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BACKGROUND: The COVID-19 pandemic had a profound impact on healthcare systems and services, including routine immunization (RI). To date, there is limited information on the effects of the COVID-19 pandemic on RI in West African countries such as Sierra Leone, which had already experienced public health emergencies that disrupted its healthcare system. Here, we describe the impact of the COVID-19 pandemic on the RI of key antigens in Sierra Leone. METHODS: We used vaccination data from the District Health Information System for BCG, measles-rubella 1 and 2, and pentavalent 1 and 3 antigens. We compared 2019, 2020, 2021, and 2022 annual coverage rates for the selected antigens at the national and district levels. We used the Pearson chi-square test to assess the difference between annual coverage rates between 2019 and 2020, 2020-2021, and 2021-2022. RESULTS: National coverage rates for all antigens declined in 2019-2020, notably measles-rubella 1 and pentavalent 3 (-5.4% and - 4.9%). Between 2020 and 2021, there was an overall increase in coverage (+ 0.2% to + 2.5%), except for measles-rubella 2 (-1.8%). Measles-rubella antigens rebounded in 2021-2022, while others decreased between - 0.5 and - 1.9% in coverage. Overall, all district-level coverage rates in 2022 were lower than those in 2019. Most districts decreased between 2019 and 2022, though a few had a continuous increase; some had an increase/recovery between 2020 and 2021; some districts had recovered 2019 levels by 2022. CONCLUSION: The COVID-19 pandemic impacted Sierra Leone's national BCG, measles-rubella, and pentavalent antigen immunization, which were not fully restored in 2022. Most districts experienced notable coverage declines during the pandemic, though a few reached or surpassed 2019 rates in 2022. Examining pandemic impact can benefit from a focus beyond the national level to identify vulnerable regions. Sierra Leone's post-pandemic RI reestablishment needs targeted strategies and continual investments for equitable access and coverage, as well as to prevent vaccine-preventable diseases.
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COVID-19 , Cobertura de Vacunación , Sierra Leona/epidemiología , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Cobertura de Vacunación/estadística & datos numéricos , Programas de Inmunización/estadística & datos numéricos , Vacuna BCG/administración & dosificación , Vacuna BCG/uso terapéuticoRESUMEN
Snake venom can vary both among and within species. While some groups of New World pitvipers-such as rattlesnakes-have been well studied, very little is known about the venom of montane pitvipers (Cerrophidion) found across the Mesoamerican highlands. Compared to most well-studied rattlesnakes, which are widely distributed, the isolated montane populations of Cerrophidion may facilitate unique evolutionary trajectories and venom differentiation. Here, we describe the venom gland transcriptomes for populations of C. petlalcalensis, C. tzotzilorum, and C. godmani from Mexico, and a single individual of C. sasai from Costa Rica. We explore gene expression variation in Cerrophidion and sequence evolution of toxins within C. godmani specifically. Cerrophidion venom gland transcriptomes are composed primarily of snake venom metalloproteinases, phospholipase A[Formula: see text]s (PLA[Formula: see text]s), and snake venom serine proteases. Cerrophidion petlalcalensis shows little intraspecific variation; however, C. godmani and C. tzotzilorum differ significantly between geographically isolated populations. Interestingly, intraspecific variation was mostly attributed to expression variation as we did not detect signals of selection within C. godmani toxins. Additionally, we found PLA[Formula: see text]-like myotoxins in all species except C. petlalcalensis, and crotoxin-like PLA[Formula: see text]s in the southern population of C. godmani. Our results demonstrate significant intraspecific venom variation within C. godmani and C. tzotzilorum. The toxins of C. godmani show little evidence of directional selection where variation in toxin sequence is consistent with evolution under a model of mutation-drift equilibrium. Cerrophidion godmani individuals from the southern population may exhibit neurotoxic venom activity given the presence of crotoxin-like PLA[Formula: see text]s; however, further research is required to confirm this hypothesis.
