Ruling out Color Transparency in Quasielastic

Quasielastic ^{12}C(e,e^{'}p) scattering was measured at spacelike 4-momentum transfer squared Q^{2}=8, 9.4, 11.4, and 14.2 (GeV/c)^{2}, the highest ever achieved to date. Nuclear transparency for this reaction was extracted by comparing the measured yield to that expected from a plane-wave impulse approximation calculation without any final state interactions. The measured transparency was consistent with no Q^{2} dependence, up to proton momenta of 8.5 GeV/c, ruling out the quantum chromodynamics effect of color transparency at the measured Q^{2} scales in exclusive (e,e^{'}p) reactions. These results impose strict constraints on models of color transparency for protons.

Probing the Deuteron at Very Large Internal Momenta.

We measure ^{2}H(e,e^{'}p)n cross sections at 4-momentum transfers of Q^{2}=4.5±0.5 (GeV/c)^{2} over a range of neutron recoil momenta p_{r}, reaching up to ∼1.0 GeV/c. We obtain data at fixed neutron recoil angles θ_{nq}=35°, 45°, and 75° with respect to the 3-momentum transfer q[over →]. The new data agree well with previous data, which reached p_{r}∼500 MeV/c. At θ_{nq}=35° and 45°, final state interactions, meson exchange currents, and isobar currents are suppressed and the plane wave impulse approximation provides the dominant cross section contribution. We compare the new data to recent theoretical calculations, where we observe a significant discrepancy for recoil momenta p_{r}>700 MeV/c.

Liver stiffness and aspartate aminotransferase levels predict the risk for liver fibrosis progression in hepatitis C virus/HIV-coinfected patients.

OBJECTIVES: The aim of the study was to investigate liver fibrosis outcome and the risk factors associated with liver fibrosis progression in hepatitis C virus (HCV)/HIV-coinfected patients. METHODS: We prospectively obtained liver stiffness measurements by transient elastography in a cohort of 154 HCV/HIV-coinfected patients, mostly Caucasian men on suppressive antiretroviral treatment, with the aim of determining the risk for liver stiffness measurement (LSM) increase and to identify the predictive factors for liver fibrosis progression. To evaluate LSM trends over time, a linear mixed regression model with LSM level as the outcome and duration of follow-up in years as the main covariate was fitted. RESULTS: After a median follow-up time of 40 months, the median increase in LSM was 1.05 kPa/year [95% confidence interval (CI) 0.72-1.38 kPa/year]. Fibrosis stage progression was seen in 47% of patients, and 17% progressed to cirrhosis. Aspartate aminotransferase (AST) levels and liver fibrosis stage at baseline were identified as independent predictors of LSM change. Patients with F3 (LSM 9.6-14.5 kPa) or AST levels ≥ 64 IU/L at baseline were at higher risk for accelerated LSM increase (ranging from 1.45 to 2.61 kPa/year), whereas LSM change was very slow among patients with both F0-F1 (LSM ≤ 7.5 kPa) and AST levels ≤ 64 IU/L at baseline (0.34 to 0.58 kPa/year). An intermediate risk for LSM increase (from 0.78 to 1.03 kPa/year) was seen in patients with F2 (LSM 7.6-9.5 kPa) and AST baseline levels ≤ 64 IU/L. CONCLUSIONS: AST levels and liver stiffness at baseline allow stratification of the risk for fibrosis progression and might be clinically useful to guide HCV treatment decisions in HIV-infected patients.

Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study. / Resultados clínicos de artroplastia total de cadera asistida por brazo robótico en España: estudio preliminar.

OBJECTIVES: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. MATERIAL AND METHODS: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. RESULTS: Average age was 67.2years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative hemoglobin decrease of 3.08±1.08g/dL, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® s results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min -12, max 3) to 1.29mm (SD: 1.96) after surgery registered with Mako®, with an increase of an average hip length of 5.64mm (SD: 3.35). Rx simple study results show a postoperative difference between both hips of 0.5±3.08mm, which is consistent with Mako® results. Native femoral offset was stable after surgery with a showing difference both pre and post operative of the intervened hip of 0.1mm (SD: 3.7), registered with Mako®. Preoperatory modified Harris punctuation was 41.6±13.3, improving to postoperative values of 74.6±9.7 after four months since the surgery. No complications were registered in immediate postoperative (4month). CONCLUSIONS: Total hip arthroplasty robot-assisted achieves an adequate precision and repeatability of the implant positioning and the postoperative hip dysmetry without showing an increase of associated complications to the technique applied. Surgery time, complications and functional results in a short-time period are similar to conventional techniques applied to great series previously published.

