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INTRODUCTION: Elevated levels of serum uric acid (SUA) are strongly associated with several components of the metabolic syndrome, particularly obesity. Previous studies have reported the correlation between SUA levels, xanthine oxidoreductase (XOR) activity, and the imbalanced adipokine levels that are characteristic of obesity. In this study, we explored the effect of febuxostat on circulating adipokine profiles in patients with overweight or obesity and asymptomatic hyperuricemia. METHODS: This study was a single-center, randomized and controlled clinical trial that enrolled 130 participants with asymptomatic hyperuricemia and obesity. 117 participants were included in the final analysis, with 60 participants in the febuxostat group and 57 in the control group. We compared the circulating adipokine levels at 3 and 6 months, including high molecular weight (HMW) adiponectin, chemerin, omentin, (monocyte chemotactic protein-1) MCP-1, asprosin, fibroblast growth factor 21 (FGF21), neuregulin-4 (Nrg4), leptin, resistin, vaspin, visfatin, adipsin, and assessed the correlation between changes in adipokine levels (Δadipokines) and changes in XOR activity (ΔXOR) after febuxostat treatment. RESULTS: The results showed that an increase in HMW adiponectin and omentin levels and a decrease in chemerin and asprosin levels at 3 or 6 months compared to the control group. Additionally, a positive correlation was observed between ΔXOR activity and Δasprosin. Furthermore, after adjusting for ΔTG (triglyceride) and ΔSUA (serum uric acid) in multiple linear regression analyses, we found that ΔXOR activity was independently correlated with Δasprosin. CONCLUSION: This study may provide important evidence that febuxostat could alleviate the imbalance in circulating adipokine levels in patients with overweight or obesity and asymptomatic hyperuricemia. Furthermore, we observed a positive correlation between changes in asprosin levels and changes in XOR activity after febuxostat treatment.
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Over 40% of all U.S. Salmonella illnesses are attributed to consumption of contaminated meat and poultry products each year. Determining which serotypes cause the most outbreak illnesses associated with specific meat and poultry types can inform prevention measures. We developed an approach to categorize serotypes using outbreak illness burden (high, moderate, low) and trajectory (increased, stable, decreased). We used data from 192 foodborne Salmonella outbreaks resulting in 7,077 illnesses, 1,330 hospitalizations, and 9 deaths associated with chicken, turkey, beef, or pork during 2012-2021. We linked each meat and poultry type to 1-3 serotypes that we categorized as high outbreak illness burden and increased trajectory during 2021. Calculation and public display of outbreak illness burden and trajectory annually could facilitate the prioritization of serotypes for prevention by federal and state health and regulatory agencies and by the meat and poultry industry.
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BACKGROUND: Cryptosporidium parvum is an apicomplexan zoonotic parasite causing the diarrheal illness cryptosporidiosis in humans and animals. To invade the host intestinal epithelial cells, parasitic proteins expressed on the surface of sporozoites interact with host cells to facilitate the formation of parasitophorous vacuole for the parasite to reside and develop. The gp40 of C. parvum, named Cpgp40 and located on the surface of sporozoites, was proven to participate in the process of host cell invasion. METHODS: We utilized the purified Cpgp40 as a bait to obtain host cell proteins interacting with Cpgp40 through the glutathione S-transferase (GST) pull-down method. In vitro analysis, through bimolecular fluorescence complementation assay (BiFC) and coimmunoprecipitation (Co-IP), confirmed the solid interaction between Cpgp40 and ENO1. In addition, by using protein mutation and parasite infection rate analysis, it was demonstrated that ENO1 plays an important role in the C. parvum invasion of HCT-8 cells. RESULTS: To illustrate the functional activity of Cpgp40 interacting with host cells, we identified the alpha-enolase protein (ENO1) from HCT-8 cells, which showed direct interaction with Cpgp40. The mRNA level of ENO1 gene was significantly decreased at 3 and 24 h after C. parvum infection. Antibodies and siRNA specific to ENO1 showed the ability to neutralize C. parvum infection in vitro, which indicated the participation of ENO1 during the parasite invasion of HCT-8 cells. In addition, we further demonstrated that ENO1 protein was involved in the regulation of cytoplasmic matrix of HCT-8 cells during C. parvum invasion. Functional study of the protein mutation illustrated that ENO1 was also required for the endogenous development of C. parvum. CONCLUSIONS: In this study, we utilized the purified Cpgp40 as a bait to obtain host cell proteins ENO1 interacting with Cpgp40. Functional studies illustrated that the host cell protein ENO1 was involved in the regulation of tight junction and adherent junction proteins during C. parvum invasion and was required for endogenous development of C. parvum.
