Serotonin receptor-mediated vasorelaxation occurs primarily through 5-HT4 activation in bovine lateral saphenous vein.

To better understand mechanisms of serotonin- (5-HT) mediated vasorelaxation, isolated lateral saphenous veins from cattle were assessed for vasoactivity using myography in response to increasing concentrations of 5-HT or selective 5-HT receptor agonists. Vessels were pre-contracted with 1 × 10-4 M phenylephrine and exposed to increasing concentrations of 5-HT or 5-HT receptor agonists that were selective for 5-HT1B, 5-HT2B, 5-HT4, and 5-HT7. Vasoactive response data were normalized as a percentage of the maximum contractile response induced by the phenylephrine pre-contraction. At 1 × 10-7 M 5-HT, a relaxation was observed with an 88.7% decrease (p < 0.01) from the phenylephrine maximum. At 1 × 10-4 M 5-HT, a contraction was observed with a 165% increase (p < 0.01) from the phenylephrine maximum. Increasing concentrations of agonists selective for 5-HT2B, 5-HT4, or 5-HT7 resulted in a 27%, 92%, or 44% (p < 0.01) decrease from the phenylephrine maximum, respectively. Of these 5-HT receptor agonists, the selective 5-HT4 receptor agonist resulted in the greatest potency (-log EC50) value (6.30) compared with 5-HT2B and 5-HT7 receptor agonists (4.21 and 4.66, respectively). To confirm the involvement of 5-HT4 in 5-HT-mediated vasorelaxation, blood vessels were exposed to either DMSO (solvent control) or a selective 5-HT4 antagonist (1 × 10-5 M) for 5-min prior to the phenylephrine pre-contraction and 5-HT additions. Antagonism of the 5-HT4 receptor attenuated the vasorelaxation caused by 5-HT. Approximately 94% of the vasorelaxation occurring in response to 5-HT could be accounted for through 5-HT4, providing strong evidence that 5-HT-mediated vasorelaxation occurs through 5-HT4 activation in bovine peripheral vasculature.

Validation of Non-invasive Detection of Hyperkalemia by Artificial Intelligence Enhanced Electrocardiography in High Acuity Settings.

BACKGROUND: Artificial intelligence (AI) electrocardiogram (ECG) analysis can enable detection of hyperkalemia. In this validation, we assessed the algorithm's performance in two high acuity settings. METHODS: An emergency department (ED) cohort (February-August 2021) and a mixed intensive care unit (ICU) cohort (August 2017-February 2018) were identified and analyzed separately. For each group, pairs of laboratory-collected potassium and 12 lead ECGs obtained within four hours of each other were identified. The previously developed AI ECG algorithm was subsequently applied to leads I and II of the 12 lead ECGs to screen for hyperkalemia (potassium > 6.0 mEq/L). RESULTS: The ED cohort (N=40,128) had a mean age of 60 years, 48% were male, and 1% (N=351) had hyperkalemia. The area under the curve (AUC) of the AI-ECG to detect hyperkalemia was 0.88, with sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio of, 80%, 80%, 3%, 99.8% and 4.0, respectively, in the ED cohort. Low-eGFR (<30 ml/min) subanalysis yielded AUC, sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio of 0.83, 86%, 60%, 15%, 98% and 2.2, respectively, in the ED cohort. The ICU cohort (N=2,636) had a mean age of 65 years, 60% were male, and 3% (N=87) had hyperkalemia. The AUC for the AI-ECG was 0.88 and yielded sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio of 82%, 82%, 14%, 99% and 4.6, respectively in the ICU cohort. Low-eGFR subanalysis yielded AUC, sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio of 0.85, 88%, 67%, 29%, 97% and 2.7, respectively in the ICU cohort. CONCLUSION: The AI-ECG algorithm demonstrated a high negative predictive value, suggesting that it is useful for ruling out hyperkalemia, but a low positive predictive value, suggesting that it is insufficient for treating hyperkalemia.

Adverse Events from Fluoroscopic versus Portable Placement of Peripherally Inserted Central Catheters and Central Venous Catheters in Pediatric Patients.

