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BACKGROUND: A significant number of chest pain patients had previous cardiac imaging tests (CIT) performed before being presented to the Emergency Department (ED). The HEART (history, electrocardiogram, age, risk factors, and troponin) score has been used to risk-stratify chest pain patients in the ED, but not particularly for patients with CIT performed. We aim to modify the current HEART score with the addition of most recent CIT findings (referred to as HEART2 score), to predict a 30-day major adverse cardiac event (MACE) among ED chest pain patients, compare the performance accuracy of using HEART versus HEART2 score for 30-day MACE outcome predictions, and further determine the value of HEART2 in a subset group of ED chest pain patients (i.e., ones with previous CIT). METHODS: This is a single-center observational study. We included chest pain patients with HEART scores calculated during their index ED visits. A modified HEART2 score was developed with the addition of CIT findings as one of the HEART2 components. Patients were divided into three groups, including low (≤ 3), moderate (4-6), and high-risk HEART/HEART2 scores (≥ 7). MACE occurrence of a patient with different risks of HEART and HEART2 scores and overall performance accuracy of HEART versus HEART2 score predicting MACE outcomes were compared. RESULTS: We included a total of 9419 chest pain patients at ED, among which one out of five patients (1874/9419) had previous CIT performed. Fewer (38.2%) of such patients had low-risk HEART scores in comparison to 55.5% of low-risk HEART2 scores (p < 0.001). The MACE outcomes were similar in low-risk HEART patients compared with low-risk HEART2 patients (2.2% versus 3.1%, p = 0.3021). The overall performance accuracy of using the HEART2 score to stratify chest pain patients with previous CIT was better than using the HEART score's (AUC 0.74 versus 0.71, p = 0.0082). CONCLUSIONS: Using the HEART2 score might be suitable to stratify low-to-moderate risk chest pain patients at ED with a similar 30-days MACE occurrence compared to the HEART score. More importantly, with the use of similar low-risk criteria (HEART2 ≤ 3), over 45% more chest pain patients with previous CIT performed could be discharged directly from ED.
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Dolor en el Pecho , Servicio de Urgencia en Hospital , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/epidemiología , Dolor en el Pecho/etiología , Electrocardiografía , Humanos , Valor Predictivo de las Pruebas , Medición de Riesgo/métodos , Factores de Riesgo , TroponinaRESUMEN
BACKGROUND: Visceral leishmaniasis (VL), due to Leishmania infantum, is a persistent intracellular parasitic infection transmitted by the bite of infected sand flies. Symptomatic VL has been reported in U.S. soldiers with Iraq deployment. Untreated symptomatic VL can be fatal; asymptomatic VL (AVL) may establish a lifelong risk of reactivation. We report prevalence and AVL risk factors in Operation Iraqi Freedom (OIF) deployers during 2002-11. METHODS: Healthy soldiers exposed to VL endemic areas in Iraq and 50 controls who never traveled to endemic regions were recruited through military healthcare facilities (2015-17). Responses to a risk factor survey and blood samples were obtained. Leishmania research diagnostics utilized included enzyme-linked immunosorbent assay (ELISA), rk39 test strips, quantitative polymerase chain reaction (PCR), and interferon gamma release (IGRA) assays. Statistical analyses included Fisher exact test, Pearson χ2 test, Mann-Whitney U test, and logistic regression. RESULTS: 200 deployed subjects were enrolled, mostly males (84.0%), of white ethnicity (79.0%), and median age 41 (range 24-61) years. 64% were seropositive for Phlebotomus alexandri saliva antibodies. Prevalence of AVL (any positive test result) was 39/200 (19.5%, 95% confidence interval 14.4%-25.8%). Two (1.0%) PCR, 10 (5%) ELISA, and 28 (14%) IGRA samples were positive. Travel to Ninewa governorate increased risk for AVL (P = .01). CONCLUSION: AVL was identified in 19.5% of OIF deployers; travel to northwest Iraq correlated with infection. Further studies are needed to inform risk for reactivation VL in US veterans and to target additional blood safety and surveillance measures.
