Specimen collection is essential for modern science.

Natural history museums are vital repositories of specimens, samples and data that inform about the natural world; this Formal Comment revisits a Perspective that advocated for the adoption of compassionate collection practices, querying whether it will ever be possible to completely do away with whole animal specimen collection.

miR-486-5p protects against rat ischemic kidney injury and prevents the transition to chronic kidney disease and vascular dysfunction.

AIM: Acute kidney injury (AKI) increases the risk for progressive chronic kidney disease (CKD). MicroRNA (miR)-486-5p protects against kidney ischemia-reperfusion (IR) injury in mice, although its long-term effects on the vasculature and development of CKD are unknown. We studied whether miR-486-5p would prevent the AKI to CKD transition in rat, and affect vascular function. METHODS: Adult male rats were subjected to bilateral kidney IR followed by i.v. injection of liposomal-packaged miR-486-5p (0.5 mg/kg). Kidney function and histologic injury were assessed after 24 h and 10 weeks. Kidney endothelial protein levels were measured by immunoblot and immunofluorescence, and mesenteric artery reactivity was determined by wire myography. RESULTS: In rats with IR, miR-486-5p blocked kidney endothelial cell increases in intercellular adhesion molecule-1 (ICAM-1), reduced neutrophil infiltration and histologic injury, and normalized plasma creatinine (P<0.001). However, miR-486-5p attenuated IR-induced kidney endothelial nitric oxide synthase (eNOS) expression (P<0.05). At 10 weeks, kidneys from rats with IR alone had decreased peritubular capillary density and increased interstitial collagen deposition (P<0.0001), and mesenteric arteries showed impaired endothelium-dependent vasorelaxation (P<0.001). These changes were inhibited by miR-486-5p. Delayed miR-486-5p administration (96 h, 3 weeks after IR) had no impact on kidney fibrosis, capillary density, or endothelial function. CONCLUSION: In rats, administration of miR-486-5p early after kidney IR prevents injury, and protects against CKD development and systemic endothelial dysfunction. These protective effects are associated with inhibition of endothelial ICAM-1 and occur despite reduction in eNOS. miR-486-5p holds promise for the prevention of ischemic AKI and its complications.

Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia.

RATIONALE: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair. OBJECTIVE: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis. METHODS: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms. RESULTS: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms. CONCLUSION: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.

Determination of sensed and paced atrial-ventricular delay in cardiac resynchronization therapy.

BACKGROUND: Optimization of atrial-ventricular delay (AVD) during atrial sensing (SAVD) and pacing (PAVD) provides the most effective cardiac resynchronization therapy (CRT). We demonstrate a novel electrocardiographic methodology for quantifying electrical synchrony and optimizing SAVD/PAVD. METHODS: We studied 40 CRT patients with LV activation delay. Atrial-sensed to RV-sensed (As-RVs) and atrial-paced to RV-sensed (Ap-RVs) intervals were measured from intracardiac electrograms (IEGM). LV-only pacing was performed over a range of SAVD/PAVD settings. Electrical dyssynchrony (cardiac resynchronization index; CRI) was measured at each setting using a multilead ECG system placed over the anterior and posterior torso. Biventricular pacing, which included multiple interventricular delays, was also conducted in a subset of 10 patients. RESULTS: When paced LV-only, peak CRI was similar (93 ± 5% vs. 92 ± 5%) during atrial sensing or pacing but optimal PAVD was 61 ± 31 ms greater than optimal SAVD. The difference between As-RVs and Ap-RVs intervals on IEGMs (62 ± 31 ms) was nearly identical. The slope of the correlation line (0.98) and the correlation coefficient r (0.99) comparing the 2 methods of assessing SAVD-PAVD offset were nearly 1 and the y-intercept (0.63 ms) was near 0. During simultaneous biventricular (BiV) pacing at short AVD, SAVD and PAVD programming did not affect CRI, but CRI was significantly (p < .05) lower during atrial sensing at long AVD. CONCLUSIONS: A novel methodology for measuring electrical dyssynchrony was used to determine electrically optimal SAVD/PAVD during LV-only pacing. When BiV pacing, shorter AVDs produce better electrical synchrony.

