The immunomodulatory effect of oral NaHCO3 is mediated by the splenic nerve: multivariate impact revealed by artificial neural networks.

Stimulation of the inflammatory reflex (IR) is a promising strategy for treating systemic inflammatory disorders. Recent studies suggest oral sodium bicarbonate (NaHCO3) as a potential activator of the IR, offering a safe and cost-effective treatment approach. However, the mechanisms underlying NaHCO3-induced anti-inflammatory effects remain unclear. We investigated whether oral NaHCO3's immunomodulatory effects are mediated by the splenic nerve. Female rats received NaHCO3 or water (H2O) for four days, and splenic immune markers were assessed using flow cytometry. NaHCO3 led to a significant increase (p < 0.05, and/or partial eta squared > 0.06) in anti-inflammatory markers, including CD11bc + CD206 + (M2-like) macrophages, CD3 + CD4 + FoxP3 + cells (Tregs), and Tregs/M1-like ratio. Conversely, proinflammatory markers, such as CD11bc + CD38 + TNFα + (M1-like) macrophages, M1-like/M2-like ratio, and SSChigh/SSClow ratio of FSChighCD11bc + cells, decreased in the spleen following NaHCO3 administration. These effects were abolished in spleen-denervated rats, suggesting the necessity of the splenic nerve in mediating NaHCO3-induced immunomodulation. Artificial neural networks accurately classified NaHCO3 and H2O treatment in sham rats but failed in spleen-denervated rats, highlighting the splenic nerve's critical role. Additionally, spleen denervation independently influenced Tregs, M2-like macrophages, Tregs/M1-like ratio, and CD11bc + CD38 + cells, indicating distinct effects from both surgery and treatment. Principal component analysis (PCA) further supported the separate effects. Our findings suggest that the splenic nerve transmits oral NaHCO3-induced immunomodulatory changes to the spleen, emphasizing NaHCO3's potential as an IR activator with therapeutic implications for a wide spectrum of systemic inflammatory conditions.

Incorporation of Carboxylate Pendant Arms into 18-Membered Macrocycles: Effects on [nat/203Pb]Pb(II) Complexation.

We present a detailed investigation on the coordination chemistry of [nat/203Pb]Pb(II) with chelators H4PYTA and H4CHX-PYTA. These chelators belong to the family of ligands derived from the 18-membered macrocyclic backbone PYAN and present varying degrees of rigidity due to the presence of either ethyl or cyclohexyl spacers. A complete study of the stable Pb(II) complexes is carried out via NMR, X-Ray crystallography, stability constant determination and computational studies. While these studies indicated that Pb(II) complexation is achieved, and the thermodynamic stability of the resulting complexes is very high, a certain degree of fluxionality does exist in both cases. Nevertheless, radiolabeling studies were carried out using SPECT (single photon emission computed tomography) compatible isotope lead-203 (203Pb, t1/2=51.9 h), and while both chelators complex the radioisotope, the incorporation of carboxylate pendant arms appears to be detrimental towards the stability of the complexes when compared to the previously described amide analogues. Additionally, incorporation of a cyclohexyl spacer does not improve the kinetic inertness of the system.

Endeavor toward Redox-Responsive Transition Metal Contrast Agents Based on the Cross-Bridge Cyclam Platform.

We present the synthesis and characterization of a series of Mn(III), Co(III), and Ni(II) complexes with cross-bridge cyclam derivatives (CB-cyclam = 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane) containing acetamide or acetic acid pendant arms. The X-ray structures of [Ni(CB-TE2AM)]Cl2·2H2O and [Mn(CB-TE1AM)(OH)](PF6)2 evidence the octahedral coordination of the ligands around the Ni(II) and Mn(III) metal ions, with a terminal hydroxide ligand being coordinated to Mn(III). Cyclic voltammetry studies on solutions of the [Mn(CB-TE1AM)(OH)]2+ and [Mn(CB-TE1A)(OH)]+ complexes (0.15 M NaCl) show an intricate redox behavior with waves due to the MnIII/MnIV and MnII/MnIII pairs. The Co(III) and Ni(II) complexes with CB-TE2A and CB-TE2AM show quasi-reversible features due to the CoIII/CoII or NiII/NiIII pairs. The [Co(CB-TE2AM)]3+ complex is readily reduced by dithionite in aqueous solution, as evidenced by 1H NMR studies, but does not react with ascorbate. The [Mn(CB-TE1A)(OH)]+ complex is however reduced very quickly by ascorbate following a simple kinetic scheme (k0 = k1[AH-], where [AH-] is the ascorbate concentration and k1 = 628 ± 7 M-1 s-1). The reduction of the Mn(III) complex to Mn(II) by ascorbate provokes complex dissociation, as demonstrated by 1H nuclear magnetic relaxation dispersion studies. The [Ni(CB-TE2AM)]2+ complex shows significant chemical exchange saturation transfer effects upon saturation of the amide proton signals at 71 and 3 ppm with respect to the bulk water signal.