PURPOSE: To compare the outcomes of fluoroscopic versus portable placement of peripherally inserted central catheters (PICCs) and central venous catheters (CVCs) in pediatric patients. MATERIALS AND METHODS: This is a single-center, retrospective review of 346 upper-extremity PICC placements (286 fluoroscopic and 60 portable; mean age, 9.83 years [SD ± 5.58]; 49.1% female) and 138 tunneled femoral CVC placements (56 fluoroscopic and 82 portable; mean age, 0.23 years [SD ± 0.36]; 57.0% female). Portable placements used mobile plain-film radiography. All lines were placed by board-certified interventional radiologists. RESULTS: Fluoroscopic PICC placements had a lower procedure time (43.9 vs 57.9 minutes; P < .001), radiation dosage (342 vs 590 mGy·cm2; P < .001), incidence of technical failure (0% vs 3.3%; P = .029), and incidence of catheter malfunction (1.7% vs 12.1%; P < .001) compared with portable PICC placements. Fluoroscopic CVC placements had a lower procedure time (42.6 vs 54.8 minutes; P < .001) and radiation dosage (63.8 vs 405 mGy·cm2; P < .001) compared with portable CVC placements. No technical failures were found in either CVC groups and the difference was nonsignificant for catheter malfunction (0% vs 7.3%; P = .081). Fluoroscopic placements of PICCs and CVCs had a lower incidence rate of central line-associated bloodstream infection compared with portable placements (0.71 vs 2.22 cases per 1,000 line-days; P = .046). Overall, fluoroscopic placements of PICCs and CVCs had fewer adverse events compared with portable placements (3.2% vs 14.8%; P < .001). Portable procedure setting was the only significant factor associated with adverse events (odds ratio, 33.77; 95% CI, 4.56-757.01). CONCLUSIONS: Fluoroscopic placements of PICCs and CVCs are associated with lower procedure time, radiation dose, and risk of adverse events compared with portable placements in pediatric patients.

5-hydroxytryphophan mitigates ergot alkaloid-induced suppression of serotonin and feed intake in cattle.

The impact of ergot toxicosis on livestock industries is detrimental and treatments are needed in many countries. The objective of this study was to evaluate the effects of acute exposure to ergot alkaloids and 5-hydroxytryptophan (5-HTP) supplementation on feed intake, serotonin metabolism, and blood metabolites in cattle. Eight Holstein steers (538 ±â€…18 kg) fitted with ruminal cannulas were used in a replicated 4 × 4 Latin Square design experiment with a 2 × 2 factorial treatment structure. The treatments were the combination of 0 (E-) or 15 µg ergovaline/kg BW (E+) and 0 (5HTP-) or 0.5 mg of 5-hydroxy-l-tryptophan/kg BW (5HTP+) administered daily for 6 d. Toxic endophyte-infected tall fescue seed was used to supply the daily dose of ergovaline. Endophyte-free seed was used to equalize seed intake between treatments. Ground seed was placed into the rumen immediately before feeding. The 5-HTP was dissolved in water and infused into the abomasum via the reticulo-omasal orifice. Blood was collected from a jugular vein catheter at 0, 1, 2, 4, 8, and 24 h after treatment administration. Ergovaline without 5-HTP (E+/5HTP-) decreased dry matter intake (DMI) in comparison to steers without ergovaline and 5-HTP (E-/5HTP-). However, 5-HTP infusion in association with ergovaline (E+/5HTP+) normalized the DMI. Although E + did not affect (P > 0.05) the area under the curve (AUC) of serum 5-HTP, 5-hydroxyindoleacetic acid, tryptophan, and kynurenine, serum and plasma serotonin concentrations were decreased (P < 0.05). The infusion of 5-HTP increased (P < 0.05) the AUC of serum 5-HTP, serum and plasma serotonin, and serum 5-hydroxyindoleacetic acid. In conclusion, acute exposure to ergot alkaloids reduced DMI and circulating serotonin in cattle but 5-HTP administration showed potential to normalize both circulating serotonin and feed intake.

