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1.
JMIR Form Res ; 8: e53977, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110968

RESUMEN

BACKGROUND: Wearable physiological monitoring devices are promising tools for remote monitoring and early detection of potential health changes of interest. The widespread adoption of such an approach across communities and over long periods of time will require an automated data platform for collecting, processing, and analyzing relevant health information. OBJECTIVE: In this study, we explore prospective monitoring of individual health through an automated data collection, metrics extraction, and health anomaly analysis pipeline in free-living conditions over a continuous monitoring period of several months with a focus on viral respiratory infections, such as influenza or COVID-19. METHODS: A total of 59 participants provided smartwatch data and health symptom and illness reports daily over an 8-month window. Physiological and activity data from photoplethysmography sensors, including high-resolution interbeat interval (IBI) and step counts, were uploaded directly from Garmin Fenix 6 smartwatches and processed automatically in the cloud using a stand-alone, open-source analytical engine. Health risk scores were computed based on a deviation in heart rate and heart rate variability metrics from each individual's activity-matched baseline values, and scores exceeding a predefined threshold were checked for corresponding symptoms or illness reports. Conversely, reports of viral respiratory illnesses in health survey responses were also checked for corresponding changes in health risk scores to qualitatively assess the risk score as an indicator of acute respiratory health anomalies. RESULTS: The median average percentage of sensor data provided per day indicating smartwatch wear compliance was 70%, and survey responses indicating health reporting compliance was 46%. A total of 29 elevated health risk scores were detected, of which 12 (41%) had concurrent survey data and indicated a health symptom or illness. A total of 21 influenza or COVID-19 illnesses were reported by study participants; 9 (43%) of these reports had concurrent smartwatch data, of which 6 (67%) had an increase in health risk score. CONCLUSIONS: We demonstrate a protocol for data collection, extraction of heart rate and heart rate variability metrics, and prospective analysis that is compatible with near real-time health assessment using wearable sensors for continuous monitoring. The modular platform for data collection and analysis allows for a choice of different wearable sensors and algorithms. Here, we demonstrate its implementation in the collection of high-fidelity IBI data from Garmin Fenix 6 smartwatches worn by individuals in free-living conditions, and the prospective, near real-time analysis of the data, culminating in the calculation of health risk scores. To our knowledge, this study demonstrates for the first time the feasibility of measuring high-resolution heart IBI and step count using smartwatches in near real time for respiratory illness detection over a long-term monitoring period in free-living conditions.

2.
J Appl Gerontol ; : 7334648241265204, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39030728

RESUMEN

Nonoperative treatment is used at varying rates among older adults with hip fractures despite the high mortality. This retrospective analysis of 7803 patients 65 and older admitted with hip fractures is to estimate the odds of nonoperative treatment and in-hospital mortality after hip fractures among community-dwelling older adults. 13.6% underwent nonoperative treatment. Compared to the group with operative treatment, the nonoperative group had a higher in-hospital mortality rate (6.51% vs. 1.32%, p < .0001). Male sex, nondisplaced fracture, and comorbidities of acute myocardial infarction, congestive heart failure, cerebrovascular disorder, dementia, and liver disease were associated with an increased likelihood of nonoperative treatment. Nonoperative treatment, advanced age, use of osteoporosis pharmacotherapy, multiple medical comorbidities, and hospital-acquired complications were associated with increased in-hospital mortality. Specific characteristics were associated with nonoperative management and in-hospital mortality among older adults with hip fractures. Additional research is necessary to improve the care of this vulnerable population.

