RESUMO

Using the 1-(m-tolyl)-1H-1,2,3-triazole-4-(4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) (TlTrzNIT) radical and metal ß-diketonate complexes [M(hfac)2(H2O)2], where hfac is hexafluoroacetylacetonato, three new 2p-3d heterospin complexes were synthesized. Their structures were solved using single crystal X-ray diffraction data, and magnetic investigation was performed by DC and AC measurements and multifrequency EPR spectroscopy. Compounds 1 and 2 are isostructural complexes with molecular formula [M3(TlTrzNIT)2(hfac)6] (MII = Mn or Cu) while compound 3 is the mononuclear [Co(TlTrzNIT)(hfac)2] complex. In all complexes, the radical acts as a bidentate ligand through the oxygen atom of the nitroxide moiety and the nitrogen atom from the triazole group. Furthermore, in compounds 1 and 2, the TlTrzNIT is bridge-coordinated between two metal centers, leading to the formation of trinuclear complexes. The fitting of the static magnetic behavior reveals antiferromagnetic and ferromagnetic intramolecular interactions for complexes 1 and 2, respectively. The EPR spectra of 1 are well described by an isolated ferrimagnetic S = 13/2 (= 5/2 - 1/2 + 5/2 - 1/2 + 5/2) ground state with a biaxial zero-field splitting (ZFS) interaction characterized, respectively, by 2nd order axial and rhombic parameters, D and E, such that E/D is close to the maximum of 0.33. Meanwhile, EPR spectra for 2 are explained in terms of a ferromagnetic model with weakly anisotropic Cu-radical exchange interactions, giving rise to an isolated S = 5/2 (= 5 × 1/2) ground state with both an anisotropic g tensor and a weak ZFS interaction. Complex 2 represents one of only a few examples of Cu-radical moieties with measurable exchange anisotropy.

RESUMO

Two tetranuclear compounds with a cubane-like structure were synthesized from a one-pot reaction between NiII and 2,2,6,6-tetramethyl-3,5-heptanedione (Hdpm) for 1 or 4,4,4-trifluoro-1-phenyl-1,3-butanedione (Hbta) for 2 in the presence of sodium methoxide. The crystal structures of both compounds have been determined by single-crystal X-ray diffraction, and their magnetic properties have been studied by SQUID magnetometry as well as by high-field electron paramagnetic resonance (HFEPR) spectroscopy. For 1, the temperature dependence of the magnetic susceptibility can be fitted by taking into account Ni···Ni ferromagnetic interactions, which leads to an S = 4 ground-state spin. For 2, both antiferromagnetic and ferromagnetic interactions are present. However, the latter are dominant, which also leads to an S = 4 ground-state spin, in good agreement with the HFEPR study.

RESUMO

PURPOSE: The Ponseti Method has dramatically altered the management of clubfoot, with particular implications for limited-resource settings. We sought to describe outcomes of care and risk factors for sub-optimal results using the Ponseti Method in Haiti. METHODS: We conducted a records review of patients presenting from 2011-2015 to a CURE Clubfoot clinic in Port-au-Prince, Haiti. We report patient characteristics (demographics and clinical), treatment patterns (cast number/duration and tenotomy rates), and outcomes (relapse and complications). We compared treatment with benchmarks in high-income nations and used generalized linear models to identify risk factors for delayed presentation, increased number of casts, and relapse. RESULTS: Amongst 168 children, age at presentation ranged from 0 days (birth) to 4.4 years, 62% were male, 35% were born at home, 63% had bilateral disease, and 46% had idiopathic clubfeet. Prior treatment (RR 6.33, 95% CI 3.18-12.62) was associated with a higher risk of delayed presentation. Risk factors for requiring ≥ 10 casts included having a non-idiopathic diagnosis (RR 2.28, 95% CI 1.08-4.83) and higher Pirani score (RR 2.78 per 0.5 increase, 95% CI 1.17-6.64). Female sex (RR 1.54, 95% CI 1.01-2.34) and higher Pirani score (RR 1.09 per 0.5 increase, 95% CI 1.00-1.17) were risk factors for relapse. Compared to North American benchmarks, children presented later (median 4.1 wks [IQR 1.6-18.1] vs. 1 wk), with longer casting (12.5 wks [SD 9.8] vs. 7.1 wks), and higher relapse (43% vs. 22%). CONCLUSIONS: Higher Pirani score, prior treatment, non-idiopathic diagnosis, and female sex were associated with a higher risk of sub-optimal outcomes in this low-resource setting. Compared to high-income nations, serial casting began later, with longer duration and higher relapse. Identifying patients at risk for poor outcomes in a low-resource setting can guide counseling, program development, and resource allocation.