RESUMEN: El veneno de las serpientes puede variar entre y dentro de las especies. Mientras algunos grupos de viperidos del Nuevo Mundocomo las cascabeleshan sido bien estudiadas, muy poco se sabe acerca del veneno de las nauyacas de frío (Cerrophidion) que se encuentran en las zonas altas de Mesoamérica. Comparadas con las extensamente estudiadas cascabeles, que estan ampliamente distribuidas, las poblaciones de Cerrophidion, aisladas en montañas, pueden poseer trayectorias evolutivas y diferenciación en su veneno unicos. En el presente trabajo, describimos el transcriptoma de las glándulas de veneno de poblaciones de C. petlalcalensis, C. tzotzilorum, y C. godmani de México, y un individuo de C. sasai de Costa Rica. Exploramos la variación en la expresión de toxinas en Cerrophidion y la evolución en las secuencias geneticas en C. godmani específicamente. El transcriptoma de la glándula de veneno de Cerrophidion esta compuesto principalmente de Metaloproteinasas de Veneno de Serpiente, Fosfolipasas A[Formula: see text] (PLA[Formula: see text]s), y Serin Proteasas de Veneno de Serpiente. Cerrophidion petlalcalensis presenta poca variación intraespecífica; sin embargo, los transcriptomas de la glandula de veneno de C. godmani y C. tzotzilorum difieren significativamente entre poblaciones geográficamente aisladas. Curiosamente, la variación intraespecífica estuvo atribuida principalmente a la expresión de las toxinas ya que no encontramos señales de selección en las toxinas de C. godmani. Adicionalmente, encontramos miotoxinas similares a PLA[Formula: see text] en todas las especies excepto C. petlalcalensis, y PLA[Formula: see text]s similares a crotoxina en la población sureña de C. godmani. Nuestros resultados demuestran la presencia de variacion intraespecífica presente en el veneno de C. godmani y C. tzotzilorum. Las toxinas de Cerrophidion godmani muestran poca evidencia de selección direccional, y la variación en la secuencias de las toxinas es consistente con evolucion bajo un modelo de equilibrio de mutación-deriva. Algunos individuos de C. godmani de la población del sur potencialmente tienen un veneno neurotóxico dada la presencia de PLA[Formula: see text]s similares a la crotoxina, sin embargo, se necesita más evidencia para corroborar esta hipótesis.
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Venenos de Crotálidos , Crotalinae , Crotoxina , Viperidae , Humanos , Animales , Crotalinae/genética , Crotalinae/metabolismo , Viperidae/metabolismo , Crotoxina/metabolismo , Venenos de Crotálidos/genética , Venenos de Crotálidos/metabolismo , Venenos de Crotálidos/toxicidad , Venenos de Serpiente/metabolismo , Poliésteres/metabolismoRESUMEN
BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A complex, time-consuming laboratory evaluation is currently required to distinguish MIS-C from other illnesses. New assays are urgently needed early in the evaluation process to expedite MIS-C workup and initiate treatment when appropriate. This study aimed to measure the performance of a monocyte anisocytosis index, obtained on routine complete blood count (CBC), to rapidly identify subjects with MIS-C at risk for cardiac complications. METHODS: We measured monocyte anisocytosis, quantified by monocyte distribution width (MDW), in blood samples collected from children who sought medical care in a single medical center from April 2020 to October 2020 (discovery cohort). After identifying an effective MDW threshold associated with MIS-C, we tested the utility of MDW as a tier 1 assay for MIS-C at multiple institutions from October 2020 to October 2021 (validation cohort). The main outcome was the early screening of MIS-C, with a focus on children with MIS-C who displayed cardiac complications. The screening accuracy of MDW was compared to tier 1 routine laboratory tests recommended for evaluating a child for MIS-C. RESULTS: We enrolled 765 children and collected 846 blood samples for analysis. In the discovery cohort, monocyte anisocytosis, quantified as an MDW threshold of 24.0, had 100% sensitivity (95% CI 78-100%) and 80% specificity (95% CI 69-88%) for identifying MIS-C. In the validation cohort, an initial MDW greater than 24.0 maintained a 100% sensitivity (95% CI 80-100%) and monocyte anisocytosis displayed a diagnostic accuracy greater that other clinically available hematologic parameters. Monocyte anisocytosis decreased with disease resolution to values equivalent to those of healthy controls. CONCLUSIONS: Monocyte anisocytosis detected by CBC early in the clinical workup improves the identification of children with MIS-C with cardiac complications, thereby creating opportunities for improving current practice guidelines.