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Infecciones Asintomáticas , Leishmania infantum , Leishmaniasis Visceral/epidemiología , Leishmaniasis Visceral/parasitología , Personal Militar , Adulto , Femenino , Geografía , Humanos , Irak/epidemiología , Leishmaniasis Visceral/diagnóstico , Masculino , Persona de Mediana Edad , Vigilancia en Salud Pública , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The molecular mechanisms of cellular changes responsible for diabetic gastroparesis, primarily seen in middle-aged women, still remain incompletely defined. We hypothesized that a decrease in the expression, dimerization, and post-translational modification of neuronal nitric oxide synthase alpha (nNOSα) is estrogen mediated and responsible for the gender-specific prevalence of this malady. METHODS: We induced diabetes by injecting male and female rats with streptozotocin. Male diabetic rats without gastroparesis were then injected with estrogen for 3 weeks and evaluated for gastroparesis development. Gastric tissues were analyzed for the elucidation of biochemical events associated with diabetes and gastroparetic dysfunction. RESULTS: Although male diabetic, gastroparetic (either streptozotocin- or estrogen-induced) rats exhibited similarity in disease pathology to that of females, the molecular mechanisms of development were different. Our results indicate that slow gastric emptying in both male diabetic, gastroparetic rat groups was not associated with the level of expression of nNOSα in gastric tissues. However, nNOSα dimerization, which reflects nNOSα activation, did decline slightly in the antrum of diabetic males with estrogen-induced gastroparesis, suggesting a possible estrogen role. Females with diabetic gastroparesis, in contrast, demonstrated significantly impaired levels and dimerization of nNOSα in the antrum and pylorus. Although the precise mechanism remains unknown, nNOSα dimerization impairment in female antrum is apparently associated with reduced phosphorylation of Ser(1416) in the activation loop of nNOSα. CONCLUSION: Taken together, these results demonstrate that gender and estrogens may be leading factors, through molecular changes involved in nitric oxide synthesis down-regulation, within the antrum and pylorus of female diabetic, gastroparetic rats.
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Diabetes Mellitus Experimental , Estradiol/metabolismo , Gastroparesia/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Animales , Western Blotting , Dimerización , Femenino , Vaciamiento Gástrico , Gastroparesia/fisiopatología , Masculino , Fosforilación , Ratas , Factores SexualesRESUMEN
OBJECTIVE: We aimed to examine the role of the HEART (history, EKG, age, risk factors, and troponin) score in the evaluation of six clinical outcomes among three groups of patients in the emergency department (ED). METHODS: We performed a retrospective observational study among three ED patient groups including White, Black, and Hispanic patients. ED providers used the HEART score to assess the need for patient hospital admission and for emergent cardiac imaging tests (CITs). HEART scores were measured using classification accuracy rates. Performance accuracies were measured in terms of HEART score in relation to four clinical outcomes (positive findings of CITs, ED returns, hospital readmissions, and 30-day major adverse cardiac events [MACE]). RESULTS: A high classification accuracy rate (87%) was found for use of the HEART score to determine hospital admission. HEART scores showed moderate accuracy (area under the receiver operating characteristic curve 0.66-0.78) in predicting results of emergent CITs, 30-day hospital readmissions, and 30-day MACE outcomes. CONCLUSIONS: Providers adhered to use of the HEART score to determine hospital admission. The HEART score may be associated with emergent CIT findings, 30-day hospital readmissions, and 30-day MACE outcomes, with no differences among White, Black, and Hispanic patient populations.
