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  • Management of Lung Nodules and Lung Cancer Screening During the COVID-19 Pandemic: CHEST Expert Panel Report

    Mazzone, P.J.; Gould, M.K.; White, C.S. (Elsevier Inc, 2020)
    Background: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic. Methods: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario. Results: Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non-small cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non-small cell lung cancer. Conclusions: There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care.
  • A distinct class of plant and animal viral proteins that disrupt mitosis by directly interrupting the mitotic entry switch Wee1-Cdc25-Cdk1

    Jin, H.; Li, G.; Zhao, R.Y. (American Association for the Advancement of Science, 2020)
    Many animal viral proteins, e.g., Vpr of HIV-1, disrupt host mitosis by directly interrupting the mitotic entry switch Wee1-Cdc25-Cdk1. However, it is unknown whether plant viruses may use this mechanism in their pathogenesis. Here, we report that the 17K protein, encoded by barley yellow dwarf viruses and related poleroviruses, delays G2/M transition and disrupts mitosis in both host (barley) and nonhost (fission yeast, Arabidopsis thaliana, and tobacco) cells through interrupting the function of Wee1-Cdc25-CDKA/Cdc2 via direct protein-protein interactions and alteration of CDKA/Cdc2 phosphorylation. When ectopically expressed, 17K disrupts the mitosis of cultured human cells, and HIV-1 Vpr inhibits plant cell growth. Furthermore, 17K and Vpr share similar secondary structural feature and common amino acid residues required for interacting with plant CDKA. Thus, our work reveals a distinct class of mitosis regulators that are conserved between plant and animal viruses and play active roles in viral pathogenesis. Copyright 2020 The Authors.
  • Novel malaria antigen Plasmodium yoelii E140 induces antibody-mediated sterile protection in mice against malaria challenge

    Smith, E.C.; Limbach, K.J.; Sacci, J.B.Jr (Public Library of Science, 2020)
    Only a small fraction of the antigens expressed by malaria parasites have been evaluated as vaccine candidates. A successful malaria subunit vaccine will likely require multiple antigenic targets to achieve broad protection with high protective efficacy. Here we describe protective efficacy of a novel antigen, Plasmodium yoelii (Py) E140 (PyE140), evaluated against P. yoelii challenge of mice. Vaccines targeting PyE140 reproducibly induced up to 100% sterile protection in both inbred and outbred murine challenge models. Although PyE140 immunization induced high frequency and multifunctional CD8+ T cell responses, as well as CD4+ T cell responses, protection was mediated by PyE140 antibodies acting against blood stage parasites. Protection in mice was long-lasting with up to 100% sterile protection at twelve weeks post-immunization and durable high titer anti-PyE140 antibodies. The E140 antigen is expressed in all Plasmodium species, is highly conserved in both P. falciparum lab-adapted strains and endemic circulating parasites, and is thus a promising lead vaccine candidate for future evaluation against human malaria parasite species. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
  • Effects of larval exposure to sublethal doses of Bacillus thuringiensis var. israelensis on body size, oviposition and survival of adult Anopheles coluzzii mosquitoes

