Real world evidence of adjuvant trastuzumab in HER2 positive early breast cancer.

Adjuvant trastuzumab in HER2+ breast cancer reduces recurrence and mortality, and has been the standard treatment since 2006. The objective was to analyze health outcomes in the real world. Observational, retrospective study of patients with HER2+ breast cancer, stages I-III, treated with adjuvant trastuzumab in the past 15 years in only one center and for the first time in Spain. Survival was analyzed according to the number of cycles and cardiotoxicity. Two hundred and seventy-five HER2positive patients (18.60%) out of 1479 received adjuvant (73%) or neoadjuvant/adjuvant (26%) trastuzumab, concomitantly (90%) or sequentially (10%) with chemotherapy. The probability of overall and disease-free survival (OS and DFS) at 5 years was 0.93 (95% CI 0.89-0.96), and 0.88 (95% CI 0.83-0.92). The number of cases with a significant and asymptomatic decrease in ventricular ejection fraction and heart failure were 54 (19.64%) and 12 (4.36%), respectively. Sixty-eight patients (24.70%) received 16 or fewer cycles, especially those older than 65 (OR 0.371, 95% CI 0.152-0.903; p = 0.029) and with cardiotoxicity (OR 15.02, 95% CI 7.437-30.335; p < 0.001). The risk of cardiotoxicity was associated with having received radiotherapy (OR 0.0362, 95% CI 0.139-0.938; p = 0.037). Arterial hypertension (HR 0.361, 95% CI 0.151-0.863, p = 0.022), neoadjuvant treatment (HR 0.314, 95% CI 0.132-0.750, p = 0.009) and cardiotoxicity (HR 2.755, 95% CI 1.235-6.143, p = 0.013) maintained significant association with OS. Only neoadjuvant treatment maintained a significant association with DFS (HR 0.437, 95% CI 0.213-0.899, p = 0.024). The effectiveness of neoadjuvant and adjuvant trastuzumab can be considered comparable to those of clinical trials. In the real world, factors such as age, hypertension, radiotherapy, neoadjuvant treatment, and cardiotoxicity should be taken into consideration to optimize outcomes.

Predictive value of major adverse cardiac events by T2-mapping texture analysis of the myocardial remote zone in patients with acute myocardial infarction.

AIM: To assess the predictive value of major adverse cardiac events (MACEs) in patients with acute myocardial infarction (AMI) by T2-mapping texture analysis (TA) of the myocardial remote zone. MATERIALS AND METHODS: Data from 155 patients, who were diagnosed with AMI and were treated with primary percutaneous coronary intervention (PPCI), and 32 healthy controls who underwent cardiac magnetic resonance imaging (CMRI) were analysed retrospectively. T2-mapping TA of the myocardial remote zone was conducted accordingly. The patients were divided into two subgroups according to the occurrence of MACEs. The primary outcome was a composite of MACEs. RESULTS: Among 155 patients, 32 (20.6%) patients suffered MACEs, and the most common event was non-sustained ventricular tachycardia (84.3%). Five independent texture features on T2-mapping were selected: Perc.50%, S(4,-4)AngScMom, S(1,1)InvDfMom, S(0,2)DifEntrp, and Horzl_LngREmph. Among them, the mean value of Horzl_LngREmph in the myocardial remote zone among all patients, MACEsnegative, and MACEs-positive was 21.64, 19.12, and 34.52, respectively. Horzl_LngREmph provided the highest area under the receiver operating characteristic (ROC) curve (AUC) value, which enabled two subgroups to be distinguished (AUC = 0.914, p<0.05). According to the results of the univariate analysis, combined with late gadolinium enhancement (LGE) extent and the presence of left ventricular hypertrophy, Horzl_LngREmph, was strongly associated with the occurrence of MACEs (p<0.05, hazard ratio: 1.64, 95% confidence interval: 1.10-4.51). CONCLUSION: Together with LGE extent, Horzl_LngREmph, a texture feature obtained from T2-mapping TA of the myocardial remote zone, could predict the occurrence of MACEs in AMI patients.

