Modeling bee movement shows how a perceptual masking effect can influence flower discovery.

Understanding how pollinators move across space is key to understanding plant mating patterns. Bees are typically assumed to search for flowers randomly or using simple movement rules, so that the probability of discovering a flower should primarily depend on its distance to the nest. However, experimental work shows this is not always the case. Here, we explored the influence of flower size and density on their probability of being discovered by bees by developing a movement model of central place foraging bees, based on experimental data collected on bumblebees. Our model produces realistic bee trajectories by taking into account the autocorrelation of the bee's angular speed, the attraction to the nest (homing), and a gaussian noise. Simulations revealed a « masking effect ¼ that reduces the detection of flowers close to another, with potential far reaching consequences on plant-pollinator interactions. At the plant level, flowers distant to the nest were more often discovered by bees in low density environments. At the bee colony level, foragers found more flowers when they were small and at medium densities. Our results indicate that the processes of search and discovery of resources are potentially more complex than usually assumed, and question the importance of resource distribution and abundance on bee foraging success and plant pollination.

Cost of Deep Brain Stimulation Infection Resulting in Explantation.

BACKGROUND: Deep brain stimulation (DBS) hardware infection is a serious complication, often resulting in multiple hardware salvage attempts, hospitalizations, and long-term antibiotic therapy. OBJECTIVES: We aimed to quantify the costs of DBS hardware-related infections in patients undergoing eventual device explantation. METHODS: Of 362 patients who underwent 530 electrode placements (1 January 2010 to 30 December 2014), 16 (4.4%) had at least 2 hardware salvage procedures. Most (n = 15 [93.8%]) required complete explantation due to recurrent infection. Financial data (itemized hospital and physician costs) were available for 13 patients and these were analyzed along with the demographic data. RESULTS: Each patient underwent 1-5 salvage procedures (mean 2.5 ± 1.4; median 2). The mean total cost for a patient undergoing the median number of revisions (n = 2), device explantation, and subsequent reimplantation after infection clearance was USD 75,505; just over half this cost (54.2% [USD 40,960]) was attributable to reimplantation, and nearly one-third (28.9% [USD 21,816]) was attributable to hardware salvage procedures. Operating-room costs were the highest cost category for hardware revision and explantation. Medical and surgical supplies accounted for the highest reimplantation cost. CONCLUSIONS: DBS infection incurs significant health care costs associated with hardware salvage attempts, explantation, and reimplantation. The highest cost categories are operating-room services and medical and surgical supplies.

Role of Coccidioides Antigen Testing in the Cerebrospinal Fluid for the Diagnosis of Coccidioidal Meningitis.

BACKGROUND: Coccidioidal meningitis (CM), a common cause of chronic meningitis in endemic area, is usually diagnosed by detection of anti-Coccidioides antibodies in cerebrospinal fluid (CSF), and findings may be negative in up to one-third of cases. CSF cultures and cytology are infrequently positive. Antigen detection has been used for the diagnosis of other forms of coccidioidomycosis and meningitis caused by other mycoses. The purpose of this study was to assess the diagnostic utility of CSF Coccidioides antigen (CAg) detection for the diagnosis of CM. METHODS: The medical records of patients with clinically suspected meningitis, in whom CSF was tested for Coccidioides antibodies and CAg, were retrospectively reviewed, and CSF CAg testing was prospectively conducted in patients with CM. All specimens were submitted for CAg testing. RESULTS: Thirty-six patients with 42 episode of CM were studied. The sensitivity and specificity of CAg were 93% and 100%, respectively. Cultures of CSF were positive in 7%, antibodies were demonstrated by immunodiffusion in 67% and complement fixation in 70%, and immunoglobulin M and G antibodies were demonstrated by enzyme immunoassay in 8% and 85%, respectively. CONCLUSIONS: Testing CSF for CAg is a useful addition to diagnostic methods in suspected CM and complements testing with CSF antibodies and culture.

