Assisted Salvage of Ischemic Fasciocutaneous Flap Using Adipose-Derived Mesenchymal Stem Cells: In-Situ Revascularization.

Adipose-derived mesenchymal stem cells (ASCs) have been shown to produce vascular endothelial growth factor (VEGF) and can increase perfusion in patients with critical limb ischemia. We will show that this concept can be applied to augment blood flow in zones of flap ischemia. We presented a case study of a 26-year-old man with a complex hand injury covered by a reverse radial perforator fasciocutaneous flap, which developed ischemic necrosis and was treated by debridement, transplantation of ASCs to enhance vascular support, and saline dressings. ASCs are found in the stromal vascular fraction (SVF), a heterogeneous collection of cells, including pericytes and endothelial cells, that is prepared from lipoaspirate using collagenase digestion followed by centrifugation. These were injected into the flap, the palmar tissues both subjacent and peripheral to the flap, and the skin-grafted donor site. The case was documented with photography, measurements at hand therapy, and follow-up angiography MRI. At 72 hours, new vessels appeared diffusely; at 1 week, the remaining tissues of flap were bleeding. The wound, 11 cm × 4 cm, contracted spontaneously and was healed at 21 days. The skin graft over the donor site demonstrated unusual suppleness and elasticity. 3D CT angiography disclosed a new layer of vascularity in the superficial tissues of the palm when compared with the normal side. The patient regained full composite flexion, pinch, opposition, and wrist extension. Application of ASCs into the supporting tissues surrounding the ischemic flap, and into the flap itself, constituted a form of in-situ revascularization (ISR) that was subjectively and objectively effective for this patient. LEVEL OF EVIDENCE: 5.

Comparative proteomic analysis of spermatozoa isolated by swim-up or density gradient centrifugation.

BACKGROUND: Reports about the morphologic and functional characteristics of spermatozoa prepared by density gradient centrifugation (DC) or swim-up (SU) have produced discordant results. We have performed a proteomic comparison of cells prepared by DC and SU providing a molecular insight into the differences between these two methods of sperm cell isolation. METHODS: Protein maps were obtained by 2-dimensional (2-D) separations consisting of isoelectrofocusing (IEF) from pI 3 to 11 followed by SDS-polyacrylamide gel electrophoresis. 2-D gels were stained with Sypro Ruby. Map images of DC and SU spermatozoa were compared using dedicated software. Intensities of a given spot were considered different between DC and SU when their group mean differed by >1.5-fold (p<0.05, Anova). RESULTS: No differences were observed for 853 spots, indicating a 98.7% similarity between DC and SU. Five spots were DC>SU and 1 was SU>DC. Proteins present in 3 of the differential spots could be identified. One DC>SU spot contained lactate dehydrogenase C and gamma-glutamylhydrolase, a second DC>SU spot contained fumarate hydratase and glyceraldehyde-3-phosphate dehydrogenase-2, and a SU>DC spot contained pyruvate kinase M1/M2. CONCLUSIONS: The differences in protein levels found on comparison of DC with SU spermatozoa indicate possible dissimilarities in their glycolytic metabolism and DNA methylation and suggest that DC cells may have a better capacitation potential.

Comparative analysis of the seminal plasma proteomes of oligoasthenozoospermic and normozoospermic men.

A comparative proteomic study of oligoasthenozoospermic and normozoospermic seminal plasmas was conducted to establish differences in protein expression. Oligoasthenozoospermia (when semen presents with a low concentration and reduced motility of spermatozoa) is common in male infertility. Two-dimensional protein maps from seminal plasma samples from 10 men with normozoospermia and 10 men with idiopathic oligoasthenozoospermia were obtained by isoelectric focusing followed by sodium dodecyl-sulphate polyacrylamide electrophoresis. Map images were analysed using dedicated software involving normalization, spot-to-spot volume comparison and statistical treatment of the results to establish the significance of differences between normal and oligoasthenozoospermic samples. Six out of 1028 spots showed over 1.5-fold relative intensity differences (P < 0.05, analysis of variance). Four proteins were identified by nano liquid chromatography-electrospray ionization-mass spectrometry/mass spectrometry of their tryptic peptides and database searches. Two proteins were more than three-fold under-expressed in oligoasthenozoospermia, namely epididymal secretory protein E1 and galectin-3-binding protein; the other (lipocalin-1 and a prolactin-inducible protein form) were over-expressed. The identity and differential expression of epididymal secretory protein E1 was verified by Western-blotting. The statistically significant differential expression of these four proteins in oligoasthenozoospermia compared with normozoospermia provides a molecular basis for further investigations into the pathogenic mechanisms underlying idiopathic oligoasthenozoospermia.

