The physiology of the pedunculopontine nucleus: implications for deep brain stimulation.

This brief review resolves a number of persistent conflicts regarding the location and characteristics of the mesencephalic locomotor region, which has in the past been described as not locomotion-specific and is more likely the pedunculopontine nucleus (PPN). The parameters of stimulation used to elicit changes in posture and locomotion we now know are ideally suited to match the intrinsic membrane properties of PPN neurons. The physiology of these cells is important not only because it is a major element of the reticular activating system, but also because it is a novel target for the treatment of gait and postural deficits in Parkinson's disease (PD). The discussion explains many of the effects reported following deep brain stimulation (DBS) of the PPN by different groups and provides guidelines for the determination of long-term assessment and effects of PPN DBS. A greater understanding of the physiology of the target nuclei within the brainstem and basal ganglia, amassed over the past decades, has enabled increasingly better patient outcomes from DBS for movement disorders. Despite these improvements, there remains a great opportunity for further understanding of the mechanisms through which DBS has its effects and for further development of appropriate technology to effect these treatments. We review the scientific basis for one of the newest targets, the PPN, in the treatment of PD and other movement disorders, and address the needs for further investigation.

Gamma band activity in the RAS-intracellular mechanisms.

Gamma band activity participates in sensory perception, problem solving, and memory. This review considers recent evidence showing that cells in the reticular activating system (RAS) exhibit gamma band activity, and describes the intrinsic membrane properties behind such manifestation. Specifically, we discuss how cells in the mesopontine pedunculopontine nucleus, intralaminar parafascicular nucleus, and pontine SubCoeruleus nucleus dorsalis all fire in the gamma band range when maximally activated, but no higher. The mechanisms involve high-threshold, voltage-dependent P/Q-type calcium channels, or sodium-dependent subthreshold oscillations. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness and provide the essential stream of information for the formulation of many of our actions. We address three necessary next steps resulting from these discoveries: an intracellular mechanism responsible for maintaining gamma band activity based on persistent G-protein activation, separate intracellular pathways that differentiate between gamma band activity during waking versus during REM sleep, and an intracellular mechanism responsible for the dysregulation in gamma band activity in schizophrenia. These findings open several promising research avenues that have not been thoroughly explored. What are the effects of sleep or REM sleep deprivation on these RAS mechanisms? Are these mechanisms involved in memory processing during waking and/or during REM sleep? Does gamma band processing differ during waking versus REM sleep after sleep or REM sleep deprivation?

Effects of mindfulness-based interventions on symptoms and interoception in trauma-related disorders and exposure to traumatic events: Systematic review and meta-analysis.

Interoception is defined as the sense of the internal state of the body. Dysfunctions in interoception are found in several mental disorders, including trauma-related conditions. Mindfulness-Based Interventions (MBIs) have been shown to influence interoceptive processes. Randomised controlled trials (RCTs) have investigated whether MBIs impact symptoms and interoception in patients with trauma-related disorders. We undertook a systematic review and meta-analysis to synthesize these data. We included RCTs with an MBI arm which enrolled adult patients with trauma related-disorders or exposure to a traumatic experience, and addressed changes in interoception and trauma-related symptoms. A random-effects multivariate meta-analytic model was performed to quantify group differences in score change from baseline to follow-up. Twelve studies were included in the systematic review, and eleven in the meta-analysis. Overall, MBIs showed small to moderate positive effects on both interoception and symptoms. Despite a high heterogeneity in results, sensitivity analyses confirmed the robustness of the findings. We conclude that the efficacy of MBIs on trauma-related symptoms and interoception is supported by randomised evidence. However, further research is needed to understand whether changes in interoception might underpin the effectiveness of MBIs in trauma-related disorders.

Drought legacy interacts with wildfire to alter soil microbial communities in a Mediterranean climate-type forest.

