Therapeutic effect of intranasal evaporative cooling in patients with migraine: a pilot study.

BACKGROUND: Cryotherapy is the most common non-pharmacological pain-relieving method. The aim of this pilot study was to ascertain whether intranasal evaporative cooling may be an effective intervention in an acute migraine attack. Studies have previously demonstrated effectiveness of a variety of cryotherapy approaches. Intranasal evaporative cooling due to vascular anatomy, allows the transfer of venous blood from nasal and paranasal mucous membranes to the dura mater, thereby providing an excellent anatomical basis for the cooling processes. METHODS: We conducted a prospective, open-label, observational, pilot study. Twenty-eight patients who satisfied the International Classification of Headache Disorders (ICHD 2) diagnostic criteria for migraine were recruited. A total of 20 treatments were administered in 15 patients. All patients provided pain severity scores and migraine-associated symptoms severity scores (based on a 0-10 visual analogue scale, [VAS]). RESULTS: Out of the 20 treatments, intranasal evaporative cooling rendered patients' pain and symptoms free immediately after treatment, in 8 of the treatments (40%), a further 10 treatments (50%) resulted in partial pain relief (headache reduced from severe or moderate to mild) and partial symptoms relief. At 2 hours, 9 treatments (45%) provided full pain and symptoms relief, with a further 9 treatments (45%) resulting in partial pain and symptoms relief. At 24 hours, 10 treatments (50%) resulted in patients reporting pain and symptom freedom and 3 (15%) provided partial pain relief. In summary 13 patients (87%) had benefit from the treatment within 2 hours that was sustained at 24 hours. CONCLUSIONS: Intranasal evaporative cooling gave considerable benefit to patients with migraine, improving headache severity and migraine-associated symptoms. A further randomised, placebo controlled, double blinded, parallel clinical trial is required to further investigate the potential of this application. TRIAL REGISTRATION: Clinicaltrials.gov registered trial, ClinicalTrials.gov Identifier: NCT01898455.

Inhaled diesel emissions alter atherosclerotic plaque composition in ApoE(-/-) mice.

Recent epidemiological studies suggest that traffic-related air pollution may have detrimental effects on cardiovascular health. Previous studies reveal that gasoline emissions can induce several enzyme pathways involved in the formation and development of atherosclerotic plaques. As a direct comparison, the present study examined the impact of diesel engine emissions on these pathways, and further examined the effects on vascular lesion pathology. Apolipoprotein E-null mice were simultaneously placed on a high-fat chow diet and exposed to four concentrations, plus a high concentration exposure with particulates (PM) removed by filtration, of diesel emissions for 6 h/day for 50 days. Aortas were subsequently assayed for alterations in matrix metalloproteinase-9, endothelin-1, and several other biomarkers. Diesel induced dose-related alterations in gene markers of vascular remodeling and aortic lipid peroxidation; filtration of PM did not significantly alter these vascular responses, indicating that the gaseous portion of the exhaust was a principal driver. Immunohistochemical analysis of aortic leaflet sections revealed no net increase in lesion area, but a significant decrease in lipid-rich regions and increasing trends in macrophage accumulation and collagen content, suggesting that plaques were advanced to a more fragile, potentially more vulnerable state by diesel exhaust exposure. Combined with previous studies, these results indicate that whole emissions from mobile sources may have a significant role in promoting chronic vascular disease.

Rhythmic contractility in the hepatic portal "corkscrew" vein of the rat snake.

Terrestrial, but not aquatic, species of snakes have hepatic portal veins with a corkscrew morphology immediately posterior of the liver. Relatively large volumes of venous blood are associated with this region, and the corkscrew vein has been proposed to function as a bidirectional valve that impedes gravitational shifts of intravascular volume. To better understand the functional significance of the corkscrew anatomy, we investigated the histology and contractile mechanisms in isolated corkscrew segments of the hepatic portal vein of a yellow rat snake (Pantherophis obsoletus). Morphologically, the corkscrew portal vein is here shown to have two distinct layers of smooth muscle--an inner circular layer, and an outer longitudinal layer, separated by a layer of collagen--whereas only a single circular layer of smooth muscle is present in the adjacent posterior caval vein. Low frequency (approximately 0.3 cycles*min(-1)) spontaneous and catecholamine-induced rhythms were observed in 11% and 89% of portal vein segments, respectively, but neither spontaneous nor agonist-induced cycling was observed in adjacent posterior (non-corkscrew) caval veins. Catecholamines, angiotensin II, or stretch increased the amplitude and/or frequency of contractile cycles. Ouabain, verapamil or indomethacin, but not tetrodotoxin, alpha-, or ss-adrenergic receptor antagonists, inhibited cyclical contractions indicating a dependence of these cycles on Na+/K+ ATPase, extracellular Ca2+ and prostanoid(s). These data suggest that the rhythmic contractility of the corkscrew segment of the ophidian portal vein may act in conjunction with its morphological features to improve venous return and to prevent retrograde shifts of blood that might otherwise pool in posterior veins.

nCounter NanoString Assay Shows Variable Concordance With Immunohistochemistry-based Algorithms in Classifying Cases of Diffuse Large B-Cell Lymphoma According to the Cell-of-Origin.