The changes of blood-based inflammatory biomarkers after non-pharmacologic interventions for chronic low back pain: a systematic review.

BACKGROUND: Chronic low back pain (CLBP) is a prevalent and debilitating condition, leading to significant challenges to both patients and the governmental healthcare system. Non-pharmacologic interventions have received increasing attention as potential strategies to alleviate chronic low back pain and improve patient outcomes. The aim of this systematic review was to comprehensively assess the changes in blood inflammatory biomarkers after non-pharmacologic interventions for CLBP patients, thus trying to understand the complex interactions between non-pharmacologic interventions and inflammatory biomarker changes in CLBP. METHODS: A thorough search (from January 1st, 2002 to October 5th, 2022) of PubMed, Medline (platform Web of Science), and the Cochrane Library (platform Wiley Online Library) were conducted, and inclusion criteria as well as exclusion criteria were refined to selection of the studies. Rigorous assessments of study quality were performed using RoB 2 from Cochrane or an adaptation of the Downs and Black checklist. Data synthesis includes alterations in inflammatory biomarkers after various non-pharmacologic interventions, including exercise, acupressure, neuro-emotional technique, and other modalities. RESULTS: Thirteen primary studies were included in this systematic review, eight randomized controlled trials, one quasi-randomized trial, and four before-after studies. The interventions studied consisted of osteopathic manual treatment (one study), spinal manipulative therapy (SMT) (three studies), exercise (two studies), yoga (two studies) and acupressure (two studies), neuro-emotional technique (one study), mindfulness-based (one study) and balneotherapy study (one study). Four studies reported some changes in the inflammatory biomarkers compared to the control group. Decreased tumor necrosis factor-alpha (TNF-α) after osteopathic manual treatment (OMT), neuro-emotional technique (NET), and yoga. Decreased interleukin (IL)-1, IL-6, IL-10, and c-reactive protein (CRP) after NET, and increased IL-4 after acupressure. Another five studies found changes in inflammatory biomarkers through pre- and post-intervention comparisons, indicating improvement outcomes after intervention. Increased IL-10 after balneotherapy; decreased TNF-α, IL-1ß, IL-8, Interferon-gamma, interferon-γ-induced protein 10-γ-induced protein 10 after exercise; decreased IL-6 after exercise and SMT; decreased CRP and chemokine ligand 3 after SMT. CONCLUSION: Results suggest a moderation of inflammatory biomarkers due to different non-pharmacologic interventions for CLBP, generally resulting in decreased pro-inflammatory markers such as TNF-α and IL-6 as well as increased anti-inflammatory markers such as IL-4, thus revealing the inhibition of inflammatory processes by different non-pharmacologic interventions. However, a limited number of high-quality studies evaluating similar interventions and similar biomarkers limits the conclusion of this review.

Prevention and treatment of cisplatin-induced ototoxicity in adults: A systematic review.

OBJECTIVES: Ototoxicity is a common disabling side effect of platinum-based chemotherapy. This study aimed to assess the evidence on the management of platinum-induced ototoxicity in adult cancer patients. METHODS: Four databases were searched up to 1 November 2022. Original studies were included if they reported on a pharmacologic or non-pharmacologic intervention to prevent or treat platinum ototoxicity in adults. The articles' quality was assessed via two grading scales. RESULTS: Nineteen randomised controlled trials and five quasi-experimental studies with 1673 patients were analysed. Eleven interventions were identified, nine pharmacological and two non-pharmacological. Six of the interventions (sodium thiosulphate, corticoids, sertraline, statins, multivitamins and D-methionine) showed mild benefits in preventing cisplatin-induced ototoxicity. Only one trial assessed corticoids as a potential treatment. Overall, only six trials were deemed with a low risk of bias. The majority of studies inadequately documented intervention-related adverse effects, thereby limiting safety conclusions. CONCLUSIONS: Current interventions have mild benefits in preventing cisplatin-induced ototoxicity in adult cancer patients. Sodium thiosulphate is the most promising intervention as a preventive strategy. Rigorous, high-quality research is warranted, encompassing an evaluation of all potential symptoms and innovative treatment modalities.