    Gowelo, S.; Chirombo, J.; McCann, R. (Springer Nature, 2020)
    BACKGROUND: Application of the larvicide Bacillus thuringiensis var. israelensis (Bti) is a viable complementary strategy for malaria control. Efficacy of Bti is dose-dependent. There is a knowledge gap on the effects of larval exposure to sublethal Bti doses on emerging adult mosquitoes. The present study examined the effect of larval exposure to sublethal doses of Bti on the survival, body size and oviposition rate in adult Anopheles coluzzii. METHODS: Third-instar An. coluzzii larvae were exposed to control and sublethal Bti concentrations at LC20, LC50 and LC70 for 48 h. Surviving larvae were reared to adults under standard colony conditions. Thirty randomly selected females from each treatment were placed in separate cages and allowed to blood feed. Twenty-five gravid females from the blood-feeding cages were randomly selected and transferred into new cages where they were provided with oviposition cups. Numbers of eggs laid in each cage and mortality of all adult mosquitoes were recorded daily. Wing lengths were measured of 570 mosquitoes as a proxy for body size. RESULTS: Exposure to LC70Bti doses for 48 h as third-instar larvae reduced longevity of adult An. coluzzii mosquitoes. Time to death was 2.58 times shorter in females exposed to LC70Bti when compared to the control females. Estimated mortality hazard rates were also higher in females exposed to the LC50 and LC20 treatments, but these differences were not statistically significant. The females exposed to LC70 concentrations had 12% longer wings than the control group (P < 0.01). No differences in oviposition rate of the gravid females were observed between the treatments. CONCLUSIONS: Exposure of An. coluzzii larvae to sublethal Bti doses reduces longevity of resultant adults and is associated with larger adult size and unclear effect on oviposition. These findings suggest that anopheline larval exposure to sublethal Bti doses, though not recommended, could reduce vectorial capacity for malaria vector populations by increasing mortality of resultant adults.
  • Long-term exposure to particulate air pollution and brachial artery flow-mediated dilation in the Old Order Amish

    Salimi, S.; Vogel, R.; Mitchell, B.D. (BioMed Central Ltd., 2020)
    Background: Atmospheric particulate matter (PM) has been associated with endothelial dysfunction, an early marker of cardiovascular risk. Our aim was to extend this research to a genetically homogenous, geographically stable rural population using location-specific moving-average air pollution exposure estimates indexed to the date of endothelial function measurement. Methods: We measured endothelial function using brachial artery flow-mediated dilation (FMD) in 615 community-dwelling healthy Amish participants. Exposures to PM &lt; 2.5 ?m (PM2.5) and PM &lt; 10 ?m (PM10) were estimated at participants' residential addresses using previously developed geographic information system-based spatio-temporal models and normalized. Associations between PM exposures and FMD were evaluated using linear mixed-effects regression models, and polynomial distributed lag (PDL) models followed by Bayesian model averaging (BMA) were used to assess response to delayed effects occurring across multiple months. Results: Exposure to PM10 was consistently inversely associated with FMD, with the strongest (most negative) association for a 12-month moving average (- 0.09; 95% CI: - 0.15, - 0.03). Associations with PM2.5 were also strongest for a 12-month moving average but were weaker than for PM10 (- 0.07; 95% CI: - 0.13, - 0.09). Associations of PM2.5 and PM10 with FMD were somewhat stronger in men than in women, particularly for PM10. Conclusions: Using location-specific moving-average air pollution exposure estimates, we have shown that 12-month moving-average estimates of PM2.5 and PM10 exposure are associated with impaired endothelial function in a rural population. Copyright 2020 The Author(s).
  • BICORN: An R package for integrative inference of de novo cis-regulatory modules

    Chen, X.; Gu, J.; Neuwald, A.F. (Nature Research, 2020)
    Genome-wide transcription factor (TF) binding signal analyses reveal co-localization of TF binding sites based on inferred cis-regulatory modules (CRMs). CRMs play a key role in understanding the cooperation of multiple TFs under specific conditions. However, the functions of CRMs and their effects on nearby gene transcription are highly dynamic and context-specific and therefore are challenging to characterize. BICORN (Bayesian Inference of COoperative Regulatory Network) builds a hierarchical Bayesian model and infers context-specific CRMs based on TF-gene binding events and gene expression data for a particular cell type. BICORN automatically searches for a list of candidate CRMs based on the input TF bindings at regulatory regions associated with genes of interest. Applying Gibbs sampling, BICORN iteratively estimates model parameters of CRMs, TF activities, and corresponding regulation on gene transcription, which it models as a sparse network of functional CRMs regulating target genes. The BICORN package is implemented in R (version 3.4 or later) and is publicly available on the CRAN server at
  • A Screening Tool for the Direct Analysis of Marine and Freshwater Phycotoxins in Organic SPATT Extracts from the Chesapeake Bay

