Publications by authors named "Ana M López"

54 Publications

Quadratus lumborum block: an imaging study of three approaches.

Reg Anesth Pain Med 2021 Jan 6;46(1):35-40. Epub 2020 Nov 6.

Anesthesiology, Clinique Sainte-Anne Saint-Remi, Brussels, Belgium

Background And Objectives: Different injection techniques for the quadratus lumborum (QL) block have been described. Data in human cadavers suggest that the transverse oblique paramedian (TOP) QL3 may reach the thoracic paravertebral space more consistently than the QL1 and QL2. However, the distribution of injectate in cadavers may differ from that in patients. Hence, we assessed the distribution of the injectate after the QL1, QL2, and TOP QL3 techniques in patients.

Materials And Methods: Thirty-four patients scheduled for abdominal surgery received QL blocks postoperatively; 26 patients received bilateral and 8 patients received unilateral blocks. Block injections were randomly allocated to QL1, QL2, or TOP QL3 techniques (20 blocks per each technique). The injections consisted of 18 mL of ropivacaine 0.375% with 2 mL of radiopaque contrast, injected lateral or posterior to the QL muscle for the QL1 and QL2 techniques, respectively. For the TOP QL3, the injection was into the plane between the QL and psoas muscles, proximal to the L2 transverse process. Two reviewers, blinded to the allocation, reviewed three-dimensional computed tomography (3D-CT) images to assess the distribution of injectate.

Results And Discussion: The QL1 block spread in the transversus abdominis plane (TAP), QL2 in the TAP, posterior aspect of the QL muscle, whereas TOP QL3 spread consistently in the anterior aspect of the QL muscle occasional spread to the lumbar and thoracic paravertebral areas.

Conclusions: The spread of injectate after QL1, QL2, and QL3 blocks, resulted in different distribution patterns, primarily in the area of injection. The TOP QL3 did not result in consistent interfascial spread toward the thoracic paravertebral space.
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http://dx.doi.org/10.1136/rapm-2020-101554DOI Listing
January 2021

Insertion of Unsaturated C-C Bonds into the O-H Bond of an Iridium(III)-Hydroxo Complex: Formation of Phosphorescent Emitters with an Asymmetrical β-Diketonate Ligand.

Inorg Chem 2020 Nov 15;59(21):15877-15887. Epub 2020 Oct 15.

Universal Display Corporation, Ewing, New Jersey 08618, United States.

A synthetic methodology to prepare iridium(III) emitters of the class [3b+3b+3b'] with two -metalated 1-phenylisoquinolines and an asymmetrical β-diketonate has been discovered. The abstraction of the chloride ligands of the dimer [Ir(μ-Cl){κ-,-(CH-isoqui)}] (, CH-isoqui = 1-phenylisoquinoline) with AgBF in acetone and the subsequent addition of water to the resulting solution affords the water solvate mononuclear complex [Ir{κ-,-(CH-isoqui)}(HO)]BF (), which reacts with KOH to give the dihydroxo-bridged dimer [Ir(μ-OH){κ-,-(CH-isoqui)}] (). Treatment of the latter with dimethyl acetylenedicarboxylate leads to Ir{κ-,-(CH-isoqui)}{κ-,-[OC(COCH)CHC(OCH)O]} (), as a result of the -addition of the O-H bond of a mononuclear [Ir(OH){κ-,-(CH-isoqui)}] fragment to the C-C triple bond of the alkyne and the coordination of one of the carboxylate substituents to the metal center. Complex also reacts with α,β-unsaturated ketones. The reaction with 3-(4-methylphenyl)-1-phenylprop-2-en-1-one affords Ir{κ-,-(CH-isoqui)}{κ-,-[OC(CH)CHC(-CHMe)O]} (), whereas methyl vinyl ketone gives a mixture of Ir{κ-,-(CH-isoqui)}{κ-,-[OC(CH)CHCHO]} () and Ir{κ-,-(CH-isoqui)}{κ-,-[OC(CH)CHC(CH═CH)O]} (). Complexes and are the result of the addition of the O-H bond of the mononuclear [Ir(OH){κ-,-(CH-isoqui)}] fragment to the C-C double bond of the α,β-unsaturated ketones and the coordination of the carbonyl group to the iridium center, to generate ,-chelates which lose molecular hydrogen to aromatize into the asymmetrical β-diketonate ligands. Complexes - are phosphorescent emitters in the red spectral region (599-672 nm) in doped poly(methyl methacrylate) (PMMA) film at 5 wt % at room temperature and 2-methyltetrahydrofuran at room temperature and 77 K. They display short lifetimes (0.8-2.5 μs) and quantum yields in both doped PMMA films and in 2-methyltetrahydrofuran at room temperature depending on the substituents of the β-diketonate: about 0.6-0.5 for and and ca. 0.35 for and .
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http://dx.doi.org/10.1021/acs.inorgchem.0c02395DOI Listing
November 2020

Phosphorescent Iridium(III) Complexes with a Dianionic C,C',N,N'-Tetradentate Ligand.

Inorg Chem 2020 Sep 28;59(17):12286-12294. Epub 2020 Aug 28.

Universal Display Corporation, Ewing, New Jersey 08618, United States.

To prepare new phosphorescent iridium(III) emitters, 2-phenyl-6-(1-phenyl-1-(pyridin-2-yl)ethyl)pyridine (HL) has been designed and its reactions with [Ir(μ-Cl)(η-COD)] (, COD = 1,5-cyclooctadiene) have been studied. The products obtained depend on the refluxing temperature of the solvent. Thus, complexes Ir(κ-'-L)Cl(CO) (), [Ir(η-COD)(κ-HL)][IrCl(η-COD)] (), and [Ir(μ-Cl)(κL)] () have been formed in 2-ethoxyethanol, propan-2-ol, and 1-phenylethanol, respectively. Complex reacts with K(acac) to give the acetylacetonate derivative Ir(κL)(acac) (). Complexes and are efficient blue-green and green emitters of classes [6tt+1m+2m] and [6tt+3b], respectively. They display lifetimes in the range of 1.1-4.5 μs and high quantum yields (0.54-0.87) in both PMMA films and 2-MeTHF at room temperature.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01377DOI Listing
September 2020

The red fox (Vulpes vulpes) as a potential natural reservoir of human cryptosporidiosis by Cryptosporidium hominis in Northwest Spain.

Transbound Emerg Dis 2020 Apr 17. Epub 2020 Apr 17.

Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.

Giardia duodenalis and Cryptosporidium spp. are ubiquitous intestinal protozoa that parasitize domestic and wild animals, as well as human beings. Due to their zoonotic potential, the objective of the present study was to determine the presence of these pathogens in the fox population (Vulpes vulpes) located in Northwest Spain. A total of 197 faecal samples from legally hunted foxes were collected in the autonomous region of Galicia. The presence of G. duodenalis and Cryptosporidium spp. was investigated by PCR-based methods amplifying the small subunit ribosomal RNA (ssu rRNA) gene of the parasites. Attempts to genotype obtained positive samples were subsequently conducted at the glutamate dehydrogenase (gdh) and β-giardin (bg) genes of G. duodenalis, and the 60 kDa glycoprotein (gp60) gene of Cryptosporidium. Giardia duodenalis and Cryptosporidium spp. were identified in 19 (9.6%) and 12 (6.1%) of the investigated samples, respectively. However, five Cryptosporidium species were detected at the ssu rRNA locus: C. hominis (33.4%, 4/12), C. canis (25.0%, 3/12), C. parvum (16.7%, 2/12), C. ubiquitum (8.3%, 1/12) and C. suis (8.3%, 1/12). An additional Cryptosporidium-positive sample was identified at the genus level only. Typing and subtyping of Giardia- and Cryptosporidium-positive samples were unsuccessful. The detection of C. hominis in wild foxes indicates the probable overlapping of sylvatic and domestic cycles of this parasite in rural settings. Besides, this finding raises the question of whether red foxes may act as natural reservoirs of C. hominis. The detection of C. parvum and C. suis is suggestive of active transmission events between farm and wild animals, opening up the possibility of transmission to human beings.
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http://dx.doi.org/10.1111/tbed.13569DOI Listing
April 2020

Comparison of the effectiveness of circumferential versus non-circumferential spread in median and ulnar nerve blocks. A double-blind randomized clinical trial.

