Estrous synchronization, coupled with natural service, provides the benefit of female cows conceiving early, but there are an increased number of females expressing estrus in a short period of time. ...Thus, considerations need to be made for the bull. Select a protocol that will distribute estrus over a longer period of time and ensure bulls pass a breeding soundness examination. Mature bulls (3 years old or older) have increased efficiency in getting cows pregnant compared with younger bulls; therefore, a ratio of 1 mature bull to 25 cows is a good recommendation within an estrous synchronized herd.
Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely ...unknown. Using the iKnife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to mutant PIK3CA genotype. Oncogenic PIK3CA results in an increase in arachidonic acid and a concomitant overproduction of eicosanoids, acting to promote cell proliferation beyond a cell-autonomous manner. Mechanistically, mutant PIK3CA drives a multimodal signaling network involving mTORC2-PKCζ-mediated activation of the calcium-dependent phospholipase A2 (cPLA2). Notably, inhibiting cPLA2 synergizes with fatty acid-free diet to restore immunogenicity and selectively reduce mutant PIK3CA-induced tumorigenicity. Besides highlighting the potential for metabolic phenotyping in stratified medicine, this study reveals an important role for activated PI3K signaling in regulating arachidonic acid metabolism, uncovering a targetable metabolic vulnerability that largely depends on dietary fat restriction.
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•The iKnife offers near real-time diagnosis of PIK3CA mutant breast cancers•Oncogenic PIK3CA promotes enhanced arachidonic acid via mTORC2-PKCζ-cPLA2 signaling•Mutant PIK3CA regulates proliferation beyond a cell autonomous manner•cPLA2 inhibition and dietary fat restriction suppress PIK3CA-induced tumorigenicity
Metabolic fingerprinting using the iKnife offers near real-time diagnosis of PIK3CA mutant breast cancers and connects oncogenic PIK3CA with enhanced arachidonic acid metabolism. cPLA2 inhibition shows remarkable synergy with dietary fat restriction to restore tumoral immune cell infiltration and inhibit growth of mutant PIK3CA-bearing breast tumors.
Syncope can be caused by serious conditions not evident during initial evaluation, which can lead to serious adverse events, including death, after disposition from the emergency department. We ...sought to develop a clinical decision tool to identify adult patients with syncope who are at risk of a serious adverse event within 30 days after disposition from the emergency department.
We prospectively enrolled adults (age ≥ 16 yr) with syncope who presented within 24 hours after the event to 1 of 6 large emergency departments from Sept. 29, 2010, to Feb. 27, 2014. We collected standardized variables at index presentation from clinical evaluation and investigations. Adjudicated serious adverse events included death, myocardial infarction, arrhythmia, structural heart disease, pulmonary embolism, serious hemorrhage and procedural interventions within 30 days.
We enrolled 4030 patients with syncope; the mean age was 53.6 years, 55.5% were women, and 9.5% were admitted to hospital. Serious adverse events occurred in 147 (3.6%) of the patients within 30 days after disposition from the emergency department. Of 43 candidate predictors examined, we included 9 in the final model: predisposition to vasovagal syncope, heart disease, any systolic pressure reading in the emergency department < 90 or > 180 mm Hg, troponin level above 99th percentile for the normal population, abnormal QRS axis (< -30° or > 100°), QRS duration longer than 130 ms, QTc interval longer than 480 ms, emergency department diagnosis of cardiac syncope and emergency department diagnosis of vasovagal syncope (C statistic 0.88, 95% confidence interval CI 0.85-0.90; optimism 0.015; goodness-of-fit p = 0.11). The risk of a serious adverse event within 30 days ranged from 0.4% for a score of -3 to 83.6% for a score of 11. The sensitivity was 99.2% (95% CI 95.9%-100%) for a threshold score of -2 or higher and 97.7% (95% CI 93.5%-99.5%) for a threshold score of -1 or higher.