[Relevance of clinical and serum parameters on severe urinary sepsis after renal obstruction.] / Importancia de los parámetros clínicos y analíticos de la sepsis grave en la uropatía obstructiva.

INTRODUCTION: Urosepsis is an underdiagnosed entity with high morbidity and mortality and significant associated costs. The delay in diagnosis leads to an increased risk of multiorgan failure and death. Although its prognosis is better than that of other sepsis, the mortality rate is 20 - 40%. OBJECTIVE: Describe the obstructive uropathy cases (OU) that are complicated by severe sepsis (SS) and identify early biomarkers of SS. MATERIAL AND METHODS: Observational and prospective study of 65 patients with urgent high OU. All patients were evaluated at three different times (0, 24 and 48 hours). An SS predictor model has been constructed and a multivariate risk analysis has been carried out. RESULTS: 64.61% (n=42) developed SS (NSS: n=13). The only statistically significant variables in the 3 moments evaluated and that obtained a good area under the curve [AUROC (>0.70)] were the elevation of neutrophils, procalcitonin, and decrease of bicarbonate. At the time of patient admission, the variable that best predicted SS was the elevation of procalcitonin (AUROC:0.919). SS risk factors (p<0.005) were the history of cancer immunosuppression, and/or urinary tract surgeries, complete UO and high blood values of lactate, potassium and decrease of bicarbonate. The potassium-lactate combination on admission predicted SS with a probability function of 0.805. CONCLUSIONS: There is an analytical profile maintained over the time characteristic of SS that allows anearly identification of patients with OU subsidiary of been complicated with SS.

INTRODUCCIÓN: La Sepsis urinaria obstructiva (SUO) es una entidad infradiagnosticada con una elevada morbimortalidad e importantes costes asociados. El retraso en su diagnóstico condiciona un mayor riesgo de fracaso multiorgánico y fallecimiento. Aunque su pronóstico es mejor que el de otros focos de sepsis, su mortalidad es del 20 - 40%. OBJETIVO: Describir los cuadros de uropatía obstructiva (UO) que se complican con sepsis grave (SG) e identificarlos biomarcadores diagnósticos de SG en la UOde forma precoz.MATERIAL Y MÉTODOS: Estudio observacional y prospectivo de 72 pacientes con UO alta ingresados de manera urgente en el Servicio de Urología del Hospital Clínico Universitario de Valladolid. Todos los pacientes del estudio fueron evaluados en tres momentos diferentes (0, 24 y 48 horas). Se ha creado un modelo predictor de SG y se ha realizado un análisis multivariante de riesgo. RESULTADOS: El 64,61% de los pacientes (n=42) desarrolló SG (NSG: n=13). Las únicas variables estadísticamente significativas en los tres momentos evaluados y que obtenían una buena área bajo la curva [AUROC (>0,70)] fueron la elevación de neutrófilos y procalcitonina y la disminución de bicarbonato. En el momento del ingreso la variable que mejor predecía SG fue la elevación de procalcitonina (AUROC: 0,919). Los factores de riesgo de SG (p<0,05) fueron los antecedentes de cáncer, la inmunosupresión y/o cirugías de vías urinarias, la UO completa y los valores elevados en sangre de lactato y potasio y la disminución del bicarbonato en la gasometría venosa. La combinación potasio-lactato al ingreso predecía SG con una función de probabilidad de 0,805. CONCLUSIONES: Existe un perfil analítico, mantenido en el tiempo, característico de SG que permite la identificación precoz de los pacientes con UO subsidiarios de complicarse con SG.

Nursing care for renal patients on hemodialysis: challenges, dilemmas and satisfactions. / El cuidado de enfermería a los enfermos renales en hemodiálisis: desafíos, dilemas y satisfacciones.