Some grass species have a symbiotic relationship with an endophytic fungus that produces toxic ergot alkaloids which have detrimental impacts on herbivores. Ergot alkaloids have a significant impact on livestock production causing annual loss to the livestock industry that likely exceeds $1 billion. Effective treatment for this toxicosis is still needed. The objective of this study was to evaluate the effects of acute exposure to ergot alkaloids and 5-hydroxytryptophan supplementation on feed intake, serotonin metabolism, and blood metabolites in cattle. We found that 5-hydroxytryptophan administration has the potential to normalize both circulating serotonin and feed intake reduced by ergot alkaloid consumption.

Levodopa attenuates the feed intake reduction caused by ergot alkaloids in cattle.

Consumption of ergot alkaloids from endophyte-infected tall fescue results in losses to the livestock industry in many countries and a means to mitigate these losses is needed. The objective of this study was to evaluate intra-abomasal infusion of the dopamine precursor, levodopa (L-DOPA), on dopamine metabolism, feed intake, and serum metabolites of steers exposed to ergot alkaloids. Twelve Holstein steers (344.9 ±â€…9.48 kg) fitted with ruminal cannula were housed with a cycle of heat challenge during the daytime (32 °C) and thermoneutral at night (25 °C). The steers received a basal diet of alfalfa cubes containing equal amounts of tall fescue seed composed of a mixture of endophyte-free (E-) or endophyte-infected tall fescue seeds (E+) equivalent to 15 µg ergovaline/kg body weight (BW) for 9 d followed by intra-abomasal infusion of water (L-DOPA-) or levodopa (L-DOPA+; 2 mg/kg BW) for an additional 9 d. Afterward, the steers were pair-fed for 5 d to conduct a glucose tolerance test. The E+ treatment decreased (P = 0.005) prolactin by approximately 50%. However, prolactin increased (P = 0.050) with L-DOPA+. Steers receiving E+ decreased (P < 0.001) dry matter intake (DMI); however, when supplemented with L-DOPA+ the decrease in DMI was less severe (L-DOPA × E, P = 0.003). Also, L-DOPA+ infusion increased eating duration (L-DOPA × E, P = 0.012) when steers were receiving E+. The number of meals, meal duration, and intake rate were not affected (P > 0.05) by E+ or L-DOPA+. The L-DOPA+ infusion increased (P < 0.05) free L-DOPA, free dopamine, total L-DOPA, and total dopamine. Conversely, free epinephrine and free norepinephrine decreased (P < 0.05) with L-DOPA+. Total epinephrine and total norepinephrine were not affected (P > 0.05) by L-DOPA+. Ergot alkaloids did not affect (P > 0.05) circulating free or total L-DOPA, dopamine, or epinephrine. However, free and total norepinephrine decreased (P = 0.046) with E+. Glucose clearance rates at 15 to 30 min after glucose infusion increased with L-DOPA+ (P < 0.001), but not with E+ (P = 0.280). Administration of L-DOPA as an agonist therapy to treat fescue toxicosis provided a moderate increase in DMI and eating time and increased plasma glucose clearance for cattle dosed with E+ seed.

Fescue has become the dominant cool-season perennial grass in the southeastern region of the United States and is also found in other countries. Endophytes from a plant­fungus symbiotic relationship produce toxic alkaloids that have caused significant annual economic losses to the livestock industry. Treatments to alleviate this toxicosis are still demanded. This study evaluates the infusion of the dopamine precursor, levodopa (L-DOPA), to mitigate the toxicosis caused by ergot alkaloids. When L-DOPA was infused, eating duration increased and the decrease in feed intake caused by ergot alkaloids was less severe. Additionally, circulating dopamine and glucose clearance increased with L-DOPA. These results suggest that L-DOPA has the potential to aid in the mitigation of the toxicosis caused by ergot alkaloids.

Exploring the Role of G Protein Expression in Sodium Butyrate-Enhanced Pancreas Development of Dairy Calves: A Proteomic Perspective.

