Disparities in Remote Learning Faced by First-Generation and Underrepresented Minority Students during COVID-19: Insights and Opportunities from a Remote Research Experience.

The COVID-19 pandemic forced an unprecedented shift to remote instruction across higher education, reducing access to critically important undergraduate research experience and potentially magnifying inequities faced by first-generation and underrepresented minority (URM) students in higher education. Through a novel course-based undergraduate research experience (CURE) at UCLA, delivered completely online, results of a unique, student-generated survey showed that the transition to remote learning was challenging for all students, increasing student workload, decreasing ability to focus on school, and limiting their ability to succeed. However, results showed significant disparities in remote learning that disproportionately impacted URM and first-generation students. These students had significantly greater expectations to help siblings with remote learning,; URM and first-generation students also suffered greater economic and food insecurity related to COVID-19. At the same time, this study demonstrates how student voices in survey development provide novel and actionable insights. While access to CUREs is often limited by laboratory space, by focusing on the research process, rather than specific laboratory skills, this study provides a scalable pedagogical model for remote undergraduate research experiences. Importantly, this model fostered student engagement and increased interest in further undergraduate research, including topics not directly related to the subject of this study, suggesting that online CUREs can be effective and impactful.

Propranolol increases the complexity of heart rate fluctuations--a mode of antiarrhythmic action?

OBJECTIVE: To study the beta-blocking effect of propranolol on heart rate and arterial blood pressure fluctuations in healthy subjects using linear methods and a set of nonlinear models. METHODS: In a randomized, double-blind, placebo-controlled study, healthy young adults received a 40 mg oral dose of propranolol (n = 12) or placebo (n = 12). The effects of propranolol and placebo were assessed using time series of the RR interval (RRI) and systolic arterial blood pressure (SAP) obtained from continuous ECG and blood pressure signal recordings. Heart rate and systolic arterial blood pressure fluctuations were analyzed using nonlinear and linear methods of time series statistics. RESULTS: Propranolol significantly increased the complexity of heart rate fluctuations in terms of symbol dynamic (SymDyn) entropy and symbol dynamic percentage of forbidden words. Propranolol augmented cross entropy between RRI and SAP and increased fractal dimension of RRI. beta-blockade also affected linear measures of RRI fluctuations by increasing parasympathetic, respiration-related high-frequency (HF) variability and arterial baroreflex-related low-frequency (LF) variability. Propranolol administration, however, had no effect on the complexity of SAP fluctuations assessed using nonlinear time series statistics. CONCLUSIONS: beta-blockade by propranolol has a differential effect on RRI and SAP fluctuations in healthy subjects. Propranolol increases the complexity of RRI fluctuations. The effect is associated with the cardiac vagotonic drug action of propranolol. SAP fluctuations are almost unchanged. The increased complexity of RRI fluctuations may be a beneficial feature of beta-blockade, since many cardiovascular diseases decrease the complexity of RRI time series by dampening cardiovascular reflex actions.

Systemic absorption of topically applied ocular atropine.

We quantitated atropine plasma levels and monitored blood pressure, heart rate, and salivary secretion after ocular application. Eight patients received 40 microliters 1% atropine in the lower cul-de-sac of one eye in connection with ocular surgery. Atropine plasma levels were determined for 90 minutes by radioreceptor assay. The peak plasma atropine concentration of 860 +/- 402 pg/ml was reached within 8 minutes in all patients. The ocular absorption of atropine was at least as rapid as that reported for intramuscular administration. Ocular atropine did not affect patients' blood pressure or heart rate when compared with those of the placebo group. Thirty minutes after administration of atropine eyedrops, the salivary secretion in the experimental group was reduced, but was statistically insignificant from the placebo group.

Beta-blocking effects of timolol at low plasma concentrations.