Reg Anesth Pain Med 2020 05 11;45(5):362-366. Epub 2020 Mar 11.

Anesthesiology, Hospital Clinic de Barcelona, Barcelona, Catalunya, Spain.

Background And Objectives: Circumferential (C) spread of local anesthetic around the nerve is recommended for a successful nerve block. We tested the hypothesis that C spread produces a more complete block than non-circumferential (NC) spread.

Methods: We randomized 124 patients undergoing open carpal tunnel syndrome surgery to receive C or NC spread ultrasound-guided median and ulnar nerve blocks. The primary outcome was the proportion of patients who developed complete sensory block measured at 5, 15 and 30 min. The loss of cold sensation was graded as: 0 (complete block), 1 (incomplete block), or 2 (no block). Secondary outcomes included motor block, nerve swelling and adverse events.

Results: In group C, complete sensory block at 5 min was 2.4 (95% CI 1.0 to 5.7; p=0.04) times more frequent in the median nerve and 3.0 (95% CI 1.2 to 7.2; p=0.01) times more frequent in the ulnar nerve compared with group C. However, at 15 and 30 min, it was similar between groups. Complete motor block was more frequent in group C than in group NC for both the median nerve: 1.5 (95% CI 1.1 to 2.2; p<0.01) at 15 min, 1.1 (95% CI 1.0 to 1.2; p=0.02) at 30 min, and the ulnar nerve: 1.7 (95% CI 1.2 to 2.6; p<0.01) at 15 min, 1.2 (95% CI 1.0 to 1.4; p<0.01) at 30 min. The incidence of nerve swelling and adverse effects was similar between groups.

Conclusions: C spread around the median and ulnar nerves at the level of the antecubital fossa generates more complete sensory and motor blocks compared with NC spread.

Trial Registration Number: EudraCT 2011-002608-34 and NCT01603680.
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http://dx.doi.org/10.1136/rapm-2019-101157DOI Listing
May 2020

Preparation and Photophysical Properties of (tridentate) Iridium(III) Emitters: Pincer Coordination of 2,6-Di(2-pyridyl)phenyl.

Inorg Chem 2020 Mar 2;59(6):3838-3849. Epub 2020 Mar 2.

Universal Display Corporation, 375 Phillips Boulevard, Ewing, New Jersey 08618, United States.

The way to prepare molecular emitters [5t + 4t'] of iridium(III) with a 5t ligand derived from the abstraction of the hydrogen atom at position 2 of the aryl group of 1,3-di(2-pyridyl)benzene (dpybH) is shown. In addition, the photophysical properties of the new emitters are compared with those of their counterparts resulting from the deprotonation of 1,3-di(2-pyridyl)-4,6-dimethylbenzene (dpyMebH), at the same position, which are also synthesized. Treatment of 0.5 equiv of the dimer [Ir(μ-Cl)(η-COE)] (COE = cyclooctene) with 1.0 equiv of Hg(dpyb)Cl leads to the iridium(III) derivative IrCl{κ-,,-(dpyb)}(η-COE) (), which reacts with 2-(1-imidazol-2-yl)-6-phenylpyridine (HNImpyCH) and 2-(1-benzimidazol-2-yl)-6-phenylpyridine (HNBzimpyCH) in the presence of NaCO to give Ir{κ-,,-(NImpyCH)}{κ-,,-(dpyb)} () and Ir{κ-,,-(NBzimpyCH)}{κ-,,-(dpyb)} (), respectively. Similar reactions of the Williams's dimer [IrCl(μ-Cl){κ-,,-(dpyMeb)}] with HNImpyCH and HNBzimpyCH in the presence of NaCO afford the dimethylated counterparts Ir{κ-,,-(NImpyCH)}{κ-,,-(dpyMeb)} () and Ir{κ-,,-(NBzimpyCH)}{κ-,,-(dpyMeb)} (), whereas 2-(6-phenylpyridine-2-yl)-1-indole (HIndpyCH) initially gives IrH{κ-,-(IndpyCH)}{κ-,,-(dpyMeb)} () and subsequently Ir{κ-,,-(IndpyCH)}{κ-,,-(dpyMeb)} (). Complexes - are phosphorescent green emitters (λ 490-550 nm), whereas is greenish yellow emissive (λ 547-624 nm). They display lifetimes in the range 0.5-9.7 μs and quantum yields in both doped poly(methyl)methacrylate films and in 2-methyltetrahydrofuran at room temperature depending upon the ligands: 0.5-0.7 for and , about 0.4 for and , and 0.3-0.2 for .
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http://dx.doi.org/10.1021/acs.inorgchem.9b03509DOI Listing
March 2020

Reduction of Benzonitriles via Osmium-Azavinylidene Intermediates Bearing Nucleophilic and Electrophilic Centers.

Inorg Chem 2019 Jul 19;58(13):8673-8684. Epub 2019 Jun 19.

Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), Centro de Innovación en Química Avanzada (ORFEO-CINQA) , Universidad de Zaragoza-CSIC , 50009 Zaragoza , Spain.

The reduction of the N≡C bond of benzonitriles promoted by OsH(PPr) (1) has been studied. Complex 1 releases a H molecule and coordinates 2,6-dimethylbenzonitrile to afford the tetrahydride OsH{κ- N-(N≡CCHMe)}(PPr) (2), which is thermally stable toward the insertion of the nitrile into one of the Os-H bonds. In contrast to 2,6-dimethylbenzonitrile, benzonitrile and 2-methylbenzonitrile undergo insertion, via Os(η-N≡CR) intermediates, to give the azavinylidene derivatives OsH(═N═CCHR)(PPr) [R = H (3) or Me (4)]. The analysis by means of computational tools (EDA-NOCV) of the bonding situation in these compounds suggests that the donor-acceptor nature of the osmium azavinylidene bond dominates over the mixed electron-sharing/donor-acceptor and pure electron-sharing bonding modes. The N atom is strongly nucleophilic, whereas one of the hydrides is electrophilic. In spite of the different nature of these centers, the migration of the latter to the N atom is kinetically prevented. However, the use of water as a proton shuttle allows hydride migration, as a consequence of a significant decrease in the activation barrier. The resulting phenylaldimine intermediates evolve by means of orthometalation to give OsH{κ- N, C-(NH═CHCHR)}(PPr) [R = H (5) or Me (6)]. The presence of electrophilic and nucleophilic centers in 3 confers upon it the ability to activate σ-bonds, including H and pinacolborane (HBpin). The reaction with the latter gives OsH{κ- N, C-[N(Bpin)═CHCH]}(PPr) (7).
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http://dx.doi.org/10.1021/acs.inorgchem.9b01013DOI Listing
July 2019

Early versus late wake therapy improves mood more in antepartum versus postpartum depression by differentially altering melatonin-sleep timing disturbances.

