Digital phenotyping of student mental health during COVID-19: an observational study of 100 college students.

Objective: This study assessed the feasibility of capturing smartphone based digital phenotyping data in college students during the COVID-19 pandemic with the goal of understanding how digital biomarkers of behavior correlate with mental health. Participants: Participants were 100 students enrolled in 4-year universities. Methods: Each participant attended a virtual visit to complete a series of gold-standard mental health assessments, and then used a mobile app for 28 days to complete mood assessments and allow for passive collection of GPS, accelerometer, phone call, and screen time data. Students completed another virtual visit at the end of the study to collect a second round of mental health assessments. Results: In-app daily mood assessments were strongly correlated with their corresponding gold standard clinical assessment. Sleep variance among students was correlated to depression scores (ρ = .28) and stress scores (ρ = .27). Conclusions: Digital Phenotyping among college students is feasible on both an individual and a sample level. Studies with larger sample sizes are necessary to understand population trends, but there are practical applications of the data today.

Effect of the Helium Background Gas Pressure on the Structural and Optoelectronic Properties of Pulsed-Laser-Deposited PbS Thin Films.

This work focuses on the dependence of the features of PbS films deposited by pulsed laser deposition (PLD) subsequent to the variation of the background pressure of helium (PHe). The morphology of the PLD-PbS films changes from a densely packed and almost featureless structure to a columnar and porous one as the He pressure increases. The average crystallite size related to the (111) preferred orientation increases up to 20 nm for PHe ≥ 300 mTorr. The (111) lattice parameter continuously decreases with increasing PHe values and stabilizes at PHe ≥ 300 mTorr. A downshift transition of the Raman peak of the main phonon (1LO) occurs from PHe = 300 mTorr. This transition would result from electron-LO-phonon interaction and from a lattice contraction. The optical bandgap of the films increases from 1.4 to 1.85 eV as PHe increases from 50 to 500 mTorr. The electrical resistivity of PLD-PbS is increased with PHe and reached its maximum value of 20 Ω·cm at PHe = 300 mTorr (400 times higher than 50 mTorr), which is probably due to the increasing porosity of the films. PHe = 300 mTorr is pointed out as a transitional pressure for the structural and optoelectronic properties of PLD-PbS films.

A comparison of the effects of selective and non-selective mineralocorticoid antagonism on glucose homeostasis of heart failure patients with glucose intolerance or type II diabetes: A randomized controlled double-blind trial.

Mineralocorticoid receptor antagonists (MRAs) decrease morbidity and mortality in patients with heart failure (HF). However, spironolactone, a non-selective MRA, has been shown to exert a harmful effect on glucose homeostasis. The objective of this multicenter, randomized, controlled, double-blind trial was to compare the effects of spironolactone to those of the selective MRA eplerenone on glucose homeostasis among 62 HF patients with glucose intolerance or type II diabetes. Trial registration number:NCT01586442.

A prospective study of the impact of AGTR1 A1166C on the effects of candesartan in patients with heart failure.

AIM: To evaluate the impact of AGTR1 A1166C (rs5186) on the response to candesartan in patients with heart failure. MATERIALS & METHODS: Prospective, multicentre, open-label study. We studied 299 symptomatic patients with heart failure presenting a left ventricular ejection fraction ≤40%. RESULTS: Reductions in the primary end points of natriuretic peptides were not significantly associated with AGTR1 A1166C. Nevertheless, carrying the 1166C allele was associated with a greater compensatory increase in renin activity (p = 0.037) after 16 weeks of treatment with candesartan and a more modest effect on aldosterone concentrations (p = 0.022). CONCLUSION: AGTR1 1166C carriers may experience a greater long-term compensatory renin-angiotensin-aldosterone system activation following treatment with candesartan. Whether these associations ultimately influence clinical outcomes requires investigation. Clinicaltrials.gov : NCT00400582.

Toward Thiophene-Annulated Graphene Nanoribbons.