Changes over time in the association between type 2 diabetes and post-discharge outcomes in decompensated chronic heart failure patients: Findings from the RICA Registry.

AIMS: Heart failure (HF) and diabetes are 2 strongly associated diseases. The main objective of this work was to analyze changes in the prognosis of patients with diabetes who were admitted for heart failure in 2 time periods. METHODS: This work is a prospective study comparing prognosis at one year of follow-up among patients with diabetes who were hospitalized for HF in either 2008-2011 or 2018. The patients are from the Spanish Society of Internal Medicine's National Heart Failure Registry (RICA, for its initials in Spanish). The primary endpoint was to analyze the composite outcome of total mortality and/or readmission due to HF in 12 months. A multivariate Cox regression model was used to evaluate the strength of association (hazard ratio [HR]) between diabetes and the outcomes between both periods. RESULTS: A total of 936 patients were included in the 2018 cohort, of which 446 (48%) had diabetes. The baseline characteristics of the populations from the 2 periods were similar. In patients with diabetes, the composite outcome was observed in 233 (47.5%) in the 2008-2011 cohort and 162 (36%) in the 2018 cohort [HR 1.48; 95% confidence interval (95%CI) 1.18-1.85; p < .001]. The proportion of readmissions (HR 1.39; 95%CI 1.07-1.80; p = .015) and total mortality (HR 1.60; 95%CI 1.20-2.14; p < .001) were also significantly higher in patients with diabetes from the 2008-2011 cohort compared to the 2018 cohort. CONCLUSIONS: In 2018, an improvement was observed in the prognosis for all-cause mortality and readmissions over one year of follow-up in patients with diabetes hospitalized for HF compared to the 2008-2011 period.

Pneumorrhachis following cervical spine surgery.

A 66-year-old man experienced symptomatic pneumorrhachis (air within the spinal canal) following a cervical laminoplasty for the excision of meningioma. Following an uneventful intraoperative course, he suffered a fluctuating hemiparesis of varying severity. Urgent imaging demonstrated extradural and intradural air in the spinal canal. Treatment with supplemental oxygen and dexamethasone was commenced, and the patient's symptoms improved over a period of three days with full resolution at six weeks. Pneumorrhachis can be avoided by allowing air to escape from the spinal canal through positioning, and displacement with irrigation fluid at the time of wound closure. However, if pneumorrhachis does occur, oxygen therapy, positioning of the patient to mitigate the gravitational effect of the air bubbles and supportive treatment are the central elements of management. Other possible causes of neurological deficit should be ruled out. This is particularly important as treatment options for some differential diagnoses can potentially cause harm if started based on clinical impression alone, for example, re-exploration for suspected haematoma. Only a small number of previous reports have described symptomatic pneumorrhachis as a complication of spinal surgery. This patient was successfully managed with conservative measures following the exclusion of other spinal cord pathologies.

Utility of capsule endoscopy in the diagnosis of gastrointestinal graft-versus-host disease.

INTRODUCTION AND AIM: Graft-versus-host disease (GvHD) is a complication of hematopoietic cell transplantation, and the small bowel is one of the main targets in the gastrointestinal tract. Capsule endoscopy is a safe procedure and can be useful in the diagnosis of GvHD. The aim of the present study was to compare the diagnostic yield of capsule endoscopy with the histopathologic findings in GvHD. MATERIALS AND METHODS: A retrospective diagnostic test study included all the patients with suspected GvHD that underwent gastroscopy and colonoscopy, with histopathologic evaluation of the biopsies taken, and capsule endoscopy, within the time frame of July 2015 and July 2019. Capsule endoscopy findings were compared with the histopathologic diagnosis, considered the gold standard. RESULTS: Twenty-one patients with GvHD (7 [33%] women; 37 ± 11.9 years of age) were included, 20 (95%) of whom had acute GvHD. The median gastric transit time of the capsule was 55 minutes (20-113) and the median small bowel transit time was 261 minutes (238-434). The entire small bowel was visualized through capsule endoscopy in 17 cases (80.95%). The histopathologic findings and capsule endoscopy findings resulted in the diagnosis of GvHD in 17 and 16 cases, respectively. There was agreement between the histopathologic and capsule endoscopy findings in 18 cases (15 positive and 3 negative). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic yield of capsule endoscopy were 88%, 75%, 94%, 60%, and 85%, respectively. CONCLUSIONS: Capsule endoscopy is a safe tool for the diagnosis of GvHD, with high sensitivity and positive predictive value, as well as moderate agreement with histopathologic findings.

Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice.

PURPOSE: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice. MATERIALS AND METHODS: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression. RESULTS: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001). CONCLUSION: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.

Huygens principle: exact and approximate wavefronts propagated through conic lenses.

Exact and approximate formulae for refracted wavefronts through singlet lenses are obtained by considering an incident plane wavefront propagating along the optical axis. We provide two different approaches for the wavefronts approximated at the second order based on the Huygens principle and the Malus-Dupin theorem. We have in the first method found a way to use iterative wavelets instead of the usual evaluated integral to arrive at these formulae, showing a physical and mathematical correspondence between both methods. Finally, we introduce a parabolic wavefront into the irradiance transport equation in order to provide an analytical solution for the distribution of illumination.

Review of medical professional organizations in developed countries: problems of decentralized membership registers.

This article provides a critical review of international experiences regarding the professional organization of physicians and the registration of doctors in developed countries. The problems faced by professional medical organizations in the EU-15 countries, Japan, the United States and Canada, are examined. Medical professional groups differ in several dimensions, including obligatory registration versus voluntary membership or types of registration (centralized, indirect, or delegated). The centralization-decentralization axis is a key aspect for the analysis. While decentralized systems are better able to adapt to the idiosyncrasy of a particular region, decentralization is identified as a source of potential problems in the organization of medical doctors. Some of these problems (discrepancies in positions on health matters, problems with the reliability of statistical information on medical demography at national level, deficient mechanisms for the control of doctors who have lost their licenses) might have consequences for the quality of the health care system.

¿Cómo seleccionar una prótesis para un reemplazo primario de cadera? Mínima supervivencia aceptable: resultados de un consenso de expertos / How to select a prosthesis for a primary hip replacement? Minimum acceptable survival: results of a consensus of experts

Resumen: Introducción: Uno de los puntos más críticos en la planeación de las artroplastías de cadera es la selección del implante, puesto que su supervivencia impacta significativamente la salud de los pacientes. Sin embargo, hasta el momento no se ha definido cuál es la supervivencia ideal que debe demostrar un implante para ser seleccionado. El objetivo de este consenso es definir los estándares mínimos de desempeño para la selección de prótesis en reemplazo primario convencional de cadera. Material y métodos: El consenso se realizó mediante la metodología de «grupo nominal¼. Esto incluyó: 1. Revisión de la evidencia disponible y definición de los temas a evaluar, 2. Reunión para la votación y discusión y 3. Análisis estadístico cuantitativo con medianas (M) y rangos intercuartílicos (RIC) y cualitativo con proporciones de los resultados obtenidos para generar recomendaciones. Resultados: La fuente primaria de información para la selección de prótesis (M: 8; RIC: 7-9) y de elección en caso de evidencia contradictoria (M: 8; RIC: 7-9) o limitada en la literatura (M: 7; RIC: 4.75-825) son los registros nacionales. El mínimo seguimiento aceptable es 10 años (M: 9; RIC: 8-9) y el mínimo de supervivencia aceptable es 90% a 10 años (M: 8; RIC: 5-8.5). Discusión: De acuerdo con estos resultados, el consenso de expertos propone que la selección del implante en el reemplazo articular primario convencional de cadera se realice con base en la información publicada en los registros nacionales y que dicha prótesis tenga un seguimiento mínimo de 10 años y demuestre una supervivencia mínima de 90%.