J Affect Disord 2019 02 5;245:608-616. Epub 2018 Nov 5.

Department of Psychiatry, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0804, United States.

Background: Peripartum major depression (MD) disables mothers and impairs emotional and neurocognitive development of offspring. We tested the hypothesis that critically-timed wake therapy (WT) relieves peripartum MD by altering melatonin and sleep timing, differentially, in antepartum vs. postpartum depressed patients (DP).

Methods: In a university clinical research center, we initially randomized 50 women - 26 antepartum (17 healthy comparison-HC, 9 DP) and 24 postpartum (8 HC, 16 DP) - to a cross-over trial of one night of early-night wake therapy (EWT: sleep 3:00-7:00 am) vs. late-night wake therapy (LWT: sleep 9:00 pm-01:00 am). Ultimately, we obtained mood, overnight plasma melatonin and polysomnography for: 15 antepartum women receiving EWT, 18 receiving LWT; 15 postpartum women receiving EWT, 14 receiving LWT.

Results: EWT improved mood more in antepartum vs. postpartum DP in conjunction with reduced (normalized) melatonin-sleep phase-angle differences (PADs) due to delayed melatonin onsets and advanced sleep onsets, and increased (from baseline) total sleep times (TST). LWT improved mood more in postpartum vs. antepartum DP in conjunction with increased TST.

Limitations: Small samples potentially rendered the study underpowered to detect group differences, making confirmation with larger samples essential. Sufficient follow-up data were not available in most women to document the duration of the mood response to wake therapy.

Conclusions: EWT benefitted antepartum DP more by realigning melatonin and sleep timing, whereas LWT benefitted postpartum DP more by increasing TST. Thus, consistent with precision medicine aims, maximum mood benefits accrue from timing sleep/wake interventions to specific peripartum circadian pathophysiologies.
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http://dx.doi.org/10.1016/j.jad.2018.11.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351205PMC
February 2019

Preparation of Tris-Heteroleptic Iridium(III) Complexes Containing a Cyclometalated Aryl-N-Heterocyclic Carbene Ligand.

Inorg Chem 2018 Sep 23;57(17):10744-10760. Epub 2018 Aug 23.

Universal Display Corporation , 375 Phillips Boulevard , Ewing , New Jersey 08618 , United States.

A new class of phosphorescent tris-heteroleptic iridium(III) complexes has been discovered. The addition of PhMeImAgI (PhMeIm = 1-phenyl-3-methylimidazolylidene) to the dimer [Ir(μ-Cl)(COD)] (1; COD = 1,5-cyclooctadiene) affords IrCl(COD)(PhMeIm) (2), which reacts with 1-phenylisoquinoline, 2-phenylpyridine, and 2-(2,4-difluorophenyl)pyridine to give the respective dimers [Ir(μ-Cl){κ- C, C-(CH-ImMe)}{κ- C, N-(CH-isoqui)}] (3), [Ir(μ-Cl){κ- C, C-(CH-ImMe)}{κ- C, N-(CH-py)}] (4), and [Ir(μ-Cl){κ- C, C-(CH-ImMe)}{κ- C, N-(CFH-py)}] (5), as a result of the N-heterocyclic carbene (NHC)- and N-heterocycle-supported o-CH bond activation of the aryl substituents and the hydrogenation of a C-C double bond of the coordinated diene. In solution, these dimers exist as a mixture of isomers a (Im trans to N) and b (Im trans to Cl), which lie in a dynamic equilibrium. The treatment of 3-5 with Kacac (acac = acetylacetonate) yields isomers a (Im trans to N) and b (Im trans to O) of Ir{κ- C, C-(CH-ImMe)}{κ- C, N-(CH-isoqui)}(κ- O, O-acac) (6a and 6b), Ir{κ- C, C-(CH-ImMe)}{κ- C, N-(CH-py)}(κ- O, O-acac) (7a and 7b), and Ir{κ- C, C-(CH-ImMe)}{κ- C, N-(CFH-py)}(κ- O, O-acac) (8a and 8b), which were separated by column chromatography. The treatment of 6a with HX in acetone-water produces the protonation of the acac ligand and the formation of the bis(aquo) complex [Ir{κ- C, C-(CH-ImMe)}{κ- C, N-(CH-isoqui)}(HO)]X [X = BF (9a[BF]), OTf (9a[OTf])]. The salt 9a[BF] reacts with 2-(2-pinacolborylphenyl)-5-methylpyridine in the presence of 40 equiv of KPO to afford Ir{κ- C, C-(CH-ImMe)}{κ- C, N-(CH-isoqui)}{κ- C, N-(CH-Mepy)} (10a). Complexes 6a, 6b, 7a, 7b, 8a, 8b, and 10a are phosphorescent emitters (λ = 465-655 nm), which display short lifetimes in the range of 0.2-5.6 μs. They show high quantum yields both in doped poly(methyl methacrylate) films (0.34-0.87) and in 2-methyltetrahydrofuran at room temperature (0.40-0.93). From the point of view of their applicability to the fabrication of organic-light-emitting-diode devices, a notable improvement with regard to those containing two cyclometalated C,N ligands is achieved. The introduction of the cyclometalated aryl-NHC group allows one to reach a brightness of 1000 cd/m at a lower voltage and appears to give rise to higher luminous efficacy and power efficacy.
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http://dx.doi.org/10.1021/acs.inorgchem.8b01367DOI Listing
September 2018

Evidence for a Bis(Elongated σ)-Dihydrideborate Coordinated to Osmium.

Inorg Chem 2018 Apr 2;57(8):4482-4491. Epub 2018 Apr 2.

Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), Centro de Innovación en Química Avanzada (ORFEO-CINQA) , Universidad de Zaragoza-CSIC , 50009 Zaragoza , Spain.

The formation and Atoms in Molecules (AIM) analysis of osmium(IV) and osmium(II) complexes containing dihydrideborate groups and primary aminoborane ligands are reported. Complex OsH(P Pr) (1) loses a hydrogen molecule and the resulting unsaturated OsH(P Pr) species coordinates 9-borabicycle[3.3.1]nonane (HBbn) and pinacolborane (HBpin) to give the dihydrideborate derivatives OsH{κ- H, H-(HBR)}(P Pr) (BR = Bbn (2), Bpin (3)). The bonding situation in these compounds and in the related osmium(II) derivative Os(Bcat){κ- H, H-(HBcat)}(CO)(P Pr) (4) (HBcat = catecholborane) has been analyzed by the AIM method. The Laplacian distributions in the Os-H-B plane exhibit a four-membered cyclic topology possessing two Os-H and two B-H bond critical points associated with one OsHHB ring critical point, which resembles that found for BH. The tetrahydride OsH(P Pr) also coordinates catecholborane, which initially affords OsH{κ- H, H-(HBcat)}(P Pr) (5). In contrast to 2 and 3, complex 5 reacts with a second molecule of HBcat to give the elongated σ-borane-{bis(elongated σ) -dihydrideborate}-osmium(II) derivative OsH(η-HBcat)(η-HBcat)(P Pr) (6). Complexes 5 and 6 have been also analyzed via the AIM method. Complex 5 displays the same topology as complexes 2-4. However, the OsHB unit of 6 shows, besides the Os-H and B-H bond critical points, an additional Os-B bond critical point, which is associated with a bond path running between these atoms. This double triangular topology is completed with the respective ring critical points. Reactions of 1 with dimethylamine-borane (HB·NHMe) and tert-butylamine-borane (HB·NHBu) give OsH(η:η-HBNR)(P Pr) (NR = NMe (7), NH Bu (8)). The AIM analyses of 7 and 8 also reveal the occurrence of an Os-B bond critical point associated with a bond path running between those atoms. However, neither Os-H bond critical points nor bond paths are observed in the latter species.
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http://dx.doi.org/10.1021/acs.inorgchem.8b00155DOI Listing
April 2018

Preparation of Phosphorescent Iridium(III) Complexes with a Dianionic C,C,C,C-Tetradentate Ligand.

