Explore the vast range of titles available.

Background In brain tissues from multiple sclerosis (MS) patients, clusters of activated HLA-DR-expressing microglia, also referred to as preactive lesions, are located throughout the normal-appearing white matter. The aim of this study was to gain more insight into the frequency, distribution and cellular architecture of preactive lesions using a large cohort of well-characterized MS brain samples. Methods Here, we document the frequency of preactive lesions and their association with distinct white matter lesions in a cohort of 21 MS patients. Immunohistochemistry was used to gain further insight into the cellular and molecular composition of preactive lesions. Results Preactive lesions were observed in a majority of MS patients (67%) irrespective of disease duration, gender or subtype of disease. Microglial clusters were predominantly observed in the vicinity of active demyelinating lesions and are not associated with T cell infiltrates, axonal alterations, activated astrocytes or blood–brain barrier disruption. Microglia in preactive lesions consistently express interleukin-10 and TNF-α, but not interleukin-4, whereas matrix metalloproteases-2 and −9 are virtually absent in microglial nodules. Interestingly, key subunits of the free-radical-generating enzyme NADPH oxidase-2 were abundantly expressed in microglial clusters. Conclusions The high frequency of preactive lesions suggests that it is unlikely that most of them will progress into full-blown demyelinating lesions. Preactive lesions are not associated with blood–brain barrier disruption, suggesting that an intrinsic trigger of innate immune activation, rather than extrinsic factors crossing a damaged blood–brain barrier, induces the formation of clusters of activated microglia.

White spot lesions (WSLs) are demineralized lesions of the enamel that form in the presence of bacterial plaque, affecting the aesthetics by modifying the refractive index of the enamel, giving the characteristic “chalky” aspect. They have various causes, including fixed orthodontic treatments, improper hygiene, fluorosis and genetic factors. Background/Objectives: Considering the latest need for dental aesthetics and the popularization of fixed orthodontic treatments, the need to effectively treat WSLs has increased. The objective of this research is to review the development of WSLs and their treatment with resin infiltration. Methods: The PubMed, Web of Science, Scopus and Google Scholar databases were searched for relevant reviews and studies. Out of all, 56 were included in this research. Results: Prophylactic measures, such as fluorized toothpaste and varnishes, have limited results. Standard caries treatment is too invasive as it removes too much healthy enamel for obturation retentivity. The resin infiltration resin process does not require drilling or tooth structure loss, making it a painless and minimally invasive treatment. The resin used has a refractive index comparable to that of healthy enamel, consequently restoring aesthetics and ensuring the prevention of caries evolvement. The treatment involves five important steps: prophylaxis, acid demineralization, alcohol drying, resin infiltration and UV light curing. Depending on the clinical case, the demineralization and drying steps may need to be repeated. Conclusions: Infiltrations with resin are painless and well tolerated by patients. Out of all minimally invasive treatments, they have an immediate satisfactory outcome, with results stable for a minimum of 45 months.

Background It is difficult to distinguish between tumor progression (TP) and treatment-related abnormalities (TRA) in treated glioblastoma patients via conventional MRI, but this distinction is crucial for treatment decision making. Glioblastoma is known to exhibit an invasive growth pattern along white matter architecture and vasculature. This study quantified lesion development patterns in treated glioblastoma lesions and their relation to white matter microstructure to distinguish TP from TRA. Materials and methods Glioblastoma patients with confirmed TP or TRA with T1-weighted contrast-enhanced and DTI MR scans from two posttreatment follow-up timepoints were reviewed. The contrast-enhancing regions were segmented, and the regions were coregistered to the DTI data. Lesion increase vectors were categorized into two groups: parallel (0–20 degrees) and perpendicular (70–90 degrees) to white matter. FA-values were also extracted. To test for a statistically significant difference between the TP and TRA groups, a Mann‒Whitney U test was performed. Results Of 73 glioblastoma patients, fifteen were diagnosed with TRA, whereas 58 patients suffered TP. TP had a 25.8% (95% CI 24.1%-27.6%) increase in parallel lesions, and TRA had a 25.4% (95% CI 20.9%-29.9%) increase in parallel lesions. The perpendicular increase was 14.7% for TP (95% CI 13.0%-16.4%) and 18.0% (95% CI 13.5%-22.5%) for TRA. These results were not significantly different ( p  = 0.978). FA value for TP showed to be 0.248 (SD = 0.054) and for TRA it was 0.231 (SD = 0.075), showing no statistically significant difference ( p  = 0.121). Conclusions Based on our results, quantifying posttreatment contrast-enhancing lesion development directionality with DTI in glioblastoma patients does not appear to effectively distinguish between TP and TRA.

