Comparative genomics of European Avian Pathogenic E. coli (APEC)

Background Avian pathogenic Escherichia coli (APEC) causes colibacillosis, which results in significant economic losses to the poultry industry worldwide. However, the diversity between isolates remains poorly understood. Here, a total of 272 APEC isolates collected from the United Kingdom (UK), Italy and Germany were characterised using multiplex polymerase chain reactions (PCRs) targeting 22 equally weighted factors covering virulence genes, R-type and phylogroup. Following these analysis, 95 of the selected strains were further analysed using Whole Genome Sequencing (WGS). Results The most prevalent phylogroups were B2 (47%) and A1 (22%), although there were national differences with Germany presenting group B2 (35.3%), Italy presenting group A1 (53.3%) and UK presenting group B2 (56.1%) as the most prevalent. R-type R1 was the most frequent type (55%) among APEC, but multiple R-types were also frequent (26.8%). Following compilation of all the PCR data which covered a total of 15 virulence genes, it was possible to build a similarity tree using each PCR result unweighted to produce 9 distinct groups. The average number of virulence genes was 6-8 per isolate, but no positive association was found between phylogroup and number or type of virulence genes. A total of 95 isolates representing each of these 9 groupings were genome sequenced and analysed for in silico serotype, Multilocus Sequence Typing (MLST), and antimicrobial resistance (AMR). The UK isolates showed the greatest variability in terms of serotype and MLST compared with German and Italian isolates, whereas the lowest prevalence of AMR was found for German isolates. Similarity trees were compiled using sequencing data and notably single nucleotide polymorphism data generated ten distinct geno-groups. The frequency of geno-groups across Europe comprised 26.3% belonging to Group 8 representing serogroups O2, O4, O18 and MLST types ST95, ST140, ST141, ST428, ST1618 and others, 18.9% belonging to Group 1 (serogroups O78 and MLST types ST23, ST2230), 15.8% belonging to Group 10 (serogroups O8, O45, O91, O125ab and variable MLST types), 14.7% belonging to Group 7 (serogroups O4, O24, O35, O53, O161 and MLST type ST117) and 13.7% belonging to Group 9 (serogroups O1, O16, O181 and others and MLST types ST10, ST48 and others). The other groups (2, 3, 4, 5 and 6) each contained relatively few strains. However, for some of the genogroups (e.g. groups 6 and 7) partial overlap with SNPs grouping and PCR grouping (matching PCR groups 8 (13 isolates on 22) and 1 (14 isolates on 16) were observable). However, it was not possible to obtain a clear correlation between genogroups and unweighted PCR groupings. This may be due to the genome plasticity of E. coli that enables strains to carry the same virulence factors even if the overall genotype is substantially different. Conclusions The conclusion to be drawn from the lack of correlations is that firstly, APEC are very diverse and secondly, it is not possible to rely on any one or more basic molecular or phenotypic tests to define APEC with clarity, reaffirming the need for whole genome analysis approaches which we describe here. This study highlights the presence of previously unreported serotypes and MLSTs for APEC in Europe. Moreover, it is a first step on a cautious reconsideration of the merits of classical identification criteria such as R typing, phylogrouping and serotyping

A Framework for Crowd Management during COVID-19 with Artificial Intelligence

COVID-19 requires crowded events to enforce restrictions, aimed to contain the spread of the virus. However, we have seen numerous events not observing these restrictions, thus becoming super spreader events. In order to contain the spread of a human to human communicable disease, a number of restrictions, including wearing face masks, maintaining social distancing, and adhering to regular cleaning and sanitization, are critical. These restrictions are absolutely essential for crowded events. Some crowded events can take place spontaneously, such as a political rally or a protest march or a funeral procession. Controlling spontaneous crowded events, like a protest march, political rally, celebration after a sporting event, or concert, can be quite difficult, especially during a crisis like the COVID-19 pandemic. In this article, we review some well-known crowded events that have taken place during the ongoing pandemic. Guided by our review, we provide a framework using machine learning to effectively organize crowded events during the ongoing and for future crises. We also provide details of metrics for the validation of some components in the proposed framework, and an extensive algorithm. Finally, we offer explanations of its various functions of the algorithm. The proposed framework can also be adapted in other crises