Tourniquet Use in the Prehospital Setting.

PURPOSE: Tourniquets are a mainstay of life-saving hemorrhage control. The US military has documented the safety and effectiveness of tourniquet use in combat settings. In civilian settings, events such as the Boston Marathon bombing and mass shootings show that tourniquets are necessary and life-saving entities that must be used correctly and whenever indicated. Much less research has been done on tourniquet use in civilian settings compared to military settings. The purpose of this study is to describe the prehospital use of tourniquets in a regional EMS system served by a single trauma center. METHODS: All documented cases of prehospital tourniquet use from 2015 to 2020 were identified via a search of EMS, emergency department, and inpatient records, and reviewed by the lead investigator. The primary outcomes were duration of tourniquet placement, success of hemorrhage control, and complications; secondary outcomes included time of day (by EMS arrival time), transport interval, extremity involved, who placed/removed the tourniquet, and mechanism of injury. RESULTS: Of 182 patients with 185 tourniquets applied, duration of application was available for 52, with a median (IQR) of 43 (56) minutes. Hemorrhage control was achieved in all but two cases (96%). Three cases (5.8%) required more than one tourniquet. Complications included five cases of temporary paresthesia, one case of ecchymosis, two cases of fasciotomy, and two cases of compression nerve injury. The serious complication rate was 7.7% (4/52). Time of day was daytime (08:01-16:00) = 15 (31.9%), evening (16:01-00:00) = 27 (57.4%), and night (00:01- 08:00) = 5 (10.6%). The median transport interval was 22 (IQR 5] minutes. The limbs most often injured were the left and right upper extremities (15 each). EMS clinicians and police officers were most often the tourniquet placers. Common mechanisms of injury included gunshot wounds, motorcycle accidents, and glass injuries. CONCLUSION: Tourniquets used in the prehospital setting have a high rate of hemorrhage control and a low rate of complications.

Protecting the kidney in sepsis: resident macrophages to the rescue.

Kidney resident macrophages exert pro-inflammatory or reparative effects in experimental acute kidney injury, but their role in sepsis is unclear. In a mouse model of sepsis, Privratsky et al. show that kidney resident F4/80hi macrophages protect against kidney injury by expressing interleukin-1 receptor antagonist, which blocks interleukin-6 production selectively from endothelial cells. Discovery of this novel autocrine loop enhances opportunities for targeted therapies to diminish kidney injury during sepsis.

The island biogeography of human population size.

For decades, biogeographers have sought a better understanding of how organisms are distributed among islands. However, the island biogeography of humans remains largely unknown. Here, we investigate how human population size varies among 486 islands at two spatial scales. At a global scale, we tested whether population size increases with island area and declines with island elevation and nearest mainland, as is common in non-human species, or whether humans escape such biogeographic constraints. At a regional scale, we tested whether population sizes vary among islands within archipelagos according to the positioning of different cultural source pools. Results illustrate that on a global scale, human populations increased in size with island area, similar to non-human species, yet they did not decline in size with elevation and distance to nearest mainland. At a regional scale, human population size often varied among islands within archipelagos relative to the location of different cultural source pools. Despite broad-scale similarities in the geographical distribution of human and non-human species among islands, results from this study indicate that the island biogeography of humans may also be influenced by archipelago-specific social, political and historical circumstances.

Comparative Analysis of Hypertensive Tubulopathy in Animal Models of Hypertension and Its Relevance to Human Pathology.