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

Background: A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC). Methods: A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained. Results: A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed. Conclusions: The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL.

Overosaurus paradasorum gen. et sp. nov., a new sauropod dinosaur (Titanosauria: Lithostrotia) from the late Cretaceous of Neuquén, Patagonia, Argentina.

A new lithostrotian sauropod, the small-sized Overosaurus paradasorum n. gen et sp. from the Anacleto Formation (Campanian, Late Cretaceous, Neuquén Group, Patagonia, Argentina) is here described. The specimen (MAU-Pv-CO-439) consists of a fully articulated vertebral series from the 10th cervical to the 20th caudal vertebra, the last cervical ribs, several dorsal ribs in articulation with their respective vertebrae, the complete right ilium and fragments of the left ilium. Overosaurus paradasorum is diagnosed by a unique combination of characters that includes (1) posterior cervical vertebrae with long pre- and postzygapophyses that project beyond the anterior and posterior borders of the centrum, respectively, (2) postspinal lamina absent in all dorsal neural spines, (3) wide and massive 9th and 10th caudal centra that are slightly excavated laterally and have relatively flat ventral surfaces, (4) laminar projection on the posterior border of the second and third dorsal rib, (5) ilium proportionally shorter anteroposteriorly and taller dorsoventrally than in other lithostrotians, and (6) the preacetabular process of the ilium strongly deflected laterally and with a ventrolaterally tapering end. Analysis of the phylogenetic relationships of Overosaurus places it within the Aeolosaurini, as the sister taxon of a monophyletic group formed by Aeolosaurus rionegrinus, A. maximus, Gondwanatitan faustoi and Pitekunsaurus macayai. Overosaurus is a new representative of a highly diversified assemblage of Campanian lithostrotians from Patagonia that includes both Aeolosaurini and saltasaurids (e.g. Saltasaurus, Neuquensaurus)--this small new taxon falls within the low end of the size spectrum represented by these Late Cretaceous sauropods.

Impact of the Semiconductor Defect Density on Solution-Processed Flexible Schottky Barrier Diodes.

Schottky barrier diodes, developed by low-cost techniques and low temperature processes (LTP-SBD), have gained attention for different kinds of novel applications, including flexible electronic fabrication. This work analyzes the behavior of the I-V characteristic of solution processed, ZnO Schottky barrier diodes, fabricated at a low temperature. It is shown that the use of standard extraction methods to determine diode parameters in these devices produce significant dispersion of the ideality factor with values from 2.2 to 4.1, as well as a dependence on the diode area without physical meaning. The analysis of simulated I-V characteristic of LTP-SBD, and its comparison with experimental measurements, confirmed that it is necessary to consider the presence of a density of states (DOS) in the semiconductor gap, to understand specific changes observed in their performance, with respect to standard SBDs. These changes include increased values of Rs, as well as its dependence on bias, an important reduction of the diode current and small rectification values (RR). Additionally, it is shown that the standard extraction methodologies cannot be used to obtain diode parameters of LTP-SBD, as it is necessary to develop adequate parameter extraction methodologies for them.

Mechanical Performance of Commercially Available Premix UHPC-Based 3D Printable Concrete.

Several recent studies have attempted to formulate printable cementitious materials to meet the printing requirements, but these materials are designed to work with specific printing equipment and printing configurations. This paper aims to systematically develop and perform characterization of a commercially available ultra-high-performance concrete-class material (UHPC) modified to be printable. Four percentages of superplasticizer were used (100%, 94%, 88%, 82%) to adjust the UHPC mixture for 3D-printing requirements. A superplasticizer amount of 88% was considered adequate to meet the requirements. Several fresh and hardened properties of UHPC were measured experimentally: shape-retention ability and green strength were investigated in fresh state, and compressive and flexural strength were evaluated in three loading directions to evaluate the anisotropic effects. Furthermore, the strength of the interlayer bond was investigated. The UHPC developed in this study met the criteria for extrudability, buildability, and shape retention to ensure printability. In comparison with mold-cast UHPC, printed UHPC exhibited superior flexural performance (15-18%), but reduced compressive strength (32-56%). Finally, the results demonstrated that a commercially available UHPC-class material can be used for 3DCP, which possesses all necessary properties, both fresh and hardened.

