Antiulcer Effect of Aqueous Ethanolic Extracts of Pseudocedrela kotschyi (Schweinf) Harms (Meliaceae) and Ximenia americana L. (Olacaceae).

Purpose: This study aimed to provide pharmacological evidence of Pseudocedrela kotschyi and Ximenia americana in preventing or healing peptic ulcers claimed by traditional healers in Burkina Faso. Methods: The trunk bark of Pseudocedrela kotschyi and the roots bark of Ximenia americana (Olacaceae) were macerated in mixed ethanol/water (80:20), respectively, to obtain dried extracts. Two models of hydrochloric acid (HCl, 0.3 M/ethanol, 60%) and hypothermic stress-induced peptic ulcer were used. The cytoprotective effect of individual or combined plant extracts was assessed at 1; 10; 30mg/kg. bw. Then, the healing effect of the extracts at 10mg/kg.bw was evaluated within 21 days of treatment on the hydrochloric acid-induced ulcer model. The extracts' antioxidant activity and phenolic content were assessed to support the plant extracts' efficiency. Results: The extracts of P. kotschyi and X. americana at 10 mg/kg.bw reduced ulceration index in hydrochloric acid- and hypothermic stress-ulcer models by more than 83% and 65%, respectively. The extract from X. americana at 10mg/kg.bw allowed complete ulcer healing but not the association of the two plant extracts. The plant extracts had IC50of inhibition of DPPH radical lower than 5µg/mL and total ferric reducing antioxidant power of more than 77 mg EQAA/100mg. The total polyphenolic content was 64.82 ±0.99 and 53.75 ±1.39 mg EGA/g of dried extract of P. kotschyi and X. americana, respectively. Conclusion: X. americana extract is better than the combined two plant extracts in gastric cytoprotection and ulcer healing. Further investigations are needed to highlight mechanism-based effects.

Adéquation des soins de santé maternelle, néonatale et infantile: de la grossesse au programme d'immunisation de l'enfant dans la Zone de Santé Kenya à Lubumbashi / NA

Introduction. Le continuum des soins pour la santé maternelle, néonatale et infantile reconnait une interrelation étroite entre la santé de la mère, du nouveau-né et de l'enfant à différents niveaux. L'objectif était de vérifier l'adéquation d'utilisation des services essentiels dans le continuum des soins de santé maternelle, néonatale et infantile. Méthodologie. Il s'agit d'une étude descriptive transversale sur interview semi-dirigée auprès des femmes ayant un enfant de 9 mois à une année pendant la période allant de mars à juin 2022. L'échantillonnage a été arrêté à 422 femmes. Résultats. La moyenne d'âge maternel était de 28,37 ± 6,41 ans dont les extrêmes étaient de 17 ans et 47 ans. Le taux de suivi de CPN était de 88,86%, la fréquence moyenne des CPN était de 2,5 ± 1,3. Pendant les CPN, 82,93% des femmes avaient bénéficié d'un contrôle de la pression artérielle (PA), 80,27% de la mesure du poids, 78,40% de dépistage du VIH, 77,33% de la vaccination contre le tétanos, 76% de la prophylaxie contre le paludisme et 73,33% d'une supplémentation martiale. Le taux de césarienne était de 18,48% et 62,56% des femmes avaient accouché à l'hôpital ; 33,18% au centre de santé ; 3,32% à domicile et 0,95% en cours de route. Ainsi, 97,15% des enfants avaient été vaccinés et avaient reçu les vaccins anti polio, VPI, BCG et 95,97% avaient reçu DTC, pneumonie et le vaccin contre l'hépatite B, 95,02% des enfants avaient reçu le VAR. Conclusion. Les soins pour la santé maternelle, néonatale et infantile pose encore des problèmes à Lubumbashi. Ainsi la compréhension de la façon dont les femmes utilisent les soins aidera à mettre en œuvre et prioriser les interventions visant à améliorer la santé maternelle, néonatale et infantile.

Dynamic Speckle Holography.

We introduce dynamic speckle holography, a new technique that combines imaging and scattering to measure three-dimensional maps of displacements as small as ten nanometers over several centimeters, greatly extending the capabilities of traditional imaging systems. We attain this sensitivity by imaging speckle patterns of light collected at three scattering angles and measuring the decay in the temporal correlation due to local motion. We use dynamic speckle holography to measure the strain field of a colloidal gel undergoing fracture and establish the surprising role of internal tension in driving the fracture.