Assessment of hypertensive tubulopathy for more than fifty animal models of hypertension in experimental pathology employs criteria that do not correspond to lesional descriptors for tubular lesions in clinical pathology. We provide a critical appraisal of experimental hypertension with the same approach used to estimate hypertensive renal tubulopathy in humans. Four models with different pathogenesis of hypertension were analyzed-chronic angiotensin (Ang) II-infused and renin-overexpressing (TTRhRen) mice, spontaneously hypertensive (SHR), and Goldblatt two-kidney one-clip (2K1C) rats. Mouse models, SHR, and the nonclipped kidney in 2K1C rats had no regular signs of hypertensive tubulopathy. Histopathology in animals was mild and limited to variations in the volume density of tubular lumen and epithelium, interstitial space, and interstitial collagen. Affected kidneys in animals demonstrated lesion values that are significantly different compared with healthy controls but correspond to mild damage if compared with hypertensive humans. The most substantial human-like hypertensive tubulopathy was detected in the clipped kidney of 2K1C rats. For the first time, our study demonstrated the regular presence of chronic progressive nephropathy (CPN) in relatively young mice and rats with induced hypertension. Because CPN may confound the assessment of rodent models of hypertension, proliferative markers should be used to verify nonhypertensive tubulopathy.

Sampling affects population genetic inference: A case study of the Allen's (Selasphorus sasin) and rufous hummingbird (Selasphorus rufus).

Gene flow can affect evolutionary inference when species are undersampled. Here, we evaluate the effects of gene flow and geographic sampling on demographic inference of 2 hummingbirds that hybridize, Allen's hummingbird (Selasphorus sasin) and rufous hummingbird (Selasphorus rufus). Using whole-genome data and extensive geographic sampling, we find widespread connectivity, with introgression far beyond the Allen's × rufous hybrid zone, although the Z chromosome resists introgression beyond the hybrid zone. We test alternative hypotheses of speciation history of Allen's, rufous, and Calliope (S. calliope) hummingbird and find that rufous hummingbird is the sister taxon to Allen's hummingbird, and Calliope hummingbird is the outgroup. A model treating the 2 subspecies of Allen's hummingbird as a single panmictic population fit observed genetic data better than models treating the subspecies as distinct populations, in contrast to morphological and behavioral differences and analyses of spatial population structure. With additional sampling, our study builds upon recent studies that came to conflicting conclusions regarding the evolutionary histories of these 2 species. Our results stress the importance of thorough geographic sampling when assessing demographic history in the presence of gene flow.

miRNA-486-5p: signaling targets and role in non-malignant disease.

MicroRNAs (miRNAs) are short non-coding RNAs, highly conserved between species, that are powerful regulators of gene expression. Aberrant expression of miRNAs alters biological processes and pathways linked to human disease. miR-486-5p is a muscle-enriched miRNA localized to the cytoplasm and nucleus, and is highly abundant in human plasma and enriched in small extracellular vesicles. Studies of malignant and non-malignant diseases, including kidney diseases, have found correlations with circulating miR-486-5p levels, supporting its role as a potential biomarker. Pre-clinical studies of non-malignant diseases have identified miR-486-5p targets that regulate major signaling pathways involved in cellular proliferation, migration, angiogenesis, and apoptosis. Validated miR-486-5p targets include phosphatase and tensin homolog (PTEN) and FoXO1, whose suppression activates phosphatidyl inositol-3-kinase (PI3K)/Akt signaling. Targeting of Smad1/2/4 and IGF-1 by miR-486-5p inhibits transforming growth factor (TGF)-ß and insulin-like growth factor-1 (IGF-1) signaling, respectively. Other miR-486-5p targets include matrix metalloproteinase-19 (MMP-19), Sp5, histone acetyltransferase 1 (HAT1), and nuclear factor of activated T cells-5 (NFAT5). In this review, we examine the biogenesis, regulation, validated gene targets and biological effects of miR-486-5p in non-malignant diseases.

EMS Non-Transport of Low-Risk COVID-19 Patients.