The concentration-effect relationship of 0.25 mg intravenous timolol with and without pretreatment with 100 mg quinidine was studied in six healthy young volunteers with a randomized, double-blind, crossover study design. Blockade of cardiac beta-adrenoceptors was assessed by determining the dose ratios (DR) of isoproterenol infusions required to increase heart rate by 25 beats/min before and after timolol infusion. The logarithm of timolol concentration in plasma was linearly related to the logarithm (DR-1) of isoproterenol infusion, with a mean Pearson correlation coefficient of 0.89 +/- 0.11 (+/- SD; n = 24) at timolol concentrations well below 1 ng/ml. The increases in cyclic adenosine monophosphate (cAMP) and norepinephrine plasma levels caused by isoproterenol infusions were attenuated after timolol. Quinidine administration increased timolol plasma levels and cardiac beta-blocking effects by 10% to 40%. It was concluded that timolol at concentrations below 1 ng/ml in plasma competitively antagonizes cardiac and noncardiac effects of isoproterenol infusions. Timolol effects are augmented after quinidine administration. The beta-blockade occurring at low plasma levels can explain side effects and actions of ocularly applied timolol.

Low-dose transdermal scopolamine decreases blood pressure in mild essential hypertension.

BACKGROUND: Increasing cardiovascular parasympathetic nervous activity could have antihypertensive effects. Low-dose transdermal scopolamine increases vagal-cardiac modulation of sinus node and baroreflex sensitivity in healthy subjects and in cardiac patients. OBJECTIVE: To study the short-term effects of transdermal scopolamine on blood pressure and cardiovascular autonomic control in patients with mild essential hypertension. DESIGN: A randomized, double-blind, placebo-controlled crossover trial with 12 untreated middle-aged [aged 39+/-5 years (mean+/-SD)] patients with mild essential hypertension. METHODS: We recorded the electrocardiogram, auscultatory sphygmomanometric and continuous photoplethysmographic finger arterial pressure, and spirometry signals with patients supine and 70 degrees tilted during controlled (0.25 Hz) breathing. Cardiovascular autonomic regulation was analyzed with power spectrum analysis of R-R interval and arterial pressure variability and a spontaneous sequence method for baroreflex sensitivity. In addition, a deep-breathing test was performed to assess maximal breathing-related sinus arrhythmia. RESULTS: Transdermal scopolamine treatment significantly decreased blood pressure both when patients lay supine and when they were in the 70 degrees tilted position. Scopolamine also slowed heart rate and increased baroreflex sensitivity and R-R interval high-frequency variability for both body positionings. In addition, scopolamine accentuated respiratory sinus arrhythmia during deep breathing and blunted the tilt-induced increase in heart rate. Scopolamine did not affect blood pressure variability. CONCLUSIONS: Transdermal scopolamine decreases arterial pressure, increases baroreflex sensitivity and accentuates vagal-cardiac modulation of sinus node in patients with mild hypertension. Our study supports the hypothesis that increasing cardiovascular parasympathetic activity could have antihypertensive effects in essential hypertension.

Vagal cardiac activity in essential hypertension: the effects of metoprolol and ramipril.

Cardiovascular parasympathetic activity is attenuated in essential hypertension. Both beta-adrenoceptor antagonists and angiotensin converting enzyme inhibitors have been reported to increase vagal modulation of heart rate and baroreflex sensitivity, but the relations between the antihypertensive and vagal cardiac effects of these drugs have remained unclear in essential hypertension. In the present study we evaluated the effects of a 4-week crossover monotherapy with metoprolol and ramipril on spectrum analysis indices of heart rate variability in the supine rest and head-up tilted positions, baroreflex sensitivity (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly untreated stage 1-2 essential hypertensive patients. Compared to the pretreatment values, both drugs decreased BP similarly and significantly. However, the drugs showed different effects on cardiac vagal activity: metoprolol increased significantly mean R-R interval, R-R interval total, and high-frequency variability at supine rest and baroreflex sensitivity, but ramipril did not significantly affect these variables. The metoprolol-induced decrease in ambulatory BP correlated with the prolongation of the R-R interval and the increase of high-frequency variability at supine rest. The present data show that 4-week treatment with metoprolol increases tonic and reflex vagal cardiac activity, whereas ramipril does not affect vagal cardiac control in essential hypertension. Increase in vagal activity may contribute to the BP-lowering effect of metoprolol in hypertensive patients.

Selectivity of acebutolol, atenolol, and metoprolol in healthy volunteers estimated by the extent the drugs occupy beta 2-receptors in the circulating plasma.