The present study evaluated the effects of sodium butyrate (SB) supplementation on exocrine and endocrine pancreatic development in dairy calves. Fourteen male Holstein calves were alimented with either milk or milk supplemented with SB for 70 days. Pancreases were collected for analysis including staining, immunofluorescence, electron microscopy, qRT-PCR, Western blotting, and proteomics. Results indicated increased development in the SB group with increases in organ size, protein levels, and cell growth. There were also exocrine enhancements manifested as higher enzyme activities and gene expressions along with larger zymogen granules. Endocrine benefits included elevated gene expression, more insulin secretion, and larger islets, indicating a rise in ß-cell proliferation. Proteomics and pathway analyses pinpointed the G protein subunit alpha-15 as a pivotal factor in pancreatic and insulin secretion pathways. Overall, SB supplementation enhances pancreatic development by promoting its exocrine and endocrine functions through G protein regulation in dairy calves.

A Quality Improvement Initiative to Increase Documentation of Preferences for Life-Sustaining Treatment in Hospitalized Adults.

BACKGROUND: Portable Orders for Life-Sustaining Treatment (POLST) forms allow patients to codify their preferences for life-sustaining treatments across inpatient and outpatient settings. In 2019 only 29.5% of our hospitalized internal medicine patients with an inpatient do-not-resuscitate (DNR) order and no DNR POLST at admission discharged with a DNR POLST. This presented an opportunity to improve POLST completion and avoid undesired or inappropriate care after discharge. METHODS: Using electronic health record (EHR) data, the authors identified hospitalized adults (age ≥ 50 years) admitted to an internal medicine service with a DNR order and discharged alive. Patient records were cross-referenced with the state's POLST registry for an active POLST form. Among patients with a missing or full-code POLST form at admission, the authors calculated the proportion with a DNR POLST form completed by discharge. These data were tracked over time with control charts to detect performance shifts following three Plan-Do-Study-Act (PDSA) cycles over 34 months, which included a single educational training on electronic POLST navigation, an EHR discharge navigator notification, and quarterly e-mailed individualized performance reports. RESULTS: The study population (N = 387) was 55.0% male and predominately non-Hispanic white (80.9%). Patients discharging to a skilled nursing facility or hospice were three times more likely to discharge with a DNR POLST compared to patients discharging home. Overall, the proportion of DNR POLST forms completed by discharge increased from 0.36 to 0.60 after three PDSA cycles (p < 0.001). CONCLUSION: This quality improvement initiative demonstrated improved POLST form completion rates in a target population of adults at elevated risk for readmission and death.

Postruminal Casein Infusion and Exogenous Glucagon-Like Peptide 2 Administration Differentially Stimulate Pancreatic α-Amylase and Small Intestinal α-Glucosidase Activity in Cattle.

BACKGROUND: Increasing luminal carbohydrate flow decreases pancreatic α-amylase activity but can increase jejunal maltase activity, suggesting that regulation of carbohydrase activity is perhaps uncoordinated in response to luminal carbohydrate flow. Increasing luminal casein flow increases pancreatic α-amylase activity in cattle, and exogenous glucagon-like peptide 2 (GLP-2) has been shown to increase small intestinal α-glucosidase activity in nonruminants. OBJECTIVES: The objective was to evaluate the effects of postruminal casein infusion, exogenous GLP-2, or their combination on endogenous pancreatic and small intestinal carbohydrase activity in cattle postruminally infused with starch. METHODS: Holstein steers [n = 24; 250 ± 23 kg body weight (BW)] received a continuous abomasal infusion of 3.94 g raw corn starch/kg of BW combined with either 0 or 1.30 g casein/kg of BW. Steers received subcutaneous injections in 2 equal portions daily of excipient (0.5% bovine serum albumin) or 100 µg GLP-2/kg of BW per day. At the end of the 7-d treatment period, steers were slaughtered for tissue collection. Data were analyzed using the MIXED procedure of SAS version 9.4 (SAS Institute Inc.). RESULTS: Postruminal casein infusion increased (P ≤ 0.03) pancreatic mass by 12.6%, total pancreatic α-amylase activity by 50%, and postruminal starch disappearance from 96.7% to 99.3%. Exogenous GLP-2 increased (P < 0.01) total small intestinal and mucosal mass by 1.2 kg and 896 g, respectively. Relative to control, GLP-2 and casein + GLP-2 increased (P = 0.04) total small intestinal α-glucosidase activity by 83.5%. Total small intestinal maltase, isomaltase, and glucoamylase activity was 90%, 100%, and 66.7% greater for GLP-2 and casein + GLP-2 steers compared with control. CONCLUSIONS: Casein increased pancreatic α-amylase activity, GLP-2 increased small intestinal α-glucosidase activity, and the combination of casein and GLP-2 increased both pancreatic α-amylase activity and small intestinal α-glucosidase activity. This novel approach provides an in vivo model to evaluate effects of increasing endogenous carbohydrase activity on small intestinal starch digestion.