[Translated article] Clinical results of total hip arthroplasty assisted by robotic arm in Spain: Preliminary study.

OBJECTIVES: Clinical, radiological and functional results of the first Spanish series of patients undergoing total hip arthroplasty assisted by Mako® (Stryker) robotic arm at the Hospital Clínico San Carlos (HCSC) in Madrid. MATERIAL AND METHODS: Prospective and descriptive study analyzing the first 25 patients who underwent robotic-assisted THA at the HCSC, with a minimum follow-up of 4 months. Demographics, imaging studies (Mako® processing, Rx and CT), clinical parameters, functionality (modified Harris) and associated complications were evaluated. RESULTS: Average age was 67.2 years (min 47, max 88), being 56% male population sample. 88% involves primary coxarthrosis, 4% post-traumatic coxarthrosis, 4% secondary avascular necrosis and 4% secondary femoroacetabular impingement. Average surgery time was 116.9min (min 92, max 150). The average time of the first five surgeries was 122.6min, and, regarding the last five interventions, it was 108.2min. Found medical intraoperative complications were four intraoperative markers loss. Average admission time was 4.4days (min 3, max 7), with an average postoperative haemoglobin decrease of 3.08±1.08g/dl, requiring a transfusion in 12% of the cases. Three medical complications have been registered in the meantime of the admission, with a relevant case of a confusional syndrome and a fall, which resulted in a non-displaced AG1 periprosthetic fracture. The analysis of the positioning of registered implants with Mako® system shows 40.55±1.53 acetabular inclination degrees and 12.2±3.6 acetabular anteversion degrees. The postoperative image study carried out on patients, are consistent with Mako® results, as it shows an acetabular inclination of 41.2±1.7 in Rx, as well as acetabular anteversion of 16±4.6 in CT. Hip length variance ranges depending on preoperative values of 3.91mm (SD: 3.9; min -12, max 3) to 1.29mm (SD: 1.96) after surgery registered with Mako®, with an increase of an average hip length of 5.64mm (SD: 3.35). Rx simple study results show a postoperative difference between both hips of 0.5±3.08mm, which is consistent with Mako® results. Native femoral offset was stable after surgery with a showing difference both pre and post operative of the intervened hip of 0.1mm (SD: 3.7), registered with Mako®. Preoperatory modified Harris punctuation was 41.6±13.3, improving to postoperative values of 74.6±9.7 after four months since the surgery. No complications were registered in immediate postoperative (4 months). CONCLUSIONS: Total hip arthroplasty robot-assisted achieves an adequate precision and repeatability of the implant positioning and the postoperative hip dysmetry without showing an increase of associated complications to the technique applied. Surgery time, complications and functional results in a short-time period are similar to conventional techniques applied to great series previously published.

Hb Extremadura [ß64(E8)Gly→Ser;ß133(H11)Val→Leu]: a new molecular analysis.

Unstable hemoglobin (Hb) variants account for 9.5% of structural hemoglobinopathies. The majority of these unstable variants are the result of gene point mutations resulting in the substitution of a single amino acid by another. The presence of two mutations in the same allele is infrequent: of the 781 variants of the ß-globin cluster described, only 32 are due to two point mutations (4.1%). Hb Extremadura is a structural variant that is included within the so-called unstable Hb anomalies. It was first described in 1989, employing the most up-to-date techniques available at that time, reversed phase high performance liquid chromatography (HPLC) to separate the abnormal chain (ß(X)) digesting it with trypsin and analysis of the fragments with an automatic analyzer.

Serum-induced translocation of mitogen-activated protein kinase to the cell surface ruffling membrane and the nucleus.