The selectivity of acebutolol, atenolol, and metoprolol in healthy volunteers was estimated by determining the extent to which the drugs occupied beta 1-receptors of rabbit lung and beta 2-receptors of rat reticulocytes in the circulating plasma after drug intake. This ex vivo method had the advantage of including all drug components contributing to the drug-receptor equilibrium in vivo and of excluding the factors regulating organ sensitivity to catecholamine stimulation. The oral doses of 400 mg acebutolol, 100 mg atenolol, and 100 mg metoprolol were administered to six healthy male volunteers using a double-blind, randomized, and cross-over study design. The three drugs occupied beta 1-receptors to a similar extent at 2 hours after drug intake. The receptor fraction occupied by metoprolol at 3 to 8 hours after drug intake was usually smaller, however (analysis of variance for repeated measures, P < .05) than that of the other drugs. Acebutolol occupied significantly larger fractions of beta 2-receptors (analysis of variance for repeated measures, P < .05) than did atenolol and metoprolol. Therefore, at an identical beta 1-receptor occupancy, the beta 2-receptor occupancy of acebutolol was larger than that of the other agents. Apparently, active metabolites decreased markedly the selectivity of acebutolol, but not that of metoprolol. The receptor occupancy of the agents was well in agreement with the literature concerning the selectivity, intensity, and time-course of drug actions after identical doses.(ABSTRACT TRUNCATED AT 250 WORDS)

A sensitive radioligand binding assay for timolol in plasma.

A sensitive and reproducible radioreceptor assay (RRA) is described for the determination of low picogram levels of timolol in plasma. The plasma or serum samples (1 mL) are prepared by selectively extracting timolol with lipophilic solvents or, alternatively, only plasma (serum) proteins are precipitated prior to binding assay. The recovery of timolol is at least 90% during the sample preparation. In the radioligand binding assay, timolol and the nonselective beta-antagonist [3H](-)-CGP-12177 compete for the binding sites present in the rat reticulocyte membranes. The detection limit for timolol (30 pg/mL) exceeds 50 times the sensitivity of the GC-MS techniques for timolol. The RRA results and GC results obtained from the same clinical samples correlate excellently (r = 0.99). There was no evidence for interference caused by timolol metabolites in the RRA. Timolol concentrations in plasma following its oral and even ocular administration were possible to monitor using the RRA. The method can be modified to also measure several other beta-antagonist drugs in picogram per milliliter quantities.

beta-blockade, atrial natriuretic peptide and exercise.

Changes in the release of atrial natriuretic peptide (ANP) and vasopressin (VP) may contribute to the final outcome of beta-adrenoceptor blocking therapy. Therefore, we administered 2 hours before a bicycle exercise test (a 30-minute exercise with 100 W work load) in a randomized, double-blind, placebo-controlled crossover study orally 50 mg atenolol, 80 mg propranolol or 10 mg pindolol to 15 healthy volunteers. Hormone release and sympathoadrenal activation were estimated by measuring plasma ANP-, VP-, adrenaline and noradrenaline concentrations. beta-blockade and -antagonism were estimated by measuring the reduction of exercise-induced tachycardia and the extent to which the drugs occupied rabbit lung beta 1- and rat reticulocyte beta 2-adrenoceptors in the circulating plasma. We noticed clear differences in the animal beta 1- and beta 2-receptor occupancy between these agents. The agents and placebo during the exercise augmented plasma ANP level similarly, on average by 34-72%. Pindolol administration enhanced the decline of plasma ANP level after exercise (ANCOVA rep meas, pindolol vs placebo, p < 0.05). Although pindolol increased the mean plasma VP level by 25% (ANCOVA rep meas for the increase, pindolol vs placebo, p < 0.05), drug effects on plasma VP-level were generally negligible. In conclusion, in healthy volunteers beta 1- and beta 2-antagonism by pindolol, atenolol and propranolol do not markedly potentiate plasma ANP- and VP-responses to physical exercise. The responses are, however, slightly influenced presumably by the beta-agonist activity of pindolol.

Beta-adrenoceptor antagonist activities and binding affinities of timolol enantiomers in rat atria.