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COVID-19 , COVID-19/complicaciones , COVID-19/diagnóstico , Niño , Humanos , Monocitos , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Síndrome de Respuesta Inflamatoria Sistémica/diagnósticoRESUMEN
BACKGROUND AND OBJECTIVES: Multisystem Inflammatory Syndrome in Children (MIS-C) is an emerging complication of COVID-19 which lacks a definitive diagnostic test and evidence-based guidelines for workup. We sought to assess practitioners' preferences when initiating a workup for pediatric patients presenting with symptoms concerning for MIS-C. METHODS: In a cross-sectional vignette-based survey, providers were presented with clinical vignettes of a patient presenting with 24 h of fever from a community with high rates of COVID-19. Respondents were asked about their general practices in pursuing a workup for potential MIS-C including testing obtained, criteria for diagnosis, and timing to confirm or rule out the diagnosis. RESULTS: Most of the 174 respondents were physicians from the United States at academic medical centers. The majority of providers would not initiate MIS-C workup for fever and non-specific symptoms unless the fever lasted more than 72 h. Skin rash, abdominal pain, and shortness of breath were symptoms that raised greatest concern for MIS-C. Most providers would obtain COVID-19 PCR or antigen testing, plus blood work, in the initial workup. The list of laboratory studies providers would obtain is extensive. Providers primarily rely on cardiac involvement to confirm a MIS-C diagnosis, and establishing a diagnosis takes 24-48 h. CONCLUSIONS: Significant heterogeneity exists amongst providers as to when to initiate the MIS-C workup, the order and content of the workup, and how to definitively diagnose MIS-C. A diagnostic test with high sensitivity and specificity for MIS-C and refined evidence-based guidelines are needed to expedite diagnosis and treatment.
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COVID-19 , COVID-19/complicaciones , COVID-19/diagnóstico , Niño , Estudios Transversales , Humanos , Síndrome de Respuesta Inflamatoria Sistémica , Estados UnidosRESUMEN
Background and Objectives: Nowadays, with the increasing laparoscopic expertise and accessibility to modern surgical tools, laparoscopic assisted ERCP (LAERCP) has become an effective approach for the management of bile stone disease in patients with modified gastrointestinal anatomy. In contrast to patients with gastric bypass in whom a transgastric LAERCP approach is usually performed, the resultant anatomy of Roux-en-Y hepaticojejunostomy precludes a gastric approach as the newly formed bilioenteric anastomosis is not reachable through the stomach. Therefore, a transjejunal approach has been described as an alternative LAERCP technique. To the best of our knowledge this is the tenth case of transjejunal LAERCP reported worldwide. Materials and Methods: We present the case of a 50-year-old female with history of biliary injury during a cholecystectomy corrected with Roux-en-Y hepaticojejunostomy who presented to our center with manifestations of acute abdomen. After laboratory and image analysis, diagnosis of intrahepatic lithiasis was confirmed. The decision to perform a transjejunal LAERCP was made due to the complex anatomy in this patient. No complications were found during surgery and in the follow up period. Conclusions: Transjejunal LAERCP is an effective approach for endoscopic management of biliary complications in patients with Roux-en-Y hepaticojejunostomy and other modified gastrointestinal anatomy. Previous recommendations by more experienced teams have been reported, nonetheless, there are too few cases reported to make definitive recommendations and conclusions. In limited settings, such as ours, some of these recommendations may not be applicable. We are certain that, with the increasing expertise and innovations in laparoscopy surgery for the management of complications that cannot be addressed by endoscopic or noninvasive measures, more cases will be reported.