Narrow thiophene-edged graphene nanoribbons (GNRs) were prepared from polychlorinated thiophene-containing poly(p-phenylene)s using the photochemical, metal-free cyclodehydrochlorination (CDHC) reaction. 1 H NMR and Raman spectroscopy confirmed the structures of the GNRs. The regioselectivity of the CDHC reaction allows the preparation of both laterally symmetrical and unsymmetrical GNRs and, consequently, the modulation of their optical and electronic properties.

Breaking Bonds and Forming Nanographene Diradicals with Pressure.

New anthanthrone-based polycyclic scaffolds possessing peripheral crowded quinodimethanes have been prepared. While the compounds adopt a closed-shell butterfly-shaped structure in the ground state, a curved-to-planar fluxional inversion is accessible with a low energy barrier through a biradicaloid transition state. Inversion is primarily driven by the release of strain associated with steric hindrance at the peri position of the anthanthrone core; a low-lying diradical state is accessible through planarization of the core, which is attained in solution at moderate temperatures. The most significant aspect of this transformation is that planarization is also achieved by application of mild pressure in the solid state, wherein the diradical remains kinetically trapped. Complementary information from quantum chemistry, 1 H NMR, and Raman spectroscopies, together with magnetic experiments, is consistent with the formation of a nanographene-like structure that possesses radical centers localized at the exo-anthanthrone carbons bearing phenyl substituents.

Heart failure with anemia: novel findings on the roles of renal disease, interleukins, and specific left ventricular remodeling processes.

BACKGROUND: Anemia is a highly prevalent and strong independent prognostic marker in heart failure (HF), yet this association is not completely understood. Whether anemia is simply a marker of disease severity and concomitant chronic kidney disease or represents the activation of other detrimental pathways remains uncertain. We sought to determine which pathophysiological pathways are exacerbated in patients with HF, reduced ejection fraction (HFrEF) and anemia in comparison with those without anemia. METHODS AND RESULTS: In a prospective study involving 151 patients, selected biomarkers were analyzed, each representing proposed contributive mechanisms in the pathophysiology of anemia in HF. We compared clinical, echocardiographic, and circulating biomarkers profiles among patients with HFrEF and anemia (group 1), HFrEF without anemia (group 2), and chronic kidney disease with preserved EF, without established HF (chronic kidney disease control group 3). We demonstrate here that many processes other than those related to chronic kidney disease are involved in the anemia-HF relationship. These are linked to the pathophysiological mechanisms pertaining to left ventricular systolic dysfunction and remodeling, systemic inflammation and volume overload. We found that levels of interleukin-6 and interleukin-10, specific markers of cardiac remodeling (procollagen type III N-terminal peptide, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase 1, left atrial volume), myocardial stretch (NT-proBNP [N-terminal probrain natriuretic peptide]), and myocyte death (troponin T) are related to anemia in HFrEF. CONCLUSIONS: Anemia is strongly associated not only with markers of more advanced and active heart disease but also with the level of renal dysfunction in HFrEF. Increased myocardial remodeling, inflammation, and volume overload are the hallmarks of patients with anemia and HF. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00834691.

Changes in cardiopulmonary reserve and peripheral arterial function concomitantly with subclinical inflammation and oxidative stress in patients with heart failure with preserved ejection fraction.

Background. Changes in cardiopulmonary reserve and biomarkers related to wall stress, inflammation, and oxidative stress concomitantly with the evaluation of peripheral arterial blood flow have not been investigated in patients with heart failure with preserved ejection fraction (HFpEF) compared with healthy subjects (CTL). Methods and Results. Eighteen HFpEF patients and 14 CTL were recruited. Plasma levels of inflammatory and oxidative stress biomarkers were measured at rest. Brain natriuretic peptide (BNP) was measured at rest and peak exercise. Cardiopulmonary reserve was assessed using an exercise protocol with gas exchange analyses. Peripheral arterial blood flow was determined by strain gauge plethysmography. Peak VO2 (12.0 ± 0.4 versus 19.1 ± 1.1 mL/min/kg, P < 0.001) and oxygen uptake efficiency slope (1.55 ± 0.12 versus 2.06 ± 0.14, P < 0.05) were significantly decreased in HFpEF patients compared with CTL. BNP at rest and following stress, C-reactive-protein, interleukin-6, and TBARS were significantly elevated in HFpEF. Both basal and posthyperemic arterial blood flow were not significantly different between the HFpEF patients and CTL. Conclusions. HFpEF exhibits a severe reduction in cardiopulmonary reserve and oxygen uptake efficiency concomitantly with an elevation in a broad spectrum of biomarkers confirming an inflammatory and prooxidative status in patients with HFpEF.