The vortex-driven dynamics of droplets within droplets.

Understanding the fluid-structure interaction is crucial for an optimal design and manufacturing of soft mesoscale materials. Multi-core emulsions are a class of soft fluids assembled from cluster configurations of deformable oil-water double droplets (cores), often employed as building-blocks for the realisation of devices of interest in bio-technology, such as drug-delivery, tissue engineering and regenerative medicine. Here, we study the physics of multi-core emulsions flowing in microfluidic channels and report numerical evidence of a surprisingly rich variety of driven non-equilibrium states (NES), whose formation is caused by a dipolar fluid vortex triggered by the sheared structure of the flow carrier within the microchannel. The observed dynamic regimes range from long-lived NES at low core-area fraction, characterised by a planetary-like motion of the internal drops, to short-lived ones at high core-area fraction, in which a pre-chaotic motion results from multi-body collisions of inner drops, as combined with self-consistent hydrodynamic interactions. The onset of pre-chaotic behavior is marked by transitions of the cores from one vortex to another, a process that we interpret as manifestations of the system to maximize its entropy by filling voids, as they arise dynamically within the capsule.

Singlet-Contrast Magnetic Resonance Imaging: Unlocking Hyperpolarization with Metabolism*.

Hyperpolarization-enhanced magnetic resonance imaging can be used to study biomolecular processes in the body, but typically requires nuclei such as 13 C, 15 N, or 129 Xe due to their long spin-polarization lifetimes and the absence of a proton-background signal from water and fat in the images. Here we present a novel type of 1 H imaging, in which hyperpolarized spin order is locked in a nonmagnetic long-lived correlated (singlet) state, and is only liberated for imaging by a specific biochemical reaction. In this work we produce hyperpolarized fumarate via chemical reaction of a precursor molecule with para-enriched hydrogen gas, and the proton singlet order in fumarate is released as antiphase NMR signals by enzymatic conversion to malate in D2 O. Using this model system we show two pulse sequences to rephase the NMR signals for imaging and suppress the background signals from water. The hyperpolarization-enhanced 1 H-imaging modality presented here can allow for hyperpolarized imaging without the need for low-abundance, low-sensitivity heteronuclei.

Rehabilitation of persons with dementia: using technology to improve participation.

OBJECTIVES: The current study examined how a technology system, "It's Never 2 Late" (iN2L), may help augment traditional rehabilitation strategies for older adults with dementia by improving engagement in therapy sessions and achieving better functional outcomes. METHOD: The study used a two group quasi-experimental design. Older adults with dementia (N = 96) were recruited from two rehabilitation departments housed within residential care communities. Participants received daily occupational and physical therapy sessions using treatment as usual (TAU) at one site (n = 49) or treatment with iN2L (n = 47) at the other site. A goal attainment approach was used to assess functional outcomes. It was hypothesized that patients whose therapists used iN2L in treatment will show greater attainment of therapy goals and greater engagement during OT and PT sessions than patients receiving TAU. It was also hypothesized that levels and improvement in engagement will mediate the association of treatment type (iN2L or TAU) with greater goal attainment. RESULTS: Participants in the iN2L treatment had significantly higher goal attainment than TAU, significantly higher levels of engagement at baseline, and significantly steeper increases in engagement over the course of therapy. The effects of treatment on goal attainment was significantly mediated by increases in engagement. CONCLUSION: Findings suggest that iN2L technology has the potential to increase treatment engagement and enhance rehabilitation outcomes among older adults with dementia.

