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El infradiagnóstico constituye un obstáculo para la eliminación de las hepatitis víricas. Las guías de práctica clínica (GPC) recomiendan realizar el cribado en pacientes con hipertransaminasemia. El objetivo del estudio fue evaluar la detección precoz de hepatitis víricasB yC implementada en nuestra área sanitaria en este grupo de población.

Human embryonic stem cell‐derived cardiomyocytes (hESC‐CMs) are at the center of new cell‐based therapies for cardiac disease, but may also serve as a useful in vitro model for cardiac cell development. An intriguing feature of hESC‐CMs is that although they express contractile proteins and have sarcomeres, they do not develop transverse‐tubules (T‐tubules) with adult‐like Ca2+release units (CRUs). We tested the hypothesis that expression of the protein BIN1 in hESC‐CMs promotes T‐tubules formation, facilitates CaV1.2 channel clustering along the tubules, and results in the development of stable CRUs. Using electrophysiology, [Ca2+]iimaging, and super resolution microscopy, we found that BIN1 expression induced T‐tubule development in hESC‐CMs, while increasing differentiation toward a more ventricular‐like phenotype. Voltage‐gated CaV1.2 channels clustered along the surface sarcolemma and T‐tubules of hESC‐CM. The length and width of the T‐tubules as well as the expression and size of CaV1.2 clusters grew, as BIN1 expression increased and cells matured. BIN1 expression increased CaV1.2 channel activity and the probability of coupled gating within channel clusters. Interestingly, BIN1 clusters also served as sites for sarcoplasmic reticulum (SR) anchoring and stabilization. Accordingly, BIN1‐expressing cells had more CaV1.2‐ryanodine receptor junctions than control cells. This was associated with larger [Ca2+]itransients during excitation–contraction coupling. Our data support the view that BIN1 is a key regulator of T‐tubule formation and CaV1.2 channel delivery. By studying the role of BIN1 during the differentiation of hESC‐CMs, we show that BIN1 is also important for CaV1.2 channel clustering, junctional SR organization, and the establishment of excitation–contraction coupling. Stem Cells2019;37:54–64 Although Human embryonic stem cell‐derived cardiomyocytes (hESC‐CM) express contractile proteins and have sarcomeres, they do not normally develop T‐tubules, which are specialized invaginations of the sarcolemma where CaV1.2 channels and ryanodine receptors (RyR) work together to release calcium. In this study, we evaluated the effect of BIN1 expression in the differentiation of hESC‐CM. BIN1 expression promotes the progressive formation of T‐tubules along hESC‐CMs differentiation and increases CaV1.2 channel clustering and activity. It also increases the formation of CaV1.2/RyR complexes and the synchronization of SR Ca2+release during excitation–contraction coupling.

Two polymorphisms in the murine double minute 2 (MDM2) gene (rs1690916 and rs2279744) have been associated with the risk of osteosarcoma (OS). When we analyzed these two polymorphisms in two new independents cohorts (Spanish and Slovenian), we found no association. In order to clarify this, we conducted a meta-analysis including six populations, with a total of 246 OS patients and 1,760 controls for rs1690916; and 433 OS patients and 1,959 controls for rs2279744. Pooled odds ratio risks and corresponding 95% CI were estimated to assess the possible associations. Our results showed that these two polymorphisms were not associated with the susceptibility of OS under any genetic model studied. In conclusion, the present meta-analysis indicates that MDM2 rs1690916 and rs2279744 cannot be considered as genetic risk factors for OS susceptibility in the different populations. Therefore, the influence of these two polymorphisms on the risk of OS may be less important than previously suggested. Future studies are needed to confirm these results.

The low-frequency (LF) noise behavior of Fully Depleted (FD) Ultrathin Buried Oxide (UTBOX) Silicon-on-Insulator (SOI) nMOSFETs is described from the perspective of the three major noise sources: 1/f-like or flicker noise, associated with carrier trapping/detrapping in the gate oxide; Generation-Recombination (GR) noise due to processing-induced defects in the thin silicon film and single-oxide-trap-related Random Telegraph Noise (RTN). It is shown that the fully depleted nature of the thin silicon films (<20 nm) offers the unique opportunity to study and demonstrate the front-back coupling of the 1/f noise. At the same time, a large variability is induced in the noise magnitude by the Lorentzian noise, related with GR events through defects in the silicon film. A method to discriminate oxide- from film-defects-related Lorentzian noise is pointed out. Finally, the implications for future fully depleted fin-type of devices will also be discussed.