Mediterranean forest ecosystems will be increasingly affected by hotter drought and more frequent and severe wildfire events in the future. However, little is known about the longer-term responses of these forests to multiple disturbances and the forests' capacity to maintain ecosystem function. This is particularly so for below-ground organisms, which have received less attention than those above-ground, despite their essential contributions to forest function. We investigated rhizosphere microbial communities in a resprouting Eucalyptus marginata forest, southwestern Australia, that had experienced a severe wildfire four years previously, and a hotter drought eight years previously. Our aim was to understand how microbial communities are affected over longer-term trajectories by hotter drought and wildfire, singularly, and in combination. Fungal and bacterial DNA was extracted from soil samples, amplified, and subjected to high throughput sequencing. Richness, diversity, composition, and putative functional groups were then examined. We found a monotonic decrease in fungal, but not bacterial, richness and diversity with increasing disturbance with the greatest changes resulting from the combination of drought and wildfire. Overall fungal and bacterial community composition reflected a stronger effect of fire than drought, but the combination of both produced the greatest number of indicator taxa for fungi, and a significant negative effect on the abundance of several fungal functional groups. Key mycorrhizal fungi, fungal saprotrophs and fungal pathogens were found at lower proportions in sites affected by drought plus wildfire. Wildfire had a positive effect on bacterial hydrogen and bacterial nitrogen recyclers. Fungal community composition was positively correlated with live tree height. These results suggest that microbial communities, in particular key fungal functional groups, are highly responsive to wildfire following drought. Thus, a legacy of past climate conditions such as hotter drought can be important for mediating the responses of soil microbial communities to subsequent disturbance like wildfire.

Concordance of diagnostic modalities in atypical skin and soft tissue infections in hospitalized patients.

Skin and soft tissue infections (SSTIs) have high rates of morbidity and mortality worldwide but lack reliable standards for diagnostic workup. As a result, atypical infections, more prevalent among immunocompromised patients, can be missed due to deviance from classic features only to be revealed later through inconsistently performed ancillary studies. Our objectives included to evaluate the sensitivities of clinical impression, histopathology, tissue culture, and molecular and non-molecular ancillary tests in diagnosing inpatient SSTIs, as well as to qualitatively discuss the unusual features making a subset of infections "atypical." To do so, we retrospectively reviewed the histopathologic reports and charts of inpatient dermatologic consults at a single tertiary care institution over a 3-year period. We identified a total of 111 cases of SSTIs evaluated by the inpatient dermatology consultation service with concurrent skin or soft tissue biopsy, with 32.4% representing atypical infections. Among these, clinical impression suggested infection in 9(25.0%), routine histopathology in 21(58.3%), specialized stains for microorganisms in 22(68.8%), and tissue culture in 15(68.2%). Due to incomplete picture that each modality by itself creates, we conclude that clinicians and pathologists should carry a low threshold for including SSTIs in their differential diagnoses and should evaluate with skin biopsy, special stains for microorganisms, and ancillary studies, particularly in critically ill individuals who necessitate timely diagnoses.

It's good to talk! Changes in coronary revascularisation practice in PCI centres without onsite surgical cover and the impact of an angiography video conferencing system.

INTRODUCTION: Percutaneous coronary intervention (PCI) activity has increased more than 6 fold in the last 15 years. Increased demand has been met by PCI centres without on-site surgical facilities. To improve communication between cardiologists and surgeons at a remote centre, we have developed a video conferencing system using standard internet links. The effect of this video data link (VDL) on referral pattern and patient selection for revascularisation was assessed prospectively after introduction of a joint cardiology conference (JCC) using the system. METHODS: Between 1st October 2005 and 31st March 2007, 1346 patients underwent diagnostic coronary angiography (CA). Of these, 114 patients were discussed at a cardiology conference (CC) attended by three consultant cardiologists (pre-VDL). In April 2007, the VDL system was introduced. Between 1st April 2007 and 30th September 2008, 1428 patients underwent diagnostic CA. Of these, 120 patients were discussed at a JCC attended by four consultant cardiologists and two consultant cardiothoracic surgeons (post-VDL). Following case-matching for patient demographics and coronary artery disease (CAD) severity and distribution, we assessed the effect upon management decisions arising from both the pre- and post-VDL JCC meetings. RESULTS: When comparing decision-making outcomes of post-VDL JCC with pre-VDL CC, significantly fewer patients were recommended for PCI (36.8% vs. 17.2% respectively, p = 0.001) and significantly more patients were recommended for surgery (21.1% vs. 48.4% respectively, p < 0.001). There were no significant differences in waiting times for PCI following JCC discussion; however, waiting times for surgical revascularisation were significantly reduced (140.9 ± 71.8 days vs. 99.4 ± 56.6 days respectively, p = 0.045). CONCLUSIONS: The VDL system provides a highly practical method for PCI centres without onsite surgical cover to discuss complex patients requiring coronary revascularisation and significantly increases the number of patients referred for surgical revascularisation rather than PCI.