Circulating levels of linoleic acid and HDL-cholesterol are major determinants of 4-hydroxynonenal protein adducts in patients with heart failure.

OBJECTIVE: Measurements of oxidative stress biomarkers in patients with heart failure (HF) have yielded controversial results. This study aimed at testing the hypothesis that circulating levels of the lipid peroxidation product 4-hydroxynonenal bound to thiol proteins (4HNE-P) are strongly associated with those of its potential precursors, namely n-6 polyunsaturated fatty acids (PUFA). METHODS AND RESULTS: Circulating levels of 4HNE-P were evaluated by gas chromatography-mass spectrometry in 71 control subjects and 61 ambulatory symptomatic HF patients along with various other clinically- and biochemically-relevant parameters, including other oxidative stress markers, and total levels of fatty acids from all classes, which reflect both free and bound to cholesterol, phospholipids and triglycerides. All HF patients had severe systolic functional impairment despite receiving optimal evidence-based therapies. Compared to controls, HF patients displayed markedly lower circulating levels of HDL- and LDL-cholesterol, which are major PUFA carriers, as well as of PUFA of the n-6 series, specifically linoleic acid (LA; P=0.001). Circulating 4HNE-P in HF patients was similar to controls, albeit multiple regression analysis revealed that LA was the only factor that was significantly associated with circulating 4HNE-P in the entire population (R (2)=0.086; P=0.02). In HF patients only, 4HNE-P was even more strongly associated with LA (P=0.003) and HDL-cholesterol (p<0.0002). Our results demonstrate that 4HNE-P levels, expressed relative to HDL-cholesterol, increase as HDL-cholesterol plasma levels decrease in the HF group only. CONCLUSION: Results from this study emphasize the importance of considering changes in lipids and lipoproteins in the interpretation of measurements of lipid peroxidation products. Further studies appear warranted to explore the possibility that HDL-cholesterol particles may be a carrier of 4HNE adducts.

Cruciform alkynylated anthanthrene derivatives: a structure-properties relationship case study.

An efficient and versatile synthetic strategy toward cruciform anthanthrene compounds using Sonogashira couplings steps was developed. Acetylenic linkers were used to effectively extend the π-conjugation of polycyclic anthanthrone and anthanthrene compounds and tune their optoelectronic properties. Structure-property relationships supported by DFT calculations indicated more effective π-conjugation along the 6,12 axis than along the 4,10 axis. These molecules displayed strong J-aggregation both in solution and in the solid state and proved to be highly photostable with reversible redox processes, which are properties of interest in materials sciences.

Sex-specific interaction effects of age, occupational status, and workplace stress on psychiatric symptoms and allostatic load among healthy Montreal workers.

Socio-demographics and workplace stress may affect men and women differently. The aim of this cross-sectional study was to assess sex-specific interactions among age, occupational status, and workplace Demand-Control-Support (D-C-S) factors in relation to psychiatric symptoms and allostatic load levels representing multi-systemic "wear and tear". It was hypothesized that beyond main effects, D-C-S factors would be moderated by occupational status and age in sex-specific directions predictive of subjective psychiatric symptoms and objective physiological dysregulations. Participants included healthy male (n = 81) and female (n = 118) Montreal workers aged 20 to 64 years (Men: M = 39.4 years, SD = 11.3; Women: M = 42.8 years, SD = 11.38). The Job Content Questionnaire was administered to assess workplace D-C-S factors that included psychological demands, decisional latitude, and social support. Occupational status was coded using the Nam--Powers--Boyd system derived from the Canadian census. Psychiatric symptoms were assessed using the Beck Anxiety Scale and the Beck Depression Inventory II. Sex-specific allostatic load indices were calculated based on fifteen biomarkers. Regression analyses revealed that higher social support was associated with less depressive symptoms in middle aged (p = 0.033) and older men (p = 0.027). Higher occupational status was associated with higher allostatic load levels for men (p = 0.035), while the reverse occurred for women (p = 0.048). Women with lower occupational status but with higher decision latitude had lower allostatic load levels, as did middle-aged (p = 0.031) and older women (p = 0.003) with higher psychological demands. In summary, age and occupational status moderated workplace stress in sex-specific ways that have occupational health implications.