Inorg Chem 2018 Apr 14;57(7):3720-3730. Epub 2018 Mar 14.

Universal Display Corporation , 375 Phillips Boulevard , Ewing , New Jersey 08618 , United States.

The preparation and photophysical properties of heteroleptic iridium(III) complexes containing a dianionic C,C,C,C-tetradentate ligand and a cyclometalated phenylpyridine group are described. Complex [Ir(μ-OMe)(COD)] (1, COD = 1,5-cyclooctadiene) reacts with 1,1-diphenyl-3,3-butylenediimidazolium iodide ([PhIm(CH)ImPh]I), in the presence NaOBu, to give [Ir(μ-I){κ- C, C, C, C-[CHIm(CH)ImCH]}] (2), which leads to {[Ir{κ- C, C, C, C-[CHIm(CH)ImCH]}](μ-OH)(μ-OMe)} (3) by treatment first with silver trifluoromethanesulfonate (AgOTf) in acetone-dichloromethane and subsequently with KOH in methanol. The reaction of 2 with AgOTf and acetonitrile affords the bis(solvento) complex [Ir{κ- C, C, C, C-[CHIm(CH)ImCH]}(CHCN)]OTf (4). The latter promotes the pyridyl-supported heterolytic ortho-CH bond activation of the phenyl group of 2-phenylpyridine, 2-(2,4-difluorophenyl)pyridine, 2-( p-tolyl)pyridine, and 5-methyl-2-phenylpyridine to yield Ir{κ- C, C, C, C-[CHIm(CH)ImCH]}{κ- C, N-[Ar-py]} (Ar-py = CH-py (5), CHF-py (6), CHMe-py (7), CH-Mepy (8)) using (piperidinomethyl)polystyrene as an external base. Complexes 5-8 are blue-green emitters, which display short lifetimes (0.6-4.8 μs) and quantum yields close to unity in both doped poly(methyl methacrylate) films at 5 wt % and in 2-methyltetrahydrofuran at room temperature.
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http://dx.doi.org/10.1021/acs.inorgchem.7b02993DOI Listing
April 2018

η -Arene Complexes as Intermediates in the Preparation of Molecular Phosphorescent Iridium(III) Complexes.

Chemistry 2017 Nov 16;23(62):15729-15737. Epub 2017 Oct 16.

Universal Display Corporation, 375 Phillips Boulevard, Ewing, New Jersey, 08618, USA.

Molecular phosphorescent heteroleptic bis-tridentate iridium(III) emitters have been prepared via η -arene intermediates. In the presence of 4.0 mol of AgOTf, the complex [(IrCl{κ -N,C,N-(pyC HMe py)})(μ-Cl)] (1; pyC H Me py=1,3-di(2-pyridyl)-4,6-dimethylbenzene) reacted with 9-(6-phenylpyridin-2-yl)-9H-carbazole (PhpyCzH) and 2-phenoxy-6-phenylpyridine (PhpyOPh) to give [Ir{κ -N,C,N-(pyC HMe py)}{κ -C,N,C'-(C H pyCzH)}]OTf (2) and [Ir{κ -N,C,N-(pyC HMe py)}{κ -C,N,C'-(C H pyOPh)}]OTf (3). The X-ray diffraction structures of 2 and 3 reveal that the carbazolyl and phenoxy substituents of the C,N,C' ligand coordinate to the metal center to form an η -arene π bond. Treatment of 2 and 3 with KOtBu led to the deprotonation of the coordinated carbon atom of the η -arene group to afford the molecular phosphorescent [5t+4t'] heteroleptic iridium(III) complexes [Ir{κ -N,C,N-(pyC HMe py)}{κ -C,N,C'-(C H pyCz)}] (4) and [Ir{κ -N,C,N-(pyC HMe py)}{κ -C,N,C'-(C H pyOC H )}] (5). These complexes are green emitters that display short lifetimes and high quantum yields of 0.73 (4) and 0.87 (5) in the solid state.
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http://dx.doi.org/10.1002/chem.201703252DOI Listing
November 2017

A randomized comparison of the Ambu AuraGain versus the LMA supreme in patients undergoing gynaecologic laparoscopic surgery.

J Clin Monit Comput 2017 Dec 26;31(6):1255-1262. Epub 2016 Nov 26.

Department of Anesthesiology, Hospital Clinic de Barcelona, Faculty of Medicine, Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain.

Second generation supraglottic airway devices providing high seal airway pressures are suitable for patients undergoing gynecologic laparoscopy. We compared the seal pressure achieved by the new Ambu AuraGain™ versus LMA Supreme™ following pneumoperitoneum in the Trendelenburg position. Sixty female patients were randomly allocated to ventilation with either the AuraGain or the Supreme. A target-controlled system was used to administer total intravenous anesthesia. Intracuff pressure was maintained below 60 cm HO. The following parameters were registered: Time, number of attempts and manoeuvres required for insertion; seal pressure and peak inspiratory pressure at four time points; ease of gastric tube insertion, flexible scope view, complications and postoperative morbidity. Both devices were quick and easily inserted, although the Supreme required less rotation manoeuvres (16 in AuraGain vs. 6 in LMA Supreme; p = 0.01). The AuraGain achieved higher seal pressures (34 ± 5 in AuraGain vs. 29 ± 5 in LMA Supreme; p = 0.0002). Following pneumoperitoneum in head-down position, peak airway pressure increased 9 ± 3 cm HO in both groups, exceeding seal pressure in 3 patients in the Supreme group (p = 0.06). The vocal cords were seen through all AuraGain and 90% of the Supreme devices; epiglottis was often visible inside the tube (68%). No differences were found in the incidence of traces of blood on the mask or postoperative symptoms. Both devices allowed effective ventilation in patients undergoing gynaecologic laparoscopic surgery with a low rate of complications. The Ambu AuraGain provided higher seal pressures and a clear view of glottic inlet in all patients offering the possibility to guide direct tracheal intubation if required.
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http://dx.doi.org/10.1007/s10877-016-9963-0DOI Listing
December 2017

Aromatic Osmacyclopropenefuran Bicycles and Their Relevance for the Metal-Mediated Hydration of Functionalized Allenes.

Angew Chem Int Ed Engl 2016 10 4;55(44):13749-13753. Epub 2016 Oct 4.

Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), Centro de Innovación en Química Avanzada (ORFEO-CINQA), Universidad de Zaragoza-CSIC, 50009, Zaragoza, Spain.

The aromatic osmacyclopropenefuran bicycles [OsTp{κ -C ,C ,O-(C H C CHC(OEt)O)}(P Pr )]BF (Tp=hydridotris(1-pyrazolyl)borate) and [OsH{κ -C ,C ,O-(C H C CHC(OEt)O)}(CO)(P Pr ) ]BF , with the metal fragment in a common vertex between the fused three- and five-membered rings, have been prepared via the π-allene intermediates [OsTp(η -CH =CCHCO Et)(OCMe )(P Pr )]BF and [OsH(η -CH =CCHCO Et)(CO)(OH )(P Pr ) ]BF , and their aromaticity analyzed by DFT calculations. The bicycle containing the [OsH(CO)(P Pr ) ] metal fragment is a key intermediate in the [OsH(CO)(OH ) (P Pr ) ]BF -catalyzed regioselective anti-Markovnikov hydration of ethyl buta-2,3-dienoate to ethyl 4-hydroxycrotonate.
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http://dx.doi.org/10.1002/anie.201606839DOI Listing
October 2016

Polyhydrides of Platinum Group Metals: Nonclassical Interactions and σ-Bond Activation Reactions.