Coronarographie et interventions chez des sujets de moins 40 ans au CHU aristide le dantec

Introduction: La coronarographie est une méthode exploratrice et thérapeutique des artères coronaires qui connait depuis quelques années des avancées remarquables, de telle sorte que ses indications peuvent s'étendre à tous les âges en fonction des orientations cliniques. L'objectif de ce travail était de décrire les aspects des artères coronaires chez les patients de moins de 40 ans explorés au CHU Aristide Le Dantec.Patients et Méthodes: Nous avons effectué une étude descriptive qui incluait tous les patients dont l'âge était inférieur ou égal à 40 ans et qui avaient eu une coronarographie suite à un consentement éclairé dans la période du 1er Mai 2014 au 31 Août 2017. Les paramètres étudiés étaient épidémiologiques, cliniques, coronarographique, incluant l'éventuelle angioplastie Résultats: Nous avions inclus 32 patients. L'âge moyen était de 33,84 ± 5,59 ans, avec un minimum de 18 ans. Le genre masculin prédominait avec 27 hommes. Le facteur de risque cardio-vasculaire le plus fréquemment retrouvé était le tabac (28,13%) suivi de la dyslipidémie (25%), de l'hérédité (18,75%) et du surpoids (15,6%). Chez deux patients (6,25%), on a noté une consommation de substance stupéfiante. Les indications de la coronarographie étaient entre autres, le syndrome coronaire aigu (72%) et l'angor d'effort à (19%). La coronarographie était normale chez 11 patients et Pathologique chez les 21 restants, incluant 15 cas (46,87%) avec des lésions serrées. Les atteintes angiographiquement significatives étaient dominées par les atteintes mono-tronculaires dans 50% des cas. L'angioplastie était réalisée avec satisfaction chez 5 patients avec une prédominance de stents nus.Conclusion : Chez le sujet jeune avec syndrome coronarien aigu ou angor d'effort, le facteur de risque le plus fréquent est le tabac et l'atteinte coronaire est le plus souvent mono tronculaire

Probing shear-induced rearrangements in Fourier space. I. Dynamic light scattering.

Understanding the microscopic origin of the rheological behavior of soft matter is a long-lasting endeavour. While early efforts concentrated mainly on the relationship between rheology and structure, current research focuses on the role of microscopic dynamics. We present in two companion papers a thorough discussion of how Fourier space-based methods may be coupled to rheology to shed light on the relationship between the microscopic dynamics and the mechanical response of soft systems. In this first companion paper, we report a theoretical, numerical and experimental investigation of dynamic light scattering coupled to rheology. While in ideal solids and simple viscous fluids the displacement field under a shear deformation is purely affine, additional non-affine displacements arise in many situations of great interest, for example in elastically heterogeneous materials or due to plastic rearrangements. We show how affine and non-affine displacements can be separately resolved by dynamic light scattering, and discuss in detail the effect of several non-idealities in typical experiments.

Probing shear-induced rearrangements in Fourier space. II. Differential dynamic microscopy.

We discuss in two companion papers how Fourier-space measurements may be coupled to rheological tests in order to elucidate the relationship between mechanical properties and microscopic dynamics in soft matter. In this second companion paper, we focus on Differential Dynamic Microscopy (DDM) under shear. We highlight the analogies and the differences with dynamic light scattering coupled to rheology, providing a theoretical approach and practical guidelines to separate the contributions to DDM arising from the affine and the non-affine part of the microscopic displacement field. We show that in DDM under shear the coherence of the illuminating source plays a key role, determining the effective sample thickness that is probed. Our theoretical analysis is validated by experiments on 2D samples and 3D gels.

Complete on/off responsive ParaCEST MRI contrast agents for copper and zinc.

Two thulium-based ParaCEST responsive contrast agents, Tm-DOTAm-py and Tm-DOTAm-ßAla-py, have been synthesized and evaluated for imaging copper and zinc. Unusual for responsive MRI contrast agents, both agents display a complete on/off response in the presence of transition metals. Both complexes function as paraCEST agents in the absence of copper and zinc, with the positively charged Tm-DOTAm-py being more sensitive than the neutrally charged Tm-DOTAm-ßAla-py. In each case, the CEST signal arises from amide protons rather than from a water molecule coordinated to Tm3+ ions. Upon binding to Cu+, Cu2+, or Zn2+, the exchange rate of the amide protons increases substantially, resulting in a complete loss of the CEST signal. This efficient mode of action along with the lack of inner-sphere water molecules both in the presence and absence of transition metals was confirmed by 1/T1 NMRD profiles, 17O NMR measurements, and molecular modelling simulations. Neither complex is selective for copper over zinc. Both form either a 1 : 1 TmL : Cu+ or a 2 : 1 TmL : Cu2+ and TmL : Zn2+ complexes with binding affinities comparable to that of other responsive MRI contrast agents and sensitivity comparable to that of other CEST contrast agents.