Sexually transmitted disease (STD) remains a major public health challenge in developed countries, exacerbated by the advent of the HIV epidemic. The objectives of this study were to assess the prevalence of serological markers of syphilis, HIV‐1/2, HTLV‐I/II, HBV, and HCV infections among immigrant sex workers in Madrid, Spain and to characterize the HIV‐1 variants in seropositive individuals. Sera from 762 immigrant commercial sex workers (75.3% from sub‐Saharan Africa, 18.2% from South America, and 6.4% from Eastern Europe) were collected between 1998 and 2003 in Madrid and examined. Antibody detection was performed by screening assays (RPR, ELISAs) and confirmed by FTA‐Abs, LIAs and Western‐blot tests. HIV‐1 subtyping was carried out by phylogenetic analyses of the proteaseand envelopegenes. Antibodies to HIV‐1 were found in 5.2%, while 3.5% tested positive for HBsAg, 3% for syphilis antibodies, 0.8% for HCV antibodies, and 0.2% for HTLV‐I antibodies. None were reactive for HIV‐2 or HTLV‐II antibodies. HIV‐1 seroprevalence among Africans and Ecuadorians was 4.5 and 10.9%, respectively. All HIV‐1 seropositive Ecuadorians were transsexual men, and 28.6% had active syphilis infection. Up to 80% of HIV‐1 positive specimens were characterized as non‐B subtypes, with subtypes G, A, and G/A recombinants being the most frequent among African individuals. In contrast, South Americans with HIV‐1 infection carried exclusively subtype B variants. A relatively high proportion of immigrant sex workers in Madrid were infected with HIV‐1 and syphilis, whereas infections with hepatitis viruses or HTLV were uncommon. J. Med. Virol. 74:521–527, 2004. © 2004 Wiley‐Liss, Inc.

The dihydride-dichloro complex OsH2Cl2(PⁱPr3)2 (1) reacts with 4.0 equiv of HSnPh3 to afford 2.0 equiv of ClSnPh3 and the tetrahydride-bis(stannyl)-osmium(VI) derivative OsH4(SnPh3)2(PⁱPr3)2 (2), which has been characterized by X-ray diffraction analysis. DFT calculations in a model system of 2, in which the bulky ligands have been replaced by small models, followed by QM/MM optimizations with the real ligands have allowed the complete determination of the hydride positions and the role played by the steric effects on the experimental structure.

Complex OsH3(SnPh2Cl){η²-CH2&dbd;C(CH3)PⁱPr2}(PⁱPr3) (1) reacts with acetophenone and benzophenone to give OsH2(SnPh2Cl){C6H4C(O)R}(PⁱPr3)2 (R = CH3 (2), Ph (3)). In the solid state, the structure of 2 determined by X-ray diffraction analysis can be described as a pentagonal bipyramid with the phosphorus atoms of the phosphines occupying axial positions. In solution the hydride ligands of 2 and 3 undergo a thermally activated site exchange process. The activation parameters for the exchange are ΔH^&thermod; = 11.9 ± 0.5 kcal·mol^-1 and ΔS^&thermod; = −0.7 ± 1.2 cal·mol^-1·K^-1 for 2 and ΔH^&thermod; = 11.8 ± 0.2 kcal·mol^-1 and ΔS^&thermod; = −2.6 ± 1.9 cal·mol^-1·K^-1 for 3. The reaction of 1 with perdeuterated benzophenone affords the hydride-deuteride Os(H)(D)(SnPh2Cl){C6D4C(O)C6D5}(PⁱPr3)2 (3-d10), suggesting that the activation takes place on the monohydride intermediate OsH(SnPh2Cl)(PⁱPr3)2. The reaction pathway for the formation of this intermediate is evaluated by DFT calculations. Complex 1 also reacts with 2,3,4,5,6-pentafluorobenzophenone, 2-fluoroacetophenone, and benzophenone imine. The reactions with the partially fluorinated ketones give OsH2(SnPh2Cl){C6H4C(O)C6F5}(PⁱPr3)2 (4) and OsH2(SnPh2Cl){C6H3FC(O)CH3}(PⁱPr3)2 (5). In solution, the hydride ligands of 4 and 5 also exchange their positions. In this case, the activation parameters are ΔH^&thermod; = 12.6 ± 0.5 kcal·mol^-1 and ΔS^&thermod; = −2.9 ± 1 cal·mol^-1·K^-1 for 4 and ΔH^&thermod; = 11.2 ± 0.4 kcal·mol^-1 and ΔS^&thermod; = −2.8 ± 1.1 cal·mol^-1·K^-1 for 5. The reaction of 1 with benzophenone imine leads to OsH2(SnPh2Cl){C6H4C(NH)C6H5}(PⁱPr3)2 (6), which has been characterized by X-ray diffraction analysis. The structure reveals an intramolecular Cl···H−N hydrogen bond between the chlorine bonded to the tin atom and the hydrogen of the imine. Treatment of 6 with KOH affords OsH2(SnPh2OH){C6H4C(NH)C6H5}(PⁱPr3)2 (7). The X-ray diffraction analysis of 7 shows a intramolecular O···H−N hydrogen bond and intermolecular HO···H interactions between the oxygen and the O−H hydrogen atom of two adjacent molecules in the crystal. DFT calculations on the model compounds OsH2{Sn(CH&dbd;CH2)2Cl}{C6H4C(O)CH3}(PH3)2 (2t) and OsH2{Sn(CH&dbd;CH2)2X}{C6H4C(NH)CH3}(PH3)2 (X = Cl (6t), OH (7t)) have allowed the complete determination of the hydride positions in 2, 6, and 7 and the full characterization of the hydrogen bonds in 6 and 7.

