GABAergic neurons comprise a major cell type in rodent visual relay nuclei: an immunocytochemical study of pretectal and accessory optic nuclei.

The enzyme glutamic acid decarboxylase (GAD) has been localized in sections of rodent brains (gerbil, rat) using conventional immunocytochemical techniques. Our findings demonstrate that large numbers of GAD-positive neurons and axon terminals (puncta) are present in the visual relay nuclei of the pretectum and the accessory optic system. The areas of highest density of these neurons are in the nucleus of the optic tract (NOT) of the pretectum, the dorsal and lateral terminal accessory optic nuclei (DTN, LTN), the ventral and dorsal subdivisions of the medial terminal accessory optic nucleus (MTNv, MTNd), and the interstitial nucleus of the posterior fibers of the superior fasciculus (inSFp). The findings indicate that 27% of the NOT neurons are GAD-positive and that these neurons are distributed over all of the NOT except the most superficial portion of the NOT caudally. The GAD-positive neurons of the NOT are statistically smaller (65.9 microns2) than the total population of neurons of the NOT (84.3 microns2) but are otherwise indistinguishable in shape from the total neuron population. The other visual relay nuclei that have been analyzed (DTN, LTN, MTNv, MTNd, inSFp) are similar in that from 21% to 31% of their neurons are GAD-positive; these neurons are smaller in diameter and are more spherical than the total populations of neurons. The data further show that a large proportion of the neurons in these visual relay nuclei are contacted by GAD-positive axon terminals. It is estimated that approximately one-half of the neurons of the NOT and the terminal accessory optic nuclei receive a strong GABAergic input and have been called "GAD-recipient neurons". Further, the morphology of the GAD-positive neurons combined with their similar distribution to the GAD-recipient neurons suggest that many of these neurons are acting as GABAergic, local circuit neurons. On the other hand, the large number of GAD-positive neurons in the NOT and MTN (20-30%) in relation to estimates of projection neurons (75%) presents the possibility that some may in fact be projection neurons. The overall findings provide morphological evidence which supports the general conclusion that GABAergic neurons play a significant role in modulating the output of the visually related NOT and terminal accessory optic nuclei

The effects on population health status of using dedicated property taxes to fund local public health agencies

<p>Abstract</p> <p>Background</p> <p>In the United States, a dedicated property tax describes the legal authority given to a local jurisdiction to levy and collect a tax for a specific purpose. We investigated for an association of locally dedicated property taxes to fund local public health agencies and improved health status in the eight states designated as the Mississippi Delta Region.</p> <p>Methods</p> <p>We analyzed the difference in health outcomes of counties with and without a dedicated public health tax after adjusting for a set of control variables using regression models for county level data from 720 counties of the Mississippi Delta Region.</p> <p>Results</p> <p>Levying a dedicated public health tax for counties with per capita income above $28,000 is associated with improved health outcomes of those counties when compared to counties without a dedicated property tax for public health. Alternatively, levying a dedicated property tax in counties with lower per capita income is associated with poor health outcomes.</p> <p>Conclusions</p> <p>There are both positive and negative consequences of using dedicated property taxes to fund public health. Policymakers should carefully examine both the positive association of improved health outcomes and negative impact of taxation on poor populations before authorizing the use of dedicated local property tax levies to fund public health agencies.</p

Subcutaneous dissociative conscious sedation (sDCS) an alternative method for airway regional blocks: a new approach

