Effect of in-hospital glycemic variability on mortality in patients with diabetes. / Efecto de la variabilidad glucémica intrahospitalaria en la mortalidad de los pacientes con diabetes.

INTRODUCTION: The aim of this study was to evaluate the impact of mean blood glucose (MBG) and glycaemic variability (GV) during hospitalisation on mortality after discharge. MATERIAL AND METHODS: We conducted a retrospective longitudinal analytical cohort study that included patients discharged form a department of internal medicine with a diabetes-related diagnosis The evaluated prognosis was mortality. During hospitalisation, the patients' clinical, laboratory and glycaemic control-related variables were recorded (MBG, GV and hypoglycaemia). The GV was measured with the coefficient of variation (CV). We calculated the mortality rates for every 1000 patient-years and compared them with Kaplan-Meier curves. We determined the predictors of mortality by performing a Cox regression. RESULTS: The study included 276 patients with a mean age of 77.6 (SD, 10.2) years. The median outpatient follow-up duration was 2.7 years. In the multivariate analysis, an MBG >140mg/dl (HR, 1.72; 95% CI 1.14-2.61; p=.01) and a CV >0.29 (HR, 1.52; 95% CI 1.12-2.06; p=.006) but not the presence of hypoglycaemia were additively and independently associated with an increased risk of mortality. An MBG >140mg/dl with a CV >0.29 increased the mortality rates (123 vs. 317 per 1000 patient-year; p <.001) and the adjusted mortality risk (HR, 2.70; 95% CI 1.71-4.27; p<.001) compared with having an MBG ≤140mg/dl. CONCLUSION: The simultaneous presence of a high MBG level and CV constitutes a powerful tool for stratifying mortality risk after hospital discharge.

Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: a systematic guideline review and expert consensus.

The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease-oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow-up: strategies in care planning, self-management and medication-related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self-management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.

Impact of noise in holography with extended references in the low signal regime.

Signal-to-noise ratio is a key factor in lensless imaging, particularly for low diffraction signal experiments in the single shot regime. We present our recent study of the noise impact on holography with extended references. Experimental data have been measured in single shot acquisition using an intense coherent soft X-ray high harmonic source. The impact of hardware and software noise under various detection conditions is discussed. A final comparison between single shot and multi-shot regimes is given.

Fourier transform holography with high harmonic spectra for attosecond imaging applications.

We demonstrate a method of using a Fourier holographic technique to utilize attosecond soft x-ray pulses to image nanometer-scale objects. A discrete frequency comb of laser-generated high-order harmonics, yielding a train of attosecond pulses, has been used to record spatially and spectrally resolved images. The individual wavelengths were also combined to form a single image, albeit with lower spatial resolution, demonstrating the applicability of the method to using isolated attosecond pulses with continuous bandwidths.

Impact of wave front and coherence optimization in coherent diffractive imaging.

We present single shot nanoscale imaging using a table-top femtosecond soft X-ray laser harmonic source at a wavelength of 32 nm. We show that the phase retrieval process in coherent diffractive imaging critically depends on beam quality. Coherence and image fidelity are measured from single-shot coherent diffraction patterns of isolated nano-patterned slits. Impact of flux, wave front and coherence of the soft X-ray beam on the phase retrieval process and the image quality are discussed. After beam improvements, a final image reconstruction is presented with a spatial resolution of 78 nm (half period) in a single 20 fs laser harmonic shot.

SEDAR/SECCE ECMO management consensus document.

ECMO is an extracorporeal cardiorespiratory support system whose use has been increased in the last decade. Respiratory failure, postcardiotomy shock, and lung or heart primary graft failure may require the use of cardiorespiratory mechanical assistance. In this scenario perioperative medical and surgical management is crucial. Despite the evolution of technology in the area of extracorporeal support, morbidity and mortality of these patients continues to be high, and therefore the indication as well as the ECMO removal should be established within a multidisciplinary team with expertise in the area. This consensus document aims to unify medical knowledge and provides recommendations based on both the recent bibliography and the main national ECMO implantation centres experience with the goal of improving comprehensive patient care.

Effect of in-hospital glycemic variability on mortality in patients with diabetes.