Enzyme functionalized microgels enable precise regulation of dissolved oxygen and anaerobe culture.

Anaerobes are a major constituent of the gut microbiome and profoundly influence the overall health of humans. However, the lack of a simple, cost-effective, and scalable system that mimics the anaerobic conditions of the human gut is hindering research on the gut microbiome and the development of therapeutics. Here, we address this gap by using glucose oxidase and catalase containing gelatin microparticles (GOx-CAT-GMPs) to precisely regulate dissolved oxygen concentration [O2] via GOx-mediated consumption of oxygen. Fluorescence images generated using conjugated polymer afterglow nanoparticles showed that [O2] can be tuned from 257.9 â€‹± â€‹6.2 to 0.0 â€‹± â€‹4.0 â€‹µM using GOx-CAT-GMPs. Moreover, when the obligate anaerobe Bacteroides thetaiotaomicron was inoculated in media containing GOx-CAT-GMPs, bacterial growth under ambient oxygen was comparable to control conditions in an anaerobic chamber (5.4 â€‹× â€‹105 and 8.8 â€‹× â€‹105 colony forming units mL-1, respectively). Finally, incorporating GOx-CAT-GMPs into a bioreactor that permitted continuous radial diffusion of oxygen and glucose generated a gut-mimetic [O2] gradient of 132.4 â€‹± â€‹2.6 â€‹µM in the outer ring of the reactor to 7.9 â€‹± â€‹1.7 â€‹µM at the core. Collectively, these results indicate that GOx-CAT-GMPs are highly effective oxygen-regulating materials. These materials can potentially be leveraged to advance gut microbiome research and fecal microbiota transplantation, particularly in low-resource settings.

Morphometric analysis of volumes and surface areas in membrane compartments during endocytosis in Acanthamoeba.

Stereologic analysis was made of cell surface membrane (PM) and two interrelated cytoplasmic membrane systems, the vacuole membranes (VM) and small vesicle membranes (SVM). Volumes and surface areas of the three membrane compartments were measured during steady-state pinocytosis, when membrane recycling is rapid, and during phagocytosis, when a shift to a lower rate of membrane uptake by endocytosis occurs (B. Bowers, 1977, Exp. Cell Res. 110:409). Total membrane area in the three compartments was 3.2 micrometers 2/micrometers 3 of protoplasmic volume and was constant throughout the experiments. In pinocytosing cells, 32% of the membrane was in the PM, 25% in the vM, and 43% in the SVM. The vacuole compartment occupies approximately 20% of the total cell volume, and the small vesicle, approximately 3%. As the endocytic uptake of membrane from the surface decreased, there was an increase in PM area and a marked decrease in SVM area. The VM area remained constant even though "empty" vacuoles were almost completely replaced by newly formed phagosomes within 45 min. This demonstrates directly a rapid flux of membrane though this compartment. A model, taking into consideration these and other data on Acanthamoeba, is proposed to account for the observed membrane shifts. The data suggest that the vacuolar (digestive) system of Acanthamoeba is central to cellular control of endocytosis and membrane recycling.

Ion-exchange in melanin: an electron spin resonance study with lanthanide probes.

Changes are induced in the electron spin resonance signal amplitude and microwave power saturation of the naturally occurring free radical in melanin by bound paramagnetic ions. The changes serve as experimental observables in competition experiments between diamagnetic and paramagnetic metal ions for melanin binding sites and between melanin and ethylenediaminetetraacetic acid for paramagnetic metal ions. Evidence is presented for the existence of several specific types of metal binding sites. The interaction of copper with free radicals leading to loss of electron spin resonance signal amplitude is magnetic in nature and not, as has been supposed, chemical.

Eumelanins and pheomelanins: characterization by electron spin resonance spectroscopy.

Synthetic dopa melanin and cysteinyldopa melanin have different electron spin resonance spectra. Data are reported for mixtures of these melanins and for dopa-cysteinyldopa copolymers, which are spectroscopically similar. A simple parameterization of the spectra allows estimation of the relative amounts of (i) dopa melanin and cysteinyldopa melanin in mixtures and of (ii) dopa and cysteinyldopa incorporated into copolymers. Several natural eumelanins and pheomelanins have been characterized and shown to be copolymers.

Statistical analysis of atom probe data: detecting the early stages of solute clustering and/or co-segregation.