Assuntos

RESUMO

Multiple Sclerosis (MS) is an inflammatory neurodegenerative disease that affects approximately 2.5 million people globally. Even though the etiology of MS remains unknown, it is accepted that it involves a combination of genetic alterations and environmental factors. Here, after performing whole exome sequencing, we found a MS patient harboring a rare and homozygous single nucleotide variant (SNV; rs61745847) of the G-protein coupled receptor (GPCR) galanin-receptor 2 (GALR2) that alters an important amino acid in the TM6 molecular toggle switch region (W249L). Nuclear magnetic resonance imaging showed that the hypothalamus (an area rich in GALR2) of this patient exhibited an important volumetric reduction leading to an enlarged third ventricle. Ex vivo experiments with patient-derived blood cells (AKT phosphorylation), as well as studies in recombinant cell lines expressing the human GALR2 (calcium mobilization and NFAT mediated gene transcription), showed that galanin (GAL) was unable to stimulate cell signaling in cells expressing the variant GALR2 allele. Live cell confocal microscopy showed that the GALR2 mutant receptor was primarily localized to intracellular endosomes. We conclude that the W249L SNV is likely to abrogate GAL-mediated signaling through GALR2 due to the spontaneous internalization of this receptor in this patient. Although this homozygous SNV was rare in our MS cohort (1:262 cases), our findings raise the potential importance of impaired neuroregenerative pathways in the pathogenesis of MS, warrant future studies into the relevance of the GAL/GALR2 axis in MS and further suggest the activation of GALR2 as a potential therapeutic route for this disease.

Assuntos

RESUMO

A new family of binuclear complexes [MnIIILnIII(dpm)4(MeO)2(MeOH)2] is reported (where Ln = LaIII (1), PrIII (2), and EuIII(3)). These compounds were obtained from a one-pot reaction between 2,2,6,6-tetramethyl-3,5-heptanodione (Hdpm), MnII, and the respective LnIII salt in the presence of sodium methoxide. The derivative containing the diamagnetic ion LaIII has been synthesized in order to characterize the local anisotropy of the MnIII ion. High-field electron paramagnetic resonance (HFEPR) spectroscopy shows that the MnIII ion, with an elongated octahedral geometry in all compounds, has a significant axial zero-field splitting and a small rhombic anisotropy. Additionally, the HFEPR measurements indicate that there is almost no exchange between the spin carriers in these compounds, all of which exhibit field-induced slow relaxation of the magnetization.

RESUMO

A family of distorted heterometallic cubanes, [Mn (III) 3Ni (II)(hmp) 3O(N 3) 3(O 2CR) 3], where O 2CR (-) is benzoate ( 1), 3-phenylpropionate ( 2), 1-adamantanecarboxylate ( 3), or acetate ( 4) and hmp (-) is the anion of 2-pyridinemethanol, was synthesized and structurally as well as magnetically characterized. These complexes have a distorted-cubane core structure similar to that found in the S = 9/2 Mn 4 cubane family of complexes. Complexes 1, 3, and 4 crystallize in rhombohedral, hexagonal, and cubic space groups, respectively, and have C 3 molecular symmetry, while complex 2 crystallizes in the monoclinic space group Cc with local C 1 symmetry. Magnetic susceptibility and magnetization hysteresis measurements and high-frequency electron paramagnetic resonance (HFEPR) spectroscopy established that complexes 1-4 have S = 5 spin ground states with axial zero-field splitting (ZFS) parameters ( D) ranging from -0.20 to -0.33 cm (-1). Magnetization versus direct-current field sweeps below 1.1 K revealed hysteresis loops with magnetization relaxation, definitely indicating that complexes 1-4 are single-molecule magnets that exhibit quantum tunneling of magnetization (QTM) through an anisotropy barrier. Complex 2 exhibits the smallest coercive field and fastest magnetization tunneling rate, suggesting a significant rhombic ZFS parameter ( E), as expected from the low C 1 symmetry. This was confirmed by HFEPR spectroscopy studies on single crystals that gave the following parameter values for complex 2: gz = 1.98, gx = gy = 1.95, D = -0.17 cm (-1), B 4 (0) = -6.68 x 10 (-5) cm (-1), E = 6.68 x 10 (-3) cm (-1), and B 4 (2) = -1.00 x 10 (-4) cm (-1). Single-crystal HFEPR data for complex 1 gave g z = 2.02, gx = gy = 1.95, D = -0.23 cm (-1), and B 4 (0) = -5.68 x 10 (-5) cm (-1), in keeping with the C 3 site symmetry of this Mn 3Ni complex. The combined results highlight the importance of spin-parity effects and molecular symmetry, which determine the QTM rates.

RESUMO

Two new heterometallic cubane molecules have been synthesized. High-frequency electron paramagnetic resonance and magnetization measurements indicate that [Mn(3)Ni(hmp)(3)O(N(3))(3)(C(7)H(5)O(2))(3)] (1) displays a well-isolated S = 5 ground state (DeltaE > 120 K), with g = 2.0, D = -0.23 cm(-1), and ferromagnetic Mn-Mn exchange interactions competing with antiferromagnetic Ni-Mn interactions. [Mn(3)Zn(hmp)(3)O(N(3))(3)(C(3)H(5)O(2))(3)] (2) possesses a S = 6 ground state (DeltaE > 105 K), with g = 2.0, D = -0.14 cm(-1), and ferromagnetic Mn-Mn exchange interactions. Magnetization vs magnetic field data for oriented single crystals of 1 and 2 indicate that both complexes are single-molecule magnets.