    Onofrio, M.D.; Mallet, C.R.; Place, A.R. (MDPI, AG, 2020)
    Many detection methods for phycotoxins, bioactive compounds produced by harmful algae, focus on one compound or a class of related compounds. Multiple harmful algal species often co-occur in the environment, however, emphasizing the need to analyze for the presence of multiple groups of marine and freshwater phycotoxins in environmental samples, e.g., extracts from solid phase adsorption toxin tracking (SPATT). Two methods were developed to screen for 13 phycotoxins (microcystin-RR, -LR, -YR, azaspiracid-1, -2, karlotoxin 3, goniodomin A, brevetoxin-2, yessotoxin, pectenotoxin-2, dinophysistoxin-1, -2, and okadaic acid) in organic SPATT extracts using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) equipped with a trapping dimension (trap) and at-column dilution (ACD). The performance of each compound under 36 combinations of chromatographic conditions was characterized, and two final methods, acidic and basic, were selected based on peak shapes, signal intensities, resolution, and the separation in time of positive and negative MS ionization modes. Injection volumes of up to 1 mL were possible through trap/ACD technology, resulting in limits of detection between 0.001 and 0.05 �g/L across the analytes. Benefits highlighted in this study, beyond the improved detection limits and co-detection of multiple toxin groups, include the ability to inject samples of 100% organic solvent, ensuring analyte stability and streamlining workflow through the elimination of laborious sample preparation steps.
  • Chronic Sympathetic Hyperactivity Triggers Electrophysiological Remodeling and Disrupts Excitation-Contraction Coupling in Heart

    Joca, H.C.; Santos?Miranda, A.; Williams, G.S.B. (Nature Research, 2020)
    The sympathetic nervous system is essential for maintenance of cardiac function via activation of post-junctional adrenergic receptors. Prolonged adrenergic receptor activation, however, has deleterious long-term effects leading to hypertrophy and the development of heart failure. Here we investigate the effect of chronic adrenergic receptors activation on excitation-contraction coupling (ECC) in ventricular cardiomyocytes from a previously characterized mouse model of chronic sympathetic hyperactivity, which are genetically deficient in the adrenoceptor ?2A and ?2C genes (ARDKO). When compared to wild-type (WT) cardiomyocytes, ARDKO displayed reduced fractional shortening (~33%) and slower relaxation (~20%). Furthermore, ARDKO cells exhibited several electrophysiological changes such as action potential (AP) prolongation (~50%), reduced L-type calcium channel (LCC) current (~33%), reduced outward potassium (K+) currents (~30%), and increased sodium/calcium exchanger (NCX) activity (~52%). Consistent with reduced contractility and calcium (Ca2+) currents, the cytosolic Ca2+ ([Ca2+]i) transient from ARDKO animals was smaller and decayed slower. Importantly, no changes were observed in membrane resting potential, AP amplitude, or the inward K+ current. Finally, we modified our existing cardiac ECC computational model to account for changes in the ARDKO heart. Simulations suggest that cellular changes in the ARDKO heart resulted in variable and dyssynchronous Ca2+-induced Ca2+ release therefore altering [Ca2+]i transient dynamics and reducing force generation. In conclusion, chronic sympathetic hyperactivity impairs ECC by changing the density of several ionic currents (and thus AP repolarization) causing altered Ca2+ dynamics and contractile activity. This demonstrates the important role of ECC remodeling in the cardiac dysfunction secondary to chronic sympathetic activity. Copyright 2020, The Author(s).
  • Challenges in the diagnosis of tuberculous meningitis