S-Timolol is an effective anti-glaucoma drug, but has potentially hazardous side effects. Recently, R-timolol, also, has been reported to be effective in lowering elevated intraocular pressure. In the present study, the beta-adrenoceptor antagonist activities and binding of R- and S-enantiomers of timolol have been examined on rat atrial preparations. The beta-antagonistic activities were investigated using spontaneously beating rat heart atria. Both timolol enantiomers inhibited (-)-isoprenaline-induced chronotropic action competitively. S-Timolol was about 54 times more potent than R-timolol. The apparent binding affinities of timolol enantiomers to beta 1- and beta 2-adrenoceptors were determined by a radioligand binding assay using (-)-[125I]iodocyanopindolol (ICYP) as a marker and CGP 20712 A as a beta 1- and ICI 118,551 as a beta 2-adrenoceptor antagonist. Both enantiomers of timolol inhibited ICYP binding in nanomolar concentrations with Hill coefficients near unity. Neither enantiomer showed selectivity between beta 1- and beta 2-adrenoceptors, but R-timolol was approximately 30 times less active than S-timolol. It is concluded that R-timolol is a relatively potent non-selective beta-adrenoceptor blocking agent, but may possibly exert a more localized beta-adrenoceptor action in the eye than S-timolol, thus improving the safety of ocular timolol therapy.

Valsalva manoeuvre can be used to study baroreflex sensitivity in pregnancy.

OBJECTIVE: The aim of this study was to assess whether baroreflex sensitivity can be measured in a non-invasive manner with the Valsalva manoeuvre in pregnancy. STUDY DESIGN: Baroreflex sensitivity was measured from the reflex response to phenylephrine injection and phase four of the Valsalva manoeuvre in nine pregnant women at 27 (range 24-33) gestational weeks. RESULTS: Both the phenylephrine test and the Valsalva manoeuvre yielded similar estimates of baroreflex sensitivity (9.3 (4.1) ms/mmHg vs. 8.0 (5.2) ms/mmHg, Pearson's correlation coefficient r = 0.81, P < 0.008, linear regression BRSValsalva (ms/mmHg) = 1.03 x BRSPhenylephrine + 1.59). Comparable changes in heart rate and blood pressure were obtained with the phenylephrine test and the Valsalva manoeuvre. CONCLUSION: The physiological challenge caused by the Valsalva manoeuvre can be used to measure baroreflex sensitivity in pregnancy. A possibility to study baroreflex function non-invasively, without pharmacological intervention, benefits future research of blood pressure regulation in pregnancy.

Cardiovascular effects of ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel.

The objective of this randomized, double-masked, cross-over study was to compare the cardiovascular effects of two glaucoma formulations, ophthalmic 0.5% timolol aqueous solution and 0.1% timolol hydrogel. Twenty-four young healthy subjects received for 2 weeks either twice daily 0.5% timolol solution or once daily 0.1% timolol hydrogel. Heart rate (HR), blood pressure, atrio-ventricular conduction (PR interval), corrected QT time (QTc) and heart rate variability (HRV) were measured in supine position and during head-up tilted position. The mean peak concentrations of timolol in plasma were significantly higher after administration of 0.5% aqueous solution than after 0.1% hydrogel. A 0.5% timolol aqueous solution decreased HR on average by 3 bpm in supine position and by 7 bpm in head-up tilted position while no significant effects were observed with 0.1% timolol hydrogel. During tilt test HR was significantly lower after administration of timolol aqueous solution than after timolol hydrogel (mean +/- SD, 77 +/- 11 bpm versus 86 +/- 13 bpm, P < 0.05). Timolol aqueous solution slightly decreased QTc during tilt (5.9 +/- 5.6 ms, P < 0.01). During tilt tests, timolol aqueous solution slightly increased atrio-ventricular conduction (7.2 ms, P = 0.02). No significant differences were found in HRV. These results indicate that in healthy volunteers, ophthalmic 0.5% timolol aqueous solution produces more pronounced cardiac beta-blocking effects than 0.1% timolol hydrogel.

A comparison of two sedative premedications for minor oral surgery under local anaesthesia.

