Thyroid Feeding From Conception and Hypo-thalamo Pituitary-Adrenal Axis Response in 30-Day-Old Rats

Author Institution: Department of Biological Sciences, Bowling Green State UniversityElevation of thyroid status in pre- and postnatal rats has been previously shown to accelerate the development of the neuroendocrine axis controlling adrenal response to stress. The present study determined the influence of feeding desiccated thyroid powder (0.03%) in the maternal diet from conception until young were 30 d old. Circulating corticosterone levels were compared in control and thyroid-fed young before stimulation, after a general stress (one min exposure to ether fumes), direct adrenal stimulation (subcutaneous adrenocorticotropin (ACTH) injection) or control injection (physiological saline subcutaneously). Corticosterone levels were measured by both fluorometric assay and radioimmunoassay (RIA). These comparisons revealed that thyroid feeding did not significantly influence basal corticosterone levels, or response to general stress or saline injection. However, injected ACTH stimulated a significantly greater adrenal response in controls than thyroid-fed rats. Since responses relying on endogenous ACTH were not altered by thyroid feeding, it is suggested that absorption of subcutaneously injected ACTH was subnormal in the experimental animals. Results were similar for both assay techniques, indicating that the advantages of precision and specificity given by RIA over fluorometric assay were not critical in this study

Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn\u27s Disease But Not Ulcerative Colitis.

BACKGROUND & AIMS: Patients with Crohn\u27s disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration. METHODS: We analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (\u3e2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes. RESULTS: Within 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P \u3c .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC. CONCLUSIONS: Patients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC

Development and Validation of Clinical Scoring Tool to Predict Outcomes of Treatment With Vedolizumab in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: We created and validated a clinical decision support tool (CDST) to predict outcomes of vedolizumab therapy for ulcerative colitis (UC). METHODS: We performed logistic regression analyses of data from the GEMINI 1 trial, from 620 patients with UC who received vedolizumab induction and maintenance therapy (derivation cohort), to identify factors associated with corticosteroid-free remission (full Mayo score of 2 or less, no subscore above 1). We used these factors to develop a model to predict outcomes of treatment, which we called the vedolizumab CDST. We evaluated the correlation between exposure and efficacy. We validated the CDST in using data from 199 patients treated with vedolizumab in routine practice in the United States from May 2014 through December 2017. RESULTS: Absence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 y or more (+3 points), baseline endoscopic activity (moderate vs severe) (+2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy. Patients in the derivation and validation cohorts were assigned to groups of low (CDST score, 26 points or less), intermediate (CDST score, 27-32 points), or high (CDST score, 33 points or more) probability of vedolizumab response. We observed a statistically significant linear relationship between probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P \u3c .001) in the derivation cohort. In the validation cohort, a cutoff value of 26 points identified patients who did not respond to vedolizumab with high sensitivity (93%); only the low and intermediate probability groups benefited from reducing intervals of vedolizumab administration due to lack of response (P = .02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy. CONCLUSIONS: We used data from a trial of patients with UC to develop a scoring system, called the CDST, which identified patients most likely to enter corticosteroid-free remission during vedolizumab therapy, but not anti-TNF therapy. We validated the vedolizumab CDST in a separate cohort of patients in clinical practice. The CDST identified patients most likely to benefited from reducing intervals of vedolizumab administration due to lack of initial response. ClinicalTrials.gov no: NCT00783718

Shorter Disease Duration Is Associated With Higher Rates of Response to Vedolizumab in Patients With Crohn's Disease But Not Ulcerative Colitis.

Background & aimsPatients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration.MethodsWe analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (>2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes.ResultsWithin 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P < .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC.ConclusionsPatients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC

A synthesis of ENSO effects on drylands in Australia, North America and South America

Fundamentally, El Niño Southern Oscillation (ENSO) is a climatic and oceanographic phenomenon, but it has profound effects on terrestrial ecosystems. Although the ecological effects of ENSO are becoming increasingly known from a wide range of terrestrial ecosystems (Holmgren et al., 2001), their impacts have been more intensively studied in arid and semiarid systems. In this brief communication, we summarize the main conclusions of a recent symposium on the effects of ENSO in these ecosystems, which was convened as part of the First Alexander von Humboldt International Conference on the El Niño Phenomenon and its Global Impact, in Guayaquil, Ecuador, from 16–20 May 2005. Participants in the symposium shared results and perspectives from research conducted in North and South America and Australia, regions where the ecological effects of ENSO have been studied in depth. Although the reports covered a wide array of organisms and ecological systems (Fig. 1), a recurring theme was the strong increase in rainfall associated with ENSO events in dry ecosystems (during the El Niño phase of the oscillation in the Americas and the La Niña phase in Australia). Because inter-annual variability in precipitation is such a strong determinant of productivity in arid and semiarid ecosystems, increased ENSO rainfall is crucial for plant recruitment, productivity and diversity in these ecosystems. Several long-term studies show that this pulse in primary productivity causes a subsequent increase in herbivores, followed by an increase in carnivores, with consequences for changes in ecosystem structure and functioning that can be quite complex

