Serum Levels of Brain-Derived Neurotrophic Factor and Insulin-Like Growth Factor 1 Are Associated With Autonomic Dysfunction and Impaired Cerebral Autoregulation in Patients With Epilepsy

Background: Brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) may regulate the autonomic nervous system (ANS) in epilepsy. The present study investigated the role of IGF-1 and BDNF in the regulation of autonomic functions and cerebral autoregulation in patients with epilepsy.Methods: A total of 57 patients with focal epilepsy and 35 healthy controls were evaluated and their sudomotor, cardiovagal, and adrenergic functions were assessed using a battery of ANS function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial doppler during the breath-holding test and the Valsalva maneuver. Interictal serum levels of BDNF and IGF-1 were measured with enzyme-linked immunosorbent assay kits.Results: During interictal period, reduced serum levels of BDNF and IGF-1, impaired autonomic functions, and decreased cerebral autoregulation were noted in patients with epilepsy compared with healthy controls. Reduced serum levels of BDNF correlated with age, adrenergic and sudomotor function, overall autonomic dysfunction, and the autoregulation index calculated in Phase II of the Valsalva maneuver, and showed associations with focal to bilateral tonic-clonic seizures. Reduced serum levels of IGF-1 were found to correlate with age and cardiovagal function, a parameter of cerebral autoregulation (the breath-hold index). Patients with a longer history of epilepsy, higher seizure frequency, and temporal lobe epilepsy had lower serum levels of IGF-1.Conclusions: Long-term epilepsy and severe epilepsy, particularly temporal lobe epilepsy, may perturb BDNF and IGF-1 signaling in the central autonomic system, contributing to the autonomic dysfunction and impaired cerebral autoregulation observed in patients with focal epilepsy

Serial increase of IL-12 response and human leukocyte antigen-DR expression in severe sepsis survivors

Introduction: Sepsis-induced immunosuppression may result in death. The mechanisms of immune suppression include loss of macrophage and monocyte expression of the major histocompatibility complex, increased anti-inflammatory cytokine expression and decreased expression of proinflammatory cytokines. In this study, we sought to determine the mechanisms of immune suppression in severe sepsis by repeated detection. Methods: We designed this prospective observational study to measure monocyte human leukocyte antigen (HLA)-DR expression, plasma cytokine levels and cytokine responses on days 1 and 7 in stimulated peripheral blood mononuclear cells (PBMCs) of healthy controls and patients with severe sepsis. Results: Of the 35 enrolled patients, 23 survived for 28 days and 12 died, 6 of whom died within 7 days. Plasma levels of IL-1 beta, IL-6, IL-10, IL-17, transforming growth factor (TGF)-beta 1 and TNF-alpha were higher, but plasma IL-12 level was lower in septic patients than those in controls. Day 1 plasma levels of IL-1 beta, IL-6, IL-10 and TGF-beta 1 in nonsurvivors were higher than those in survivors. Day 7 plasma IL-10 levels in nonsurvivors were higher than in survivors. IL-1 beta response was higher, but IL-12 and TNF-alpha responses were lower in septic patients than in controls. Day 1 IL-6 response was lower, but day 1 TGF-beta 1 response was higher in nonsurvivors than in survivors. Plasma IL-6 and IL-10 levels were decreased in survivors after 6 days. IL-6 response was decreased in survivors after 6 days, but IL-12 response was increased. Monocyte percentage was higher, but positive HLA-DR percentage in monocytes and mean fluorescence intensity (MFI) of HLA-DR were lower in septic patients than in controls. MFI of HLA-DR was increased in survivors after 6 days. Conclusions: Monocyte HLA-DR expression and IL-12 response from PBMCs are restored in patients who survive severe sepsis

Quantitative thermal testing as a screening and follow-up tool for diabetic sensorimotor polyneuropathy in patients with type 2 diabetes and prediabetes