INTRODUCTION: The aim of this study was to evaluate the impact of mean blood glucose (MBG) and glycaemic variability (GV) during hospitalisation on mortality after discharge. MATERIAL AND METHODS: We conducted a retrospective longitudinal analytical cohort study that included patients discharged form a department of internal medicine with a diabetes-related diagnosis. The evaluated prognosis was mortality. During hospitalisation, the patients' clinical, laboratory and glycaemic control-related variables were recorded (MBG, GV and hypoglycaemia). The GV was measured with the coefficient of variation (CV). We calculated the mortality rates for every 1000 patient-years and compared them with Kaplan-Meier curves. We determined the predictors of mortality by performing a Cox regression. RESULTS: The study included 276 patients with a mean age of 77.6 (SD, 10.2) years. The median outpatient follow-up duration was 2.7 years. In the multivariate analysis, an MBG > 140 mg/dL (HR = 1.72; 95% CI 1.14-2.61; p = .01) and a CV > 0.29 (HR = 1.52; 95% CI 1.12-2.06; p = .006), but not the presence of hypoglycaemia, were additively and independently associated with an increased risk of mortality. An MG > 140 mg/dL with a CV > 0.29 increased the mortality rates (123 vs. 317 per 1000 patient-year; p < .001) and the adjusted mortality risk (HR = 2.70; 95% CI 1.71-4.27; p < .001) compared with having an MBG ≤ 140 mg/dL. CONCLUSION: The simultaneous presence of a high MBG level and CV constitutes a powerful tool for stratifying mortality risk after hospital discharge.

Chlorobenzene, chloroform, and carbon tetrachloride adsorption on undoped and metal-doped sol-gel substrates (SiO(2), Ag/SiO(2), Cu/SiO(2) and Fe/SiO(2)).

Adsorption isotherms of chlorobenzene, chloroform and carbon tetrachloride vapors on undoped SiO(2), and metal-doped Ag/SiO(2), Cu/SiO(2) and Fe/SiO(2) substrates were measured in the temperature range of 398-593K. These substrates were prepared from a typical sol-gel technique in the presence of metal dopants that rendered an assortment of microporous-mesoporous solids. The relevant characteristic of these materials was the different porosities and micropore to mesopore volume ratios that were displayed; this was due to the effect that the cationic metal valence exerts on the size of the sol-gel globules that compose the porous solid. The texture of these SiO(2) materials was analyzed by X-ray diffraction (XRD), FTIR, and diverse adsorption methods. The pore-size distributions of the adsorbents confirmed the existence of mesopores and supermicropores, while ultramicropores were absent. The Freundlich adsorption model approximately fitted the chlorinated compounds adsorption data on the silica substrates by reason of a heterogeneous energy distribution of adsorption sites. The intensity of the interaction between these organic vapors and the surface of the SiO(2) samples was analyzed through evaluation of the isosteric heat of adsorption and standard adsorption energy; from these last results it was evident that the presence of metal species within the silica structure greatly affected the values of both the amounts adsorbed as well as of the isosteric heats of adsorption.

Microbiological analysis of cryopreserved human heart valves after storage: a survey of 3 banks in Spain.

Several reports have shown liquid nitrogen containers as not being sterile. Microorganism transmission has been observed in different cells and tissues stored under this condition, but there is no data on contamination of stored human valves. We performed a survey on heart valve banking in Spain. Regarding the questionnaire, we have a complete microbiological analysis of 304 thawed tissues prior to implant. In six cases positive culture results were observed. Patient follow-up did not reveal any adverse effects. Although some other possibilities should be stated, contamination of heart valves during storage in liquid nitrogen should be considered as a risk element in tissue banking. Strategies to asses and prevent microbial transmission from liquid nitrogen to heart valve banking ought to be further developed.

Inhibition of α-amylase by flavonoids: Structure activity relationship (SAR).