3.
HCA Healthc J Med ; 5(1): 11-18, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38560394

RESUMEN

Background: In this study, we aimed to assess the hospital course, outcomes after hospitalization, and predictors of outcomes in patients with ankylosing spondylitis (AS). Methods: We included 1403 patients with AS between 2016 and 2021 who were identified using International Classification of Disease (ICD) codes from a large for-profit healthcare system database. Demographics and clinical characteristics were compared between those who had a favorable outcome, defined as being discharged to home without readmission within 3 months of discharge, versus those who had an unfavorable outcome. A stepwise logistic regression was used to identify demographic and clinical characteristics associated with home discharge and readmission. Results: The mean age for all AS patients was 56.06 ± 17.01 years, which was younger in the favorable outcome group, and 82.47% of patients were discharged to home after the average length of stay of 3.72 ± 4.09 days, also shorter in the favorable outcome group. Of 1403 patients, 37.56% were readmitted within 3 months of discharge, at a lower rate in the group with home discharge. Opioids were the most commonly used medication during hospitalization (67.07%), prescribed at a lower rate in the favorable outcome group. Medical coverage by Medicare and Medicaid, fall at admission, hospital-acquired anemia, steroid, acetaminophen, muscle relaxant use, and an increased dose of morphine milligram equivalent at discharge were significantly associated with decreased odds of home discharge. Surgical procedures during admission, gastrointestinal complications, discharge to inpatient rehabilitation units, and use of benzodiazepine were associated with an increased risk of readmission within 3 months. Conclusion: Recognizing factors that put patients with AS at risk of unfavorable outcomes is useful information to improve patient care during hospitalization.

4.
Am J Phys Med Rehabil ; 103(7): e86-e89, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38466152

RESUMEN

ABSTRACT: The addition of aromatase inhibitors has improved cancer-related outcomes in postmenopausal patients with estrogen receptor-positive breast cancer. However, aromatase inhibitor can be associated with a constellation of adverse musculoskeletal effects that comprises bone loss, arthralgia, myalgia, and tendinopathy. This medication complication, known as aromatase inhibitor-associated musculoskeletal syndrome, can limit treatment tolerability in many patients because of the high prevalence of aromatase inhibitor-associated musculoskeletal syndrome among those on aromatase inhibitor. The hand and wrist are the most affected joints in aromatase inhibitor-associated musculoskeletal syndrome, with patients presenting with symmetric arthralgia, stiffness, and tendinopathy. Radioulnar joint subluxation with extensor tendon tear has not been previously reported in patients with aromatase inhibitor-associated musculoskeletal syndrome. This is a case report of a 72-yr-old breast cancer survivor on an aromatase inhibitor presenting with chronic dominant wrist pain, weakness, and 5th digit finger drop. An extensor digitorum minimi tendon tear and radioulnar instability were identified using diagnostic musculoskeletal ultrasonography. This case illustrates the utility of in-office ultrasonography combined with dynamic examination for the often underrecognized pathology associated with aromatase inhibitor-associated musculoskeletal syndrome in breast cancer survivors.


Asunto(s)
Inhibidores de la Aromatasa , Neoplasias de la Mama , Inestabilidad de la Articulación , Humanos , Femenino , Inhibidores de la Aromatasa/efectos adversos , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Inestabilidad de la Articulación/inducido químicamente , Articulación de la Muñeca/diagnóstico por imagen , Traumatismos de los Tendones/inducido químicamente , Traumatismos de los Tendones/diagnóstico por imagen , Ultrasonografía
5.
J Spinal Cord Med ; 46(6): 900-909, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-35532310

RESUMEN

OBJECTIVES: To evaluate the clinical characteristics, hospital courses, outcomes after hospitalization, and factors associated with outcomes in patients with nontraumatic spinal cord injuries (NTSCI). DESIGN: Retrospective analysis. SETTING: A large for-profit United States health care system. PARTICIPANTS: 2807 inpatients with NTSCI between 2014 and 2020 were identified using International Classification of Disease codes. MAIN OUTCOME MEASURE: Demographic, clinical characteristics, hospital course, and disposition data collected from electronic health record. RESULTS: The mean age was 57.91 ± 16.41 years with 69.83% being male. Incomplete cervical level injury was the most common injury type, spinal stenosis was the most common diagnostic etiology and central cord syndrome was the most common clinical syndrome. The average length of stay was 9.52 ± 15.8 days, with the subgroup of 1308 (46.6%) patients who were discharged home demonstrating a shorter length of stay (6.42 ± 10.24 days). Falls were the most common hospital-acquired complication (n = 424, 15.11%) and 83 patients deceased. There were increased odds of non-home discharge among patients with the following characteristics: older age, Medicare insurance, non-black racial minority, increased Charlson Comorbidity Index (CCI), intensive care unit (ICU) stay, use of steroid or anticoagulant medications, and hospital-acquired pulmonary complications. Increased in-hospital mortality was observed in those with Medicaid insurance, ICU stay, increased CCI, diagnosis of degenerative spine disease, other unspecified level of injury, and hospital-acquired pulmonary complications. CONCLUSIONS: NTSCI in this sample were predominantly incomplete cervical central SCIs. Increased CCI, ICU stay, and hospital-acquired pulmonary complications were associated with poorer outcomes after acute care hospitalization among patients with NTSCI.