The Canadian Syncope Risk Score showed good discrimination and calibration for 30-day risk of serious adverse events after disposition from the emergency department. Once validated, the tool will be able to accurately stratify the risk of serious adverse events among patients presenting with syncope, including those at low risk who can be discharged home quickly.
The beef industry relies on multiple focused segments (e.g., cow-calf, stocker/feeder, and meat packing) to supply the world with beef. Thus, the potential impact of developmental programming on the ...beef industry needs to be evaluated with regards to the different production traits that drive profitability within each segment. For example, when nutrient restriction of dams occurred early in gestation embryo survival was decreased and the ovarian reserve of heifer progeny was negatively affected. Restriction during mid- to late gestation negatively impacted first service conception rates and pregnancy success of daughters. Even non-nutrient stress has been reported to impact transgenerational embryo development through the male progeny. Primary and secondary muscle fibers form during months two to eight (Days 60–240) of gestation. Therefore, external stimuli (nutrition or environmental) during this window have the potential to decrease the postnatal number of muscle fibers; which has an irreversible impact on animal growth and performance. Nutrient restriction during the last third of gestation resulted in decreased weaning weights, and in some instances decreased dry mater intake, hot carcass weight, and marbling scores. Protein supplementation during late gestation; however, increased weaning weight and ADG to weaning, but progeny of dams restricted in protein in late gestation had greater ribeye area. The importance of developmental programming is recognized; however, its precise application depends on comprehension of its integrated effects across the multiple-focused segments of the beef industry.
•The beef industry segments (Cow-calf, stockers/feeders, and meat packers) each having separate goals of production.•Nutrient restriction of dams early in gestation decreased the ovarian reserve.•Nutrient restriction of dams during mid- to late gestation decreased conception rates and pregnancy success.•Nutrient restriction during late gestation resulted in decreased weaning weights, hot carcass weight, and marbling scores.
IMPORTANCE Three clinical decision rules were previously derived to identify patients with headache requiring investigations to rule out subarachnoid hemorrhage. OBJECTIVE To assess the accuracy, ...reliability, acceptability, and potential refinement (ie, to improve sensitivity or specificity) of these rules in a new cohort of patients with headache. DESIGN, SETTING, AND PATIENTS Multicenter cohort study conducted at 10 university-affiliated Canadian tertiary care emergency departments from April 2006 to July 2010. Enrolled patients were 2131 adults with a headache peaking within 1 hour and no neurologic deficits. Physicians completed data forms after assessing eligible patients prior to investigations. MAIN OUTCOMES AND MEASURES Subarachnoid hemorrhage, defined as (1) subarachnoid blood on computed tomography scan; (2) xanthochromia in cerebrospinal fluid; or (3) red blood cells in the final tube of cerebrospinal fluid, with positive angiography findings. RESULTS Of the 2131 enrolled patients, 132 (6.2%) had subarachnoid hemorrhage. The decision rule including any of age 40 years or older, neck pain or stiffness, witnessed loss of consciousness, or onset during exertion had 98.5% (95% CI, 94.6%-99.6%) sensitivity and 27.5% (95% CI, 25.6%-29.5%) specificity for subarachnoid hemorrhage. Adding “thunderclap headache” (ie, instantly peaking pain) and “limited neck flexion on examination” resulted in the Ottawa SAH Rule, with 100% (95% CI, 97.2%-100.0%) sensitivity and 15.3% (95% CI, 13.8%-16.9%) specificity. CONCLUSIONS AND RELEVANCE Among patients presenting to the emergency department with acute nontraumatic headache that reached maximal intensity within 1 hour and who had normal neurologic examination findings, the Ottawa SAH Rule was highly sensitive for identifying subarachnoid hemorrhage. These findings apply only to patients with these specific clinical characteristics and require additional evaluation in implementation studies before the rule is applied in routine clinical care.