Maternal and paternal ages at conception of index child and risk of childhood acute leukaemia: A multicentre case-control study in Greater Mexico City.

BACKGROUND: The parental age at conception has been reported to be a risk factor for childhood acute leukaemia (AL); however, the relationship is controversial. The aim of the present study was to investigate the association between parental age at conception and the risk of AL in Mexican children, a population with a high incidence of the disease and a high prevalence of pregnancies in adolescents and young adults. METHODS: A multicentre case-control study was conducted. Incident AL cases younger than 17 years of age diagnosed between 2010 and 2015 were included. Controls were matched with cases according to age, sex, and health institution. Using logistic regression analysis, adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) were calculated for each maternal stratum after adjusting for paternal age at conception of index child. The maternal age between 25 and 29.99 years was selected as the reference category. RESULTS: In most strata where maternal and paternal ages were assessed, no association was found with the risk of developing acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring. An increased risk for AML was observed when the mother was between 20 and 24.99 years of age and the father aged 25-29.99 years (aOR, 1.94; 95 % CI, 1.03-3.67). In addition, there was a positive association for ALL when the mother´s age was between 20 and 24.99 years and the father was <20 years of age, however, a very wide confidence interval was noted (aOR, 12.26; 95 % CI, 1.41-106.83). CONCLUSION: In the present study, maternal and paternal ages assessed in different strata showed little association with risk of developing ALL and AML in children. Positive associations between risk of both types of childhood AL were observed with younger paternal and maternal ages.

Extracellular Vesicles in Mycobacterial Infections: Their Potential as Molecule Transfer Vectors.

Extracellular vesicles are membrane-bound structures released by living cells and present in body fluids. Their composition includes proteins, lipids, carbohydrates, and nucleic acids and are involved in transfers between cells. Extracellular vesicles can deliver molecules to cells and tissues even if distant. As a consequence, they have a role in information transmission and in the modulation of the biological function of recipient cells. Among other things, they are involved in antigen presentation and the induction of secretion events by immune cells. Thus, extracellular vesicles participate in the regulation of immune responses during infections. We will discuss their potential as effectors and disease biomarkers concerning only mycobacterial infections.

Left main coronary artery stenosis treatment with two paclitaxel-eluting stents in a patient with cardiac allograft vasculopathy.

Cardiac transplantation is a well defined therapy for end stage heart failure. After the first year of transplantation, allograft coronary artery disease (ACAD) is the second main cause of death. The ACAD is defined as a diffuse process affecting the entire length of epicardial vessels. Once ACAD has been established, treatments such as coronary angioplasty, coronary stenting, and coronary bypass are performed. We present a case of successful stenting of the left main coronary artery (LMCA) in a patient with ACAD. The patient's medical history was significant for heart transplantation due to ischemic heart failure. Four years after transplantation the patient was admitted again due to sudden worsening of New York Heart Association functional class and extreme fatigue. Coronary angiogram showed a severe stenosis in the proximal segment of the LMCA; we performed stenting with a paclitaxel-eluting stent (PES). Six months after the procedure, the patient had an elective angiogram, where we discovered a new severe occlusion distally to the former stent; a second PES was implanted. Fourteen months after the second stenting, a new elective angiogram was performed without evidence of in-stent restenosis. After a 8-year follow-up since transplantation, the patient is free from dyspnea, angina, and adverse cardiovascular events. Our report suggests the efficacy of PES as ACAD treatment of the unprotected LMCA.

Downregulation of glutamic acid decarboxylase in Drosophila TDP-43-null brains provokes paralysis by affecting the organization of the neuromuscular synapses.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that affects the motor system, comprised of motoneurons and associated glia. Accordingly, neuronal or glial defects in TDP-43 function provoke paralysis due to the degeneration of the neuromuscular synapses in Drosophila. To identify the responsible molecules and mechanisms, we performed a genome wide proteomic analysis to determine differences in protein expression between wild-type and TDP-43-minus fly heads. The data established that mutant insects presented reduced levels of the enzyme glutamic acid decarboxylase (Gad1) and increased concentrations of extracellular glutamate. Genetic rescue of Gad1 activity in neurons or glia was sufficient to recuperate flies locomotion, synaptic organization and glutamate levels. Analogous recovery was obtained by treating TDP-43-null flies with glutamate receptor antagonists demonstrating that Gad1 promotes synapses formation and prevents excitotoxicity. Similar suppression of TDP-43 provoked the downregulation of GAD67, the Gad1 homolog protein in human neuroblastoma cell lines and analogous modifications were observed in iPSC-derived motoneurons from patients carrying mutations in TDP-43, uncovering conserved pathological mechanisms behind the disease.