OBJECTIVE: To identify the challenges, dilemmas and satisfactions presented by nursing professionals in hemodialysis services during the care of renal patients. METHOD: Institutional ethnography was used, and 18 semi-structured interviews were conducted with nine members of the nursing staff. Conventional content analysis was performed. RESULTS: For the nursing staff, care presents challenges such as the complex physical and emotional condition of patients, the management of technology for care, and coping with the suffering and death of patients with whom they have established a close relationship. The dilemmas are related to providing care for patients who refuse to receive it, and the personal and family costs involved in treatment in contrast to the limited quality of life of some patients. The main satisfactions are collaborative work, the sufficiency of resources and the confidence and recognition for performing independent work. CONCLUSION: The findings of the study are associated with the presence of professional burnout and interference in the ability to build satisfactory interpersonal relationships, lower job satisfaction and quality of care.

Changes in bacterial community structure associated with coastal copper enrichment.

Marine bacterial communities isolated from the water column, sediment, the rock surface, and the green seaweed Ulva compressa were studied in an intertidal ecosystem. The study area included a coastal zone chronically affected by copper mine waste disposals. Bacterial community composition was analyzed by terminal restriction fragment length polymorphism (T-RFLP) of 16S rRNA genes, and multivariate analyses of T-RFLP data sets were used for comparisons. Results showed that diversity and richness indexes were not able to detect differences among compartments. However, comparisons within the same compartment clearly showed that copper enrichment was associated with changes in the composition of the bacterial communities and revealed that the magnitude of the effect depends on the compartment being considered. In this context, communities from sediments appeared as the most affected by copper enrichment. The present study also demonstrated that intertidal bacterial communities were dominated by Gammaproteobacteria, Firmicutes, and Actinobacteria and the changes in these communities were mainly due to changes in their relative abundances.

Neurocysticercosis in the HIV era: a case report and review of the literature.

The prevalence of HIV is increasing in countries where neurocysticercosis is endemic. Co-infection rates are expected to rise; however, no systematic reviews of the subject are available. We performed a literature review of neurocysticercosis (NCC) occurring in HIV-infected patients and described the clinical and immunophenotypic characteristics of a NCC case presenting with probable immune reconstitution inflammatory syndrome. We identified 27 cases of NCC-HIV co-infection. The most frequent presentation (61%) was with multiple parenchymal lesions. Seven patients (30%) had other concomitant neurologic infections (e.g., tuberculosis, toxoplasmosis). Thirteen patients received cysticidal therapy, and 85% responded to therapy. Only three patients died (12%). Immunohistochemistry of brain tissue in our case revealed abundant CD3+, CD8+, and CD68+ cells. NCC should be included in the differential diagnosis of neurologic infections in HIV patients in endemic populations. Consideration of the patient's immune status should alert the clinician to potential atypical presentations.

Spinal Coccidioidomycosis: A Current Review of Diagnosis and Management.

OBJECTIVE: Coccidioidomycosis is an invasive fungal disease that may present with extrathoracic dissemination. Patients with spinal coccidioidomycosis require unique medical and surgical management. We review the risk factors and clinical presentations, discuss the indications for surgical intervention, and evaluate outcomes and complications after medical and surgical management. METHODS: A review of the English-language literature was performed. Eighteen articles included the management of 140 patients with spinal coccidioidomycosis. RESULTS: For the 140 patients, risk factors included male sex (95%), African American ethnicity (52%), and a recent visit to endemic areas (16%). The most frequent clinical presentation was pain (n = 80, 57%), followed by neurologic compression (52%). One-third of patients had concurrent pulmonary disease. The sensitivity of culture and histology for coccidioidomycosis was 80% and 90%, respectively. Complement fixation titers >1:128 suggest extensive or refractory vertebral infection. The most commonly affected spinal segments were the thoracic and lumbar spine (69%); an additional 40 patients (29%) had epidural and paravertebral abscesses. All patients received therapy with azoles (60%) and/or amphotericin B (43%). Surgical and medical management were used conjunctively to treat 110 patients (79%), with debridement (95% [105/110]) and fusion (64% [70/110]) being the most common surgical procedures. Clinical outcome improved/remained unchanged in 83 patients (59%) and worsened in 4 patients (3%). The mortality was 7%. Infection recurrence and disease progression were the most frequent complications. CONCLUSIONS: Emphasis should be placed on continuous and lifelong appropriate azole therapy. Spinal instability and neurologic compromise are surgical indications for decompression and fusion.