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Dolor en el Pecho , Servicio de Urgencia en Hospital , Humanos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Substance P (SP) and neuropeptide Y (NPY), excitatory and inhibitory neuropeptides, respectively, may impact gastric motility in patients with diabetic mellitus (DM). We investigated these neuropeptide levels, NPY receptors, total nitric oxide synthase (NOS) levels, and neuronal NOS alpha (nNOSα) activation status and levels in streptozotocin-induced type I diabetes in male rats. METHODS: Rats were grouped based on serum glucose and gastric emptying time: normal untreated control (CM), diabetic (DM) and diabetic gastroparesis (DM + GP). Neuropeptide serum levels were determined by enzyme-linked immunosorbent assay (ELISA). Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting measured NPY receptors, Y1 and Y2, and nNOSα expression. Low-temperature SDS-PAGE followed by western blotting was used to measure the dimerization of nNOSα. An NOS colorimetric assay kit was used to measure total NOS activity. RESULTS: SP levels were significantly decreased (P < 0.05) in DM and DM + GP compared to CM. NPY levels were significantly decreased (P < 0.05) in DM compared to CM, and DM + GP had a more significantly decreased NPY when compared to both DM and CM. Protein levels of neuropeptide receptor Y1 (NPY-Y1) in the smooth muscle of pylorus were significantly increased in DM, but not in DM + GP when compared to CM. Neuropeptide receptor Y2 (NPY-Y2) was not detected. Changes in nNOSα activity and their protein levels, as well as total NOS activity, among the groups were insignificant. CONCLUSIONS: Increased expression of pylorus NPY-1R and decreased serum NPY are present in diabetes. A more pronounced decreased serum NPY with no NPY-1R upregulation in pyloric smooth muscle is associated with gastroparesis. NPY levels show no relationship with nNOSα levels, their activation status, or total NOS activity in pyloric smooth muscle. These data suggest a pathophysiological role of severely depleted NPY and absence of NPY-Y1 upregulation for gastroparesis phenotype.
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Controversy exists regarding the appropriate timing for placement of permanent intra-abdominal mesh after inadvertent enterotomy during elective hernia repair. The aim of this study was to examine mesh placement at variable postoperative periods and the subsequent risk of infection. Fifty rodents were divided into five groups. Groups one to four underwent laparotomy, enterotomy, and repair. Physiomesh® was placed at the index operation one, three, or seven days postoperatively in Groups 1, 2, 3, and 4. Group 5 underwent mesh placement only. Necropsy with mesh harvest was performed seven days after placement. Cultures of mesh were obtained and Fisher's exact test was used to compare groups. Bacterial growth postsonication was identified in 30, 30, 50, and 90 per cent versus 20 per cent in controls. Compared with controls, there was significantly increased risk of mesh infection when it was placed seven days after enterotomy (P = 0.006). There was no significant difference in bacterial growth when mesh was placed at the time of enterotomy, one or three days later. The risk of bacterial contamination of permanent mesh placed immediately after inadvertent enterotomy during elective hernia repair is as safe as placing mesh at one or three days. Placing mesh at seven days significantly increased the risk of mesh contamination.