A Framework for Crowd Management during COVID-19 with Artificial Intelligence

COVID-19 requires crowded events to enforce restrictions, aimed to contain the spread of the virus. However, we have seen numerous events not observing these restrictions, thus becoming super spreader events. In order to contain the spread of a human to human communicable disease, a number of restrictions, including wearing face masks, maintaining social distancing, and adhering to regular cleaning and sanitization, are critical. These restrictions are absolutely essential for crowded events. Some crowded events can take place spontaneously, such as a political rally or a protest march or a funeral procession. Controlling spontaneous crowded events, like a protest march, political rally, celebration after a sporting event, or concert, can be quite difficult, especially during a crisis like the COVID-19 pandemic. In this article, we review some well-known crowded events that have taken place during the ongoing pandemic. Guided by our review, we provide a framework using machine learning to effectively organize crowded events during the ongoing and for future crises. We also provide details of metrics for the validation of some components in the proposed framework, and an extensive algorithm. Finally, we offer explanations of its various functions of the algorithm. The proposed framework can also be adapted in other crises

Prevalence and Significance of Pyuria in Chronic Kidney Disease Patients in Saudi Arabia

Chronic kidney disease (CKD) is considered a major health problem, which poses a burden for health care systems worldwide. It has been estimated that 10% of the population worldwide have CKD; however, most of the cases are undiagnosed. If left untreated, CKD could lead to kidney failure, which highlights the importance of early diagnosis and treatment. Pyuria has been reported in CKD patients, and could be the result of several comorbidities, such as diabetes, or urinary tract infections (UTIs). A few studies have shown that pyuria is associated with the late stages of CKD. However, there are limited data on the prevalence of non-UTI (sterile) and UTI–pyuria in different CKD patient populations, and its association with the decline in kidney function and progression of CKD. In this retrospective study, we report the prevalence of pyuria (sterile and UTI) in 754 CKD patients of King Fahd Specialist Hospital, Buraydah, Saudi Arabia. Our data showed that 164/754 CKD patients (21.8%) had pyuria, whereas 590 patients (78.2%) presented with no pyuria. There was a significantly higher percentage of late-stage (stage 4) CKD patients in the pyuric group compared to the non-pyuric group (36.6% vs. 11.9%). In line with the previous data, proteinuria was detected in a significantly higher percentage of pyuric patients, in addition to significantly higher levels of serum creatinine and urea, compared to non-pyuric patients. Furthermore, 13.4% of the pyuric CKD patients had UTI, whereas 86.6% presented with sterile pyuria. E. coli was indicated as the causative agent in 45.5% of UTI patients. Our patient data analysis showed that a significantly higher percentage of UTI–pyuric CKD patients, than sterile pyuric patients (63.6% vs. 19.7%), had higher numbers of urinary white blood cells (>50/HPF, WBCs). The data also showed that a higher percentage of UTI–pyuric patients were late-stage CKD patients, compared to sterile pyuric patients (50% vs. 34.5%). Our findings indicate that a high level of pyuria could be considered as a marker for late-stage CKD, and that UTI is an important risk factor for the decline in kidney function and the progression to late-stage CKD. We believe that further studies are needed to correlate pyuria to kidney function, which could be helpful in monitoring the progression of CKD. Moreover, the management of comorbidities, such as diabetes and UTIs, which are risk factors for CKD and associated pyuria, could help to control the progression of CKD to the late stages

Multiplex PCR results.xls

<p>276 APEC were investigated for R type, phylogroup and virulence factors using multiplex pcr as described in </p><p> </p><p>Comparative genomics of European Avian Pathogenic E. coli (APEC) (in press)</p