Abstract: Background: One of the most critical points in the planning of hip replacement surgeries is the selection of the implant, since its survival significantly impacts the patients' health. However, the ideal survival time that an implant must prove to be selected has not been defined. The objective of this consensus is to define minimum performance standards for the selection of conventional primary hip replacement prosthesis. Material and methods: The consensus was carried out using the methodology of 'nominal group'. This included: 1. A review of the available evidence and the issues to be evaluated, 2. Meeting for the vote and discussion, 3. Quantitative statistical analysis with median (M) and interquartile range (IQR) and qualitative one with proportions of the results to generate recommendations. Results: The primary source of information for prosthesis selection (M: 8; IQR: 7-9), choice in the event of conflicting evidence (M: 8; IQR: 7-9), or limited evidence in the literature (M: 7; IQR: 4.75-825) should be national registries. The minimum acceptable follow-up is 10 years (M: 9; IQR: 8-9) and the minimum acceptable survival is 90% at 10 years (M: 8; IQR: 5-8.5). Discussion: According to these results, the consensus of experts proposed that the selection of the implant for conventional primary hip replacement must be based on the information published in the national registries and that the prosthesis must have a minimum follow-up of 10 years and show a minimum survival of 90%.

Intranasal delivery of dexamethasone efficiently controls LPS-induced murine neuroinflammation.

Neuroinflammation is the hallmark of several infectious and neurodegenerative diseases. Synthetic glucocorticoids (GCs) are the first-line immunosuppressive drugs used for controlling neuroinflammation. A delayed diffusion of GCs molecules and the high systemic doses required for brain-specific targeting lead to severe undesirable effects, particularly when lifelong treatment is required. Therefore, there is an urgent need for improving this current therapeutic approach. The intranasal (i.n.) route is being employed increasingly for drug delivery to the brain via the olfactory system. In this study, the i.n. route is compared to the intravenous (i.v.) administration of GCs with respect to their effectiveness in controlling neuroinflammation induced experimentally by systemic lipopolysaccharide (LPS) injection. A statistically significant reduction in interleukin (IL)-6 levels in the central nervous system (CNS) in the percentage of CD45+ /CD11b+ /lymphocyte antigen 6 complex locus G6D [Ly6G+ and in glial fibrillary acidic protein (GFAP) immunostaining was observed in mice from the i.n.-dexamethasone (DX] group compared to control and i.v.-DX-treated animals. DX treatment did not modify the percentage of microglia and perivascular macrophages as determined by ionized calcium binding adaptor molecule 1 (Iba1) immunostaining of the cortex and hippocampus. The increased accumulation of DX in brain microvasculature in DX-i.n.-treated mice compared with controls and DX-IV-treated animals may underlie the higher effectiveness in controlling neuroinflammation. Altogether, these results indicate that IN-DX administration may offer a more efficient alternative than systemic administration to control neuroinflammation in different neuropathologies.

Theoretical Confirmation of the Low Experimental 3C/3D f-Value Ratio in Fe xvii.

Radiative transition probabilities (A values) are computed for the Fe xvii L-shell lines in a Breit-Pauli configuration-interaction method with the autostructure atomic structure code. It is shown that, by carefully taking into account the fine-tuning of the relativistic coupling and 2p-orbital relaxation, the measured A values of the M1 and M2 lines and, for the first time, the low f(3C)/f(3D) oscillator-strength ratio are satisfactorily reproduced by the theory. The present ratio f(3C)/f(3D)=2.82 compares well with the measurement of 2.61±0.23 by x-ray laser spectroscopy.

Th1/Th2 balance in the liver and hepatic lymph nodes of vaccinated and unvaccinated sheep during acute stages of infection with Fasciola hepatica.