Asunto(s)
Traumatismos de la Médula Espinal , Humanos , Masculino , Anciano , Estados Unidos/epidemiología , Adulto , Persona de Mediana Edad , Femenino , Traumatismos de la Médula Espinal/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento , Medicare , Atención a la Salud , Hospitales , Tiempo de Internación
6.
Bioinformatics ; 38(12): 3252-3258, 2022 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-35441678

RESUMEN

MOTIVATION: As the number of public data resources continues to proliferate, identifying relevant datasets across heterogenous repositories is becoming critical to answering scientific questions. To help researchers navigate this data landscape, we developed Dug: a semantic search tool for biomedical datasets utilizing evidence-based relationships from curated knowledge graphs to find relevant datasets and explain why those results are returned. RESULTS: Developed through the National Heart, Lung and Blood Institute's (NHLBI) BioData Catalyst ecosystem, Dug has indexed more than 15 911 study variables from public datasets. On a manually curated search dataset, Dug's total recall (total relevant results/total results) of 0.79 outperformed default Elasticsearch's total recall of 0.76. When using synonyms or related concepts as search queries, Dug (0.36) far outperformed Elasticsearch (0.14) in terms of total recall with no significant loss in the precision of its top results. AVAILABILITY AND IMPLEMENTATION: Dug is freely available at https://github.com/helxplatform/dug. An example Dug deployment is also available for use at https://search.biodatacatalyst.renci.org/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Motor de Búsqueda , Semántica , Ecosistema , Indización y Redacción de Resúmenes
7.
Ecol Appl ; 32(2): e2508, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34870359

RESUMEN

Invasive forest insects have significant direct impacts on forest ecosystems and they are also generating new risks, uncertainties, and opportunities for forest landowners. The growing prevalence and inexorable spread of invasive insects across the United States, combined with the fact that the majority of the nation's forests are controlled by thousands of autonomous private landowners, raises an important question: To what extent will private landowners alter their harvest practices in response to insect invasions? Using a quasi-experimental design, we conducted a causal analysis to investigate the influence of the highly impactful emerald ash borer (EAB) on (1) annual probability of harvest; (2) intensity of harvest; and (3) diameter of harvested trees, for both ash and non-ash species on private land throughout the Midwest and mid-Atlantic regions of the United States. We found that EAB detection had a negative impact on annual harvest probability and a positive impact on harvest intensity, resulting in a net increase in harvested biomass. Furthermore, our estimates suggest that EAB detection will influence private landowners to harvest greater quantities of ash, relative to non-ash species. We also found that harvested trees in EAB-infested areas had smaller diameters, on average, compared with those unaffected by EAB. These results can help policymakers, forest managers, and extension programs to anticipate and better advise landowners and managers about their options and the associated outcomes for forests.