Objectives: COVID-19 infections in the community have the potential to overwhelm both prehospital and in-hospital resources. Transport of well-appearing patients, in the absence of available emergency department treatment capacity, increases strain on the hospital and EMS system. In May of 2020, the Connecticut Office of EMS issued a voluntary, EMS-initiated, non-transport protocol for selected low-risk patients with symptoms consistent with COVID-19. We evaluated the implementation of this non-transport protocol in a mixed urban/suburban EMS system.Methods: We conducted a retrospective review of contemporaneously recorded quality improvement documentation for uses of the Connecticut COVID-19 non-transport protocol by EMS clinicians within our EMS system during two implementations: from 12/14/2020 to 5/1/21, and again from 1/3/22 to 2/18/22, which coincided with large COVID-19 case surges in our region.Results: The vast majority of patients treated under the non-transport protocol were not reevaluated by EMS or in our emergency departments in the subsequent 24 hours. There was reasonable adherence to the protocol, with 83% of cases appropriate for the non-transport protocol. The most common reasons for protocol violations were age outside of protocol scope (pediatric patients), failure of documentation, or vital signs outside of the established protocol parameters. We did not find an increased 24-hour ED visit rate in patients who were inappropriately triaged to the protocol. Of patients who had ED visits within 24 hours, only two were admitted, none to higher levels of care.Conclusion: Within this small study, EMS clinicians in our system were able to safely and accurately apply a non-transport protocol for patients presenting with symptoms consistent with COVID-19. This is consistent with previous literature suggesting that EMS-initiated non-transport is a viable strategy to reduce the burden on health systems.

An Evaluation of Prehospital Adenosine Use.

BACKGROUND: Adenosine has been safely used by paramedics for the treatment of stable supraventricular tachycardia since the mid-1990s. However, there continues to be variability in paramedics' ability to identify appropriate indications for adenosine administration. As the first of a planned series of studies aimed at improving the accuracy of SVT diagnosis and successful administration of adenosine by paramedics, this study details the current usage patterns of adenosine by paramedics. METHODS: This cross-sectional retrospective study investigated adenosine use within a large northeast EMS region from January 1, 2019, through September 30, 2021. Excluding pediatric and duplicate case reports, we created a dataset containing patient age, sex, and vital signs before, during, and after adenosine administration; intravenous line location; and coded medical history from paramedic narrative documentation, including a history of atrial fibrillation, suspected arrhythmia diagnosis, and effect of adenosine. In cases with available prehospital electrocardiograms (EKGs) for review, two physicians independently coded the arrhythmia diagnosis and outcome of adenosine administration. Statistical analysis included interrater reliability with Cohen's kappa statistic. RESULTS: One hundred eighty-three cases were included for final analysis, 84 did not have a documented EKG for review. Categorization of presenting rhythms in these cases occurred by a physician reviewing EMS narrative and documentation. Forty of these 84 cases (48%) were adjudicated as SVT likely, 32 (38%) as SVT unlikely and 12 (14%) as uncategorized due to lack of supporting documentation. Of the 99 cases with EKGs available to review, there was substantial agreement of arrhythmia diagnosis interpretation between physician reviewers (Cohen's kappa 0.77-1.0); 54 cases were adjudicated as SVT by two physician reviewers. Other identified cardiac rhythms included atrial fibrillation (16), sinus tachycardia (11), and ventricular tachycardia (2). Adenosine cardioversion occurred in 47 of the 99 cases with EKGs available for physician review (47.5%). Adenosine cardioversion was also deemed to occur in 87% (47/54) of cases when the EKG rhythm was physician adjudicated SVT. CONCLUSIONS: This study supports the use of adenosine as a prehospital treatment for SVT while highlighting the need for continued efforts to improve paramedics' identification and management of tachyarrhythmias.

LungMAP Portal Ecosystem: Systems-Level Exploration of the Lung.

An improved understanding of the human lung necessitates advanced systems models informed by an ever-increasing repertoire of molecular omics, cellular, imaging, and pathological datasets. To centralize and standardize information across broad lung research efforts we expanded the LungMAP.net website into a new gateway portal. This portal connects a broad spectrum of research networks, bulk and single-cell multi-omics data and a diverse collection of image data that span mammalian lung development, and disease. The data are standardized across species and technologies using harmonized data and metadata models that leverage recent advances including those from the Human Cell Atlas, diverse ontologies, and the LungMAP CellCards initiative. To cultivate future discoveries, we have aggregated a diverse collection of single-cell atlases for multiple species (human, rhesus, mouse), to enable consistent queries across technologies, cohorts, age, disease, and drug treatment. These atlases are provided as independent and integrated queryable datasets, with an emphasis on dynamic visualization, figure generation, re-analysis, cell-type curation, and automated reference-based classification of user-provided single-cell genomics datasets (Azimuth). As this resource grows, we intend to increase the breadth of available interactive interfaces, supported data types, data portals and datasets from LungMAP and external research efforts.

