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Introduction Many primary prevention heart failure (HF) patients with an implantable cardiac defibrillator (ICD) rarely experience life‐threatening ventricular arrhythmias (VA). New strategies are required to identify patients most at risk of VA and sudden cardiac death who would benefit from an ICD. One potential method is the detection of fragmented QRS (fQRS) on the electrocardiogram. The aim was to assess the predictive capacity of fQRS for VA and mortality in ischemic (ICM) and non‐ischemic cardiomyopathy (NICM) primary prevention HF patients. Methods and Results A systematic review and meta‐analysis of studies examining fQRS in HF patients with or without an ICD who met primary prevention indications with reduced ejection fraction ≤40%. Outcome measures were VA (or appropriate ICD therapy) and all‐cause mortality. Ten studies involving 3885 patients were included for analysis. Most patients were male with non‐fQRS patients being significantly younger (−1.5[−2.66, −0.42], p = .03). Diabetes was more likely in fQRS patients (1.12[1.01, 1.25], p = .03) while non‐fQRS patients were 28% more likely to have a history of atrial fibrillation (0.82[0.67,1.00], p = .05). Ventricular arrhythmias were significantly 1.5 times more likely in patients with fQRS (1.51[1.02, 2.25], p = .04). HF patients were 1.7 times more likely to die of any cause if fQRS was present (1.68[1.13, 2.52], p = .01). NICM patients with fQRS have a significant 2.6‐fold increased incidence of death compared with ICM patients (2.55[1.63, 3.98], p < .0001). Conclusion fQRS is associated with VA and all‐cause mortality and may be a novel marker in the risk stratification of primary prevention HF patients indicated for ICD implantation.

Identifying patients with high-risk heart failure (HF) who would benefit from an implantable cardioverter-defibrillator (ICD) remains controversial. A potential marker for arrhythmic sudden death is fragmented QRS (fQRS). fQRS is the notching and slurring of the QRS complex in a 12-lead ECG and it indicates abnormal ventricular depolarisation and myocardial scarring and fibrosis. However, before fQRS complex can be included into selection criteria for ICD therapy, more complete reporting is required on their association with malignant arrhythmias, left ventricular remodelling and myocardial scarring/fibrosis in patients with HF. The molecular basis of the fQRS-arrhythmia-fibrosis connection in HF also needs to be explored. It is not widely appreciated that changes in the QRS complex and phases 0 and 1 of the ventricular action potential occur before contraction and predetermine Ca2+ release during contraction and later Ca2+ sparks. It is currently not known whether the different zig-zag patterns of the QRS are associated with aberrant Ca2+ cycling and arrhythmogenic sparks in patients with HF.

For decades, left ventricular ejection fraction (LVEF < 35%) has been a mainstay for identifying heart failure (HF) patients most likely to benefit from an implantable cardioverter defibrillator (ICD). However, LVEF is a poor predictor of sudden cardiac death (SCD) and ignores 50% of HF patients with mildly reduced and preserved LVEF. The current international guidelines for primary prophylaxis ICD therapy are inadequate. Instead of LVEF, which is not a good measure of LV contractility or hemodynamic characterization, we hypothesize ventriculo-arterial (VA) coupling combined with fragmented QRS (fQRS) will improve risk stratification and patient suitability for an ICD. Quantifying cardiac and aortic mechanics, and predicting active arrhythmogenic substrate, from varying fQRS morphologies, may help to stratify ischemic and non-ischemic patients with different functional capacities and predisposition for lethal arrhythmias. We propose HF patients with a low physiological reserve may not benefit from ICD therapy, whereas those patients with higher reserves and extensive arrhythmogenic substrate may benefit. Our hypothesis combining VA coupling with fQRS changes has the potential to widen HF patient participation (low and high LVEF) and advance personalized medicine for HF patients at high risk of SCD.

