Field testing of an onsite sanitation system on apartment building blackwater using biological treatment and electrochemical disinfection

The Closed Loop Advanced Sanitation System (CLASS) was designed to treat, disinfect, and recycle toilet blackwater from existing flush toilets in a multi-story apartment building. Two systems were tested at two unique sites in Coimbatore, India for a combined 7500+ treatment hours resulting in more than 180 000 L of treated water. The CLASS prototypes used a combination of biological pretreatment and electrochemical oxidation processes to produce treated water that nearly met the stringent requirements outlined in the standard ISO 30500. The nutrient and organic loading from the toilet blackwater was predominantly reduced by over 85–95% and 80–87%, respectively, through biological processes that were achieved using either a sequencing batch reactor (SBR, site A) or an anaerobic–aerobic biodigester (EcoSan, site B). Complete disinfection of E. coli with nil CFU per ml was achieved using electrochemical processes that also served to remove the remaining organic and nutrient loading to over 90–96%. The treated water was reused for flushing by the residents of the apartment building for 89 days

Sodium-glucose cotransporter 2 inhibitors in patients with heart failure: a systematic review and meta-analysis of randomized trials.

AIMS: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have now been evaluated for the treatment of heart failure in several placebo-controlled randomized controlled trials (RCTs) across various ejection fraction ranges, but these trials were powered for composite outcomes rather than individual clinical endpoints. We therefore performed a meta-analysis to assess their safety and efficacy on all-cause mortality, cardiovascular mortality, and heart failure hospitalizations. METHODS AND RESULTS: We performed a prospectively registered random-effects meta-analysis of all RCTs comparing SGLT-2 inhibitors to placebo in patients with heart failure. The pre-specified primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, heart failure hospitalizations, and the composite of cardiovascular mortality or heart failure hospitalization. Four trials with 15 684 patients were eligible. The SGLT-2 inhibitor tested was empagliflozin in two trials, dapagliflozin in one trial, and sotagliflozin in one trial. The weighted-mean follow-up was 20.0 months. The hazard ratio (HR) for all-cause mortality was 0.91, 95% confidence interval (CI) 0.82-1.01, P = 0.071. There was a 12% reduction in cardiovascular mortality (HR 0.88, 95% CI 0.79 to 0.97, P = 0.012), and a 30% reduction in heart failure hospitalization (HR 0.70, 95% CI 0.64 to 0.77, P < 0.001). CONCLUSION: SGLT-2 inhibitors significantly reduced cardiovascular mortality and heart failure hospitalizations in patients with heart failure. The effect appears consistent across three drugs studied in four trials. SGLT-2 inhibitors should become standard care for patients with heart failure

Cerebral Embolic Protection in Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) is a treatment option for patients with symptomatic severe aortic stenosis across the entire spectrum of surgical risk. Recent trial data have led to the expansion of TAVR into lower-risk patients. With iterative technological advances and successive increases in procedural experience, the occurrence of complications following TAVR has declined. One of the most feared complications remains stroke, and patients consider stroke a worse outcome than death. There has therefore been great interest in strategies to mitigate the risk of stroke in patients undergoing TAVR. In this paper, we will discuss mechanisms and predictors of stroke after TAVR and describe the currently available cerebral embolic protection devices, including their design and relevant clinical studies pertaining to their use. We will also review the current overall evidence base for cerebral embolic protection during TAVR and ongoing randomized controlled trials. Finally, we will discuss our pragmatic recommendations for the use of cerebral embolic protection devices in patients undergoing TAVR

Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation

We previously reported that activation of the host autophagic protein, Beclin1, by HIV-1 infection represents an essential mechanism in controlling HIV replication and viral-induced inflammatory responses in microglial cells. Existing antiretroviral therapeutic approaches have been limited in their ability to cross the blood-brain barrier effectively and recognize and selectively eliminate persistent HIV-infected brain reservoirs. In the present study and for the first time, the bio-distribution and efficacy of noninvasive intranasal delivery of small interfering RNA (siRNA) against the Beclin1 gene using the cationic linear polyethylenimines (PEI) as a gene carrier was investigated in adult mouse brain. Fluorescein isothiocyanate (FITC)-labeled control siRNA delivered intranasally was found in the cytoplasm of neurons and glial cells of the prefrontal cortex at 4 and 24 hours post-delivery, with no major adverse immune reaction encountered. Intranasal delivery of the siRNA targeting Beclin1 significantly depleted the target protein expression levels in brain tissues with no evidence of toxicity. Binding of siRNA to PEI-polymer was characterized and confirmed by Raman spectroscopy. These results indicate that the intranasal drug delivery allows for the direct delivery of the PEI-siRNA nano-complex to the central nervous system, which could potentially offer an efficient means of gene silencing-mediated therapy in the HIV-infected brain

Field testing of an onsite sanitation system on apartment building blackwater using biological treatment and electrochemical disinfection

The Closed Loop Advanced Sanitation System (CLASS) was designed to treat, disinfect, and recycle toilet blackwater from existing flush toilets in a multi-story apartment building. Two systems were tested at two unique sites in Coimbatore, India for a combined 7500+ treatment hours resulting in more than 180 000 L of treated water. The CLASS prototypes used a combination of biological pretreatment and electrochemical oxidation processes to produce treated water that nearly met the stringent requirements outlined in the standard ISO 30500. The nutrient and organic loading from the toilet blackwater was predominantly reduced by over 85–95% and 80–87%, respectively, through biological processes that were achieved using either a sequencing batch reactor (SBR, site A) or an anaerobic–aerobic biodigester (EcoSan, site B). Complete disinfection of E. coli with nil CFU per ml was achieved using electrochemical processes that also served to remove the remaining organic and nutrient loading to over 90–96%. The treated water was reused for flushing by the residents of the apartment building for 89 days

Long-Term Outcomes of Randomized Controlled Trials Comparing Percutaneous Left Atrial Appendage Closure to Oral Anticoagulation for Nonvalvular Atrial Fibrillation: A Meta-Analysis.