Renin-Angiotensin System Pathway Therapeutics Associated With Improved Outcomes in Males Hospitalized With COVID-19.

OBJECTIVES: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components. DESIGN: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup ( n = 46), recorded d -dimer ( n = 967), comparing males with females. SETTING: ARBs CORONA I is a multicenter Canadian observational cohort of patients hospitalized with acute COVID-19. This analysis includes patients admitted to 10 large urban hospitals across the four most populated provinces. PATIENTS: One-thousand six-hundred eighty-six patients with polymerase chain reaction-confirmed COVID-19 (February 2020 to March 2021) for acute COVID-19 illness were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Males on ARBs before admission had decreased use of ventilation (adjusted odds ratio [aOR] = 0.52; p = 0.007) and vasopressors (aOR = 0.55; p = 0.011) compared with males not on ARBs or ACE inhibitors. No significant effects were observed in females for these outcomes. The test for interaction was significant for use of ventilation ( p = 0.006) and vasopressors ( p = 0.044) indicating significantly different responses to ARBs according to sex. Males had significantly higher plasma ACE-1 at baseline and angiotensin II at day 7 and 14 than females. CONCLUSIONS: ARBs use was associated with less ventilation and vasopressors in males but not females. Sex-based differences in RAS dysregulation may contribute to sex-based differences in outcomes and responses to ARBs in COVID-19.

Performance of the 2021 Race-Free CKD-EPI Creatinine- and Cystatin C-Based Estimated GFR Equations Among Kidney Transplant Recipients.

RATIONALE & OBJECTIVE: Race-free estimated glomerular filtration rate (eGFR) equations incorporating creatinine with and without cystatin C were recently developed and recommended for routine use. However, the performance of these equations among kidney transplant recipients (KTRs) remains unknown. STUDY DESIGN: Cross-sectional study to validate the 2021 race-free Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) eGFR equation based on creatinine alone (eGFRcr) or based on creatinine and cystatin C (eGFRcr-cys) among KTRs. SETTING & PARTICIPANTS: KTRs in stable condition (N = 415) from Canada and New Zealand with same-day measurements of creatinine, cystatin C, and glomerular filtration rate (GFR) using radiolabeled diethylenetriaminepentaacetic acid. TESTS COMPARED: The 2009 CKD-EPI eGFRcr, 2021 CKD-EPI eGFRcr, 2012 CKD-EPI eGFRcr-cys, 2021 CKD-EPI eGFRcr-cys, 2012 CKD-EPI eGFRcys, and Modification of Diet in Renal Disease (MDRD) Study eGFR equations were compared with measured GFR. OUTCOMES: Bias, precision, accuracy, and correct classification by CKD stage. Bias was defined as the difference between estimated and measured GFR. Precision was represented by the interquartile range. Accuracy was defined as the percentages of participants with eGFRs within 10%/20%/30% (P10/P20/P30) of measured GFR, root mean square error, and mean absolute error. RESULTS: 87% of patients studied were White, 3% Black, and 10% other races. Mean measured GFR was 53 ± 19 (SD) mL/min/1.73 m2. The 2009 and 2021 CKD-EPI eGFRcr equations demonstrated similar median bias (-2.3 vs -0.2 mL/min/1.73 m2, respectively), precision (14.5 vs 14.9 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/65%/84% vs 33%/63%/84%). The 2012 and 2021 CKD-EPI eGFRcr-cys equations also demonstrated similar median bias (-3.6 vs 0.3 mL/min/1.73 m2, respectively), precision (13.3 vs 14.3 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/63%/80% vs 32%/67%/83%). No clear difference in performance was detected between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations among KTRs. The proportion of correct classification by CKD stage was similar across all eGFR equations. LIMITATIONS: Moderate sample size, few patients had a GFR <30 mL/min/1.73 m2, and the large majority of patients were White. CONCLUSIONS: Among KTRs, the 2021 race-free CKD-EPI eGFR equations perform similarly to the previous CKD-EPI equations that included race correction terms. No significant difference in performance was observed between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations in the kidney transplant population.

