipidaemia, hypertension and metabolic syndrome in people with and without SMI.</p> <p>Methods</p> <p>We systematically searched MEDLINE, EMBASE, CINAHL & PsycINFO. We hand searched reference lists of key articles. We employed three search main themes: SMI, cardiovascular disease, and each cardiovascular risk factor. We selected cross-sectional, case control, cohort or intervention studies comparing one or more risk factor in both SMI and a reference group. We excluded studies without any reference group. We extracted data on: study design, cardiovascular risk factor(s) and their measurement, diagnosis of SMI, study setting, sampling method, nature of comparison group and data on key risk factors.</p> <p>Results</p> <p>Of 14592 citations, 134 papers met criteria and 36 were finally included. 26 reported on diabetes, 12 hypertension, 11 dyslipidaemia, and 4 metabolic syndrome. Most studies were cross sectional, small and several lacked comparison data suitable for extraction. Meta-analysis was possible for diabetes, cholesterol and hypertension; revealing a pooled risk ratio of 1.70 (1.21 to 2.37) for diabetes and 1.11 (0.91 to 1.35) of hypertension. Restricting SMI to schizophreniform illnesses yielded a pooled risk ratio for diabetes of 1.87 (1.68 to 2.09). Total cholesterol was not higher in people with SMI (Standardized Mean Difference -0.10 (-0.55 to 0.36)) and there were inconsistent data on HDL, LDL and triglycerides with some, but not all, reporting lower levels of HDL cholesterol and raised triglyceride levels. Metabolic syndrome appeared more common in SMI.</p> <p>Conclusion</p> <p>Diabetes (but not hypertension) is more common in SMI. Data on other risk factors were limited by poor quality or inconsistent research findings, but a small number of studies show greater prevalence of the metabolic syndrome in SMI.</p