Differences in biomarkers in patients with heart failure with a reduced vs a preserved left ventricular ejection fraction.

BACKGROUND: The differences in concentrations of biomarkers between heart failure (HF) patients with a preserved left ventricular ejection fraction (LVEF), or HF-PEF, and patients with HF with reduced LVEF (HF-REF) have yet to be defined. The objectives of this study were to compare the concentrations and correlation of biomarkers of inflammation, extracellular matrix (ECM) turnover and neurohormonal activation between these populations. METHODS: We performed a cross-sectional study of 29 subjects with symptomatic HF-REF (LVEF = 25.6 ± 5.1%) and 29 subjects with symptomatic HF-PEF (LVEF = 63.3 ± 5.3%). Concentrations of N-terminal proB-type natriuretic peptide (NT-proBNP), high sensitivity C-reactive protein (hsCRP), procollagen type III amino-terminal peptide (PIIINP), matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of MMP (TIMP)-1 were measured. RESULTS: Although NT-proBNP and PIIINP concentrations were higher in patients with HF-REF compared with patients with HF-PEF (both P < 0.05), the only significant difference between the groups remaining after adjusting for possible confounding variables was NT-proBNP (P = 0.02). In patients with HF-REF, NT-proBNP correlated with PIIINP (P < 0.05), TIMP-1 (P < 0.05), and MMP-2 (P = 0.002), while PIIINP correlated with TIMP-1 (P < 0.05) and MMP-2 (P < 0.0001). In patients with a HF-PEF, only high sensitivity C-reactive protein correlated significantly with MMP-2 (P = 0.002). CONCLUSIONS: Patients with HF-REF or HF-PEF presenting similar symptoms and functional limitations exhibit similar concentrations of biomarkers of ECM and inflammation. However, patients with HF-REF exhibit significantly higher NT-proBNP concentrations than patients with HF-PEF. The differences in the correlations observed between the biomarkers between these 2 populations suggest some heterogeneity and differences in the mechanisms related to the release or clearance of biomarkers in HF-REF vs HF-PEF.

Left ventricular versus simultaneous biventricular pacing in patients with heart failure and a QRS complex ≥120 milliseconds.

BACKGROUND: Left ventricular (LV) pacing alone may theoretically avoid deleterious effects of right ventricular pacing. METHODS AND RESULTS: In a multicenter, double-blind, crossover trial, we compared the effects of LV and biventricular (BiV) pacing on exercise tolerance and LV remodeling in patients with an LV ejection fraction ≤35%, QRS ≥120 milliseconds, and symptoms of heart failure. A total of 211 patients were recruited from 11 centers. After a run-in period of 2 to 8 weeks, 121 qualifying patients were randomized to LV followed by BiV pacing or vice versa for consecutive 6-month periods. The greatest improvement in New York Heart Association class and 6-minute walk test occurred during the run-in phase before randomization. Exercise duration at 75% of peak Vo(2) (primary outcome) increased from 9.3±6.4 to 14.0±11.9 and 14.3±12.5 minutes with LV and BiV pacing, respectively, with no difference between groups (P=0.4327). LV ejection fraction improved from 24.4±6.3% to 31.9±10.8% and 30.9±9.8% with LV and BiV pacing, respectively, with no difference between groups (P=0.4530). Reductions in LV end-systolic volume were likewise similar (P=0.6788). The proportion of clinical responders (≥20% increase in exercise duration) to LV and BiV pacing was 48.0% and 55.1% (P=0.1615). Positive remodeling responses (≥15% reduction in LV end-systolic volume) were observed in 46.7% and 55.4% (P=0.0881). Overall, 30.6% of LV nonresponders improved with BiV and 17.1% of BiV nonresponders improved with LV pacing. CONCLUSION: LV pacing is not superior to BiV pacing. However, nonresponders to BiV pacing may respond favorably to LV pacing, suggesting a potential role as tiered therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00901212.

