On the origin and application of the Bruggeman correlation for analysing transport phenomena in electrochemical systems

The widely used Bruggeman equations correlate tortuosity factors of porous media with their porosity. Finding diverse application from optics to bubble formation, it received considerable attention in fuel cell and battery research, recently. The ability to estimate tortuous mass transport resistance based on porosity alone is attractive, because direct access to the tortuosity factors is notoriously difficult. The correlation, however, has limitations, which are not widely appreciated owing to the limited accessibility of the original manuscript. We retrace Bruggeman's derivation, together with its initial assumptions, and comment on validity and limitations apparent from the original work to offer some guidance on its use

Neurexin 3 Regulates Synaptic Connections Between Central Amygdala Neurons and Excitable Cells of the Lateral Parabrachial Nucleus in Rats with Varicella Zoster Induced Orofacial Pain

Phillip R Kramer,1 Rebecca S Hornung,1 Mikhail Umorin,1 M Douglas Benson,1 Paul R Kinchington2 1Department of Biomedical Sciences, Texas A&M University School of Dentistry, Dallas, TX, USA; 2Department of Ophthalmology and of Molecular Microbiology and Genetics, University of Pittsburgh, Pittsburgh, PA, USACorrespondence: Phillip R Kramer, Email [email protected]: Herpes Zoster in humans is the result of varicella zoster virus (VZV) infection. Injecting rats with varicella zoster virus produces pain similar to herpes zoster “shingles” pain in humans. . In a previous study, orofacial pain was induced by injecting the whisker pad of male rats with VZV and the pain response increased after attenuating neurexin 3 (Nrxn3) expression in the central amygdala. Neurons descend from the central amygdala to the lateral parabrachial nucleus and orofacial pain signals ascend to the lateral parabrachial nucleus. GABAergic neurons within the central amygdala regulate pain by inhibiting activity within the lateral parabrachial nucleus. Attenuating Nrxn3 expression in the central amygdala increased GABA release in the lateral parabrachial nucleus suggesting Nrxn3 controls pain by regulating GABA release. Nrxn3 can also control synaptic connections between neurons, and we hypothesized that Nrxn3 knockdown in the central amygdala would reduce the number of GABAergic synaptic connections in the lateral parabrachial nucleus and increase VZV associated pain.Methods: To test this idea, the number of synaptic connections between GABAergic cells of the central amygdala and excitatory or dynorphin positive neurons within the lateral parabrachial nucleus were quantitated after infusion of a virus expressing synaptophysin. Synaptophysin is a synaptic vesicle protein that labels neuronal synaptic connections. These connections were measured in rats with and without whisker pad injection of VZV and knockdown of Nrxn3 within the central amygdala. Orofacial pain was measured using a place escape avoidance paradigm.Results: GABAergic synaptic connections were reduced in the lateral parabrachial nucleus after Nrxn3 knockdown. Rats with a reduction in the number of connections had an increase in VZV associated orofacial pain. Immunostaining with the pain marker prodynorphin indicated that the reduction in GABAergic connections was primarily associated with prodynorphin positive neurons.Discussion: The results suggest Nrxn3 reduces VZV associated orofacial pain, in part, by enhancing synaptic connections between GABA cells of the central amygdala and pain neurons within the lateral parabrachial nucleus.Keywords: orofacial pain, zoster, shingles, varicella zoster, post-herpetic neuralgia, synaptic plasticit

Sub-Second Dopamine Detection in Human Striatum

Fast-scan cyclic voltammetry at carbon fiber microelectrodes allows rapid (sub-second) measurements of dopamine release in behaving animals. Herein, we report the modification of existing technology and demonstrate the feasibility of making sub-second measurements of dopamine release in the caudate nucleus of a human subject during brain surgery. First, we describe the modification of our electrodes that allow for measurements to be made in a human brain. Next, we demonstrate in vitro and in vivo, that our modified electrodes can measure stimulated dopamine release in a rat brain equivalently to previously determined rodent electrodes. Finally, we demonstrate acute measurements of dopamine release in the caudate of a human patient during DBS electrode implantation surgery. The data generated are highly amenable for future work investigating the relationship between dopamine levels and important decision variables in human decision-making tasks

Relationship Between Obesity and Diabetes in a US Adult Population: Findings from the National Health and Nutrition Examination Survey, 1999–2006