Two commonly used drug combinations were studied as premedications before surgical 3rd molar removal under local anaesthesia. The study was randomized, crossover and double-blind in 12 patients. Our routine premedication for lengthy operations, consisting of diazepam 10 mg p.o. plus i.m. scopolamine 0.006 mg/kg and morphine 0.2 mg/kg, was compared with a combination of diazepam 10 mg p.o. plus metoprolol 50 mg p.o. The latter combination was expected to cause fewer central nervous system side effects and be more suitable for out-patient surgery. Drug levels in blood, physiological and biochemical indicators of operation-related stress, CNS side effects, and the patients' subjective preferences were monitored. Both combinations were equally accepted by the patients, but the diazepam/scopolamine/morphine combination caused clearly more side effects after discharge than diazepam/metoprolol. The operation-related haemodynamic changes and plasma catecholamine responses were similar after both premedications.

Alcohol, pancreatic muscarinic receptors and acute pancreatitis.

Recently, a new theory about the pathogenesis of acute alcoholic pancreatitis was proposed. The aim of the present work was to further study the basis of this cholinergic theory about the pathogenesis of acute alcoholic pancreatitis. The results indicated that already a short-term alcohol consumption induces in some rats a dramatic decrease in the number of pancreatic muscarinic receptors. This decrease may predispose to acute alcoholic pancreatitis by increasing the cholinergic tone, since excessive cholinergic tone invariably leads to acute pancreatitis both in experimental animals and in man. Thus, the pathogenetic mechanism triggering acute alcoholic pancreatitis might be similar to the mechanism triggering acute pancreatitis caused by the scorpion sting, intoxication with an antiacetylcholine-esterase-containing insecticides or after excessive cholinergic stimulation.

Chronic alcohol intake and carbachol-induced acute pancreatitis in the rat.

Alcohol-induced changes in cholinergic and pancreozymin pathways regulating exocrine pancreatic secretion have been proposed to play a crucial role in the pathogenesis of acute alcoholic pancreatitis. In the present study we investigated the role of chronic alcohol intake in an experimental acute pancreatitis induced in rats by cholinergic hyperstimulation. Chronic alcohol intake interfered with the function of rat pancreatic muscarinic receptors in carbachol-induced acute pancreatitis. However, chronic alcohol intake did not sensitize the experimental animals to cholinergic hyperstimulation. Whether this increased resistance at the level of pancreatic muscarinic receptors contributes to acute alcoholic pancreatitis is discussed in the present article.

Muscarinic receptors and insulin concentration in the rat pancreas after chronic alcohol intake and cholinergic stimulation.

The effects of chronic alcohol intake and carbachol stimulation on pancreatic muscarinic receptor binding and insulin concentrations were studied in the rat pancreas. There was a strong correlation between the number of muscarinic receptors and the concentration of insulin in the pancreas. The concentration of insulin decreased in the pancreas after long-term ethanol exposure and increased after carbachol stimulation. These results indicate that the secretion of insulin is mediated via the muscarinic receptor pathway, and that the changes in the number of muscarinic receptors may have a role in insulin deficiency after long-term alcohol consumption.

Effects of atipamezole--a selective alpha-adrenoceptor antagonist--on cardiac parasympathetic regulation in human subjects.

1 This double-blind, cross-over, placebo-controlled study on six healthy male volunteers was designed to evaluate the effects of alpha2-adrenoceptor antagonism on cardiac parasympathetic regulation. 2 The subjects received atipamezole intravenously as a three-step infusion, which aimed at steady-state serum concentrations of 10, 30 and 90 ng ml(-1) at 50-min intervals. 3 Drug effects were assessed with repeated recordings of blood pressure and electrocardiogram, in which the high-frequency (0.15-0.40 Hz) R-R interval variation is supposed to reflect cardiac parasympathetic efferent neuronal activity. 4 At the end of the three steps of the infusion, the mean (+/-SD) concentrations of atipamezole were 10.5 (3.9), 26.8 (5.6) and 81.3 (21.1) ng ml(-1). 5 Within this concentration range, atipamezole appeared to reduce slightly the high-frequency R-R interval fluctuations, indicating a minor vagolytic effect in the heart. 6 Atipamezole increased systolic and diastolic arterial pressure, on average by 20 and 14 mmHg (maxima at the second step of the infusion), which evidently reflects an overall sympathetic augmentation.