Classifying diffuse large B-cell lymphoma (DLBCL) according to the cell-of-origin (COO) was first proposed using gene expression profiling; accordingly, DLBCL is classified into germinal-center B-cell type and activated B-cell type. Immunohistochemistry (IHC)-based classification using different algorithms is used widely due to the ability to use formalin-fixed paraffin-embedded tissue. Recently, newer techniques using RNA expression from formalin-fixed paraffin-embedded were introduced including the nCounter NanoString platform assay. In this brief report, we study the degree of concordance between the NanoString assay and 6 commonly utilized IHC-based algorithms to classify DLBCL cases by COO. Stains for CD10, BCL2, BCL6, FOXP-1, MUM-1, and LOM2 were used to classify a cohort of DLBCL by COO according to the respective IHC-algorithms. Then, RNA was extracted from the same cases for NanoString assay classification. The degree of concordance was calculated between the NanoString classification and each IHC-algorithm as well as among the different IHC-algorithm themselves. The concordance in COO classification of DLBCL between NanonoString assay and IHC-based algorithms is variable depending on the used IHC-algorithm; the highest concordance is seen with the Visco algorithm (κ=0.69; P=0.001). Therefore, discrepancies between the recently introduced NanoString assay and the commonly utilized IHC-algorithms are expected to some extent and should be taken into consideration when interpreting conflicting results.

Impact of warm compresses on local injection-site reactions with self-administered glatiramer acetate.

Patients with multiple sclerosis (MS) report a number of adverse events related to immunomodulator injections, including local injection-site reactions (LISRs). Reactions characterized by pain, swelling, redness, or inflammation have been experienced by patients who self-inject glatiramer acetate, interferon beta-1b, or interferon beta-1a. Although these reactions rarely are serious, they can foster negative attitudes about self-injection and undermine a patient's commitment to treatment, especially in the early stages of therapy. This randomized crossover study of 50 patients who had initiated or restarted glatiramer acetate therapy within the 3 months before the study examined whether applying a warm compress to the injection site before self-injection would lower the incidence of LISRs compared with the patients' usual methods of injection preparation. Fewer LISRs were reported both 2 minutes and 5 minutes postinjection when warm compresses were used compared with the usual injection-site preparation (p < .001). Patients also were less bothered by LISRs when using warm compresses, as shown by mean scores on the Bothersome Scale (p = .02). Because warm compresses are easy to apply and appear to be at least modestly effective, they should be considered when recommending alternatives for patients who experience LISRs associated with glatiramer acetate. Warm compresses may be of particular benefit for those who have recently begun therapy with glatiramer acetate to help improve the likelihood of adherence to long-term treatment.

Strong NFκB Expression is Associated With High-grade Dysplasia in Barrett's Esophagus.

Nuclear factor kappa B (NFκB) is a transcription factor that regulates the activation of genes involved in proinflammatory response and growth. In this study, we utilized immunohistochemical stains for 2 of the NFκB molecules (RELA and NFκB-1) to evaluate the expression of NFκB in Barrett's esophagus (BE). Forty-three cases of BE [17 cases with no dysplasia, 16 cases with low-grade dysplasia (LGD), and 10 cases with high-grade dysplasia (HGD)], 10 normal esophageal biopsies, and 9 cases of esophageal adenocarcinoma were evaluated. Expression of NFκB-1 and RELA did not occur in normal esophageal squamous mucosa. BE without dysplasia showed weak expression of RELA and NFκB-1 in 35% and 65% of cases, respectively. BE with LGD showed weak expression of RELA and NFκB-1 in 50% and 75% of cases, respectively. Strong expression of RELA and NFκB-1 did not occur in BE without dysplasia or with LGD. BE with HGD showed strong expression of RELA and NFκB-1 in 80% and 90% of cases, respectively. All cases of adenocarcinoma showed strong expression of both RELA and NFκB-1. There was a progressive increase in staining intensity of RELA and NFκB-1 along the metaplasia-dysplasia-adenocarcinoma pathway. Strong expression of NFκB is associated with HGD and adenocarcinoma (P<0.0001). We showed that strong expression of NFκB-1 and RELA correlates highly with BE with HGD and adenocarcinoma.

Self-report computer-based survey of technology use by people with intellectual and developmental disabilities.

Advancements of technologies in the areas of mobility, hearing and vision, communication, and daily living for people with intellectual and developmental disabilities has the potential to greatly enhance independence and self-determination. Previous research, however, suggests that there is a technological divide with regard to the use of such technologies by people with intellectual and developmental disabilities when compared with the use reported by the general public. To provide current information with regard to technology use by people with intellectual and developmental disabilities by examining the technology needs, use, and barriers to such use experienced by 180 adults with intellectual and developmental disabilities, we used QuestNet, a self-directed computer survey program. Results suggest that although there has been progress in technology acquisition and use by people with intellectual and developmental disabilities, an underutilization of technologies across the population remains.