Donor Radii in Rare-Earth Complexes.

We present a set of donor radii for the rare-earth cations obtained from the analysis of structural data available in the Cambridge Structural Database (CSD). Theoretical calculations using density functional theory (DFT) and wave function approaches (NEVPT2) demonstrate that the Ln-donor distances can be broken down into contributions of the cation and the donor atom, with the minimum in electron density (ρ) that defines the position of (3,-1) critical points corresponding well with Shannon's crystal radii (CR). Subsequent linear fits of the experimental bond distances for all rare earth cations (except Pm3+) afforded donor radii (rD) that allow for the prediction of Ln-donor distances regardless of the nature of the rare-earth cation and its oxidation state. This set of donor radii can be used to rationalize structural data and identify particularly weak or strong interactions, which has important implications in the understanding of the stability and reactivity of complexes of these metal ions. A few cases of incorrect atom assignments in X-ray structures were also identified using the derived rD values.

Effect of Magnetic Anisotropy on the 1H NMR Paramagnetic Shifts and Relaxation Rates of Small Dysprosium(III) Complexes.

We present a detailed analysis of the 1H NMR chemical shifts and transverse relaxation rates of three small Dy(III) complexes having different symmetries (C3, D2 or C2). The complexes show sizeable emission in the visible region due to 4F9/2 → 6HJ transitions (J = 15/2 to 11/2). Additionally, NIR emission is observed at ca. 850 (4F9/2 → 6H7/2), 930 (4F9/2 → 6H5/2), 1010 (4F9/2 → 6F9/2), and 1175 nm (4F9/2 → 6F7/2). Emission quantum yields of 1-2% were determined in aqueous solutions. The emission lifetimes indicate that no water molecules are present in the inner coordination sphere of Dy(III), which in the case of [Dy(CB-TE2PA)]+ was confirmed through the X-ray crystal structure. The 1H NMR paramagnetic shifts induced by Dy(III) were found to be dominated by the pseudocontact mechanism, though, for some protons, contact shifts are not negligible. The analysis of the pseudocontact shifts provided the magnetic susceptibility tensors of the three complexes, which were also investigated using CASSCF calculations. The transverse 1H relaxation data follow a good linear correlation with 1/r6, where r is the distance between the Dy(III) ion and the observed proton. This indicates that magnetic anisotropy is not significantly affecting the relaxation of 1H nuclei in the family of complexes investigated here.

Thermodynamic Stability of Mn(II) Complexes with Aminocarboxylate Ligands Analyzed Using Structural Descriptors.

We present a quantitative analysis of the thermodynamic stabilities of Mn(II) complexes, defined by the equilibrium constants (log KMnL values) and the values of pMn obtained as -log[Mn]free for total metal and ligand concentrations of 1 and 10 µM, respectively. We used structural descriptors to analyze the contributions to complex stability of different structural motifs in a quantitative way. The experimental log KMnL and pMn values can be predicted to a good accuracy by adding the contributions of the different motifs present in the ligand structure. This allowed for the identification of features that provide larger contributions to complex stability, which will be very helpful for the design of efficient chelators for Mn(II) complexation. This issue is particularly important to develop Mn(II) complexes for medical applications, for instance, as magnetic resonance imaging (MRI) contrast agents. The analysis performed here also indicates that coordination number eight is more common for Mn(II) than is generally assumed, with the highest log KMnL values generally observed for hepta- and octadentate ligands. The X-ray crystal structure of [Mn2(DOTA)(H2O)2], in which eight-coordinate [Mn(DOTA)]2- units are bridged by six-coordinate exocyclic Mn(II) ions, is also reported.