The mitogen-activated protein (MAP) kinase signal transduction pathway represents an important mechanism by which growth factors regulate cell function. Targets of the MAP kinase pathway are located within several cellular compartments. Signal transduction therefore requires the localization of MAP kinase in each sub-cellular compartment that contains physiologically relevant substrates. Here, we show that serum treatment causes the translocation of two human MAP kinase isoforms, p40mapk and p41mapk, from the cytosol into the nucleus. In addition, we report that p41mapk (but not p40mapk) is localized at the cell surface ruffling membrane in serum-treated cells. To investigate whether the protein kinase activity of MAP kinase is required for serum-induced redistribution within the cell, we constructed mutated kinase-negative forms of p40mapk and p41mapk. The kinase-negative MAP kinases were not observed to localize to the cell surface ruffling membrane. In contrast, the kinase-negative MAP kinases were observed to be translocated to the nucleus. Intrinsic MAP kinase activity is therefore required only for localization at the cell surface and is not required for transport into the nucleus. Together, these data demonstrate that the pattern of serum-induced redistribution of p40mapk is different from p41mapk. Thus, in addition to common targets of signal transduction, it is possible that these MAP kinase isoforms may differentially regulate targets located in distinct sub-cellular compartments.

An RGD sequence in the P2Y(2) receptor interacts with alpha(V)beta(3) integrins and is required for G(o)-mediated signal transduction.

The P2Y(2) nucleotide receptor (P2Y(2)R) contains the integrin-binding domain arginine-glycine-aspartic acid (RGD) in its first extracellular loop, raising the possibility that this G protein-coupled receptor interacts directly with an integrin. Binding of a peptide corresponding to the first extracellular loop of the P2Y(2)R to K562 erythroleukemia cells was inhibited by antibodies against alpha(V)beta(3)/beta(5) integrins and the integrin-associated thrombospondin receptor, CD47. Immunofluorescence of cells transfected with epitope-tagged P2Y(2)Rs indicated that alpha(V) integrins colocalized 10-fold better with the wild-type P2Y(2)R than with a mutant P2Y(2)R in which the RGD sequence was replaced with RGE. Compared with the wild-type P2Y(2)R, the RGE mutant required 1,000-fold higher agonist concentrations to phosphorylate focal adhesion kinase, activate extracellular signal-regulated kinases, and initiate the PLC-dependent mobilization of intracellular Ca(2+). Furthermore, an anti-alpha(V) integrin antibody partially inhibited these signaling events mediated by the wild-type P2Y(2)R. Pertussis toxin, an inhibitor of G(i/o) proteins, partially inhibited Ca(2+) mobilization mediated by the wild-type P2Y(2)R, but not by the RGE mutant, suggesting that the RGD sequence is required for P2Y(2)R-mediated activation of G(o), but not G(q). Since CD47 has been shown to associate directly with G(i/o) family proteins, these results suggest that interactions between P2Y(2)Rs, integrins, and CD47 may be important for coupling the P2Y(2)R to G(o).

Capillary electrophoresis and mutational images of hemoglobin sendagi [Β42 (CD1) PHE → VAL; HBB: C.127T→G].

We report two cases of hemoglobin Sendagi in a Romanian family residing in Spain: a four-year-old boy and his mother, who had been previously diagnosed with another type of congenital hemolytic anemia and had undergone splenectomy in her country during childhood. The unstable hemoglobin variant, hemoglobin Sendagi, is characterized by decreased oxygen affinity caused by replacement of one of the critical amino acid residues, phenylalanine beta 42 (CD1) of the beta-chain, with valine in the heme pocket, resulting in methemoglobin formation. As a result of migratory movements in Europe, new disease-causing hemoglobin variants are emerging in our country. Here, capillary electrophoresis enabled the identification of the variant and a molecular study was used to establish an accurate diagnosis.

Tension subcutaneous haematomas associated with anticoagulants in the elderly: Do they have earlier morbidity and mortality than hip fractures? / Hematomas subcutáneos a tensión por anticoagulantes en ancianos: ¿más morbimortalidad precoz que las fracturas de cadera?