IntroductionThe diagnosis and assessment of neuropathy severity of diabetic sensorimotor polyneuropathy (DSPN) are mainly based on clinical neuropathy scores and electrophysiologic studies. This study aimed to determine whether quantitative thermal testing (QTT) can be used as a screening and follow-up tool for DSPN of prediabetes and type 2 diabetes at baseline and at 1-year follow-up.MethodsAll patients were assessed using the Toronto Clinical Neuropathy Score (TCNS) and underwent electrophysiological testing, including a nerve conduction study (NCS) and QTT, at baseline and at a 1-year follow-up. The TCNS and the composite scores of nerve conduction were used to assess the severity of DSPN. The DSPN status at the 1-year follow-up was classified as remaining no DSPN, remaining DSPN, regression to no DSPN, or progression to DSPN.ResultsDiabetic sensorimotor polyneuropathy was initially diagnosed in 89 patients with prediabetes and type 2 diabetes (22%). The regressed to no DSPN in 29 patients and progressed to DSPN in 20 patients at the 1-year follow-up. TCNS was significantly correlated with composite scores of nerve conduction, hand cold detection threshold (CDT), hand warm detection threshold (WDT), foot CDT, and foot WDT. Stepwise logistic regression demonstrated that the foot CDT (p < 0.0001) was independently associated with the presence of DSPN. The TCNS, composite scores of the nerve conduction, hand WDT, hand CDT, foot WDT, and foot CDT were all statistically significant among the four different DSPN status groups at two different time periods (baseline and the 1-year follow-up).ConclusionThe foot CDT can be used as an initial screening tool for DSPN alternatively. The characteristics of nerve damage after 1 year of DSPN can be progressive or reversible, and the neurological functions of large and small fibers have a parallel trend, which can be objectively measured by NCS and QTT

Patient-oriented simulation based on Monte Carlo algorithm by using MRI data

<p>Abstract</p> <p>Background</p> <p>Although Monte Carlo simulations of light propagation in full segmented three-dimensional MRI based anatomical models of the human head have been reported in many articles. To our knowledge, there is no patient-oriented simulation for individualized calibration with NIRS measurement. Thus, we offer an approach for brain modeling based on image segmentation process with <it>in vivo </it>MRI T1 three-dimensional image to investigate the individualized calibration for NIRS measurement with Monte Carlo simulation.</p> <p>Methods</p> <p>In this study, an individualized brain is modeled based on <it>in vivo </it>MRI 3D image as five layers structure. The behavior of photon migration was studied for this individualized brain detections based on three-dimensional time-resolved Monte Carlo algorithm. During the Monte Carlo iteration, all photon paths were traced with various source-detector separations for characterization of brain structure to provide helpful information for individualized design of NIRS system.</p> <p>Results</p> <p>Our results indicate that the patient-oriented simulation can provide significant characteristics on the optimal choice of source-detector separation within 3.3 cm of individualized design in this case. Significant distortions were observed around the cerebral cortex folding. The spatial sensitivity profile penetrated deeper to the brain in the case of expanded CSF. This finding suggests that the optical method may provide not only functional signal from brain activation but also structural information of brain atrophy with the expanded CSF layer. The proposed modeling method also provides multi-wavelength for NIRS simulation to approach the practical NIRS measurement.</p> <p>Conclusions</p> <p>In this study, the three-dimensional time-resolved brain modeling method approaches the realistic human brain that provides useful information for NIRS systematic design and calibration for individualized case with prior MRI data.</p

The significance of seizures and other predictive factors during the acute illness for the long-term outcome after bacterial meningitis