Health Care Policy and Congenital Heart Disease: 2020 Focus on Our 2030 Future

The congenital heart care community faces a myriad of public health issues that act as barriers toward optimum patient outcomes. In this article, we attempt to define advocacy and policy initiatives meant to spotlight and potentially address these challenges. Issues are organized into the following 3 key facets of our community: patient population, health care delivery, and workforce. We discuss the social determinants of health and health care disparities that affect patients in the community that require the attention of policy makers. Furthermore, we highlight the many needs of the growing adults with congenital heart disease and those with comorbidities, highlighting concerns regarding the inequities in access to cardiac care and the need for multidisciplinary care. We also recognize the problems of transparency in outcomes reporting and the promising application of telehealth. Finally, we highlight the training of providers, measures of productivity, diversity in the workforce, and the importance of patient– family centered organizations in advocating for patients. Although all of these issues remain relevant to many subspecialties in medicine, this article attempts to illustrate the unique needs of this population and highlight ways in which to work together to address important opportunities for change in the cardiac care community and beyond. This article provides a framework for policy and advocacy efforts for the next decade

Characterizing the Therapeutic Potential of a Potent BET Degrader in Merkel Cell Carcinoma

Studies on the efficacy of small molecule inhibitors in Merkel cell carcinoma (MCC) have been limited and largely inconclusive. In this study, we investigated the therapeutic potential of a potent BET degrader, BETd-246, in the treatment of MCC. We found that MCC cell lines were significantly more sensitive to BETd-246 than to BET inhibitor treatment. Therapeutic targeting of BET proteins resulted in a loss of “MCC signature” genes but not MYC expression as previously described irrespective of Merkel cell polyomavirus (MCPyV) status. In MCPyV+ MCC cells, BETd-246 alone suppressed downstream targets in the MCPyV-LT Ag axis. We also found enrichment of HOX and cell cycle genes in MCPyV− MCC cell lines that were intrinsically resistant to BETd-246. Our findings uncover a requirement for BET proteins in maintaining MCC lineage identity and point to the potential utility of BET degraders for treating MCC