Renal Hemodynamics and Renin-Angiotensin-Aldosterone System Profiles in Patients With Heart Failure.

OBJECTIVE: Understanding cardiorenal pathophysiology in heart failure (HF) is of clinical importance. We sought to characterize the renal hemodynamic function and the transrenal gradient of the renin-angiotensin-aldosterone system (RAAS) markers in patients with HF and in controls without HF. METHODS: In this post hoc analysis, the glomerular filtration rate (GFRinulin), effective renal plasma flow (ERPFPAH) and transrenal gradients (arterial-renal vein) of angiotensin converting enzyme (ACE), aldosterone, and plasma renin activity (PRA) were measured in 47 patients with HF and in 24 controls. Gomez equations were used to derive afferent (RA) and efferent (RE) arteriolar resistances. Transrenal RAAS gradients were also collected in patients treated with intravenous dobutamine (HF, n = 11; non-HF, n = 11) or nitroprusside (HF, n = 18; non-HF, n = 5). RESULTS: The concentrations of PRA, aldosterone and ACE were higher in the renal vein vs the artery in patients with HF vs patients without HF (P < 0.01). In patients with HF, a greater ACE gradient was associated with greater renal vascular resistance (r = 0.42; P 0.007) and greater arteriolar resistances (RA: r = 0.39; P = 0.012; RE: r = 0.48; P = 0.002). Similarly, a greater aldosterone gradient was associated with lower GFR (r = -0.51; P = 0.0007) and renal blood flow (RBF), r = -0.32; P = 0.042) whereas greater PRA gradient with lower ERPF (r = -0.33; P = 0.040), GFR (r = -0.36; P = 0.024), and RBF (r = -0.33; P = 0.036). Dobutamine and nitroprusside treatment decreased the transrenal gradient of ACE (P = 0.012, P < 0.0001, respectively), aldosterone (P = 0.005, P = 0.030) and PRA (P = 0.014, P = 0.002) in patients with HF only. CONCLUSIONS: A larger transrenal RAAS marker gradient in patients with HF suggests a renal origin for neurohormonal activation associated with a vasoconstrictive renal profile.

Implementation of Baltimore City's COVID-19 Isolation Hotel.

In May 2020, Baltimore City, Maryland, implemented the Lord Baltimore Triage, Respite, and Isolation Center (LBTC), a multiagency COVID-19 isolation and quarantine site tailored for people experiencing homelessness. In the first year, 2020 individuals were served, 78% completed isolation at LBTC, and 6% were transferred to a hospital. Successful isolation can mitigate outbreaks in shelters and residential recovery programs, and planning for sustainable isolation services integrated within these settings is critical as the COVID-19 pandemic continues. (Am J Public Health. 2022;112(6):876-880. https://doi.org/10.2105/AJPH.2022.306778).

Early Changes in Patient Access Interval during the COVID-19 Pandemic.