The Evolution of HD2 Proteins in Green Plants.

In eukaryotes, protein deacetylation is carried out by two well-conserved histone deacetylase (HDAC) families: RPD3/HDA1 and SIR2. Intriguingly, model plants such as Arabidopsis express an additional plant-specific HDAC family, termed type-2 HDACs (HD2s). Transcriptomic analyses from more than 1300 green plants generated by the 1000 plants (1KP) consortium showed that HD2s appeared early in green plant evolution, the first members being detected in several streptophyte green alga. The HD2 family has expanded via several rounds of successive duplication; members are expressed in all major green plant clades. Interestingly, angiosperm species express new HD2 genes devoid of a zinc-finger domain, one of the main structural features of HD2s. These variants may have been associated with the origin and/or the biology of the ovule/seed.

The release of Doxorubicin from liposomes monitored by MRI and triggered by a combination of US stimuli led to a complete tumor regression in a breast cancer mouse model.

The work aimed at developing a novel MRI-based theranostic protocol for improving the anticancer efficacy of a Doxil-like liposomal formulation. The goal was achieved stimulating the intratumor release of the drug from the nanocarrier and favoring its diffusion in the lesion by the sequential application of low-intensity pulsed ultrasound. The protocol was tested on mice bearing a syngeneic breast cancer model. The combination of acoustic waves with different characteristics allowed for: i) the release of the drug and the co-encapsulated MRI agent (Gadoteridol) from the liposomes in the vessels of the tumor region, and ii) the extravasation of the released material, as well as intact liposomes, in the tumor stroma. The MR-T1 contrast enhancement measured in the tumor reported on the delivery and US-triggered release of Doxorubicin. The developed protocol resulted in a marked increase in the intratumor drug concentration that, in turn, led to the complete regression of the lesion. The protocol has a good clinical translatability because all the components of the theranostic agent (Doxorubicin, liposomes, Gadoteridol) are approved for human use.

An efficient scheme for sampling fast dynamics at a low average data acquisition rate.

We introduce a temporal scheme for data sampling, based on a variable delay between two successive data acquisitions. The scheme is designed so as to reduce the average data flow rate, while still retaining the information on the data evolution on fast time scales. The practical implementation of the scheme is discussed and demonstrated in light scattering and microscopy experiments that probe the dynamics of colloidal suspensions using CMOS or CCD cameras as detectors.

A stress-controlled shear cell for small-angle light scattering and microscopy.

We develop and test a stress-controlled, parallel plates shear cell that can be coupled to an optical microscope or a small angle light scattering setup, for simultaneous investigation of the rheological response and the microscopic structure of soft materials under an imposed shear stress. In order to minimize friction, the cell is based on an air bearing linear stage, the stress is applied through a contactless magnetic actuator, and the strain is measured through optical sensors. We discuss the contributions of inertia and of the small residual friction to the measured signal and demonstrate the performance of our device in both oscillating and step stress experiments on a variety of viscoelastic materials.

Evaluation of the dose enhancement of combined ¹°B + ¹57Gd neutron capture therapy (NCT).

An innovative molecule, GdBLDL, for boron neutron capture therapy (BNCT) has been developed and its effectiveness as a BNCT carrier is currently under evaluation using in vivo experiments on small animal tumour models. The molecule contains both (10)B (the most commonly used NCT agent) and (157)Gd nuclei. (157)Gd is the second most studied element to perform NCT, mainly thanks to its high cross section for the capture of low-energy neutrons. The main drawback of (157)Gd neutron capture reaction is the very short range and low-energy secondary charged particles (Auger electrons), which requires (157)Gd to be very close to the cellular DNA to have an appreciable biological effect. Treatment doses were calculated by Monte Carlo simulations to ensure the optimised tumour irradiation and the sparing of the healthy organs of the irradiated animals. The enhancement of the absorbed dose due to the simultaneous presence of (10)B and (157)Gd in the experimental set-up was calculated and the advantage introduced by the presence of (157)Gd was discussed.

In Vivo MR Imaging of Fibrin in a Neuroblastoma Tumor Model by Means of a Targeting Gd-Containing Peptide.