Defensiveness and metabolic syndrome: impact of sex and age.

The association between defensiveness and metabolic burden, as well as the moderating effects of sex and age were evaluated in 199 healthy working men (N=81) and women (N=118), aged 20-64 years (M=41; S.D.=11.45). Defensiveness (Marlowe-Crowne Social Desirability Scale) and parameters of metabolic syndrome (MS; waist circumference, HDL, triglycerides, glucose, 24h ambulatory blood pressure) were obtained. In men, defensiveness was inversely related to MS burden (Beta=-.288; p=.001), as well as to individual measures of SBP, DBP, glucose and waist circumference (p<.05). In older women, high defensiveness was associated with a greater MS burden (p=.050) and glucose level (p=.005) while the reverse was true in younger women (p=.012). In conclusion, defensiveness was associated with a worse metabolic profile in older women but may be protective for men and younger women. Understanding the pathophysiological processes underlying these associations could elucidate sex and age differences and inform prevention efforts.

Effects of AGTR1 A1166C gene polymorphism in patients with heart failure treated with candesartan.

BACKGROUND: The benefits of angiotensin II receptor blockers (ARBs) in patients with heart failure who are treated with standard pharmacotherapy, including an angiotensin-converting enzyme (ACE) inhibitor, were demonstrated in 2 large randomized trials. It is currently impossible to determine which patient will benefit from the addition of an ARB. OBJECTIVE: To explore the impact of selected candidate genes on the hemodynamic, neurohormonal, and antiinflammatory effects of candesartan in patients with heart failure who are already being treated with an ACE inhibitor. METHODS: We investigated the impact of 10 candidate genetic polymorphisms on the effects of candesartan in patients with heart failure who are treated with an ACE inhibitor. We evaluated their impact on acute (2 wk) and long-term (24 wk) changes in blood pressure and N-terminal proB-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) during treatment with candesartan. RESULTS: Thirty-one patients were included. Homozygotes of the AGTR1 A1166 allele (n = 13) had a greater decrease in systolic (-9.1 +/- 4.7 vs 1.1 +/- 3.3 mm Hg; p = 0.04 by analysis of variance [ANOVA], adjusting for dose) and diastolic blood pressure (-5.1 +/- 1.5 vs 1.9 +/- 1.9 mm Hg; p = 0.005 by ANOVA, adjusting for dose) compared with C1166 allele carriers (n = 18) following 2 weeks of treatment. After 6 months of treatment, C1166 carriers experienced a greater decrease in NT-proBNP (-151.4 [-207; -19.8] ng/L vs 147.3 [-61.3; 882.9] ng/L; p = 0.03) and hsCRP (-0.8 [-2.2; -0.03] mg/L) vs 0.2 [-1.8; 5.3] mg/L; p = 0.09) compared with patients carrying the AA1166 genotype. No other significant association was found. CONCLUSIONS: The results of this proof-of concept study provide the first evidence that the AGTR1 A1166C polymorphism could influence the response to candesartan in patients with heart failure who are receiving ACE inhibitors. Validation of these exploratory findings in larger populations is required before use of the AGTR1 A1166C genotype can be incorporated into clinical practice.

Effects of combined candesartan and ACE inhibitors on BNP, markers of inflammation and oxidative stress, and glucose regulation in patients with symptomatic heart failure.