<p>Abstract</p> <p>Background</p> <p>Predicted difficult airway is a definite indication for awake intubation and spontaneous ventilation. Airway regional blocks which are commonly used to facilitate awake intubation are sometimes impossible or forbidden. On the other hand deep sedation could be life threatening in the case of compromised airway.</p> <p>The aim of this study is evaluating "Subcutaneous Dissociative Conscious Sedation" (sDCS) as an alternative method to airway regional blocks for awake intubation.</p> <p>Methods</p> <p>In this prospective, non-randomized study, 30 patients with predicted difficult airway (laryngeal tumors), who were scheduled for direct laryngoscopic biopsy (DLB), underwent "Subcutaneous Dissociative Conscious Sedation" (sDCS) exerted by intravenous fentanyl 3-4ug/kg and subcutaneous ketamine 0.6-0.7 mg/kg. The tongue and pharynx were anesthetized with lidocaine spray (4%<b>)</b>. 10 minutes after a subcutaneous injection of ketamine direct laryngoscopy was performed. Extra doses of fentanyl 50-100 ug were administered if the patient wasn't cooperative enough for laryngoscopy.</p> <p>Patients were evaluated for hemodynamic stability (heart rate and blood pressure), oxygen saturation (Spo₂), patient cooperation (obedient to open the mouth for laryngoscopy and the number of tries for laryngoscopy), patient comfort (remaining moveless), hallucination, nystagmus and salivation (need for aspiration before laryngoscopy).</p> <p>Results</p> <p>Direct laryngoscopy was performed successfully in all patients. One patient needed extra fentanyl and then laryngoscopy was performed successfully on the second try. All patients were cooperative enough during laryngoscopy. Hemodynamic changes more than 20% occurred in just one patient. Oxygen desaturation (spo₂< 90%) didn't occur in any patient.</p> <p>Conclusions</p> <p>Subcutaneous Dissociative Conscious Sedation (sDCS) as a new approach to airway is an acceptable and safe method for awake intubation and it can be suggested as a noninvasive substitute of low complication rate for regional airway blocks.</p> <p>Registration ID in IRCT</p> <p>IRCT201012075333N1</p

Synthesis and Exciton Dynamics of Donor-Orthogonal Acceptor Conjugated Polymers: Reducing the Singlet-Triplet Energy Gap

The presence of energetically low-lying triplet states is a hallmark of organic semiconductors. Even though they present a wealth of interesting photophysical properties, these optically dark states significantly limit optoelectronic device performance. Recent advances in emissive charge-transfer molecules have pioneered routes to reduce the energy gap between triplets and "bright" singlets, allowing thermal population exchange between them and eliminating a significant loss channel in devices. In conjugated polymers, this gap has proved resistant to modification. Here, we introduce a general approach to reduce the singlet-triplet energy gap in fully conjugated polymers, using a donor-orthogonal acceptor motif to spatially separate electron and hole wave functions. This new generation of conjugated polymers allows for a greatly reduced exchange energy, enhancing triplet formation and enabling thermally activated delayed fluorescence. We find that the mechanisms of both processes are driven by excited-state mixing between π-π*and charge-transfer states, affording new insight into reverse intersystem crossing.Part of this work was funded by EU project 679789 – 455 CONTREX, EC H2020 SYNCHRONICS (643238), EC H2020 SOLEDLIGHT (643791) and EPSRC (EP/M005143/1) A.J.M. was supported by the EPSRC (EP/456M01083X). J.M.F. was supported by EPSRC (EP/K016288/1). F.C. is a Royal Society Wolfson Research Merit Award holder. H.L.S. was supported by the Winton Programme 457 for the Physics of Sustainability. We are grateful to the Imperial College High Performance Computing Service (doi: 10.14469/hpc/2232)

An investigation to assess ankle mobility in healthy individuals from the application of multi-component compression bandages and compression hosiery

Background An investigation was undertaken to compare the effect of multi-component compression bandages and compression hosiery kits on individuals’ range of ankle motion whilst wearing typical and medical footwear, and barefoot. Methods A convenience sample of 30 healthy individuals recruited from the staff and student population at the University of Huddersfield, UK. Plantarflexion/dorsiflexion range of ankle motion (ROAM) was measured in participants over 6 steps in every combination of typical, medical and no footwear; and multi-component bandages, compression hosiery and no garments. Results Controlling for age, gender and garments, the use of typical footwear was associated with a mean increase in ROAM of 2.54° at best estimate compared with barefoot; the use of medical footwear was associated with a mean decrease in ROAM of 1.12° at best estimate compared with barefoot. Controlling for age, gender and footwear, the use of bandaging was associated with a mean decrease in ROAM of 2.51° at best estimate compared with no garments. Controlling for age, gender and footwear, the use of hosiery was not associated with a significant change in ROAM compared with no garments. Conclusions Bandages appear to restrict ROAM more than hosiery when used in conjunction with a variety of footwear types

Pathway analysis comparison using Crohn's disease genome wide association studies