Complex OsH2Cl2(PⁱPr3)2 (1) reacts with 2.0 equiv of HSnPh3 to give the tetrahydride-stannyl derivative OsH4Cl(SnPh3)(PⁱPr3)2 (2) and ClSnPh3. The structure of 2 has been determined by X-ray diffraction analysis. In the solid state and in solution at temperatures lower than 298 K, the coordination geometry around the osmium atom can be rationalized as derived from a distorted dodecahedron. In the presence of diphenylacetylene, complex 2 gives OsH3(SnClPh2){η²-CH2&dbd;C(CH3)PⁱPr2}(PⁱPr3) (3), cis-stilbene, and benzene. In the solid state, the structure of 3 determined by X-ray diffraction analysis can be described as a very distorted pentagonal bipyramid, with the phosphorus atom of the triisopropylphosphine ligand and the midpoint of the olefinic bond of the isopropenyl group of the dehydrogenated phosphine occupying axial positions. In solution, at temperatures higher than 233 K, the coordinated olefin is released. Complex 3 reacts with molecular hydrogen to afford the pentahydride OsH5(SnClPh2)(PⁱPr3)2 (4), as a result of the hydrogenation of the coordinated olefinic bond and the d⁴−d² oxidative addition of hydrogen. The structure of 4 in the solid state also has been determined by X-ray diffraction. The coordination geometry around the osmium atom can be rationalized as a distorted dodecahedron. In solution, complex 4 does not have a rigid structure even at 193 K. DFT calculations in model systems of 2, 3, and 4, in which the bulky ligands have been replaced by small models, followed by QM/MM optimizations with the real ligands have allowed the complete determination of the hydride positions and of the role played by steric effects in the experimental structures.

The complex [OsH2(κ²-O2CCH3)(H2O)(PⁱPr3)2]BF4 (1) reacts with aniline, pyridine, and trimethyl phosphite. The reaction with aniline affords the dihydride derivative [OsH2(κ²-O2CCH3)(NH2Ph)(PⁱPr3)2]BF4 (2), while in the presence of pyridine a 7:1 equilibrium mixture of the dihydride [OsH2(κ²-O2CCH3)(py)(PⁱPr3)2]BF4 (3a) and the elongated dihydrogen-containing complex [Os(η²-Η2)(κ²-O2CCH3)(py)(PⁱPr3)2]BF4 (3b) is obtained. The reaction with trimethyl phosphite leads to the elongated dihydrogen complex [Os(η²-H2)(κ²-O2CCH3){P(OMe)3}(PⁱPr3)2]BF4 (4). The structures of 2 and 4 have been determined by X-ray diffraction analysis.