Flavonoids are recognized to regulate animals' food digestion processes trough interaction with digestive enzymes. The binding capacity of hesperetin (HES), luteolin (LUT), quercetin (QUE), catechin (CAT) and rutin (RUT) with pancreatic α-amylase were evaluated, using UV-Vis spectroscopy, fluorescence and molecular docking. Using p-nitrophenyl-α-d-maltopentoside (pNPG5) as substrate analog, LUT showed the best inhibitory capacity, even better than that of the positive control, acarbose (ACA). A mixed-type inhibition was observed for HES, LUT and QUE, a competitive-type for ACA, while no inhibition was observed with CAT and RUT. In agreement with kinetic results, α-amylase presented a higher affinity for LUT, when analyzed by fluorescence quenching. The binding of flavonoids to amylase followed a static mechanism, where the binding of one flavonoid per enzyme molecule was observed. Docking analysis showed that flavonoids bound near to enzyme active site, while ACA bound in another site behind the catalytic triad. Extrinsic fluorescence analysis, together with docking analysis pointed out that hydrophobic interactions regulated the flavonoid-α-amylase interactions. The present study provides evidence to understand the relationship of flavonoids structure with their inhibition mechanism.

Patterns of variation in the intergenic spacers of ribosomal DNA in Drosophila melanogaster support a model for genetic exchanges during X-Y pairing.

Detailed analysis of variation in intergenic spacer (IGS) and internal transcribed spacer (ITS) regions of rDNA drawn from natural populations of Drosophila melanogaster has revealed contrasting patterns of homogenization although both spacers are located in the same rDNA unit. On the basis of the role of IGS regions in X-Y chromosome pairing, we proposed a mechanism of single-strand exchanges at the IGS regions, which can explain the different evolutionary trajectories followed by the IGS and the ITS regions. Here, we provide data from the chromosomal distribution of selected IGS length variants, as well as the detailed internal structure of a large number of IGS regions obtained from specific X and Y chromosomes. The variability found in the different internal subrepeat regions of IGS regions isolated from X and Y chromosomes supports the proposed mechanism of genetic exchanges and suggests that only the "240" subrepeats are involved. The presence of a putative site for topoisomerase I at the 5' end of the 18S rRNA gene would allow for the exchange between X and Y chromosomes of some 240 subrepeats, the promoter, and the ETS region, leaving the rest of the rDNA unit to evolve along separate chromosomal lineages. The phenomenon of localized units (modules) of homogenization has implications for multigene family evolution in general.

Multigene family of ribosomal DNA in Drosophila melanogaster reveals contrasting patterns of homogenization for IGS and ITS spacer regions. A possible mechanism to resolve this paradox.

The multigene family of rDNA in Drosophila reveals high levels of within-species homogeneity and between-species diversity. This pattern of mutation distribution is known as concerted evolution and is considered to be due to a variety of genomic mechanisms of turnover (e.g., unequal crossing over and gene conversion) that underpin the process of molecular drive. The dynamics of spread of mutant repeats through a gene family, and ultimately through a sexual population, depends on the differences in rates of turnover within and between chromosomes. Our extensive molecular analysis of the intergenic spacer (IGS) and internal transcribed spacer (ITS) spacer regions within repetitive rDNA units, drawn from the same individuals in 10 natural populations of Drosophila melanogaster collected along a latitudinal cline on the east coast of Australia, indicates a relatively fast rate of X-Y and X-X interchromosomal exchanges of IGS length variants in agreement with a multilineage model of homogenization. In contrast, an X chromosome-restricted 24-bp deletion in the ITS spacers is indicative of the absence of X-Y chromosome exchanges for this region that is part of the same repetitive rDNA units. Hence, a single lineage model of homogenization, coupled to drift and/or selection, seems to be responsible for ITS concerted evolution. A single-stranded exchange mechanism is proposed to resolve this paradox, based on the role of the IGS region in meiotic pairing between X and Y chromosomes in D. melanogaster.

A race-specific insertion of transposable element IS801 in Pseudomonas syringae pv. phaseolicola.

The isolation and cloning of a random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) band specific for Pseudomonas syringae pv. phaseolicola race 1 allowed us to design a pair of primers that amplify 1.2-kb race 1-specific and 2.7-kb race 2-specific fragments, providing a rapid method for the identification of races by standard PCR methods. Restriction analysis revealed identical endonuclease sites in both fragments but the race 2 fragment contains a 1.5-kb insertion, identified as transposable element IS801 by sequence comparison. One complete and one partial open reading frame (ORF), each with a high probability of encoding a protein, have been identified in the 1.2-kb fragment common to both race 1 and race 2 sequences. As IS801 disrupts the partial ORF in the race 2 fragment, the complete sequence of this ORF has been obtained as well as its promoter region. The possibility that it may encode an avirulence gene is discussed as well as the role of transposable elements in pathogen evolution.