Study objective Recent-onset atrial fibrillation and flutter are the most common arrhythmias managed in the emergency department (ED). We evaluate the management and 30-day outcomes for recent-onset ...atrial fibrillation and flutter patients in Canadian EDs, where cardioversion is commonly practiced. Methods We conducted a prospective cohort study in 6 academic hospital EDs and enrolled patients who had atrial fibrillation and flutter onset within 48 hours. Patients were followed for 30 days by health records review and telephone. Adverse events included death, stroke, acute coronary syndrome, heart failure, subsequent admission, or ED electrocardioversion. Results We enrolled 1,091 patients with mean age 63.9 years, atrial fibrillation 84.7%, atrial flutter 15.3%, hospital admission 9.0%, and converted to sinus rhythm 80.1%. Although 10.5% of recent-onset atrial fibrillation and flutter patients had adverse events within 30 days, there were no related deaths and 1 stroke (0.1%). Adjusted odds ratios for factors associated with adverse event were hours from onset (1.03/hour; 95% confidence interval CI 1.01 to 1.05), history of stroke or transient ischemic attack (2.09; 95% CI 1.01 to 4.36), and pulmonary congestion on chest radiograph (7.37; 95% CI 2.40 to 22.64). Patients who left the ED in sinus rhythm were much less likely to experience an adverse event ( P <.001). Conclusion Although most recent-onset atrial fibrillation and flutter patients were treated aggressively in the ED, there were few 30-day serious outcomes. Physicians underprescribed oral anticoagulants. Potential risk factors for adverse events include longer duration from arrhythmia onset, previous stroke or transient ischemic attack, pulmonary congestion on chest radiograph, and not being in sinus rhythm at discharge. An ED strategy of sinus rhythm restoration and discharge in most patients is effective and safe.
Mammalian females are born with a finite number of follicles in their ovaries that is referred to as the ovarian reserve. There is a large amount of variation between females in the number of antral ...follicles that they are born with, but this number is positively correlated to size of the ovarian reserve, has a strong repeatability within a female, and a moderate heritability. Although the heritability is moderate, numerous external factors including health, nutrition, ambient temperature, and litter size influence the size and function of the ovarian reserve throughout life. Depletion of the ovarian reserve contributes to reproductive senescence, and genetic and epigenetic factors can lead to a more rapid decline in follicle numbers in some females than others. The relationship of the size of the ovarian reserve to development of the reproductive tract and fertility is generally positive, although some studies report antagonistic associations of these traits. It seems likely that management decisions and environmental factors that result in epigenetic modifications to the genome throughout life may cause variability in the function of ovarian genes that influence fecundity and fertility, leading to differences in reproductive longevity among females born with ovarian reserves of similar size. This review summarizes our current understanding of factors influencing size of the ovarian reserve in cattle, sheep, and pigs and the relationship of the ovarian reserve to reproductive tract development and fertility. It provides strategies to apply this knowledge to improve diagnostics for better assessment of fertility and reproductive longevity in female livestock.
•The size of the ovarian reserve and reproductive tract are positively correlated.•Developmental programming influences follicle number and reproductive tract size.•Developmental programming may change how the ovarian reserve influences fertility.
To retrospectively assess the prevalence and clinical outcomes of unreported vertebral compression fractures at abdominal computed tomography (CT).
This HIPAA-compliant study had institutional review ...board approval; the need for informed consent was waived for this retrospective analysis. A total of 2041 consecutive adult patients (1640 women, 401 men; age range, 19-94 years) underwent both abdominal multidetector CT and dual-energy x-ray absorptiometry (DXA) within 6 months of each other between 2000 and 2007, before sagittal CT reconstructions were obtained routinely. Transverse (axial) and retrospective sagittal multidetector CT reconstructions were reviewed for the presence of moderate or severe vertebral body compression fractures of the lower thoracic and lumbar spine by using the Genant visual semiquantitative method. Twenty-six patients were excluded for evidence of pathologic fracture or for technical factors limiting compression fracture detection. Electronic medical records were reviewed for patients with moderate or severe compression fractures to determine whether the fracture was reported at prospective CT interpretation, was known previously, or was diagnosed subsequently. Correlation was made with central DXA T scores. Statistical analysis was performed with the Student t test and Fisher exact test.
