Potential Surrogate Research Articles

Dynamics of SARS-CoV-2 in wastewater in three districts of the Buenos Aires metropolitan region, Argentina, throughout nine months of surveillance: A pilot study

In the current pandemic of COVID-19, sewage surveillance of SARS-CoV-2 genome has been used to complement viral epidemiology in different countries. The aim of this work was to introduce and evaluate this wastewater-based tool in the metropolitan region of Buenos Aires, Argentina. As a pilot study, surveillance of SARS-CoV-2 in wastewater from three districts of this area was performed for more than nine months from June 2020 to April 2021. Viruses present in the samples were concentrated using polyethylene glycol precipitation and quantified using RT-qPCR CDC N1 assay. Virus recovery for SARS-CoV-2 and a potential surrogate, bovine coronavirus Mebus strain, that shares the Betacoronavirus genus and structural characteristics with SARS-CoV-2, were evaluated after concentration and detection procedures. Recovery of both viruses did not differ significantly, with a median for SARS-CoV-2 and BCoV of 0.085 (95% CI: 0.021-0.179) and 0.262 (95% CI: 1.18 × 10-5-0.564) respectively. The concentration of SARS-CoV-2 genome in wastewater ranged from 10 -1 to 10 3 cg/ml, depending on the wastewater treatment plant, type of collection site, viral recovery of the concentration method and the epidemiological situation of the outbreaks. Significant correlations were observed between SARS-CoV-2 concentration in wastewater and reported clinical cases, reinforcing the utility of this approach to monitor the epidemiological status of populations.

Quantitative susceptibility mapping in ischemic stroke patients after successful recanalization

Quantitative susceptibility mapping (QSM) is a novel processing method for gradient-echo magnetic resonance imaging (MRI). Higher magnetic susceptibility in cortical veins have been observed on susceptibility maps in the ischemic hemisphere of stroke patients, indicating an increased oxygen extraction fraction (OEF). Our goal was to investigate susceptibility in veins of stroke patients after successful recanalization in order to analyze the value of QSM in predicting tissue prognosis and clinical outcome. We analyzed MR images of 23 patients with stroke due to unilateral middle cerebral artery (MCA)-M1/M2 occlusion acquired 24–72 h after successful thrombectomy. The susceptibilities of veins were obtained from QSM and compared between the stroke territory, the ipsilateral non-ischemic MCA territory and the contralateral MCA territory. As outcome variables, early infarct size and functional disability (modified Rankin Scale, mRS) after 3–5 months was used. The median susceptibility value of cortical veins in the ischemic core was 41% lower compared to the ipsilateral non-ischemic MCA territory and 38% lower than on the contralateral MCA territory. Strikingly, in none of the patients prominent vessels with high susceptibility signal were found after recanalization. Venous susceptibility values within the infarct did not correlate with infarct volume or functional disability after 3–5 months. Low venous susceptibility within the infarct core after successful recanalization of the occluded vessel likely indicates poor oxygen extraction arising from tissue damage. We did not identify peri-infarct tissue with increased susceptibility values as potential surrogate of former penumbral areas. We found no correlation of QSM parameters with infarct size or outcome.

The assessment of sarcopenia using psoas muscle thickness per height is not predictive of post-operative complications in IBD