“Escala de valoración de capacidad de autocuidado” y su relación con conductas y condiciones de salud en adultos mayores / "Self-care capacity assessment scale" and its relationship with health behaviors and conditions in older adults

Este trabajo tuvo por objetivo contribuir en el estudio de la validez de la “Escala de valoración de la capacidad de autocuidado” (escala ASA) en adultos mayores y analizar su asociación con conductas y condiciones relacionadas con la salud. Se construyó un cuestionario y se aplicó a 165 adultos mayores residentes de Michoacán (México). Se realizó un análisis factorial confirmatorio del modelo unidimensional de la escala, así como un análisis de consistencia interna, así como un análisis de relación con otras variables basado en comparaciones de grupos, explorando el efecto de la eliminación de ítems inversos. La escala reducida tuvo mejor desempeño en general, aunque el modelo unidimensional mantuvo un ajuste limitado en el análisis factorial confirmatorio. La consistencia interna fue satisfactoria en ambas escalas (α= 0,806 y 0,826, respectivamente), además se identificaron algunas comparaciones de grupo importantes con mediciones antropométricas. En conclusión, se encontraron pruebas que apoyan la validez de la escala ASA en adultos mayores, aunque continúa pendiente generar más evidencia en cuanto a su validez de constructo y criterio (AU)

The objective of this work was to contribute to the study of the validity of the “Appraisal of Self-care Agency Scale” (ASA scale) in older adults and to analyze its association with health-related behaviors and conditions. A questionnaire was constructed and applied to 165 elderly residents of Michoacán, Mexico. A confirmatory factor analysis of the scale's one-dimensional model was carried out, and also an analysis of internal consistency, as well as an analysis of the relationship with other variables based on group comparisons, exploring the effect of the elimination of inverse items. Overall, the reduced scale performed better although the one-dimensional model maintained a limited fit in the confirmatory factor analysis. Internal consistency was satisfactory in both scales (α coefficient= .806 and .826, respectively). In addition, some important group comparisons were identified with anthropometric measurements. In conclusion, tests were found supporting the validity of the ASA scale in older adults, although more evidence is still needed regarding its construct and criterion validity (AU)

Patient outcomes and surgical complications in coccidioidomycosis-related hydrocephalus: an institutional review.

OBJECTIVES: Coccidioidomycosis is a common fungal infection in the southwestern US. Hydrocephalus is a serious complication of cranial coccidioidomycosis, and the surgical management of coccidioidomycosis-related hydrocephalus has unique challenges. The authors reviewed their institutional experience with hydrocephalus in the setting of coccidioidomycosis. METHODS: The authors retrospectively identified 44 patients diagnosed with coccidioidomycosis-related hydrocephalus at their institution since 1990, who underwent a total of 99 shunting procedures. The authors examined patient demographics, type of shunt and valve used, pressure settings, failure rates, medical treatment, ventricular response to shunting, and other variables. RESULTS: The majority of patients were young (average age 37 years) men (male/female ratio 28:16) with a mean follow-up of 63 months. Patients of Asian and African descent were overrepresented in the cohort compared with regional demographic data. The overall shunt failure rate during follow-up was 50%, and the average number of revisions required if the shunt failed was 2.5 (range 1-8). Low to moderate draining pressures (mean 88 mm H2O) were used in this cohort. Fourteen patients received intrathecal antifungals, and a trend of initiating intrathecal therapy after need for a shunt revision was observed (p = 0.051). The majority of shunt failures (81%) were due to mechanical blockages in the drainage system. Most patients (59%) had at least partial persistent postoperative ventriculomegaly despite successful CSF diversion. Four patients (9%) died due to coccidioidomycosis during the follow-up period. CONCLUSIONS: Coccidioidomycosis-related hydrocephalus more often affected young males in the study's cohort, especially those of African and Asian descent. Despite the best medical therapy, there was a high rate of shunt failure due to clogged catheters or valves due to the underlying disease process. Many patients continued to have ventriculomegaly even with adequate CSF diversion. The morbidity and mortality of this chronic disease process must be recognized by the treatment team, and patients should be appropriately counseled.