Artificial Intelligence for the Detection and Treatment of Atrial Fibrillation.

AF is the most common clinically relevant cardiac arrhythmia associated with multiple comorbidities, cardiovascular complications (e.g. stroke) and increased mortality. As artificial intelligence (AI) continues to transform the practice of medicine, this review article highlights specific applications of AI for the screening, diagnosis and treatment of AF. Routinely used digital devices and diagnostic technology have been significantly enhanced by these AI algorithms, increasing the potential for large-scale population-based screening and improved diagnostic assessments. These technologies have similarly impacted the treatment pathway of AF, identifying patients who may benefit from specific therapeutic interventions. While the application of AI to the diagnostic and therapeutic pathway of AF has been tremendously successful, the pitfalls and limitations of these algorithms must be thoroughly considered. Overall, the multifaceted applications of AI for AF are a hallmark of this emerging era of medicine.

Influence of Anti-Coccidial Compounds and Phytogenic Saponin Extracts on In Vitro and In Vivo Ruminal Fermentation and Methane Production of Cattle.

Four experiments were conducted to evaluate sources of anti-coccidial compounds and phytogenic saponin extracts on in vitro and in vivo ruminal fermentation and CH4 production at multiple inclusion levels. In experiment 1, eight steers were fed either a finishing diet or a finishing diet supplemented with 0.5 mg/kg BW decoquinate (DCQ) and 3.33 mg/kg BW Yucca schidigera extract (YSE), and respiratory gas exchange was measured. In experiment 2, four ruminally-cannulated steers were fed the same treatments as experiment 1, and ruminal fermentation was evaluated. Anti-coccidial sources (experiment 3; monensin, DCQ, amprolium) and saponin sources (experiment 4; YSE, Quillaja saponaria extract) and levels were evaluated for effects on in vitro ruminal fermentation and CH4 production. DCQ + YSE supplementation did not influence (p ≥ 0.24) in vivo respiratory gas consumption/production, in situ DM degradation, or liquid passage kinetics. Ruminal propionate proportion tended to increase (p = 0.09) with DCQ + YSE. Monensin decreased (p ≤ 0.04) in vitro acetate:propionate and CH4 production; saponin supplementation linearly increased (p < 0.01) propionate proportion but did not influence (p ≥ 0.38) in vitro CH4 production. Saponins and non-antibiotic anti-coccidials did not influence in vitro or in vivo CH4 production with finishing diets.

Dual Atrioventricular Nodal Non-Re-Entrant Tachycardia.

A patient presented with symptoms of palpitations. Her standard 12-lead electrocardiogram captured 3 potential causes of her symptoms (premature atrial contractions, junctional rhythm, and narrow complex tachycardia). Further workup uncovered dual atrioventricular node physiology with 1:2 sinus conduction and resultant alternating QRS from a slow and fast conduction pathway. (Level of Difficulty: Intermediate.).

Duration of ergovaline exposure influences serotonin-mediated vasoactivity of bovine mesenteric vasculature.