INTRODUCTION: Complications related to anticoagulant therapy have been widely described, although tension haematomas in the extremities are frequently undervalued, and commonly considered banal pathologies. MATERIAL AND METHOD: Retrospective descriptive study between 2014 and 2017, including patients with limb haematomas after minimal trauma related with anticoagulant therapy, and surgically treated by Traumatology. RESULTS: 32 cases were eventually included, 81% were women, average age of 83.56 years, and a mean aCCI of 5.97. Anatomical location of haematomas was 65.6% in leg/foot, 15.6% in thigh/buttock, and 18.8% in the upper limb. Seventy-eight point thirteen percent received acenocoumarol, 15.63% LMWH, and 3.13% NOACs. Of the cases, 59.38% were due to AF, 15.63% to valvular heart disease/valve prosthesis, and 12.5% to PE/DVT. The mean time from diagnosis to surgical drainage was 2.66 days, mainly as a result of alterations in coagulation parameters. Forty-six point eighty-eight percent were reoperated for new drainage, cure or skin defect coverage, and 3 patients required embolisation. Of the patients, 78% needed consultation with other specialties. The average length of stay was 22.34 days, and the in-hospital mortality rate was 9.38%. CONCLUSION: Tension haematomas in the extremities associated with anticoagulants occur in patients with multiple comorbidities that make them vulnerable. Surgical drainage is usually delayed by numerous factors which lead to skin defects that require further surgical operations, and prolonged hospital stays that are associated with medical complications. In our study, the average length of stay and in-hospital mortality rate were higher than those for hip fractures, so we should not underestimate this pathology.

Caveolins in glial cell model systems: from detection to significance.

Glial cells prevail in number and in diversity of cellular phenotypes in the nervous system. They have also gained prominence due to their multiple physiological and pathophysiological roles. Our current knowledge of the asymmetry and heterogeneity of the plasma membrane demands an in depth analysis of the diverse array of membrane microdomains postulated to exist in the context of glial cells. This review focuses and analyzes the studies reported to date on the detection of caveolae membrane rafts and the caveolin family members in glial cell model systems, the conditions leading to changes in their level of expression, and their functional and clinical significance. Outstanding in this work emerge the ubiquitous expression of caveolins, including the typically regarded 'muscle-specific' cav3, in diverse glial cell model systems, their participation in reactive astrogliosis, cancer, and their key relevance to calcium signaling. The knowledge obtained to date demands incorporation of the caveolins and caveolae membrane rafts in our current models on the role of glial cells in heath and neurological disease.

Genomic loci of human mitogen-activated protein kinases.

Mitogen-activated protein (MAP) kinases [also known as Erks] have been established to function as important mediators of signal transduction by growth factor receptors. Several components of the MAP kinase signal transduction pathway have been demonstrated to be oncogenically activated in malignant tumors. These include growth factor receptors, the GTP-binding protein Ras, and the protein kinase Raf. The genes that encode MAP kinases therefore represent potential targets of carcinogenic insults. Here, we report the genomic loci of three MAP kinase genes are widely distributed within the human genome: p41mapk (Erk2) at 22q11.2; p44mapk (Erk1) at 16p11.2; and p63mapk (Erk3-related) at 18q12-21.

Extracellular ATP and some of its analogs induce transient rises in cytosolic free calcium in individual canine keratinocytes.

Changes in intracellular free calcium ([Ca++]i) play an important role in a variety of biochemical reactions that lead to cellular responses such as proliferation and differentiation. The response of [Ca++]i to extracellular nucleotides (ATP, UTP, ITP, and AMP-PNP) was determined in individual canine keratinocytes using the fluorescent probe fura-2 and digital video fluorescence imaging microscopy. In the presence of 1.8 mM extracellular Ca++, 100 and 500 microM ATP caused a rapid (less than 9 sec) three- to twelvefold rise in [Ca++]i above resting levels of 50-150 nM followed by occasional fluctuations. Small responses were elicited with doses as low as 0.1 microM ATP. The response of cells stimulated with 500 microM ATP in Ca(++)-free medium was characterized by 1.5 to 3 times rapid initial peak followed by a decrease of [Ca++]i below resting levels. Loss of response occurred in the majority of keratinocytes preincubated for 30 min in Ca(++)-free medium. UTP was as effective as ATP in stimulating rises in [Ca++]i in keratinocytes. Smaller elevations in [Ca++]i up to four- to fivefold resting levels were noted with 100 microM AMP-PNP or 500 microM ITP. Desensitization of cells was demonstrated when a second stimulation followed the primary ATP or UTP treatment. These results are suggestive of the presence of purinergic receptors in the cytoplasmic membrane of canine keratinocytes. Experiments using the calcium channel blocker lanthanum suggest that ATP-induced initial rises and sustained levels of [Ca++]i are dependent on the release of Ca++ from intracellular stores. These intracellular Ca++ stores appear to be rapidly depleted after removal of extracellular calcium ([Ca++]e), thereby abolishing ATP-induced [Ca++]i increases.