Infective Endocarditis in Patients on Chronic Hemodialysis

295sinoneBackground: Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives: This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods: Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results: A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non–HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p &lt; 0.001). Cardiac surgery was less frequently performed among HD patients (30.6% vs. 46.2%; p &lt; 0.001), whereas relapses were higher (9.4% vs. 2.7%; p &lt; 0.001). Risk factors for 6-month mortality included Charlson score (hazard ratio [HR]: 1.26; 95% confidence interval [CI]: 1.11 to 1.44; p = 0.001), CNS emboli and other emboli (HR: 3.11; 95% CI: 1.84 to 5.27; p &lt; 0.001; and HR: 1.73; 95% CI: 1.02 to 2.93; p = 0.04, respectively), persistent bacteremia (HR: 1.79; 95% CI: 1.11 to 2.88; p = 0.02), and acute onset heart failure (HR: 2.37; 95% CI: 1.49 to 3.78; p &lt; 0.001). Conclusions: HD-IE is a health care–associated infection chiefly caused by S. aureus, with increasing rates of enterococcal IE. Mortality and relapses are very high and significantly larger than in non–HD-IE patients, whereas cardiac surgery is less frequently performed.nonePericas J.M.; Llopis J.; Jimenez-Exposito M.J.; Kourany W.M.; Almirante B.; Carosi G.; Durante-Mangoni E.; Fortes C.Q.; Giannitsioti E.; Lerakis S.; Montagna-Mella R.; Ambrosioni J.; Tan R.-S.; Mestres C.A.; Wray D.; Pachirat O.; Moreno A.; Chu V.H.; de Lazzari E.; Fowler V.G.; Miro J.M.; Clara L.; Sanchez M.; Casabe J.; Cortes C.; Nacinovich F.; Oses P.F.; Ronderos R.; Sucari A.; Thierer J.; Altclas J.; Kogan S.; Spelman D.; Athan E.; Harris O.; Kennedy K.; Tan R.; Gordon D.; Papanicolas L.; Korman T.; Kotsanas D.; Dever R.; Jones P.; Konecny P.; Lawrence R.; Rees D.; Ryan S.; Feneley M.P.; Harkness J.; Post J.; Reinbott P.; Gattringer R.; Wiesbauer F.; Andrade A.R.; Passos de Brito A.C.; Guimaraes A.C.; Grinberg M.; Mansur A.J.; Siciliano R.F.; Varejao Strabelli T.M.; Campos Vieira M.L.; de Medeiros Tranchesi R.A.; Paiva M.G.; de Oliveira Ramos A.; Weksler C.; Ferraiuoli G.; Golebiovski W.; Lamas C.; Karlowsky J.A.; Keynan Y.; Morris A.M.; Rubinstein E.; Jones S.B.; Garcia P.; Cereceda M.; Fica A.; Mella R.M.; Fernandez R.; Franco L.; Gonzalez J.; Jaramillo A.N.; Barsic B.; Bukovski S.; Krajinovic V.; Pangercic A.; Rudez I.; Vincelj J.; Freiberger T.; Pol J.; Zaloudikova B.; Ashour Z.; El Kholy A.; Mishaal M.; Osama D.; Rizk H.; Aissa N.; Alauzet C.; Alla F.; Campagnac C.C.; Doco-Lecompte T.; Selton-Suty C.; Casalta J.-P.; Fournier P.