The expression of IFNγ and IL4 was quantified using q-PCR in the liver and hepatic lymph nodes (HLN) of sheep during early stages of infection with Fasciola hepatica (1, 3, 9 and 18days post-infection, dpi). A group of animals (Group 1) were vaccinated with Fasciola hepatica recombinant cathepsin L1 (FhCL1) in montanide 70 VG prior to infection, a second group (group 2) was used as infected control and a third (group 3) was used as uninfected control. To study vaccine efficacy three additional groups were sacrificed 19 weeks post-infection (group 4 immunized with CL1, group 5 with the adjuvant and group 6 was used as infected control). The vaccinated group did not show significant fluke reduction compared to the adjuvant group and infected control group. IL4 expression was observed to increase at 9 dpi and was further elevated at 18 dpi in the liver and HLN of vaccinated and infected control groups compared to the uninfected group. IFNγ expression exhibited different dynamics in the liver and HLN compared to IL4; thus, in the liver this cytokine increased at 9 dpi in the vaccinated and at 18 dpi in vaccinated and infected control groups, while in the HLN it decreased gradually and significantly from 1 dpi onwards. These results suggest that a marked Th2 polarization is present from 9 dpi in HLN and from 18 dpi in the liver. The increase of IFNγ in the liver may correspond with tissue damage response with granuloma formation. The FhCL1 vaccine did not alter the Th1/Th2 balance when compared to unvaccinated and infected sheep. The study of IFNγ and IL4 in the various tissue compartments in sheep could facilitate selection of new adjuvants inducing a strong Th1 response for a more rationale vaccine formulation.

Apoptosis of peritoneal leucocytes during early stages of Fasciola hepatica infections in sheep.

Several immunomodulatory properties have been described in Fasciola hepatica infections. Apoptosis has been shown to be an effective mechanism to avoid the immune response in helminth infections. The aim of the present work was to study apoptosis in peritoneal leucocytes of sheep experimentally infected with F. hepatica during the early stages of infection. Five groups (n=5) of sheep were used. Groups 2-5 were orally infected with 200 metacercariae (mc) and sacrificed at 1, 3, 9 and 18days post-infection (dpi), respectively. Group 1 was used as the uninfected control (UC). Apoptosis was detected using three different methods 1) immunocytochemistry (ICC) with a polyclonal antibody anti-active caspase-3; 2) an annexin V flow cytometry assay using the Annexin V-FITC/propidium iodide (PI); and 3) transmission electron microscopy (TEM). The differential leucocyte count revealed that the majority of peritoneal granulocytes were eosinophils, which increased significantly at 9 and 18 dpi with respect to the uninfected controls. The ICC study revealed that the percentage of caspase-3+ apoptotic peritoneal leucocytes increased significantly from 3 dpi onwards with respect to the uninfected controls. The flow cytometry annexin V assay detected a very significant (P<0.001) increase of apoptotic peritoneal macrophages, lymphocytes and granulocytes, which remained higher than in the UC until 18 dpi. Transmission electron microscopy studies also confirmed the presence of apoptosis in peritoneal eosinophils at 18 dpi. This is the first report of apoptosis induced by F. hepatica in the peritoneal leucocytes of sheep in vivo. The results of this work suggest the importance of apoptosis induction for the survival of the juvenile parasites in the peritoneal migratory stages of infection.

Maternal obesity, gestational diabetes, breastfeeding and childhood overweight at age 2 years.