Restoration of lung surfactant protein D by IL-6 protects against secondary pneumonia following hemorrhagic shock.

OBJECTIVES: To identify novel approaches to improve innate immunity in the lung following trauma complicated by hemorrhagic shock (T/HS) for prevention of nosocomial pneumonia. METHODS: We developed a rat model of T/HS followed by Pseudomonas aeruginosa (PA) pneumonia to assess the effect of alveolar epithelial cell (AEC) apoptosis, and its prevention by IL-6, on lung surfactant protein (SP)-D protein levels, lung bacterial burden, and survival from PA pneumonia, as well as to determine whether AEC apoptosis is a consequence of the unfolded protein response (UPR). Lung UPR transcriptome analysis was performed on rats subjected to sham, T/HS, and T/HS plus IL-6 protocols. Group comparisons were performed via Kaplan-Meier or ANOVA. RESULTS: T/HS decreased lung SP-D by 1.8-fold (p < 0.05), increased PA bacterial burden 9-fold (p < 0.05), and increased PA pneumonia mortality by 80% (p < 0.001). IL-6, when provided at resuscitation, normalized SP-D levels (p < 0.05), decreased PA bacterial burden by 4.8-fold (p < 0.05), and prevented all mortality from PA pneumonia (p < 0.001). The UPR transcriptome was significantly impacted by T/HS; IL-6 treatment normalized the T/HS-induced UPR transcriptome changes (p < 0.05). CONCLUSIONS: Impaired innate lung defense occurs following T/HS and is mediated, in part, by reduction in SP-D protein levels, which, along with AEC apoptosis, may be mediated by the UPR, and prevented by use of IL-6 as a resuscitation adjuvant.

Increased apoptosis of peripheral blood neutrophils is associated with reduced incidence of infection in trauma patients with hemorrhagic shock.

OBJECTIVE: We aimed to describe the relationship between early peripheral leukocyte apoptosis and incidence of subsequent infection in trauma patients with hemorrhagic shock (T/HS). METHODS: T/HS patients requiring emergency surgery were prospectively enrolled. Nucleosome ELISA and TUNEL staining were performed on peripheral blood drawn pre-operatively, post-operatively and at 24 h. Subjects were followed for 30 days or until death or hospital discharge to record all episodes of infection. RESULTS: Forty-one subjects were enrolled. Six died within 24 h of surgery and were not included in the analysis. Nucleosome levels peaked post-operatively and dropped to baseline levels at 24 h (p = 0.03). TUNEL analysis revealed that polymorphonuclear neutrophils (PMNs) accounted for 72% of apoptotic leukocytes; the remaining apoptotic cells were mainly lymphocytes. Increased post-operative leukocyte apoptosis was associated with decreased systemic inflammatory response syndrome (SIRS) severity. Seventeen of the 35 survivors (48.6%) developed infections, while 18 (51.4%) did not. Pre-operative and post-operative nucleosome levels were 2.5 and 3 times higher, respectively, in T/HS patients who did not develop infection compared to those who did. Increased nucleosome levels were associated in particular with protection against sepsis (p=0.03) and multiple infections (p = 0.01). CONCLUSION: Peripheral blood PMN apoptosis in the early resuscitative period is associated with decreased incidence of subsequent infection in T/HS patients.

IL-6-mediated activation of Stat3α prevents trauma/hemorrhagic shock-induced liver inflammation.