-E.; Habib G.; Raoult D.; Thuny F.; Delahaye F.; Delahaye A.; Vandenesch F.; Donal E.; Donnio P.Y.; Flecher E.; Michelet C.; Revest M.; Tattevin P.; Chevalier F.; Jeu A.; Remadi J.P.; Rusinaru D.; Tribouilloy C.; Bernard Y.; Chirouze C.; Hoen B.; Leroy J.; Plesiat P.; Naber C.; Neuerburg C.; Mazaheri B.; Sophia Athanasia C.N.; Deliolanis I.; Giamarellou H.; Thomas T.; Mylona E.; Paniara O.; Papanicolaou K.; Pyros J.; Skoutelis A.; Papanikolaou K.; Sharma G.; Francis J.; Nair L.; Thomas V.; Venugopal K.; Hannan M.M.; Hurley J.P.; Wanounou M.; Gilon D.; Israel S.; Korem M.; Strahilevitz J.; Iossa D.; Orlando S.; Ursi M.P.; Pafundi P.C.; D'Amico F.; Bernardo M.; Cuccurullo S.; Dialetto G.; Covino F.E.; Manduca S.; Della Corte A.; De Feo M.; Tripodi M.F.; Cecchi E.; De Rosa F.; Forno D.; Imazio M.; Trinchero R.; Grossi P.; Lattanzio M.; Toniolo A.; Goglio A.; Raglio A.; Ravasio V.; Rizzi M.; Suter F.; Magri S.; Signorini L.; Kanafani Z.; Kanj S.S.; Sharif-Yakan A.; Abidin I.; Tamin S.S.; Martinez E.R.; Soto Nieto G.I.; van der Meer J.T.M.; Chambers S.; Holland D.; Morris A.; Raymond N.; Read K.; Murdoch D.R.; Dragulescu S.; Ionac A.; Mornos C.; Butkevich O.M.; Chipigina N.; Kirill O.; Vadim K.; Vinogradova T.; Edathodu J.; Halim M.; Liew Y.-Y.; Lejko-Zupanc T.; Logar M.; Mueller-Premru M.; Commerford P.; Commerford A.; Deetlefs E.; Hansa C.; Ntsekhe M.; Almela M.; Azqueta M.; Brunet M.; Castro P.; Falces C.; Fuster D.; Fita G.; Garcia- de- la- Maria C.; Garcia-Gonzalez J.; Gatell J.M.; Marco F.; Miro J.M.; Ortiz J.; Ninot S.; Pare J.C.; Pericas J.M.; Quintana E.; Ramirez J.; Rovira I.; Sandoval E.; Sitges M.; Tellez A.; Tolosana J.M.; Vidal B.; Vila J.; Anguera I.; Font B.; Guma J.R.; Bermejo J.; Bouza E.; Garcia Fernandez M.A.; Gonzalez-Ramallo V.; Marin M.; Munoz P.; Pedromingo M.; Roda J.; Rodriguez-Creixems M.; Solis J.; Fernandez-Hidalgo N.; Tornos P.; de Alarcon A.; Parra R.; Alestig E.; Johansson M.; Olaison L.; Snygg-Martin U.; Pachirat P.; Pussadhamma B.; Senthong V.; Casey A.; Elliott T.; Lambert P.; Watkin R.; Eyton C.; Klein J.L.; Bradley S.; Kauffman C.; Bedimo R.; Corey G.R.; Crowley A.L.; Douglas P.; Drew L.; Holland T.; Lalani T.; Mudrick D.; Samad Z.; Sexton D.; Stryjewski M.; Wang A.; Woods C.W.; Cantey R.; Steed L.; Dickerman S.A.; Bonilla H.; DiPersio J.; Salstrom S.-J.; Baddley J.; Patel M.; Peterson G.; Stancoven A.; Levine D.; Riddle J.; Rybak M.; Cabell C.H.Pericas, J. M.; Llopis, J.; Jimenez-Exposito, M. J.; Kourany, W. M.; Almirante, B.; Carosi, G.; Durante-Mangoni, E.; Fortes, C. Q.; Giannitsioti, E.; Lerakis, S.; Montagna-Mella, R.; Ambrosioni, J.; Tan, R. -S.; Mestres, C. A.; Wray, D.; Pachirat, O.; Moreno, A.; Chu, V. H.; de Lazzari, E.; Fowler, V. G.; Miro, J. M.; Clara, L.; Sanchez, M.; Casabe, J.; Cortes, C.; Nacinovich, F.; Oses, P. F.; Ronderos, R.; Sucari, A.; Thierer, J.; Altclas, J.; Kogan, S.; Spelman, D.; Athan, E.; Harris, O.; Kennedy, K.; Tan, R.; Gordon, D.; Papanicolas, L.; Korman, T.; Kotsanas, D.; Dever, R.; Jones, P.; Konecny, P.; Lawrence, R.; Rees, D.; Ryan, S.; Feneley, M. P.; Harkness, J.; Post, J.; Reinbott, P.; Gattringer, R.; Wiesbauer, F.; Andrade, A. R.; Passos de Brito, A. C.; Guimaraes, A. C.; Grinberg, M.; Mansur, A. J.; Siciliano, R. F.; Varejao Strabelli, T. M.; Campos Vieira, M. L.; de Medeiros Tranchesi, R. A.; Paiva, M. G.; de Oliveira