Ergovaline (ERV), produced in toxic endophyte-infected tall fescue, causes potent vasoconstriction of bovine peripheral and visceral vasculature. Ergovaline acts as both an agonist and an antagonist in bovine gut blood vessels through serotonin (5-HT) receptors and it appears that the type of action could be influenced by the extent of ERV exposure. Because it was unclear how the duration of ERV exposure influences 5-HT-mediated vasoactivity, experiments were designed to evaluate how simultaneous or prior ERV exposure influenced 5-HT-mediated vasoactivity of mesenteric artery (MA) and vein (MV) segments from Holstein steers (N = 10). Vessels were incubated in Krebs-Henseleit buffer containing 0, 0.01, or 0.1 µM ERV for 24 h prior to the 5-HT dose-response or exposed to fixed concentrations of 0, 0.01, or 0.1 µM ERV simultaneously during the 5-HT dose-response. Vessels were suspended in chambers of a multimyograph containing Krebs-Henseleit buffer and equilibrated to 1 g tension for 90 min. Vessels were exposed to increasing concentrations of 5-HT (5 × 10-8 M to 1 × 10-4 M) every 15 min and contractile responses were normalized as a percentage of the maximum contractile response induced by 120 mM KCl reference addition. Two-way analysis of variance was used to separately analyze data for each vessel type and duration of exposure using the MIXED procedure of SAS. When 5-HT concentration increased from 5 × 10-8 to 1 × 10-6 M, simultaneous addition of 0.1 µM ERV increased (P < 0.01) the contractile response of MV compared with additions of 0 and 0.01 µM ERV. At 1 × 10-4 M 5-HT, the simultaneous presence of 0.01 and 0.1 µM ERV decreased (P < 0.01) the contractile response of both MA and MV compared with 0 µM ERV addition. As 5-HT concentrations increased, the contractile response increased (P < 0.01) in both MA and MV with no previous ERV exposure, but decreased in MA and MV with 24 h prior exposure to 0.01 and 0.1 µM ERV. These data demonstrate that the duration of ERV exposure influences 5-HT-mediated vasoconstriction and likely vasorelaxation in bovine mesenteric vasculature. If ERV and 5-HT exposure occur simultaneously, ERV can act as a partial agonist of 5-HT-mediated vasoconstriction. If 5-HT exposure occurs after blood vessels have had prior ERV exposure, it appears that 5-HT may induce vasorelaxation of blood vessels. More research is needed to identify cellular and molecular mechanisms involved with 5-HT-mediated vasoactivity.

Consumption of ergot alkaloids found in endophyte-infected tall fescue can lead to symptoms of fescue toxicosis, such as vasoconstriction, in ruminant livestock species. Ergovaline is one of the primary ergot alkaloids responsible for causing vasoconstriction when toxic varieties of fescue are consumed. It has been previously shown that ergovaline causes vasoconstriction by interacting with vascular serotonin receptors in cattle and sheep. Depending on when ergovaline exposure occurs, ergovaline can function as an agonist (stimulant) or antagonist (inhibitor) of vascular activity. However, it is unclear how the duration of ergovaline exposure affects vasoconstriction caused by serotonin. Experiments were conducted using the bovine mesenteric artery and mesenteric vein that were exposed to either 0, 0.01, or 0.1 µM ergovaline for 24-h prior to serotonin additions or simultaneously with serotonin additions. Maximum contractile response data were recorded using a multimyograph system and normalized as a percentage of the contractile response produced by the reference compound, KCl. The results of these experiments demonstrated that the duration of ergovaline exposure influences serotonin-mediated vasoconstriction and possibly vasorelaxation in bovine mesenteric vasculature. If ergovaline and serotonin exposure occur simultaneously, ergovaline can act as an agonist or antagonist of serotonin-mediated vasoconstriction. If serotonin exposure occurs after prior ergovaline exposure, serotonin can induce vasorelaxation of blood vessels. Understanding how complex interactions between ergovaline and serotonin occur and affect vascular function will aid in the development of strategies to mitigate sustained vasoconstriction caused during fescue toxicosis.

Dramatic elevation of LDL cholesterol from ketogenic-dieting: A Case Series.

High-fat, low carb dieting, also known as the "ketogenic diet," has increased in popularity as a rapid weight-loss tool. Previous studies describe a modest elevation in cholesterol in the average keto-diet participant without specific cardiovascular impact. We hypothesize that patients with a genetic predisposition to cholesterol metabolism dysregulation may have a disproportionate elevation in cholesterol in response to ketogenic dieting.