Versatile Macrocyclic Platform for the Complexation of [natY/90Y]Yttrium and Lanthanide Ions.

We report a macrocyclic ligand (H3L6) based on a 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane platform containing three acetate pendant arms and a benzyl group attached to the fourth nitrogen atom of the macrocycle. The X-ray structures of the YL6 and TbL6 complexes reveal nine coordination of the ligand to the metal ions through the six nitrogen atoms of the macrocycle and three oxygen atoms of the carboxylate pendants. A combination of NMR spectroscopic studies (1H, 13C, and 89Y) and DFT calculations indicated that the structure of the YL6 complex in the solid state is maintained in an aqueous solution. The detailed study of the emission spectra of the EuL6 and TbL6 complexes revealed Ln3+-centered emission with quantum yields of 7.0 and 60%, respectively. Emission lifetime measurements indicate that the ligand offers good protection of the metal ions from surrounding water molecules, preventing the coordination of water molecules. The YL6 complex is remarkably inert with respect to complex dissociation, with a lifetime of 1.7 h in 1 M HCl. On the other hand, complex formation is fast (∼1 min at pH 5.4, 2 × 10-5 M). Studies using the 90Y-nuclide confirmed fast radiolabeling since [90Y]YL6 is nearly quantitatively formed (radiochemical yield (RCY) > 95) in a short time over a broad range of pH values from ca. 2.4 to 9.0. Challenging experiments in the presence of excess ethylenediaminetetraacetic acid (EDTA) and in human serum revealed good stability of the [90Y]YL6 complex. All of these experiments combined suggest the potential application of H3L6 derivatives as Y-based radiopharmaceuticals.

Persistent increases of PKMζ in memory-activated neurons trace LTP maintenance during spatial long-term memory storage.

PKMζ is an autonomously active PKC isoform crucial for the maintenance of synaptic long-term potentiation (LTP) and long-term memory. Unlike other kinases that are transiently stimulated by second messengers, PKMζ is persistently activated through sustained increases in protein expression of the kinase. Therefore, visualizing increases in PKMζ expression during long-term memory storage might reveal the sites of its persistent action and thus the location of memory-associated LTP maintenance in the brain. Using quantitative immunohistochemistry validated by the lack of staining in PKMζ-null mice, we examined the amount and distribution of PKMζ in subregions of the hippocampal formation of wild-type mice during LTP maintenance and spatial long-term memory storage. During LTP maintenance in hippocampal slices, PKMζ increases in the pyramidal cell body and stimulated dendritic layers of CA1 for at least 2 hr. During spatial memory storage, PKMζ increases in CA1 pyramidal cells for at least 1 month, paralleling the persistence of the memory. During the initial expression of the memory, we tagged principal cells with immediate-early gene Arc promoter-driven transcription of fluorescent proteins. The subset of memory-tagged CA1 cells selectively increases expression of PKMζ during memory storage, and the increase persists in dendritic compartments within stratum radiatum for 1 month, indicating long-term storage of information in the CA3-to-CA1 pathway. We conclude that persistent increases in PKMζ trace the molecular mechanism of LTP maintenance and thus the sites of information storage within brain circuitry during long-term memory.

Lanthanide(III) Complexes Based on an 18-Membered Macrocycle Containing Acetamide Pendants. Structural Characterization and paraCEST Properties.

We report a detailed investigation of the coordination properties of macrocyclic lanthanide complexes containing a 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane scaffold functionalized with four acetamide pendant arms. The X-ray structures of the complexes with the large Ln3+ ions (La and Sm) display 12- and 10-coordinated metal ions, where the coordination sphere is fulfilled by the six N atoms of the macrocycle, the four O atoms of the acetamide pendants, and a bidentate nitrate anion in the La3+ complex. The analogous Yb3+ complex presents, however, a 9-coordinated metal ion because one of the acetamide pendant arms remains uncoordinated. 1H NMR studies indicate that the 10-coordinated form is present in solution throughout the lanthanide series from La to Tb, while the smaller lanthanides form 9-coordinated species. 1H and 89Y NMR studies confirm the presence of this structural change because the two species are present in solution. Analysis of the 1H chemical shifts observed for the Tb3+ complex confirms its D2 symmetry in aqueous solution and evidences a highly rhombic magnetic susceptibility tensor. The acetamide resonances of the Pr3+ and Tb3+ complexes provided sizable paraCEST effects, as demonstrated by the corresponding Z-spectra recorded at different temperatures and studies on tube phantoms recorded at 22 °C.