Asunto(s)
Escarabajos , Fraxinus , Animales , Escarabajos/fisiología , Ecosistema , Insectos , Larva/fisiología
8.
BDJ Open ; 7(1): 26, 2021 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-34257267

RESUMEN

OBJECTIVES: To evaluate a 0.454% stannous fluoride/5% sodium tripolyphosphate (STP) toothpaste's ability to provide relief from dentinal hypersensitivity (DH) applied using 'focused brushing.' MATERIALS AND METHODS: In two randomised, examiner-blind, parallel-group studies, a SnF2/STP toothpaste was applied by brushing two selected sensitive teeth before 1 min whole-mouth brushing, compared to 1 min whole-mouth brushing only, with a negative control toothpaste. DH was assessed via evaporative (air) (Schiff scale) and tactile (Yeaple probe) stimuli after 7 and 14 d of twice-daily brushing. RESULTS: In total, 141 (Study 1)/142 (Study 2) participants were randomised. In Study 1, the test treatment significantly reduced DH at 7/14 d versus baseline (7/14 d Schiff difference: -0.74 [-0.84,-0.65]/-1.39 [-1.54,-1.23]; tactile: 6.00 [4.88,7.13]/15.30 [13.34,17.26]); whereas the Control treatment did not (7/14 d Schiff difference -0.03 [-0.13,0.06]/-0.10 [-0.25,0.06]; tactile: 0.77 [-0.36,1.90]/0.77 [-1.20,2.74]). Differences between Test and Control were statistically significant (p < 0.0001 all cases). In Study 2, both treatments reduced DH compared to baseline by both measures, but there were no significant between-treatment differences. Toothpastes were generally well-tolerated. DISCUSSION AND CONCLUSIONS: Previous studies and Study 1 support SnF2/5% STP toothpaste efficacy; Study 2 results may have been influenced by placebo/Hawthorne effects. DH study design needs to, where possible, negate such effects.

9.
J Clin Periodontol ; 46(11): 1105-1115, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31381157

RESUMEN

AIM: To evaluate effects of a 0.454% stannous fluoride test toothpaste on dentine hypersensitivity (DH) applied by fingertip, then 3 days' brushing, versus a sodium monofluorophosphate-based control. MATERIALS AND METHODS: In three randomized clinical studies, DH was assessed using evaporative (Schiff scale) and tactile (Yeaple probe) stimuli. Participants applied toothpaste to two sensitive teeth by fingertip (60 s each); DH was re-assessed, prior to brushing. Test treatment participants brushed their sensitive teeth, with all participants then brushing all teeth for ≥60 s, twice daily for 3 days. DH was re-assessed. Data were analysed by study and then pooled. RESULTS: In two studies, test treatment significantly reduced DH versus control treatment after fingertip application and 3 days' brushing (both measures). In one study, both treatments significantly reduced DH without between-treatment differences. Mean Schiff differences (95% confidence intervals) for fingertip/3d were as follows: Study 1: -0.09 (-0.280, 0.092)/ -0.18 (-0.442, 0.072); Study 2: -0.72 (-0.839, -0.610)/ -1.02 (-1.150, -0.882); and Study 3: -0.26 (-0.387, -0.123)/ -0.92 (-1.055, -0.793). Pooled analysis indicated test treatment significantly reduced DH versus control (both timepoints, both measures). Toothpastes were generally well-tolerated. CONCLUSION: Studies indicated that single, fingertip application of a SnF2 toothpaste reduced DH versus a control. DH relief increased over 3 days.


Asunto(s)
Desensibilizantes Dentinarios , Sensibilidad de la Dentina , Método Doble Ciego , Fluoruros , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Fluoruro de Sodio , Pastas de Dientes , Resultado del Tratamiento
10.
Int J Cardiol ; 271: 60-65, 2018 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-30223379