Background Sarcopenia is associated with postoperative complications in inflammatory bowel disease. It has most commonly been defined using the skeletal muscle index, computed after analysis of cross-sectional muscle area at L3. Psoas muscle thickness normalized to height (PMTH), which is easier to derive, is a potential surrogate of SMI and sarcopenia in patients with cirrhosis and chronic pancreatitis. We investigate whether sarcopenia defined by PMTH has utility in predicting post-operative outcomes in patients with inflammatory bowel disease. Methods We performed a retrospective study of adults undergoing IBD-related surgery from 2009 to 2019 at two hospitals. Sarcopenia was defined by sex-specific PMTH at the umbilicus on cross-sectional imaging using a 50th percentile median cutoff. Predictive models were created using variables (BMI, age, sex, smoking status, albumin, INR, platelets, hemoglobin, hypertension, diabetes, CAD, medications) that may be associated with complications (mortality, reoperation, readmission, transfusions, ICU admission, infection, DVT/PE), and sarcopenia for comparison. Results 85 patients with IBD were included. Lower albumin level (OR = 0.52, p = 0.039) and biologic use (OR = 5.92, p = 0.006) were associated with postoperative complications. There was no significant difference using PMTH compared to a model incorporating hypoalbuminemia and biologic use in predicting complications. Sarcopenia on univariate analysis was associated with a lower 30 day rate of reoperation (p = 0.04). Conclusions A low status of PMTH was not associated with increased postoperative complications, however hypoalbuminemia and biologic use were. PMTH as a surrogate for sarcopenia requires further study, ideally with prospective studies comparing PMTH with accepted radiographic surrogates for sarcopenia, to determine its role in clinical decision making.

UV filters used in sunscreens-A lack in current coral protection?

Ultraviolet (UV) filters used in sunscreens are among the anthropogenic substances that may enter the marine environment by both indirect (via wastewater) and direct pathways (leisure activities). Owing to the recent global decline in coral population, the impact of those UV filters on the coral health is currently under increased investigation. First results from scientists suggest that some of the filters may be toxic to various coral life stages, but an initial cross comparison with existing data from other freshwater organisms does not indicate that corals are specifically more susceptible to UV filters than other standard species. In fact, the available data leading to this conclusion is still vague and based on toxicity and bioaccumulation tests with corals, which are both still at the research stage. To facilitate a proper hazard assessment, robust experimental procedures for coral ecotoxicological studies are considered mandatory. In other words, additional steps should be taken to standardize and validate such new test systems to generate reliable results, which then can be used in regulatory decision making. Furthermore, to facilitate a more detailed and site-specific environmental risk assessment in the marine area, an application-based exposure scenario must be developed. Until these data and tools become available, environmental hazard and risk assessments may be carried out using existing data from freshwater organisms and existing tonnage-based exposure scenarios as a potential surrogate. Integr Environ Assess Manag 2021;17:926-939. © 2021 SETAC.

Plant spectral diversity as a surrogate for species, functional and phylogenetic diversity across a hyper‐diverse biogeographic region

AbstractAimWith plant biodiversity under global threat, there is an urgent need to monitor the spatial distribution of multiple axes of biodiversity. Remote sensing is a critical tool in this endeavour. One remote sensing approach for detecting biodiversity is based on the hypothesis that the spectral diversity of plant communities is a surrogate of multiple dimensions of biodiversity. We investigated the generality of this ‘surrogacy’ for spectral, species, functional and phylogenetic diversity across 1,267 plots in the Greater Cape Floristic Region (GCFR), a hyper‐diverse region comprising several biomes and two adjacent global biodiversity hotspots.LocationThe GCFR centred in south‐western and western South Africa.Time periodAll data were collected between 1978–2014.Major taxa studiedVascular plants within the GCFR.MethodsSpectral diversity was calculated using leaf reflectance spectra (450–950 nm) and was related to other dimensions of biodiversity via linear models. The accuracy of different spectral diversity metrics was compared using 10‐fold cross‐validation.ResultsWe found that a distance‐based spectral diversity metric was a robust predictor of species, functional and phylogenetic biodiversity. This result serves as a proof‐of‐concept that spectral diversity is a potential surrogate of biodiversity across a hyper‐diverse biogeographic region. While our results support the generality of spectral diversity as a biodiversity surrogate, we also find that relationships vary between different geographic subregions and biomes, suggesting that differences in broad‐scale community composition can affect these relationships.Main conclusionsSpectral diversity was shown to be a robust surrogate of multiple dimensions of biodiversity across biomes and a widely varying biogeographic region. We also extend these surrogacy relationships to ecological redundancy to demonstrate the potential for additional insights into community structure based on spectral reflectance.

The capacity to designate a surrogate is distinct from decisional capacity: normative and empirical considerations

The capacity to designate a surrogate (CDS) is not simply another kind of medical decision-making capacity (DMC). A patient with DMC can express a preference, understand information relevant to that...