BACKGROUND: Maternal obesity, excessive gestational weight gain (EGWG), gestational diabetes mellitus (GDM) and breastfeeding are four important factors associated with childhood obesity. OBJECTIVES: The objective of the study was to assess the interplay among these four factors and their independent contributions to childhood overweight in a cohort with standard clinical care. METHODS: The cohort included 15 710 mother-offspring pairs delivered in 2011. Logistic regression was used to assess associations between maternal exposures and childhood overweight (body mass index >85th percentile) at age 2 years. RESULTS: Mothers with pre-pregnancy obesity or overweight were more likely to have EGWG, GDM and less likely to breastfeed ≥6 months. Mothers with GDM had 40-49% lower EGWG rates and similar breastfeeding rates compared with mothers without GDM. Analysis adjusted for exposures and covariates revealed an adjusted odds ratio (95% confidence interval) associated with childhood overweight at age 2 years of 2.34 (2.09-2.62), 1.50 (1.34-1.68), 1.23 (1.12-1.35), 0.95 (0.83-1.10) and 0.76 (0.69-0.83) for maternal obesity, overweight, EGWG, GDM and breastfeeding ≥6 months vs. <6 months, respectively. CONCLUSIONS: In this large clinical cohort, GDM was not associated with, but maternal pre-pregnancy obesity or overweight and EGWG were independently associated with an increased risk, and breastfeeding ≥6 months was associated with a decreased risk of childhood overweight at age 2 years.

[How to select a prosthesis for a primary hip replacement? Minimum acceptable survival: results of a consensus of experts]. / ¿Cómo seleccionar una prótesis para un reemplazo primario de cadera? Mínima supervivencia aceptable: resultados de un consenso de expertos.

BACKGROUND: One of the most critical points in the planning of hip replacement surgeries is the selection of the implant, since its survival significantly impacts the patients health. However, the ideal survival time that an implant must prove to be selected has not been defined. The objective of this consensus is to define minimum performance standards for the selection of conventional primary hip replacement prosthesis. MATERIAL AND METHODS: The consensus was carried out using the methodology of nominal group. This included: 1. A review of the available evidence and the issues to be evaluated, 2. Meeting for the vote and discussion, 3. Quantitative statistical analysis with median (M) and interquartile range (IQR) and qualitative one with proportions of the results to generate recommendations. RESULTS: The primary source of information for prosthesis selection (M: 8; IQR: 7-9), choice in the event of conflicting evidence (M: 8; IQR: 7-9), or limited evidence in the literature (M: 7; IQR: 4.75-825) should be national registries. The minimum acceptable follow-up is 10 years (M: 9; IQR: 8-9) and the minimum acceptable survival is 90% at 10 years (M: 8; IQR: 5-8.5). DISCUSSION: According to these results, the consensus of experts proposed that the selection of the implant for conventional primary hip replacement must be based on the information published in the national registries and that the prosthesis must have a minimum follow-up of 10 years and show a minimum survival of 90%.

INTRODUCCIÓN: Uno de los puntos más críticos en la planeación de las artroplastías de cadera es la selección del implante, puesto que su supervivencia impacta significativamente la salud de los pacientes. Sin embargo, hasta el momento no se ha definido cuál es la supervivencia ideal que debe demostrar un implante para ser seleccionado. El objetivo de este consenso es definir los estándares mínimos de desempeño para la selección de prótesis en reemplazo primario convencional de cadera. MATERIAL Y MÉTODOS: El consenso se realizó mediante la metodología de «grupo nominal¼. Esto incluyó: 1. Revisión de la evidencia disponible y definición de los temas a evaluar, 2. Reunión para la votación y discusión y 3. Análisis estadístico cuantitativo con medianas (M) y rangos intercuartílicos (RIC) y cualitativo con proporciones de los resultados obtenidos para generar recomendaciones. RESULTADOS: La fuente primaria de información para la selección de prótesis (M: 8; RIC: 7-9) y de elección en caso de evidencia contradictoria (M: 8; RIC: 7-9) o limitada en la literatura (M: 7; RIC: 4.75-825) son los registros nacionales. El mínimo seguimiento aceptable es 10 años (M: 9; RIC: 8-9) y el mínimo de supervivencia aceptable es 90% a 10 años (M: 8; RIC: 5-8.5). DISCUSIÓN: De acuerdo con estos resultados, el consenso de expertos propone que la selección del implante en el reemplazo articular primario convencional de cadera se realice con base en la información publicada en los registros nacionales y que dicha prótesis tenga un seguimiento mínimo de 10 años y demuestre una supervivencia mínima de 90%.

Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide.