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Colangiopancreatografia Retrógrada Endoscópica , Colecistectomía Laparoscópica , Yeyunostomía , Femenino , Derivación Gástrica , Humanos , Persona de Mediana Edad , Estómago/cirugíaRESUMEN
BACKGROUND: Children account for approximately 33 million annual emergency department (ED) visits in the United States. The spectrum and frequency of children with a critical illness presenting to an ED has not been previously analyzed. OBJECTIVE: The purpose of this study was to examine the range of critical illness presenting to a tertiary Children's Hospital ED. METHODS: This study was a retrospective chart review of all pediatric patients requiring immediate care in the medical resuscitation bay during a 25-month period from August 2005 to September 2007. Data are from a single center, academic, tertiary care pediatric hospital. A log of all patients requiring immediate care is kept in the medical resuscitation bay. Patients recorded in the log for a period of 25 consecutive months were reviewed for type of critical illness, frequency of critical illness, mode of arrival, and outcome. Trauma patients were excluded. RESULTS: There were approximately 45,000 pediatric visits per year with a total of 87,766 patients seen during the study period. There were 249 pediatric patients who required care in the medical resuscitation bay during the reviewed period. Complete data were obtained from 242 subjects' charts. Patients requiring immediate care accounted for 0.28% of all the visits. CONCLUSIONS: This study documents the infrequent need for pediatric critical care in the ED of a nonacademic tertiary children's hospital in the United States and reinforces the need to provide protocols, mock codes, and simulation labs in preparation for critically ill children.
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Cuidados Críticos/estadística & datos numéricos , Enfermedad Crítica/epidemiología , Resucitación/estadística & datos numéricos , Adolescente , Niño , Preescolar , Enfermedad Crítica/terapia , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Hospitales Pediátricos , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Centros de Atención TerciariaRESUMEN
BACKGROUND AND OBJECTIVE: Weight estimation for pediatric resuscitation occurs frequently in emergency departments. Historically, different approaches to estimation have been studied with varied results. With increasing obesity rates among inner-city children, this study aims to determine the best method for pediatric weight estimation in our population. METHODS: This is a prospective, nonblinded, observational study. A total of 324 patients (aged 1 month to 12 years) were enrolled in the study to exceed sample size calculations. The accuracy of 4 methods for weight estimation--the Broselow tape, advanced pediatric life support formulas, the PAWPER tape, and mid-arm circumference formula--were compared across age ranges and body sizes to determine the most appropriate method for our population. RESULTS: In this inner-city population, 32% of the patients 2 to 12 years of age were found to be overweight or obese. This rate increased to 41% for patients 6 to 12 years of age. In this setting, the PAWPER tape outperformed the other 3 methods, estimating patients' weight within ±5% of actual weight in 35.2% of our cohort. When compared with the other 3 methods tested, the PAWPER tape was statistically superior with a P value less than .02 in each case. CONCLUSION: Each of the methods tested in our population performed poorly. Current methods for weight estimation should be used with caution, especially for populations with an increased prevalence of obesity. Efforts should be dedicated to improving or deriving new methods for weight estimation that perform better in this vulnerable population.
