Role of burn severity and posttraumatic stress symptoms in the co-occurrence of itch and neuropathic pain after burns: A longitudinal study.

Itch and pain are common after burns. Neuropathic mechanisms may underlie both modalities but remain not well-understood. This study aims to prospectively document neuropathic pain symptoms and to identify potential itch symptom profiles that differ regarding duration and co-occurrence with neuropathic pain which may inform underlying pathophysiological mechanisms and respond to different treatments. Adult burn survivors (n = 192) self-reported itch and neuropathic pain at 2 weeks post-discharge, 3, 6, 12, and 18 months post-burn. Based on the presence of itch and pain symptoms over time, participants were allocated to one itch profile: transient itch/pain, chronic itch, or chronic itch & pain. Profiles were compared on itch intensity over time using General Linear Modeling. Age, gender, burn severity, posttraumatic stress (PTS) symptoms and baseline itch intensity were examined as potential predictors of the profiles in a Multi-nominal regression analysis. Neuropathic pain occurred in 54% after discharge which decreased to 24% 18 months later. Itch intensity was highest in the chronic itch & pain profile. Compared to the transient itch profile, the chronic itch & pain profile was associated with higher burn severity and more PTS symptoms. Compared to the chronic itch profile, the chronic itch & pain profile was associated with more PTS symptoms. Findings suggest that biological and psycho-dermatological processes underlie both chronic neuropathic pain and itch processes in burn scars. Further research should elucidate the mechanisms underlying the different itch profiles, with specific focus on skin innervation and psychological factors.

PD-L1 (Programmed Death Ligand 1) Regulates T-Cell Differentiation to Control Adaptive Venous Remodeling.

OBJECTIVE: Patients with end-stage renal disease depend on hemodialysis for survival. Although arteriovenous fistulae (AVF) are the preferred vascular access for hemodialysis, the primary success rate of AVF is only 30% to 50% within 6 months, showing an urgent need for improvement. PD-L1 (programmed death ligand 1) is a ligand that regulates T-cell activity. Since T cells have an important role during AVF maturation, we hypothesized that PD-L1 regulates T cells to control venous remodeling that occurs during AVF maturation. Approach and results: In the mouse aortocaval fistula model, anti-PD-L1 antibody (200 mg, 3×/wk intraperitoneal) was given to inhibit PD-L1 activity during AVF maturation. Inhibition of PD-L1 increased T-helper type 1 cells and T-helper type 2 cells but reduced regulatory T cells to increase M1-type macrophages and reduce M2-type macrophages; these changes were associated with reduced vascular wall thickening and reduced AVF patency. Inhibition of PD-L1 also inhibited smooth muscle cell proliferation and increased endothelial dysfunction. The effects of anti-PD-L1 antibody on adaptive venous remodeling were diminished in nude mice; however, they were restored after T-cell transfer into nude mice, indicating the effects of anti-PD-L1 antibody on venous remodeling were dependent on T cells. CONCLUSIONS: Regulation of PD-L1 activity may be a potential therapeutic target for clinical translation to improve AVF maturation.

Knockout of the NONO Gene Inhibits Neointima Formation in a Mouse Model of Vascular Injury.

[Figure: see text].

Inhibition of T-Cells by Cyclosporine A Reduces Macrophage Accumulation to Regulate Venous Adaptive Remodeling and Increase Arteriovenous Fistula Maturation.

OBJECTIVE: Arteriovenous fistulae (AVF) are the preferred vascular access for hemodialysis, but the primary success rate of AVF remains poor. Successful AVF maturation requires vascular wall thickening and outward remodeling. A key factor determining successful AVF maturation is inflammation that is characterized by accumulation of both T-cells and macrophages. We have previously shown that anti-inflammatory (M2) macrophages are critically important for vascular wall thickening during venous remodeling; therefore, regulation of macrophage accumulation may be an important mechanism promoting AVF maturation. Since CD4+ T-cells such as T-helper type 1 cells, T-helper type 2 cells, and regulatory T-cells can induce macrophage migration, proliferation, and polarization, we hypothesized that CD4+ T-cells regulate macrophage accumulation to promote AVF maturation. Approach and Results: In a mouse aortocaval fistula model, T-cells temporally precede macrophages in the remodeling AVF wall. CsA (cyclosporine A; 5 mg/kg, sq, daily) or vehicle (5% dimethyl sulfoxide) was administered to inhibit T-cell function during venous remodeling. CsA reduced the numbers of T-helper type 1 cells, T-helper type 2, and regulatory T-cells, as well as M1- and M2-macrophage accumulation in the wall of the remodeling fistula; these effects were associated with reduced vascular wall thickening and increased outward remodeling in wild-type mice. However, these effects were eliminated in nude mice, showing that the effects of CsA on macrophage accumulation and adaptive venous remodeling are T-cell-dependent. CONCLUSIONS: T-cells regulate macrophage accumulation in the maturing venous wall to control adaptive remodeling. Regulation of T-cells during AVF maturation may be a strategy that can improve AVF maturation. Graphic Abstract: A graphic abstract is available for this article.