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Criptosporidiosis , Cryptosporidium parvum , Cryptosporidium , Humanos , Animales , Cryptosporidium parvum/genética , Criptosporidiosis/parasitología , Esporozoítos/metabolismo , Proteínas Protozoarias/metabolismo , Proteínas de la Membrana/metabolismo , Fosfopiruvato Hidratasa/genética , Fosfopiruvato Hidratasa/metabolismo , Proteínas de Unión al ADN/metabolismo , Biomarcadores de Tumor/metabolismo , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Rapid adaptation of metabolic capabilities is crucial for bacterial survival in habitats with fluctuating nutrient availability. In such conditions, the bacterial stringent response is a central regulatory mechanism activated by nutrient starvation or other stressors. This response is primarily controlled by exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GPPA) enzymes. To gain further insight into these enzymes, the high-resolution crystal structure of PPX from Zymomonas mobilis (ZmPPX) was determined at 1.8 Å. The phosphatase activity of PPX was strictly dependent on the presence of divalent metal cations. Notably, the structure of ZmPPX revealed the presence of two magnesium ions in the active site center, which is atypical compared to other PPX structures where only one divalent ion is observed. ZmPPX exists as a dimer in solution and belongs to the "long" PPX group consisting of four domains. Remarkably, the dimer configuration exhibits a substantial and deep aqueduct with positive potential along its interface. This aqueduct appears to extend towards the active site region, suggesting that this positively charged aqueduct could potentially serve as a binding site for polyP.
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Magnesio , Zymomonas , Zymomonas/metabolismo , Ácido Anhídrido Hidrolasas/química , Ácido Anhídrido Hidrolasas/metabolismo , Bacterias/metabolismo , IonesRESUMEN
Listeria monocytogenes can cause severe foodborne illness, including miscarriage during pregnancy or death in newborn infants. When outbreaks of L. monocytogenes illness occur, it may be possible to determine the food source of the outbreak. However, most reported L. monocytogenes illnesses do not occur as part of a recognized outbreak and most of the time the food source of sporadic L. monocytogenes illness in people cannot be determined. In the United States, L. monocytogenes isolates from patients, foods, and environments are routinely sequenced and analyzed by whole genome multilocus sequence typing (wgMLST) for outbreak detection by PulseNet, the national molecular surveillance system for foodborne illnesses. We investigated whether machine learning approaches applied to wgMLST allele call data could assist in attribution analysis of food source of L. monocytogenes isolates. We compiled isolates with a known source from five food categories (dairy, fruit, meat, seafood, and vegetable) using the metadata of L. monocytogenes isolates in PulseNet, deduplicated closely genetically related isolates, and developed random forest models to predict the food sources of isolates. Prediction accuracy of the final model varied across the food categories; it was highest for meat (65%), followed by fruit (45%), vegetable (45%), dairy (44%), and seafood (37%); overall accuracy was 49%, compared with the naive prediction accuracy of 28%. Our results show that random forest can be used to capture genetically complex features of high-resolution wgMLST for attribution of isolates to their sources.
