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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
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
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
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
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
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.
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Polifosfatos , Porphyromonas gingivalis , Ácido Anhídrido Hidrolasas/química , Magnesio , Polifosfatos/metabolismo , Porphyromonas gingivalis/metabolismoRESUMEN
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
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
BACKGROUND: A clinical diagnosis model include thyroid functions, thyroid antibodies and radioactive iodine uptake (RAIU) of patients with hyperthyroidism were established and as new evaluation indicators for the differentiation of the Graves' disease (GD) and Hashimoto's thyroiditis (HT). METHODS: Clinical data of patients with newly diagnosed hyperthyroidism including gender, age, thyroid function, thyroid antibodies (FT3, FT4, TSH, TPOAb, TGAb, TRAb), RAIU (2 h, 6 h, 24 h) were collected. A stepwise regression analysis was performed to establish a model based on these variables. RESULTS: Model 1 was subjected to stepwise regression analysis. After screening, the variables that entered the model included FT3, TGAb, TPOAb, TRAb, 2-h RAIU, 24-h RAIU and gender, in which the variables FT3, TGAb, TRAb, 2-h RAIU, 24-h RAIU, and gender were significantly different. Model 2 without RAIU was also subjected to stepwise regression analysis. After screening, the variables that entered the model included FT4, TGAb, TPOAb, TRAb and gender were statistical significant. The larger value of each variable in the two models indicated the higher probability to diagnose GD. The area under the receiver operating characteristic (ROC) curve of model 1 was 0.843 (95% CI 0.779-0.894), and the area under the ROC curve of model 2 was 0.806 (95% CI 0.685-0.824), which showed good differential diagnostic value. CONCLUSIONS: GD and HT diagnosis model was established according to the variables including gender, FT3, TGAb, TRAb, the 2-h RAIU, the 24-h RAIU in the model 1, and the variables FT4, TGAb, TPOAb, TRAb and gender in the model 2 that did not include RAIU. These models had high value to differentiate GD and HT for patients with early hyperthyroidism.
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Enfermedad de Graves/diagnóstico , Enfermedad de Hashimoto/diagnóstico , Modelos Biológicos , Adolescente , Adulto , Anciano , Área Bajo la Curva , Femenino , Enfermedad de Graves/patología , Enfermedad de Hashimoto/patología , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de Riesgo , Sensibilidad y Especificidad , Adulto JovenRESUMEN
To determine the prevalence of Cryptosporidium in dairy cattle in Guangdong Province, South China, 1440 fecal samples were collected from 10 farms and screened for Cryptosporidium with PCR. The overall prevalence of Cryptosporidium was 4.38% (63/1440), and the infection rates in preweaned calves, postweaned calves, heifers and adults were 6.4% (19/297), 6.19% (33/533), 1.48% (4/271) and 2.06% (7/339), respectively. Three Cryptosporidium species, Cryptosporidium andersoni (n = 33), Cryptosporidium bovis (n = 22) and Cryptosporidium ryanae (n = 8) were detected by DNA sequence analysis of the 63 positive samples, and C. andersoni was identified as the most common species on the dairy cattle farms. In preweaned calves, C. bovis was the most prevalent species (9/19, 47.4%). In contrast, C. andersoni was the predominant species (19/33, 57.6%) in postweaned calves and the only species found in heifers and adults. The zoonotic species Cryptosporidium parvum was not detected in this study. Twenty-four C. andersoni isolates were successfully classified into three multilocus sequence typing (MLST) subtypes. MLST subtype A4,A4,A4,A1 was the predominant subtype, and MLST subtype A2,A5,A2,A1, previously found in sheep, was detected in cattle for the first time. A linkage disequilibrium analysis showed that the C. andersoni isolates had a clonal genetic population structure. However, further molecular studies are required to better understand the epidemiology of Cryptosporidium in Guangdong.