Statistical analysis of atom probe data has improved dramatically in the last decade and it is now possible to determine the size, the number density and the composition of individual clusters or precipitates such as those formed in reactor pressure vessel (RPV) steels during irradiation. However, the characterisation of the onset of clustering or co-segregation is more difficult and has traditionally focused on the use of composition frequency distributions (for detecting clustering) and contingency tables (for detecting co-segregation). In this work, the authors investigate the possibility of directly examining the neighbourhood of each individual solute atom as a means of identifying the onset of solute clustering and/or co-segregation. The methodology involves comparing the mean observed composition around a particular type of solute with that expected from the overall composition of the material. The methodology has been applied to atom probe data obtained from several irradiated RPV steels. The results show that the new approach is more sensitive to fine scale clustering and co-segregation than that achievable using composition frequency distribution and contingency table analyses.

Characterisation of the early stages of solute clustering in 1Ni-1.3Mn welds containing Cu.

Microstructural characterisation of neutron irradiated low alloy steels is important for developing mechanistic understanding of irradiation embrittlement. This work is focused on the early stages of irradiation-induced clustering in a low Cu (0.03wt%), high Ni ( approximately 1wt%) weld. The weld was irradiated at a very high dose rate and then examined by atom probe (energy-compensated position-sensitive atom probe (ECOPoSAP) and local electrode atom probe (LEAP)) with supporting microstructural information obtained by small angle neutron scattering (SANS) and positron annihilation (PALA). It was demonstrated that extreme care must be taken optimising parameters used to characterise the extent of clustering. This is particularly important during the early stages of irradiation-damage when the clusters are poorly defined and significant compositional variations are present in what is traditionally described as matrix. Analysis of the irradiated materials showed increasing clustering of Cu, Mn, Ni and Si with dose. In the low Cu steel the results showed that initially the irradiation damage results in clustering of Mn, Ni and Si, but at very high doses, at very high dose rates, redistribution of Si is significantly more advanced than that for Mn and Ni.

Coupling of Waveguide and Resonator by Inductive and Capacitive Irises for EPR Spectroscopy.

An analytic circuit model for slot coupling from a waveguide to a loop-gap resonator (LGR) in a context of electron paramagnetic resonance (EPR) spectroscopy is presented. The physical dimensions of the waveguide, iris, LGR, and aqueous sample are transformed into circuit values of inductance, capacitance, and resistance. These values are used in a solution of circuit equations that results in a prediction of the rf currents, magnitude and phase, frequency, and magnetic and electric stored energies near critical coupling. The circuit geometry reflects magnetic flux conservation between the iris and LGR as well as modification of the outer loop LGR currents by the iris. Unlike conventional models, coupling is not explicitly based on a mutual inductance between the iris and LGR. Instead, the conducting wall high frequency rf boundary condition is used to define surface currents, regions, and circuit topology with lumped-circuit values of self-inductance, capacitance, and resistance. Match is produced by a combination of self-inductive and capacitive circuit coupling. Two conditions must be met to achieve match. First, the equivalent resistance of the LGR as seen by the iris must be transformed into the waveguide characteristic impedance. This transformation is met at a particular frequency relative to the natural LGR resonance frequency. The frequency shift magnitude is largely determined by the LGR properties, weakly dependent on iris length and placement, and independent of other iris dimensions. The second condition for match is that the iris reactance at this frequency shift must cancel the residual reactance of the LGR. This second condition is sensitive to the iris dimensions. If both conditions are not simultaneously satisfied, overcoupling or undercoupling results. A slotted iris of equal length to the size of the large dimension of the waveguide is found to have many properties opposite to a conventional iris of shorter length. Notably, the magnetic field near the iris tends to reinforce rather than oppose the magnetic field in the resonator. The long iris improves the LGR EPR performance by providing increased rf magnetic field homogeneity at the sample, higher signal, and reduced total frequency shift since the shifts due to sample and iris tend to cancel. Investigations reveal that the first match condition can be adjusted by LGR dimensional changes and such adjustment can eliminate the frequency shift. Results are consistent with Ansoft High Frequency Structure Simulator (Version 10.1, Ansoft Corporation, Pittsburgh, PA) simulations and can be extended to cavity resonators.

Cryptic speciation in the vermilion rockfish (Sebastes miniatus) and the role of bathymetry in the speciation process.