Trauma complicated by hemorrhagic shock (T/HS) is the leading cause of morbidity and mortality in the United States for individuals under the age of 44 years. Initial survivors are susceptible to developing multiple organ failure (MOF), which is thought to be caused, at least in part, by excessive or maladaptive activation of inflammatory pathways. We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required, and the mechanism(s) for the IL-6 protective effect have not been reported. In the experiments described here, we demonstrated that the extent of liver inflammation induced by T/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver inflammation and is associated with increased Stat3 activation. Global assessment of the livers showed that the main effect of IL-6 was to normalize the T/HS-induced inflammation transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver inflammation and to normalize the T/HS-induced liver inflammation transcriptome. Genetic deletion of a Stat3ß, a naturally occurring, dominant-negative isoform of the Stat3, attenuated T/HS-induced liver inflammation, confirming a role for Stat3, especially Stat3α, in preventing T/HS-mediated liver inflammation. Thus, T/HS-induced liver inflammation depends on the duration of hypotension and requires resuscitation; IL-6 administration at the start of resuscitation reverses T/HS-induced liver inflammation, through activation of Stat3α, which normalized the T/HS-induced liver inflammation transcriptome.

Adjunctive globe magnetic resonance imaging in the diagnosis of posterior scleritis.

OBJECTIVE: To report 4 cases of posterior scleritis with unusually unremarkable ultrasonography findings in which diagnosis was based on magnetic resonance imaging (MRI) examination. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Four patients. METHODS: Patients suffering from suspected posterior scleritis and previously misdiagnosed with a range of conditions after an unremarkable B-scan ultrasonography. A new and thorough review of systems, including MRI examination of the eye/orbit, was carried out. RESULTS: All included patients were diagnosed with posterior scleritis based on MRI findings. Systemic treatment with immunosuppressors (2 patients), antibiotics (1 patient), or no treatment (1 patient) got their inflammatory condition under control. CONCLUSIONS: MRI may play a potential role in the diagnosis of posterior scleritis particularly in those clinically suspicious cases with nondefinitive ultrasonography. Further studies on this matter are warranted.

Importancia de los parámetros clínicos y analíticos de la sepsis grave en la uropatía obstructiva / Relevance of clinical and serum parameters on severe urinary sepsis after renal obstruction

INTRODUCCIÓN: La Sepsis urinaria obstructiva (SUO) es una entidad infradiagnosticada con una elevada morbimortalidad e importantes costes asociados. El retraso en su diagnóstico condiciona un mayor riesgo de fracaso multiorgánico y fallecimiento. Aunque su pronóstico es mejor que el de otros focos de sepsis, su mortalidad es del 20 - 40%. OBJETIVO: Describir los cuadros de uropatía obstructiva (UO) que se complican con sepsis grave (SG) e identificarlos biomarcadores diagnósticos de SG en la UOde forma precoz. MATERIAL Y MÉTODOS: Estudio observacional y prospectivo de 72 pacientes con UO alta ingresados de manera urgente en el Servicio de Urología del Hospital Clínico Universitario de Valladolid. Todos los pacientes del estudio fueron evaluados en tres momentos diferentes (0, 24 y 48 horas). Se ha creado un modelo predictor de SG y se ha realizado un análisis multivariante de riesgo. RESULTADOS: El 64,61% de los pacientes (n=42) desarrolló SG (NSG: n=13). Las únicas variables estadísticamente significativas en los tres momentos evaluados y que obtenían una buena área bajo la curva [AUROC (>0,70)] fueron la elevación de neutrófilos y procalcitonina y la disminución de bicarbonato. En el momento del ingreso la variable que mejor predecía SG fue la elevación de procalcitonina (AUROC: 0,919). Los factores de riesgo de SG (p < 0,05) fueron los antecedentes de cáncer, la inmunosupresión y/o cirugías de vías urinarias, la UO completa y los valores elevados en sangre de lactato y potasio y la disminución del bicarbonato en la gasometría venosa. La combinación potasio-lactato al ingreso predecía SG con una función de probabilidad de 0,805. CONCLUSIONES: Existe un perfil analítico, mantenido en el tiempo, característico de SG que permite la identificación precoz de los pacientes con UO subsidiarios de complicarse con SG