    Foppiano Palacios, C.; Saleeb, P.G. (Elsevier Ltd, 2020)
    Tuberculosis (TB) continues to pose a significant public health problem. Tuberculous meningitis (TBM) is the most severe form of extra-pulmonary TB. TBM carries a high mortality rate, including for those receiving treatment for TB. Diagnosis of TBM is difficult for clinicians as it can clinically present similarly to other forms of meningitis. The difficulty in diagnosis often leads to a delay in treatment and subsequent mortality. Those who survive are left with long-term sequelae leading to lifelong disability. The microbiologic diagnosis of TBM requires the isolation of Mycobacterium tuberculosis from the cerebrospinal fluid (CSF) of an infected patient. The diagnosis of tuberculous meningitis continues to be challenging for clinicians. Unfortunately, many cases of TBM cannot be confirmed based on clinical and imaging findings as the clinical findings are nonspecific, while laboratory techniques are largely insensitive or slow. Until recently, the lack of accessible and timely tests has contributed to a delay in diagnosis and subsequent morbidity and mortality for many patients, particularly those in resourcelimited settings. The availability of Xpert Ultra and point-of-care lipoarabinomannan (LAM) testing could represent a new era of prompt diagnosis and early treatment of tuberculous meningitis. However, clinicians must be cautious when ruling out TBM with Xpert Ultra due to its low negative predictive value. Due to the limitations of current diagnostics, clinicians should utilize a combination of diagnostic modalities in order to prevent morbidity in patients with TBM. Copyright 2020 The Author(s)
  • Medical management of primary hyperparathyroidism in pregnancy: A case report and brief literature review

    Ning, X.; Rahman, W.; Malek, R. (Elmer Press, 2020)
    There is no established standard of care for the medical management of primary hyperparathyroidism in pregnancy for those patients who are not surgical candidates. We present a case of primary hyperpar-athyroidism in the third trimester that was managed with cinacalcet and a literature review on the various modalities for the medical management of primary hyperparathyroidism in pregnancy. The primary aim of this case report is to document a case of hyperparathyroidism in pregnancy that was managed medically and to perform a brief systematic review of the literature available on the medical management of primary hyperparathyroidism in pregnancy. The secondary aim is to contribute to the literature available on the use of cinacalcet in pregnancy. A 37-year-old woman with untreated primary hyperpar-athyroidism presented at 32 weeks of gestation with hypercalcemia that was not amenable to surgical intervention. We treated her with in-creasing doses of cinacalcet with improvement in her serum calcium until developing pre-eclampsia which prompted emergent cesarean delivery of the infant. The neonate developed respiratory distress after delivery but did not develop hypocalcemia after birth. The neonate became transiently hypercalcemic in the setting of calcium gluconate infusions given to prevent hypocalcemia. The patient underwent surgical removal of a parathyroid adenoma and required calcium sup-plementation for 1 month afterwards. Hypercalcemic crisis during pregnancy is associated with significant maternal and fetal morbidity. There is limited information regarding the medical management of primary hyperparathyroidism due to the lack of high-powered studies and prospective studies owing to the relative rarity of the condition. No serious adverse maternal events were reported for either bisphos-phonate or cinacalcet use. Adverse neonatal events include transient hypocalcemia of the infant with cinacalcet use and possibly low birth weight, infantile hypocalcemia, and shortened gestational periods with bisphosphonate use. Copyright The authors.
  • Dental sealant empowered by 1,3,5-Tri acryloyl hexahydro-1,3,5-triazine and α-tricalcium phosphate for anti-caries application

    Monteiro, J.C.; Melo, M.A.; Stürmer, M. (MDPI AG, 2020)
    Quaternary ammonium compounds and calcium phosphates have been incorporated into dental materials to enhance their biointeractivity and preventive effects. This study aimed at evaluating the physical and chemical properties and effects against Streptococcus mutans of a dental sealant containing 1,3,5-tri acryloyl hexahydro-1,3,5-triazine (TAT) and ?-tricalcium phosphate (ff-TCP). A methacrylate-based dental sealant was initially formulated. ?-TCP and TAT (G?-TCPTAT) were added to the experimental sealant at 2 wt.% each. One group was formulated without ?-TCP and TAT and used as control (GCTRL). All tested resins were analyzed for polymerization kinetics and degree of conversion (DC %), Knoop hardness (KHN), softening in solvent (DKHN%), ultimate tensile strength (UTS), the contact angle with water or with ?-bromonaphthalene, surface free energy (SFE) and antibacterial activity against Streptococcus mutans in biofilm and in planktonic cells. The polymerization kinetic was different between groups, but without statistical differences in the DC % (p < 0.05). KHN and DKHN% did not change between groups (p > 0.05), but Gff-TCPTAT presented greater UTS compared to GCTRL (p < 0.05). No differences were found for contact angle (p > 0.05) or SFE (p > 0.05). Gff-TCPTAT showed greater antibacterial activity in comparison to GCTRL (p < 0.05). The formulation of dental sealants containing TAT and ff-TCP can be characterized by improved mechanical and antibacterial properties. Copyright 2020 by the authors.
  • Harnessing data science to advance radiation oncology