Cross-taxon congruence between predatory arthropods and plants across Mediterranean agricultural landscapes

Although arthropods are among the most diverse, abundant and ecologically important animals in terrestrial ecosystems, they are generally neglected in most biodiversity inventories due to their complex systematics and overwhelming diversity, coupled with the current decline in the number of taxonomists. For this reason, several surrogate groups for arthropod diversity have been proposed, with plants being identified as a good putative cross-taxon indicator. By sampling plants and three groups of ground-dwelling arthropods (rove beetles, ground beetles and spiders) in 300 sites across 15 landscapes including multiple semi-natural and agricultural habitats, we tested for habitat-dependence and scale-dependence in the cross-taxon congruence. Plant species richness was a poor predictor of the species richness of predatory arthropods. Among the predator groups, ground beetles appeared as the best potential surrogate for the other ground-dwelling predators. This is backed by the fact that ground beetles were extremely diverse and abundant in all habitats and are usually easier to identify than both rove beetles and spiders. Decreasing the scale at which the cross-taxon congruence was tested improved the strength of the cross-taxon congruence. Although plant species richness was not a suitable indicator for the diversity of predatory arthropods, vegetation structure played a significant role in influencing cross-taxon congruence in both natural and agricultural habitats. Our results highlight the need to explore the cross-taxon relationships at a fine habitat resolution scale, as strong correlations were obtained only by taking into account habitat identity.

Radiological society of North America: 106th annual meeting, November 29 to December 5, 2020

Radiological society of North America: 106th annual meeting, November 29 to December 5, 2020

Breast Milk–Derived Retinol Is a Potential Surrogate for Serum in the 13C-Retinol Isotope Dilution Test in Zambian Lactating Women with Vitamin A Deficient and Adequate Status

BackgroundVitamin A (VA) deficiency (VAD) affects ∼19 million pregnant women worldwide. The extent of VAD in Zambian women of reproductive age is unknown owing to lack of survey inclusion or the use of static serum retinol concentrations, a low-sensitivity biomarker. ObjectivesThis cross-sectional study employed isotopic techniques to determine VA status with serum and milk among women aged 18–49 y (n = 197) either lactating with infants aged 0–24 mo or nonlactating with or without infants. MethodsAssistants were trained and piloted data collection. Demographic data, anthropometry, and relevant histories were obtained including malaria and anemia. For retinol isotope dilution (RID), baseline fasting blood and casual breast milk samples were collected before administration of 2.0 μmol 13C2-retinyl acetate and 24-h dietary recalls. On day 14, blood (n = 144) and milk (n = 66) were collected. Prevalence of total liver VA reserves (TLR) ≤0.10 μmol/g was defined as VAD with comparison to the DRI assumption of 0.07 μmol/g as minimally acceptable for North Americans. ResultsWhen a 20% adjustment for dose lost to milk was made in the RID equation for lactation, mean total body VA stores (TBS) for lactating women were 25% lower than for nonlactating women (P < 0.01), which was not the case without adjustment (P = 0.3). Mean ± SD TLR for all women were 0.15 ± 0.11 μmol/g liver. Using retinol purified from breast milk instead of serum for RID analysis yielded similar TBS and TLR, which were highly correlated between methods (P < 0.0001). Serum retinol ≤0.70 μmol/L had 0% sensitivity using either VAD liver cutoff and milk retinol ≤1.0 μmol/L had 42% sensitivity for VAD at 0.10 μmol/g. ConclusionsDetermining accurate VA status among women of reproductive age, especially lactating women, forms a basis for extrapolation to the general population and informing policy development and program implementation.

Seeking surrogates for taxonomic and functional evaluations of leaf-litter ant faunas

Comprehensive biodiversity inventories are expensive and time-consuming to achieve, especially for groups of megadiverse organisms. One approach to resolve such situations is to utilize biological substitutes, referred to as surrogates. A surrogate should provide meaningful information at a lower cost and/or effort than the original level of resolution. Studies have shown that species richness is often not the best or most appropriate component or predictor of biodiversity. Functional diversity can be used as a measurement of the ecological differentiation between habitats or between biological functions. We evaluated the use of several taxonomic metrics as potential surrogates for leaf-litter ant assemblages distributed in 65 Atlantic rainforest sites. Our goal was to find reliable and economic substitutes for both taxonomic and functional leaf-litter ant diversity and composition. We tested four potential surrogate approaches for taxonomic metrics and three for functional group metrics. Additionally, we also evaluated the time and costs involved. We used a large leaf-litter ant database that comprises 364 ant species, respectively classified into 13 or 26 ant functional groups based on either a general and specific resolution. Subfamily was found to be an unacceptable surrogate for both taxonomic and functional group metrics. Mixed-level and indicator taxa metrics were rated as ‘excellent’ taxonomic surrogates. Mixed-level and genus metrics were rated as ‘excellent’ or ‘acceptable’ functional group surrogates when considering the most general functional resolution, while mixed-level and genus were considered as ‘excellent’ surrogates when considering the more specific resolution. The monetary and time costs to identify ants to genus level were lower than those using indicator taxa and mixed-level metrics. The use of a certain higher taxon functional and taxonomic surrogates allows a reduction of survey and analysis costs while still enabling the analysis of biological diversity from the taxonomic and functional point of view.

Use of mathematic models to describe the microbial inactivation on baby carrots by gaseous chlorine dioxide

This study investigated the behavior of Shiga toxin-producing Escherichia coli (STEC), Salmonella, and potential surrogate bacteria (nonpathogenic E. coli and attenuated Salmonella) subjected to gaseous chlorine dioxide (ClO2). Pathogenic and surrogate bacteria were separately inoculated on carrots (400 g) and treated with gaseous ClO2 at low (1 g) or high (6 g) ClO2 precursor inputs for 0, 15, 30, and 60 min in a 35 L enclosed chamber. Overall, significant log reductions (P < 0.05) were observed for all treatments after 30 min compared to untreated control. The Weibull model demonstrated a better fit to the experimental data (RMSE = 0.0–0.2), compared to the first-order model (RMSE = 0.3–0.9), which indicated a nonlinear trend. The Weibull model calculated times for a 3-log reduction at the high inputs (6 g ClO2 precursor) were 15.6 and 60.3 min for surrogate E. coli and Salmonella, and 24.6 and 31.3 min for the pathogen counterparts, respectively. Whereas at the low inputs (1 g ClO2 precursor), the times to achieve 3-log reductions increased to 110.3 and 816.6 min for surrogate E. coli and Salmonella, 805.3 and 409.5 min for pathogenic E. coli and Salmonella, respectively. This study provided useful treatment times and concentrations for an effective 3-log microbial reduction via modeling. In addition, potential surrogates were validated for future pilot-scale trials in the processing environment.

Quantifying the synaptic vesicle‐associated protein, VAMP2, to verify changes in cerebrospinal fluid in preclinical stages of Alzheimer’s disease

AbstractBackgroundSynapse loss, a pathological hallmark of Alzheimer’s disease (AD), is quantified in the brain using synaptophysin in western blot and immunohistochemistry, while the in vivo imaging compound 11C‐UCB‐J targets synaptic vesicle glycoprotein 2A (SV2A). Both proteins are characteristic of synaptic vesicles (SVs) and are found in the majority of synapses. Since synaptophysin is not stable in CSF or serum, it is not a suitable marker to monitor synaptic integrity in fluids (Schlaf et al., 1998). Vesicle‐associated membrane protein 2 (VAMP2), another SV component critical for vesicular trafficking, was identified as potential fluid surrogate for synapse loss using relative quantification (Lleo et al., 2019). Here, we have developed a new digital immunoassay for VAMP2 and evaluated its CSF profile in 226 samples from the AD continuum. For comparison the more established post‐synaptic marker Neurogranin (Ng) was included, which is expressed in dendrites of excitatory glutaminergic neurons.MethodThe immunoassay (Simoa) for VAMP2 was established using a commercial rabbit mAb and a novel high‐affinity mouse mAb 15E4. CSF was measured in duplicate on the HD‐1 analyzer across cognitively normal controls (n=68), preclinical AD stage 1 (Amyloidosis +, n=31), preclinical AD stage 2 (Amyloidosis +, neurodegeneration +, n=8), prodromal AD (n=80) and AD dementia (n=39). Ng was quantified with ELISA (EUROIMMUN).ResultThe assay was able to quantify VAMP2 in all CSF samples with an average CV below 10%. Three quality control samples had an inter‐/intra‐assay variability below 10%. VAMP2 levels correlated strongly with Ng in all AD stages (r=0.78‐0.96, p&lt;0.0001). VAMP2 (p&lt;0.0001) and Ng (p&lt;0.0001) were decreased by 40% in preclinical AD stage 1. They were both elevated in the prodromal (VAMP2 25%, p=0.0009; Ng 70%, p&lt;0.0001) and dementia group (VAMP2 25%, p=0.014; Ng 50%, p&lt;0.0001).ConclusionA novel immunoassay for VAMP2 is capable of detecting changes in different AD stages. CSF changes in VAMP2 and Ng precede clinical symptoms and CSF neurodegeneration markers in the AD continuum. In line with observations that CSF‐tau and CSF‐Aβ abnormality precede plaque and tangle load via PET imaging, future longitudinal studies relating synaptic fluid markers with synaptic PET ligands (i.e. 11C‐UCB‐J) could extend these findings.

P017 Sarcopenia Defined by Psoas Muscle Thickness is Not a Predictor of Post-Operative Outcomes in IBD Patients.

BACKGROUND: Sarcopenia, or muscle mass loss, has been associated with post-operative complications in inflammatory bowel disease (IBD). It is commonly diagnosed by skeletal muscle index (SMI), which is computed by specialized software using several cross-sectional muscle areas at the L3 vertebral body level and is labor intensive. In contrast, psoas muscle thickness normalized to height (PMTH) is calculated quickly without specific software and has potential for routine community use. PMTH is a potential surrogate of SMI and sarcopenia in cirrhosis and chronic pancreatitis. Our aim was to investigate whether sarcopenia defined by PMTH has utility in a predictive model for post-operative complications in IBD. METHODS: We performed a retrospective study of adults undergoing IBD related surgical resections from 2009 to 2019 at two hospitals. Patients with MRI or CT scans within 90 days preoperatively to 7 days postoperatively were included. Sarcopenia was defined by sex-specific PMTH at the level of the umbilicus on MRI or CT images using a 50th percentile median cutoff (17.8 mm/m in males, 14.8 mm/m in females). Predictive models were created using variables (BMI, age, gender, smoking status, albumin level, INR, platelet count, hemoglobin level, hypertension, diabetes, coronary artery disease, steroid/immunomodulator/biologic use) associated with complications (defined as mortality within 30 days, reoperation within 30 days, readmission within 90 days, RBC transfusion, ICU admission, sepsis, any infection, or DVT/PE). Additional predictive models were created incorporating sarcopenia for comparison. P-values were obtained using univariate logistic regression with P < 0.05 significant. True area under the curve (AUC) was estimated to be within 0.7 to 0.9, with 0.8 as a cut point for clinical relevance. RESULTS: A total of 85 patients (66% Crohn's disease, 34% Ulcerative colitis, 48 male, 37 female) with mean age 42.5 ± 14.6 were included. Eighty-four patients were on at least one medication for IBD, including 52.4% on steroids, 23.8% on immunomodulators, and 23.8% on biologics. Albumin level (OR = 0.52, P = 0.039) and biologic use (OR = 5.92, P = 0.006) were significantly associated with post-operative complications. The predictive models incorporating sarcopenia, either as a dichotomous variable or PMTH as a continuous variable, were not significantly different from a model with hypoalbuminemia and biologic use (P = 0.73). Sarcopenia on univariate analysis was only significantly associated with lower rate of 30-day reoperation (P = 0.04). CONCLUSION: While PMTH as a surrogate marker for sarcopenia was not a predictor of post-operative outcomes, hypoalbuminemia and biologic use were. An unexpected association between sarcopenia and lower 30-day reoperation rates may be due to hesitancy to take sarcopenic patients back to the operating room. Sarcopenia defined by PMTH may have a role in decision making with nutritional markers, however larger studies that compare PMTH with accepted radiographic surrogates for sarcopenia and risk assessment in IBD patients are needed.