INTRODUCTION: Urosepsis is an underdiagnosed entity with high morbidity and mortality and significant associated costs. The delay in diagnosis leads to an increased risk of multiorgan failure and death. Although its prognosis is better than that of other sepsis, the mortality rate is 20 - 40%. OBJECTIVE: Describe the obstructive uropathy cases (OU) that are complicated by severe sepsis (SS) and identify early biomarkers of SS. MATERIAL AND METHODS: Observational and prospective study of 65 patients with urgent high OU. All patients were evaluated at three different times (0, 24 and 48 hours). An SS predictor model has been constructed and a multivariate risk analysis has been carried out. RESULTS: 64.61% (n=42) developed SS (NSS: n=13). The only statistically significant variables in the 3 moments evaluated and that obtained a good area under the curve [AUROC (>0.70)] were the elevation of neutrophils, procalcitonin, and decrease of bicarbonate. At the time of patient admission, the variable that best predicted SS was the elevation of procalcitonin (AUROC: 0.919). SS risk factors (p < 0.05) were the history of cancer, immunosuppression, and/or urinary tract surgeries, complete UO and high blood values of lactate, potassium and decrease of bicarbonate. The potassium-lactate combination on admission predicted SS with a probability function of 0.805. CONCLUSIONS: There is an analytical profile maintained over the time characteristic of SS that allows an early identification of patients with OU subsidiary of been complicated with SS

Prevention of trauma/hemorrhagic shock-induced lung apoptosis by IL-6-mediated activation of Stat3.

Acute lung injury (ALI) occurs in up to 37% of patients following trauma/hemorrhagic shock (T/HS) and, in other settings, is due to alveolar epithelial cell (AEC) apoptosis. To determine if AEC apoptosis is a key contributor to ALI following T/HS and whether or not signal transducer and activator of translation (Stat)3 activation can prevent it, rats were pretreated with a Stat3 inhibitor or placebo and subjected to T/HS or sham protocol and resuscitated without or with interleukin (IL)-6. T/HS induced apoptosis in up to 15% of lung cells, 82% of which were AEC. Apoptosis increased with increasing duration of shock and required resuscitation. IL-6 treatment stimulated lung Stat3 activation and prevented AEC apoptosis. Pretreatment of rats with a Stat3 inhibitor blocked the antiapoptotic effect of IL-6. Mice deficient in Stat3 beta, a naturally occurring dominant negative isoform of Stat3, were resistant to T/HS-induced lung apoptosis. T/HS altered the expression of 87% of apoptosis-related genes. IL-6 treatment normalized expression of 75% of the genes altered by T/HS; Stat3 inhibition prevented normalization of 65% of the gene whose expression was normalized by IL-6. Thus, T/HS-induced AEC apoptosis, which depended on the duration of hypotension, required resuscitation and was prevented by IL-6-mediated activation of Stat3, which acted to normalize the apoptosis transcriptome.

Prevention of trauma and hemorrhagic shock-mediated liver apoptosis by activation of stat3alpha.

Trauma is a major cause of mortality in the United States. Death among those surviving the initial insult is caused by multiple organ failure (MOF) with the liver among the organs most frequently affected. We previously demonstrated in rodents that trauma complicated by hemorrhagic shock (trauma/HS) results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required and the mechanism for the IL-6 protective effect have not been reported. In the experiments reported here, we demonstrated that the extent of liver apoptosis induced by trauma/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver apoptosis and is associated with increased Stat3 activation. Microarray analysis of the livers showed that the main effect of IL-6 was to normalize the trauma/HS-induced apoptosis transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver apoptosis and to normalize the trauma/HS- induced liver apoptosis transcriptome. Genetic deletion of a Stat3beta, a naturally occurring, dominant-negative isoform of the Stat3, attenuated trauma/HS-induced liver apoptosis, confirming a role for Stat3, especially Stat3alpha, in preventing trauma/HS-mediated liver apoptosis. Thus, trauma/HS-induced liver apoptosis depends on the duration of hypotension and requires resuscitation. IL-6 administration at the start of resuscitation reverses HS-induced liver apoptosis, through activation of Stat3alpha, which normalizes the trauma/HS-induced liver apoptosis transcriptome.