PURPOSE: A magnetic resonance imaging contrast agent based on a tetrameric Gd-DTPA-like system linked to a fibrin-targeting peptide (Gd-F) has been designed for in vivo tumor characterization. PROCEDURES: Gd-F was synthesized following Fmoc-SPPS strategy. Binding was measured using soluble fibrin DD(E) fragment and a dried fibrin assay. Contrast efficiency was tested on human and mouse clots and in vivo on Neuro2A tumor model. An anti-thrombotic drug was used to evaluate Gd-F sensitivity for changes in fibrin availability at the tumor site. RESULTS: The high relaxivity of Gd-F (42 mM(-1) s(-1), per molecule) yielded a strong signal enhancement in human and murine clots. High contrast was also measured in vivo in Neuro2A tumors, with a persistent enhancement in tumor rim and stroma. Upon treatment with an anti-thrombotic drug, the contrast uptake was significantly reduced in the tumor area confirming the specificity of the probe. CONCLUSIONS: Gd-F resulted to be an efficient probe for tumor delineation and for monitoring fibrin deposits during tumor progression and anti-thrombotic therapy.

Preparation and in vitro characterization of chitosan nanobubbles as theranostic agents.

Theranostic delivery systems are nanostructures that combine the modality of therapy and diagnostic imaging. Polymeric micro- and nanobubbles, spherical vesicles containing a gas core, have been proposed as new theranostic carriers for MRI-guided therapy. In this study, chitosan nanobubbles were purposely tuned for the co-delivery of prednisolone phosphate and a Gd(III) complex, as therapeutic and MRI diagnostic agent, respectively. Perfluoropentane was used for filling up the internal core of the formulation. These theranostic nanobubbles showed diameters of about 500nm and a positive surface charge that allows the interaction with the negatively charged Gd-DOTP complex. Pluronic F68 was added to the nanobubble aqueous suspension as stabilizer agent. The encapsulation efficiency was good for both the active compounds, and a prolonged drug release profile was observed in vitro. The effect of ultrasound stimulation on prednisolone phosphate release was evaluated at 37°C. A marked increase on drug release kinetics with no burst effect was obtained after the exposure of the system to ultrasound. Furthermore, the relaxivity of the MRI probe changed upon incorporation in the nanobubble shell, thereby offering interesting opportunity in dual MRI-US experiments. The ultrasound characterization showed a good in vitro echogenicity of the theranostic nanobubbles. In summary, chitosan drug-loaded nanobubbles with Gd(III) complex bound to their shell might be considered a new platform for imaging and drug delivery with the potential of improving anti-cancer treatments.

Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells.

In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 µg ml(-1) (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation.

Sonosensitive theranostic liposomes for preclinical in vivo MRI-guided visualization of doxorubicin release stimulated by pulsed low intensity non-focused ultrasound.

The main goal of this study was to assess the theranostic performance of a nanomedicine able to generate MRI contrast as a response to the release from liposomes of the antitumor drug Doxorubicin triggered by the local exposure to pulsed low intensity non focused ultrasounds (pLINFU). In vitro experiments showed that Gadoteridol was an excellent imaging agent for probing the release of Doxorubicin following pLINFU stimulation. On this basis, the theranostic system was investigated in vivo on a syngeneic murine model of TS/A breast cancer. MRI offered an excellent guidance for monitoring the pLINFU-stimulated release of the drug. Moreover, it provided: i) an in vivo proof of the effective release of the liposomal content, and ii) a confirmation of the therapeutic benefits of the overall protocol. Ex vivo fluorescence microscopy indicated that the good therapeutic outcome was originated from a better diffusion of the drug in the tumor following the pLINFU stimulus. Very interestingly, the broad diffusion of the drug in the tumor stroma appeared to be mediated by the presence of the liposomes themselves. The results of this study highlighted either the great potential of US-based stimuli to safely trigger the release of a drug from its nanocarrier or the associated significant therapeutic improvement. Finally, MRI demonstrated to be a valuable technique to support chemotherapy and monitoring the outcome. Furthermore, in this specific case, the theranostic agent developed has a high clinical translatability because the MRI agent utilized is already approved for human use.

A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies.