Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

The immune response of the scallop Argopecten purpuratus is associated with changes in the host microbiota structure and diversity.

All organisms live in close association with a variety of microorganisms called microbiota. Furthermore, several studies support a fundamental role of the microbiota on the host health and homeostasis. In this context, the aim of this work was to determine the structure and diversity of the microbiota associated with the scallop Argopecten purpuratus, and to assess changes in community composition and diversity during the host immune response. To do this, adult scallops were immune challenged and sampled after 24 and 48 h. Activation of the immune response was established by transcript overexpression of several scallop immune response genes in hemocytes and gills, and confirmed by protein detection of the antimicrobial peptide big defensin in gills of Vibrio-injected scallops at 24 h post-challenge. Then, the major bacterial community profile present in individual scallops was assessed by denaturing gradient gel electrophoresis (DGGE) of 16S rDNA genes and dendrogram analyses, which indicated a clear clade differentiation of the bacterial communities noticeable at 48 h post-challenge. Finally, the microbiota structure and diversity from pools of scallops were characterized using 16S deep amplicon sequencing. The results revealed an overall modulation of the microbiota abundance and diversity according to scallop immune status, allowing for prediction of some changes in the functional potential of the microbial community. Overall, the present study showed that changes in the structure and diversity of bacterial communities associated with the scallop A. purpuratus are detected after the activation of the host immune response. Now, the relevance of microbial balance disruption in the immune capacity of the scallop remains to be elucidated.

Identification and characterization of two variants of the Hfq-sRNA-chaperone in the fish pathogen Piscirickettsia salmonis.

Small RNA and chaperone proteins form synergistic duos that play pivotal roles in controlling gene expression in bacteria. This is the case for Hfq, a highly pleiotropic pretranslational modulator of general protein expression, which responds to harsh environmental conditions and influences fitness and virulence in a wide range of pathogenic Enterobacteria. Given this relevancy, we evaluated the presence and potential role of Hfq in the fish pathogen Piscirickettsia salmonis, a Gram-negative bacterium that threatens the sustainability of Chilean salmon production. Using bioinformatics tools were identified and characterized two variants of Hfq, which share the consensus RNA-binding domains and the active sites described functional Hfq other bacteria. Additionally, we demonstrated that hfq-1 and hfq-2 were transcriptionally active when growing in cell-free media and in infected susceptible fish cell line. Expression of both genes differed under different growth conditions and under stress, suggesting that their roles might be independent and different, depending on the bacterial physiological status. In conclusion, we demonstrate the existence of two different and functional ORF coding for the hfq marker in marine bacteria and a preliminary analysis indicating that these two novel proteins might have relevant roles in the biology and pathogenic potential of P. salmonis.

Are there intracellular Ca2+ oscillations correlated with flagellar beating in human sperm? A three vs. two-dimensional analysis.

STUDY QUESTION: Are there intracellular Ca2+ ([Ca2+]i) oscillations correlated with flagellar beating in human sperm? SUMMARY ANSWER: The results reveal statistically significant [Ca2+]i oscillations that are correlated with the human sperm flagellar beating frequency, when measured in three-dimensions (3D). WHAT IS KNOWN ALREADY: Fast [Ca2+]i oscillations that are correlated to the beating flagellar frequency of cells swimming in a restricted volume have been detected in hamster sperm. To date, such findings have not been confirmed in any other mammalian sperm species. An important question that has remained regarding these observations is whether the fast [Ca2+]i oscillations are real or might they be due to remaining defocusing effects of the Z component arising from the 3D beating of the flagella. STUDY DESIGN, SIZE, DURATION: Healthy donors whose semen samples fulfill the WHO criteria between the age of 18-28 were selected. Cells from at least six different donors were utilized for analysis. Approximately the same number of experimental and control cells were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Motile cells were obtained by the swim-up technique and were loaded with Fluo-4 (Ca2+ sensitive dye) or with Calcein (Ca2+ insensitive dye). Ni2+ was used as a non-specific plasma membrane Ca2+ channel blocker. Fluorescence data and flagella position were acquired in 3D. Each cell was recorded for up to 5.6 s within a depth of 16 microns with a high speed camera (coupled to an image intensifier) acquiring at a rate of 3000 frames per second, while an oscillating objective vibrated at 90 Hz via a piezoelectric device. From these samples, eight experimental and nine control sperm cells were analyzed in both 2D and 3D. MAIN RESULTS AND THE ROLE OF CHANCE: We have implemented a new system that allows [Ca2+]i measurements of the human sperm flagellum beating in 3D. These measurements reveal statistically significant [Ca2+]i oscillations that correlate with the flagellar beating frequency. These oscillations may arise from intracellular sources and/or Ca2+ transporters, as they were insensitive to external Ni2+, a non-specific plasma membrane Ca2+ channel blocker. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Analysis in 3D needs a very fast image acquisition rate to correctly sample a volume containing swimming sperm. This condition requires a very short exposure time per image making it necessary to use an image intensifier which also increases noise. The lengthy analysis time required to obtain reliable results limited the number of cells that could be analyzed. WIDER IMPLICATIONS OF THE FINDINGS: The possibility of recording flagellar [Ca2+]i oscillations described here may open a new avenue to better understand ciliary and flagellar beating that are fundamental for mucociliary clearance, oocyte transport, fertilization, cerebrospinal fluid pressure regulation and developmental left-right symmetry breaking in the embryonic node. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by Consejo Nacional de Ciencia y Tecnología (CONACyT) (grants 253952 to G.C.; 156667 to F.M.M. and Fronteras 71 39908-Q to A.D. and Post-doctoral scholarships 366844 to P.H.-H. and 291028 to F.M.) and the Dirección General de Asuntos del Personal Académico of the Universidad Nacional Autónoma de México (DGAPA-UNAM) (grants CJIC/CTIC/4898/2016 to F.M. and IN205516 to A.D.). There are no conflicts of interest to declare.

BackCLIP: a tool to identify common background presence in PAR-CLIP datasets.

MOTIVATION: PAR-CLIP, a CLIP-seq protocol, derives a transcriptome wide set of binding sites for RNA-binding proteins. Even though the protocol uses stringent washing to remove experimental noise, some of it remains. A recent study measured three sets of non-specific RNA backgrounds which are present in several PAR-CLIP datasets. However, a tool to identify the presence of common background in PAR-CLIP datasets is not yet available. RESULTS: We used the measured sets of non-specific RNA backgrounds to build a common background set. Each element from the common background set has a score that reflects its presence in several PAR-CLIP datasets. We present a tool that uses this score to identify the amount of common backgrounds present in a PAR-CLIP dataset, and we provide the user the option to use or remove it. We used the proposed strategy in 30 PAR-CLIP datasets from nine proteins. It is possible to identify the presence of common backgrounds in a dataset and identify differences in datasets for the same protein. This method is the first step in the process of completely removing such backgrounds. AVAILABILITY: The tool was implemented in python. The common background set and the supplementary data are available at https://github.com/phrh/BackCLIP. CONTACT: phreyes@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Winter is coming: hibernation reverses the outcome of sperm competition in a fly.

Sperm commonly compete within females to fertilize ova, but research has focused on short-term sperm storage: sperm that are maintained in a female for only a few days or weeks before use. In nature, females of many species store sperm for months or years, often during periods of environmental stress, such as cold winters. Here we examine the outcome of sperm competition in the fruit fly Drosophila pseudoobscura, simulating the conditions in which females survive winter. We mated females to two males and then stored the female for up to 120 days at 4°C. We found that the outcome of sperm competition was consistent when sperm from two males was stored for 0, 1 or 30 days, with the last male to mate fathering most of the offspring. However, when females were stored in the cold for 120 days, the last male to mate fathered less than 5% of the offspring. Moreover, when sperm were stored long term the first male fathered almost all offspring even when he carried a meiotic driving sex chromosome that drastically reduces sperm competitive success under short-term storage conditions. This suggests that long-term sperm storage can radically alter the outcome of sperm competition.

Stress-induced adaptive islet cell identity changes.

The different forms of diabetes mellitus differ in their pathogenesis but, ultimately, they are all characterized by progressive islet ß-cell loss. Restoring the ß-cell mass is therefore a major goal for future therapeutic approaches. The number of ß-cells found at birth is determined by proliferation and differentiation of pancreatic progenitor cells, and it has been considered to remain mostly unchanged throughout adult life. Recent studies in mice have revealed an unexpected plasticity in islet endocrine cells in response to stress; under certain conditions, islet non-ß-cells have the potential to reprogram into insulin producers, thus contributing to restore the ß-cell mass. Here, we discuss the latest findings on pancreas and islet cell plasticity upon physiological, pathological and experimental conditions of stress. Understanding the mechanisms involved in cell reprogramming in these models will allow the development of new strategies for the treatment of diabetes, by exploiting the intrinsic regeneration capacity of the pancreas.

Molecular characterization of an inhibitor of NF-κB in the scallop Argopecten purpuratus: First insights into its role on antimicrobial peptide regulation in a mollusk.

Inhibitors of nuclear factor kappa B (IκBs) are major control components of the Rel/NF-κB signaling pathway, a key regulator in the modulation of the expression of immune-related genes in vertebrates and invertebrates. The activation of the Rel/NF-κB signaling pathway depends largely in the degradation of IκB proteins and thus, IκBs are a main target for the identification of genes whose expression is controlled by Rel/NF-κB pathway. In order to identify such regulation in bivalve mollusks, the cDNA sequence encoding an IκB protein was characterized in the scallop Argopecten purpuratus, ApIκB. The cDNA sequence of ApIκB is comprised of 1480 nucleotides with a 1086 bp open reading frame encoding for 362 amino acids. Bioinformatics analysis showed that ApIκB displays the conserved features of IκB proteins. The deduced amino acid sequence consists of a 39.7 kDa protein, which has an N-terminal degradation motif, six ankyrin repeats and a C-terminal phosphorylation site motif. Phylogenetic analysis revealed a high degree of identity between ApIκB and other IκBs from mollusks, but also to arthropod cactus proteins and vertebrate IκBs. Tissue expression analysis indicated that ApIκB is expressed in all examined tissues and it is upregulated in circulating hemocytes from scallops challenged with the pathogenic Gram-negative bacterium Vibrio splendidus. After inhibiting ApIκB gene expression using the RNA interference technology, the gene expression of the antimicrobial peptide big defensin was upregulated in hemocytes from non-challenged scallops. Results suggest that ApIκB may control the expression of antimicrobial effectors such as big defensin via a putative Rel/NF-κB signaling pathway. This first evidence will help to deepen the knowledge of the Rel/NF-κB conserved pathway in scallops.

Chronic exposure to biomass fuel smoke and markers of endothelial inflammation.

Indoor smoke exposure may affect cardiovascular disease (CVD) risk via lung-mediated inflammation, oxidative stress, and endothelial inflammation. We sought to explore the association between indoor smoke exposure from burning biomass fuels and a selected group of markers for endothelial inflammation. We compared serum concentrations of amyloid A protein, E-selectin, soluble intercellular adhesion molecule 1 (ICAM-1) and VCAM-1, von Willebrand factor (vWF), and high-sensitivity C-reactive protein (hs-CRP) in 228 biomass-exposed vs. 228 non-exposed participants living in Puno, Peru. Average age was 56 years (s.d. = 13), average BMI was 26.5 kg/m(2) (s.d. = 4.4), 48% were male, 59.4% completed high school, and 2% reported a physician diagnosis of CVD. In unadjusted analysis, serum levels of soluble ICAM-1 (330 vs. 302 ng/ml; P < 0.001), soluble VCAM-1 (403 vs. 362 ng/ml; P < 0.001), and E-selectin (54.2 vs. 52.7 ng/ml; P = 0.05) were increased in biomass-exposed vs. non-exposed participants, respectively, whereas serum levels of vWF (1148 vs. 1311 mU/ml; P < 0.001) and hs-CRP (2.56 vs. 3.12 mg/l; P < 0.001) were decreased, respectively. In adjusted analyses, chronic exposure to biomass fuels remained positively associated with serum levels of soluble ICAM-1 (P = 0.03) and VCAM-1 (P = 0.05) and E-selectin (P = 0.05), and remained negatively associated with serum levels of vWF (P = 0.02) and hs-CRP (P < 0.001). Daily exposure to biomass fuel smoke was associated with important differences in specific biomarkers of endothelial inflammation and may help explain accelerated atherosclerosis among those who are chronically exposed.

Asymmetrical proliferative pattern loss during malignant transformation of the oral mucosa.

OBJECTIVES: The aim of this study was to study the loss of asymmetrical proliferation in oral tumorigenesis. MATERIALS AND METHODS: Samples: 92 oral squamous cell carcinomas (OSCC) with associated non-tumor epithelia (NTE). NTE and tumor were classified as distant from or close to the invasion point. Immunohistochemistry was performed using Mib-1 antibody. Ki-67 was assessed in basal, parabasal layer, medium and upper third, counting total and positive cells. Proliferative patterns were classified according to the ki-67 expression: 1 = expression in parabasal layers of well-differentiated tumor nest (WDTN); 2 = expression in parabasal and basal layers of WDTN; 3 = ki-67 expression in <20% cells in tumor tissue without WDTN; 4 = ki-67 expression in ≥20% of cells in tumor tissue without WDTN; and 5 = ki-67 expression exclusively found in basal layers of WDTN. RESULTS: Ki-67 expression was highest in parabasal layers of both close and distant NTE (39.7 ± 27.6 and 30.1 ± 20) and was also elevated in the close (43.4 ± 21.3) and distant (48.8 ± 21.9) tumor tissue samples. Close tumors largely corresponded to proliferation patterns 2 and 4, while distant tumors generally followed pattern 4. Of the 92 close NTE samples, 23 showed reduced basal proliferation with increased parabasal proliferation. Tumors derived from these epithelia followed patterns 2 (52%, 12/23 cases) or 4 (30.4%, 7/23 cases). Parabasal proliferation in distant NTE was significantly increased in patients with multiple vs. single tumors (36.7% vs. 25.4%; P = 0.032). CONCLUSION: The change from asymmetrical to symmetrical division appears to be an oncogenic mechanism in oral carcinogenesis.

[Validation of a brief screening test to assess functional capacity in Chilean older people]. / Validación de un test breve para el diagnóstico de capacidad funcional en adultos mayores en Chile.

BACKGROUND: The Pfeffer Functional Activities Questionnaire (PFAQ) is a validated instrument used in Chile to diagnose dependency in older people. AIM: To suggest a shorter and easier version of the PFAQ, with appropriate levels of sensitivity and specificity, which may be applied to the general older population. MATERIAL AND METHODS: Three Chilean surveys applied to older people were used, namely the Survey of Life Events of the Elderly, (n = 1,371) and the 2010 and 2013 National Surveys of Quality of Life of Older People (n = 1,954 and 2,644 respectively). To evaluate the instrument, we performed correlation analysis between items and principal components analysis. We calculated internal consistency using Cronbach alpha, we computed sensitivity and specificity indicators, and analyzed convergent and predictive validity. RESULTS: After constructing different scales, the one that gave more information and had the best balance between sensitivity and specificity was chosen. Items with less weight factor and greater gender bias were eliminated, keeping seven questions from the original PFAQ. Reliability was verified using Cronbach alpha's coefficient and from correlations between the new instrument and key variables. CONCLUSIONS: According to our goals, the proposed scale is solely conformed by items that do not have gender bias. It discriminates in the general population adequately, allowing the design of a shorter test, of easier implementation.

Prioritizing Colombian plant genetic resources for investment in research using indicators about the geographic origin, vulnerability status, economic benefits, and food security importance.

Germplasm banks are the most significant repository for plant genetic resources for food and agriculture (PGRFA) worldwide. Despite their strategic importance, national germplasm banks of tropical megadiverse developing countries such as Colombia have extremely limited funds. Therefore, making strategic decisions about research investment is essential. Here, we designed a data-driven approach to build an index that sorts Colombian PGRFA into three groups: high, medium, or low priority, based on four pillars of information from open-access databases and aligned with the sustainable goals of no poverty and zero hunger: Geographic origin, vulnerability status, economic benefits, and food security importance. We analyzed 345 PGRFA using the index, separating them into two groups, 275 already conserved in the Colombian germplasm bank (BGVCOL group) and 70 not currently conserved in the BGVCOL (NCB group). We used fuzzy logic to classify each PGRFA by each pillar and integrate it to obtain a priority index. Missing data for native crops were frequent in the BGVCOL group. Therefore we adopted an imputation strategy to fill the gaps and calculated the uncertainty. After applying the index, PGRFA with higher priority were 24 (8.72%) from the BGVCOL (i.e., 15 potatoes, three tomatoes, two tree tomatoes, pineapple, cocoa, papaya, and yacon) and one from NCB (i.e., coffee). We concluded that this methodology successfully prioritized PGRFA in Colombia and shows the big holes of knowledge for future research and alternatives to improve this index. The versatility of this methodology could be helpful in other genebanks with budget limitations for research investment. Supplementary Information: The online version contains supplementary material available at 10.1007/s10531-023-02599-7.

Plant-based beverages as milk alternatives? Nutritional and functional approach through food labelling.

Plant-based beverages (PBB) market is largely growing. In this study, 136 beverages made of soy, oat, almond, rice, tigernut, and others (mixtures of various plant materials), from the Spanish market were evaluated through labelling information. Energy value and fat content were intermediate between skimmed and whole cow milk; while fatty acids profile was quite different. Carbohydrate content was usually higher than cow milk, and highly dependent on the addition of sugars. All products provided some dietary fibre. With the exception of soy-based drinks, samples presented lower protein and calcium content than milk (1/3 samples studied were Ca-fortified), and 23% were vitamin D enriched. The claim "No added sugars" was in more than 50% samples. A right labelling and nutritional education of consumers is essential to make adequate choices, since the appearing of many claims is not always indicative of a better-quality product. Plant-based beverages cannot be considered as an alternative to milk, but as a different product, with their own nutritional and functional entity. Their inclusion in a diversified balanced diet can provide interesting functional components, such as soluble fibre or unsaturated fatty acids (mainly soybean and almond drink), which can help improve the health status of the population.

Plant-based drinks for vegetarian or vegan toddlers: Nutritional evaluation of commercial products, and review of health benefits and potential concerns.

There is an increasing trend today towards plant-based diets in western society, often resulting in milk restriction. In the case of very young children, the direct substitution of milk by other foods, without proper nutritional advice, may lead to a lack of nutrients and hence to growth and development alterations. This study focuses on the nutritional assessment of various commercially available plant-based drinks, to determine their adequacy as alternatives to ruminant milk, in relation to the nutritional requirements of toddlers (1-3 years old), and to establish whether other sources of nutrient supplementation may be needed, as well as any other possible positive and /or negative health effects associated to their consumption. A sample of 179 commercial plant-based drinks (almond, coconut, hemp, oat, rice, soy, tigernut) were chosen and their nutrient contents were compared to the EFSA nutrient reference values for toddlers. The scientific literature on the presence of bioactive and/or undesirable compounds was reviewed. None of the plant-based drinks studied should be considered as a milk substitute, since they are different food products with a different composition. However, from the results obtained, the best choice for toddlers who do not consume milk would be to consume at least 250 mL/day of fortified soy drink (for its higher amount and quality of protein, polyunsaturated fatty acids and phytosterols), and always in the context of a carefully-balanced diet. Almond, hemp or oat drinks are other alternatives that can be used in combination or for soy-allergic toddlers. The key nutrients that should be fortified in plant-based drinks are: vitamins A and B12, calcium, zinc and iodine, as they represent the most significant nutritional differences with milk; vitamin D would also be desirable. Of these, vitamins A, B12, D and calcium, are easily found in many commercial plant-based drinks on the Spanish market (most frequently in soy drinks), unlike iodine and zinc, which were not added to any. Given the fish restriction in vegetarians/vegans and the fact that plant-based drinks provide high amounts of phytates and tannins, which act as antinutrients, a good strategy for the industry would be to fortify plant-based drinks with iodine and zinc to improve the nutritional value of products aimed to vegetarians/vegans.

Expression of a tumor necrosis factor alpha transgene in murine pancreatic beta cells results in severe and permanent insulitis without evolution towards diabetes.

Mice bearing a tumor necrosis factor (TNF) alpha transgene controlled by an insulin promoter developed an increasingly severe lymphocytic insulitis, apparently resulting from the induction of endothelial changes with features similar to those observed in other places of intense lymphocytic traffic. This was accompanied by dissociation of the endocrine tissue (without marked decrease in its total mass), islet fibrosis, and the development of intraislet ductules containing, by places, beta cells in their walls, suggesting a regenerative capacity. Islet disorganization and fibrosis did not result from lymphocytic infiltration, since they were also observed in SCID mice bearing the transgene. Diabetes never developed, even though a number of potentially inducing conditions were used, including the prolonged perfusion of interferon gamma and the permanent expression of a nontolerogenic viral protein on beta cells (obtained by using mice bearing two transgenes). It is concluded that (a) a slow process of TNF release in pancreatic islets induces insulitis, and may be instrumental in the insulitis resulting from local cell-mediated immune reactions, but (b) that insulitis per se is not diabetogenic, lymphocyte stimulation by cells other than beta cells being necessary to trigger extensive beta cell damage. This provides an explanation for the discrepancy between the occurrence of insulitis and that of clinical disease in autoimmune diabetes.

Development of two multiplex mini-sequencing panels of ancestry informative SNPs for studies in Latin Americans: an application to populations of the State of Minas Gerais (Brazil).

Admixture occurs when individuals from parental populations that have been isolated for hundreds of generations form a new hybrid population. Currently, interest in measuring biogeographic ancestry has spread from anthropology to forensic sciences, direct-to-consumers personal genomics, and civil rights issues of minorities, and it is critical for genetic epidemiology studies of admixed populations. Markers with highly differentiated frequencies among human populations are informative of ancestry and are called ancestry informative markers (AIMs). For tri-hybrid Latin American populations, ancestry information is required for Africans, Europeans and Native Americans. We developed two multiplex panels of AIMs (for 14 SNPs) to be genotyped by two mini-sequencing reactions, suitable for investigators of medium-small laboratories to estimate admixture of Latin American populations. We tested the performance of these AIMs by comparing results obtained with our 14 AIMs with those obtained using 108 AIMs genotyped in the same individuals, for which DNA samples is available for other investigators. We emphasize that this type of comparison should be made when new admixture/population structure panels are developed. At the population level, our 14 AIMs were useful to estimate European admixture, though they overestimated African admixture and underestimated Native American admixture. Combined with more AIMs, our panel could be used to infer individual admixture. We used our panel to infer the pattern of admixture in two urban populations (Montes Claros and Manhuaçu) of the State of Minas Gerais (southeastern Brazil), obtaining a snapshot of their genetic structure in the context of their demographic history.

[Histopathological findings and biomarker analysis in cutaneous graft-versus-host disease ]. / Histología y biomarcadores en la enfermedad del injerto contra el huésped cutánea.

Graft-versus-host disease (GVHD) remains the greatest source of morbidity-mortality in allogenic transplant patients. Although in most cases the more easily obtainable clinical and laboratory test parameters suffice to confirm the diagnosis and establish the stage of the disease biopsies of the affected organ are sometimes needed. At present there is great Interest in the study of factors allowing a prognosis of the course and type of response to treatment in patients with CVHD. In this sense, It would be necessary to objectively Identify and validate biomarkers capable of predicting biological or pathological processes in patients with cVHD. To this effect we have performed serial analyses of skin tissue using peripheral blood and tissue biomarkers in a prospective observational study conducted in three transplant centers. The still preliminary results Indicate that certain histopathological findings classically attributed to CVHD ore also seen in patients not clinically affected by the disease--this probably being related to other physiopathological phenomena occurring during transplantation. The study of these findings, combined with biomarker analysis, will allow improved understanding of the underlying etiopathogenesis, as well as the definition of new diagnostic, prognostic and response-evaluating criteria.

[Mortality following cardiac surgery in the National Health Service Hospitals of the Community of Valencia in 2007: a descriptive analysis]. / Análisis descriptivo de mortalidad en cirugía cardiaca en los hospitales públicos de la Comunidad Valenciana en el año 2007.

OBJECTIVE: To analyze clinical records of cardiac surgery patients in an attempt to identify factors associated with mortality in the postoperative critical care units of the public health service hospitals in the Community of Valencia, Spain, in 2007. METHODS: Retrospective study of cases from January 1, 2007 to December 31, 2007. The charts of all patients who underwent cardiac surgery with or without extracorporeal circulation were reviewed. A data collection protocol was followed to obtain information on age, sex, body mass index (BMI), presurgical risk factors, type of surgery, duration of extracorporeal circulation, duration of ischemia, cause of death, and length of stay in the postoperative critical care unit. RESULTS: The study population consisted of 2113 patients at 5 public hospitals; 124 patients (70 men, 54 women) died. The mean (SD) age was 70 (9.43) years (range, 36-91 years). The mean BMI was 28.19 kg/m2 (maximum, 42 kg/m2). The mean Euroscore was 21.92 (maximum, 94.29). Hypertension was present as a preoperative risk factor in most patients (74.2%); dyslipidemia was present in 51.6%, diabetes mellitus in 38.7%, stroke in 73%, and renal failure in 2.4%. It was noteworthy was that the group who underwent coronary revascularization had the highest mortality rate (nearly 35% of the 124 patients). The next highest mortality rate (19.4%) was in patients who had combined procedures (valve repair or substitution plus coronary revascularization). Mortality was 18.5% in the group undergoing aortic valve surgery and 11.3% in those undergoing mitral valve surgery. The mean duration of extracorporeal circulation was 148.63 minutes. The mean duration of myocardial ischemia was 94.91 minutes. The most frequent cause of death was cardiogenic shock (54.8%). This was followed by distributive shock (29.8%) and hemorrhagic shock (8.9%). The mean length of stay in the postoperative critical care unit was 13.6 days. Overall mortality was 5.87%. CONCLUSIONS: The highest mortality rate among cardiac surgery patients in postoperative critical care units in hospitals in the Community of Valencia in 2007 was in patients who underwent coronary revascularization. The most prevalent preoperative risk factor was hypertension. Cardiogenic shock and distributive shock were the most frequent causes of death in these patients. A system for classifying risk is needed in order to predict mortality in critical care units and improve perioperative care.

Near-infrared spectroscopy and spectral mapping of Jupiter and the Galilean satellites: results from Galileo's initial orbit.

The Near Infrared Mapping Spectrometer performed spectral studies of Jupiter and the Galilean satellites during the June 1996 perijove pass of the Galileo spacecraft. Spectra for a 5-micrometer hot spot on Jupiter are consistent with the absence of a significant water cloud above 8 bars and with a depletion of water compared to that predicted for solar composition, corroborating results from the Galileo probe. Great Red Spot (GRS) spectral images show that parts of this feature extend upward to 240 millibars, although considerable altitude-dependent structure is found within it. A ring of dense clouds surrounds the GRS and is lower than it by 3 to 7 kilometers. Spectra of Callisto and Ganymede reveal a feature at 4. 25 micrometers, attributed to the presence of hydrated minerals or possibly carbon dioxide on their surfaces. Spectra of Europa's high latitudes imply that fine-grained water frost overlies larger grains. Several active volcanic regions were found on Io, with temperatures of 420 to 620 kelvin and projected areas of 5 to 70 square kilometers.

Transgenic and other experimental models of pancreas and islet damage.

To unravel the cellular and molecular mechanisms involved in beta-cell renewal and expansion throughout life, several different experimental models were devised in the past. A number of experimental approaches and transgenic models have been engineered to trigger specifically pancreatic injury and thus explore regeneration. Globally, three main strategies are followed to induce pancreas damage: surgical, chemical and genetic. Some of the most relevant studies regarding these three approaches are briefly summarized in this short overview. Although significant progress has been achieved in recent years, there is much room for improving our understanding of many fundamental processes regulating beta-cell mass maintenance.