Plague and Climate: Scales Matter

Plague is enzootic in wildlife populations of small mammals in central and eastern Asia, Africa, South and North America, and has been recognized recently as a reemerging threat to humans. Its causative agent Yersinia pestis relies on wild rodent hosts and flea vectors for its maintenance in nature. Climate influences all three components (i.e., bacteria, vectors, and hosts) of the plague system and is a likely factor to explain some of plague's variability from small and regional to large scales. Here, we review effects of climate variables on plague hosts and vectors from individual or population scales to studies on the whole plague system at a large scale. Upscaled versions of small-scale processes are often invoked to explain plague variability in time and space at larger scales, presumably because similar scale-independent mechanisms underlie these relationships. This linearity assumption is discussed in the light of recent research that suggests some of its limitations

Clinical knee findings in floor layers with focus on meniscal status

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the prevalence of self-reported and clinical knee morbidity among floor layers compared to a group of graphic designers, with special attention to meniscal status.</p> <p>Methods</p> <p>We obtained information about knee complaints by questionnaire and conducted a bilateral clinical and radiographic knee examination in 134 male floor layers and 120 male graphic designers. After the exclusion of subjects with reports of earlier knee injuries the odds ratio (OR) with 95% confidence intervals (CI) of knee complaints and clinical findings were computed among floor layers compared to graphic designers, using logistic regression. Estimates were adjusted for effects of body mass index, age and knee straining sports. Using radiographic evaluations, we conducted side-specific sensitivity analyses regarding clinical signs of meniscal lesions after the exclusion of participants with tibiofemoral (TF) osteoarthritis (OA).</p> <p>Results</p> <p>Reports of knee pain (OR = 2.7, 95% CI = 1.5–4.6), pain during stair walking (OR = 2.2, 95% CI = 1.3–3.9) and symptoms of catching of the knee joint (OR = 2.9, 95% CI = 1.4–5.7) were more prevalent among floor layers compared to graphic designers. Additionally, significant more floor layers than graphic designers had clinical signs suggesting possible meniscal lesions: a positive McMurray test (OR = 2.4, 95% CI = 1.1–5.0) and TF joint line tenderness (OR = 5.4, 95% CI = 2.4–12.0). Excluding floor layers (n = 22) and graphic designers (n = 15) with radiographic TF OA did not alter this trend between the two study groups: a positive McMurray test (OR = 2.2, 95% CI = 1.0–4.9), TF joint line tenderness (OR = 5.0, 95% CI = 2.0–12.5).</p> <p>Conclusion</p> <p>Results indicate that floor layers have a high prevalence of both self-reported and clinical knee morbidity. Clinical knee findings suggesting possible meniscal lesions were significant more prevalent among floor layers compared to a group of low-level exposed graphic designers and an association with occupational kneeling could be possible. However, causality cannot be confirmed due to the cross-sectional study design.</p

Clinical knee findings in floor layers with focus on meniscal status

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the prevalence of self-reported and clinical knee morbidity among floor layers compared to a group of graphic designers, with special attention to meniscal status.</p> <p>Methods</p> <p>We obtained information about knee complaints by questionnaire and conducted a bilateral clinical and radiographic knee examination in 134 male floor layers and 120 male graphic designers. After the exclusion of subjects with reports of earlier knee injuries the odds ratio (OR) with 95% confidence intervals (CI) of knee complaints and clinical findings were computed among floor layers compared to graphic designers, using logistic regression. Estimates were adjusted for effects of body mass index, age and knee straining sports. Using radiographic evaluations, we conducted side-specific sensitivity analyses regarding clinical signs of meniscal lesions after the exclusion of participants with tibiofemoral (TF) osteoarthritis (OA).</p> <p>Results</p> <p>Reports of knee pain (OR = 2.7, 95% CI = 1.5–4.6), pain during stair walking (OR = 2.2, 95% CI = 1.3–3.9) and symptoms of catching of the knee joint (OR = 2.9, 95% CI = 1.4–5.7) were more prevalent among floor layers compared to graphic designers. Additionally, significant more floor layers than graphic designers had clinical signs suggesting possible meniscal lesions: a positive McMurray test (OR = 2.4, 95% CI = 1.1–5.0) and TF joint line tenderness (OR = 5.4, 95% CI = 2.4–12.0). Excluding floor layers (n = 22) and graphic designers (n = 15) with radiographic TF OA did not alter this trend between the two study groups: a positive McMurray test (OR = 2.2, 95% CI = 1.0–4.9), TF joint line tenderness (OR = 5.0, 95% CI = 2.0–12.5).</p> <p>Conclusion</p> <p>Results indicate that floor layers have a high prevalence of both self-reported and clinical knee morbidity. Clinical knee findings suggesting possible meniscal lesions were significant more prevalent among floor layers compared to a group of low-level exposed graphic designers and an association with occupational kneeling could be possible. However, causality cannot be confirmed due to the cross-sectional study design.</p