Ramos, A.; Weksler, C.; Ferraiuoli, G.; Golebiovski, W.; Lamas, C.; Karlowsky, J. A.; Keynan, Y.; Morris, A. M.; Rubinstein, E.; Jones, S. B.; Garcia, P.; Cereceda, M.; Fica, A.; Mella, R. M.; Fernandez, R.; Franco, L.; Gonzalez, J.; Jaramillo, A. N.; Barsic, B.; Bukovski, S.; Krajinovic, V.; Pangercic, A.; Rudez, I.; Vincelj, J.; Freiberger, T.; Pol, J.; Zaloudikova, B.; Ashour, Z.; El Kholy, A.; Mishaal, M.; Osama, D.; Rizk, H.; Aissa, N.; Alauzet, C.; Alla, F.; Campagnac, C. C.; Doco-Lecompte, T.; Selton-Suty, C.; Casalta, J. -P.; Fournier, P. -E.; Habib, G.; Raoult, D.; Thuny, F.; Delahaye, F.; Delahaye, A.; Vandenesch, F.; Donal, E.; Donnio, P. Y.; Flecher, E.; Michelet, C.; Revest, M.; Tattevin, P.; Chevalier, F.; Jeu, A.; Remadi, J. P.; Rusinaru, D.; Tribouilloy, C.; Bernard, Y.; Chirouze, C.; Hoen, B.; Leroy, J.; Plesiat, P.; Naber, C.; Neuerburg, C.; Mazaheri, B.; Sophia Athanasia, C. N.; Deliolanis, I.; Giamarellou, H.; Thomas, T.; Mylona, E.; Paniara, O.; Papanicolaou, K.; Pyros, J.; Skoutelis, A.; Papanikolaou, K.; Sharma, G.; Francis, J.; Nair, L.; Thomas, V.; Venugopal, K.; Hannan, M. M.; Hurley, J. P.; Wanounou, M.; Gilon, D.; Israel, S.; Korem, M.; Strahilevitz, J.; Iossa, D.; Orlando, S.; Ursi, M. P.; Pafundi, P. C.; D'Amico, F.; Bernardo, M.; Cuccurullo, S.; Dialetto, G.; Covino, F. E.; Manduca, S.; Della Corte, A.; De Feo, M.; Tripodi, M. F.; Cecchi, E.; De Rosa, F.; Forno, D.; Imazio, M.; Trinchero, R.; Grossi, P.; Lattanzio, M.; Toniolo, A.; Goglio, A.; Raglio, A.; Ravasio, V.; Rizzi, M.; Suter, F.; Magri, S.; Signorini, L.; Kanafani, Z.; Kanj, S. S.; Sharif-Yakan, A.; Abidin, I.; Tamin, S. S.; Martinez, E. R.; Soto Nieto, G. I.; van der Meer, J. T. M.; Chambers, S.; Holland, D.; Morris, A.; Raymond, N.; Read, K.; Murdoch, D. R.; Dragulescu, S.; Ionac, A.; Mornos, C.; Butkevich, O. M.; Chipigina, N.; Kirill, O.; Vadim, K.; Vinogradova, T.; Edathodu, J.; Halim, M.; Liew, Y. -Y.; Lejko-Zupanc, T.; Logar, M.; Mueller-Premru, M.; Commerford, P.; Commerford, A.; Deetlefs, E.; Hansa, C.; Ntsekhe, M.; Almela, M.; Azqueta, M.; Brunet, M.; Castro, P.; Falces, C.; Fuster, D.; Fita, G.; Garcia- de- la- Maria, C.; Garcia-Gonzalez, J.; Gatell, J. M.; Marco, F.; Miro, J. M.; Ortiz, J.; Ninot, S.; Pare, J. C.; Pericas, J. M.; Quintana, E.; Ramirez, J.; Rovira, I.; Sandoval, E.; Sitges, M.; Tellez, A.; Tolosana, J. M.; Vidal, B.; Vila, J.; Anguera, I.; Font, B.; Guma, J. R.; Bermejo, J.; Bouza, E.; Garcia Fernandez, M. A.; Gonzalez-Ramallo, V.; Marin, M.; Munoz, P.; Pedromingo, M.; Roda, J.; Rodriguez-Creixems, M.; Solis, J.; Fernandez-Hidalgo, N.; Tornos, P.; de Alarcon, A.; Parra, R.; Alestig, E.; Johansson, M.; Olaison, L.; Snygg-Martin, U.; Pachirat, P.; Pussadhamma, B.; Senthong, V.; Casey, A.; Elliott, T.; Lambert, P.; Watkin, R.; Eyton, C.; Klein, J. L.; Bradley, S.; Kauffman, C.; Bedimo, R.; Corey, G. R.; Crowley, A. L.; Douglas, P.; Drew, L.; Holland, T.; Lalani, T.; Mudrick, D.; Samad, Z.; Sexton, D.; Stryjewski, M.; Wang, A.; Woods, C. W.; Cantey, R.; Steed, L.; Dickerman, S. A.; Bonilla, H.; Dipersio, J.; Salstrom, S. -J.; Baddley, J.; Patel, M.; Peterson, G.; Stancoven, A.; Levine, D.; Riddle, J.; Rybak, M.; Cabell, C. H