7 & 7 Synch and 7-day progesterone- based protocols for estrus synchronization prior fixedtime artificial insemination in multiparous beef sucked cows

PosterEstrogen-based protocols combined with a progestinreleasing intravaginal device (P4RID) and prostaglandin (PG) synchronize follicle wave emergence prior to artificial insemination (AI) in Bos taurus, with pregnancies per AI (P/AI) ranging from 40 to 60%. Gonadotropin-releasing hormone (GnRH) based protocols + P4RID + PG rely on the presence of a physiologically mature dominant follicle at initial GnRH. Failure to induce ovulation represents a major obstacle to improve P/AI. Pre-synchronization by PG + P4RID 7 days in advance of GnRH increase likelihood of ovulation following GnRH. The aim of this trial was to evaluate fertility in suckled beef cows using GnRH or estrogen treatments with or without pre-synchronizationEEA BarrowFil: Ferré, Luis Bernardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Chacra Experimental Integrada Barrow; Argentina.Fil: Jaeschke, J. Biogénesis Bagó; Argentina.Fil: Gatti, J. Biogénesis Bagó; Argentina.Fil: Baladón, G. Biogénesis Bagó; Argentina.Fil: Bellocq, E. Biogénesis Bagó; Argentina.Fil: Fernández, G. Actividad privada; Argentina.Fil: Thomas, J. University of Missouri. Division of Animal Sciences; Estados Unido

Association of body surface scanner-based abdominal volume with parameters of the Metabolic Syndrome and comparison with manually measured waist circumference

To investigate abdominal volume determined by a new body scanner algorithm as anthropometric marker for Metabolic Syndrome (MetS) and its parameters compared to manually measured waist circumference (WC), we performed body scans in 411 participants (38% men, 20-81 years). WC and triglyceride, HDL-cholesterol, and fasting glucose concentrations, and blood pressure were assessed as MetS parameters. We used Spearman correlations and linear regression to investigate associations and goodness-of-fit (R(2), BIC) of abdominal volume and WC with MetS parameters, and logistic regression to analyse the discriminative power of WC and abdominal volume to assess likelihoods of MetS components and MetS. Correlations with triglyceride, HDL-cholesterol, and glucose concentration were slightly stronger for abdominal volume (r; 0.32, −0.32, and 0.34, respectively) than for WC (0.28, −0.28, and 0.29, respectively). Explained variances in MetS parameters were slightly higher and goodness-of-fit slightly better for abdominal volume than for WC, but differences were small. Exemplarily, glucose levels were 0.28 mmol/L higher (R² = 0.25; BIC = 945.5) per 1-SD higher WC, and 0.35 mmol/L higher (R² = 0.28; BIC = 929.1) per 1-SD higher abdominal volume. The discriminative power to estimate MetS components was similar for WC and abdominal volume. Our data show that abdominal volume allows metabolic characterization comparable to established WC

On inversions and Doob hh-transforms of linear diffusions

Let $X$ be a regular linear diffusion whose state space is an open interval $E\subseteq\mathbb{R}$. We consider a diffusion $X^*$ which probability law is obtained as a Doob $h$-transform of the law of $X$, where $h$ is a positive harmonic function for the infinitesimal generator of $X$ on $E$. This is the dual of $X$ with respect to $h(x)m(dx)$ where $m(dx)$ is the speed measure of $X$. Examples include the case where $X^*$ is $X$ conditioned to stay above some fixed level. We provide a construction of $X^*$ as a deterministic inversion of $X$, time changed with some random clock. The study involves the construction of some inversions which generalize the Euclidean inversions. Brownian motion with drift and Bessel processes are considered in details.Comment: 19 page

3D Quantification of Vascular-Like Structures in z Stack Confocal Images

Optical slice microscopy is commonly used to characterize the morphometric features of 3D cellular cultures, such as in vitro vascularization. However, the quantitative analysis of those structures is often performed on a single 2D maximum intensity projection image, limiting the accuracy of data obtained from 3D cultures. Here, we present a protocol for the quantitative analysis of z stack images, utilizing Fiji, Amira, and WinFiber3D. This protocol facilitates the in-depth examination of vascular-like structures within 3D cell culture models