Understanding the Effect of the Electron Spin Relaxation on the Relaxivities of Mn(II) Complexes with Triazacyclononane Derivatives.

Investigating the relaxation of water 1H nuclei induced by paramagnetic Mn(II) complexes is important to understand the mechanisms that control the efficiency of contrast agents used in diagnostic magnetic resonance imaging (MRI). Herein, a series of potentially hexadentate triazacyclononane (TACN) derivatives containing different pendant arms were designed to explore the relaxation of the electron spin in the corresponding Mn(II) complexes by using a combination of 1H NMR relaxometry and theoretical calculations. These ligands include 1,4,7-triazacyclononane-1,4,7-triacetic acid (H3NOTA) and three derivatives in which an acetate group is replaced by sulfonamide (H3NO2ASAm), amide (H2NO2AM), or pyridyl (H2NO2APy) pendants. The analogue of H3NOTA containing three propionate pendant arms (H3NOTPrA) was also investigated. The X-ray structure of the derivative containing two acetate groups and a sulfonamide pendant arm [Mn(NO2ASAm)]- evidenced six-coordination of the ligand to the metal ion, with the coordination polyhedron being close to a trigonal prism. The relaxivities of all complexes at 20 MHz and 25 °C (1.1-1.3 mM-1 s-1) are typical of systems that lack water molecules coordinated to the metal ion. The nuclear magnetic relaxation profiles evidence significant differences in the relaxivities of the complexes at low fields (<1 MHz), which are associated with different spin relaxation rates. The zero field splitting (ZFS) parameters calculated by using DFT and CASSCF methods show that electronic relaxation is relatively insensitive to the nature of the donor atoms. However, the twist angle of the two tripodal faces that delineate the coordination polyhedron, defined by the N atoms of the TACN unit (lower face) and the donor atoms of the pendant arms (upper face), has an important effect in the ZFS parameters. A twist angle close to the ideal value for an octahedral coordination (60°), such as that in [Mn(NOTPrA)]-, leads to a small ZFS energy, whereas this value increases as the coordination polyhedron approaches to a trigonal prism.

Pentacyclic Triterpene Profile and Its Biosynthetic Pathway in Cecropia telenitida as a Prospective Dietary Supplement.

Promising research over the past decades has shown that some types of pentacyclic triterpenes (PTs) are associated with the prevention of type 2 diabetes (T2D), especially those found in foods. The most abundant edible sources of PTs are those belonging to the ursane and oleanane scaffold. The principal finding is that Cecropia telenitida contains abundant oleanane and ursane PT types with similar oxygenation patterns to those found in food matrices. We studied the compositional profile of a rich PT fraction (DE16-R) and carried out a viability test over different cell lines. The biosynthetic pathway connected to the isolated PTs in C. telenitida offers a specific medicinal benefit related to the modulation of T2D. This current study suggests that this plant can assemble isobaric, positional isomers or epimeric PT. Ursane or oleanane scaffolds with the same oxygenation pattern are always shared by the PTs in C. telenitida, as demonstrated by its biosynthetic pathway. Local communities have long used this plant in traditional medicine, and humans have consumed ursane and oleanane PTs in fruits since ancient times, two key points we believe useful in considering the medicinal benefits of C. telenitida and explaining how a group of molecules sharing a closely related scaffold can express effectiveness.

Assessment of an Assistive Control Approach Applied in an Active Knee Orthosis Plus Walker for Post-Stroke Gait Rehabilitation.