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Enfermedades de los Bovinos/epidemiología , Criptosporidiosis/epidemiología , Cryptosporidium/genética , Distribución por Edad , Animales , Secuencia de Bases , Bovinos , Enfermedades de los Bovinos/parasitología , China/epidemiología , Criptosporidiosis/parasitología , Cryptosporidium/clasificación , Cryptosporidium/fisiología , ADN Protozoario/química , ADN Protozoario/aislamiento & purificación , Electroforesis en Gel de Agar/veterinaria , Heces/parasitología , Femenino , Desequilibrio de Ligamiento , Epidemiología Molecular , Reacción en Cadena de la Polimerasa/veterinaria , Prevalencia , Análisis de RegresiónRESUMEN
Cryptosporidium is a genus of protozoal parasites that affects the gastrointestinal epithelium of a variety of hosts. Several models of experimental infection have been described to study the susceptibility, infectivity and pathogenicity among different Cryptosporidium species and isolates. This study aimed to establish an experimental infection of Cryptodporidium canis in canids. Infectivity and pathogenicity have been measured by evaluating the clinical status, pattern of oocyst excretion and histological examination. Results showed that C. canis was not infective for immunocompetent dogs or mice with severe combined immunodeficiency syndrome (SCID). Oocysts were first detected in the feces of immunosuppressed dogs on day 3 post-infection (p.i.), with levels peaking twice on days 10 and 17 p.i. during the patent period. cryptosporidial developmental stages were found in the duodenum and jejunum of dogs in histological sections stained with hematoxylin and eosin (H & E) and using scanning electron microscopy (SEM). Histopathological changes in the intestinal tract of infected dogs were characterized by epithelial metaplasia and dilatation; the integrity of intestinal mucosal epithelial cells was distinctly damaged with whole sheets of cilia sloughed away. Ultrastructural observation data were consistent with histological observations. Based on these findings, the canine model described in this work will be useful to evaluate clinical, parasitological and histological aspects of C. canis infection and will be useful for the further understanding of cryptosporidiosis, drug development, and vaccine development.
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Criptosporidiosis/parasitología , Modelos Animales de Enfermedad , Perros , Huésped Inmunocomprometido , Animales , Criptosporidiosis/patología , Cryptosporidium/aislamiento & purificación , Cryptosporidium/ultraestructura , Diarrea/parasitología , Duodeno/parasitología , Duodeno/patología , Duodeno/ultraestructura , Heces/parasitología , Yeyuno/parasitología , Yeyuno/patología , Yeyuno/ultraestructura , Ratones , Ratones SCID , Microscopía Electrónica de Rastreo , Microvellosidades/parasitología , Microvellosidades/patología , Microvellosidades/ultraestructura , Oocistos/aislamiento & purificaciónRESUMEN
PURPOSE: A systematic review and meta-analysis based on randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of steroid injection in total knee or hip arthroplasty (TKA/THA). METHODS: A systematical electronic search identified the relevant RCTs in the databases of PubMed, EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials. Two reviewers independently completed data collection and assessment of methodological quality. Meta-analysis was performed for the outcomes of visual analogue pain score, range of motion (ROM), postoperative nausea and vomiting (PONV), morphine consumption, length of stay and complications. RESULTS: A total of 863 participants were enrolled. Patients who received steroid injection had a significant reduction in the incidence of PONV and improvement in short-term pain score, and ROM (p < 0.05). Regarding morphine consumption and hospitalization time, the steroid group showed a significant reduction in TKA but no statistically significant difference in THA. In addition, there were no significant differences in complications (n.s.). CONCLUSIONS: The current evidence suggests that steroid injection in TKA/THA provides short-term advantages in pain relief and antiemetic effects. The optimal dose and long-term effects of steroid injection still require numerous studies. LEVEL OF EVIDENCE: II.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Glucocorticoides/administración & dosificación , Dolor Postoperatorio/prevención & control , Analgésicos Opioides/administración & dosificación , Utilización de Medicamentos , Humanos , Inyecciones Intraarticulares , Tiempo de Internación , Morfina/administración & dosificación , Dimensión del Dolor , Náusea y Vómito Posoperatorios/prevención & controlRESUMEN
To estimate the prevalence and public health significance of cryptosporidiosis in goats in China, 1265 fecal samples from seven farms in Henan province and Chongqing city were examined for Cryptosporidium oocysts. The overall infection rate of Cryptosporidium spp. was 3.48% (44/1256). Significant difference was observed among age groups, with the post weaned kids having the highest infection rate (4.58%; ρ<0.01). Cryptosporidium spp. were characterized by PCR-restriction fragment length polymorphism (RFLP) analysis and DNA sequence analysis of the small subunit (SSU) rRNA gene. The SSU rRNA-based PCR identified three Cryptosporidium species, including Cryptosporidium ubiquitum (24/44) in Henan and Chongqing, and Cryptosporidium andersoni (16/44) and Cryptosporidium xiaoi (4/44) in Henan. Among which, the C. ubiquitum and C. andersoni were first identified in goats thus far and were found in all age groups except no C. andersoni being found in the postparturition nannies, whereas the C. xiaoi was detected in pre-weaned kids and pregnant nannies. Subtyping C. ubiquitum by DNA sequence analysis of the 60 kDa glycoprotein (gp60) gene suggested the isolates identified all belonged to zoonotic XIIa subtype 2. Thus, the dominant C. ubiquitum found in this study and the XIIa subtype 2 has been found in humans indicated goats are a potential source for zoonotic infections with the C. ubiquitum. More studies are needed for better understanding of differences in the transmission and public health significance of cryptosporidiosis in goats.