Lung diseases that are frequently seen in young people, such as bronchial asthma, pneumonia, and tuberculosis, occur with comparable prevalence in pregnant women. Their treatments do not greatly differ from those used in the nonpregnant state. However, pharmacokinetics of these drugs undergo changes due to the physiologic variations induced by pregnancy that we must consider. On the other hand, some drugs used for lung disease have a teratogenic potential and thus carry a risk for the fetus. In this article, we review the drugs most commonly used for the treatment of respiratory diseases in pregnancy and lactation and discuss the current data of their possible effects on the fetus and neonate. Asthma is the most common potentially serious medical disease complicating pregnancy and should be treated as aggressively in pregnant women as in nonpregnant women, because the perceived risk to the fetus caused by pharmacologic therapy is much less than the risk of uncontrolled asthma and the resulting hypoxia. Antepartum pneumonia and tuberculosis require prompt evaluation and empiric antimicrobial therapy. The clinician must choose antimicrobial agents considering efficacy as well as safety for both mother and fetus. Among the agents for antithrombotic therapy, heparin is the anticoagulant of choice during pregnancy. Data on the use of low molecular weight heparins are encouraging, but clinical experience with these agents is still limited. Oral anticoagulant therapy should be avoided because of its teratogenic potential and increased risk of fetal complications, and the use of thrombolytic agents must be limited to life-threatening situations.

We report the case of a woman, with a 15-year history of high-dosage oral contraceptive use, who came to our center for a gynecological screening. Elevated liver enzymes were detected in blood samples and an abdominal ultrasound showed a hypoechogenic nodular image of 8 cm in the right hepatic lobe of the liver. Routine examinations, including hepatitis B surface antigen, hepatitis C viral antibody and α-fetoprotein, were all negative. Imaging studies, including computerized tomography scan, magnetic resonance imaging, sulfur colloid gammagraphy and hepatic angiography, were performed and confirmed the presence of the lesion, detecting the characteristic central scar structure of focal nodular hyperplasia. Discontinuation of oral contraceptives and follow-up showed no change in lesion size so that a surgical approach was adopted in order to remove the hepatocellular carcinoma. Pathological findings confirmed focal nodular hyperplasia.

The dihydride−osmium(IV) complex [OsH2(κ²-O2CCH3)(H2O)(PⁱPr3)2]BF4 (1) reacts with acetylene (1 atm) at 0 °C to give polyacetylene and the vinyl−carbyne derivative [Os(CH&dbd;CH2)(κ²-O2CCH3)(&tbd1;CCH3)(PⁱPr3)2]BF4 (2). Both polyacetylene and 2 can also be obtained by reaction of [OsH(κ²-O2CCH3)(&tbd1;CCH3)(PⁱPr3)2]BF4 (3) with acetylene. Under an acetylene atmosphere, complex 2 yields polyacetylene in a slow but constant manner. Complex 2 reacts with carbon monoxide to give initially the carbene derivative [Os(κ²-O2CCH3){&dbd;C(CH&dbd;CH2)CH3}(CO)(PⁱPr3)2]BF4 (4), by migratory insertion of the carbyne ligand of 2 into the Os−vinyl bond. Under a carbon monoxide atmosphere, complex 2 is unstable and evolves into [Os(κ²-O2CCH3)(CO)2(PⁱPr3)2]BF4 (5). Treatment of 2 with KOH in methanol produces the deprotonation of the carbyne ligand and the formation of the vinyl−vinylidene derivative Os(CH&dbd;CH2)(κ²-O2CCH3)(&dbd;C&dbd;CH2)(PⁱPr3)2 (6), which reacts with carbon monoxide to give the butadienyl compound Os{C(CH&dbd;CH2)&dbd;CH2}{κ¹-OC(O)CH3}(CO)2(PⁱPr3)2 (7) by migratory insertion of the vinylidene ligand into the Os−vinyl bond. The structure of 7 has been determined by X-ray diffraction analysis. The geometry around the osmium atom can be rationalized as a distorted octahedron with the phosphine ligands occupying opposite positions. The remaining perpendicular plane is formed by the butadienyl ligand, the acetate, and the carbonyl groups mutually cis disposed. The Os−butadienyl distance is 2.195(5) Å, whereas the torsion angle in the diene is 50.7(8)°. The butadienyl ligand of 7 acts as a diene in Diels−Alder reactions. Thus, the addition of dimethyl acetylenedicarboxylate and maleic anhydride to benzene solutions of 7 affords the corresponding cycloaddition products Os{C&dbd;CHCH2C(CO2Me)&dbd;C(CO2Me)CH2{κ¹-OC(O)CH3}(CO)2(PⁱPr3)2 (8) and Os{C&dbd;CHCH2CH[C(O)OC(O)]CHCH2}{κ¹-OC(O)CH3}(CO)2(PⁱPr3)2 (9). Treatment of 8 with HBF4·OEt2 gives 5 and dimethyl 1,4-cyclohexadiene-1,2-dicarboxylate.

