Corticosteroids Modulate Angiogenic Soluble Factors in Ulcerative Colitis Patients

Aims  

The aim of this study was to compare angiogenic factors in serum levels of active ulcerative colitis (UC) patients and in healthy controls, and to analyze these angiogenic levels depending on the achievement of remission after oral corticosteroid treatment throughout treatment, and according to the Truelove–Witts activity index.     

Predictors of Poor Outcome in ANCA-Associated Vasculitis (AAV)

It is important to recognize factors that might predict poor outcome and prognosis in patients with AAV. The predictors reported in the literature encompass genetic, histopathological, and clinical ones. Genetic studies (genetic predictors) have found genes that are associated with prediction of poor response to treatment, deterioration of renal function, and risk of mortality. Histopathological studies (histopathological predictors) have shown that sclerotic renal lesions are associated with increased risk of progression to end-stage renal disease and death. Lastly, scores (clinical predictors) obtained with tool as FFS, Maldini risk score, VDI, and emerging new biomarkers could potentially be helpful in assessment of prognosis in the future.     

La inervación del disco intervertebral

Until very recently, intervertebral disc innervation was a subject of considerable debate.Nowadays, the introduction of inmunohistochemical techniques associated to specific antibodies and studies with retrograde tracers in nerves have allowed greater understanding of disc innervation in physiological and pathological conditions and also endings characteristics and their patterns of distribution in both situations. The existing controversies regarding structural basis of discogenic pain, have raised the interest of knowing the influence of innervation in back pain from discal origin and its characteristics.Today, we know that pathologic neoinnervation accompanying radial fissures is an important factor in the genesis of discogenic pain; within a complex mechanism in which other neurobiomechemical, inflammatory and biomechanical factors are involved.     

Dissociating Arabic Numeral Reading and Basic Calculation: A Case Study

This study is about JS, a patient who suffered from anomia, phonological dyslexia and severe writing problems following a left hemispheric stroke. He showed good arabic numeral comprehension as evidenced in number-comparison tasks, but impairment in transcoding arabic numerals into verbal numbers and verbal numbers into arabic numerals. Although JS had several operand reading errors, the four arithmetic operations were not affected. In calculations with arabic numerals, he produced the correct results both in oral and written responses. For instance, when presented with the multiplication “7×3”, JS read the operation as “four times five”, but provided the correct response orally “twenty one” and written “21”. This behavior goes against those hypotheses which posit that multiplication facts are verbally-based, and those which establish the same route for verbal number production in calculation and arabic numeral reading.     

Prenatal Exposure to Glyphosate and Its Environmental Degradate,Aminomethylphosphonic Acid (AMPA), and Preterm Birth: A Nested Case–Control Study in the PROTECT Cohort (Puerto Rico)

Background: Glyphosate (GLY) is the most heavily used herbicide in the world. Despite nearly ubiquitous exposure, few studies have examined prenatal GLY exposure and potentially adverse pregnancy outcomes. Preterm birth (PTB) is a risk factor for neonatal mortality and adverse health effects in childhood.Objectives: We examined prenatal exposure to GLY and a highly persistent environmental degradate of GLY, aminomethylphosphonic acid (AMPA), and odds of PTB in a nested case–control study within the ongoing Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort in northern Puerto Rico.Methods: GLY and AMPA in urine samples collected at 18±2 (Visit 1) and 26±2 (Visit 3) wk gestation (53 cases/194 randomly selected controls) were measured using gas chromatography tandem mass spectrometry. Multivariable logistic regression was used to estimate associations with PTB (delivery <37wk completed gestation).Results: Detection rates in controls were 77.4% and 77.5% for GLY and 52.8% and 47.7% for AMPA, and geometric means (geometric standard deviations) were 0.44 (2.50) and 0.41 (2.56)μg/L for GLY and 0.25 (3.06) and 0.20 (2.87)μg/L for AMPA, for Visits 1 and 3, respectively. PTB was significantly associated with specific gravity–corrected urinary GLY and AMPA at Visit 3, whereas associations with levels at Visit 1 and the Visits 1–3 average were largely null or inconsistent. Adjusted odds ratios (ORs) for an interquartile range increase in exposure at Visit 3 were 1.35 (95% CI: 0.99, 1.83) and 1.67 (95% CI: 1.26, 2.20) for GLY and AMPA, respectively. ORs for Visit 1 and the visit average were closer to the null.Discussion: Urine GLY and AMPA levels in samples collected near the 26th week of pregnancy were associated with increased odds of PTB in this modestly sized nested case–control study. Given the widespread use of GLY, multiple potential sources of AMPA, and AMPA’s persistence in the environment, as well as the potential for long-term adverse health effects in preterm infants, further investigation in other populations is warranted. https://doi.org/10.1289/EHP7295     

An inducible transgenic mouse breast cancer model for the analysis of tumor antigen specific CD8+ T-cell responses

In Simian virus 40 (SV40) transgenic BALB/c WAP-T mice tumor development and progression is driven by SV40 tumor antigens encoded by inducible transgenes. WAP-T mice constitute a well characterized mouse model for breast cancer with strong similarities to the corresponding human disease. BALB/c mice mount only a weak cellular immune response against SV40 T-antigen (T-Ag). For studying tumor antigen specific CD8⁺ T-cell responses against transgene expressing cells, we created WAP-T_NP mice, in which the transgene additionally codes for the NP_118–126-epitope contained within the nucleoprotein of lymphocytic choriomeningitis virus (LCMV), the immune-dominant T-cell epitope in BALB/c mice. We then investigated in WAP-T_NP mice the immune responses against SV40 tumor antigens and the NP-epitope within the chimeric T-Ag/NP protein (T-Ag_NP). Analysis of the immune-reactivity against T-Ag in WAP-T and of T-Ag_NP in WAP-T_NP mice revealed that, in contrast to wild type (wt) BALB/c mice, WAP-T and WAP-T_NP mice were non-reactive against T-Ag. However, like wtBALB/c mice, WAP-T as well as WAP-T_NP mice were highly reactive against the immune-dominant LCMV NP-epitope, thereby allowing the analysis of NP-epitope specific cellular immune responses in WAP-T_NP mice. LCMV infection of WAP-T_NP mice induced a strong, LCMV NP-epitope specific CD8⁺ T-cell response, which was able to specifically eliminate T-Ag_NP expressing mammary epithelial cells both prior to tumor formation (i.e. in cells of lactating mammary glands), as well as in invasive tumors. Elimination of tumor cells, however, was only transient, even after repeated LCMV infections. Further studies showed that already non-infected WAP-T_NP tumor mice contained LCMV NP-epitope specific CD8⁺ T-cells, albeit with strongly reduced, though measurable activity. Functional impairment of these ‘endogenous’ NP-epitope specific T-cells seems to be caused by expression of the programmed death-1 protein (PD1), as anti-PD1 treatment of splenocytes from WAP-T_NP tumor mice restored their activity. These characteristics are similar to those found in many tumor patients and render WAP-T_NP mice a suitable model for analyzing parameters to overcome the blockade of immune checkpoints in tumor patients.