A greater birthweight increases the risk of acute leukemias in Mexican children-experience from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL).

In Mexico, due to the high rates of diabetes, overweight, and obesity, there has also been noted an increased newborn weight, which may be contributing to the elevated incidence rate of childhood acute leukemia (AL). We conducted a case-control study in public hospitals of Mexico City aimed to know whether a greater weight at birth is associated with a higher risk of developing leukemia. We included incident cases with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) diagnosed between 2010 and 2015. Controls were frequency-matched to the cases by age, sex, and health institution. Logistic regression analysis was performed adjusting risks by child's sex, overcrowding index, birth order, and mother's age at the time of pregnancy. Adjusted odds ratios (aORs) and 95% confidence intervals were calculated. A total of 1455 cases and 1455 controls were included. An evident association between ALL and child's birthweight ≥2500 g was found (aOR 2.06; 95% CI: 1.59, 2.66) and also, in those with birthweight ≥3500 g (aOR 1.19; 95% CI: 1.00, 1.41). In AML patients with birthweight ≥2500 g and ≥3500 g, an aOR of 1.77 (95% CI: 1.07, 2.94) and 1.42 (95% CI: 1.03-1.95) was observed, respectively. No association was noticed with either type of AL and a birthweight ≥4000 g. To sum up, we found a moderate association between not having a low birthweight and an increased risk of acute leukemias. Birthweight ≥3500 g was also a risk factor for both types of leukemia. This suggests that a greater birthweight may increase the risk of acute leukemias in Mexican children.

[Cardiogenic shock continues to be the most serious complication of the acute myocardial infarction]. / La cirugía de revascularización coronaria. Hay avances que han impactado en este escenario: En su manejo y el contexto de las complicaciones mecánicas?

The actual therapeutic guidelines, look to conceive reperfusion of the infarcted myocardial areas in less time with pharmacological treatment, interventionist procedures or surgery for revascularization. CABG should be consider as a therapeutic modality that can be use for the treatment of cardiogenic shock, in well selected patients, as in those who primary angioplasty could not be achieved as treatment for the acute myocardial infarction. We revised the patients characteristics, the useful modalities and benefits that CABG can offer in this pathology.

[The cardiovascular surgeon and the Syntax score]. / El cirujano cardiovascular y la puntuación Syntax.

The Syntax score has been established as a tool to determine the complexity of coronary artery disease and as a guide for decision-making among coronary artery bypass surgery and percutaneous coronary intervention. The purpose of this review is to systematically examine what the Syntax score is, and how the surgeon should integrate the information in the selection and treatment of patients. We reviewed the results of the SYNTAX Trial, the clinical practice guidelines, as well as the benefits and limitations of the score. Finally we discuss the future directions of the Syntax score.

[Inhaled iloprost, a selective pulmonary vasodilator. Clinical evidence from its use in perioperative pulmonary hypertension cardiovascular surgery]. / Iloprost inhalado, un vasodilatador pulmonar selectivo. Evidencia clínica de su uso en la hipertensión pulmonar del perioperatorio de cirugía cardiovascular.

Inhaled iloprost is one of the most recent drugs from prostanoids group's in the treatment of pulmonary arterial hypertension. His place in pulmonary hypertension seen in the perioperative cardiovascular surgery has not been defined. In this review we analyze pulmonary hypertension group's susceptibles of cardiac surgery and its importance, besides the current clinical evidence from drug use in this context.

Mycobacteria-containing phagosomes associate less annexins I, VI, VII and XI, but not II, concomitantly with a diminished phagolysosomal fusion.

We have studied the intracellular localization of annexins I,II, VI, VII, and XI in cells containing latex beads or Mycobacterium avium at different times after ingestion in order to establish whether a correlation existed between the association of annexins to phagosomes and phagolysosomal fusion, since the intracellular survival of mycobacteria is linked to an impairment of phagosome maturation. We demonstrate an important decrease in the levels of association of annexins I, VI, VII and XI, but not II to phagosomes containing either live or killed mycobacteria compared with phagosomes containing inert latex particles. The reduced association of annexins observed was detected only on M. avium-containing phagosomes and not in other cell membrane nor in cytosolic fractions from infected cells, and was apparent from 8 hours through to 4 days after phagocytosis. These findings add elements to the present knowledge of the phagosomal modifications that accompany the survival of intracellular pathogens, suggesting that annexins I, VI, VII, and XI play a secondary role in phagosomal fusion events while annexin II does not seem to be related to the mechanism of regulation of endolysosomal fusion.