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Criptosporidiosis/veterinaria , Cryptosporidium/aislamiento & purificación , Enfermedades de las Cabras/parasitología , Distribución por Edad , Animales , Secuencia de Bases , China/epidemiología , Criptosporidiosis/epidemiología , Criptosporidiosis/parasitología , Cryptosporidium/clasificación , Cryptosporidium/genética , ADN Protozoario/química , ADN Protozoario/aislamiento & purificación , Heces/parasitología , Femenino , Técnicas de Genotipaje/veterinaria , Enfermedades de las Cabras/epidemiología , Cabras , Datos de Secuencia Molecular , Oocistos/química , Filogenia , Reacción en Cadena de la Polimerasa/veterinaria , Polimorfismo de Longitud del Fragmento de Restricción , Embarazo , Complicaciones Parasitarias del Embarazo/epidemiología , Complicaciones Parasitarias del Embarazo/parasitología , Complicaciones Parasitarias del Embarazo/veterinaria , Prevalencia , ARN Ribosómico/genética , Mapeo Restrictivo/veterinaria , Zoonosis/epidemiología , Zoonosis/parasitologíaRESUMEN
PURPOSE: A systematic review and meta-analysis based on randomized controlled trials (RCTs) were conducted to evaluate the efficiency and safety of periarticular multimodal drug injection in total knee arthroplasty (TKA). METHODS: Periarticular injection with the use of multimodal drugs is an efficient alternative for postoperative analgesia in TKA. A systematical electronic search was performed to identify the eligible RCTs in the databases of PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and the Chinese Biomedical Literature Database. Two independent reviewers completed data collection and assessment of methodological quality. The quality of evidence of outcomes was judged using GRADE criteria. Meta-analysis was performed for the outcomes of pain, straight leg raise, operating time, hospital stay and complications. RESULTS: Ten RCTs including eight studies with 1,216 TKAs in 835 patients met the inclusion criteria. Periarticular injection with multimodal drugs in TKA was associated with short-term benefits in terms of pain relief, straight leg raise, narcotic consumption, and the rates of nausea, vomiting, rash and pruritus. There were no statistically significant differences in operating time, hospital stay, wound complications and deep vein thrombosis between both groups. CONCLUSIONS: The current evidence suggests that periarticular multimodal drug injection in TKA provides short-term advantages in pain relief, straight leg raise and postoperative complications.
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Artralgia/tratamiento farmacológico , Artroplastia de Reemplazo de Rodilla , Dolor Postoperatorio/tratamiento farmacológico , Analgésicos Opioides/administración & dosificación , Anestésicos Locales/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Epinefrina/administración & dosificación , Glucocorticoides/administración & dosificación , Humanos , Inyecciones Intraarticulares , Manejo del Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
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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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
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
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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The efficacy of periarticular multimodal drug injection (PMDI) to reduce pain after total knee or hip arthroplasty (TKA or THA) still remains controversial. Our study aimed at evaluating the efficacy of PMDI after TKA or THA. A fully recursive literature search was conducted to identify relevant randomized controlled trials. Ultimately, 21 studies were included in the analysis. Pooled results showed that the PMDI group had better pain relief, less opioid consumption, larger range of motion, and lower rates of nausea and vomiting than the placebo group. No significant difference was seen in regard to the length of hospital stay between the two groups. In conclusion, PMDI should be recommended for the pain management after TKA or THA.
Asunto(s)
Analgésicos/administración & dosificación , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Dolor Postoperatorio/tratamiento farmacológico , Humanos , Inyecciones , Inyecciones Intraarticulares , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
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.