Effects of artepillin C on model membranes displaying liquid immiscibility.

It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (lo) and liquid-disordered (ld) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of lo phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface.

Effects of nicotine on rat adrenal gland: crosstalk between oxidative and inflammatory markers, and amelioration by melatonin.

Although the risks of smoking are well known, the effects of exposure to nicotine on endocrine functions remain unclear. We investigated the deleterious effects of nicotine on the adrenal gland and the mechanisms of these changes in rats. The role of melatonin in ameliorating pathological changes also was investigated. We used 24 rats divided into four groups of six: group 1, control; group 2, nicotine treated; group 3, nicotine and melatonin treated; group 4, melatonin treated. We used histology; immunohistochemistry of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and tyrosine hydroxylase (TH); measured oxidative and antioxidative markers, malondialdehyde (MDA) and glutathione (GSH); and performed real-time PCR for NF-κB 65, IL1-B and IL6. We also performed histomorphometric analysis. Indentation and lamellar separation of the adrenal capsule, vacuolated degenerated cells and lymphocytic infiltration were observed in group 2. Vacuolated cells and cells with pyknotic nuclei also were detected in the zona reticularis and medulla of the same group. We observed improved shape and cellular lining of the gland in groups 3 and 4. Widespread expression of iNOS, VEGF and TH, increased area percent collagen, decreased GSH (56%) and increased MDA, NF-κB, IL1-B and IL-6 were observed in group 2. All parameters were ameliorated in groups 3 and 4. The effects of nicotine on the adrenal gland can be attributed to oxidative and inflammatory stress; melatonin ameliorates these effects.

Effects of artepillin C on model membranes displaying liquid immiscibility

It has been hypothesized that the therapeutic effects of artepillin C, a natural compound derived from Brazilian green propolis, are likely related to its partition in the lipid bilayer component of biological membranes. To test this hypothesis, we investigated the effects of the major compound of green propolis, artepillin C, on model membranes (small and giant unilamelar vesicles) composed of ternary lipid mixtures containing cholesterol, which display liquid-ordered (lo) and liquid-disordered (ld) phase coexistence. Specifically, we explored potential changes in relevant membrane parameters upon addition of artepillin C presenting both neutral and deprotonated states by means of small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and confocal and multiphoton excitation fluorescence microscopy. Thermotropic analysis obtained from DSC experiments indicated a loss in the lipid cooperativity of lo phase at equilibrium conditions, while at similar conditions spontaneous formation of unilamellar vesicles from SAXS experiments showed that deprotonated artepillin C preferentially located at the surface of the membrane. Time-resolved experiments using fluorescence microscopy showed that at doses above 100 µM, artepillin C in its neutral state interacted with both liquid-ordered and liquid-disordered phases, inducing curvature stress and promoting dehydration at the membrane interface.

Catastrophizing, pain and traumatic stress symptoms following burns: A prospective study.

