Protein and micronutrient deficiencies in patients with radiation cystitis and outcome after hyperbaric oxygen therapy.

BACKGROUND & AIMS: Haemorrhagic radiation cystitis (HRC) is a late complication of pelvic radiotherapy. Severe cases are difficult to treat due to persistent or recurrent bleeding, despite urological and hyperbaric oxygen therapy (HBOT). However, wound healing requires a good nutritional status. In this respect, we aimed at analysing the nutritional status of patients with HRC prior to the onset of HBOT and at highlighting predictive nutritional factors of outcome. METHODS: Data were retrospectively collected from a cohort of 179 patients with HRC (between 2011 and 2015). Haematuria was graded according to the Subjective, Objective, Management, Analytic scale (SOMA): grade-4 (n = 46) was compared with grade-3 (n = 56), and with grades 1 and 2 (n = 77). S-albumin, prealbumin, vitamins C, D and B6, zinc, selenium, and essential fatty acids were evaluated before HBOT. HBOT response was measured at 3 months according to the haematuria SOMA grade. The Mann-Whitney test, Fisher's exact test and principal-component analysis were used to compare groups. RESULTS: Patients with higher haematuria grades (3 and 4) harboured significant deficiencies in S-albumin, prealbumin, vitamins C, D and B6, zinc, selenium and essential fatty acids. Moreover, grade-4 patients without improvement after 3 months of HBOT had significant lower initial levels of S-albumin, vitamin C, selenium and linoleic acid. Vitamin C levels <2.5 mg/L were strongly associated with HBOT non-response (OR 23.14, 95% CI 3.73-143.69, p = 0.002). CONCLUSIONS: Our analyses show serious nutritional deficiencies associated with higher grades of HRC and worse prognoses. Patients with haemorrhagic cystitis might benefit from an adequate dietary supplementation to support healing of their bladder mucosa.

Neural signature of coma revealed by posteromedial cortex connection density analysis.

Posteromedial cortex (PMC) is a highly segregated and dynamic core, which appears to play a critical role in internally/externally directed cognitive processes, including conscious awareness. Nevertheless, neuroimaging studies on acquired disorders of consciousness, have traditionally explored PMC as a homogenous and indivisible structure. We suggest that a fine-grained description of intrinsic PMC topology during coma, could expand our understanding about how this cortical hub contributes to consciousness generation and maintain, and could permit the identification of specific markers related to brain injury mechanism and useful for neurological prognostication. To explore this, we used a recently developed voxel-based unbiased approach, named functional connectivity density (CD). We compared 27 comatose patients (15 traumatic and 12 anoxic), to 14 age-matched healthy controls. The patients' outcome was assessed 3 months later using Coma Recovery Scale-Revised (CRS-R). A complex pattern of decreased and increased connections was observed, suggesting a network imbalance between internal/external processing systems, within PMC during coma. The number of PMC voxels with hypo-CD positive correlation showed a significant negative association with the CRS-R score, notwithstanding aetiology. Traumatic injury specifically appeared to be associated with a greater prevalence of hyper-connected (negative correlation) voxels, which was inversely associated with patient neurological outcome. A logistic regression model using the number of hypo-CD positive and hyper-CD negative correlations, accurately permitted patient's outcome prediction (AUC = 0.906, 95%IC = 0.795-1). These points might reflect adaptive plasticity mechanism and pave the way for innovative prognosis and therapeutics methods.

Assessing the effect of selection with deltamethrin on biological parameters and detoxifying enzymes in Aedes aegypti (L.).

BACKGROUND: Resistance to insecticides through one or several mechanisms has a cost for an insect in various parameters of its biological cycle. The present study evaluated the effect of deltamethrin on detoxifying enzymes and biological parameters in a population of Aedes aegypti selected for 15 generations. The enzyme activities of alpha- and beta-esterases, mixed-function oxidases and glutathione-S-transferases were determined during selection, along with biological parameters. RESULTS: Overexpression of mixed-function oxidases as a mechanism of metabolic resistance to deltamethrin was found. There were decreases in percentages of eggs hatching, pupation and age-specific survival and in total survival at the end of the selection (F16 ). Although age-specific fecundity was not affected by selection with deltamethrin, total fertility, together with lower survival, significantly affected gross reproduction rate, gradually decreasing due to deltamethrin selection. Similarly, net reproductive rate and intrinsic growth rate were affected by selection. CONCLUSION: Alterations in life parameters could be due to the accumulation of noxious effects or deleterious genes related to detoxifying enzymes, specifically those coding for mixed-function oxidases, along with the presence of recessive alleles of the V1016I and F1534C mutations, associating deltamethrin resistance with fitness cost in Ae. aegypti. © 2017 Society of Chemical Industry.