Background: Despite major advances in treating patients with severe heart failure, deciding who should receive an implantable cardiac defibrillator (ICD) remains challenging.Objective: To study the risk factors and mortality in patients after receiving an ICD (January 2008–December 2015) in a regional hospital in Australia.Methods: Eighty-two primary prevention patients received an ICD for ischemic cardiomyopathy (ICM, n = 41) and non-ischemic cardiomyopathy (NICM, n = 40) with 4.8-yrs follow-up. One patient had mixed ICM/NICM indications. Ventricular arrhythmias were assessed using intracardiac electrograms. Statistical analysis compared the total population and ICM and NICM groups using Kaplan-Meier for survival, Cox regression for mortality predictors, and binary logistic regression for predictors of ventricular arrhythmias ( p < 0.05).Results: Major risk factors were hypercholesterolemia (70.7%), hypertension (47.6%), and obesity (41.5%). Severe obstructive sleep apnea (OSA) was found exclusively in NICM patients (23.7%, p = 0.001). Mortality was 30.5% after 4.8-yrs. The majority of patients (n=67) had no sustained ventricular arrhythmias yet 28% received therapy ( n = 23), 18.51% were appropriate ( n = 15), and 13.9% inappropriate ( n = 11). Patients receiving ≥2 incidences of inappropriate shocks were 18-times more likely to die ( p = 0.013). Three sudden cardiac deaths (SCD) (3.7%) were prevented by the ICD.Conclusion: Patients implanted with an ICD in Townsville had 30.5% all-cause mortality after 4.8-yrs. Only 28% of patients received ICD therapy and 13.9% were inappropriate. OSA may have contributed to the fourfold increase in inappropriate therapy in NICM patients. Our study raises important efficacy, ethical and healthcare cost questions about who should receive an ICD, and possible regional and urban center disparities.

Building codes in the United States derive principally from English precedents. Their adoption can be understood as acceptance by mid-nineteenth-century Americans of those utilitarian values which made it possible to restrict some individual freedoms, like shoddy building practices, in favour of general health, safety and welfare. The political will to pass such legislation was, no doubt, strongly influenced by a series of devastating fires that damaged or destroyed eleven nineteenth-century American cities and the chronic outbreaks of typhus, yellow fever and smallpox that plagued many other cities (AIA 1990: 9). These crises were inevitably followed by legislation and the founding of institutions intent on eliminating those building practices that would most obviously contribute to repeat fires and epidemics. Historians generally refer to this phenomenon as the era of ‘sanitary reform’ or the ‘public health movement’.

Since the emergence of SARS-CoV-2 and the COVID-19 pandemic, a wide range of treatment options have been evaluated in preclinical studies and clinical trials, with several being approved for use in humans. Immunomodulatory drugs have shown success in dampening the deleterious inflammatory response seen in severe COVID-19 patients, but there remains an urgent need for development of additional therapeutic options for COVID-19 treatment. A potential drug target is the CCR5-CCL5 axis, and blocking this pathway may protect against severe disease. Here we evaluated whether OB-002, an analog of human CCL5 and a potent antagonist of CCR5, provides therapeutic benefit in SARS-CoV-2 infected Syrian hamsters. Daily treatment with OB-002 altered immune gene transcription in the lungs, and reduced pathology following infection, but did not prevent weight loss or viral replication in the lungs of infected animals, even in combination with the antiviral drug remdesivir. Our data suggest that targeting the CCR5-CCL5 pathway in SARS-CoV-2 infection in hamsters is insufficient to significantly impact disease development in this model.

Abstract Farmington Bay (FB), UT, has undergone major water quality changes due to human interventions. An arm of the Great Salt Lake (GSL), FB, is an endorheic body, actively accumulating nutrients. Human impacts to FB began in 1847 when European settlers arrived and major ecosystem changes have resulted through local development. Major impacts include anthropogenically impacted discharges (AID), causeway construction, and water-level declines. AID includes raw and treated sewage, septic leachate, irrigation returns, and feedlot or pasture runoff. Causeway construction produced freshening (hypersaline to fresh-brackish) via hydrodynamic isolation, whereas diversions and a drying climate prevent AID from mixing with the rest of the GSL. The timing of human interventions is known, allowing identification of ecosystem response in three sediment cores analyzed for 210Pb chronology, mineralogy, C and N isotopes, pyrolysis, porewater chemistry, and diatom stratigraphy. From these proxies, three events have profoundly altered FB. A sewage canal (1911) brought raw effluent from Salt Lake City, causing a rise in the d15N of organic matter (OM). A corresponding increase in carbonate production occurred as enhanced productivity led to higher pH. Causeway construction (1969) spurred algal growth as FB freshened. Declining water levels (> 1990) resulted in a shrinking volume of bay water, resulting in increased eutrophication. P is elevated in porewater due to OM decay. ~ 0.9 gm−2 year−1 phosphate is released to the water column, compared to an estimated 3.0 gm−2 year−1 surface inflow loading. Although ecosystem improvements may result from AID reductions, improvements in water quality are most easily achieved by restoring surface inflows to FB.