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Enfermedades Transmitidas por los Alimentos , Listeria monocytogenes , Listeriosis , Lactante , Recién Nacido , Humanos , Estados Unidos/epidemiología , Listeriosis/epidemiología , Bosques Aleatorios , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/epidemiología , Tipificación de Secuencias Multilocus , Brotes de Enfermedades , Verduras , GenómicaRESUMEN
Background: Campylobacter is the most common cause of bacterial diarrhea in the United States; resistance to macrolides and fluoroquinolones limits treatment options. We examined the epidemiology of US Campylobacter infections and changes in resistance over time. Methods: The Foodborne Diseases Active Surveillance Network receives information on laboratory-confirmed Campylobacter cases from 10 US sites, and the National Antimicrobial Resistance Monitoring System receives a subset of isolates from these cases for antimicrobial susceptibility testing. We estimated trends in incidence of Campylobacter infection, adjusting for sex, age, and surveillance changes attributable to culture-independent diagnostic tests. We compared percentages of isolates resistant to erythromycin or ciprofloxacin during 2005-2016 with 2017-2018 and used multivariable logistic regression to examine the association of international travel with resistance. Results: Adjusted Campylobacter incidence remained stable or decreased for all groups analyzed since 2012. Among 2449 linked records in 2017-2018, the median patient age was 40.2 years (interquartile range, 21.6-57.8 years), 54.8% of patients were male, 17.2% were hospitalized, and 0.2% died. The percentage of resistant infections increased from 24.5% in 2005-2016 to 29.7% in 2017-2018 for ciprofloxacin (P < .001) and from 2.6% to 3.3% for erythromycin (P = .04). Persons with recent international travel had higher odds than nontravelers of having isolates resistant to ciprofloxacin (adjusted odds ratio [aOR] varied from 1.7 to 10.6 by race/ethnicity) and erythromycin (aOR = 1.7; 95% confidence interval, 1.3-2.1). Conclusions: Campylobacter incidence has remained stable or decreased, whereas resistance to antimicrobials recommended for treatment has increased. Recent international travel increased the risk of resistance.
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Cryptosporidium is a protozoan parasite capable of infecting humans and animals and is a leading cause of diarrheal disease and early childhood mortality. The molecular mechanisms underlying invasive infection and its pathogenesis remain largely unknown. To better understand the molecular mechanism of the interaction between C. parvum and host cells, we profiled the changes of host cells membrane proteins extracted using native membrane protein extraction kit between C. parvum-infected HCT-8 cells and the control group after C. parvum infected 6 h combined with quantitative Tandem Mass Tags (TMT) liquid chromatography-dual mass spectrometry proteomic analysis. Among the 4844 quantifiable proteins identified, the expression levels of 625 were upregulated, and those of 116 were downregulated at 6 h post-infection compared with controls (1.5-fold difference in abundance, p < 0.05). Enrichment analysis of the function, protein domain and Kyoto Encyclopedia of Genes and Genomes pathway of the differentially expressed proteins revealed that the differentially expressed proteins were mainly related to biological functions related to the cytoskeleton and cytoplasmic matrix. We also found that infection with C. parvum may destroy HCT-8 intercellular space adhesion. Six proteins were further verified using quantitative real-time reverse transcription polymerase chain reaction and western blotting. Through systematic analysis of proteomics related to HCT-8 cell membranes infected by C. parvum, we found many host membrane proteins that can serve as potential receptors in C. parvum adhesion or invasion. C. parvum infection destroyed host cell barrier function and caused extensive changes in host cytoskeleton proteins, providing a deeper understanding of the molecules and their functions involved in the host-C. parvum interaction. SIGNIFICANCE: There is a lack of systematic research on the molecular mechanisms underlying the interaction of C. parvum with host cells. Changes of host cell membrane proteins after C. parvum infection may be used to examine the host cell receptors for parasite adhesion and invasion, and how the parasite interacts with these receptors. It is of great significance that host cells undergo membrane fusion to mediate invasion. Through proteomic studies on the host cell membrane after infection with HCT-8 cells by C. parvum, we observed disruption of the host cell cellular barrier function and widespread alteration of host cytoskeletal proteins caused by C. parvum infection, providing a deeper understanding of the molecules and their functions involved in host-C. parvum interaction.