Chem Rev 2016 Aug 6;116(15):8770-847. Epub 2016 Jun 6.

Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), Centro de Innovación en Química Avanzada (ORFEO-CINQA), Universidad de Zaragoza-CSIC , 50009 Zaragoza, Spain.

The preparation, structure, dynamic behavior in solution, and reactivity of polyhydride complexes of platinum group metals, described during the last three decades, are contextualized from both organometallic and coordination chemistry points of view. These compounds, which contain dihydrogen, elongated dihydrogen, compressed dihydride, and classical dihydride ligands promote the activation of B-H, C-H, Si-H, N-H, O-H, C-C, C-N, and C-F, among other σ-bonds. In this review, it is shown that, unlike other more mature areas, the chemistry of polyhydrides offers new exciting conceptual challenges and at the same time the possibility of interacting with other fields including the conversion and storage of regenerative energy, organic synthetic chemistry, drug design, and material science. This wide range of possible interactions foresees promising advances in the near future.
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http://dx.doi.org/10.1021/acs.chemrev.6b00080DOI Listing
August 2016

Host erythrocyte environment influences the localization of exported protein 2, an essential component of the Plasmodium translocon.

Eukaryot Cell 2015 Apr 6;14(4):371-84. Epub 2015 Feb 6.

Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University, Philadelphia, Pennsylvania, USA

Malaria parasites replicating inside red blood cells (RBCs) export a large subset of proteins into the erythrocyte cytoplasm to facilitate parasite growth and survival. PTEX, the parasite-encoded translocon, mediates protein transport across the parasitophorous vacuolar membrane (PVM) in Plasmodium falciparum-infected erythrocytes. Proteins exported into the erythrocyte cytoplasm have been localized to membranous structures, such as Maurer's clefts, small vesicles, and a tubovesicular network. Comparable studies of protein trafficking in Plasmodium vivax-infected reticulocytes are limited. With Plasmodium yoelii-infected reticulocytes, we identified exported protein 2 (Exp2) in a proteomic screen of proteins putatively transported across the PVM. Immunofluorescence studies showed that P. yoelii Exp2 (PyExp2) was primarily localized to the PVM. Unexpectedly, PyExp2 was also associated with distinct, membrane-bound vesicles in the reticulocyte cytoplasm. This is in contrast to P. falciparum in mature RBCs, where P. falciparum Exp2 (PfExp2) is exclusively localized to the PVM. Two P. yoelii-exported proteins, PY04481 (encoded by a pyst-a gene) and PY06203 (PypAg-1), partially colocalized with these PyExp2-positive vesicles. Further analysis revealed that with P. yoelii, Plasmodium berghei, and P. falciparum, cytoplasmic Exp2-positive vesicles were primarily observed in CD71(+) reticulocytes versus mature RBCs. In transgenic P. yoelii 17X parasites, the association of hemagglutinin-tagged PyExp2 with the PVM and cytoplasmic vesicles was retained, but the pyexp2 gene was refractory to deletion. These data suggest that the localization of Exp2 in mouse and human RBCs can be influenced by the host cell environment. Exp2 may function at multiple points in the pathway by which parasites traffic proteins into and through the reticulocyte cytoplasm.
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http://dx.doi.org/10.1128/EC.00228-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385806PMC
April 2015

ProSeal Laryngeal Mask Airway Attenuates Systemic and Cerebral Hemodynamic Response During Awakening of Neurosurgical Patients: A Randomized Clinical Trial.

J Neurosurg Anesthesiol 2015 Jul;27(3):194-202

Departments of *Anesthesiology ‡Neurosurgery †Biostatistics and Data Management Platform, IDIBAPS, Hospital Clinic, de Barcelona, University of Barcelona, Barcelona, Spain.

Background: Extubation and emergence from anesthesia may lead to systemic and cerebral hemodynamic changes that endanger neurosurgical patients. We aimed to compare systemic and cerebral hemodynamic variables and cough incidence in neurosurgery patients emerging from general anesthesia with the standard procedure (endotracheal tube [ETT] extubation) or after replacement of the ETT with a laryngeal mask airway (LMA).

Materials And Methods: Forty-two patients undergoing supratentorial craniotomy under general anesthesia were included in a randomized open-label parallel trial. Patients were randomized (sealed envelopes labeled with software-generated randomized numbers) to awaken with the ETT in place or after its replacement with a ProSeal LMA. We recorded mean arterial pressure as the primary endpoint and heart rate, middle cerebral artery flow velocity, regional cerebral oxygen saturation, norepinephrine plasma concentrations, and coughing.

Results: No differences were found between groups at baseline. All hemodynamic variables increased significantly from baseline in both groups during emergence. The ETT group had significantly higher mean arterial pressure (11.9 mm Hg; 95% confidence interval [CI], 2.1-21.8 mm Hg) (P=0.017), heart rate (7.2 beats/min; 95% CI, 0.7-13.7 beats/min) (P=0.03), and rate-pressure product (1045.4; 95% CI, 440.8-1650) (P=0.001). Antihypertensive medication was administered to more ETT-group patients than LMA-group patients (9 [42.9%] vs. 3 [14.3%] patients, respectively; P=0.04). The percent increase in regional cerebral oxygen saturation was greater in the ETT group by 26.1% (95% CI, 9.1%-43.2%) (P=0.002), but no between-group differences were found in MCA flow velocity. Norepinephrine plasma concentrations rose in both groups between baseline and the end of emergence: LMA: from 87.5±7.1 to 125.6±17.3 pg/mL; and ETT: from 118.1±14.1 to 158.1±24.7 pg/mL (P=0.007). The differences between groups were not significant. The incidence of cough was higher in the ETT group (87.5%) than in the LMA group (9.5%) (P<0.001).

Conclusions: Replacing the ETT with the LMA before neurosurgical patients emerge from anesthesia results in a more favorable hemodynamic profile, less cerebral hyperemia, and a lower incidence of cough.
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http://dx.doi.org/10.1097/ANA.0000000000000108DOI Listing
July 2015

Frailty, dependency and mortality predictors in a cohort of Cuban older adults, 2003-2011.

MEDICC Rev 2014 Jan;16(1):24-30

Finlay-Albarrán Faculty of Medical Sciences, Medical University of Havana, Cuba.

Introduction: Population aging translates into more people with chronic non-communicable diseases, disability, frailty and dependency. The study of frailty--a clinical syndrome associated with an increased risk of falls, disability, hospitalization, institutionalization and death--is important to improve clinical practice and population health indicators.

Objectives: In a cohort of older adults in Havana and Matanzas provinces, Cuba, estimate prevalence of frailty and its risk factors; determine incidence of dependency; estimate mortality risk and identify mortality predictors.

Methods: A prospective longitudinal study was conducted door to door, from June 2003 through July 2011, in a cohort of 2813 adults aged ≥65 years living in selected municipalities of Havana and Matanzas provinces; mean followup time was 4.1 years. Independent variables included demographics, behavioral risk factors and socioeconomic indicators, chronic non-communicable diseases (hypertension, stroke, dementia, depression, diabetes, anemia), number of comorbidities, and APOE ε4 genotype. Dependent variables were frailty, dependency and mortality. Criteria for frailty were slow walking speed, exhaustion, weight loss, low physical activity and cognitive decline. Prevalence and frailty risk were estimated by Poisson regression, while dependency and mortality risks and their predictors were determined using Cox regression.