BACKGROUND: Neuroinflammation (NI) is a key feature in the pathogenesis and progression of infectious and non-infectious neuropathologies, and its amelioration usually improves the patient outcome. Peripheral inflammation may promote NI through microglia and astrocytes activation, an increased expression of inflammatory mediators and vascular permeability that may lead to neurodegeneration. Several anti-inflammatory strategies have been proposed to control peripheral inflammation. Among them, electrical stimulation of the vagus nerve (VNS) recently emerged as an alternative to effectively attenuate peripheral inflammation in a variety of pathological conditions with few side effects. Considering that NI underlies several neurologic pathologies we explored herein the possibility that electrically VNS can also exert anti-inflammatory effects in the brain. METHODS: NI was experimentally induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS) in C57BL/6 male mice; VNS with constant voltage (5 Hz, 0.75 mA, 2 ms) was applied for 30 s, 48 or 72 h after lipopolysaccharide injection. Twenty four hours later, pro-inflammatory cytokines (IL-1ß, IL-6, TNFα) levels were measured by ELISA in brain and spleen extracts and total brain cells were isolated and microglia and macrophage proliferation and activation was assessed by flow cytometry. The level of ionized calcium binding adaptor molecule (Iba-1) and glial fibrillary acidic protein (GFAP) were estimated in whole brain extracts and in histologic slides by Western blot and immunohistochemistry, respectively. RESULTS: VNS significantly reduced the central levels of pro-inflammatory cytokines and the percentage of microglia (CD11b/CD45low) and macrophages (CD11b/CD45high), 24 h after the electrical stimulus in LPS stimulated mice. A significantly reduced level of Iba-1 expression was also observed in whole brain extracts and in the hippocampus, suggesting a reduction in activated microglia. CONCLUSIONS: VNS is a feasible therapeutic tool to attenuate the NI reaction. Considering that NI accompanies different neuropathologies VNS is a relevant alternative to modulate NI, of particular interest for chronic neurological diseases.

Fasciola hepatica induces eosinophil apoptosis in the migratory and biliary stages of infection in sheep.

The aim of the present work was to evaluate the number of apoptotic eosinophils in the livers of sheep experimentally infected with Fasciola hepatica during the migratory and biliary stages of infection. Four groups (n=5) of sheep were used; groups 1-3 were orally infected with 200 metacercariae (mc) and sacrificed at 8 and 28 days post-infection (dpi), and 17 weeks post-infection (wpi), respectively. Group 4 was used as an uninfected control. Apoptosis was detected using immunohistochemistry with a polyclonal antibody against anti-active caspase-3, and transmission electron microscopy (TEM). Eosinophils were identified using the Hansel stain in serial sections for caspase-3, and by ultrastructural features using TEM. At 8 and 28 dpi, numerous caspase-3(+) eosinophils were mainly found at the periphery of acute hepatic necrotic foci. The percentage of caspase -3(+) apoptotic eosinophils in the periphery of necrotic foci was high (46.1-53.9) at 8 and 28 dpi, respectively, and decreased in granulomas found at 28 dpi (6%). Transmission electron microscopy confirmed the presence of apoptotic eosinophils in hepatic lesions at 8 and 28 dpi. At 17 wpi, apoptotic eosinophils were detected in the infiltrate surrounding some enlarged bile ducts containing adult flukes. This is the first report of apoptosis induced by F. hepatica in sheep and the first study reporting apoptosis in eosinophils in hepatic inflammatory infiltrates in vivo. The high number of apoptotic eosinophils in acute necrotic tracts during the migratory and biliary stages of infection suggests that eosinophil apoptosis may play a role in F. hepatica survival during different stages of infection.