SummaryBackgroundSeizures are important neurological complications of bacterial meningitis, but no information about its epidemiology and the outcomes of seizures after community-acquired bacterial meningitis (CABM) in an adult population have been reported.AimsTo determine the frequency, clinical relevance, subtypes of seizures during the acute phase of bacterial meningitis, and the long-term outcomes of seizure complicating adult CABM.MethodsIn this 12-year retrospective study, 117 adult patients were identified with culture-proven CABM. A comparison was made between the clinical data of the patients with and without seizures during hospitalization.ResultsThirty-one patients had seizures during CABM, accounting for 27% (31/117) of the episodes. The time interval between the onset of bacterial meningitis and the seizures was 1–21 days (mean, 4 days). Furthermore, 80% (25/31) of the episodes occurred within 24h of presentation. Ten patients who had seizures progressed to status epilepticus. At follow-up after completing treatment, 10 patients completely recovered and were seizure-free, 19 died of meningitis during the acute stage and the other two progressed to chronic epilepsy.ConclusionA log-rank test demonstrated that the long-term outcome of adult CABM with acute seizures produced worse outcomes than for those who had no seizures, though no difference was noted between focal and generalized seizures. None of our patients without seizures in the acute phase of bacterial meningitis developed late seizures during the follow-up periods. Poor outcome in this study may attribute to neurological complications such as seizure, hydrocephalus, infection itself, or a combination of complications

Flexible a-IGZO phototransistor for instantaneous and cumulative UV-exposure monitoring for skin health

Flexible thin‐film phototransistors based on amorphous indium‐gallium‐zinc‐oxide semiconductor and a novel read‐out scheme allow for both real time and cumulative measurement of the ultraviolet light intensity. Furthermore, encapsulation in polydimethylsiloxane and lamination to human skin, as well as mechanical stability of the device is presented

On dynamic network entropy in cancer

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte

Paradox of low field enhancement factor for field emission nanodiodes in relation to quantum screening effects

We put forward the quantum screening effect in field emission [FE] nanodiodes, explaining relatively low field enhancement factors due to the increased potential barrier that impedes the electron Fowler-Nordheim tunneling, which is usually observed in nanoscale FE experiments. We illustratively show this effect from the energy band diagram and experimentally verify it by performing the nanomanipulation FE measurement for a single P-silicon nanotip emitter (Φ = 4.94eV), with a scanning tungsten-probe anode (work function, Φ = 4.5eV) that constitutes a 75-nm vacuum nanogap. A macroscopic FE measurement for the arrays of emitters with a 17-μm vacuum microgap was also performed for a fair comparison

Clinical characteristics and prognosis of acute bacterial meningitis in elderly patients over 65: a hospital-based study

<p>Abstract</p> <p>Background</p> <p>To examine the clinical characteristics of bacterial meningitis in elderly patients.</p> <p>Methods</p> <p>261 patients with adult bacterial meningitis (ABM), collected during a study period of 11 years (2000-2010), were included for study. Among them, 87 patients aged ≥ 65 years and were classified as the elderly group. The clinical and laboratory characteristics and prognostic factors were analyzed, and a clinical comparison with those of non-elderly ABM patients was also made.</p> <p>Results</p> <p>The 87 elderly ABM patients were composed of 53 males and 34 females, aged 65-87 years old (median = 71 years). Diabetes mellitus (DM) was the most common underlying condition (34%), followed by end stage renal disease (7%), alcoholism (4%) and malignancies (4%). Fever was the most common clinical manifestation (86%), followed by altered consciousness (62%), leukocytosis (53%), hydrocephalus (38%), seizure (30%), bacteremia (21%) and shock (11%). Thirty-nine of these 87 elderly ABM patients had spontaneous infection, while the other 48 had post-neurosurgical infection. Forty-four patients contracted ABM in a community-acquired state, while the other 43, a nosocomial state. The therapeutic results of the 87 elderly ABM patients were that 34 patients expired and 53 patients survived. The comparative results of the clinical and laboratory characteristics between the elderly and non-elderly ABM patients showed that only peripheral blood leukocytosis was significant. Presence of shock and seizure were significant prognostic factors of elderly ABM patients.</p> <p>Conclusions</p> <p>Elderly ABM patients accounted for 34.8% of the overall ABM cases, and this relatively high incidence rate may signify the future burden of ABM in the elderly population in Taiwan. The relative frequency of implicated pathogens of elderly ABM is similar to that of non-elderly ABM. Compared with non-elderly patients, the elderly ABM patients have a significantly lower incidence of peripheral blood leukocytosis. The mortality rate of elderly ABM remains high, and the presence of shock and seizures are important prognostic factors.</p