Results: Frailty syndrome prevalence was 21.6% (CI 17.9%-23.8%) at baseline; it was positively associated with advanced age, anemia and presence of comorbidities (stroke, dementia, depression, three or more physically debilitating diseases). Male sex, higher educational level, married or partnered status, and more household amenities were inversely associated with frailty prevalence. In followup, dependency incidence was 33.1 per 1000 person-years (CI 29.1-37.6) and mortality was 55.1 per 1000 person-years. Advanced age, male sex, lower occupational status during productive years, dependency, frailty, dementia, depression, cerebrovascular disease and diabetes were all associated with higher risk of death.

Conclusions: Given the challenge for developing countries presented by demographic and epidemiologic transition; the high prevalence in older adults of frailty syndrome, dependency and chronic non-communicable diseases; and the association of all these with higher mortality, attention should be targeted to older adults as a risk group. This should include greater social protection, age-appropriate health services, and modification and control of cardiovascular risk factors.
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January 2014

Antepartum depression severity is increased during seasonally longer nights: relationship to melatonin and cortisol timing and quantity.

Chronobiol Int 2013 Nov 3;30(9):1160-73. Epub 2013 Sep 3.

Department of Psychiatry, University of California, San Diego , La Jolla, California , USA.

Current research suggests that mood varies from season to season in some individuals, in conjunction with light-modulated alterations in chronobiologic indices such as melatonin and cortisol. The primary aim of this study was to evaluate the effects of seasonal variations in darkness on mood in depressed antepartum women, and to determine the relationship of seasonal mood variations to contemporaneous blood melatonin and cortisol measures; a secondary aim was to evaluate the influence of seasonal factors on measures of melancholic versus atypical depressive symptoms. We obtained measures of mood and overnight concentrations of plasma melatonin and serum cortisol in 19 depressed patients (DP) and 12 healthy control (HC) antepartum women, during on-going seasonal variations in daylight/darkness, in a cross-sectional design. Analyses of variance showed that in DP, but not HC, Hamilton Depression Rating Scale (HRSD) scores were significantly higher in women tested during seasonally longer versus shorter nights. This exacerbation of depressive symptoms occurred when the dim light melatonin onset, the melatonin synthesis offset, and the time of maximum cortisol secretion (acrophase) were phase-advanced (temporally shifted earlier), and melatonin quantity was reduced, in DP but not HC. Serum cortisol increased across gestational weeks in both the HC and DP groups, which did not differ significantly in cortisol concentration. Nevertheless, serum cortisol concentration correlated positively with HRSD score in DP but not HC; notably, HC showed neither significant mood changes nor altered melatonin and cortisol timing or quantity in association with seasonal variations. These findings suggest that depression severity during pregnancy may become elevated in association with seasonally related phase advances in melatonin and cortisol timing and reduced melatonin quantity that occur in DP, but not HC. Thus, women who experience antepartum depression may be more susceptible than their nondepressed counterparts to phase alterations in melatonin and cortisol timing during seasonally longer nights. Interventions that phase delay melatonin and/or cortisol timing-for example, increased exposure to bright evening light-might serve as an effective intervention for antepartum depressions whose severity is increased during seasonally longer nights.
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http://dx.doi.org/10.3109/07420528.2013.808652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4041493PMC
November 2013

A chimeric Plasmodium falciparum merozoite surface protein vaccine induces high titers of parasite growth inhibitory antibodies.

Infect Immun 2013 Oct 29;81(10):3843-54. Epub 2013 Jul 29.

Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.

The C-terminal 19-kDa domain of Plasmodium falciparum merozoite surface protein 1 (PfMSP119) is an established target of protective antibodies. However, clinical trials of PfMSP142, a leading blood-stage vaccine candidate which contains the protective epitopes of PfMSP119, revealed suboptimal immunogenicity and efficacy. Based on proof-of-concept studies in the Plasmodium yoelii murine model, we produced a chimeric vaccine antigen containing recombinant PfMSP119 (rPfMSP119) fused to the N terminus of P. falciparum merozoite surface protein 8 that lacked its low-complexity Asn/Asp-rich domain, rPfMSP8 (ΔAsn/Asp). Immunization of mice with the chimeric rPfMSP1/8 vaccine elicited strong T cell responses to conserved epitopes associated with the rPfMSP8 (ΔAsn/Asp) fusion partner. While specific for PfMSP8, this T cell response was adequate to provide help for the production of high titers of antibodies to both PfMSP119 and rPfMSP8 (ΔAsn/Asp) components. This occurred with formulations adjuvanted with either Quil A or with Montanide ISA 720 plus CpG oligodeoxynucleotide (ODN) and was observed in both inbred and outbred strains of mice. PfMSP1/8-induced antibodies were highly reactive with two major alleles of PfMSP119 (FVO and 3D7). Of particular interest, immunization with PfMSP1/8 elicited higher titers of PfMSP119-specific antibodies than a combined formulation of rPfMSP142 and rPfMSP8 (ΔAsn/Asp). As a measure of functionality, PfMSP1/8-specific rabbit IgG was shown to potently inhibit the in vitro growth of blood-stage parasites of the FVO and 3D7 strains of P. falciparum. These data support the further testing and evaluation of this chimeric PfMSP1/8 antigen as a component of a multivalent vaccine for P. falciparum malaria.
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http://dx.doi.org/10.1128/IAI.00522-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811772PMC
October 2013

B-H activation and H-H formation: two consecutive heterolytic processes on an osmium-hydrogensulfide bond.

Chem Commun (Camb) 2013 Sep;49(68):7543-5

Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain.

Heterolytic B-H activation and H-H formation on an Os-SH bond give borylthiolate-dihydrogen derivatives. These species exchange borylthiol by borane to afford σ-borane derivatives or release H2 and undergo a hydride-boryl exchange to yield boryl-hydrogensulfide complexes depending on the boryl group bonded to the sulfur atom.
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http://dx.doi.org/10.1039/c3cc44102dDOI Listing
September 2013

Influence of seasonality on the chemical composition of oysters (Crassostrea rhizophorae).

Food Chem 2013 Jun 29;138(2-3):786-90. Epub 2012 Nov 29.

School of Nutrition, Federal University of Alagoas (UFAL), Brazil.

This paper aimed to evaluate the influence of seasonality on the chemical composition of oysters (Crassostrea rhizophorae). Samples were collected during summer and winter from the estuary and lagoon complex of the municipality of Barra de São Miguel, Alagoas, Brazil. Statistical differences (p<0.05) between summer and winter were observed in relation to chemical composition. The oysters cultivated in the winter presented some nutritional advantages because of the higher levels of proteins and functional nutrients, such as the eicosapentaenoic-docosahexaenoic acid combination and percentages of polyunsaturated fatty acids (n-3 and n-6), and the lower levels of saturated fatty acids. Therefore, the animals in winter presented a higher content of cholesterol oxides. The levels of cholesterol oxides found in these products during winter may encourage researchers to investigate the composition of oysters cultivated in different climates all over the world.
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http://dx.doi.org/10.1016/j.foodchem.2012.11.088DOI Listing
June 2013

Anti-ganglioside anti-idiotypic vaccination: more than molecular mimicry.

Front Oncol 2012 20;2:170. Epub 2012 Nov 20.

Tumor Immunology Direction, Center of Molecular Immunology Habana, Cuba.