In vitro gas production kinetics are influenced by grain processing, flake density, starch retrogradation, and Aspergillus oryzae fermentation extract containing α-amylase activity.

Grain processing such as particle size, flake density, or starch retrogradation can influence ruminal degradability characteristics; however, it is unclear how exogenous α-amylase supplementation interacts with different processed grains. Four experiments were conducted to compare the effects of Aspergillus oryzae fermentation extract (Amaize; Alltech Biotechnology Inc., Nicholasville, KY) supplementation on in vitro gas production kinetics of grain substrates with different processing methods that are common in the feedlot industry. In experiment 1, corn processing (dry-rolled, high-moisture, steam-flaked) and Amaize supplementation (0 or 15 U α-amylase activity/100 mL) were evaluated in a 3 × 2 factorial arrangement of treatments. The rate of gas production for dry-rolled corn was higher (P < 0.001) with Amaize supplementation. In experiment 2, flake density (296, 322, 348, 373, and 399 g/L) and starch retrogradation (storage in heat-sealed foil bags for 3 d at 23 or 55°C) were evaluated in a 5 × 2 factorial arrangement of treatments. There was a flake density × starch retrogradation interaction (P < 0.01) for the rate of gas production because the decrease in the rate of gas production with starch retrogradation was greater at lighter flake densities compared with heavier flake densities. In experiment 3, Amaize supplementation was evaluated across flake densities of nonretrograded steam-flaked corn (stored at 23°C) used in experiment 2. There was a flake density × Amaize interaction (P < 0.01) for the rate of gas production where Amaize supplementation resulted in a lower rate of gas production at lighter flake densities (296, 322, and 348 g/L) but a higher rate of gas production at heavier flake densities (373 and 399 g/L). In experiment 4, Amaize supplementation was evaluated across flake densities of retrograded steam-flaked corn (stored at 55°C) used in experiment 2. Gas production was lower after 24 h with Amaize supplementation for retrograded flakes produced to a density of 322 and 399 g/L while Amaize supplementation did not influence gas production at 24 h at other flake densities. There was a flake density × Amaize interaction for the rate of gas production because Amaize supplementation resulted in a faster (P < 0.01) rate of gas production for all flake densities except retrograded flakes produced to a density of 296 g/L. Enzymatic starch availability was positively correlated with the rate of gas production. These data demonstrate that supplementation of 15 U/100 mL of Amaize resulted in greater rates of gas production for dry-rolled corn, corn steam-flaked to heavier densities, and retrograded steam-flaked corn.

Grain processing has been used for decades to improve digestibility of finishing cattle diets, leading to improved growth and feed efficiency. Grain processing methods that result in changes in particle size, flake density, or starch retrogradation have all been shown to affect the degradability characteristics of nutrients in the rumen. Supplementation of feed additives containing exogenous enzyme activity could have the potential to improve digestibility, growth performance, and feed efficiency of livestock. However, it is unknown how supplementation of exogenous α-amylase activity influences degradability characteristics of different processed grains. The objectives of this study were to compare the effects of Aspergillus oryzae fermentation extract supplementation on in vitro gas production kinetics of grain substrates with different processing methods that are common in the feedlot industry. Enzymatic starch availability of steam-flaked corn, but not dry-rolled or high-moisture corn, was reflective of the rate of in vitro gas production. Increasing flake density and increasing starch retrogradation decreased the rate of in vitro gas production. Supplementation of A. oryzae fermentation extract resulted in increased rates of gas production for dry-rolled corn, corn steam-flaked at heavier densities, and retrograded steam-flaked corn.

The Digitization and Decentralization of Clinical Trials.

Now, more than ever, digital technology has made its way into the daily lives of billions across the globe, and the widespread use of this technology has also allowed a digital window into consumers' and patients' daily lives, respectively. In a similar way, the practice of medicine has digitally evolved with the application of electronic health records and development of wearable/portable consumer-based medical devices (eg, Apple Watch ECG and Kardia Mobile by AliveCor). Alongside the increased use of digital technology in clinical care (eg, telehealth and wearable arrhythmia detection), clinical investigators have harnessed this powerful stockpile of data to gain insight into what happens to patients beyond the clinic walls. In this thematic review, we show the impact of digital advancements on the clinical trial process from recruitment and enrollment to interventions and data collection. We also show the pragmatism of this decentralized process and how it will mitigate the limitations of conventional randomized controlled trials. Finally, while pushing the boundaries of tech, we also describe a few limitations of this rapidly growing field to understand better what gaps need to be bridged in the future.