Potential Surrogates for Evaluation of Decontamination Methods Under Field Study Conditions or BSL-2 Biosecurity Lab Conditions: A Review

Surrogate species are commonly used to evaluate the ability of decontamination, sterilization, and/or disinfectant methods to sanitize bio-contaminated surfaces, equipment, facilities, soil, or water. As new decontamination technologies become commercialized there is an ongoing need to evaluate them using field studies, or on-site for large, stationary systems, to determine if they are more environmentally friendly, less expensive, or more effective than the current sanitation practices. This surrogate review compares potential surrogate species such as MS2 bacteriophage, Clostridium difficile, Bacillus subtilis, and Cytisus scoparius for their ability to accurately estimate the efficacy of decontamination, sterilization methods or commercial systems when evaluated under field conditions. Evaluation of decontamination systems, using field or on-site studies conducted under real-world conditions provides realistic estimates of sanitation and insights into potential risks to health or the environment. Multi-stage decontamination systems, or semi-sterilization methods, such as concentrated, or high-level, disinfectants, pressure washing equipment with steam, or extended ultra-violet (UV-C) radiation, require hard-to-kill surrogates, such as B. subtilis, to determine effective treatments. Use of multiple surrogates for decontamination or sterilization research alleviates several concerns about selecting a single surrogate species that may only perform well only under specific treatments or environmental conditions.

Pharmacokinetics of Hydrochlorothiazide in Children: A Potential Surrogate for Renal Secretion Maturation.

Hydrochlorothiazide (HCTZ) is a thiazide diuretic used in adults and children for the treatment of hypertension and edema. The pharmacokinetic (PK) properties of HCTZ in children are not well characterized, particularly among children with obesity who frequently suffer from hypertension and may, therefore, benefit from HCTZ therapy. HCTZ is excreted in the kidney via organic anion transporters 1 and 3 (OAT1 and OAT3). The ontogeny of OAT1 and OAT3 remain unknown, but HCTZ clearance may serve as a surrogate marker of OAT1 and OAT3 maturation. Population PK modeling was performed in NONMEM, and the model was leveraged to conduct dose-exposure simulations. This study examined 83 plasma samples from 49 participants (69% male) taking enteral HCTZ. The median (range) postnatal age was 6.7 years (0.03-19.5 years), and 17 (34%) participants were obese or morbidly obese. The median (range) dose of HCTZ was 0.654 mg/kg (0.11-1.8 kg) and the median number of doses recorded per participant was 5 (1-8). HCTZ PK was well characterized by a 1-compartment PK model. Body weight and a maturation model based on postmenstrual age were significant covariates for apparent clearance, but the presence of obesity was not. Dosing simulations were performed with a standardized 1mg/kg. Simulated exposure (area under the curve and maximum HCTZ concentrations) decreased with age and was likely due to older children receiving the maximum absolute doses of HCTZ. Further studies with more patients in each age group are required to confirm these PK findings of HCTZ in the children.

Genomic Modeling as an Approach to Identify Surrogates for Use in Experimental Validation of SARS-CoV-2 and HuNoV Inactivation by UV-C Treatment.

Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic that continues to pose significant public health concerns. While research to deliver vaccines and antivirals are being pursued, various effective technologies to control its environmental spread are also being targeted. Ultraviolet light (UV-C) technologies are effective against a broad spectrum of microorganisms when used even on large surface areas. In this study, we developed a pyrimidine dinucleotide frequency based genomic model to predict the sensitivity of select enveloped and non-enveloped viruses to UV-C treatments in order to identify potential SARS-CoV-2 and human norovirus surrogates. The results revealed that this model was best fitted using linear regression with r2 = 0.90. The predicted UV-C sensitivity (D90 – dose for 90% inactivation) for SARS-CoV-2 and MERS-CoV was found to be 21.5 and 28 J/m2, respectively (with an estimated 18 J/m2 obtained from published experimental data for SARS-CoV-1), suggesting that coronaviruses are highly sensitive to UV-C light compared to other ssRNA viruses used in this modeling study. Murine hepatitis virus (MHV) A59 strain with a D90 of 21 J/m2 close to that of SARS-CoV-2 was identified as a suitable surrogate to validate SARS-CoV-2 inactivation by UV-C treatment. Furthermore, the non-enveloped human noroviruses (HuNoVs), had predicted D90 values of 69.1, 89, and 77.6 J/m2 for genogroups GI, GII, and GIV, respectively. Murine norovirus (MNV-1) of GV with a D90 = 100 J/m2 was identified as a potential conservative surrogate for UV-C inactivation of these HuNoVs. This study provides useful insights for the identification of potential non-pathogenic (to humans) surrogates to understand inactivation kinetics and their use in experimental validation of UV-C disinfection systems. This approach can be used to narrow the number of surrogates used in testing UV-C inactivation of other human and animal ssRNA viral pathogens for experimental validation that can save cost, labor and time.

Body composition on low dose chest CT is a significant predictor of poor clinical outcome in COVID-19 disease - A multicenter feasibility study

PurposeLow-dose computed tomography (LDCT) of the chest is a recommended diagnostic tool in early stage of COVID-19 pneumonia. High age, several comorbidities as well as poor physical fitness can negatively influence the outcome within COVID-19 infection. We investigated whether the ratio of fat to muscle area, measured in initial LDCT, can predict severe progression of COVID-19 in the follow-up period. MethodWe analyzed 58 individuals with confirmed COVID-19 infection that underwent an initial LDCT in one of two included centers due to COVID-19 infection. Using the ratio of waist circumference per paravertebral muscle circumference (FMR), the body composition was estimated. Patient outcomes were rated on an ordinal scale with higher numbers representing more severe progression or disease associated complications (hospitalization/ intensive care unit (ICU)/ tracheal intubation/ death) within a follow-up period of 22 days after initial LDCT. ResultsIn the initial LDCT a significantly higher FMR was found in patients requiring intensive care treatment within the follow-up period. In multivariate logistic regression analysis, FMR (p < .001) in addition to age (p < .01), was found to be a significant predictor of the necessity for ICU treatment of COVID-19 patients. ConclusionFMR as potential surrogate of body composition and obesity can be easily determined in initial LDCT of COVID-19 patients. Within the multivariate analysis, in addition to patient age, low muscle area in proportion to high fat area represents an additional prognostic information for the patient outcome and the need of an ICU treatment during the follow-up period within the next 22 days.This multicentric pilot study presents a method using an initial LDCT to screen opportunistically for obese patients who have an increased risk for the need of ICU treatment. While clinical capacities, such as ICU beds and ventilators, are more crucial than ever to help manage the current global corona pandemic, this work introduces an approach that can be used for a cost-effective way to help determine the amount of these rare clinical resources required in the near future.

Left Ventricular Mass Index as Potential Surrogate of Muscularity in Patients With Systemic Sclerosis Without Cardiovascular Disease.

Systemic sclerosis (SSc) may be associated with protein-energy malnutrition. It was demonstrated that left ventricular mass (LVM) reflected poor nutrition status in SSc patients, and no data are available on LVM as a surrogate measure of muscularity. We aimed to evaluate, in SSc patients, the relationship between muscle mass and LVM as a novel indicator of muscularity in this setting. SSc patients and healthy controls (HCs) were considered and underwent echocardiography to assess LVM and LVM index (LVMI). Body composition, including fat-free mass index (FFMI), phase angle (PhA), and body cell mass index (BCMI), was analyzed by multifrequency bioelectrical impedance analysis. Sixty-four SSc patients (aged 51 ± 13 years) and 30 HCs (aged 46 ± 13 years) were enrolled. BCMI and PhA were lower in SSc patients compared with HCs (P < .001). LVM and LVMI were not different between SSc patients and HCs (P = .068, P = .14, respectively). In SSc patients, a significant correlation was shown between LVMI and FFMI (τ = 0.192, P = .026); in multiple regression analysis, FFMI was significantly associated with the Malnutrition Universal Screening Tool (P < .0001), LVMI (P = .01), and disease severity scale (P = .02). Changes in body composition were present in SSc patients, particularly in terms of BMCI and PhA. A correlation between LVMI and FFMI as indexes of muscularity exists in this cohort, suggesting that cardiac mass might be used as a surrogate of nutrition status in this setting.