Background: COVID-19 was first reported in the United States in January 2020. Its spread throughout the country required EMS systems to rapidly adapt to patient needs while protecting EMS personnel. EMS agencies developed protocols requiring personnel to don enhanced personal protective equipment prior to patient contact. We hypothesized that the Patient Access Interval (PAI), defined as the time from wheels stopped on scene to initial patient contact, had increased during the COVID pandemic. This had the potential to affect patient outcomes, particularly in time-sensitive emergencies such as cardiac arrest or respiratory distress. Methods: This retrospective cohort study used commercial ambulance data from the four largest cities in Connecticut at two different time points: (Pre-COVID) March-May 2019, and (COVID) March-May 2020. PAI was calculated from contemporaneously reported scene times. Total cases were analyzed, and sub-analyses performed for calls located at extended care facilities (ECFs), for all emergent (Echo/Delta) calls, and for medical cardiac arrest calls. Results: 92,846 total cases were evaluated: 50,083 from 2019, and 42,763 from 2020. Cases that did not include necessary time data for PAI were removed, yielding 75,796 total cases (41,852 from 2019, 33,944 from 2020). The average PAI increased from 1 minute 55 seconds (1 m:55s) Pre-COVID to 2 m:18s COVID. ECF PAI increased from 2 m:39s to 3 m:42s. Echo/Delta PAI increased from 1 m:42s to 2 m:07s. Medical cardiac arrest PAI increased from 1 m:27s to 2 m:04s, and ECF cardiac arrest PAI increased from 2 m:18s to 4 m:35s (all comparisons p < 0.01). Conclusions: There were statistically significant increases in all studied PAIs during COVID. The 23 second increase in PAI for all calls may not have been clinically significant in most cases; however, for life-threatening patient presentations, the increase may have been particularly relevant. The increased PAI was compounded in the ECF environment, possibly due to state-mandated screening and temperature checks of EMS personnel before entering facilities. This was highlighted in the ECF cardiac arrest data, which demonstrated a clinically significant increase in PAI of 2m:17s. While this study was limited by the accuracy of contemporaneous time reports by EMS, the results support our hypothesis that PAI had increased during the COVID pandemic.

Xenbase: deep integration of GEO & SRA RNA-seq and ChIP-seq data in a model organism database.

Xenbase (www.xenbase.org) is a knowledge base for researchers and biomedical scientists that employ the amphibian Xenopus as a model organism in biomedical research to gain a deeper understanding of developmental and disease processes. Through expert curation and automated data provisioning from various sources Xenbase strives to integrate the body of knowledge on Xenopus genomics and biology together with the visualization of biologically significant interactions. Most current studies utilize next generation sequencing (NGS) but until now the results of different experiments were difficult to compare and not integrated with other Xenbase content. Xenbase has developed a suite of tools, interfaces and data processing pipelines that transforms NCBI Gene Expression Omnibus (GEO) NGS content into deeply integrated gene expression and chromatin data, mapping all aligned reads to the most recent genome builds. This content can be queried and visualized via multiple tools and also provides the basis for future automated 'gene expression as a phenotype' and gene regulatory network analyses.

Relationship between QRS duration and resynchronization window for CRT optimization: Implications for CRT in narrow QRS patients.

AIMS: Cardiac resynchronization therapy (CRT) response is proportional to QRS duration (QRSd). We hypothesize that this is, in part, due to slower conduction velocity and hence wider range of programmed device settings that produce adequate electrical wavefront fusion and resynchronization in wider QRSd patients. METHODS: CRT patients (n = 122) with left ventricular (LV) conduction delay, sinus rhythm and intact atrioventricular node conduction were studied. Patients were categorized by QRSd: narrow (<120 ms; n = 20); moderate (120-150 ms, n = 37); and prolonged (≥150 ms; n = 65). Electrocardiographic data was acquired during native rhythm and LV-only pacing at varying atrioventricular delays (AVDs). Electrical synchrony was quantified as cardiac resynchronization index (CRI) using multi­lead electrocardiographic systems and a proprietary algorithm that quantified wavefront fusion. A Gaussian distribution equation was fitted to CRI response. RESULTS: Peak CRI was high (87.6 ± 6.3%) and similar (p = 0.716) across QRSd groups. The standard deviation of the Gaussian distribution significantly correlated with QRSd (R = 0.614, p < 0.001), and progressively and significantly (p < 0.001) increased as QRSd increased from narrow (34.8 ± 10.0 ms), to moderate (50.6 ± 8.4 ms), to prolonged (67.6 ± 18.3 ms). At AVDs 20 and 40 ms from optimal, CRI differed significantly (p < 0.001) between groups, with progressively higher CRI values as native QRSd increased. CONCLUSION: Electrical resynchronization with optimally programmed LV-only pacing was similar between patients with varying QRSd, including patients with narrow QRSd. The resynchronization window that corresponded with optimal electrical resynchronization decreased as native QRSd decreased. This finding provides one potential explanation for the lack of significant benefit of CRT in narrow QRSd patients in previous studies.