Surgery, chemotherapy, and radiation therapy are standard modalities for cancer treatment, but the effectiveness of these treatments has reached a plateau. Thus, other strategies are being explored to combine with the current treatment paradigms in order to reach better clinical results. One of these approaches is the active immunotherapy based on the induction of anti-tumor responses by anti-idiotypic vaccination. This approach arose from Jerne's idiotypic network theory, which postulates that B lymphocytes forms a functional network, with a role in the establishment of the immune repertoires, in the regulation of natural antibody production and even in the establishment of natural tolerance. Due to the large potential diversity of the immunoglobulin variable regions, the idiotypes repertoire can mimic the universe of self and foreign epitopes, even those of non-protein nature, like gangliosides. Gangliosides are sialic acid-containing glycolipids that have been considered attractive targets for cancer immunotherapy, based on the qualitative and quantitative changes they suffer during malignant transformation and due to their importance for tumor biology. Although any idiotype could be able to mimic any antigen, only those related to antigens involved in functions relevant for organism homeostasis, and that in consequence has been fixed by evolution, would be able not only to mimic, but also to activate the idiotypic cascades related with the nominal antigen. The present review updates the results, failures and hopes, obtained with ganglioside mimicking anti-idiotypic antibodies and presents evidences of the existence of a natural response against gangliosides, suggesting that these glycolipids could be idiotypically relevant antigens.
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http://dx.doi.org/10.3389/fonc.2012.00170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501824PMC
November 2012

Ultrasound-guided ankle block for forefoot surgery: the contribution of the saphenous nerve.

Reg Anesth Pain Med 2012 Sep-Oct;37(5):554-7

Department of Anesthesiology, Hospital Clínic, Barcelona, Spain.

Background: Ankle blocks typically include the block of 5 nerves, the 4 branches that trace their origin back to the sciatic nerve plus the saphenous nerve (SaN). The sensory area of the SaN in the foot is variable. Based on our clinical experience, we decided to study the sensory distribution of the SaN in the foot and determine whether the block of this nerve is necessary as a component of an ultrasound-guided ankle block for bunion surgery.

Methods: One hundred patients scheduled for bunion surgery under ankle block were prospectively studied. We performed ultrasound-guided individual blocks of the tibial, deep peroneal, superficial peroneal, and sural nerves. After obtaining complete sensory block of these nerves, we mapped the SaN sensory territory as such area without anesthesia on the medial side of the foot.

Results: Every nerve block was successful within 10 minutes of injection. The saphenous territory extended into the foot to 57 ± 13 mm distal to the medial malleolus. This distal margin was 22 ± 11 mm proximal to the first tarsometatarsal joint. The proximal end of the surgical incision was located 1 cm distal to the first tarsometatarsal joint. In only 3 patients (3%), the area of SaN innervation reached the proximal end of the planned incision.

Conclusions: Ultrasound-guided ankle block is a highly effective technique for bunion surgery. The sensory territory of the SaN in the foot seems to extend only to the midfoot. According to our sample, 97% of the patients undergoing bunion surgery under an ankle block would not benefit from having a SaN block.
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http://dx.doi.org/10.1097/AAP.0b013e3182611483DOI Listing
June 2013

Evaluation of the immunogenicity and vaccine potential of recombinant Plasmodium falciparum merozoite surface protein 8.

Infect Immun 2012 Jul 14;80(7):2473-84. Epub 2012 May 14.

Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.

The C-terminal 19-kDa domain of merozoite surface protein 1 (MSP1₁₉) is the target of protective antibodies but alone is poorly immunogenic. Previously, using the Plasmodium yoelii murine model, we fused P. yoelii MSP1₁₉ (PyMSP1₁₉) with full-length P. yoelii merozoite surface protein 8 (MSP8). Upon immunization, the MSP8-restricted T cell response provided help for the production of high and sustained levels of protective PyMSP1₁₉- and PyMSP8-specific antibodies. Here, we assessed the vaccine potential of MSP8 of the human malaria parasite, Plasmodium falciparum. Distinct from PyMSP8, P. falciparum MSP8 (PfMSP8) contains an N-terminal asparagine and aspartic acid (Asn/Asp)-rich domain whose function is unknown. Comparative analysis of recombinant full-length PfMSP8 and a truncated version devoid of the Asn/Asp-rich domain, PfMSP8(ΔAsn/Asp), showed that both proteins were immunogenic for T cells and B cells. All T cell epitopes utilized mapped within rPfMSP8(ΔAsn/Asp). The dominant B cell epitopes were conformational and common to both rPfMSP8 and rPfMSP8(ΔAsn/Asp). Analysis of native PfMSP8 expression revealed that PfMSP8 is present intracellularly in late schizonts and merozoites. Following invasion, PfMSP8 is found distributed on the surface of ring- and trophozoite-stage parasites. Consistent with a low and/or transient expression of PfMSP8 on the surface of merozoites, PfMSP8-specific rabbit IgG did not inhibit the in vitro growth of P. falciparum blood-stage parasites. These studies suggest that the further development of PfMSP8 as a malaria vaccine component should focus on the use of PfMSP8(ΔAsn/Asp) and its conserved, immunogenic T cell epitopes as a fusion partner for protective domains of poor immunogens, including PfMSP1₁₉.
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http://dx.doi.org/10.1128/IAI.00211-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416454PMC
July 2012

Ultrasound-guided popliteal sciatic block with a single injection at the sciatic division results in faster block onset than the classical nerve stimulator technique.

Anesth Analg 2012 May 24;114(5):1121-7. Epub 2012 Feb 24.

Department of Anesthesiology, Hospital Clínic, Universitat de Barcelona, C/Villarroel 170, 08036 Barcelona, Spain.

Background: For successful, fast-onset sciatic popliteal block (SPB), either a single injection above the division of the sciatic nerve, or 2 injections to block the tibial nerve (TN) and common peroneal nerve (CPN) separately have been recommended. In this study, we compared the traditional nerve stimulator (NS)-guided SPB above the division of the sciatic nerve with the ultrasound (US)-guided block with single injection of local anesthetic (LA) between the TN and CPN at the level of their division. We hypothesized that US-SPB with a single injection between TN and CPN would result in faster block onset than a single-injection NS-SPB.

Methods: Fifty-two patients were randomized to receive either an NS-SPB or a US-SPB. For both blocks, a single injection of 20 mL mepivacaine 1.5% was given using an automated injection pump while controlling for injection force. For NS-SPB, a TN response below 0.5 mA was sought 7 cm above the popliteal fossa crease (and proximal to the divergence of the TN and peroneal nerves). For US-SPB, the injection was made after a US-guided needle was inserted between the TN and CPN at the level of their separation. Motor response was not actively sought but registered if present. The location and spread of LA were evaluated by US in both groups. Onset of motor and sensory blocks was serially assessed in 5-minute intervals in the TN and CPN divisions and compared between the groups.

Results: All patients in both groups had successful block at 30 minutes after the injection, defined as sensory block to allow surgery without supplementation. A higher proportion of patients in the US-SPB group had a complete sensory (80% vs 4%, P < 0.001) and motor block (60% vs 8%, P < 0.001), defined as anesthesia and paralysis in all nerve territories, at 15 minutes after injection. US signs of intraepineural injection were present in 19 patients (73%) in the NS-SPB group and 25 patients (100%) in the US-SPB group (P < 0.001).

Conclusions: A single injection of LA in US-SPB with needle insertion at the separation of the TN and CPN results in a similar success rate at 30 minutes; however, more patients in the US-SPB group than in the NS-SPB group had complete block at 15 minutes.
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http://dx.doi.org/10.1213/ANE.0b013e318248e1b3DOI Listing
May 2012

The relationship of nocturnal melatonin to estradiol and progesterone in depressed and healthy pregnant women.