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Criptosporidiosis , Cryptosporidium parvum , Cryptosporidium , Humanos , Preescolar , Animales , Criptosporidiosis/genética , Criptosporidiosis/metabolismo , Criptosporidiosis/parasitología , Cryptosporidium parvum/genética , Proteómica , Proteínas de la MembranaRESUMEN
Shiga toxin-producing Escherichia coli (STEC) causes acute diarrheal illness. To determine risk factors for non-O157 STEC infection, we enrolled 939 patients and 2,464 healthy controls in a case-control study conducted in 10 US sites. The highest population-attributable fractions for domestically acquired infections were for eating lettuce (39%), tomatoes (21%), or at a fast-food restaurant (23%). Exposures with 10%-19% population attributable fractions included eating at a table service restaurant, eating watermelon, eating chicken, pork, beef, or iceberg lettuce prepared in a restaurant, eating exotic fruit, taking acid-reducing medication, and living or working on or visiting a farm. Significant exposures with high individual-level risk (odds ratio >10) among those >1 year of age who did not travel internationally were all from farm animal environments. To markedly decrease the number of STEC-related illnesses, prevention measures should focus on decreasing contamination of produce and improving the safety of foods prepared in restaurants.
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Infecciones por Escherichia coli , Escherichia coli Shiga-Toxigénica , Animales , Bovinos , Estados Unidos/epidemiología , Infecciones por Escherichia coli/epidemiología , Estudios de Casos y Controles , Factores de Riesgo , Diarrea/epidemiologíaRESUMEN
Diabetic kidney disease (DKD) is a major public health issue because of its refractory nature. Ferroptosis is a newly coined programmed cell death characterized by the accumulation of lipid reactive oxygen species (ROS). However, the prognostic and diagnostic value of ferroptosis-related genes (FRGs) and their biological mechanisms in DKD remain elusive. The gene expression profiles GSE96804, GSE30566, GSE99339 and GSE30528 were obtained and analyzed. We constructed a reliable prognostic model for DKD consisting of eight FRGs (SKIL, RASA1, YTHDC2, SON, MRPL11, HSD17B14, DUSP1 and FOS). The receiver operating characteristic (ROC) curves showed that the ferroptosis-related model had predictive power with an area under the curve (AUC) of 0.818. Gene functional enrichment analysis showed significant differences between the DKD and normal groups, and ferroptosis played an important role in DKD. Consensus clustering analysis showed four different ferroptosis types, and the risk score of type four was significantly higher than that of other groups. Immune infiltration analysis indicated that the expression of macrophages M2 increased significantly, while that of neutrophils and mast cells activated decreased significantly in the high-risk group. Our study identified and validated the molecular mechanisms of ferroptosis in DKD. FRGs could serve as credible diagnostic biomarkers and therapeutic targets for DKD.
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Diabetes Mellitus , Nefropatías Diabéticas , Ferroptosis , Humanos , Ferroptosis/genética , Nefropatías Diabéticas/genética , Apoptosis , Área Bajo la Curva , Biología Computacional , 17-Hidroxiesteroide Deshidrogenasas , Proteína Activadora de GTPasa p120RESUMEN
BACKGROUND: Cryptosporidium parvum is a zoonotic parasitic protozoan that can infect a variety of animals and humans and is transmitted between hosts via oocysts. The oocyst wall provides strong protection against hostile environmental factors; however, research is limited concerning the oocyst wall at the proteomic level. METHODS: A comprehensive analysis of the proteome of oocyst wall of C. parvum was performed using label-free qualitative high-performance liquid chromatography (HPLC) fractionation and mass spectrometry-based qualitative proteomics technologies. Among the identified proteins, a surface protein (CpSP1) encoded by the C. parvum cgd7_5140 (Cpcgd7_5140) gene was predicted to be located on the surface of the oocyst wall. We preliminarily characterized the sequence and subcellular localization of CpSP1. RESULTS: A total of 798 proteins were identified, accounting for about 20% of the CryptoDB proteome. By using bioinformatic analysis, functional annotation and subcellular localization of the identified proteins were examined for better understanding of the characteristics of the oocyst wall. To verify the localization of CpSP1, an indirect immunofluorescent antibody assay demonstrated that the protein was localized on the surface of the oocyst wall, illustrating the potential usage as a marker for C. parvum detection in vitro. CONCLUSION: The results provide a global framework about the proteomic composition of the Cryptosporidium oocyst wall, thereby providing a theoretical basis for further study of Cryptosporidium oocyst wall formation as well as the selection of targets for Cryptosporidium detection.