BACKGROUND: Pain and posttraumatic stress disorder (PTSD) symptoms are significant problems in the aftermath of a burn injury and they often co-occur. Catastrophizing has been linked to both phenomena. The aim of this study was to investigate the underlying role of catastrophizing in PTSD symptoms and pain following burns. METHODS: This prospective study included 216 patients with burns. PTSD symptoms and pain were measured during hospitalization (T1) and 6 (T2) and 12 months (T3) postburn. The Impact of Event Scale-Revised (IES-R) indexed PTSD symptoms. Acute pain (T1) was the mean pain during the first two weeks of hospitalization measured using an 11-point graphic numeric rating scale. Chronic pain was indexed using the single item 'average' pain from the Brief Pain Inventory (BPI). Catastrophizing was measured at T1 and T2 using the Cognitive Emotion Regulation Questionnaire (CERQ). Data were analysed using structural equation modelling (SEM). RESULTS: The results showed that T2 catastrophizing mediated between acute and chronic PTSD symptoms, and T3 pain. Furthermore, the study revealed significant associations between catastrophizing, PTSD symptoms and pain at the respective measurements, and significant longitudinal associations between the constructs. CONCLUSION: A negative cognitive-affective response to a burn event, such as catastrophizing, mediated the relationship between acute and chronic PTSD symptoms and later chronic pain. Screening for catastrophizing and acute PTSD symptoms is recommended to identify persons at risk for chronic PTSD symptoms and pain. SIGNIFICANCE: The identification of individuals who have the tendency to catastrophize may assist in finding those at risk for development of both chronic PTSD symptoms and chronic pain. Individuals may benefit from early psychological therapy focussing on catastrophizing and acute PTSD symptoms that may ameliorate both chronic PTSD symptoms and pain.

Analysis of the effects of climate variables on Apis mellifera pollen foraging performance / Análise dos efeitos de variáveis climáticas no desempenho de forrageamento de pólen de abelhas Apis mellifera

Pollination services performed by bees are essential for the reproduction of a great part of flowering plants. The pollen collected by Apis mellifera while performing pollination (bee pollen), has been incorporated into the human diet for its favorable nutritional components. Around 1,500 tons of bee pollen are produced annually worldwide, especially in Spain, China, Australia, Argentina, and Brazil. Despite the importance of bee pollen within apiculture, little is known about the effects of climate variations on bee pollen collection and production. We monitored the pollen collection performance of 24 different honey bee colonies in different climate conditions within a period of one year. We then analyzed the statistical interaction among the number of worker bees returning with pollen loads and 12 climatic variables, to produce a predictive mixed linear model. The results obtained showed that 7 climatic variables were statistically correlated to the pollen collection observed: Maximum temperature of the day, minimum temperature of the day, dew point temperature, relative humidity, cloud cover, rainfall, and the date of the sample. This research brings information for the development of a more effective pollen productive system.(AU)

Serviços de polinização são essenciais para a reprodução de uma grande parte das plantas com flores. Além de fundamental para produtividade agrícola e segurança alimentar no planeta, a atividade de polinização por Apis mellifera também possibilita a produção do pólen apícola. Devido a sua riqueza nutricional, o pólen apícola vem sendo incorporado às dietas humanas e de animais de interesse zootécnico. Cerca de 1.500 toneladas de pólen de abelha são produzidas anualmente em todo o mundo, especialmente em países como Espanha, China, Austrália, Argentina e Brasil. Apesar da importância do pólen na cadeia produtiva apícola, muito pouco se conhece sobre os efeitos das variações climáticas sobre a coleta e a produtividade de pólen. Neste estudo, foi monitorado o desempenho da coleta de pólen de 24 colônias de abelhas africanizadas, em diferentes condições climáticas, por um período de um ano. Analisaram-se estatisticamente as interações dos dados obtidos para o número de abelhas operárias que retornaram com cargas de pólen nas corbículas e 12 variáveis climáticas, a fim de se produzir um modelo estatístico preditivo. Os resultados obtidos mostraram que sete variáveis climáticas influenciaram significativamente a coleta de pólen: temperatura máxima do dia, temperatura mínima do dia, temperatura do ponto de orvalho, umidade relativa, cobertura de nuvens, precipitação pluviométrica e data da amostragem. Esta pesquisa traz informações importantes para o desenvolvimento de um sistema produtivo de pólen apícola mais eficaz.(AU)

Genetic Diversity in Nannotrigona testaceicornis (Hymenoptera: Apidae) Aggregations in Southeastern Brazil.

The Meliponini, also known as stingless bees, are distributed in tropical and subtropical areas of the world and plays an essential role in pollinating many wild plants and crops These bees can build nests in cavities of trees or walls, underground or in associations with ants or termites; interestingly, these nests are sometimes found in aggregations. In order to assess the genetic diversity and structure in aggregates of Nannotrigona testaceicornis (Lepeletier), samples of this species were collected from six aggregations and genetically analyzed for eight specific microsatellite loci. We observed in this analysis that the mean genetic diversity value among aggregations was 0.354, and the mean expected and observed heterozygosity values was 0.414 and 0.283, respectively. The statistically significant Fis value indicated an observed heterozygosity lower than the expected heterozygosity in all loci studied resulting in high homozygosis level in these populations. In addition, the low number of private alleles observed reinforces the absence of structuring that is seen in the aggregates. These results can provide relevant information about genetic diversity in aggregations of N. testaceicornis and contribute to the management and conservation of these bees' species that are critical for the pollination process.