Prevention of hypovolemic circulatory collapse by IL-6 activated Stat3.

Half of trauma deaths are attributable to hypovolemic circulatory collapse (HCC). We established a model of HCC in rats involving minor trauma plus severe hemorrhagic shock (HS). HCC in this model was accompanied by a 50% reduction in peak acceleration of aortic blood flow and cardiomyocyte apoptosis. HCC and apoptosis increased with increasing duration of hypotension. Apoptosis required resuscitation, which provided an opportunity to intervene therapeutically. Administration of IL-6 completely reversed HCC, prevented cardiac dysfunction and cardiomyocyte apoptosis, reduced mortality 5-fold and activated intracardiac signal transducer and activator of transcription (STAT) 3. Pre-treatment of rats with a selective inhibitor of Stat3, T40214, reduced the IL-6-mediated increase in cardiac Stat3 activity, blocked successful resuscitation by IL-6 and reversed IL-6-mediated protection from cardiac apoptosis. The hearts of mice deficient in the naturally occurring dominant negative isoform of Stat3, Stat3beta, were completely resistant to HS-induced apoptosis. Microarray analysis of hearts focusing on apoptosis related genes revealed that expression of 29% of apoptosis related genes was altered in HS vs. sham rats. IL-6 treatment normalized the expression of these genes, while T40214 pretreatment prevented IL-6-mediated normalization. Thus, cardiac dysfunction, cardiomyocyte apoptosis and induction of apoptosis pathway genes are important components of HCC; IL-6 administration prevented HCC by blocking cardiomyocyte apoptosis and induction of apoptosis pathway genes via Stat3 and warrants further study as a resuscitation adjuvant for prevention of HCC and death in trauma patients.

Role of eukaryotic microbiota in soil survival and catabolic performance of the 2,4-D herbicide degrading bacteria Cupriavidus necator JMP134.

Cupriavidus necator (formerly Ralstonia eutropha) JMP134, harbouring the catabolic plasmid pJP4, is the best-studied 2,4-dichlorophenoxyacetic acid (2,4-D) herbicide degrading bacterium. A study of the survival and catabolic performance of strain JMP134 in agricultural soil microcosms exposed to high levels of 2,4-D was carried out. When C. necator JMP134 was introduced into soil microcosms, the rate of 2,4-D removal increased only slightly. This correlated with the poor survival of the strain, as judged by 16S rRNA gene terminal restriction fragment length polymorphism (T-RFLP) profiles, and the semi-quantitative detection of the pJP4-borne tfdA gene sequence, encoding the first step in 2,4-D degradation. After 3 days of incubation in irradiated soil microcosms, the survival of strain JMP134 dramatically improved and the herbicide was completely removed. The introduction of strain JMP134 into native soil microcosms did not produce detectable changes in the structure of the bacterial community, as judged by 16S rRNA gene T-RFLP profiles, but provoked a transient increase of signals putatively corresponding to protozoa, as indicated by 18S rRNA gene T-RFLP profiling. Accordingly, a ciliate able to feed on C. necator JMP134 could be isolated after soil enrichment. In native soil microcosms, C. necator JMP134 survived better than Escherichia coli DH5alpha (pJP4) and similarly to Pseudomonas putida KT2442 (pJP4), indicating that species specific factors control the survival of strains harbouring pJP4. The addition of cycloheximide to soil microcosms strongly improved survival of these three strains, indicating that the eukaryotic microbiota has a strong negative effect in bioaugmentation with catabolic bacteria.