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Obesity is one of the most important modifiable risk factors for the prevention of type 2 diabetes. The aim of this study was to examine the prevalence of diabetes with increasing severity of obesity and the distribution of HbA1c levels in diabetics participating in the latest National Health and Nutrition Examination Survey (NHANES). Methods Data from a representative sample of adults with diabetes participating in the NHANES between 1999 and 2006 were reviewed. The prevalence of diabetes and levels of fasting glucose, insulin, c-peptide, and HbA1c were examined across different weight classes with normal weight, overweight, and obesity classes 1, 2, and 3 were defined as body mass index (BMI) of <25.0, 25.0–29.9, 30.0–34.9, 35.0–39.9, and equal to 40.0, respectively. The distribution of HbA1c levels among adults with diabetes was also examined. Results There were 2,894 adults with diabetes (13.6%) among the 21,205 surveyed participants. Among the adults with diabetes, the mean age was 59 years, the mean fasting glucose was 155±2 mg/dl, and the mean HbA1c was 7.2%; 80.3 % of diabetics were considered overweight (BMI≥25) and 49.1 % of diabetics were considered obese (BMI≥30). Presented as a poster presentation at the American Society fo

The interplay of intrinsic and extrinsic bounded noises in genetic networks

After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a genetic network. The influence of intrinsic and extrinsic noises on genetic networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: $(i)$ the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, $(ii)$ a model of enzymatic futile cycle and $(iii)$ a genetic toggle switch. In $(ii)$ and $(iii)$ we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possibile functional role of bounded noises

Focal Cerebral Magnetic Resonance Changes Associated with Partial Status Epilepticus

We report 2 patients with transient abnormalities on magnetic resonance imaging (MRI) associated with partial status epilepticus (SE). A man with a 4-month history of partial seizures had complex partial SE for 9 days, with left temporal maximum on ictal EEG. Left temporal lobe T 2 signal was increased on MRI during SE, but cerebral MRI was normal 9 weeks later. A woman with “cryptogenic” temporal lobe epilepsy for 16 years had complex partial SE for 1 week, with right temporal maximum on ictal EEG. T 2 Signal was increased over the entire right temporal lobe, extending into the insula, without mass effect, on MRI 1 month after SE ended. Repeat MRI 1 month later showed marked decrease in volume of increased T 2 intensity, without gadolinium enhancement, but with mild mass effect over the right anteroinferomesial temporal areas. A gemistocytic astrocytoma was resected. Focal cerebral MRI abnormalities consistent with cerebral edema may be due to partial SE but also may indicate underlying glioma, even in long-standing partial epilepsy. Focal structural imaging changes consistent with neoplasm should be followed to full resolution after partial SE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65221/1/j.1528-1157.1994.tb02909.x.pd

Paliperidone ER and oral risperidone in patients with schizophrenia: a comparative database analysis

<p>Abstract</p> <p>Background</p> <p>To compare the efficacy and tolerability of paliperidone extended-release (ER) with risperidone immediate-release using propensity score methodology.</p> <p>Methods</p> <p>Six double-blind, randomized, placebo-controlled, short-term clinical trials for acute schizophrenia with availability of individual patient-level data were identified (3 per compound). Propensity score pairwise matching was used to balance observed covariates between the paliperidone ER and risperidone patient populations. Scores were generated using logistic regression models, with age, body mass index, race, sex, baseline Positive and Negative Syndrome Scale (PANSS) total score and baseline Clinical Global Impressions–Severity (CGI-S) score as factors. The dosage range of paliperidone ER (6-12 mg/day) was compared with 2 risperidone dosage ranges: 2-4 and 4-6 mg/day. The primary efficacy measure was change in PANSS total score at week 6 end point. Tolerability end points included adverse event (AE) reports and weight. AEs with rates ≥5% and with a ≥2% difference between paliperidone ER and risperidone were identified.</p> <p>Results</p> <p>Completion rates for placebo-treated subjects in paliperidone ER trials (n = 95) and risperidone trials (n = 122) groups were 36.8% and 51.6%, respectively; end point changes on PANSS total scores were similar (p = 0.768). Completion rates for subjects receiving paliperidone ER 6-12 mg/day (n = 179), risperidone 2-4 mg/day (n = 113) or risperidone 4-6 mg/day (n = 129) were 64.8%, 54.0% and 66.7%, respectively (placebo-adjusted rates: paliperidone ER vs risperidone 2-4 mg/day, p = 0.005; paliperidone ER vs risperidone 4-6 mg/day, p = 0.159). PANSS total score improvement with paliperidone ER was greater than with risperidone 2-4 mg/day (difference in mean change score, -6.7; p < 0.05) and similar to risperidone 4-6 mg/day (0.2; p = 0.927). Placebo-adjusted AEs more common with paliperidone ER were insomnia, sinus tachycardia and tachycardia; more common with risperidone were somnolence, restlessness, nausea, anxiety, salivary hypersecretion, akathisia, dizziness and nasal congestion. Weight changes with paliperidone ER and risperidone were similar (paliperidone ER vs risperidone 2-4 mg/day, p = 0.489; paliperidone ER vs risperidone 4-6 mg/day, p = 0.236).</p> <p>Conclusions</p> <p>This indirect database analysis suggested that paliperidone ER 6-12 mg/day may be more efficacious than risperidone 2-4 mg/day and as efficacious as risperidone 4-6 mg/day. The AE-adjusted incidence rates suggest differences between treatments that may be relevant for individual patients. Additional randomized, direct, head-to-head clinical trials are needed to confirm these findings.</p