The aim was to clarify the role of vimentin, an intermediate filament protein abundantly expressed in activated macrophages and foam cells, in macrophages during atherogenesis. Global gene expression, lipid uptake, ROS, and inflammation were analyzed in bone-marrow derived macrophages from vimentin-deficient ( Vim −/− ) and wild-type ( Vim +/+ ) mice. Atherosclerosis was induced in Ldlr −/− mice transplanted with Vim −/− and Vim +/+ bone marrow, and in Vim −/− and Vim +/+ mice injected with a PCSK9 gain-of-function virus. The mice were fed an atherogenic diet for 12–15 weeks. We observed impaired uptake of native LDL but increased uptake of oxLDL in Vim −/− macrophages. FACS analysis revealed increased surface expression of the scavenger receptor CD36 on Vim −/− macrophages. Vim −/− macrophages also displayed increased markers of oxidative stress, activity of the transcription factor NF-κB, secretion of proinflammatory cytokines and GLUT1-mediated glucose uptake. Vim −/− mice displayed decreased atherogenesis despite increased vascular inflammation and increased CD36 expression on macrophages in two mouse models of atherosclerosis. We demonstrate that vimentin has a strong suppressive effect on oxidative stress and that Vim −/− mice display increased vascular inflammation with increased CD36 expression on macrophages despite decreased subendothelial lipid accumulation. Thus, vimentin has a key role in regulating inflammation in macrophages during atherogenesis.

• In wheat (Triticum aestivum cv. Soissons) plants grown under three different fertilisation treatments, we quantified the effect of leaf rust (Puccinia triticina) on flag leaf photosynthesis during the whole sporulation period. • Bastiaans' model: Y = (1-x)β was used to characterize the relationship between relative leaf photosynthesis (Y) and disease severity (x). The evolution of the different types of symptoms induced by the pathogen (sporulating, chlorotic and necrosed tissues) was evaluated using image analysis. • The β-values varied from 2 to 11, 1.4-2, and 0.8-1 during the sporulation period, when considering the proportion of sporulating, sporulating + necrotic, and total diseased area, respectively. Leaf nitrogen (N) content did not change the effect of the disease on host photosynthesis. • We concluded that leaf rust has no global effect on the photosynthesis of the symptomless parts of the leaves and that the large range in the quantification of leaf rust effect on the host, which is found in the literature, can be accounted for by considering the different symptom types. We discuss how our results could improve disease assessments and damage prediction in a wheat crop.