J Womens Health (Larchmt) 2012 Jun 9;21(6):649-55. Epub 2012 Feb 9.

The Center for Chronobiology, Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093-0804, USA.

Purpose: To assess the relationship between nocturnal plasma melatonin and serum estradiol (E(2)) and progesterone (P(4)) levels in depressed pregnant women (DW) and matched healthy women (HW).

Methods: We used analysis of variance (ANOVA) and linear regression analyses on data obtained from pregnant HW and DW.

Results: Log E(2) and log P(4) were positively correlated with measures of melatonin quantity in HW (p<0.05) but not DW, controlling for age. Log E(2) and log P(4) were positively correlated with melatonin offset and duration in DW (p<0.01) but not HW.

Conclusions: Pregnant DW may be less sensitive than HW to modulation of melatonin secretion by E(2) and P(4). That melatonin timing measures are more sensitive to E(2) and P(4) variation in DW may reflect a circadian system more attuned to the need for realignment in DW than in HW. These altered sensitivities to reproductive hormones may reflect a biologic vulnerability that predisposes some pregnant women to depression.
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http://dx.doi.org/10.1089/jwh.2011.3191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366092PMC
June 2012

A clinical exploratory study with itolizumab, an anti-CD6 monoclonal antibody, in patients with rheumatoid arthritis.

Results Immunol 2012 21;2:204-11. Epub 2012 Nov 21.

Clinical Research Division, Center of Molecular Immunology, Havana, Cuba.

T cells are involved in the pathogenesis of rheumatoid arthritis (RA). CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes, that has been linked to autoreactive responses. The purpose of this study was to evaluate the safety, immunogenicity and preliminary efficacy of itolizumab, a humanized anti-CD6 monoclonal antibody, in patients with active rheumatoid arthritis. Fifteen patients were enrolled in a phase I, open-label, dose-finding study. Five cohorts of patients received a weekly antibody monotherapy with a dose-range from 0.1 to 0.8 mg/kg. Itolizumab showed a good safety profile, with no severe or serious adverse events reported so far. No signs or symptoms associated with immunosuppression were observed in the study. Objective clinical responses were achieved in more than 80% of patients after treatment completion, and these responses tend to be sustained afterwards. This clinical study constitutes the first evidence of the safety and positive clinical effect of a monotherapy using an anti-CD6 antibody in patients with rheumatoid arthritis.
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http://dx.doi.org/10.1016/j.rinim.2012.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862386PMC
December 2013

Dementia and other chronic diseases in older adults in Havana and Matanzas: the 10/66 study in Cuba.

MEDICC Rev 2011 Oct;13(4):30-7

Alzheimer Studies Center, Finlay-Albarrán Medical Faculty of the Medical University of Havana, Cuba.

Introduction: Chronic non-communicable diseases are the leading cause of death worldwide, except in Sub-Saharan Africa. Nonetheless, one of these conditions, dementia, is the major contributor to disability-adjusted life years in people aged ≥60 years. Few epidemiological studies exist of the prevalence and impact of dementia and selected chronic diseases in older adults in Latin America.

Objective: Describe prevalence of dementia, other chronic vascular diseases and cardiovascular risk factors, as well as resulting disabilities and care needs generated in adults aged ≥65 years in Havana City and Matanzas provinces, Cuba.

Methods: The 10/66 study is a prospective longitudinal study involving a cohort of 3015 adults aged ≥65 years in municipalities of Havana City and Matanzas provinces, divided into two phases: a cross-sectional door-to-door study conducted in 2003-2006, and a follow-up and assessment phase in 2007-2010. This article reports findings from the first phase. Hypertension diagnosis was based on criteria from the International Society for Hypertension; diabetes mellitus on American Diabetes Association criteria; stroke according to WHO definitions; and dementia according to criteria of the American Psychiatric Society's Diagnostic and Statistical Manual of Mental Disorders DSM-IV and the 10/66 International Dementia Research Group. Ischemic heart disease was defined by self-report of previous physician diagnosis. Study variables included age, sex, educational level, substance use (alcohol, tobacco) and dietary habits. A structured physical and neurological exam, including blood pressure measurement, was performed on all participants. Laboratory tests included complete blood count, fasting blood glucose, total cholesterol and lipoprotein fractions, triglycerides and apolipoprotein E genotype. Prevalence and standardized morbidity ratios (crude and adjusted) were calculated for chronic diseases studied with 95% confidence intervals, using a Poisson regression model and indirect standardization.

Results: The study assessed 2944 older adults (response rate 97.6%) and found high prevalence of vascular risk factors and of chronic non-communicable diseases: hypertension 73.0% (95% CI 71.4-74.7), diabetes mellitus 24.8% (95% CI 22.9-26.5), ischemic heart disease 14.1% (95% CI 12.9-15.4), dementia 10.8% (95% CI 9.7-12.0) and stroke 7.8% (95% CI 6.9-8.8). The majority of participants (85%) had more than one cardiovascular risk factor. The main cause of disability and dependency in the study population was dementia.

Conclusion: The high prevalence of chronic diseases observed in the elderly--with the consequent morbidity, disability and dependency--highlights the need for prevention, early diagnosis and risk factor control, particularly given the demographic and epidemiologic transition faced by Cuba and other developing countries.
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October 2011

No clinical or electrophysiologic evidence of nerve injury after intraneural injection during sciatic popliteal block.

Anesthesiology 2011 Sep;115(3):589-95

Department of Anesthesiology, Hospital Clinic, University of Barcelona, Barcelona, Spain.

Background: Intraneural injection during nerve-stimulator-guided sciatic block at the popliteal fossa may be a common occurrence. Although intraneural injections have not resulted in clinically detectable neurologic injury in small studies in human subjects, intraneural injections result in postinjection inflammation in animal models. This study used clinical, imaging, and electrophysiologic measures to evaluate the occurrence of any subclinical neurologic injury in patients with intraneural injection during sciatic popliteal block.

Methods: Twenty patients undergoing popliteal block were enrolled; 17 patients completed the study protocol. After tibial nerve response was achieved by nerve stimulation (0.3-0.5 mA; 2 Hz; 0.1 ms), 20 ml mixture of mepivacaine (1.25%) and radiopaque contrast (2 ml) were injected. Location and spread of the injectant were assessed by ultrasound measurements of the sciatic nerve area before and after injection, and by computed tomography. In addition to clinical neurologic evaluations, serial electrophysiologic studies (nerve conduction and late response studies using predefined criteria) were performed at baseline and at 1 week and 3 weeks after the block for signs of subclinical neurologic dysfunction.

Results: Sixteen injections (94%, 95% CI: 71-100%) met criteria for an intraneural injection. Postinjection nerve area on ultrasound increased by 45% (95% CI: 29-58%), P < 0.001. Computed tomography demonstrated fascicular separation in 70% (95% CI: 44-90%), air within the nerve in 29% (95% CI: 10-56%), contrast along bifurcations in 65% (95% CI: 38-86%), and concentric contrast layers in 100% (95% CI: 84-100%). Neither clinical nor electrophysiologic studies detected neurologic dysfunction indicating injury to the nerve.

Conclusions: Nerve-stimulator-guided sciatic block at the popliteal fossa often results in intraneural injection that may not lead to clinical or electrophysiologic nerve injury.
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http://dx.doi.org/10.1097/ALN.0b013e3182276d10DOI Listing
September 2011