The effects of an Internet based self-help course for reducing panic symptoms - Don't Panic Online: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Internet based self-help for panic disorder (PD) has proven to be effective. However, studies so far have focussed on treating a full-blown disorder. Panic symptoms that do not meet DSM-IV criteria are more prevalent than the full-blown disorder and patients with sub-clinical panic symptoms are at risk of developing PD. This study is a randomised controlled trial aimed to evaluate an Internet based self-help intervention for sub-clinical and mild PD compared to a waiting list control group.</p> <p>Methods</p> <p>Participants with mild or sub-clinical PD (N = 128) will be recruited in the general population. Severity of panic and anxiety symptoms are the primary outcome measures. Secondary outcomes include depressive symptoms, quality of life, loss of production and health care consumption. Assessments will take place on the Internet at baseline and three months after baseline.</p> <p>Discussion</p> <p>Results will indicate the effectiveness of Internet based self-help for sub-clinical and mild PD. Strengths of this design are the external validity and the fact that it is almost completely conducted online.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1639">NTR1639</a> The Netherlands Trial Register is part of the Dutch Cochrane Centre.</p

Local CD4 and CD8 T-Cell Reactivity to HSV-1 Antigens Documents Broad Viral Protein Expression and Immune Competence in Latently Infected Human Trigeminal Ganglia

Herpes simplex virus type 1 (HSV-1) infection results in lifelong chronic infection of trigeminal ganglion (TG) neurons, also referred to as neuronal HSV-1 latency, with periodic reactivation leading to recrudescent herpetic disease in some persons. HSV-1 proteins are expressed in a temporally coordinated fashion during lytic infection, but their expression pattern during latent infection is largely unknown. Selective retention of HSV-1 reactive T-cells in human TG suggests their role in controlling reactivation by recognizing locally expressed HSV-1 proteins. We characterized the HSV-1 proteins recognized by virus-specific CD4 and CD8 T-cells recovered from human HSV-1-infected TG. T-cell clusters, consisting of both CD4 and CD8 T-cells, surrounded neurons and expressed mRNAs and proteins consistent with in situ antigen recognition and antiviral function. HSV-1 proteome-wide scans revealed that intra-TG T-cell responses included both CD4 and CD8 T-cells directed to one to three HSV-1 proteins per person. HSV-1 protein ICP6 was targeted by CD8 T-cells in 4 of 8 HLA-discordant donors. In situ tetramer staining demonstrated HSV-1-specific CD8 T-cells juxtaposed to TG neurons. Intra-TG retention of virus-specific CD4 T-cells, validated to the HSV-1 peptide level, implies trafficking of viral proteins from neurons to HLA class II-expressing non-neuronal cells for antigen presentation. The diversity of viral proteins targeted by TG T-cells across all kinetic and functional classes of viral proteins suggests broad HSV-1 protein expression, and viral antigen processing and presentation, in latently infected human TG. Collectively, the human TG represents an immunocompetent environment for both CD4 and CD8 T-cell recognition of HSV-1 proteins expressed during latent infection. HSV-1 proteins recognized by TG-resident T-cells, particularly ICP6 and VP16, are potential HSV-1 vaccine candidates