Molecular characterization of a new human minisatellite that is able to form single-stranded loops in vitro and is recognized by nuclear proteins.

We report the isolation of a new low polymorphic GC-rich human minisatellite locus (MsH42) that contains different recombination motifs and is homologous to sequences involved in immunoglobulin class-switching. Furthermore, we show that MsH42 undergoes slipped-strand mispairing during PCR indicating its ability to generate single-stranded loops. Specific DNA-protein complexes were detected in band-shifting experiments using nuclear extracts from mouse testes and human NC-37 cells. The possible implications of this minisatellite in recombination events is discussed.

Higher values of hepatic lipase activity in postmenopause: relationship with atherogenic intermediate density and low density lipoproteins.

OBJECTIVE: To investigate the enzymatic activity of hepatic lipase (HL) in postmenopausal women (PMW) and reproductive age women (RAW); and to evaluate the relationship between this enzyme and the atherogenic intermediate density lipoproteins (IDL) and low density lipoproteins (LDL), and antiatherogenic high density lipoproteins (HDL) and its subfractions (HDL2 and HDL3). DESIGN: We studied 55 PMW receiving no hormonal treatment in a cross-sectional study in comparison with a control group of 55 RAW, matched by body mass index. Follicle-stimulating hormone was > 40 mUI/ml in PMW and 3-12 mUI/ml in RAW. PMW presented at least 1 year of natural menopause and no more than 10 years of amenorrhea with E2 serum concentration < 15 pg/ml. RESULTS: HL activity was significantly higher in PMW versus RAW (14.0 +/- 1.4 vs. 10.9 +/- 0.4 micromol of fatty acids/ml of postheparin plasma, respectively, mean +/- SEM, p < 0.001). In PMW, IDL cholesterol showed a positive correlation with LDL cholesterol (r = 0.28, p < 0.05), and HDL2 cholesterol was inversely correlated with HL activity (r = 0.31, p < 0.05). HL was positively correlated with plasma concentration of LDL cholesterol in both groups (r = 0.27, p < 0.05). The higher values of HL activity and IDL cholesterol were independent of age. CONCLUSIONS: Higher HL activity is associated with a more atherogenic profile in PMW.

An analysis of the GLVQ algorithm.

Generalized learning vector quantization (GLVQ) has been proposed in as a generalization of the simple competitive learning (SCL) algorithm. The main argument of GLVQ proposal is its superior insensitivity to the initial values of the weights (code vectors). In this paper we show that the distinctive characteristics of the definition of GLVQ disappear outside a small domain of applications. GLVQ becomes identical to SCL when either the number of code vectors grows or the size of the input space is large. Besides that, the behavior of GLVQ is inconsistent for problems defined on very small scale input spaces. The adaptation rules fluctuate between performing descent and ascent searches on the gradient of the distortion function.

[Fibromyalgia syndrome (fibrositis): as frequent as it is unknown]. / Síndrome de fibromialgia (fibrositis): tan frecuente como desconocido.

Fibromyalgia syndrome is characterized by generalized musculoskeletal pain and abnormal sensitivity to palpation of characteristic myofascial areas. We evaluated its prevalence in the 673 patients seen as first consultations in a hospital rheumatological outpatient clinic during one year, and we made an automatized review of the Spanish literature about this condition in the last 17 years. We found 70 cases (10.4%) of fibromyalgia syndrome, none of which had been referred to the hospital with this diagnosis. We report their clinical features. In our bibliographical search we found only one article describing this condition. We conclude that it is a common clinical syndrome, unknown in nonspecialized milieus. Generally, the patients are inadequately diagnosed and treated, and/or referred to hospital.

[Outbreak of multiresistant tuberculosis]. / Brote de tuberculosis multirresistente.