Reaction of OsH2(κ²-OCOCH3){κ¹-OC(O)CH3}(PⁱPr3)2 (1) with 1/2HBF4·OEt2 leads to the dimer [{OsH2(κ²-OCOCH3)(PⁱPr3)2}2(μ-OCOCH3)]BF4 (2), while the reaction with HBF4·OH2 gives the aquo-derivative [OsH2(κ²-OCOCH3)(H2O)(PⁱPr3)2]BF4 (3). The structure of 2 in the solid state has been determined by an X-ray diffraction study. The structure consists of two OsH2(κ²-OCOCH3)(PⁱPr3)2 units connected through an acetate bridge. Complex 3 reacts with phenylacetylene and 1,1-diphenyl-2-propyn-1-ol to give the metallacyclopropene complexes [OsH(κ²-OCOCH3){C(Ph)CH2}(PⁱPr3)2]BF4 (4) and OsH(κ²-OCOCH3){C[C(OH)Ph2]CH2}(PⁱPr3)2]BF4 (7), respectively. The structure of 4 in the solid state has been determined by an X-ray diffraction study. The geometry around the metal center can best be described as a pentagonal bipyramid with the two phosphorus atoms of the phosphines occupying apical positions. The equatorial plane is defined by the hydride, the acetate ligand, and the two carbon atoms of the metallacyclopropene. Reaction of 3 with tert-butylacetylene or trimethylsilylacetylene affords the carbyne complexes [OsH(κ²-OCOCH3)(&tbd1;CCH2R)(PⁱPr3)2]BF4 [R = CMe3 (8), H (9)], respectively. Deprotonation of 8 and 9 with KOH gives the vinylidene derivatives OsH(κ²-OCOCH3)(&dbd;C&dbd;CHR)(PⁱPr3)2 [R = CMe3 (10), H (11)]. The carbyne analogue of 8 and 9 bearing a phenyl group, [OsH(κ²-OCOCH3)(&tbd1;CCH2Ph)(PⁱPr3)2]BF4 (5), can be obtained upon protonation of OsH(κ²-OCOCH3)(&dbd;C&dbd;CHPh)(PⁱPr3)2 (6) with HBF4·OEt2. In agreement with the experimental results, DFT (B3PW91) calculations show that the cyclopropene product is thermodynamically preferred for phenylacetylene, while the carbyne isomer is preferred for tert-butylacetylene.

The hydrido−carbyne complex OsHCl2(&tbd1;CCH2Ph)(PⁱPr3)2 (1) reacts with pyrazole in the presence of KOH to afford the six-coordinate hydrido−vinylidene OsH(pz)(&dbd;C&dbd;CHPh)(Hpz)(PⁱPr3)2 (2). The structure of 2 in the solid state has been determined by an X-ray diffraction study. The geometry around the metal center could be described as a distorted octahedron with the two phosphorus atoms of the phosphines occupying apical positions. The equatorial plane is defined by the hydride, the vinylidene, the pyrazole, and the pyrazolato ligands. The N−H hydrogen atom of the pyrazole lies between this azole group and the pyrazolate, forming an intramolecular N···H···N hydrogen bond. Reaction of 2 with HBF4 leads to the fluoro−carbyne derivative [OsHF(&tbd1;CCH2Ph)(Hpz)(PⁱPr3)2]BF4 (3), whose structure has been determined by an X-ray diffraction study. The geometry around the metal center could be also described as a distorted octahedron with the two phosphorus atoms of the phosphines occupying apical positions. The equatorial plane is defined by the hydride, the carbyne, the pyrazole group, and the fluoride ligand. The X-ray structure analysis of 3 shows that the N−H hydrogen atom of the pyrazole and the fluoride ligand are involved in intra- and intermolecular F···H−pz hydrogen bonding. Reaction of [OsHCl(&tbd1;CCH2Ph)(H2O)(PⁱPr3)2]BF4 (4) with pyrazole and acetonitrile leads to [OsHCl(&tbd1;CCH2Ph)(Hpz)(PⁱPr3)2]BF4 (5) and [OsHCl(&tbd1;CCH2Ph)(CH3CN)(PⁱPr3)2]BF4 (6), respectively. Similarly to the fluoro−carbyne complex, the N−H hydrogen atom of the pyrazole group and the chloro ligand of complex 5 are involved in hydrogen bonding.