Thermal and behavioral response of horses submitted to functional exercises and acupuncture

ABSTRACT: The present research evaluated muscle activation degrees and relaxation of patrolling horses submitted to dynamic mobilization exercises, associated or not with acupuncture. Twelve mixed breed gelding, aged 10 ± 2.0 years, were distributed in three treatments. Treatment with a single session of dynamic mobilization exercises (longitudinal cervical flexion of head between hooves, between carpus and to up to chest); treatment with a single acupuncture session during 20 minutes, and treatment with a single session of dynamic mobilization exercises with acupuncture. Thermographic images were analyzed before and after applying treatments to the cervical, thoracic, dorsal, abdominal and pelvic regions. Animal behavior was assessed through five minutes filming, before and ten minutes after the end of each treatment application, in an uninterrupted way. Increase in animals body temperature at the end of the single session of functional exercises (P < 0.0001) at all animal regions were reported, being cervical and thoracic areas with highest final temperature values. There was no temperature variation for other treatments (P > 0.05). All treatments stimulated higher expression frequency (P < 0.05) of relaxation behaviors. A single dynamic mobilization exercises session is enough to promote intense muscular response in entire horse body; and with acupuncture, individually or associated, promoted muscle and mental relaxation, interfering positively in animal welfare.

Variable Expression of the Disialoganglioside GD2 in Breast Cancer Molecular Subtypes

The disialoganglioside GD2 is a tumor-associated antigen that may allow for the application of targeted immunotherapies (anti-GD2 antibodies, GD2 CAR T cells) in patients with neuroblastoma and other solid tumors. We retrospectively investigated GD2 expression in a breast cancer cohort, using immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays (TMAs), and its impact on survival. GD2 expression on IHC (n = 568) and IF (n = 503) was investigated in relation to subtypes and patient outcome. Overall, 50.2% of the 568 IHC-assessed samples and 69.8% of the 503 IF-assessed samples were GD2-positive. The highest proportion of GD2-positive tumors was observed in luminal tumors. Significantly fewer GD2-positive cases were detected in triple-negative breast cancer (TNBC) compared with other subtypes. The proportion of GD2-expressing tumors were significantly lower in HER2-positive breast cancer in comparison with luminal tumors on IF staining (but not IHC). GD2 expression of IHC or IF was not significantly associated with disease-free or overall survival, in either the overall cohort or in individual subtypes. However, GD2 expression can be seen in more than 50% of breast cancer cases, with the highest frequency in hormone receptor-positive tumors. With this high expression frequency, patients with GD2-positive advanced breast cancer of all subtypes may benefit from GD2-targeting immunotherapies, which are currently subject to clinical testing.

Binary outcomes of enhancer activity underlie stable random monoallelic expression

Mitotically stable random monoallelic gene expression (RME) is documented for a small percentage of autosomal genes. Here we investigated the role of enhancers in the RME of natural killer (NK) cell receptor genes. Enhancers were accessible and enriched in H3K27ac on silent and active alleles alike, decoupling enhancer activation and expression. Enhancers controlled gene expression frequency, as predicted by the binary model of enhancer action, and enhancer deletion converted the broadly expressed Nkg2d into an RME gene, recapitulating natural variegation. The results suggested that RME is a consequence of general enhancer properties and therefore many genes may be subject to some degree of RME, which was borne out by analysis of a panel of genes previously thought to be universally expressed within defined hematopoietic lineages: Nkg2d, Cd45, Cd8a and Thy1. We propose that previously documented RME is an extreme on a continuum of intrinsically probabilistic gene expression.

Indicators of Secretory Activation in Mothers of Preterm Very Low Birth Weight Infants

Background Inconsistent information exists regarding indicators of secretory activation in mothers delivering very low birth weight infants. Research aims To compare time to the onset of secretory activation using three separate indicators. A secondary aim examined the association between indicators of secretory activation and milk production. Methods Indicators of secretory activation included maternal perception, volume attainment (production of ≥ 20 mL in two consecutive expression sessions) and biomarkers (sodium and lactose) obtained at volume attainment. Milk production was measured on Days 1–7 and then weekly for 6 weeks. Results In 69 mothers of infants born ≤ 32 weeks’ gestation and < 1500 g, we found no correlation in time to secretory activation between indicators. Earlier volume attainment was associated with increased milk production on Days 1–7, 14, 21, and 28 (all p < .007). Participants who exhibited both normal lactose and sodium levels produced more milk on Days 28 and 42 ( p = .028 and .011), those with only normal lactose levels produced more on Day 42 ( p = .026) and those with only normal sodium levels on Day 28 ( p = .036). Earlier secretory activation by volume attainment was associated with increased expression frequency during Days 2–5 (all p < .014) and participants with normal biomarkers expressed more frequently during Days 2–5 (all p < .020). Conclusion Mothers of very low birth weight infants are at risk for delayed secretory activation, which may decrease their milk production. Frequent expression during the first 5 days postpartum may promote earlier secretory activation. Valid methods of determining secretory activation are necessary to develop interventions promoting earlier secretory activation.