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Peso Corporal , Pesos y Medidas Corporales/métodos , Obesidad Infantil/complicaciones , Resucitación/métodos , Pesos y Medidas Corporales/instrumentación , Pesos y Medidas Corporales/normas , Niño , Preescolar , Precisión de la Medición Dimensional , Femenino , Humanos , Lactante , Masculino , Estudios Prospectivos , Reproducibilidad de los Resultados , Estados Unidos , Salud UrbanaRESUMEN
OBJECTIVES: To evaluate the impact of aspirin resistance on the incidence of preeclampsia and maternal serum biomarker levels in pregnant individuals at high-risk of preeclampsia receiving low dose aspirin (LDA). STUDY DESIGN: We performed a secondary analysis of a randomized, placebo-controlled trial of LDA (60 mg daily) for preeclampsia prevention in high-risk individuals (N = 524) on pregnancy outcomes and concentrations of PLGF, IL-2, IL-6, thromboxane B2 (TXB2), sTNF-R1 and sTNF-R2 from maternal serum. MAIN OUTCOME MEASURES: LDA-resistant individuals were defined as those having a TXB2 concentration >10 ng/ml or <75 % reduction in concentration at 24-28 weeks after LDA administration. Comparisons of outcomes were performed using a Fisher's Exact Test. Mean concentrations of maternal serum biomarkers were compared using a Student's t-test. Pearson correlation was calculated for all pairwise biomarkers. Longitudinal analysis across gestation was performed using linear mixed-effects models accounting for repeated measures and including BMI and maternal age as covariates. RESULTS: We classified 60/271 (22.1 %) individuals as LDA-resistant, 179/271 (66.1 %) as LDA-sensitive, and 32/271 (11.8 %) as non-adherent. The prevalence of preeclampsia was not significantly different between the LDA and placebo groups (OR = 1.43 (0.99-2.28), p-value = 0.12) nor between LDA-sensitive and LDA-resistant individuals (OR = 1.27 (0.61-2.8), p-value = 0.60). Mean maternal serum IL-2 concentrations were significantly lower in LDA-resistant individuals relative to LDA-sensitive individuals (FDR < 0.05). CONCLUSIONS: These results suggest a potential role for IL-2 in the development of preeclampsia modulated by an individuals' response to aspirin, presenting an opportunity to optimize aspirin prophylaxis on an individual level to reduce the incidence of preeclampsia.
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We aimed to assess whether early exposure of medical students to robotic surgery training influences their interest in a surgical career and improves scores on objective simulation tasks. Medical students were invited to participate in robotic online training modules, robotic simulation exercises followed by a hands-on robotic dry-lab session. Pre- and post-simulator scores were recorded. A 29-question anonymous survey was recorded before and after the lab. Seventy percent reported that the training had a positive impact on influencing their decision to pursue a general surgery career. Students showed significantly improved skill and performance on simulation activities post-training. After the training, students felt knowledgeable about robotics, more comfortable operating robotically, and thought that robotic surgery would hold a significant place in the future of surgery. Exposing students to robotic training positively impacts their perception of surgery as a career choice and results in improvement in objective scores on simulation tasks.
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Procedimientos Quirúrgicos Robotizados , Robótica , Entrenamiento Simulado , Estudiantes de Medicina , Humanos , Procedimientos Quirúrgicos Robotizados/educación , Selección de Profesión , Competencia Clínica , Simulación por Computador , Entrenamiento Simulado/métodosRESUMEN
BACKGROUND: We previously developed the Pelvic Surgery Difficulty Index for predicting intraoperative events and postoperative outcomes associated with rectal mobilization with or without proctectomy ("deep pelvic dissection"). The aim of this study was to validate the scoring system as a prognostic tool for outcomes of pelvic dissection, regardless of the cause of dissection. METHODS: Consecutive patients who underwent elective deep pelvic dissection at our institution from 2009 to 2016 were reviewed. Pelvic Surgery Difficulty Index score (0-3) was calculated from the following parameters: male sex (+1), prior pelvic radiotherapy (+1), and linear distance from sacral promontory to pelvic floor >13 cm (+1). Patient outcomes stratified by Pelvic Surgery Difficulty Index score were compared. The outcomes assessed included operative blood loss, operative time, length of hospital stay, cost, and postoperative complications. RESULTS: A total of 347 patients were included. Higher Pelvic Surgery Difficulty Index scores were associated with significantly more blood loss, operative time, postoperative complications, hospital costs, and hospital stay. The model achieved good discrimination with area under the curve ≥0.7 for most outcomes. CONCLUSION: Preoperative prediction of the morbidity associated with difficult pelvic dissection is possible with an objective, feasible, and validated model. Such a tool may facilitate preoperative preparation and allow for better risk stratification and uniform quality control across centers.