Restoring Cytokine Balance in HIV-Positive Individuals with Low CD4 T Cell Counts.

HIV infects and destroys CD4+ T cells leading to a compromised immune system. In a double-blinded study, a group of HIV-infected individuals with CD4+ T cell counts below 350 cells/mm3 were given either an empty liposomal supplement or a liposomal glutathione (L-GSH) supplement to take over a 3-month period. Baseline measurements in HIV-positive subjects show a significant decrease in levels of interleukin (IL)-12, IL-2, and interferon (IFN)-γ, along with a substantial increase in the levels of IL-6, IL-10, transforming growth factor (TGF)-ß, and free radicals, compared to healthy individuals. Supplementation of HIV-positive subjects with L-GSH for 3 months resulted in a notable increase in the levels of IL-12, IL-2, and IFN-γ, with a concomitant decrease in the levels of IL-6, IL-10, and free radicals, and stabilization in the levels of TGF-ß, IL-1, and IL-17, compared to their placebo counterparts. Levels of free radicals in CD4+ T cells stabilized, while GSH levels increased in the treatment group. Those in the placebo group showed no significant difference throughout the study. In summary, supplementation with L-GSH in HIV-infected individuals with CD4+ T cell counts below 350 cells/mm3 can help restore redox homeostasis and cytokine balance, therefore aiding the immune system to control opportunistic infections.

Data on pro-inflammatory cytokines IL-1ß, IL-17, and IL-6 in the peripheral blood of HIV-infected individuals.

Our most recent data indicate differences in the levels of pro-inflammatory cytokines (IL-1ß, IL-17, and IL-6) and malondialdehyde (MDA), a stable end-product of lipid peroxidation in the plasma samples between HIV positive individuals with low CD4 T cell counts <200 mm(3) and HIV positive individuals with CD4 T cell counts between 200 and 300 mm(3) (ee). The data lend support and provide valuable correlation between CD4 T cell counts and the levels of inflammatory cytokines in HIV positive individuals.

Mecanismos de resistencia a la permetrina en dos poblaciones de Aedes aegypti del occidente de Venezuela / Mechanisms of Permethrin resistance in two populations of Aedes aegypti in westernVenezuela

Se determinó la resistencia a la permetrina en Aedes aegypti de los estados Trujillo y Zulia mediante bioensayos de botella. Los insectos derribados durante la hora de exposición fueron registrados y usados para calcular la Concentración Knock-down cincuenta (CK50) y los muertos a las 24 horas para la Concentración Letal cincuenta(CL50). La resistencia al derribo y post-recuperación fueron determinadas calculando del Factor de Resistencia FRCK50 y FRCL50, comparando los valores de CK50 y CL50de las poblaciones de Ae. aegypti de campo con los de la cepa susceptible New Orleans obtenidos mediante análisis de regresión log-probit. Mecanismos metabólicos y no metabólicos asociados a la resistencia, fueron evaluados midiendo los niveles de las enzimas alfa-esterasas, beta-esterasas, oxidasas de función múltiple y glutatión-S-transferasas mediante la técnica de microplacas y determinando la frecuencia alélica I1016 por PCR alelo específico. Ambas poblaciones mostraron baja resistencia al derribo (FRCK50 < 5) y moderada resistencia post-recuperación (FRCL50 entre 5 y 10). Sobre-expresión de alfa-esterasas fue observada en la población Loma Linda la cual se correlacionó significativamente con la CL50. En la población Pampanito la frecuencia del alelo I1016 fue de 0,1 y en Loma Linda de 0,17, observándose homocigotos mutantes solo en esta última población. Se evidencia la presencia de mecanismos metabólicos y no metabólicos asociados a la resistencia al derribo y post-recuperación a la permetrina en las poblaciones bajo estudio, lo cual debe ser considerado antes de la aplicación de piretroides para el control de Ae. aegypti en la zona de estudio.