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Cryptosporidium parvum , Oocistos , Animales , Cryptosporidium parvum/química , Cryptosporidium parvum/genética , Proteínas de la Membrana/genética , Proteoma , Proteómica , Proteínas Protozoarias/genéticaRESUMEN
BACKGROUND: Case-control studies are commonly used to explore factors associated with enteric bacterial diseases. Control of confounding is challenging due to a large number of exposures of interest and the low frequencies of many of them. METHODS: We evaluated nearest-neighbors matching in a case-control study (originally 1:1 matched, published in 2004) of sporadic Campylobacter infections that included information on 433 exposures in 2632 subjects during 1998-1999. We performed multiple imputations of missing data (m = 100) and calculated Gower distances between cases and controls using all possible confounders for each exposure in each dataset. We matched each case with ≤20 controls within a data-determined distance. We calculated odds ratios and population attributable fractions (PAFs). RESULTS: Examination of pairwise correlation between exposures found very strong associations for 1046 pairs of exposures. More than 100 exposures were associated with campylobacteriosis, including nearly all risk factors identified using the previously published approach that included only 16 exposures and some less studied, rare exposures such as consumption of chicken liver and raw clams. Consumption of chicken and nonpoultry meat had the highest PAFs (62% and 59%, respectively). CONCLUSIONS: Nearest-neighbors matching appear to provide an improved ability to examine rare exposures and better control for numerous highly associated confounders.
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Infecciones por Campylobacter , Gastroenteritis , Infecciones por Campylobacter/epidemiología , Infecciones por Campylobacter/microbiología , Estudios de Casos y Controles , Humanos , Carne , Oportunidad Relativa , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Giardia duodenalis is the underlying cause of a significant number of outbreaks of gastrointestinal illness in humans and animals worldwide. The purpose of this study was to elucidate the prevalence and genetic diversity of G. duodenalis in captive alpine musk deer (Moschus chrysogaster) in China. A total of 202 fecal samples were collected from three farms in Gansu Province, China. Identification of G. duodenalis was conducted by nested PCR targeting the genes coding for SSU rRNA, ß-giardin (bg), glutamate dehydrogenase (gdh) and triosephosphate isomerase (tpi). The overall prevalence of G. duodenalis in captive alpine musk deer in surveyed area was 19.3% (39/202). Two G. duodenalis genetic assemblages were identified, namely assemblage A and E. Mixed genotype infections (A+E) were found in 15.4% (6/39) of positive samples. Multilocus genotyping (MLG) analysis of G. duodenalis isolates revealed six novel assemblage A MLGs formed by two newly-described MLG-subtypes which belonged to sub-assemblage AI. To the best of our knowledge, this is the first report on MLG of G. duodenalis isolates in captive alpine musk deer in China. The presence of zoonotic assemblages and sub-assemblages of G. duodenalis in deer species suggests that these animals may potentially act as a reservoir of this protozoan for humans.
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Ciervos , Giardia lamblia , Giardiasis , Animales , China/epidemiología , Ciervos/parasitología , Heces , Genotipo , Giardia lamblia/genética , Giardiasis/epidemiología , Giardiasis/veterinaria , Tipificación de Secuencias Multilocus , Filogenia , Prevalencia , RumiantesRESUMEN
We sought to determine which Salmonella serotypes cause illness related to the Thanksgiving holiday in the United States and to foods disproportionately eaten then (e.g., turkey). Using routine surveillance for 1998-2018 and a case-crossover design, we found serotype Reading to be most strongly associated with Thanksgiving.