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Laparoscopía , Neoplasias del Recto , Humanos , Masculino , Neoplasias del Recto/cirugía , Pelvis/cirugía , Disección , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Estudios RetrospectivosRESUMEN
Introduction: Although SARS-CoV-2 infection can lead to severe COVID-19 in children, the role of biomarkers for assessing the risk of progression to severe disease is not well established in the pediatric population. Given the differences in monocyte signatures associated with worsening COVID-19 in adults, we aimed to determine whether monocyte anisocytosis early in the infectious course would correspond with increasing severity of COVID-19 in children. Methods: We performed a multicenter retrospective study of 215 children with SARS-CoV-2 infection, Multisystem Inflammatory Syndrome in Children (MIS-C), convalescent COVID-19, and healthy age-matched controls to determine whether monocyte anisocytosis, quantified by monocyte distribution width (MDW) on complete blood count, was associated with increasing severity of COVID-19. We performed exploratory analyses to identify other hematologic parameters in the inflammatory signature of pediatric SARS-CoV-2 infection and determine the most effective combination of markers for assessing COVID-19 severity in children. Results: Monocyte anisocytosis increases with COVID-19 severity and need for hospitalization. Although other inflammatory markers such as lymphocyte count, neutrophil/lymphocyte ratio, C-reactive protein, and cytokines correlate with disease severity, these parameters were not as sensitive as MDW for identifying severe disease in children. An MDW threshold of 23 offers a sensitive marker for severe pediatric COVID-19, with improved accuracy when assessed in combination with other hematologic parameters. Conclusion: Monocyte anisocytosis corresponds with shifting hematologic profiles and inflammatory markers in children with COVID-19, and MDW serves as a clinically accessible biomarker for severe COVID-19 in children.
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Using a murine model of cysticercosis caused by the Taenia crassiceps ORF strain, we developed a fluorescent quantitative evaluation of the action of two well known anti-helminthic drugs: albendazole sulfoxide and praziquantel. The fluorescence emitted by a biotransformed CellTracker Probe known as CellTracker Green CMFDA in the vesicular fluids of cysticerci was estimated, and the results were compared with macroscopic observations of the parasites. The pharmacological EC(50) value of each drug and changes in the level of biotransformation of the fluorescent tracker caused by the drugs could be easily calculated. These drug-induced changes in biotransformation could be related to changes in the GSH/GSSG ratio of parasites. Both the cysticercosis murine model and the CMFDA biotransformation assay could be used as an in vitro screening method to evaluate potential or well known cysticidal drugs.