    Vogelius, I.R.; Petersen, J.; Bentzen, S.M. (John Wiley and Sons Ltd., 2020)
    Radiation oncology, a major treatment modality in the care of patients with malignant disease, is a technology- and computer-intensive medical specialty. As such, it should lend itself ideally to data science methods, where computer science, statistics, and clinical knowledge are combined to advance state-of-the-art care. Nevertheless, data science methods in radiation oncology research are still in their infancy and successful applications leading to improved patient care remain scarce. Here, we discuss data interoperability issues within and across organizational boundaries that hamper the introduction of big data and data science techniques in radiation oncology. At the semantic level, creating common underlying models and codification of the data, including the use of data elements with standardized definitions, an ontology, remains a work in progress. Methodological issues in data science and in the use of large population-based health data registries are identified. We show that data science methods and big data cannot replace randomized clinical trials in comparative effectiveness research by reviewing a series of instances where the outcomes of big data analyses and randomized trials are at odds. We also discuss the modern wave of machine learning and artificial intelligence as represented by deep learning and convolutional neural networks. Finally, we identify promising research avenues and remain optimistic that the data sources in radiation oncology can be linked to yield important insights in the near future. We argue that data science will be a valuable complement to, but not a replacement of, the traditional hypothesis-driven translational research chain and the randomized clinical trials that form the backbone of evidence-based medicine. Copyright 2020 The Authors.
  • Mechanosensing of Mechanical Confinement by Mesenchymal-Like Cells

    Doolin, M.T.; Moriarty, R.A.; Stroka, K.M. (Frontiers Media S.A., 2020)
    Mesenchymal stem cells (MSCs) and tumor cells have the unique capability to migrate out of their native environment and either home or metastasize, respectively, through extremely heterogeneous environments to a distant location. Once there, they can either aid in tissue regrowth or impart an immunomodulatory effect in the case of MSCs, or form secondary tumors in the case of tumor cells. During these journeys, cells experience physically confining forces that impinge on the cell body and the nucleus, ultimately causing a multitude of cellular changes. Most drastically, confining individual MSCs within hydrogels or confining monolayers of MSCs within agarose wells can sway MSC lineage commitment, while applying a confining compressive stress to metastatic tumor cells can increase their invasiveness. In this review, we seek to understand the signaling cascades that occur as cells sense confining forces and how that translates to behavioral changes, including elongated and multinucleated cell morphologies, novel migrational mechanisms, and altered gene expression, leading to a unique MSC secretome that could hold great promise for anti-inflammatory treatments. Through comparison of these altered behaviors, we aim to discern how MSCs alter their lineage selection, while tumor cells may become more aggressive and invasive. Synthesizing this information can be useful for employing MSCs for therapeutic approaches through systemic injections or tissue engineered grafts, and developing improved strategies for metastatic cancer therapies. Copyright � 2020 Doolin, Moriarty and Stroka.
  • Respiratory Protection Considerations for Healthcare Workers During the COVID-19 Pandemic