Permethrin resistance was determined in Aedes aegypti populations from Trujillo and Zulia states using the bottle bioassay method. Insect knock-down rates during 1h of exposure were recorded and used to calculate the 50% knock-down concentration (KC50) and the mortality after 24 h (LC50). Knock-down and post-recovery resistance were determined by calculating the resistance factors, FRKC50 and FRLC50 . This was done by comparing the KC50 and LC50 values (obtained by regression analysis log-probit) of the field populations with a susceptible New Orleans strain. Metabolic and non-metabolic mechanisms associated with resistance were assessed by measuring the levels of the following enzymes: alpha-esterases, beta-esterases, mixed function oxidases (MFOs) and glutathione-S-transferases (GSTs) using the microplate technique. We also determined the alellic frequency of I1016 by allele specific PCR. Both populations showed a low knock-down resistance (FRKC50 < 5) and moderate post-recovery resistance (FRLC50 between 5 and 10). Overexpression of alpha-esterases was observed in the Loma Linda population and was significantly correlated with the LC50 . The frequency of the I1016 allele was 0.1 for the Pampanito population and 0.17 for the Loma Linda population, and in the latter we also observed homozygous mutants. The existence of metabolic and non-metabolic mechanisms associated with knockdown resistance and post-recovery to permethrin in the populations studied was demonstrated. This should be taken into account before introducing these insecticides to control populations of Ae. aegypti in the region.

Cerebral and extracerebral vulnerability to hypoxic insults after diffuse traumatic brain injury in rats.

The post-traumatic brain vulnerability suggests that after traumatic brain injury (TBI), the brain may be more susceptible to posttraumatic hypoxic insults. This concept could be extended to 'peripheral' organs, as non-neurologic organ failure is common after TBI. This study aims to characterize and quantify cerebral and extracerebral tissue hypoxia with pimonidazole resulting from a standardized hypoxia-hypotension (HH) phase occurring after a diffuse experimental TBI in rats. Rats were allocated to Sham (n=5), TBI (n=7), HH (n=7) and TBI+HH (n=7) groups. Then, pimonidazole was injected and brain, liver, heart and kidneys were analysed. In the cerebral cortex, post-treatment hypoxia was higher in TBI+HH group than Sham group (p=0.003), HH group (p=0.003) and TBI group (p=0.002). Large trends in thalamus, hippocampus and striatum for the TBI+HH group compared to the other groups were observed. For the heart and liver, the 4 groups were comparable. For the kidneys, post-treatment hypoxia was higher in the TBI group compared to the Sham and HH groups, but not more than TBI+HH group. This study reveals that a posttraumatic hypoxic insult occurring after a severe TBI has major hypoxic consequences on brain structures. However, TBI by itself appears to induce renal hypoxia that is not enhanced by posttraumatic hypoxic insult.

Mecanismos asociados a la resistencia al derribo "kdr" a la deltametrina en Aedes aegypti del occidente de Venezuela / Mechanisms associated with knockdown resistance to deltamethrin in Aedes aegypti from western Venezuela

Se determinaron los mecanismos bioquímicos y moleculares involucrados con la resistencia al derribo "kdr" a la deltametrina en poblaciones de Aedes aegypti de los estados Trujillo, Lara y Táchira. Las poblaciones fueron expuestas a CK50 previamente determinadas mediante bioensayos con botellas impregnadas siguiendo la metodología de Brogdon (1989) por 1h. Posteriormente los insectos fueron colocados en envases post-recuperación libres de insecticidas y separados en 4 fenotipos: los no derribados luego de 1h, los recuperados a las 4h, los supervivientes y los muertos a las 24 horas post-exposición. Todos los ejemplares fueron seccionados; con cabeza y tórax se determinaron los niveles de esterasas α y β, oxidasas de función múltiple, glutation S transferasas y acetilcolinesterasa insensible y con el abdomen se extrajo ADN y se realizaron PCR para amplificar los alelos específicos Val1016 e Ile1016. Las enzimas desintoxicantes se incrementaron en la mayoría de las poblaciones entre las 4 y 24h posteriores a la exposición a la deltametrina sin encontrarse diferencia significativa con los niveles expresados en la cepa susceptible New Orleans (NO), excepto en la población de Ureña donde se encontró aumento significativo en las β-esterasas siendo superiores en el fenotipo superviviente con respecto al fenotipo muertos a las 24h. El genotipo silvestre V1016/V1016 prevaleció sobre el heterocigoto y homocigoto mutante en los cuatro fenotipos, en la mayoría de las poblaciones estudiadas, con excepción de la población Ureña donde el homocigoto mutante I1016/I1016 fue el genotipo predominante en los no derribados, lo cual se vio reflejado en la frecuencia alélica. Se asocia la mutación V1016I con la resistencia al derribo mostrada en las poblaciones evaluadas, destacando la importancia de la temprana detección de esta y otras mutaciones en el canal del sodio asociadas con resistencia a piretroides, lo cual debe ser considerado antes de incorporar el uso de deltametrina en el programa de control de Ae. aegypti en estas poblaciones.