Vasomotor rhinitis and the systemic absorption of ipratropium bromide.

Plasma concentrations of nasally administered ipratropium bromide were analyzed in 10 subjects suffering from severe vasomotor rhinitis and 10 age-sex matched control subjects. The rate of salivary secretion and heart rate were monitored in order to measure systemic anticholinergic effects. A total dose of 360 micrograms of ipratropium bromide (60 micrograms into each nostril, repeated twice at 15 min intervals) were administered nasally to the subjects in randomized order. Ipratropium bromide was rapidly absorbed from the nasal mucosa into the systemic circulation in both groups. The peak plasma concentrations were detected within 10 min after the last drug administration. The peak concentrations were about 50% higher (380 +/- 153 pg/ml) in patients than in control subjects (245 +/- 134 pg/ml). The AUCs/0-15 min (1970 +/- 1140 pg/ml X min) in patients were about 100% higher than in the control subjects (960 +/- 560 pg/ml X min). During the experiment there was a small decrease in the heart rate (8 bpm) and salivary secretion (10%) in both groups. In conclusion, the vasomotor rhinitis increases the systemic absorption of nasally administered ipratropium bromide, but the small increase in the absorption is not likely to have any clinical consequences.

Evaluation of the systemic anticholinergic activity of nasally administered ipratropium bromide.

Plasma concentrations of nasally inhaled ipratropium bromide were analyzed in eight healthy volunteers by using a sensitive radioreceptor assay (RRA). The rate of saliva secretion, heart rate and changes in visual accommodation were quantitated in order to measure possible systemic anticholinergic drug effects. 240 micrograms of ipratropium bromide (40 micrograms each nostril, repeated twice at 15 min intervals) were inhaled nasally in a double blind, randomized, placebo-controlled experiment. Ipratropium bromide absorbed fast, and peak plasma concentrations of the drug (257 +/- 55 pg/ml) were detected as soon as 5 min after the last inhalation (at 35 min from the beginning). The plasma levels of ipratropium bromide decreased rapidly, being only 86 +/- 7 pg/ml one hour after the last inhalation. These low concentrations of ipratropium bromide indicate that only a small portion of it absorbs after nasal application, which is consistent with the lack of any systemic anticholinergic drug effects in our subjects. It is concluded that nasally applied ipratropium bromide is not likely to cause systemic anticholinergic side-effects, even in doses exceeding the therapeutic recommendations.

Pharmacokinetics of glycopyrrolate in children.

STUDY OBJECTIVE: To investigate the pharmacokinetics of glycopyrrolate in children. DESIGN: Open study with three parallel groups. SETTING: Pediatric surgery department at a university hospital. PATIENTS: 26 healthy ASA physical status I children undergoing minor surgery. INTERVENTIONS: Patients were assigned to 1 of 3 groups: under 1 year of age (Group 1, n = 8), between 1 and 3 years of age (Group 2, n = 7), and over 3 years of age (Group 3, n = 11). Glycopyrrolate 5 micrograms/kg was given as a single intravenous (i.v.) injection before induction of general anesthesia. Blood samples (for determination of drug concentrations in plasma) were collected via venous cannula inserted into the contralateral antecubital vein. MEASUREMENTS AND MAIN RESULTS: ECG was observed continuously, blood pressure was measured with an automatic noninvasive device, and blood samples were taken just before and at 2, 4, 6, 10, 15, 30, 60, 120, 180, 240, 360, and 480 minutes after injection of glycopyrrolate. Glycopyrrolate concentrations in plasma were determined with a radioreceptor assay. The only significant difference in the pharmacokinetic parameters was the shortened elimination half-life in patients between 1 and 3 years of age. Glycopyrrolate 5 micrograms/kg i.v. did not cause any significant alterations in heart rate. CONCLUSIONS: There were no significant changes in the distribution volume or clearance of glycopyrrolate in children of different ages. The shortened elimination half-life in children between 1 and 3 years of age is of minor clinical importance.