Postdevelopment Performance and Validation of the Artificial Intelligence-Enhanced Electrocardiogram for Detection of Cardiac Amyloidosis.

BACKGROUND: We have previously applied artificial intelligence (AI) to an electrocardiogram (ECG) to detect cardiac amyloidosis (CA). OBJECTIVES: In this validation study, the authors observe the postdevelopment performance of the AI-enhanced ECG to detect CA with respect to multiple potential confounders. METHODS: Amyloid patients diagnosed after algorithm development (June 2019-January 2022) with a 12-lead ECG were identified (n = 440) and were required to have CA. A 15:1 age- and sex-matched control group was identified (n = 6,600). Area under the receiver operating characteristic (AUC) was determined for the cohort and subgroups. RESULTS: The average age was 70.4 ± 10.3 years, 25.0% were female, and most patients were White (91.3%). In this validation, the AI-ECG for amyloidosis had an AUC of 0.84 (95% CI: 0.82-0.86) for the overall cohort and between amyloid subtypes, which is a slight decrease from the original study (AUC 0.91). White, Black, and patients of "other" races had similar algorithm performance (AUC >0.81) with a decreased performance for Hispanic patients (AUC 0.66). Algorithm performance shift over time was not observed. Low ECG voltage and infarct pattern exhibited high AUC (>0.90), while left ventricular hypertrophy and left bundle branch block demonstrated lesser performance (AUC 0.75 and 0.76, respectively). CONCLUSIONS: The AI-ECG for the detection of CA maintained an overall strong performance with respect to patient age, sex, race, and amyloid subtype. Lower performance was noted in left bundle branch block, left ventricular hypertrophy, and ethnically diverse populations emphasizing the need for subgroup-specific validation efforts.

Survey of Vaccine Hesitancy in Patients Visiting Three Tertiary-care Emergency Departments in Southeast Louisiana.

Objectives: Vaccine hesitancy has been a barrier to achieving herd immunity during the coronavirus 2019 (COVID-19) pandemic. Having low socioeconomic status and education levels, and being a person of color, are associated with higher COVID-19 infection risk and worse outcomes. These same groups are associated with higher vaccine hesitancy. The state of Louisiana has one of the lowest vaccination rates in the country. In this study we aimed to identify demographic, perspective, and health behavior factors associated with vaccine hesitancy in emergency departments (ED) in Southeast Louisiana. Methods: A cross-sectional survey was distributed at three tertiary-care hospital EDs. Patients >18 years old and not in acute distress were recruited between April-July 2021. The 37-item questionnaire addressed socioeconomic demographics, social determinants of health, COVID-19 safety practices, thoughts and perceptions on COVID-19 and vaccines, sources of COVID-19 and vaccine information, and trust in the healthcare system. Results: Overall, 247 patients completed our survey. Of those, 29.6% reported they were vaccine hesitant. These respondents were significantly more likely, when compared to vaccine-acceptant respondents, to never have married, to have some college education, make less than <$25,000 in household earnings yearly, be unsure whether vaccines prevent disease, not have discussed the COVID-19 vaccine with their primary care doctor, and to prefer to do their own research for COVID-19 vaccine information. We observed no statistically significant differences based on gender, race/ethnicity, parental status, area of living, or their perceived risk of needing hospitalization for treatment or dying from the virus. Conclusion: Vaccine hesitancy was associated with multiple socioeconomic factors, perspectives, and beliefs. Vaccine-hesitant individuals were more uncertain about the safety of the COVID-19 vaccine, the feasibility of obtaining the vaccine, and its efficacy. Public health interventions aimed at these findings and improving public trust in healthcare systems are needed to increase vaccine acceptance.