The goal of this study is the assessment of an assistive control approach applied to an active knee orthosis plus a walker for gait rehabilitation. The study evaluates post-stroke patients and healthy subjects (control group) in terms of kinematics, kinetics, and muscle activity. Muscle and gait information of interest were acquired from their lower limbs and trunk, and a comparison was conducted between patients and control group. Signals from plantar pressure, gait phase, and knee angle and torque were acquired during gait, which allowed us to verify that the stance control strategy proposed here was efficient at improving the patients' gaits (comparing their results to the control group), without the necessity of imposing a fixed knee trajectory. An innovative evaluation of trunk muscles related to the maintenance of dynamic postural equilibrium during gait assisted by our active knee orthosis plus walker was also conducted through inertial sensors. An increase in gait cycle (stance phase) was also observed when comparing the results of this study to our previous work. Regarding the kinematics, the maximum knee torque was lower for patients when compared to the control group, which implies that our orthosis did not demand from the patients a knee torque greater than that for healthy subjects. Through surface electromyography (sEMG) analysis, a significant reduction in trunk muscle activation and fatigability, before and during the use of our orthosis by patients, was also observed. This suggest that our orthosis, together with the assistive control approach proposed here, is promising and could be considered to complement post-stroke patient gait rehabilitation.

Understanding the Optical and Magnetic Properties of Ytterbium(III) Complexes.

The absorption and emission spectra of three Yb3+ complexes possessing D3, D2, and C2 symmetries were analyzed with the aid of ab initio calculations based on Complete Active Space (CAS) self-consistent field wave functions (CAS(13,7)). The absorption spectra present contributions from both cold and hot bands, involving thermally populated excited sublevels of the 2F7/2 manifold. The high-resolution emission spectrum of the tris-picolinate complex [Yb(DPA)3]3- recorded at 77 K presents four components, while the complexes with macrocyclic ligands show both cold and hot emission bands, resulting in more than four components for the 2F5/2 → 2F7/2 transition. The combined information provided by the absorption and emission spectra allowed to identify most of the crystal field sublevels of the 2F5/2 and 2F7/2 states. The energies of these crystal field components are well-reproduced by the ab initio calculations, with deviations typically lower than 100 cm-1. The crystal field splitting is very sensitive to subtle changes of the Yb3+ coordination environment. The magnetic anisotropy of [Yb(DPA)3]3- obtained with ab initio calculations was found to be extremely sensitive to changes in the twist angle of the upper and lower faces of the tricapped trigonal prismatic coordination polyhedron. Ab initio ligand field theory provides a straightforward chemical justification for the changes in magnetic anisotropy, which are responsible for the observed pseudocontact shifts in the NMR spectra.

Recurrent epibulbar dermoid cyst treated with amniotic membrane implant a case report.

BACKGROUND: The dermoid cyst considered a cystic teratoma derived from embryonic germinal epithelium is a slow-growing benign tumour. Dermoid cysts may occur in the orbital and periorbital region in paediatric patients and are often recurrent. The surgical approach depends upon the site of the lesion, superficial or deep. To our knowledge, this is the first described case of a patient with resection of dermoid cyst treated with human amniotic membrane implant and topical application of 0.02% mitomycin C. CASE PRESENTATION: We present a case of a 12-year-old male with a tumour in the superotemporal region of the right eye (RE). Symptoms included decreased visual acuity (VA), burning eye, foreign body sensation, and photophobia of the affected eye. A physical examination detected blepharospasm. Ophthalmic examination of his RE, fingers count from a 1-2 m distance, showed no improvement with pinhole. Visual acuity was 20/20 on the left eye (LE). The bio-microscopic examination confirmed the presence of a tumour mass (15 mm × 12 mm) on the surface of the RE, invading the superotemporal sector. The tumour had a lobulated appearance, a shiny and vascularized surface covered by conjunctiva, a pearlescent-pink colour, a medium consistency, was renitent and painless. An ultrasound scan revealed atrophy of the pigmented retinal epithelium with scleral indentation of the RE. A computed tomography (CT) scan revealed a recurrent lesion consistent with an epibulbar dermoid cyst. Surgical excision of the lesion was performed and a human amniotic membrane (HAM) graft and topical 0.02% mitomycin C (MMC) were applied. Histopathological analysis confirmed the diagnosis of recurrent dermoid cyst. CONCLUSION: In this case report, we describe a case of recurrent epibulbar dermoid cyst treated with complete resection; topical MMC and HAM implant with good clinical outcome of the lesion and implant adhesion. Resection of a cyst of the ocular surface is not recommended when a large epibulbar dermoid tissue needs to be resected and no HAM graft is available.

The Relationship between NMR Chemical Shifts of Thermally Polarized and Hyperpolarized 89 Y Complexes and Their Solution Structures.