BACKGROUND: Oral anticoagulation (OAC) has been considered the standard of care for stroke prophylaxis for patients with nonvalvular atrial fibrillation; however, many individuals are unable or unwilling to take long-term OAC. The safety and efficacy of percutaneous left atrial appendage closure (LAAC) have been controversial, and new trial data have recently emerged. We therefore sought to perform an updated meta-analysis of randomized clinical trials (RCTs) comparing OAC to percutaneous LAAC, focusing on individual clinical endpoints. METHODS: We performed a systematic search of the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 2000 through December 2021 for all RCTs comparing percutaneous LAAC to OAC in patients with nonvalvular atrial fibrillation. Fixed and random effects meta-analyses of hazard ratios (HRs) were performed using the longest follow-up duration available by intention-to-treat. The prespecified primary endpoint was all-cause mortality. RESULTS: Three RCTs enrolling 1516 patients were identified. The weighted mean follow-up was 54.7 months. LAAC was associated with a reduced risk of all-cause mortality (HR 0.76; 95% confidence interval [CI], 0.59-0.96; p = 0.023), hemorrhagic stroke (HR 0.24; 95% CI, 0.09-0.61; p = 0.003), and major nonprocedural bleeding (HR 0.52; 95% CI, 0.37-0.74; p < 0.001). There was no significant difference between LAAC and OAC for any other endpoints. CONCLUSIONS: The available evidence from RCTs suggests LAAC therapy is associated with reduced long-term risk of death compared with OAC. This may be driven by reductions in hemorrhagic stroke and major nonprocedural bleeding. There were no significant differences in the risk of all stroke. Further large-scale clinical trials are needed to validate these findings

(Carbonato-κ2 O,O′)bis­(5,5′-dimethyl-2,2′-bipyridyl-κ2 N,N′)cobalt(III) bromide trihydrate

In the title complex, [Co(CO3)(C12H12N2)2]Br·3H2O, the CoIII cation has a distorted octa­hedral coordination environment. It is chelated by four N atoms of two different 5,5′-dimethyl-2,2′-bipyridyl (dmbpy) ligands in axial and equatorial positions, and by two O atoms of a carbonate anion completing the equatorial positions. Although the water mol­ecules are disordered and their H atoms were not located, there are typical O⋯O distances between 2.8 and 3.0 Å, indicating O—H⋯O hydrogen bonding. The crystal packing is consolidated by C—H⋯O and C—H⋯Br hydrogen bonds, as well as π–π stacking inter­actions between adjacent pyridine rings of the dmbpy ligands, with centroid–centroid distances of 3.694 (3) and 3.7053 (3) Å

Clinical Research on Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valve Disease: Principles, Challenges, and an Agenda for the Future.

Bicuspid aortic valve disease (BAVD) is present in up to half of all patients referred for surgical aortic valve replacement (SAVR) yet was an exclusion criterion for all randomized controlled trials (RCTs) comparing transcatheter aortic valve replacement (TAVR) to SAVR. Nonetheless, approximately 10% of patients currently treated with TAVR have BAVD and available observational data for performing TAVR in these patients are limited by selection bias. Many in the cardiovascular community have advocated for RCTs in this population, but none have been performed. The Heart Valve Collaboratory (HVC) is a multidisciplinary community of stakeholders with the aim of creating significant advances in valvular heart disease by stimulating clinical research, engaging in educational activities, and advancing regulatory science. In December 2020, the HVC hosted a Global Multidisciplinary workshop involving over 100 international experts in the field. Following this 2-day symposium, working groups with varied expertise were convened to discuss BAVD, including the need for and design of RCTs. This review, conducted under the auspices of the HVC, summarizes available data and knowledge gaps regarding procedural therapy for BAVD, outlining specific challenges for trials in this population. We also propose several potential studies that could be performed and discuss respective strengths and weaknesses of each approach. Finally, we present a roadmap for future directions in clinical research in TAVR for BAVD with an emphasis both on RCTs and also prospective registries focused on disease phenotyping to develop parameters and risk scores that could ultimately be applied to patients to inform clinical decision-making

Clinical Research on Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valve Disease: Principles, Challenges, and an Agenda for the Future

Bicuspid aortic valve disease (BAVD) is present in up to half of all patients referred for surgical aortic valve replacement (SAVR) yet was an exclusion criterion for all randomized controlled trials (RCTs) comparing transcatheter aortic valve replacement (TAVR) to SAVR. Nonetheless, approximately 10% of patients currently treated with TAVR have BAVD and available observational data for performing TAVR in these patients are limited by selection bias. Many in the cardiovascular community have advocated for RCTs in this population, but none have been performed. The Heart Valve Collaboratory (HVC) is a multidisciplinary community of stakeholders with the aim of creating significant advances in valvular heart disease by stimulating clinical research, engaging in educational activities, and advancing regulatory science. In December 2020, the HVC hosted a Global Multidisciplinary workshop involving over 100 international experts in the field. Following this 2-day symposium, working groups with varied expertise were convened to discuss BAVD, including the need for and design of RCTs. This review, conducted under the auspices of the HVC, summarizes available data and knowledge gaps regarding procedural therapy for BAVD, outlining specific challenges for trials in this population. We also propose several potential studies that could be performed and discuss respective strengths and weaknesses of each approach. Finally, we present a roadmap for future directions in clinical research in TAVR for BAVD with an emphasis both on RCTs and also prospective registries focused on disease phenotyping to develop parameters and risk scores that could ultimately be applied to patients to inform clinical decision-making