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Herniorrafia/efectos adversos , Intestinos/lesiones , Intestinos/cirugía , Complicaciones Intraoperatorias/cirugía , Mallas Quirúrgicas , Infección de la Herida Quirúrgica/prevención & control , Animales , Procedimientos Quirúrgicos Electivos , Herniorrafia/instrumentación , Herniorrafia/métodos , Masculino , Proyectos Piloto , Ratas , Ratas Sprague-Dawley , Mallas Quirúrgicas/microbiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/microbiología , Factores de TiempoRESUMEN
BACKGROUND: Gastroparesis is a significant co-morbidity affecting up to 50% of patients with diabetes and is disproportionately found in women. Prior studies have suggested that loss of interstitial cells of Cajal, hyperglycemia, and nitric oxide dysfunction are potential causes of gastroparesis. Since diabetic gastroparesis affects more women than men, we performed an exploratory study with a diabetic rat model to determine if sex hormone signaling is altered in those where gastroparesis develops. METHODS: We injected male rats with streptozotocin (STZ) to model type I diabetes, as confirmed by blood glucose levels. Gastroparesis was determined by acetaminophen gavage and serum acetaminophen levels. Rats were grouped based on acetaminophen and blood glucose data: diabetic (DM), diabetic and gastroparetic (DM + GP), and control (CM). Serum levels of testosterone, estrogen, and insulin were determined as well as aromatase expression in pyloric tissue and serum. Androgen receptor and estrogen receptor α (ERα) and ß (ERß) were also measured in the pylorus. RESULTS: Compared to CM, estrogen increased and testosterone decreased in both DM and DM + GP rats. Sex hormone levels were not different between DM and DM + GP. Serum aromatase was increased in DM and DM + GP rats; however, pyloric tissue levels were not significantly different from controls. ERα was unchanged and androgen receptor decreased in DM and DM + GP. ERß was increased only in DM + GP animals. CONCLUSION: Our study implicates increased pyloric ERß in the development of gastroparesis in STZ-induced male diabetic rats. Increased serum aromatase is likely responsible for altered sex hormone levels. Our study supports the implication of sex hormone signaling in diabetic development and demonstrates a potential unique role for pyloric ERß in male diabetic gastroparesis.
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A short-term, time-dependent smoke exposure of rats in a nose-only chamber to burning wood and 24-h recovery time revealed inflammation of the airways with varying degrees of injury from loss of cilia, degeneration of epithelium, and squamous metaplasia to submucosal edema. These histological changes were reflected in variable expression of the secretory Muc5AC and low expression of membrane-associated Muc4 mucin genes. 20-min smoke exposure in extended recovery experiments showed marked disorder of tracheal epithelium for up to 72 h of recovery with a return to normal by 7 days. Gene expressions were elevated at 24 and 48 h of recovery. 30-min smoke exposure showed a more severe degeneration of the epithelium and a longer recovery time. Muc5AC expression decreased after 72 h of recovery, while there was upregulation of Muc4 gene from 48 through 96 h. Because Muc4 upregulation and histological results correlate and it has reportedly been associated with epithelium renewal, Muc4 gene may be a useful marker for the regeneration of tracheal epithelium.
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Mucinas/genética , Lesión por Inhalación de Humo/fisiopatología , Humo/efectos adversos , Madera , Animales , Antioxidantes/metabolismo , Biomarcadores , Modelos Animales de Enfermedad , Exposición a Riesgos Ambientales , Femenino , Expresión Génica , Masculino , Mucina 5AC , Mucina 4 , Ratas , Ratas Sprague-Dawley , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/fisiopatología , Lesión por Inhalación de Humo/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Helicobacter pylori causes disease manifestations in humans including chronic gastric and peptic ulcers, gastric cancer, and lymphoid tissue lymphoma. Increasing rates of H. pylori clarithromycin resistance has led to higher rates of disease development. Because antibiotic resistance involves modifications of outer membrane proteins (OMP) in other Gram-negative bacteria, this study focuses on identification of H. pylori OMP's using comparative proteomic analyses of clarithromycin-susceptible and -resistant H. pylori strains. Comparative proteomics analyses of isolated sarcosine-insoluble OMP fractions from clarithromycin-susceptible and -resistant H. pylori strains were performed by 1) one dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis protein separation and 2) in-gel digestion of the isolated proteins and mass spectrometry analysis by Matrix Assisted Laser Desorption Ionization-tandem mass spectrometry. Iron-regulated membrane protein, UreaseB, EF-Tu, and putative OMP were down-regulated; HopT (BabB) transmembrane protein, HofC, and OMP31 were up-regulated in clarithromycin-resistant H. pylori. Western blotting and real time PCR, respectively, validated UreaseB subunit and EF-Tu changes at the protein level, and mRNA expression of HofC and HopT. This limited proteomic study provides evidence that alteration of the outer membrane proteins' profile may be a novel mechanism involved in clarithromycin resistance in H. pylori.