Heterogeneous expression of four MAP kinase isoforms in human tissues.

Mitogen-activated protein kinases (MAP kinases) are a group of closely related enzymes implicated in signal transduction pathways. We report the molecular cloning of four human proteins (p40mapk, p41mapk, p44mapk and p63mapk) with high homology to members of the MAP kinase family. Sequence analysis demonstrated that p44mapk and p63mapk were the products of distinct genes. However, the p40mapk and p41mapk were found to be related, and are likely to result from alternative processing of transcripts from a single gene. The heterogeneous expression of these human MAP kinase isoforms in different tissues may reflect the diversity of signal transduction pathways in differentiated cells.

Interaction between a 3-nitrobenzothiazolo (3,2-a) quinolinium antitumour drug and deoxyribonucleic acid.

The interaction of 3-nitrobenzothiazolo (3,2-a) quinolinium (NBQ) perchlorate with DNA was studied by u.v.-visible and fluorescence spectrophotometry as well as by hydrodynamic methods. On binding to DNA, the absorption spectrum underwent bathochromic and hypochromic shifts, and the fluorescence was quenched. Binding parameters, determined from spectrophotometric measurements by Scatchard analysis according to an excluded-site model, indicated a binding constant of 2.4 X 10(5)M-1 for calf thymus DNA at ionic strength 0.01. The interaction was markedly suppressed by increasing the salt concentration. Binding to the GC-rich DNA of Micrococcus lysodeikticus was weaker than the binding to calf thymus DNA at ionic strength 0.01 NBQ increased the viscosity of sonicated rod-like DNA fragments, producing a calculated increment in length of 2.4 A/bound drug molecule. It removed and reversed the supercoiling of closed circular duplex plasmid pBR322 DNA by virtue of a helix-unwinding angle estimated as approximately 13 degrees/bound ligand molecule. We conclude that the binding of NBQ to DNA occurs by a mechanism of intercalation, which probably accounts for its reported antitumor activity.

Prostaglandin E2 production in astrocytes: regulation by cytokines, extracellular ATP, and oxidative agents.

Upregulation and activation of phospholipases A2 (PLA2) and cyclooxygenases (COX) leading to prostaglandin E2(PGE2) production have been implicated in a number of neurodegenerative diseases. In this study, we investigated PGE2 production in primary rat astrocytes in response to agents that activate PLA2 including pro-inflammatory cytokines (IL-1beta, TNFalpha and IFNgamma), the P2 nucleotide receptor agonist ATP, and oxidants (H2O2 and menadione). Exposure of astrocytes to cytokines resulted in a time-dependent increase in PGE2 production that was marked by increased expression of secretory sPLA2 and COX-2, but not COX-1 and cytosolic cPLA2. Although astrocytes responded to ATP or phorbol ester (PMA) with increased cPLA2 phosphorylation and arachidonic acid release, ATP or PMA only caused a small increase in levels of PGE2. However, when astrocytes were first treated with cytokines, further exposure to ATP or PMA, but not H2O2 or menadione, markedly increased PGE2 production. These results suggest that ATP release during neuronal excitation or injury can enhance the inflammatory effects of cytokines on PGE2 production and may contribute to chronic inflammation seen in Alzheimer's disease.

Occurrence of BCR-ABL rearrangement in a Philadelphia chromosome-negative patient with 5q and 13q deletions and myeloproliferative syndrome.

We report the case of a patient with a myeloproliferative syndrome and traits of myelodysplasia and myelofibrosis whose karyotype showed 5q and 13q deletions, as well as Philadelphia chromosome negativity. A molecular biology study performed by Southern blot, with a probe covering the M-bcr region, led to detection of three bands other than the germinal ones, which hints at the possible existence of two cut points in the M-bcr region of an allele, or participation of both alleles. The patient presented a complex hematological picture, which might be explained on the basis of the cytogenetic and molecular findings.