The Nyack floodplain is located on the Middle Fork of the Flathead River, an unregulated, pristine, fifth-order stream in Montana, USA, bordering Glacier National Park. The hyporheic zone is a nutritionally heterogeneous floodplain component harboring a diverse array of microbial assemblages essential in fluvial biogeochemical cycling, riverine ecosystem productivity, and trophic interactions. Despite these functions, microbial community structure in pristine hyporheic systems is not well characterized. The current study was designed to assess whether physical habitat heterogeneity within the hyporheic zone of the Nyack floodplain was sufficient to drive bacterial β diversity between three different hyporheic flow path locations. Habitat heterogeneity was assessed by measuring soluble reactive phosphorous, nitrate, dissolved organic carbon, dissolved oxygen, and soluble total nitrogen levels seasonally at surface water infiltration, advection, and exfiltration zones. Significant spatial differences were detected in dissolved oxygen and nitrate levels, and seasonal differences were detected in dissolved oxygen, nitrate, and dissolved organic carbon levels. Denaturing gradient gel electrophoresis (DGGE) and cell counts indicated that bacterial diversity increased with abundance, and DGGE fingerprints covaried with nitrate levels where water infiltrated the hyporheic zone. The ribosomal gene phylogeny revealed that hyporheic habitat heterogeneity was sufficient to drive β diversity between bacterial assemblages. Phylogenetic (P) tests detected sequence disparity between the flow path locations. Small distinct lineages of Firmicutes, Actinomycetes, Planctomycetes, and Acidobacteria defined the infiltration zone and α- and β-proteobacterial lineages delineated the exfiltration and advection zone communities. These data suggest that spatial habitat heterogeneity drives hyporheic microbial community development and that attempts to understand functional differences between bacteria inhabiting nutritionally heterogeneous hyporheic environments might begin by focusing on the biology of these taxa.

Recombination occurring during meiosis is critical for creating genetic variation and plays an essential role in plant evolution. In addition to creating novel gene combinations, recombination can affect genome structure through altering GC patterns. In maize ( ) and other grasses, another intriguing GC pattern exists. Maize genes show a bimodal GC content distribution that has been attributed to nucleotide bias in the third, or wobble, position of the codon. Recombination may be an underlying driving force given that recombination sites are often associated with high GC content. Here we explore the relationship between recombination and genomic GC patterns by comparing GC gene content at each of the three codon positions (GC , GC , and GC , collectively termed GC ) to instances of a variable GC-rich motif that underlies double strand break (DSB) hotspots and to meiocyte-specific gene expression. Surprisingly, GC bimodality in maize cannot be fully explained by the codon wobble hypothesis. High GC genes show a strong overlap with the DSB hotspot motif, possibly providing a mechanism for the high evolutionary rates seen in these genes. On the other hand, genes that are turned on in meiosis (early prophase I) are biased against both high GC genes and genes with the DSB hotspot motif, possibly allowing important meiotic genes to avoid DSBs. Our data suggests a strong link between the GC-rich motif underlying DSB hotspots and high GC genes.

We investigated changes in UV attenuation and macrozooplankton community structure in a set of lakes along a deglaciation chronosequence in Glacier Bay Alaska. Terrestrial succession in the watersheds of these lakes results in increasing dissolved organic carbon (DOC) content over time. Due to the primary role of DOC in controlling UV attenuation in lakes, one would suspect a gradient in UV attenuation and potentially zooplankton community structure in lakes of different ages. Field measurements of UV in seven lakes of different ages revealed that UV attenuation depths (1% of surface irradiance at 320 nm) ranged from 0.6 m in the oldest lake in the set (90 yr old), to more than 14 m in the youngest lake (10 yr old). Zooplankton community structure also changed across lakes of different ages. Patterns of distribution and abundance of the zooplankton both among and within lakes were consistent with the hypothesis that UV influences zooplankton community structure. The major differences in species composition among lakes were the absence of two primarily epilimnetic species (Asplanchna priodonta and Ceriodaphnia quadrangula) in all but the oldest lake, and the absence of Bosmina longirostris in the four youngest lakes. Transplant experiments in which UV radiation was manipulated in situ revealed that all three of these \"delayed colonizer\" species perish within only a few days when exposed to UV levels found in the surface waters (0.5 m depth) of the youngest lake. The strong dependence of UV radiation transparency on terrestrially derived DOC suggests a linkage between development of terrestrial plant communities within the watershed, changes in lake hydrology, and the early succession of zooplankton communities following deglaciation.