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Albendazol/análogos & derivados , Antihelmínticos/farmacología , Cysticercus/efectos de los fármacos , Fluoresceínas , Colorantes Fluorescentes , Praziquantel/farmacología , Albendazol/farmacología , Animales , Biotransformación , Cysticercus/metabolismo , Femenino , Fluoresceínas/farmacocinética , Colorantes Fluorescentes/farmacocinética , Ratones , Ratones Endogámicos BALB C , Microscopía FluorescenteRESUMEN
BACKGROUND: Children with short-bowel syndrome (SBS) have significant morbidity and mortality from bloodstream infections (BSIs). We studied the prevalence of BSI in children with SBS and identified possible predictors of BSI. METHODS: This retrospective cohort study included patients with SBS who presented to Holtz Children's Hospital from April 1, 2009, to June 30, 2014, with fever or reported fever. Data including vital signs, white blood cell (WBC) count, C-reactive protein (CRP) levels, and blood and urine cultures were reviewed. We calculated the prevalence of BSI and its confidence level. We also assessed the odds of BSI with increases in WBC and CRP values. RESULTS: A total of 246 encounters were evaluated. The adjusted calculated prevalence rate for BSI in children with SBS and fever was 55% (95% CI, 42.3%-65.4%). There were 114 gram-negative infections (72.6%), 46 gram-positive infections (29.3%), and 17 fungal infections (10.8%). Using the regression model, each additional 10 units above 20 mg/L CRP increased the odds of BSI by 26%. There was no association between WBC count and the presence of BSI. CONCLUSION: Children with fever and SBS are at high risk for BSI with gram-positive and gram-negative organisms as well as fungus. WBC count at presentation is a poor predictor of BSI. Though elevated CRP increased the odds of BSI, its low negative predictive value made it a poor predictor of BSI in these patients. Children with SBS and fever should be treated urgently with broad-spectrum antibiotics.
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Bacteriemia , Servicio de Urgencia en Hospital , Sepsis , Bacteriemia/epidemiología , Niño , Humanos , Prevalencia , Estudios RetrospectivosRESUMEN
Based on morphological data collected from treefrogs related to Sarcohyla hazelae, we describe a new species of the genus Sarcohyla from the cloud forest of the Sierra Madre del Sur of Guerrero, Mexico. We compare physical charactersitics of this new species to its closest relatives within the genus Sarcohyla, including dorsal and ventral coloration, head shape, tympanum distinctiveness, morphometrics and the condition of the tubercles on hands and feet. We analyze accoustic data from the advertisement call of males of the new species. We discuss the relationship of the species described herein with several of its cogeners, plus we resurrect the Sarcohyla hazelae group for these frogs. We describe habitat and distribution species related to Sarcohyla hazelae and also comment on the conservation priorities of these frogs.
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Anuros , Bosques , Animales , Ecosistema , Pie , Masculino , México , FilogeniaRESUMEN
The carotid body receptors participate in glucose regulation sensing glucose levels in blood entering the cephalic circulation. The carotid body receptors information, is initially processed within the nucleus tractus solitarius (NTS) and elicits changes in circulating glucose and brain glucose uptake. Previous work has shown that gamma-aminobutyric acid (GABA) in NTS modulates respiratory reflexes, but the role of GABA within NTS in glucose regulation remains unknown. Here we show that GABA(B) receptor agonist (baclofen) or antagonists (phaclofen and CGP55845A) locally injected into NTS modified arterial glucose levels and brain glucose retention. Control injections outside NTS did not elicit these responses. In contrast, GABA(A) agonist and antagonist (muscimol or bicuculline) produced no significant changes in blood glucose levels. When these GABAergic drugs were applied before carotid body receptors stimulation, again, only GABA(B) agonist or antagonist significantly affected glycemic responses; baclofen microinjection significantly reduced the hyperglycemic response and brain glucose retention observed after carotid body receptors stimulation, while phaclofen produced the opposite effect, increasing significantly hyperglycemia and brain glucose retention. These results indicate that activation of GABA(B), but not GABA(A), receptors in the NTS modulates the glycemic responses after anoxic stimulation of the carotid body receptors, and suggest the presence of a tonic inhibitory mechanism in the NTS to avoid hyperglycemia.
