The AHA/ACC/HFSA 2022 Heart Failure Guidelines: Changing the Focus to Heart Failure Prevention

The prevalence of heart failure (HF) in the United States (U.S.) is estimated at over 6 million adults, with the incidence continuing to increase. A large proportion of the U.S. population is also at risk of HF due to the high prevalence of established HF risk factors, such as hypertension, diabetes, and obesity. Many individuals have multiple risk factors, placing them at even higher risk. In addition, these risk factors disproportionately impact various racial and ethnic groups. Recognizing the rising health and economic burden of HF in the U.S., the 2022 American Heart Association / American College of Cardiology / Heart Failure Society of America (AHA/ACC/HFSA) Heart Failure Guideline placed a strong emphasis on prevention of HF. The purpose of this review is to highlight the role of both primary and secondary prevention in HF, as outlined by the recent guideline, and address the role of the preventive cardiology community in reducing the prevalence of HF in at-risk individuals

Optimization of a Novel Series of TRPV4 Antagonists with In Vivo Activity in a Model of Pulmonary Edema

High-throughput screening and subsequent hit optimization identified 1-piperidinylbenzimidazoles, exemplified by compound <b>1</b>, as TRPV4 inhibitors. Lead optimization identified potent TRPV4 blocker <b>19</b>, which has good target activity and pharmacokinetic properties. Inhibitor <b>19</b> was then profiled in an in vivo rat model, demonstrating its ability to inhibit TRPV4-mediated pulmonary edema

Multi-year inter-laboratory exercises for the analysis of illicit drugs and metabolites in wastewater: development of a quality control system

Thirty-seven laboratories from 25 countries present the development of an inter-laboratory testing scheme for the analysis of seven illicit drug residues in standard solutions, tap- and wastewater. Almost 10 000 concentration values were evaluated: triplicates of up to five samples and 26 laboratories per year. The setup was substantially improved with experiences gained across the six repetitions (e.g. matrix type, sample conditions, spiking levels). From this, (pre-)analytical issues (e.g. pH adjustment, filtration) were revealed for specific analytes which resulted in formulation of best-practice protocols for inter-laboratory setup and analytical procedures. The results illustrate the effectiveness of the inter-laboratory setup to assess laboratory performance in the framework of wastewater-based epidemiology. The exercise proved that measurements of laboratories were of high quality (>80% satisfactory results for six out of seven analytes) and that analytical follow-up is important to assist laboratories in improving robustness of wastewater-based epidemiology results

Differential Protein Pathways in 1,25-Dihydroxyvitamin D-3 and Dexamethasone Modulated Tolerogenic Human Dendritic Cells

Transplantation and autoimmunit

Spatio‐temporal assessment of illicit drug use at large scale: evidence from 7 years of international wastewater monitoring

Background and aims Wastewater‐based epidemiology is an additional indicator of drug use that is gaining reliability to complement the current established panel of indicators. The aims of this study were to: (i) assess spatial and temporal trends of population‐normalized mass loads of benzoylecgonine, amphetamine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in raw wastewater over 7 years (2011–17); (ii) address overall drug use by estimating the average number of combined doses consumed per day in each city; and (iii) compare these with existing prevalence and seizure data. Design Analysis of daily raw wastewater composite samples collected over 1 week per year from 2011 to 2017. Setting and Participants Catchment areas of 143 wastewater treatment plants in 120 cities in 37 countries. Measurements Parent substances (amphetamine, methamphetamine and MDMA) and the metabolites of cocaine (benzoylecgonine) and of Δ9‐tetrahydrocannabinol (11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol) were measured in wastewater using liquid chromatography–tandem mass spectrometry. Daily mass loads (mg/day) were normalized to catchment population (mg/1000 people/day) and converted to the number of combined doses consumed per day. Spatial differences were assessed world‐wide, and temporal trends were discerned at European level by comparing 2011–13 drug loads versus 2014–17 loads. Findings Benzoylecgonine was the stimulant metabolite detected at higher loads in southern and western Europe, and amphetamine, MDMA and methamphetamine in East and North–Central Europe. In other continents, methamphetamine showed the highest levels in the United States and Australia and benzoylecgonine in South America. During the reporting period, benzoylecgonine loads increased in general across Europe, amphetamine and methamphetamine levels fluctuated and MDMA underwent an intermittent upsurge. Conclusions The analysis of wastewater to quantify drug loads provides near real‐time drug use estimates that globally correspond to prevalence and seizure data