Techniques for RNA extraction from cells cultured in starPEG-heparin hydrogels

Three-dimensional (3D) cell culture models that provide a biologically relevant microenvironment are imperative to investigate cell–cell and cell–matrix interactions in vitro. Semi-synthetic star-shaped poly(ethylene glycol) (starPEG)–heparin hydrogels are widely used for 3D cell culture due to their highly tuneable biochemical and biomechanical properties. Changes in gene expression levels are commonly used as a measure of cellular responses. However, the isolation of high-quality RNA presents a challenge as contamination of the RNA with hydrogel residue, such as polymer or glycosaminoglycan fragments, can impact template quality and quantity, limiting effective gene expression analyses. Here, we compare two protocols for the extraction of high-quality RNA from starPEG–heparin hydrogels and assess three subsequent purification techniques. Removal of hydrogel residue by centrifugation was found to be essential for obtaining high-quality RNA in both isolation methods. However, purification of the RNA did not result in further improvements in RNA quality. Furthermore, we show the suitability of the extracted RNA for cDNA synthesis of three endogenous control genes confirmed via quantitative polymerase chain reaction (qPCR). The methods and techniques shown can be tailored for other hydrogel models based on natural or semi-synthetic materials to provide robust templates for all gene expression analyses

Critical appraisal skills of family physicians in Ontario, Canada

BACKGROUND: Our primary objective in this study was to measure family physicians' knowledge of the key elements that go into assessing the validity and interpreting the results in three different types of studies: i) a randomized controlled trial (RCT); ii) a study evaluating a diagnostic test; and iii) a systematic review (SR). Our secondary objectives were to determine the relationship between the above skills and age, gender, and type of practice. METHODS: We obtained a random sample of 1000 family physicians in Ontario from the College of Family Physicians of Canada database. These physicians were sent a questionnaire in the mail with follow-up mailings to non-responders at 3 and 8 weeks. The questionnaire was designed to measure knowledge and understanding of the basic concepts of critical appraisal skills. Based on the responses to the questions an Evidence Based Medicine (EBM) Knowledge Score was determined for each physician. RESULTS: A response rate of 30.2% was achieved. The respondents were younger and more likely to be recent graduates than the population of Ontario Family Physicians as a whole. This was an expected outcome. Just over 50% of respondents were able to answer questions concerning the critical appraisal of methods and the interpretation of results of research articles satisfactorily. The average score on the 12-point EBM Knowledge Scale was 6.4. The younger physicians scored higher than the older physicians, and academic physicians scored higher than community-based physicians. Scores of male and female physicians did not differ. CONCLUSIONS: We have shown that in a population of physicians which is younger than the general population of physicians, about 50% have reasonable knowledge regarding the critical appraisal of the methods and the interpretation of results of a research article. In general, younger physicians were more knowledgeable than were older physicians. EBM principles were felt to be important to the practice of medicine by 95% of respondents

Interpreting the results of patient reported outcome measures in clinical trials: The clinician's perspective

This article deals with the problem of interpreting health-related quality of life (HRQL) outcomes in clinical trials. First, we will briefly describe how dichotomization and item response theory can facilitate interpretation. Based on examples from the medical literature for the interpretation of HRQL scores we will show that dichotomies may help clinicians understand information provided by HRQL instruments in RCTs. They can choose thresholds to calculate proportions of patients benefiting based on absolute scores or change scores. For example, clinicians interpreting clinical trial results could consider the difference in the proportion of patients who achieve a mean score of 50 before and after an intervention on a scale from 1 to 100. For the change score approach, they could consider the proportion of patients who have changed by a score of 5 or more. Finally, they can calculate the proportion of patients benefiting and transform these numbers into a number needed to treat or natural frequencies. Second, we will describe in more detail an approach to the interpretation of HRQL scores based on the minimal important difference (MID) and proportions. The MID is the smallest difference in score in the outcome of interest that informed patients or informed proxies perceive as important, either beneficial or harmful, and that would lead the patient or clinician to consider a change in the management. Any change in management will depend on the downsides, including cost and inconvenience, associated with the intervention. Investigators can help with the interpretation of HRQL scores by determining the MID of an HRQL instrument and provide mean differences in relation to the MID. For instance, for an MID of 0.5 on a seven point scale investigators could provide the mean change on the instrument as well as the proportion of patients with scores greater than the MID. Thus, there are several steps investigators can take to facilitate this process to help bringing HRQL information closer to the bedside

Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress

Currently approved repetitive transcranial magnetic stimulation (rTMS) protocols for the treatment of major depressive disorder (MDD) involve once-daily (weekday) stimulation sessions, with 10 Hz or intermittent theta burst stimulation (iTBS) frequencies, over 4–6 weeks. Recently, accelerated treatment protocols (multiple daily stimulation sessions for 1–2 weeks) have been increasingly studied to optimize rTMS treatments. Accelerated protocols might confer unique advantages for adolescents and young adults but there are many knowledge gaps related to dosing in this age group. Off-label, clinical practice frequently outpaces solid evidence as rigorous clinical trials require substantial time and resources. Murine models present an opportunity for high throughput dose finding studies to focus subsequent clinical trials in humans. This project investigated the brain and behavioural effects of an accelerated low-intensity rTMS (LI-rTMS) protocol in a young adult rodent model of chronic restraint stress (CRS). Depression and anxiety-related behaviours were induced in young adult male Sprague Dawley rats using the CRS model, followed by the 3-times-daily delivery of 10 Hz LI-rTMS, for two weeks. Behaviour was assessed using the Elevated Plus Maze and Forced Swim Test, and functional, chemical, and structural brain changes measured using magnetic resonance imaging techniques. CRS induced an agitated depression-like phenotype but therapeutic effects from the accelerated protocol were not detected. Our findings suggest that the age of rodents may impact response to CRS and LI-rTMS. Future studies should also examine higher intensities of rTMS and accelerated theta burst protocols

Apoptosis versus oncotic necrosis in hepatic ischemia/reperfusion injury

AbstractWarm and cold hepatic ischemia followed by reperfusion leads to necrotic cell death (oncosis), which often occurs within minutes of reperfusion. Recent studies also suggest a large component of apoptosis after ischemia/reperfusion. Here, we review the mechanisms underlying adenosine triphosphate depletion—dependent oncotic necrosis and caspase-dependent apoptosis, with emphasis on shared features and pathways. Although apoptosis causes internucleosomal DNA degradation that can be detected by terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling and related assays, DNA degradation also occurs after oncotic necrosis and leads to pervasive terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick-end labeling staining far in excess of that for apoptosis. Similarly, although apoptosis can occur in a physiological setting without inflammation, in pathophysiological settings apoptosis frequently induces inflammation because of the onset of secondary necrosis and stimulation of cytokine and chemokine formation. In liver, the mitochondrial permeability transition represents a shared pathway that leads to both oncotic necrosis and apoptosis. When the mitochondrial permeability transition causes severe adenosine triphosphate depletion, plasma membrane failure and necrosis ensue. If adenosine triphosphate is preserved, at least in part, cytochrome c release after the mitochondrial permeability transition activates caspase-dependent apoptosis. Mitochondrial permeability transition-dependent cell death illustrates the concept of necrapoptosis, whereby common pathways lead to both necrosis and apoptosis. In conclusion, oncotic necrosis and apoptosis can share features and mechanisms, which sometimes makes discrimination between the 2 forms of cell death difficult. However, elucidation of critical cell death pathways under clinically relevant conditions will show potentially important therapeutic intervention strategies in hepatic ischemia/reperfusion injury

The new COSMIN guidelines confront traditional concepts of responsiveness

The recently published "COSMIN" guidelines aim to rate properties of outcome instruments and state two issues with regard to responsiveness which is the instrument's ability to detect change over time. These issues are comparison of score changes with change of an external criterion using correlations and the judgement of traditional methods as inappropriate. The latter are the "transition" concept, a global rating of change, and parametric measures of responsiveness, for example, effect sizes. It can be shown that the methodology proposed by the guidelines has important weaknesses and that denunciation of traditional methods is not appropriate. Some claims of the guidelines about responsiveness do not match the demands of clinical reality and confront findings of numerous epidemiological studies