Differential performance of honey bee colonies selected for bee-pollen production through instrumental insemination and free-mating technique / Comparação do desempenho de colônias de abelhas melíferas selecionadas para maiores produções de pólen apícola, por meio de inseminação instrumental e acasalamento livre

The use of bee-pollen as a nutritional supplement or as a production-enhancing agent in livestock has increased the demand for this product worldwide. Despite the current importance of this niche within the apiculture industry, few studies have addressed the pollen production. We tested the performance of free-mated (FM) and instrumentally inseminated queens (IQ) in order to establish the effect of different breeding systems on pollen production. The F1 generation of IQ queens produced 153.95±42.83g/day, showing a significant improvement on the pollen production (2.74 times) when compared to the parental generation (51.83±7.84g/day). The F1 generation of free-mated queens produced 100.07±8.23 g/day, which increased by 1.78 times when compared to the parental generation. Furthermore, we observed a statistically significant difference between the pollen production between colonies from the IQ and FM treatments. This study suggests that inseminated queens should be considered by beekeepers that aim to increase pollen production.(AU)

O uso do pólen apícola como suplemento nutricional humano e animal tem aumentado significativamente a demanda por este produto em todo o mundo. Apesar da importância atual desse nicho dentro da apicultura, poucos estudos têm abordado melhorias no sistema produtivo de pólen. Testamos o desempenho de rainhas fecundadas através de acasalamento livre (FM) e inseminação instrumental (QI), a fim de analisar o efeito de diferentes técnicas de melhoramento genético no ganho produtivo de pólen apícola. A geração F1 de rainhas QI produziu 153,95±42,83g de pólen por dia, mostrando uma melhora significativa na produção (2,74 vezes) quando comparado à geração parental (51,83±7,84g/dia). A geração F1 de rainhas de livre acasalamento produziu 100,07±8,23g/dia, o que significou um aumento de 1,78 vezes. Além disso, observou-se uma diferença estatisticamente significativa entre a produção de pólen entre as colônias dos tratamentos QI e FM. Este estudo sugere que a técnica de inseminação instrumental deve ser incorporada nos sistemas produtivos de pólen apícola brasileiro.(AU)

Negative correlation between tumour size and cortisol/ACTH ratios in patients with Cushing's disease harbouring microadenomas or macroadenomas.

PURPOSE: Pituitary macroadenomas (MACs) represent 10-30 % of Cushing's disease (CD) cases. The aim of this study was to report the clinical, laboratorial and imaging features and postsurgical outcomes of microadenoma (MIC) and MAC patients. METHODS: Retrospective study with 317 CD patients (median 32 years old, range 9-71 years) admitted between 1990 and 2014, 74 (23.3 %) of whom had MAC. RESULTS: Hirsutism, plethora facial, muscular weakness and muscular atrophy were more frequent in the MIC patients. Nephrolithiasis, osteopenia, hyperprolactinaemia and galactorrhoea were more prevalent in MAC patients. The morning serum cortisol (Fs), nocturnal salivary cortisol (NSC), nocturnal Fs (Fs 2400 h), low- and high-dose dexamethasone suppression test results and CRH and desmopressin test results were similar between the subgroups. MIC patients showed higher urinary cortisol at 24 h (UC), and MAC patients presented higher ACTH levels but lower Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. There were negative correlations of tumour size with Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. Overall, the postsurgical remission and recurrence rates were similar between MIC and MAC. However, patients in remission (MIC + MAC) showed smaller tumour diameters and a lower prevalence of invasion and extension on MRI. CONCLUSIONS: Despite exhibiting higher plasma ACTH levels, CD patients with MAC presented lower cortisol/ACTH ratios than did patients with MIC, with a negative correlation between tumour size and cortisol/ACTH ratios. The overall postsurgical remission and recurrence rates were similar between MIC and MAC patients, with those with larger and/or invasive tumours showing a lower remission rate.