Decay of SARS-CoV-2 and surrogate murine hepatitis virus RNA in untreated wastewater to inform application in wastewater-based epidemiology

Wastewater-based epidemiology (WBE) demonstrates potential for COVID-19 community transmission monitoring; however, data on the stability of SARS-CoV-2 RNA in wastewater are needed to interpret WBE results. The decay rates of RNA from SARS-CoV-2 and a potential surrogate, murine hepatitis virus (MHV), were investigated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in untreated wastewater, autoclaved wastewater, and dechlorinated tap water stored at 4, 15, 25, and 37 °C. Temperature, followed by matrix type, most greatly influenced SARS-CoV-2 RNA first-order decay rates (k). The average T90 (time required for 1-log10 reduction) of SARS-CoV-2 RNA ranged from 8.04 to 27.8 days in untreated wastewater, 5.71 to 43.2 days in autoclaved wastewater, and 9.40 to 58.6 days in tap water. The average T90 for RNA of MHV at 4 to 37 °C ranged from 7.44 to 56.6 days in untreated wastewater, 5.58–43.1 days in autoclaved wastewater, and 10.9 to 43.9 days in tap water. There was no statistically significant difference between RNA decay of SARS-CoV-2 and MHV; thus, MHV is suggested as a suitable persistence surrogate. Decay rate constants for all temperatures were comparable across all matrices for both viral RNAs, except in untreated wastewater for SARS-CoV-2, which showed less sensitivity to elevated temperatures. Therefore, SARS-CoV-2 RNA is likely to persist long enough in untreated wastewater to permit reliable detection for WBE application.

Enrichment differentiation of human induced pluripotent stem cells into sinoatrial node-like cells by combined modulation of BMP, FGF, and RA signaling pathways

BackgroundBiological pacemakers derived from pluripotent stem cell (PSC) have been considered as a potential therapeutic surrogate for sick sinus syndrome. So it is essential to develop highly efficient strategies for enrichment of sinoatrial node-like cells (SANLCs) as seed cells for biological pacemakers. It has been reported that BMP, FGF, and RA signaling pathways are involved in specification of different cardiomyocyte subtypes, pacemaker, ventricular, and atrial cells. We aimed to investigate whether combined modulation of BMP, FGF, and RA signaling pathways could enrich the differentiation of SANLC from human pluripotent stem cell (hiPSC).MethodsDuring the differentiation process from human induced pluripotent stem cell to cardiomyocyte through small molecule-based temporal modulation of the Wnt signaling pathway, signaling of BMP, FGF, and RA was manipulated at cardiac mesoderm stage. qRT-PCR, immunofluorescence, flow cytometry, and whole cell patch clamp were used to identify the SANLC.ResultsqRT-PCR results showed that manipulating each one of bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and retinoid acid (RA) signaling was effective for the upregulation of SANLC markers. Moreover, combined modulation of these three pathways displayed the best efficiency for the expression of SANLC markers, which was further confirmed at protein level using immunofluorescence and flow cytometry. Finally, the electrophysiological characteristics of upregulated SANLC were verified by patch clamp method.ConclusionAn efficient transgene-independent differentiation protocol for generating SANLC from hiPSC was developed, in which combined modulating BMP, FGF, and RA signaling at cardiac mesoderm stage generates SANLC at high efficiency. This may serve as a potential approach for biological pacemaker construction.