RESUMEN

BACKGROUND: Myocardial dysfunction has been implicated in gradual heart failure in transposition of the great arteries (TGA) with a systemic right ventricle (RV). Fibrosis can be assessed using the extracellular volume fraction (ECV). Our aim was to measure ECV and determine its associations with clinical findings and outcomes. METHODS: We prospectively measured ECV in systemic RV subjects (either D-loop after atrial switch or L-loop) and healthy controls. T1 measurements for a single mid-ventricular short-axis plane before and 3, 7, and 15 min after gadolinium contrast were used to quantify systemic ventricular ECV. Individuals with elevated ECV were compared to those without. RESULTS: In 53 TGA subjects (age 34.6 ±â€¯10.3 years, 41% female) the mean ECV for the systemic RV (28.7 ±â€¯4.4%) was significantly higher than the left ventricle in 22 controls (26.1 ±â€¯2.8%, P = 0.0104). Those with an elevated ECV (n = 15, 28.3%) had a higher b-type natriuretic peptide (BNP) (P < 0.011) and a longer 6-min walk distance (P = 0.021), but did not differ by age, arrhythmia history, ventricular volume, function, or circulating collagen byproducts. At follow-up (median 4.4 years), those experiencing major cardiovascular endpoints (new arrhythmia, arrhythmia device, heart failure hospitalization, listing for transplantation, mechanical support, or cardiovascular death, n = 14) had a higher ECV. ECV, age, and BNP were independent predictors of cardiac events in Cox-proportional hazard models. CONCLUSIONS: Myocardial fibrosis is common in the systemic RV and associated with a higher BNP. Elevated CMR-derived ECV was associated with adverse clinical outcome. The findings suggest a role of diffuse myocardial fibrosis in clinical deterioration of the systemic RV.


Asunto(s)
Insuficiencia Cardíaca/diagnóstico por imagen , Transposición de los Grandes Vasos/diagnóstico por imagen , Transposición de los Grandes Vasos/cirugía , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/cirugía , Adulto , Femenino , Fibrosis , Estudios de Seguimiento , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Miocardio/patología , Estudios Prospectivos , Transposición de los Grandes Vasos/fisiopatología , Resultado del Tratamiento , Disfunción Ventricular Derecha/fisiopatología
11.
Heart ; 104(22): 1832-1835, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-29794244

RESUMEN

OBJECTIVE: Cardiac auscultation is a key clinical skill, particularly for the diagnosis of valvular heart disease (VHD). However, its utility has declined due to the widespread availability of echocardiography and diminishing emphasis on the importance of clinical examination. We aim to determine the contemporary accuracy of auscultation for diagnosing VHD in primary care. METHODS: Cardiac auscultation was undertaken by one of two experienced general practitioners (primary care/family doctors) in a subset of 251 asymptomatic participants aged >65 years undergoing echocardiography within a large community-based screening study of subjects with no known VHD. Investigators were blinded to the echocardiographic findings. Newly detected VHD was classified as mild (mild regurgitation of any valve or aortic sclerosis) or significant (at least moderate regurgitation or mild stenosis of any valve). RESULTS: Newly identified VHD was common, with mild disease in 170/251 participants (68%) and significant disease in 36/251 (14%). The sensitivity of auscultation was low for the diagnosis of mild VHD (32%) but slightly higher for significant VHD (44%), with specificities of 67% and 69%, respectively. Likelihood ratios were not statistically significant for the diagnosis of either mild or significant VHD in the overall cohort, but showed possible value for auscultation in non-overweight subjects (body mass index <25 kg/m2). CONCLUSION: Cardiac auscultation has limited accuracy for the detection of VHD in asymptomatic patients and is a poor diagnostic screening tool in primary care, particularly for overweight subjects. Ensuring easy access to echocardiography in patients with symptoms suggesting VHD is likely to represent a better diagnostic strategy.


Asunto(s)
Auscultación Cardíaca , Enfermedades de las Válvulas Cardíacas/diagnóstico , Atención Primaria de Salud , Anciano , Anciano de 80 o más Años , Enfermedades Asintomáticas , Ecocardiografía , Inglaterra/epidemiología , Femenino , Médicos Generales , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/epidemiología , Enfermedades de las Válvulas Cardíacas/fisiopatología , Humanos , Masculino , Valor Predictivo de las Pruebas , Prevalencia , Estudios Prospectivos , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad
12.
Genome Announc ; 4(5)2016 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-27587823

RESUMEN

Bacillus cereus UW85 was isolated from a root of a field-grown alfalfa plant from Arlington, WI, and identified for its ability to suppress damping off, a disease caused by Phytophthora megasperma f. sp. medicaginis on alfalfa. Here, we report the draft genome sequence of B. cereus UW85, obtained by a combination of Sanger and Illumina sequencing.

13.
J Gastrointest Oncol ; 7(3): E64-71, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27284491

RESUMEN

Patients with Lynch syndrome often present with multiple synchronous or metachronous colorectal cancers (CRCs). The presence of multiple CRCs with distinct genetic profiles and driver mutations could complicate treatment as each cancer may respond differently to therapy. Studies of sporadic CRCs suggested that synchronous tumors have distinct etiologies, but could not rule out differences in genetic background. The presence of multiple cancers in a patient with a predisposing mutation provides an opportunity to profile synchronous cancers in the same genetic background. Here, we describe the case of a patient with Lynch syndrome that presented with six synchronous CRCs. Microsatellite instability (MSI) and genomic profiling indicated that each lesion had a unique pattern of instability and a distinct profile of affected genes. These findings support the idea that in Lynch syndrome, synchronous CRCs can develop in parallel with distinct mutation profiles and that these differences may inform treatment decisions.

14.
J Clin Dent ; 27(4): 97-104, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28391662

RESUMEN

OBJECTIVES: Calcium sodium phosphosilicate (CSPS) is a particulate bioactive material incorporated into oral healthcare products for the treatment of dentin hypersensitivity (DH). This study aimed to determine whether a dentifrice containing 5% CSPS and fluoride as sodium fluoride (NaF; "Test dentifrice") was non-inferior to a dentifrice containing 5% CSPS and fluoride as sodium monofluorophosphate (SMFP; "Comparator dentifrice") in reducing DH after eight weeks' twice-daily brushing. METHODS: This was a randomized, examiner-blind, parallel-group, non-inferiority study in healthy adults with self-reported and clinically diagnosed DH. After an initial lead-in period, subjects were randomized to either the Test (n = 150) or Comparator dentifrice (n = 154) and instructed to brush twice daily for the next eight weeks. DH was assessed at baseline and following four and eight weeks of dentifrice use by response to a tactile stimulus (tactile threshold) and evaporative (air) stimulus (Schiff sensitivity score and 100 mm visual analog scale [VAS]). The non-inferiority margin was defined as 6 mm on the VAS. RESULTS: Both dentifrices were associated with statistically significant reductions in DH from baseline after four and eight weeks' use for all efficacy parameters (all p < 0.0001). There were no statistically significant differences between the groups. After eight weeks' use, the between-treatment difference in VAS scores was 2.67 mm (per-protocol analysis) in favor of the Comparator dentifrice; the upper limit of the 95% confidence interval (CI) of the between-treatment difference in VAS scores exceeded the pre-specified non-inferiority margin of 6 mm (upper 95% CI = 7.4). The non-inferiority margin was also exceeded after four weeks. Both dentifrices were generally well tolerated. CONCLUSIONS: The pre-defined non-inferiority margin of 6 mm was not met, thus it is not possible to conclude from the present analysis that the Test dentifrice is non-inferior to the Comparator. However, for all efficacy measures, a statistically significant reduction in DH was observed for both dentifrice groups. There were no statistically significant differences between dentifrice groups, suggesting that changing the source of fluoride from SMFP to NaF does not affect the overall efficacy of the dentifrice in alleviating DH.