PD-1 and PD-L1 Expression in Peripheral CD4/CD8+ T Cells Is Restored in the Partial Remission Phase in Type 1 Diabetes

Context Partial remission (PR) in type 1 diabetes (T1D) is accompanied by downregulation of the immune response. Programmed cell death-1 (PD-1) and its ligand (PD-L1) are important immunosuppressive molecules, but their changes in the PR phase are unclear. Objective We investigated the dynamic changes of PD-1/PD-L1 expression on T cells around the PR phase in T1D. Methods Ninety-eight T1D patients were recruited cross-sectionally and grouped according to PR status into nonremitters (individuals who did not undergo PR during the disease course; n = 39), pre-PR (n = 15), mid-PR (n = 30), and post-PR (n = 14) subgroups. PR was defined according to C-peptide level ≥300 pmol/L or index of insulin-adjusted hemoglobin A1c ≤9 as recommended. Among all the 98 patients, 29 newly diagnosed individuals were prospectively followed up for 1 year. The dynamic changes of PD-1/PD-L1 expression, frequency of regulatory T cells (Tregs) and IL-35+ Tregs among peripheral CD4/CD8+ T cells were determined. Results PD-1/PD-L1 on CD4+/CD8+ T cells showed a dynamic change around the PR phase: lowest in pre-PR phase, restored in mid-PR phase, and declined again in post-PR phase. Conversely, this pattern did not occur for nonremitters. Notably, PD-1 expression on CD8+ T cells in mid-PR was positively correlated with the length of the PR phase. The percentages of circulating Tregs and IL-35+ Tregs showed no relation to PR. Conclusions The PR phase is associated with restoration of PD-1/PD-L1 on CD4+ and CD8+ T cells, suggesting that PD-1/PD-L1 may be a potential target for prolonging this phase in T1D.

Abnormal Platelet Phenotypes in Patients with Myelodysplastic Syndromes

Background: Hemorrhage and infection are two main causes of death in patients with myelodysplastic syndromes (MDS), mainly due to thrombocytopenia and neutropenia respectively. However, it is becoming increasingly clear that platelet dysfunction can also affect the process of hemostasis and anti-infection. Several studies have evaluated platelet activation in MDS and found platelet dysfunction, but immune-related function of platelets in patients with MDS has not been investigated yet. The aim of this study was to evaluate activation function and immune-related function of platelets in MDS by testing platelet activation-associated phenotypes and immune-associated phenotypes. Methods: We included 29 MDS patients and 22 healthy subjects, and MDS patients were divided into different subgroups (low-risk group and high-risk group; untreated group and treated group; pre-transfusion group and post-transfusion group) according to IPSS-R score, hypomethylating agents (HMAs) therapy and platelet transfusion history to observe phenotype changes under different factors. Platelet light scatter properties, expression of CD41a, expression of activation-associated phenotypes (CD62p and CD63) and expression of immune-associated phenotypes (CD154 and TLR4) were systematically detected by multi-parameter flow cytometry (MFC). Then correlations between phenotypes and clinical indexes were analyzed. Results: Compared to the healthy controls, decreased expression of platelet-specific antigen CD41a was shown in MDS patients (P<0.05). No difference was found in platelet light scatter properties between MDS patients and healthy subjects (P>0.05). Significantly decreased expression frequency and intensity of activation phenotype CD63 were found in patients with MDS (P<0.05). Low-risk MDS showed lower expression frequency while high-risk MDS showed reduced mean fluorescence intensity (MFI) of CD63. Decreased expression of CD154 and TLR4 was found in MDS patients (P<0.05) which was significantly elevated after HMAs therapy (P<0.05). Particularly, high-risk MDS patients again exhibited reduced MFI of CD154 and TLR4 (P<0.05). Correlation analysis showed that the expression of activation-associated phenotypes was not significantly correlated with the severity of bleeding events, but expression of CD62p was negatively correlated with white blood cell count (WBC) (r=-0.496, P=0.006; r=-0.498, P=0.006), absolute neutrophil count (ANC) (r=-0.512, P=-0.005; r=-0.442, P=0.016), fibrinogen (FIB) (r=-0.415, P=0.025; r=-0.510, P=0.005), and D-dimer (DD) (r=-0.547, P=0.002; r=-0.601, P=0.001), and positively correlated with prothrombin time (PT) (r=0.409, P =0.028; r=0.489, P=0.007). Expression of immune-associated phenotypes was not significantly correlated with the severity of infection events (P > 0.05). Conclusion: MDS patients displayed defective expression of both activation- and immune-associated platelet phenotypes, with differential mechanisms between low-risk and high-risk group regarding phenotype alterations. CD62p showed clinical relevance in regard to WBC count and coagulation indexes, and HMAs treatment significantly improved CD154 and TLR4 expression on platelets. Taken together, the findings confirmed impaired platelet phenotypes in MDS which may assist in the diagnosis and identification of MDS patients. Disclosures No relevant conflicts of interest to declare.

Evaluation of Microvascularity by CD34 Expression in Esophagus and Oral Squamous Cell Carcinoma

ABSTRACT Aim The present study was scheduled to evaluate microvascularity by CD34 expression in esophagus and oral squamous cell carcinoma. Materials and methods This study was scheduled using 40 paraffin blocked samples including 20 of oral SCC and 20 of esophagus ones and Immunohistochemical staining was conducted using CD34 monoclonal antibody. Exact fisher test was used to evaluate frequency of expression between two studied groups. Results There was significant correlation between age and tumor size with CD34 expression in oral SCC samples (p < 0.05) and no significant correlation between sex and tumor differentiation level (grading) (p > 0.05). Also, there was no significant correlation between age, sex, tumor size and tumor differentiation level (grading) with CD34 expression in esophagus SCC samples (p > 0.05). There was no significant difference of CD34 expression frequency in oral and esophagus SCC (p = 0/583). Finally, CD34 expression was reported ‘high’ for major cases of esophagus and oral SCCs. Conclusion It seems, other angiogenetic or nonangiogenetic factors except CD34 may play more important role and explain the different clinical behavior of SCC at recent different locations. Clinical significance Other factors would be considered along with CD34 expression to interpret different clinical behavior of SCC at recent different locations. How to cite this article Shahsavari F, Farhadi S, Sadri D, Sedehi M, Evaluation of Microvascularity by CD34 Expression in Esophagus and Oral Squamous Cell Carcinoma. J Contemp Dent Pract 2015;16(6):458-462.