Footpad dermatitis (FPD) is a type of skin inflammation that causes necrotic lesions on the plantar surface of the footpads in commercial poultry, with significant animal welfare, and economic implications. To identify biomarkers for FPD development and wound healing, a battery cage trial was conducted in which a paper sheet was put on the bottom of cages to hold feces to induce FPD of broilers. Day-of-hatch Ross 308 male broiler chicks were fed a corn-soybean meal diet and assigned to 3 treatments with 8 cages per treatment and 11 birds per cage. Cages without paper sheets were used as a negative control (NEG). Cages with paper sheets during the entire growth period (d 0-30) were used as a positive control (POS) to continually induce FPD. Cages with paper sheets during d 0-13 and without paper sheets during d 14-30 were used to examine the dynamic of FPD development and lesion wound healing (LWH). Footpad lesions were scored to grade (G) 1-5 with no lesion in G1 and most severe lesion in G5. Covering with paper sheets in POS and LWH induced 99% incidence of G3 footpads on d 13. Removing paper sheets from LWH healed footpad lesions by d 30. One representative bird, with lesions most close to pen average lesion score, was chosen to collect footpad skin samples for biomarker analysis. Total collagen protein and mRNA levels of tenascin X (TNX), type I α1 collagen (COL1A1), type III α1 collagen (COL3A1), tissue inhibitor of metalloproteinase 3 (TIMP3), and integrin α1 (ITGA1) mRNA levels were decreased (P < 0.05), while mRNA levels of tenascin C (TNC), tumor necrosis factor (TNF) α, Toll-like receptor (TLR) 4 and vascular endothelial growth factor (VEGF), IL-1β, and the ratio of MMP2 to all TIMP were increased (P < 0.03) in G3 footpads in POS and LWH compared to G1 footpads in NEG on d 14. These parameters continued to worsen with development of more severe lesions in POS. After paper sheets were removed (i.e., LWH), levels of these parameters gradually or rapidly returned to levels measured in NEG. Regression analysis indicated significant quadratic changes of these parameters to footpad lesion scores. In summary, these biomarkers were interrelated with dynamic changes of footpad lesion scores, suggesting they may be used as potential biomarkers for footpad lesion development and wound healing process.

Variation between plant species of in-planta concentration and effectiveness of low-volume phosphite spray on lesion development of Phytophthora cinnamomi was determined for 14 species in two native communities of the South-West Botanical Province of Western Australia and 10 species in a glasshouse environment. There was considerable variation in stem phosphite concentrations between environments, phosphite treatment and taxa following low-volume spray. Average stem phosphite concentrations for taxa in the glasshouse environment were 8-fold greater than those in natural environments. In 48% of taxa, phosphite concentrations in stems of plants sprayed with 48 kg phosphite/ha were significantly greater than that for plants sprayed with 24 kg phosphite/ha. There was a 22 to 28-fold difference in stem tissue phosphite concentrations between taxa in the native communities and a 31 to 63-fold difference between taxa in the glasshouse environment. Phosphite was effective in 46% of the taxa based on rate of visible lesion development being significantly less in plants sprayed with 24 or 48 kg phosphite/ha than plants not sprayed. There were significant linear relationships between in-planta phosphite concentration and lesion development. Variation in phosphite effectiveness can be extended into a general hypothesis that plant species may differ in species-specific in-planta phosphite concentration thresholds that must be exceeded before effective control of P. cinnamomi can be achieved. Databases of species falling into phosphite effective or not effective groups can be used to assess variation in phosphite effectiveness between different threatened communities and assist in the development of application procedures aimed at overcoming ineffectiveness of the fungicide.

The present study is intended to investigate and compare the hemodynamics in two different sizes of hemodialysis arteriovenous grafts for upper arm hemodialysis vascular access: 8-mm tapered to 6-mm at the arterial side and straight 6 mm. A computational simulation approach is presented for this study, which is validated against the available experimental and numerical pressure measurements in the literature. The imposed boundary conditions at the arterial inlet and venous outlet boundaries of the models are physiological velocity and pressure waveforms, respectively. Blood flow fields and distribution patterns of the hemodynamic indices including wall shear stress (WSS) as one of the major hemodynamic parameters of the cardiovascular system and spatial wall shear stress gradient (SWSSG) as an indicator of disturbed flow patterns and hence susceptible sites of lesion developments are analyzed and compared between the two grafts. The tapered 6- to 8-mm graft seemingly is associated with less disturbed flow patterns within the venous anastomosis (VA) and the vein downstream while benefiting from higher blood flow rates within. Also, it shows a definitive advantage in terms of WSS and SWSSG distribution patterns around the VA and throughout the vein downstream with significantly lower values, which reduce the risk of thrombosis formation and stenotic lesion developments. The only disadvantage encountered in using 6- to 8-mm tapered graft is higher values of hemodynamic parameters at the arterial junction attributable to its significantly higher mean blood flow rate within. The results clearly indicate that the tapered 6- to 8-mm graft entirely outperforms straight 6-mm graft hemodynamically as an upper arm hemodialysis vascular access graft and confirms clinical data in the literature, which suggests advantageous use of tapered 6- to 8-mm grafts in the creation of upper arm brachioaxillary hemodialysis vascular access grafts in selected groups of patients with expectably higher patency rates and lower complications.