Asunto(s)
Dentífricos/uso terapéutico , Sensibilidad de la Dentina/terapia , Fluoruro de Sodio/uso terapéutico , Adulto , Aire , Desensibilizantes Dentinarios , Método Doble Ciego , Femenino , Fluoruros , Humanos , Masculino , Fosfatos , Autoinforme , Método Simple Ciego , Resultado del Tratamiento
15.
Infect Immun ; 83(1): 396-404, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25385794

RESUMEN

Enterococcus faecalis is a commensal and pathogen of humans and insects. In Manduca sexta, E. faecalis is an infrequent member of the commensal gut community, but its translocation to the hemocoel results in a commensal-to-pathogen switch. To investigate E. faecalis factors required for commensalism, we identified E. faecalis genes that are upregulated in the gut of M. sexta using recombinase-based in vivo expression technology (RIVET). The RIVET screen produced 113 clones, from which we identified 50 genes that are more highly expressed in the insect gut than in culture. The most frequently recovered gene was locus OG1RF_11582, which encodes a 6-phosphogluconolactonase that we designated pglA. A pglA deletion mutant was impaired in both pathogenesis and gut persistence in M. sexta and produced enhanced biofilms compared with the wild type in an in vitro polystyrene plate assay. Mutation of four other genes identified by RIVET did not affect persistence in caterpillar guts but led to impaired pathogenesis. This is the first identification of genetic determinants for E. faecalis commensal and pathogenic interactions with M. sexta. Bacterial factors identified in this model system may provide insight into colonization or persistence in other host-associated microbial communities and represent potential targets for interventions to prevent E. faecalis infections.


Asunto(s)
Hidrolasas de Éster Carboxílico/metabolismo , Enterococcus faecalis/enzimología , Interacciones Huésped-Patógeno , Manduca/microbiología , Animales , Hidrolasas de Éster Carboxílico/genética , Enterococcus faecalis/genética , Tracto Gastrointestinal/microbiología , Eliminación de Gen , Perfilación de la Expresión Génica
17.
mBio ; 2(3): e00065-11, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21586646

RESUMEN

UNLABELLED: A dynamic homeostasis is maintained between the host and native bacteria of the gastrointestinal tract in animals, but migration of bacteria from the gut to other organs can lead to disease or death. Enterococcus faecalis is a commensal of the gastrointestinal tract; however, Enterococcus spp. are increasingly frequent causes of nosocomial infections with a high mortality rate. We investigated the commensal-to-pathogen switch undergone by E. faecalis OG1RF in the lepidopteran model host Manduca sexta associated with its location in the host. E. faecalis persists in the harsh midgut environment of M. sexta larvae without causing apparent illness, but injection of E. faecalis directly into the larval hemocoel is followed by rapid death. Additionally, oral ingestion of E. faecalis in the presence of Bacillus thuringiensis insecticidal toxin, a pore-forming toxin that targets the midgut epithelium, induces an elevated mortality rate. We show that the loss of gut integrity due to B. thuringiensis toxin correlates with the translocation of E. faecalis from the gastrointestinal tract into the hemolymph. Upon gaining access to the hemolymph, E. faecalis induces an innate immune response, illustrated by hemocyte aggregation, in larvae prior to death. The degree of hemocyte aggregation is dependent upon the route of E. faecalis entry. Our data demonstrate the efficacy of the M. sexta larval model system in investigating E. faecalis-induced sepsis and clarifies controversies in the field regarding the events leading to larval death following B. thuringiensis toxin exposure. IMPORTANCE: This study advances our knowledge of Enterococcus faecalis-induced sepsis following translocation from the gut and provides a model for mammalian diseases in which the spatial distribution of bacteria determines disease outcomes. We demonstrate that E. faecalis is a commensal in the gut of Manduca sexta and a pathogen in the hemocoel, resulting in a robust immune response and rapid death, a process we refer to as the "commensal-to-pathogen" switch. While controversy remains regarding Bacillus thuringiensis toxin-induced killing, our laboratory previously found that under some conditions, the midgut microbiota is essential for B. thuringiensis toxin killing of Lymantria dispar (N. A. Broderick, K. F. Raffa, and J. Handelsman, Proc. Natl. Acad. Sci. U. S. A. 103:15196-15199, 2006; B. Raymond, et al., Environ. Microbiol. 11:2556-2563, 2009; P. R. Johnston, and N. Crickmore, Appl. Environ. Microbiol. 75:5094-5099, 2009). We and others have demonstrated that the role of the midgut microbiota in B. thuringiensis toxin killing is dependent upon the lepidopteran species and formulation of B. thuringiensis toxin (N. A. Broderick, K. F. Raffa, and J. Handelsman, Proc. Natl. Acad. Sci. U. S. A. 103:15196-15199, 2006; N. A. Broderick, et al., BMC Biol. 7:11, 2009). This work reconciles much of the apparently contradictory previous data and reveals that the M. sexta-E. faecalis system provides a model for mammalian sepsis.