BASIS: Six cases of multiresistant tuberculosis diagnosed in the Hospital of Navarra in 1996 were studied. MATERIAL AND METHODS: Sensitivity tests were carried out using the BACTEC 460TB system against four main anti-tuberculosis medicines: Isoniazid, Streptomycin, Rifampizin and Ethambutol. "Fingerprinting" techniques by means of RFLP with IS 6110 were used in the epidemiological study. RESULTS: Four of the patients were also infected with HIV. All of them had a fatal short-term prognosis. These four showed resistance to the drugs under study; in three resistance was primary, and secondary in the fourth. The molecular study showed that three HIV+ patients had identical patterns of restriction fragment length polymorphism (RFLP). Two were brothers and nosocomial infection was demonstrated in the third. On the other hand, the RPLF pattern of these patients showed great similarity to that of one of the HIV- patients, which suggests a clone origin of the strains, no other epidemiological relationship being found. The RPLF pattern of the other HIV+ patient was identical to that of another of his strains, isolated 14 months before, with the first strain sensitive. The other two patients were HIV- women, and they evolved favourably. In one, who was diabetic, a multiresistant tuberculosis had been diagnosed 7 years before, remaining asymptomatic up until the present. The other involved a secondary resistance due to deficient treatment. CONCLUSIONS: The appearance of multiresistant tuberculosis is a very serious problem amongst HIV+ patients, especially at a time when their life expectancy has improved considerably due to the new therapies. In HIV- patients, multiresistant tuberculosis has a better prognosis. Typification by means of restriction fragment length polymorphism is very useful in clarifying the origin of the cases.

Cost analysis of an integrated vaccine-preventable disease surveillance system in Costa Rica.

INTRODUCTION: Following World Health Organization recommendations set forth in the Global Framework for Immunization Monitoring and Surveillance, Costa Rica in 2009 became the first country to implement integrated vaccine-preventable disease (iVPD) surveillance, with support from the U.S. Centers for Disease Control and Prevention (CDC) and the Pan American Health Organization (PAHO). As surveillance for diseases prevented by new vaccines is integrated into existing surveillance systems, these systems could cost more than routine surveillance for VPDs targeted by the Expanded Program on Immunization. OBJECTIVES: We estimate the costs associated with establishing and subsequently operating the iVPD surveillance system at a pilot site in Costa Rica. METHODS: We retrospectively collected data on costs incurred by the institutions supporting iVPD surveillance during the preparatory (January 2007 through August 2009) and implementation (September 2009 through August 2010) phases of the iVPD surveillance project in Costa Rica. These data were used to estimate costs for personnel, meetings, infrastructure, office equipment and supplies, transportation, and laboratory facilities. Costs incurred by each of the collaborating institutions were also estimated. RESULTS: During the preparatory phase, the estimated total cost was 128,000 U.S. dollars (US$), including 64% for personnel costs. The preparatory phase was supported by CDC and PAHO. The estimated cost for 1 year of implementation was US$ 420,000, including 58% for personnel costs, 28% for laboratory costs, and 14% for meeting, infrastructure, office, and transportation costs combined. The national reference laboratory and the PAHO Costa Rica office incurred 64% of total costs, and other local institutions supporting iVPD surveillance incurred the remaining 36%. CONCLUSIONS: Countries planning to implement iVPD surveillance will require adequate investments in human resources, laboratories, data management, reporting, and investigation. Our findings will be valuable for decision makers and donors planning and implementing similar strategies in other countries.

[Study of the nutritional status of elders in Cantabria]. / Estudio del estado nutricional de los ancianos de Cantabria.

INTRODUCTION: Population ageing is a main concern under the biosanitary point of view. AIM: To assess the nutritional status of people 65 year-old and older in Cantabria (Spain) METHOD: A total of 1605 persons were studied by means of the MNA (Mini Nutritional Assessment); a) by primary care (59.9% in the unit, and 4.7% at home) and, b) in nursing homes (35.4%). RESULTS: Nutritional score (NS) was 23.4 ± 4.1 for women and 24.4 ± 4 in males (p < 0.001). We emphasize the fact that 22.3% of people studied in the nursing homes were malnourished or at risk of malnutrition, compared with 14.2% of those studied at the unit, and only 3.3% of the home visited elders. The correlation between the value of the NS and the subjective estimation of nutrition status showed a high value (0.65). We emphasize the negative correlation (-0.53) between BNI value and the incidence of skin lesions. CONCLUSION: Our results highlight the importance of identifying malnutrition or its risk in elders in order to prevent the negative consequences of this deficiency.