At least one moderate or severe vertebral body compression fracture was identified retrospectively at CT in 97 patients (mean age, 70.8 years). Fractures involved one level in 67 and multiple levels in 30 patients, for a total of 141 fractures. In 81 (84%) patients, prospective CT diagnosis was not made. Patients in whom fractures were reported prospectively were significantly older and were more likely to have a severe compression fracture (P < .05). In 52 (64%) patients with an unreported fracture, the vertebral compression fracture was not known clinically. In 18 patients, subsequent diagnosis of a compression fracture was determined by means of another imaging study (median interval, 7 months). At DXA, 39 (48%) of 81 patients with unreported vertebral body compression fractures had a nonosteoporotic T score (greater than -2.5).
Most clinically important vertebral body compression fractures in nontrauma patients at risk for low bone mineral density may go unreported at abdominal multidetector CT if sagittal reconstructions are not routinely evaluated.
Objective To derive a simple clinical prediction rule identifying patients at high risk of developing new-onset postoperative atrial fibrillation (POAF) after cardiac surgery. Design Retrospective ...analysis on prospectively collected observational data. Setting A university-affiliated cardiac hospital. Participants Adult patients undergoing coronary artery bypass grafting and/or valve surgery. Interventions Observation for the occurrence of new-onset postoperative atrial fibrillation. Measurements and Main Results Details on 28 preoperative variables from 999 patients were collected and significant predictors (p<0.2) were inserted into multivariable logistic regression and reconfirmed with recursive partitioning. A total of 305 (30.5%) patients developed new-onset POAF. Eleven variables were associated significantly with atrial fibrillation. A multivariable logistic regression model included left atrial dilatation, mitral valve disease, and age. Coefficients from the model were converted into a simple 7-point predictive score. The risk of POAF per score is: 15.0%, if 0; 20%, if 1; 27%, if 2; 35%, if 3; 44%, if 4; 53%, if 5; 62%, if 6; and 70%, if 7. A score of 4 has a sensitivity of 44% and a specificity of 82% for POAF. A score of 6 has a sensitivity of 11% and a specificity of 97%. Bootstrapping with 5,000 samples confirmed the final model provided consistent predictions. Conclusions This study proposed a simple predictive score incorporating three risk variables to identify cardiac surgical patients at high risk of developing new-onset POAF. Preventive treatment should target patients≥65 years with left atrial dilatation and mitral valve disease.
Objective To measure the sensitivity of modern third generation computed tomography in emergency patients being evaluated for possible subarachnoid haemorrhage, especially when carried out within six ...hours of headache onset.Design Prospective cohort study.Setting 11 tertiary care emergency departments across Canada, 2000-9.Participants Neurologically intact adults with a new acute headache peaking in intensity within one hour of onset in whom a computed tomography was ordered by the treating physician to rule out subarachnoid haemorrhage.Main outcome measures Subarachnoid haemorrhage was defined by any of subarachnoid blood on computed tomography, xanthochromia in cerebrospinal fluid, or any red blood cells in final tube of cerebrospinal fluid collected with positive results on cerebral angiography.Results Of the 3132 patients enrolled (mean age 45.1, 2571 (82.1%) with worst headache ever), 240 had subarachnoid haemorrhage (7.7%). The sensitivity of computed tomography overall for subarachnoid haemorrhage was 92.9% (95% confidence interval 89.0% to 95.5%), the specificity was 100% (99.9% to 100%), the negative predictive value was 99.4% (99.1% to 99.6%), and the positive predictive value was 100% (98.3% to 100%). For the 953 patients scanned within six hours of headache onset, all 121 patients with subarachnoid haemorrhage were identified by computed tomography, yielding a sensitivity of 100% (97.0% to 100.0%), specificity of 100% (99.5% to 100%), negative predictive value of 100% (99.5% to 100%), and positive predictive value of 100% (96.9% to 100%).Conclusion Modern third generation computed tomography is extremely sensitive in identifying subarachnoid haemorrhage when it is carried out within six hours of headache onset and interpreted by a qualified radiologist.
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