RESPUESTA DE FITONEMATODOS DE PLÁTANO Musa AAB SIMMONDS A ESTRATEGIAS DE MANEJO INTEGRADO DEL SUELO Y NUTRICIÓN / PLANTAIN Musa AAB SIMMONDS PHYTONEMATODES RESPONSE TO SOIL INTEGRATED MANAGEMENT STRATEGIES AND NUTRITION

En Colombia el cultivo de plátano ocupa uno de los principales renglones de la economía; hace parte de la canasta familiar y es una fuente de empleo en las zonas donde se cultiva. La producción de este frutal se ve amenazada por el ataque de nematodos fitoparásitos que afectan el sistema radical, disminuyen la absorción de nutrientes y sirven como puerta de entrada a patógenos. Debido a esto, se requieren manejos que permitan la regulación de las poblaciones mediante estrategias que no atenten contra el equilibrio del ecosistema y que presenten una ventaja competitiva frente a los tratamientos tradicionales. En este estudio se evaluó la respuesta poblacional de fitonematodos del plátano Dominico Hartón, la presencia de hongos micorrícicoarbusculares (HMA) y la actividad de lombrices a la inoculación con HMA, lixiviado de compost de raquis de plátano y lombricompost. Los resultados obtenidos en la investigación sugieren que la respuesta de la población de fitonematodos a los tratamientos evaluados, mostró gran dependencia de las características parasíticas de cada género y que la aplicación de lombricompost, HMA y lixiviado de raquis de plátano pueden tener potencial en la regulación de las poblaciones de fitonematodos en el cultivo.

Plantain cultivation in Colombia occupies one of the main areas of the economy: plantain is part of the shopping basket and is a source of employment in the areas where it is cultivated. The production of this fruit is threatened by the attack of phytoparasitic nematodes affecting the root system, reducing the absorption of nutrients and serving as a gateway to pathogens. Because of this, maneuvers which allow the regulation of populations through strategies that do not threaten the balance of the ecosystem and that show a competitive advantage over traditional treatments. The phytonematodes population response of Dominico-Harton plantain, the presence of arbuscular mycorrhizal fungi (AMF) and earthworm activity to HMA inoculation, leachate from plantain compost rachis and earthworm compost were evaluated in this study. The results obtained from this research suggest that the phytonematodes population response to the treatments evaluated, showed strong dependence on parasitic characteristics of each gender and than the application of earthworm compost, AMF and leachate from plantain compost rachis may have a potential in the regulation of phytonematodes populations in cultivation.

[Sepsis in children with cancer: problems to detect it and challenges for diminishing it]. / Sepsis en el niño con cáncer: problemas en su identificación y retos para su disminución.

Since 1992 the availability of the criteria of systemic inflammatory response syndrome (SIRS) has improved the identification of subjects with sepsis. Sepsis remains a major hospital complication worldwide, responsible for thousands of deaths in children with cancer. Different biomarkers have been proposed for discrimination of septic child, who is not, but its introduction and routine use in control programs and surveillance has not been possible so far. The challenge in septic cancer remains valid subject and makes it a public health problem. The research accompanying the treatment of these children and introducing them, depend on their effectiveness, financing and universal availability of methods; but especially strategic planning based on that knowledge.

Biomass and lipid production of a local isolate Chlorella sorokiniana under mixotrophic growth conditions.

A local Chlorella sp. isolate with 97% rbcL sequence identity to Chlorella sorokiniana was evaluated in terms of its biomass and lipid production under mixotrophic growth conditions. Glucose-supplemented cultures exhibited increasing growth rate and biomass yield with increasing glucose concentration. Highest growth rate and biomass yield of 1.602 day(-1) and 687.5 mg L(-1), respectively, were achieved under 2 g L(-1) glucose. Nitrogen starvation up to 75% in the 1.0 g L(-1) glucose-supplemented culture was done to induce lipid accumulation and did not significantly affect the growth. Lipid content ranges from 20% to 27% dry weight. Nile Red staining showed more prominent neutral lipid bodies in starved mixotrophic cultures. C. sorokiniana exhibited enhanced biomass production under mixotrophy and more prominent neutral lipid accumulation under nitrogen starvation with no significant decrease in growth; hence, this isolate could be further studied to establish its potential for biodiesel production.