The biochemical and molecular mechanisms associated with resistance to deltamethrin were determined in female Aedes aegypti taken from different mosquito populations captured in Trujillo, Lara and Tachira states. Individuals from each population were subjected to 1 h of exposure to deltamethrin using the CK50 previously determined by the bottle bioassay. The mosquitoes were then placed in containers free from insecticide and separated into 4 phenotypes: mosquitoes that were not knocked down after 1 h of exposure, those that recovered 4 h after exposure, those that were still alive 24 h after exposure and those that were dead at 24 h. Each of the mosquitoes in these groups was then dissected to separate the head-thorax, and abdomen. Biochemical tests were performed on the head-thorax to determine the presence of resistance-related enzymes including: α-and β-esterases, glutathione S-transferase and insensitive acetylcholinesterase. The abdomen was used for molecular tests to amplify the specific allele Val 1016 and Ile 1016. The quantities of detoxifying enzymes increased between 4 and 24 h after exposure to deltamethrin in mosquitoes from most of the populations tested although no significant differences between these and the susceptible New Orleans strain (NO) were found, except for mosquitoes from the Ureña population which showed a significant increase in β-esterase with higher values in the "survivors" phenotype compared to the "dead" phenotype at 24 h. The wild genotype V1016/V1016 prevailed over the heterozygous and homozygous mutants in the four phenotypes in the majority of the populations studied, with exception of the Ureña population where the resistant homozygote I1016/I1016 was the predominant genotype. The V1016I mutation was associated with the knockdown resistance observed in the evaluated populations emphasizing the importance of the early detection of this and other mutations in the sodium channel which have been linked with resistance to pyrethroids. These aspects should be considered before applying deltamethrin to control these Ae. Aegypti populations.

Recuento absoluto de linfocitos como factor predictivo en el trasplante hematopoyético / Absolute lymphocyte count as a predictor in hematopoietic transplantation

La recuperación temprana de linfocitos es un factor pronóstico que está relacionado con una mayor supervivencia libre de eventos y supervivencia global en pacientes trasplantados. Se realizó una revisión bibliográfica con el objetivo de determinar el valor pronóstico del recuento absoluto de linfocitos en pacientes con hemopatías malignas, tratados con trasplante. Los pacientes con trasplantes autólogos alcanzan un recuento absoluto de linfocitos el día + 15 (RAL15) e 500 x mm³, más temprano que los alogénicos. El RAL15 cuando se utiliza sangre periférica es mayor que cuando se emplea la médula ósea. Los factores pronósticos asociados a una peor supervivencia global fueron la sepsis, el RAL15 < 500x mm³ y la recaída. Varios estudios muestran una mejor supervivencia global y supervivencia libre de eventos a los cinco años, en los pacientes con RAL15 e 500 x mm³. El RAL15 e 500 x mm³ es una herramienta simple y útil para predecir un mejor resultado en pacientes sometidos a trasplante hematopoyético(AU)

Early recovery of lymphocytes is a prognostic factor that is related to a higher event-free survival and overall survival after haematopoietic stem cell transplantation. A literature review was conducted in order to determine the prognostic value of absolute lymphocyte count in patients with hematological malignancies after transplantation. Autologous transplant patients reach an absolute lymphocyte count on day + 15 (RAL15) e 500 x mm³, earlier than allogeneic. The RAL15 when peripheral blood is used is greater than when using the bone marrow. Prognostic factors associated with worse overall survival were sepsis, RAL 15 <500x mm³ and relapse. Several studies show a better overall survival and event-free survival at five years in patients with e 500 x RAL15 mm³. The RAL15 e 500 x mm³ is a simple and useful tool to predict a better outcome in patients undergoing hematopoietic transplantation(AU)

Recuento absoluto de linfocitos como factor predictivo en el trasplante hematopoyético / Absolute lymphocyte count as a predictor in hematopoietic transplantation

La recuperación temprana de linfocitos es un factor pronóstico que está relacionado con una mayor supervivencia libre de eventos y supervivencia global en pacientes trasplantados. Se realizó una revisión bibliográfica con el objetivo de determinar el valor pronóstico del recuento absoluto de linfocitos en pacientes con hemopatías malignas, tratados con trasplante. Los pacientes con trasplantes autólogos alcanzan un recuento absoluto de linfocitos el día + 15 (RAL15) e 500 x mm³, más temprano que los alogénicos. El RAL15 cuando se utiliza sangre periférica es mayor que cuando se emplea la médula ósea. Los factores pronósticos asociados a una peor supervivencia global fueron la sepsis, el RAL15 < 500x mm³ y la recaída. Varios estudios muestran una mejor supervivencia global y supervivencia libre de eventos a los cinco años, en los pacientes con RAL15 e 500 x mm³. El RAL15 e 500 x mm³ es una herramienta simple y útil para predecir un mejor resultado en pacientes sometidos a trasplante hematopoyético

