Synergistic impact of innate immunity hyper-activation and endothelial dysfunction on the magnitude of organ failure in the infection-sepsis continuum.

OBJECTIVES: Identifying host response biomarkers implicated in the emergence of organ failure during infection is key to improving the early detection of this complication. METHODS: Twenty biomarkers of innate immunity, T-cell response, endothelial dysfunction, coagulation, and immunosuppression were profiled in 180 surgical patients with infections of diverse severity (IDS) and 53 with no infection (nIDS). Those better differentiating IDS/nIDS in the area under the curve were combined to test their association with the sequential organ failure assessment score by linear regression analysis in IDS. Results were validated in another IDS cohort of 174 patients. RESULTS: C-reactive protein, procalcitonin, pentraxin-3, lipocalin-2 (LCN2), tumoral necrosis factor-α, angiopoietin-2, triggering receptor expressed on myeloid cells-1 (TREM-1) and interleukin (IL)-15 yielded an area under the curve ≥0.75 to differentiate IDS from nIDS. The combination of LCN2, IL-15, TREM-1, angiopoietin-2 (Dys-4) showed the strongest association with sequential organ failure assessment score in IDS (adjusted regression coefficient; standard error; P): Dys-4 (3.55;0.44; <0.001), LCN2 (2.24; 0.28; <0.001), angiopoietin-2 (1.92; 0.33; <0.001), IL-15 (1.78; 0.40; <0.001), TREM-1(1.74; 0.46; <0.001), tumoral necrosis factor-α (1.60; 0.31; <0.001), pentraxin-3 (1.12; 0.18; <0.001), procalcitonin (0.85; 0.12; <0.001). Dys-4 provided similar results in the validation cohort. CONCLUSIONS: There is a synergistic impact of innate immunity hyper-activation (LCN2, IL-15, TREM-1) and endothelial dysfunction (angiopoietin-2) on the magnitude of organ failure during infection.

Development of a Patient Decision Aid for the Treatment of Osteoporosis Among Filipino Postmenopausal Women.

BACKGROUND: Guidelines for osteoporosis have provided recommendations on when to offer pharmacologic management for postmenopausal women, but do not specify which "best" medication to start. The choice of therapy depends on the efficacy, safety/tolerability of the drug and the patient's profile and preferences. Patient decision aids (PtDA) are tools designed to facilitate shared decision-making (SDM) between the patient and health care provider for conditions where there are several available options, and the "best" choice is unclear. We aimed to develop a culturally acceptable patient decision aid on the treatment of osteoporosis among Filipino postmenopausal women at risk of osteoporotic fractures. METHODOLOGY: A qualitative approach and an iterative process was employed in this study following the guidance of the International Patient Decision Aid Standards (IPDAS). Phase 1 (Needs Assessment) involved interviews with 8 physicians who are involved in the care of women with osteoporosis and focus group discussions with 19 postmenopausal women with osteoporosis who have received treatment. Phase 2 (PtDA Development) involved a systematic review of evidence and development of an initial prototype through several iterations with an expert panel. The final prototype was pilot tested in actual clinical encounters (Phase 3). RESULTS: The final PtDA consists of 6 laminated flashcards, which illustrate the different considerations that are important to patients when selecting an anti-osteoporosis treatment (efficacy, method, frequency of administration, side effects and cost), and a fracture worksheet to illustrate individualized effects of the treatments on the patient's fracture risk. These are accompanied by a clinician guide on how to use the PtDA during consultations, which includes information on non-pharmacologic management of osteoporosis. The PtDA was acceptable to physicians and patients. CONCLUSION: With the integration of decisional needs assessment, clinical expertise, user preference and iterative revision testing, we were able to develop a culturally adapted PtDA on the treatment of osteoporosis among Filipino postmenopausal woman at risk of osteoporotic fractures for use during clinical encounters.

Exploiting xylan as sugar donor for the synthesis of an antiproliferative xyloside using an enzyme cascade.