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Vacaciones y Feriados , Salmonella , Animales , Salmonella/genética , Serogrupo , Pavos , Estados Unidos/epidemiologíaRESUMEN
To find out whether and how the prevalence and genetic diversity of Cryptosporidium in neonatal calves vary with the season, 380 fecal samples from neonatal calves on two large-scale farms in Xinjiang (Alar and Wensu) were studied using molecular biology techniques. Cryptosporidium was detected in 48.7% (185/380) of the samples and was most frequent in summer (56.8%), followed by spring (50.0%), winter (46.8%), and autumn (41.7%; p > 0.05). Calves with diarrhea seem to be more likely infected by Cryptosporidium than those without diarrhea (p < 0.01). We also found that C. parvum (n = 173), C. bovis (n = 7), and C. ryanae (n = 3) were the Cryptosporidium species detected in this study, and co-infections of these three species (n = 2) were also identified. Two subtypes (IIdA14G1 and IIdA15G1) of C. parvum were identified, and both can infect human. These results also show that neonatal calves commonly suffer diarrhea caused by C. parvum throughout the year.
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Enfermedades de los Bovinos , Criptosporidiosis , Cryptosporidium , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , China/epidemiología , Criptosporidiosis/epidemiología , Cryptosporidium/genética , Diarrea/epidemiología , Diarrea/veterinaria , Granjas , Heces , Variación Genética , Humanos , Prevalencia , Estaciones del AñoRESUMEN
BACKGROUND: Cryptosporidium andersoni initiates infection by releasing sporozoites from oocysts through excystation. However, the proteins involved in excystation are unknown. Determining the proteins that participate in the excystation of C. andersoni oocysts will increase our understanding of the excystation process. METHODS: Cryptosporidium andersoni oocysts were collected and purified from the feces of naturally infected adult cows. Tandem mass tags (TMT), coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis, were used to investigate the proteomic expression profiles of C. andersoni oocysts before and after excystation. RESULTS: Proteomic analysis identified a total of 1586 proteins, of which 17 were differentially expressed proteins (DEPs) upon excystation. These included 10 upregulated and seven downregulated proteins. The 17 proteins had multiple biological functions associated with control of gene expression at the level of transcription and biosynthetic and metabolic processes. Quantitative real-time RT-PCR of eight selected genes validated the proteomic data. CONCLUSIONS: This study provides information on the protein composition of C. andersoni oocysts as well as possible excystation factors. The data may be useful in identifying genes for diagnosis, vaccine development, and immunotherapy for Cryptosporidium.
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Cryptosporidium/clasificación , Regulación del Desarrollo de la Expresión Génica/fisiología , Oocistos/fisiología , Proteínas Protozoarias/metabolismo , Regulación hacia Abajo , Proteómica , Proteínas Protozoarias/genética , Reproducibilidad de los Resultados , Esporozoítos , Transcriptoma , Regulación hacia ArribaRESUMEN
A highly diastereoselective dearomative trifunctionalization of pyridinium salts with multifunctional o-hydroxyl aromatic azomethine ylides has been established, which not only provided a convenient and rapid method to assemble challenging and architecturally crowded chroman-pyrrolidine-hydrogenated pyridine fused pentacycles, but also represented a rare successful example of the higher-order multifunctionalization of pyridiniums.