Early recovery of lymphocytes is a prognostic factor that is related to a higher event-free survival and overall survival after haematopoietic stem cell transplantation. A literature review was conducted in order to determine the prognostic value of absolute lymphocyte count in patients with hematological malignancies after transplantation. Autologous transplant patients reach an absolute lymphocyte count on day + 15 (RAL15) e 500 x mm³, earlier than allogeneic. The RAL15 when peripheral blood is used is greater than when using the bone marrow. Prognostic factors associated with worse overall survival were sepsis, RAL 15 <500x mm³ and relapse. Several studies show a better overall survival and event-free survival at five years in patients with e 500 x RAL15 mm³. The RAL15 e 500 x mm³ is a simple and useful tool to predict a better outcome in patients undergoing hematopoietic transplantation

Factors influencing the implementation of antibiotic de-escalation and impact of this strategy in critically ill patients.

INTRODUCTION: A rational use of antibiotics is of paramount importance in order to prevent the emergence of multidrug resistant bacteria that can lead to therapeutic impasse, especially in intensive care units (ICUs). A de-escalation strategy is therefore naturally advocated as part of better antibiotics usage. However, the clinical impact of such a strategy has not been widely studied. We aimed to assess the feasibility and the clinical impact of a de-escalation strategy in a medical ICU and to identify factors associated when de-escalation was possible. METHODS: We performed a retrospective study of patients hospitalized in a medical ICU over a period of six months. Independent factors associated with de-escalation and its clinical impact were assessed. RESULTS: Two hundred and twenty-nine patients were included in the study. Antibiotics were de-escalated in 117 patients (51%). The appropriateness of initial antibiotic therapy was the only independent factor associated with the performance of de-escalation (OR = 2.9, 95% CI, 1.5-5.7; P = 0.002). By contrast, inadequacy of initial antibiotic therapy (OR = 0.1, 0.0 to 0.1, P <0.001) and the presence of multidrug resistant bacteria (OR = 0.2, 0.1 to 0.7, P = 0.006) prevented from de-escalation. There were no differences in terms of short (ICU) or long-term (at 1 year) mortality rates or any secondary criteria such as ICU length of stay, duration of antibiotic therapy, mechanical ventilation, incidence of ICU-acquired infection, or multi-drug resistant bacteria emergence. CONCLUSIONS: De-escalation appears feasible in most cases without any obvious negative clinical impact in a medical ICU.

Determinación de dosis diagnósticas y tiempos letales en lutzomyia youngi de Las Calderas Trujillo-Venezuela a cuatro insecticidas / Determination of diagnostic doses and letal times in lutzomya youngi of las calderas, Trujillo-Venezuela to four insecticidas

Lutzomyia Youngi es el principal vector de leishmaniasis cutánea en la ciudad de Trujillo, Venezuela, donde la enfermedad es altamente endémica. Se ha obtenido información acerca del comportamiento de estos insectos frente algunos insecticidas de uso común en Venezuela, exponiendo hembras silvestres de Lutzomya Youngi procedentes de la localidad Las Calderas, a papeles impregnados con diferentes concentraciones de DDT, malation, propuxur y lambdacyhalotrina para determinar las concentraciones letales 50 y 95 dosis diagnosticas, siguiendo la técnica de la OMS (1970). Se obtuvieron valores para las CL, CL95 y dosis diagnostica con DDT de 0,29 por ciento, 1,04 por ciento y 3,54 por ciento; para malation 0,23 por ciento, 0,64 por ciento y 1,9 por ciento; para propoxur 0,0068 por ciento, 0,011 por ciento y 0,026 por ciento y para lamdacyhalotrina 0,0004 por ciento, 0,0015 por ciento y 0,0056 por ciento respectivamente. Posteriormente se determinaron los tiempos letales 50 y 95 usando las dosis diagnosticas calculadas excepto con lambdacyhalotrina que se uso el equivalente a la CL99, encontrándose valores de 6.10 min. y 13.17 min con DDT; 15.6 min y 38.21 min para malation; 18.3 min y 36.7 min para propoxur y 11.08 min y 33.4 para lamdacyalotrina que se uso el equivalente a la CL99, encontrándose valores de 6.10 min. y 13.17 min con DTT; 15.6 min y 38.21 para malation; 18.3 min y 36.7 min para propoxur y 11.08 min y 33.4 min para lamdacyalotrina en relación. LU. youngi resultó ser mas sensible al insecticida piretroide lamdacyalotrina en relación con los otros insecticidas evaluados, sugiriendo que este piretroide tiene mayor efecto toxico sobre la especie estudiada (au)