BACKGROUND: Currently, industrial societies are seeking for green alternatives to conventional chemical synthesis. This demand has merged with the efforts to convert lignocellulosic biomass into value-added products. In this context, xylan, as one of main components of lignocellulose, has emerged as a raw material with high potential for advancing towards a sustainable economy. RESULTS: In this study, the recombinant endoxylanase rXynM from the ascomycete Talaromyces amestolkiae has been heterologously expressed in Pichia pastoris and used as one of the catalysts of an enzyme cascade developed to synthesize the antiproliferative 2-(6-hydroxynaphthyl) ß-D-xylopyranoside, by transglycosylation of 2,6-dihydroxynaphthalene. The approach combines the use of two fungal xylanolytic enzymes, rXynM and the ß-xylosidase rBxTW1 from the same fungus, with the cost-effective substrate xylan. The reaction conditions for the cascade were optimized by a Central Composite Design. Maximal productions of 0.59 and 0.38 g/L were reached using beechwood xylan and birchwood xylan, respectively. For comparison, xylans from other sources were tested in the same reaction, suggesting that a specific optimization is required for each xylan variety. The results obtained using this enzyme cascade and xylan were similar or better to those previously reported for a single catalyst and xylobiose, an expensive sugar donor. CONCLUSIONS: Beechwood and birchwood xylan, two polysaccharides easily available from biomass, were used in a novel enzyme cascade to synthetize an antiproliferative agent. The approach represents a green alternative to the conventional chemical synthesis of 2-(6-hydroxynaphthyl) ß-D-xylopyranoside using a cost-effective substrate. The work highlights the role of xylan as a raw material for producing value-added products and the potential of fungal xylanolytic enzymes in the biomass conversion.

Bile-induced promoters for gene expression in Lactobacillus strains.

Bioengineering of probiotics allows the improvement of their beneficial characteristics. In this work, we develop a molecular tool that would allow the activation of desirable traits in probiotics once they reach the intestine. The activity of upstream regions of bile-inducible genes of Lactobacillus casei BL23 and Lactobacillus plantarum WCFS1 was analyzed using plasmids encoding an anaerobic fluorescent protein as reporter. The promoter P16090 from Lb. casei BL23 was selected and its bile induction confirmed in Lb. casei BL23, Lb. plantarum WCFS1, and in Lactobacillus rhamnosus and Lactobacillus reuteri strains. However, the induction did not occur in Lactococcus lactis MG1363 or Bifidobacterium strains. Studies with different bile compounds revealed the importance of cholic acid in the bile induction process. Induction of fluorescence was also confirmed for transformed Lb. casei BL23 under simulated colonic conditions and in the presence of intestinal microbiota. The developed vector, pNZ:16090-aFP, constitutes a promising tool suitable for the expression of genes of interest under intestinal conditions in probiotic strains of the species Lb. casei, Lb. plantarum, Lb. rhamnosus, and Lb. reuteri.

Vascular complications in the diabetic pregnancy.

Long-standing hyperglycemia frequently leads to vasculopathy. Microvascular disease is characterized by retinopathy and nephropathy, while macrovascular involvement can affect coronary arteries. Diabetic autonomic neuropathy, when present, is generally associated with retinal and/or renal involvement. Early identification of these diabetic complications allows appropriate counseling and early treatment. Among women with diabetic vasculopathy, nephropathy, chronic hypertension, preeclampsia, preterm delivery, and fetal growth restriction are frequently observed. Furthermore, women with impaired renal function in early pregnancy have increased risk of long-term deterioration of glomerular filtration rate. Proliferative retinopathy can progress during pregnancy and 1 year after delivery, but long-term effects are not likely to occur. When coronary artery disease or gastroparesis diabeticorum are present, excessive maternal and fetal morbidity is observed. When modern management is synchronized with early medical care, favorable maternal and perinatal outcomes can be expected.

Infección intrahospitalaria en pacientes con cáncer / Nosocomial infection in patients with cancer

Se efectuó una investigación descriptiva y transversal de todos los pacientes con cáncer que presentaron alguna infección intrahospitalaria en el Hospital Oncológico Provincial "Conrado Benítez" de Santiago de Cuba, desde enero hasta septiembre del 2009, a fin de caracterizarles clinicoepidemiológicamente. Del total de egresados, se infectaron 41 (1,5 por ciento), mientras que en la casuística predominaron el sexo masculino y el grupo etáreo de 40-59 años, así como los estadios clínicos III y IV, los cuales se hallaron entre los principales factores de riesgo, junto a la intervención quirúrgica y los problemas estructurales en el quirófano. Los microorganismos más frecuentes fueron: Pseudomonas aeruginosa en el cáncer de laringe y Escherichia coli en los tumores urológicos. De las infecciones, la mayoría se localizaron en heridas quirúrgicas; y de los pacientes infectados, gran parte presentaron leucocitosis y neutrofilia.

A descriptive and cross-sectional study was conducted in all cancer patients that had some nosocomial infection at "Conrado Benítez" Provincial Oncology Hospital of Santiago de Cuba, from January to September 2009, in order to characterize them clinically and epidemiologically. Of the discharged patients 41 were infected (1,5 percent), while male sex and age group of 40-59 years prevailed in the case material, as well as clinical stages III and IV, which were among the main risk factors together with surgical intervention and structural problems in the operating room. The most frequent microorganisms were Pseudomonas aeruginosa in larynx cancer and Escherichia coli in urologic tumors. Most of the infections were found in surgical wounds; and most of the infected patients had leukocytosis and neutrophilia.