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INTRODUCTION: Severe COVID-19 illness in adults has been linked to underlying medical conditions. This study identified frequent underlying conditions and their attributable risk of severe COVID-19 illness. METHODS: We used data from more than 800 US hospitals in the Premier Healthcare Database Special COVID-19 Release (PHD-SR) to describe hospitalized patients aged 18 years or older with COVID-19 from March 2020 through March 2021. We used multivariable generalized linear models to estimate adjusted risk of intensive care unit admission, invasive mechanical ventilation, and death associated with frequent conditions and total number of conditions. RESULTS: Among 4,899,447 hospitalized adults in PHD-SR, 540,667 (11.0%) were patients with COVID-19, of whom 94.9% had at least 1 underlying medical condition. Essential hypertension (50.4%), disorders of lipid metabolism (49.4%), and obesity (33.0%) were the most common. The strongest risk factors for death were obesity (adjusted risk ratio [aRR] = 1.30; 95% CI, 1.27-1.33), anxiety and fear-related disorders (aRR = 1.28; 95% CI, 1.25-1.31), and diabetes with complication (aRR = 1.26; 95% CI, 1.24-1.28), as well as the total number of conditions, with aRRs of death ranging from 1.53 (95% CI, 1.41-1.67) for patients with 1 condition to 3.82 (95% CI, 3.45-4.23) for patients with more than 10 conditions (compared with patients with no conditions). CONCLUSION: Certain underlying conditions and the number of conditions were associated with severe COVID-19 illness. Hypertension and disorders of lipid metabolism were the most frequent, whereas obesity, diabetes with complication, and anxiety disorders were the strongest risk factors for severe COVID-19 illness. Careful evaluation and management of underlying conditions among patients with COVID-19 can help stratify risk for severe illness.
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COVID-19 , Complicaciones de la Diabetes , Hospitalización/estadística & datos numéricos , Multimorbilidad , Enfermedades no Transmisibles/epidemiología , Obesidad , Trastornos Fóbicos , Factores de Edad , Anciano , COVID-19/mortalidad , COVID-19/terapia , Comorbilidad , Complicaciones de la Diabetes/diagnóstico , Complicaciones de la Diabetes/epidemiología , Femenino , Humanos , Masculino , Mortalidad , Obesidad/diagnóstico , Obesidad/epidemiología , Trastornos Fóbicos/diagnóstico , Trastornos Fóbicos/epidemiología , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiologíaRESUMEN
About 800 foodborne disease outbreaks are reported in the United States annually. Few are associated with food recalls. We compared 226 outbreaks associated with food recalls with those not associated with recalls during 2006-2016. Recall-associated outbreaks had, on average, more illnesses per outbreak and higher proportions of hospitalisations and deaths than non-recall-associated outbreaks. The top confirmed aetiology for recall-associated outbreaks was Salmonella. Pasteurised and unpasteurised dairy products, beef and molluscs were the most frequently implicated foods. The most common pathogen-food pairs for outbreaks with recalls were Escherichia coli-beef and norovirus-molluscs; the top pairs for non-recall-associated outbreaks were scombrotoxin-fish and ciguatoxin-fish. For outbreaks with recalls, 48% of the recalls occurred after the outbreak, 27% during the outbreak, 3% before the outbreak, and 22% were inconclusive or had unknown recall timing. Fifty per cent of recall-associated outbreaks were multistate, compared with 2% of non-recall-associated outbreaks. The differences between recall-associated outbreaks and non-recall-associated outbreaks help define the types of outbreaks and food vehicles that are likely to have a recall. Improved outbreak vehicle identification and traceability of rarely recalled foods could lead to more recalls of these products, resulting in fewer illnesses and deaths.
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Contaminación de Alimentos , Enfermedades Transmitidas por los Alimentos/epidemiología , Brotes de Enfermedades , Contaminación de Alimentos/legislación & jurisprudencia , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/microbiología , Humanos , Legislación Alimentaria , Estados UnidosRESUMEN
The enzymes exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GppA) play important roles in the bacterial stringent response. PPX degrades inorganic polyphosphate (polyP), a polymer composed of a few to hundreds of phosphate residues supporting cell survival in the stationary phase. The crystal structure of PPX from Porphyromonas gingivalis (PgPPX) in complex with catalytic magnesium ions and several sulfate ions was solved. PgPPX contained two domains and represented a "closed" configuration. Four sulfate ions forming a linear dispersed chain were observed in the aqueduct of the PPX dimer, which the long polyP chain most likely occupied. The side chain of R255 stretched into the cavity where polyP could be located, obstructing the entrance of larger substrates such as NTP and NDP. This study provided the first view into the structure of the PPX/GppA homolog in complex with magnesium ions and substrate analogs and explained how PgPPX implemented its functionality.