    Friese, C.R.; Veenema, T.G.; Chang, J.C. (Mary Ann Liebert, 2020)
    The COVID-19 pandemic has resulted in a surge of patients that exceeds available human and physical resources in many settings, triggering the implementation of crisis standards of care. High-quality respiratory protection is essential to reduce exposure among healthcare workers, yet dire shortages of personal protective equipment in the United States threaten the health and safety of this essential workforce. In the context of rapidly changing conditions and incomplete data, this article outlines 3 important strategies to improve healthcare workers' respiratory protection. At a minimum, healthcare workers delivering care to patients with confirmed or suspected COVID-19 should wear N95 respirators and full-face shields. Several mechanisms exist to boost and protect the supply of N95 respirators, including rigorous decontamination protocols, invoking the Defense Production Act, expanded use of reusable elastomeric respirators, and repurposing industrial N95 respirators. Finally, homemade facial coverings do not protect healthcare workers and should be avoided. These strategies, coupled with longer-term strategies of investments in protective equipment research, infrastructure, and data systems, provide a framework to protect healthcare workers immediately and enhance preparedness efforts for future pandemics.
  • Radiation therapy considerations during the COVID-19 Pandemic: Literature review and expert opinions

    Mohindra, P.; Buckey, C.R.; Chen, S. (American Institute of Physics, 2020)
    COVID-19 is an unprecedented pandemic that has already reached over 2 million confirmed cases globally, with at least 140,000 deaths as reported by the World Health Organization (WHO) as of April 16, 2020 1 . More than 662,000 cases have been reported in the United States with more than 29,000 deaths2 . The overall crude mortality rate now stands at 6.6% (may possibly be lower due to under-testing and under-reporting of total confirmed cases), and is highly dependent on age group, comorbidities, and the locoregional resources medically1 . A report from the United States presented age-stratified COVID-19 associated hospitalization rates among 1,482 patients during March 1-28, 2020, highlighting an alarmingly high rate of 74.5% at age > 50 years with underlining medical conditions3 . Based on a data summary report provided by New York City Health, as of April 14, 2020, the shares of a total of 6839 deaths reached 0.04%, 4.5%, 23.1%, 24.6%, and 47.7% for the age groups of 0-17, 18-44, 45-64, 65-74, and 75+ years old4 . All data suggest that adults at a more advanced age group are facing higher morbidity and mortality risks.
  • Crystal Structure and Active Site Engineering of a Halophilic ?-Carbonic Anhydrase

    Vogler, M.; DasSarma, P.; DasSarma, S. (Frontiers Media S.A., 2020)
    Environments previously thought to be uninhabitable offer a tremendous wealth of unexplored microorganisms and enzymes. In this paper, we present the discovery and characterization of a novel γ-carbonic anhydrase (γ-CA) from the polyextreme Red Sea brine pool Discovery Deep (2141 m depth, 44.8°C, 26.2% salt) by single-cell genome sequencing. The extensive analysis of the selected gene helps demonstrate the potential of this culture-independent method. The enzyme was expressed in the bioengineered haloarchaeon Halobacterium sp. NRC-1 and characterized by X-ray crystallography and mutagenesis. The 2.6 Å crystal structure of the protein shows a trimeric arrangement. Within the ?-CA, several possible structural determinants responsible for the enzyme's salt stability could be highlighted. Moreover, the amino acid composition on the protein surface and the intra- and intermolecular interactions within the protein differ significantly from those of its close homologs. To gain further insights into the catalytic residues of the ?-CA enzyme, we created a library of variants around the active site residues and successfully improved the enzyme activity by 17-fold. As several ?-CAs have been reported without measurable activity, this provides further clues as to critical residues. Our study reveals insights into the halophilic ?-CA activity and its unique adaptations. The study of the polyextremophilic carbonic anhydrase provides a basis for outlining insights into strategies for salt adaptation, yielding enzymes with industrially valuable properties, and the underlying mechanisms of protein evolution. Copyright 2020 The Authors.
  • Escherichia coli ST131 clones harbouring AggR and AAF/V fimbriae causing bacteremia in Mozambican children: Emergence of new variant of fimH27 subclone

