Particulate air pollution, metabolic syndrome, and heart rate variability: the multi-ethnic study of atherosclerosis (MESA).

BACKGROUND: Cardiac autonomic dysfunction has been suggested as a possible biologic pathway for the association between fine particulate matter ≤ 2.5 µm in diameter (PM2.5) and cardiovascular disease (CVD). We examined the associations of PM2.5 with heart rate variability, a marker of autonomic function, and whether metabolic syndrome (MetS) modified these associations. METHODS: We used data from the Multi-Ethnic Study of Atherosclerosis to measure the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences (rMSSD) of 5,465 participants 45-84 years old who were free of CVD at the baseline examination (2000-2002). Data from the U.S. regulatory monitor network were used to estimate ambient PM2.5 concentrations at the participants' residences. MetS was defined as having three or more of the following criteria: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, high blood pressure, and high fasting glucose. RESULTS: After controlling for confounders, we found that an interquartile range (IQR) increase in 2-day average PM2.5 (10.2 µg/m3) was associated with a 2.1% decrease in rMSSD [95% confidence interval (CI), -4.2 to 0.0] and nonsignificantly associated with a 1.8% decrease in SDNN (95% CI, -3.7 to 0.1). Associations were stronger among individuals with MetS than among those without MetS: an IQR elevation in 2-day PM2.5 was associated with a 6.2% decrease in rMSSD (95% CI, -9.4 to -2.9) among participants with MetS, whereas almost no change was found among participants without MetS (p-interaction = 0.005). Similar effect modification was observed in SDNN (p-interaction = 0.011). CONCLUSION: These findings suggest that autonomic dysfunction may be a mechanism through which PM exposure affects cardiovascular risk, especially among persons with MetS.http://deepblue.lib.umich.edu/bitstream/2027.42/78311/1/ParkAuchincloss2010_EnvironHealthPersp.pd

Rational Addiction with Optimal Inventories: Theory and Evidence from Cigarette Purchases in Japan

A model of rational addiction (RA) with optimal inventories is developed and empirically tested using data on purchases in Japan. If a consumer has information regarding a future price increase, then she may hoard addictive goods; in this case, the optimal inventory period increases with the price hike but decreases with the inventory cost. Owing to the creation of such inventories by consumers, the absolute value of the price elasticity of demand is smaller in the case of a price increase than in that of a price decrease, and this difference is especially salient in the short-run. The evidence provided by daily cigarette purchases is consistent with this asymmetric price effect. Monthly cigarette purchase data do not support the RA hypothesis when inventory is ignored, as inventory becomes an omitted variable that correlates with price; however, this hypothesis does find support if inventory is identified in the demand equation.The Seventh ISER-Moriguchi Prize (2005) Awarded Paper

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

{2-[1-(2-Methoxy-6-oxidophenyl-κO6)ethylidene]-N-methylhydrazinecarbothioamidato-κ2N2,S}(triphenylphosphane-κP)palladium(II) ethanol monosolvate

In the title compound, [Pd(C11H13N3O2S)(C18H15P)]·C2H5OH, the PdII atom is tetracoordinated in a slightly distorted square-planar environment by three donor atoms (NOS) from a thiosemicarbazonate ligand, forming five- and six-membered chelate rings, and a P atom from a neutral triphenylphosphane group. The five-membered ring adopts a distorted envelope conformation with PdII as the flap atom, while the six-membered ring forms a slightly twisted screw-boat conformation. A slightly distorted screw-boat form of a methoxyphenyl group is fused to the six-membered ring. Weak C—H...O interactions form dimers in the asymmetric unit and along [001] which help to stabilize the crystal packing

2-[1-(2-Hydroxy-6-methoxyphenyl)ethylidene]-N-methylhydrazinecarbothioamide acetonitrile monosolvate

In the title compound, C11H15N3O2S·C2H3N, the dihedral angle between the benzene ring and the mean plane of the hydrazinecarbothioamide group is 75.1 (2)°. In the crystal, the main molecule is linked to the solvent molecule by a weak N—H...N hydrogen bond while O—H...S hydrogen bonds link the molecules into columns along [100]

Avian influenza rapidly induces antiviral genes in duck lung and intestine

Ducks are the natural reservoir of influenza A and survive infection by most strains. To characterize the duck immune response to influenza, we sought to identify innate immune genes expressed early in an infection. We used suppressive subtractive hybridization (SSH) to construct 3 libraries enriched in differentially expressed genes from lung RNA of a duck infected with highly pathogenic avian influenza virus A/Vietnam/1203/04 (H5N1), or lung and intestine RNA of a duck infected with low pathogenic avian influenza A/mallard/BC/500/05 (H5N2) compared to a mock-infected duck. Sequencing of 1687 clones identified a transcription profile enriched in genes involved in antiviral defense and other cellular processes. Major histocompatibility complex class I (MHC I), interferon induced protein with tricopeptide repeats 5 (IFIT5), and 2′–5′oligoadenylate synthetase-like gene (OASL) were increased more than 1000-fold in relative transcript abundance in duck lung at 1 dpi with highly pathogenic VN1203. These genes were induced much less in lung or intestine following infection with low pathogenic BC500. The expression of these genes following infection suggests that ducks initiate an immediate and robust response to a potentially lethal influenza strain, and a minimal response a low pathogenic strain