Theiler's murine encephalitis virus (TMEV) infection in mice is an established model of CNS demyelinating diseases. The aim of the study was to determine the chronological pattern of lesion development in this model of monophasic fulminant demyelinating disease. We followed six highly susceptible interferon-gamma receptor knockout mice with serial in vivo brain magnetic resonance imaging (MRI) studies to determine changes in overall T2 lesion load and gadolinium enhancement. Altogether, 163 individual lesions were followed over 52 days. The number of lesions increased linearly with time. Four chronological patterns of lesion development were seen: (a) expanding lesions (48.5% of all lesions, 54.05% volume contribution); (b) expanding–retracting lesions (20.85% of all lesions, 15.03% volume contribution); (c) fluctuating lesions (16.6% of all lesions, 28.8% volume contribution); (d) stable lesions (14.05% of all lesions, 2.12% volume contribution). Gadolinium enhancement was not seen in the evolution of every lesion. Enhancement was both time- and lesion type-dependent. Early in the disease course (<43 days after infection), enhancement was almost always seen, later on (>43 days after infection) it was only seen in 8% of new lesions. All of fluctuating, 85.3% of expanding, 83.5% of expanding–retracting, and 56.5% of stable lesions were associated with gadolinium enhancement. We conclude that the MRI features of TMEV-induced demyelination in this model showed four unique chronological patterns, and inconsistent gadolinium enhancement. These novel findings may provide new insights into the pathogenesis of acute fulminant multiple sclerosis (MS).

Low Carbohydrate High Protein diet represents a popular strategy to achieve weight loss. The aim of this study was to characterize effects of low carbohydrate, high protein diet (LCHP) on atherosclerotic plaque development in brachiocephalic artery (BCA) in apoE/LDLR−/− mice and to elucidate mechanisms of proatherogenic effects of LCHP diet. Atherosclerosis plaques in brachiocephalic artery (BCA) as well as in aortic roots, lipoprotein profile, inflammation biomarkers, expression of SREBP-1 in the liver as well as mortality were analyzed in Control diet (AIN-93G) or LCHP (Low Carbohydrate High Protein) diet fed mice. Area of atherosclerotic plaques in aortic roots or BCA from LCHP diet fed mice was substantially increased as compared to mice fed control diet and was characterized by increased lipids and cholesterol contents (ORO staining, FT-IR analysis), increased macrophage infiltration (MOMA-2) and activity of MMPs (zymography). Pro-atherogenic phenotype of LCHP fed apoE/LDLR−/− mice was associated with increased plasma total cholesterol concentration, and in LDL and VLDL fractions, increased TG contents in VLDL, and a modest increase in plasma urea. LCHP diet increased SCD-1 index, activated SREBP-1 transcription factor in the liver and triggered acute phase response as evidence by an increased plasma concentration of haptoglobin, CRP or AGP. Finally, in long-term experiment survival of apoE/LDLR−/− mice fed LCHP diet was substantially reduced as compared to their counterparts fed control diet suggesting overall detrimental effects of LCHP diet on health. The pro-atherogenic effect of LCHP diet in apoE/LDLR−/− mice is associated with profound increase in LDL and VLDL cholesterol, VLDL triglicerides, liver SREBP-1 upregulation, and systemic inflammation.