Infección intrahospitalaria en pacientes con cáncer / Nosocomial infection in patients with cancer

Se efectuó una investigación descriptiva y transversal de todos los pacientes con cáncer que presentaron alguna infección intrahospitalaria en el Hospital Oncológico Provincial Conrado Benítez de Santiago de Cuba, desde enero hasta septiembre del 2009, a fin de caracterizarles clinicoepidemiológicamente. Del total de egresados, se infectaron 41 (1,5 por ciento), mientras que en la casuística predominaron el sexo masculino y el grupo etáreo de 40-59 años, así como los estadios clínicos III y IV, los cuales se hallaron entre los principales factores de riesgo, junto a la intervención quirúrgica y los problemas estructurales en el quirófano. Los microorganismos más frecuentes fueron: Pseudomonas aeruginosa en el cáncer de laringe y Escherichia coli en los tumores urológicos. De las infecciones, la mayoría se localizaron en heridas quirúrgicas; y de los pacientes infectados, gran parte presentaron leucocitosis y neutrofilia(AU)

A descriptive and cross-sectional study was conducted in all cancer patients that had some nosocomial infection at Conrado Benítez Provincial Oncology Hospital of Santiago de Cuba, from January to September 2009, in order to characterize them clinically and epidemiologically. Of the discharged patients 41 were infected (1,5 per cent), while male sex and age group of 40-59 years prevailed in the case material, as well as clinical stages III and IV, which were among the main risk factors together with surgical intervention and structural problems in the operating room. The most frequent microorganisms were Pseudomonas aeruginosa in larynx cancer and Escherichia coli in urologic tumors. Most of the infections were found in surgical wounds; and most of the infected patients had leukocytosis and neutrophilia(AU)

Microorganismos aislados de recién nacidos ingresados en salas de neonatología abiertas y cerradas / Microorganisms isolated from newborns admitted to opened and closed neonatology rooms

Se realizaron 138 aislamientos de microorganismos en los recién nacidos ingresados en los servicios de neonatología de los hospitales provinciales de la ciudad de Santiago de Cuba durante el semestre mayo -octubre del 2006. Entre las bacterias predominantes en servicios abiertos figuraron las grampositivas (fundamentalmente estafilococo coagulasa negativo y Staphilococcus aureus), pero en los cerrados prevalecieron las gramnegativas (sobre todo Klepsiella sp, Escherichia coli y Pseudomnas). En 58,2 por ciento de la casuística se registraba el antecedente de infección vaginal en la madre, en 14,9 por ciento de prematuridad y en 12,7 por ciento de rotura prematura de la membrana. No se hallaron estreptococos del grupo B.

One hundred and thirty eight isolations of microorganisms were performed in newborns admitted to the provincial hospital neonatology services in Santiago de Cuba city from May to October, 2006. Among the predominant bacteria in opened services are gram-positive (mainly coagulase-negative staphylococcus and Staphylococcus aureus), but in closed services gramnegative agents prevailed (mainly Klepsiella sp, Escherichia coli and Pseudomonas). History of vaginal infection in mothers was recorded in 58,2 percent, of prematurity in 14,9 percent and of early membrane rupture in 12,7 percent of the case material. No streptococci of group B were observed.

Microorganismos aislados de recién nacidos ingresados en salas de neonatología abiertas y cerradas / Microorganisms isolated from newborns admitted to opened and closed neonatology rooms

Se realizaron 138 aislamientos de microorganismos en los recién nacidos ingresados en los servicios de neonatología de los hospitales provinciales de la ciudad de Santiago de Cuba durante el semestre mayo -octubre del 2006. Entre las bacterias predominantes en servicios abiertos figuraron las grampositivas (fundamentalmente estafilococo coagulasa negativo y Staphilococcus aureus), pero en los cerrados prevalecieron las gramnegativas (sobre todo Klepsiella sp, Escherichia coli y Pseudomnas). En 58,2 por ciento de la casuística se registraba el antecedente de infección vaginal en la madre, en 14,9 por ciento de prematuridad y en 12,7 por ciento de rotura prematura de la membrana. No se hallaron estreptococos del grupo B(AU)

One hundred and thirty eight isolations of microorganisms were performed in newborns admitted to the provincial hospital neonatology services in Santiago de Cuba city from May to October, 2006. Among the predominant bacteria in opened services are gram-positive (mainly coagulase-negative staphylococcus and Staphylococcus aureus), but in closed services gramnegative agents prevailed (mainly Klepsiella sp, Escherichia coli and Pseudomonas). History of vaginal infection in mothers was recorded in 58,2 percent, of prematurity in 14,9 percent and of early membrane rupture in 12,7 percent of the case material. No streptococci of group B were observed (AU)