Recently developed dynamic nuclear polarization (DNP) technology offers the potential of increasing the NMR sensitivity of even rare nuclei for biological imaging applications. Hyperpolarized 89 Y is an ideal candidate because of its narrow NMR linewidth, favorable spin quantum number (I=1/2 ), and long longitudinal relaxation times (T1 ). Strong NMR signals were detected in hyperpolarized 89 Y samples of a variety of yttrium complexes. A dataset of 89 Y NMR data composed of 23 complexes with polyaminocarboxylate ligands was obtained using hyperpolarized 89 Y measurements or 1 H,89 Y-HMQC spectroscopy. These data were used to derive an empirical equation that describes the correlation between the 89 Y chemical shift and the chemical structure of the complexes. This empirical correlation serves as a guide for the design of 89 Y sensors. Relativistic (DKH2) DFT calculations were found to predict the experimental 89 Y chemical shifts to a rather good accuracy.

Magnetic Anisotropies in Rhombic Lanthanide(III) Complexes Do Not Conform to Bleaney's Theory.

We report a complete set of magnetic susceptibilities of lanthanide complexes with a macrocyclic ligand based on a 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane platform containing four hydroxyethyl pendant arms (L(1)). The [LnL(1)](3+) complexes are isostructural along the lanthanide series from Ce(3+) to Yb(3+), with the only structural change observed along the series being the monotonous shortening of the Ln-donor distances due to lanthanide contraction. The (1)H NMR spectra point to a D2 symmetry of the [LnL(1)](3+) complexes in aqueous solution, which provides a unique opportunity for analysis of the rhombic magnetic anisotropies with an unequivocal location of the magnetic axes. The contact contributions for the observed paramagnetic shifts have been estimated with density functional theory calculations on the [GdL(1)](3+) complex. Subsequently, the pseudocontact shifts could be factored out, thereby giving access to the axial and rhombic contributions of the magnetic susceptibility tensor. Our results show that the calculated magnetic anisotropies do not follow the trends predicted by Bleaney's theory, particularly in the case of Ho(3+) and Er(3+) complexes.

An IMU-to-Body Alignment Method Applied to Human Gait Analysis.

This paper presents a novel calibration procedure as a simple, yet powerful, method to place and align inertial sensors with body segments. The calibration can be easily replicated without the need of any additional tools. The proposed method is validated in three different applications: a computer mathematical simulation; a simplified joint composed of two semi-spheres interconnected by a universal goniometer; and a real gait test with five able-bodied subjects. Simulation results demonstrate that, after the calibration method is applied, the joint angles are correctly measured independently of previous sensor placement on the joint, thus validating the proposed procedure. In the cases of a simplified joint and a real gait test with human volunteers, the method also performs correctly, although secondary plane errors appear when compared with the simulation results. We believe that such errors are caused by limitations of the current inertial measurement unit (IMU) technology and fusion algorithms. In conclusion, the presented calibration procedure is an interesting option to solve the alignment problem when using IMUs for gait analysis.

Exceptionally Inert Lanthanide(III) PARACEST MRI Contrast Agents Based on an 18-Membered Macrocyclic Platform.

We report a macrocyclic ligand based on a 3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane platform containing four hydroxyethyl pendant arms (L(1)) that forms extraordinary inert complexes with Ln(3+) ions. The [EuL(1)](3+) complex does not undergo dissociation in 1 M HCl over a period of months at room temperature. Furthermore, high concentrations of phosphate and Zn(2+) ions at room temperature do not provoke metal-complex dissociation. The X-ray crystal structures of six Ln(3+) complexes reveal ten coordination of the ligand to the metal ions through the six nitrogen atoms of the macrocycle and the four oxygen atoms of the hydroxyethyl pendant arms. The analysis of the Yb(3+)- and Pr(3+)-induced paramagnetic (1)H NMR shifts show that the solid-state structures are retained in aqueous solution. The intensity of the (1)H NMR signal of bulk water can be modulated by saturation of the signals of the hydroxy protons of Pr(3+), Eu(3+), and Yb(3+) complexes following chemical-exchange saturation transfer (CEST). The ability of these complexes to provide large CEST effects at 25 and 37 °C and pH 7.4 was confirmed by using CEST magnetic resonance imaging experiments.