[Evaluation of predisposing factors for mediastinal bleeding in myocardial revascularization surgery. Role of acetylsalicylic acid, other platelet adhesion inhibitors, and anticoagulants]. / Evaluación de factores predisponentes para el sangrado mediastinal en cirugía de revascularización miocárdica. Papel del ácido acetilsalicílico, otros antiagregantes plaquetarios, y anticoagulantes.

OBJECTIVE: To determine the main factors for perioperative mediastinal bleeding during coronary artery by-pass grafting and to establish the role of acetylsalicylic acid, other inhibitors of platelet adhesion, and anticoagulants in its occurrence. METHODS: A multivariate analysis was performed to the data obtained from 251 patients subjected to coronary artery by-pass grafting in the year 2002. RESULTS: There were no significant differences for the occurrence of perioperative bleeding induced by the preoperative administration of acetylsalicylic acid. No significant increment in the need for blood, platelet, or cryoprecipitates transfusion existed. Patients receiving non-fractionated or low molecular weight heparin had a significantly greater (p < 0.001) transoperative bleeding than patients without this drug. Administration of the other studied drugs did not increase either mediastinal bleeding or the need for blood derivatives. CONCLUSIONS: No statistical evidence was found to suspend administration of inhibitors of platelet adhesion in patients with coronary syndromes, subjected to coronary artery by-pass grafting. However, data obtained suggest the convenience of suspending administration of low molecular weight or non-fractionated heparin to patients subjected electively to coronary artery by-pass grafting.

Analysis of oxidative stress enzymes and structural and functional proteins on human aortic tissue from different aortopathies.

The role of oxidative stress in different aortopathies is evaluated. Thirty-two tissue samples from 18 men and 14 women were divided into: 4 control (C) subjects, 11 patients with systemic arterial hypertension (SAH), 4 with variants of Marfan's syndrome (MV), 9 with Marfan's syndrome (M), 2 with Turner's syndrome, and 2 with Takayasu's arteritis (TA). Aorta fragments were homogenized. Lipoperoxidation (LPO), copper-zinc and manganese superoxide dismutase (Mn and Cu-Zn-SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), endothelial nitric oxide synthase (eNOS), nitrates and nitrites (NO3(-)/NO2(-)), and type IV collagen, and laminin were evaluated. There was an increase in Mn- and Cu-Zn-SOD activity in SAH, MV, M, and Turner's syndrome. There was also an increase in CAT activity in M and Turner' syndrome. GPx and GST activity decreased and LPO increased in all groups. eNOS was decreased in SAH, MV, and M and NO3 (-)/NO2 (-) were increased in SAH and TA. Type IV collagen was decreased in Turner's syndrome and TA. Laminin γ-1 was decreased in MV and increased in M. In conclusion, similarities and differences in oxidative stress in the different aortopathies studied including pathologies with aneurysms were found with alterations in SOD, CAT, GPx, GST, and eNOS activity that modify subendothelial basement membrane proteins.

An extragranular compartment of blood eosinophils contains eosinophil protein X/eosinophil-derived neurotoxin (EPX/EDN).

Serum and plasma profiles of eosinophil protein X (EPX/EDN) and those of other eosinophil proteins differ in various conditions, suggesting a different mobilisation from storage granules. This work studied the subcellular localisation of EPX/EDN in non-primed and in vivo primed blood eosinophils from healthy and allergic subjects, during and out of the pollen season. Primed eosinophils contain easily mobilisable secretory proteins. By fractionation on sucrose density gradients, EPX/EDN localised in the specific granules as well as in a cytoplasmic extra-granular compartment of low equilibrium density that partially overlapped with vesicular structures, cytosolic proteins and plasma membranes. This compartment was clearly separate from the low density peak of ECP that increases during the pollen season. There were no significant differences in the amounts of EPX/EDN present in the low density peak of healthy and allergic subjects. Immuno-gold labelling electron microscopy showed EPX/EDN in specific granules, cytoplasm and associated to plasma membranes. In conclusion, substantial amounts of EPX/EDN localise in an extra-granular, low equilibrium density compartment of human eosinophils.