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Cuerpo Carotídeo/efectos de los fármacos , Glucosa/metabolismo , Receptores de GABA-B/fisiología , Núcleo Solitario/efectos de los fármacos , Análisis de Varianza , Animales , Baclofeno/administración & dosificación , Baclofeno/análogos & derivados , Baclofeno/farmacología , Bicuculina/administración & dosificación , Bicuculina/farmacología , Glucemia/análisis , Cuerpo Carotídeo/fisiología , Agonistas del GABA/administración & dosificación , Agonistas del GABA/farmacología , Antagonistas del GABA/administración & dosificación , Antagonistas del GABA/farmacología , Microinyecciones , Muscimol/administración & dosificación , Muscimol/farmacología , Ratas , Receptores de GABA-A/fisiología , Núcleo Solitario/metabolismo , Núcleo Solitario/fisiologíaRESUMEN
Solvent-free oxidative couplings of naphthols have been optimized by co-spotting catalysts and substrates directly on silica TLC plates and heating, followed by chromatography, staining, and qualitative visualization.
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BACKGROUND AND AIMS: Carotid body (CB) sinus perfusion with different glucose concentrations modifies arterial glucose concentration and brain glucose retention, thereby changing the brain's threshold to hypoxia. Because nitric oxide (NO) modulates hypoxic chemoreception, we investigated the relationship between NO- and CB-receptor pathways on arterial glucose and brain arteriovenous (a-v) glucose difference after hypoxic stimulation under hyperglycemic conditions. METHODS: Normoglycemic and streptozotocin (STZ, 50 mg/kg i.p.)-induced hyperglycemic Sprague Dawley rats were infused with the NO donor, sodium nitroprusside (SNP), or the NOS inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME) into the circulatory isolated carotid sinus after (30 sec) local anoxic CB chemoreceptor stimulation with sodium cyanide (NaCN). RESULTS: L-NAME abolished the hyperglycemia and the increase in brain a-v glucose concentration difference induced by CB chemoreceptor stimulation in normoglycemic rats, whereas the same treatment in hyperglycemic rats did not change the glucose variables studied. However, SNP infused under the same conditions induced a bigger rise in arterial glucose and brain a-v glucose concentration difference only in normoglycemic rats, when compared with the results obtained in sham-2-control rats. CB stimulation plus SNP treatment also resulted in an increase in nitrite levels in cephalic venous blood in normoglycemic, but not in hyperglycemic, rats. CONCLUSIONS: We showed a clear concomitant effect of SNP infusion into local CB circulation and anoxic cyanide stimulation, enhancing hyperglycemia and brain a-v glucose concentration difference. Importantly, at high glucose levels, nitrergic drugs did not modify glucose variables when compared with the corresponding sham controls.
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Glucemia/metabolismo , Encéfalo/metabolismo , Cuerpo Carotídeo/fisiología , Células Quimiorreceptoras/metabolismo , Glucosa/metabolismo , Hiperglucemia/metabolismo , Óxido Nítrico/metabolismo , Animales , Cuerpo Carotídeo/citología , Circulación Cerebrovascular/efectos de los fármacos , Células Quimiorreceptoras/citología , Células Quimiorreceptoras/efectos de los fármacos , Diabetes Mellitus Experimental , Inhibidores Enzimáticos/farmacología , Masculino , NG-Nitroarginina Metil Éster/farmacología , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Cianuro de Sodio/farmacologíaRESUMEN
The D3-dopaminergic agonist (+/-) 7-hydroxy-dipropylaminotetralin (7-OH-DPAT) prolonged cycle length and action potential duration, depolarized maximum diastolic potential, and reduced the upstroke velocity of the action potential of rabbit sinoatrial node cells. These effects were not mediated by D3-dopaminergic receptors. In cat Purkinje fibers, the drug increased action potential duration. In voltage-clamped cat ventricular myocytes, 7-OH-DPAT blocked the rapid component of the delayed rectifier potassium current, IKr. This effect was corroborated in experiments studying the effect of the drug on human Ether-a-go-go-related Gene channels expressed in Xenopus oocytes and in HEK293 cells. We conclude that the direct electrophysiologic effects of 7-OH-DPAT on cardiac tissues are caused by the blockade of the rapid component of the delayed rectifier potassium current, IKr.