BACKGROUND: We assessed the effects of candesartan in addition to angiotensin-converting enzyme (ACE) inhibitors on N-terminal pro-type natriuretic peptide (Nt-proBNP), systemic markers of inflammation and oxidative stress as well as on glucose regulation in patients with heart failure (HF). METHODS AND RESULTS: Eighty patients with HF ages 62.5 +/- 8.4 years presenting mostly with New York Heart Association class II symptoms (class II = 57.5%, III = 41.3%), and mean left ventricular ejection fraction 27.1 +/- 7.3% were recruited. The patients were randomized to receive candesartan titrated to 32 mg 1 per day versus placebo in double-blind fashion for 6 months. Nt-proBNP, markers of inflammation and oxidative stress, glucose, insulin, and fasting insulin resistance index were analyzed. Candesartan decreased Nt-proBNP (median value = 12.4% versus -20.4%; [candesartan] P = .05), and high-sensitivity C-reactive protein (hsCRP) (+5.32% versus -20.3% [candesartan]; P = 0.046), without significantly influencing serum interleukin-6, interleukin-18, adhesion molecules, or markers of oxidative stress. Blood glucose decreased in patients treated with candesartan with a significantly greater effect in patients with higher blood glucose levels (P < .01 for interaction). CONCLUSIONS: The addition of candesartan to ACE inhibitor and beta-blocker decreases Nt-proBNP and hsCRP, but does not change the other markers of inflammation or oxidative stress in patients with heart failure. Dual angiotensin-II suppression also decreased blood glucose with a greater impact in patients with higher blood glucose level.

Randomized controlled trial of pericardial blood processing with a cell-saving device on neurologic markers in elderly patients undergoing coronary artery bypass graft surgery.

BACKGROUND: Processing of pericardial shed blood with a cell-saving device was claimed to prevent lipid microembolization and to protect from neurocognitive dysfunction after cardiopulmonary bypass. The present study tested the hypothesis that processing of pericardial shed blood with a cell-saving device during cardiopulmonary bypass would significantly decrease serum levels of protein S100B, and improve brain oxygen saturation and neurologic outcome, all markers of brain injury in elderly patients. METHODS: Forty patients, 65 years of age and older, undergoing coronary artery bypass graft with cardiopulmonary bypass, were prospectively randomly assigned to processing of pericardial shed blood with a cell-saving device or to conventional use of a standard closed venous reservoir where cardiotomy blood was collected and reinfused through the arterial circuit (control group). Serum in S100B was measured 30 minutes, 4 hours, 24 hours, and 48 hours after surgery. Near-infrared spectroscopy monitoring was performed during the procedure and the National Institutes of Health stroke scale was measured before surgery and at the time of discharge of the hospital. RESULTS: Patients in the cell-saving device group averaged 72 +/- 3 years of age and underwent 3.1 +/- 0.7 coronary artery grafts with a mean of 62 +/- 20 minutes of cardiopulmonary bypass time. Patients in the control group averaged 75 +/- 4 years of age (p = 0.03) and underwent 3.3 +/- 0.6 coronary artery grafts (p = 0.49) with a mean of 75 +/- 25 minutes of cardiopulmonary bypass time (p = 0.12). The quantity of blood administered from the cell-saving device averaged 281 +/- 162 mL per patient. Serum protein S100B levels averaged 0.06 +/- 0.03 before surgery and 0.51 +/- 0.23 microg/L 30 minutes after surgery in the cell-saving device patients compared with 0.076 +/- 0.04 before surgery (p = 0.32) and 1.48 +/- 0.66 (p < 0.0001) in the control patients. The near-infrared spectroscopy baseline mean value of left and right cortical region was 58% +/- 12% and 55% +/- 7% in the cell-saving device group versus 59% +/- 7% and 53% +/- 6% in the control group (p = 0.67 and 0.36), and no difference occurred over time in each group. The National Institutes of Health stroke score before and after surgery was similar in the two groups. There was one cerebrovascular complication in the control group (1 of 20, 5%) after surgery. CONCLUSIONS: The difference between the two groups occurred 30 minutes after surgery, at which time serum levels of protein S100B were significantly higher in the control group compared with cell-saving device patients. Although use of the cell-saving device was not associated with higher brain oxygen saturation nor changes in the National Institutes of Health stroke score, it is associated with lesser release of nonspecific markers of brain injury in elderly patients.