    Mandomando, I.; Vubil, D.; Levine, M.M. (Public Library of Science, 2020)
    Multidrug-resistant Escherichia coli ST131 fimH30 responsible for extra-intestinal pathogenic (ExPEC) infections is globally distributed. However, the occurrence of a subclone fimH27 of ST131 harboring both ExPEC and enteroaggregative E. coli (EAEC) related genes and belonging to commonly reported O25:H4 and other serotypes causing bacteremia in African children remain unknown. We characterized 325 E. coli isolates causing bacteremia in Mozambican children between 2001 and 2014 by conventional multiplex polymerase chain reaction and whole genome sequencing. Incidence rate of EAEC bacteremia was calculated among cases from the demographic surveillance study area. Approximately 17.5% (57/325) of isolates were EAEC, yielding an incidence rate of 45.3 episodes/105 children-years-at-risk among infants; and 44 of isolates were sequenced. 72.7% (32/44) of sequenced strains contained simultaneously genes associated with ExPEC (iutA, fyuA and traT); 88.6% (39/44) harbored the aggregative adherence fimbriae type V variant (AAF/V). Sequence type ST-131 accounted for 84.1% (37/44), predominantly belonging to serotype O25:H4 (59% of the 37); 95.6% (35/44) harbored fimH27. Approximately 15% (6/41) of the children died, and five of the six yielded ST131 strains (83.3%) mostly (60%; 3/5) due to serotypes other than O25:H4. We report the emergence of a new subclone of ST-131 E. coli strains belonging to O25:H4 and other serotypes harboring both ExPEC and EAEC virulence genes, including agg5A, associated with poor outcome in bacteremic Mozambican children, suggesting the need for prompt recognition for appropriate management.
  • The Surge after the Surge: Cardiac Surgery post-COVID-19

    Salenger, R.; Etchill, E.W.; Gammie, J.S. (Elsevier, Inc., 2020)
    BACKGROUND: The COVID-19 pandemic has dramatically reduced adult cardiac surgery case volumes as institutions and surgeons curtail non-urgent operations. There will be a progressive increase in deferred cases during the pandemic that will require completion within a limited time frame once restrictions ease. We investigated the impact of various levels of increased post-pandemic hospital operating capacity on the time to clear the backlog of deferred cases. METHODS: We collected data from four cardiac surgery programs across two health systems. We recorded case rates at baseline and during the COVID-19 pandemic. We created a mathematical model to quantify the cumulative surgical backlog based on the projected pandemic duration. We then used our model to predict the time required to clear the backlog depending on the level of increased operating capacity. RESULTS: Cardiac surgery volumes fell to 54% of baseline after restrictions were implemented. Assuming a service restoration date of either June 1 or July 1, we calculated the need to perform 216% or 263% of monthly baseline volume, respectively, to clear the backlog in one month. The actual duration required to clear the backlog is highly dependent on hospital capacity in the post-COVID time period, and ranges from one to eight months depending on when services are restored and degree of increased capacity. CONCLUSIONS: Cardiac surgical operating capacity during the COVID-19 recovery period will have a dramatic impact on the time to clear the deferred cases backlog. Inadequate operating capacity may cause substantial delays and increase morbidity and mortality. If only pre-pandemic capacity is available, the backlog will never clear.
  • Single-cell transcription analysis of Plasmodium vivax blood-stage parasites identifies stage- and species-specific profiles of expression

    Cannon, M.V.; Serre, D.; Sà, J.M. (Public Library of Science, 2020)
    Plasmodium vivax and P. falciparum, the parasites responsible for most human malaria worldwide, exhibit striking biological differences, which have important clinical consequences. Unfortunately, P. vivax, unlike P. falciparum, cannot be cultivated continuously in vitro, which limits our understanding of its biology and, consequently, our ability to effectively control vivax malaria. Here, we describe single-cell gene expression profiles of 9,215 P. vivax parasites from bloodstream infections of Aotus and Saimiri monkeys. Our results show that transcription of most P. vivax genes occurs during short periods of the intraerythrocytic cycle and that this pattern of gene expression is conserved in other Plasmodium species. However, we also identify a strikingly high proportion of species-specific transcripts in late schizonts, possibly associated with the specificity of erythrocyte invasion. Our findings provide new and robust markers of blood-stage parasites, including some that are specific to the elusive P. vivax male gametocytes, and will be useful for analyzing gene expression data from laboratory and field samples.

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