A recent phylogenetic review of the genus Sebastes suggested the existence of a cryptic species of vermilion rockfish (Sebastes miniatus). To evaluate the geographical and bathymetric range of the Type 1 and Type 2 forms reported in that study, cytochrome b sequences were examined from 548 fish. Type 1 fish were found primarily south of Point Conception on reefs deeper than 100 m. Type 2 fish were common range-wide at sites shallower than 100 m. Reproductive isolation between the two types was tested using nine microsatellite loci. Estimates of genetic divergence were made using the fixation index (F(ST)) and correspondence between haplotype and genotype was tested by Bayesian population assignment and multivariate plotting of individual genotypes. Microsatellite analyses gave strong support for the presence of two distinct groups of genotypes. All fish with Type 1 haplotypes and fish with Type 2 haplotypes from < 100 m depth had genotypes unique to their haplotype group. However, most (68%) fish with Type 2 haplotypes from > 100 m depth assigned strongly to the Type 1 genotype group. Morphometric comparisons between the two genotypic groups revealed significant differences at three of the six examined measurements. Differences in both genetics, depth of occurrence, and morphology suggest these are separate species. This observation along with evidence of depth segregation in many recent species pairs led us to hypothesize a speciation model for Sebastes spp. by which the loss or truncation of a depth-related ontogenetic migration can lead to the creation of reproductively isolated populations.

Interventions to increase self-efficacy in the context of addiction behaviours: a systematic literature review.

This article describes the effectiveness of interventions aimed at increasing self-efficacy and consequently, changing addiction behaviours. Electronic databases were searched and bibliographies of retrieved references scanned. Ten studies targeting tobacco smoking, alcohol and illicit drug use met the inclusion criteria. The interventions ranged from computer-generated tailored letters to intensive group-based interventions. Seven of the 10 studies reported positive effects of interventions upon self-efficacy. The two that assessed behaviour change reported a significant effect but as neither performed mediation analyses, behaviour change could not reliably be attributed to self-efficacy change. In conclusion, self-efficacy can be increased using a range of methods. There is, however, little evidence to determine whether such increases change behaviour.

Regulation of the rat liver sodium-dependent bile acid cotransporter gene by prolactin. Mediation of transcriptional activation by Stat5.

The intracellular mechanism(s) underlying the upregulation of the hepatic Na+/taurocholate cotransporting polypeptide (ntcp) by prolactin (PRL) are unknown. In this report, we demonstrate a time-dependent increase in nuclear translocation of phosphorylated liver Stat5 (a member of the ignal ransducers and ctivators of ranscription family) that correlated with suckling-induced increases in serum PRL levels. In electrophoretic mobility gel shift assays, nuclear Stat5 exhibited specific DNA-binding ability towards IFN-gamma-activated sequence (GAS)-like elements (GLEs; 5'TTC/A-PyNPu-G/TAA-3') located in the -937 to -904 bp region of the ntcp promoter. Transient cotransfections in HepG2 cells revealed that PRL inducibility (2.5-3-fold) required coexpression of the long form of the PRL receptor (PRLRL) and Stat5. Deletion analysis mapped the PRLinducible region to -1237 to -758 bp of the ntcp promoter. Linking this 0.5-kb region to a heterologous thymidine kinase (tk) promoter, or linking multimerized ntcp GLEs either upstream of the ntcp minimal promoter (-158 to +47 bp) or the heterologous promoter conferred dose-dependent PRL responsiveness. The short form of the PRL receptor failed to transactivate ntcp GLEs. These results indicate that PRL acts via the PRLRL to facilitate Stat5 binding to ntcp-GLEs and to transcriptionally regulate ntcp.

Identifying efficient dairy producers using data envelopment analysis.

The objective of this research was to calculate the efficiency of a group of Pennsylvania dairy farms to determine factors that contributed to efficiency in production and business management. Data envelopment analysis (DEA) was used to estimate the efficiency. Two models were developed to measure the efficient use of physical (land, cows, and labor) inputs to produce physical (milk and butterfat) outputs, and the use of physical and economic (debt capital) inputs to produce physical and economic (income) outputs. The results showed that about 29% of the producers in our sample were DEA-efficient and demonstrated that there was no combination of inputs used by efficient producers that was best. In addition, the method of analysis illustrated the benefits of DEA in that it is possible to identify the set of efficient producers that inefficient producers can benchmark to in an effort to achieve similar levels of efficiency. Finally, the analysis demonstrated that producers should not benchmark to the highest level of production, but rather should combine resources in land, labor, cows, and debt capital to achieve an efficient level of production, which indeed may be less than the maximum production level of the group.