<p>Abstract</p> <p>Background</p> <p>The use of biological annotation such as genes and pathways in the analysis of gene expression data has aided the identification of genes for follow-up studies and suggested functional information to uncharacterized genes. Several studies have applied similar methods to genome wide association studies and identified a number of disease related pathways. However, many questions remain on how to best approach this problem, such as whether there is a need to obtain a score to summarize association evidence at the gene level, and whether a pathway, dominated by just a few highly significant genes, is of interest.</p> <p>Methods</p> <p>We evaluated the performance of two pathway-based methods (Random Set, and Binomial approximation to the hypergeometric test) based on their applications to three data sets of Crohn's disease. We consider both the disease status as a phenotype as well as the residuals after conditioning on IL23R, a known Crohn's related gene, as a phenotype.</p> <p>Results</p> <p>Our results show that Random Set method has the most power to identify disease related pathways. We confirm previously reported disease related pathways and provide evidence for IL-2 Receptor Beta Chain in T cell Activation and IL-9 signaling as Crohn's disease associated pathways.</p> <p>Conclusions</p> <p>Our results highlight the need to apply powerful gene score methods prior to pathway enrichment tests, and that controlling for genes that attain genome wide significance enable further biological insight.</p

Cancer treatment-related neuropathic pain:proof of concept study with menthol—a TRPM8 agonist

PURPOSE: Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol. PATIENTS AND METHODS: Patients with problematic treatment-related neuropathic pain underwent a baseline assessment using validated questionnaires, psychophysical testing, and objective functional measures. The painful area was treated with topical 1 % menthol cream twice daily. Assessments were repeated at 4–6 weeks. The primary outcome was the change in Brief Pain Inventory total scores at 4–6 weeks. Secondary outcomes included changes in function, mood and skin sensation. RESULTS: Fifty-one patients (female/male, 32/19) were recruited with a median age of 61 (ranging from 20 to 89). The commonest aetiology was CIPN (35/51), followed by scar pain (10/51). Thirty-eight were evaluable on the primary outcome. Eighty-two per cent (31/38) had an improvement in total Brief Pain Inventory scores (median, 47 (interquartile range, 30 to 64) to 34 (6 to 59), P < 0.001). Improvements in mood (P = 0.0004), catastrophising (P = 0.001), walking ability (P = 0.008) and sensation (P < 0.01) were also observed. CONCLUSION: This proof-of-concept study indicates that topical menthol has potential as a novel analgesic therapy for cancer treatment-related neuropathic pain. Improvements in patient-rated measures are supported by changes in objective measures of physical function and sensation. Further systematic evaluation of efficacy is required

Tetralogy of Fallot

Tetralogy of Fallot is a congenital cardiac malformation that consists of an interventricular communication, also known as a ventricular septal defect, obstruction of the right ventricular outflow tract, override of the ventricular septum by the aortic root, and right ventricular hypertrophy

Ly6Chi monocyte recruitment is responsible for Th2 associated host-protective macrophage accumulation in liver inflammation due to schistosomiasis

Accumulation of M2 macrophages in the liver, within the context of a strong Th2 response, is a hallmark of infection with the parasitic helminth, Schistosoma mansoni, but the origin of these cells is unclear. To explore this, we examined the relatedness of macrophages to monocytes in this setting. Our data show that both monocyte-derived and resident macrophages are engaged in the response to infection. Infection caused CCR2-dependent increases in numbers of Ly6Chi monocytes in blood and liver and of CX3CR1+ macrophages in diseased liver. Ly6Chi monocytes recovered from liver had the potential to differentiate into macrophages when cultured with M-CSF. Using pulse chase BrdU labeling, we found that most hepatic macrophages in infected mice arose from monocytes. Consistent with this, deletion of monocytes led to the loss of a subpopulation of hepatic CD11chi macrophages that was present in infected but not naïve mice. This was accompanied by a reduction in the size of egg-associated granulomas and significantly exacerbated disease. In addition to the involvement of monocytes and monocyte-derived macrophages in hepatic inflammation due to infection, we observed increased incorporation of BrdU and expression of Ki67 and MHC II in resident macrophages, indicating that these cells are participating in the response. Expression of both M2 and M1 marker genes was increased in liver from infected vs. naive mice. The M2 fingerprint in the liver was not accounted for by a single cell type, but rather reflected expression of M2 genes by various cells including macrophages, neutrophils, eosinophils and monocytes. Our data point to monocyte recruitment as the dominant process for increasing macrophage cell numbers in the liver during schistosomiasis