Asunto(s)
Traslocación Bacteriana , Enterococcus faecalis/crecimiento & desarrollo , Enterococcus faecalis/patogenicidad , Manduca/microbiología , Animales , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/toxicidad , Agregación Celular , Endotoxinas/toxicidad , Tracto Gastrointestinal/microbiología , Hemocitos/inmunología , Hemocitos/microbiología , Hemolinfa/microbiología , Proteínas Hemolisinas/toxicidad , Larva/microbiología , Análisis de Supervivencia
18.
Vet Rec ; 168(19): 520; discussion 520, 2011 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-21571859
20.
BMC Biol ; 7: 11, 2009 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-19261175

RESUMEN

BACKGROUND: Gut microbiota contribute to the health of their hosts, and alterations in the composition of this microbiota can lead to disease. Previously, we demonstrated that indigenous gut bacteria were required for the insecticidal toxin of Bacillus thuringiensis to kill the gypsy moth, Lymantria dispar. B. thuringiensis and its associated insecticidal toxins are commonly used for the control of lepidopteran pests. A variety of factors associated with the insect host, B. thuringiensis strain, and environment affect the wide range of susceptibilities among Lepidoptera, but the interaction of gut bacteria with these factors is not understood. To assess the contribution of gut bacteria to B. thuringiensis susceptibility across a range of Lepidoptera we examined larval mortality of six species in the presence and absence of their indigenous gut bacteria. We then assessed the effect of feeding an enteric bacterium isolated from L. dispar on larval mortality following ingestion of B. thuringiensis toxin. RESULTS: Oral administration of antibiotics reduced larval mortality due to B. thuringiensis in five of six species tested. These included Vanessa cardui (L.), Manduca sexta (L.), Pieris rapae (L.) and Heliothis virescens (F.) treated with a formulation composed of B. thuringiensis cells and toxins (DiPel), and Lymantria dispar (L.) treated with a cell-free formulation of B. thuringiensis toxin (MVPII). Antibiotics eliminated populations of gut bacteria below detectable levels in each of the insects, with the exception of H. virescens, which did not have detectable gut bacteria prior to treatment. Oral administration of the Gram-negative Enterobacter sp. NAB3, an indigenous gut resident of L. dispar, restored larval mortality in all four of the species in which antibiotics both reduced susceptibility to B. thuringiensis and eliminated gut bacteria, but not in H. virescens. In contrast, ingestion of B. thuringiensis toxin (MVPII) following antibiotic treatment significantly increased mortality of Pectinophora gossypiella (Saunders), which was also the only species with detectable gut bacteria that lacked a Gram-negative component. Further, mortality of P. gossypiella larvae reared on diet amended with B. thuringiensis toxin and Enterobacter sp. NAB3 was generally faster than with B. thuringiensis toxin alone. CONCLUSION: This study demonstrates that in some larval species, indigenous gut bacteria contribute to B. thuringiensis susceptibility. Moreover, the contribution of enteric bacteria to host mortality suggests that perturbations caused by toxin feeding induce otherwise benign gut bacteria to exert pathogenic effects. The interaction between B. thuringiensis and the gut microbiota of Lepidoptera may provide a useful model with which to identify the factors involved in such transitions.


Asunto(s)
Bacillus thuringiensis/fisiología , Lepidópteros/microbiología , Animales , Antibacterianos/farmacología , Bacterias/clasificación , Bacterias/efectos de los fármacos , Biodiversidad , Enterobacter/fisiología , Tracto Gastrointestinal/microbiología , Lepidópteros/efectos de los fármacos , Mortalidad
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