Improved Magneto-Microfluidic Separation of Nanoparticles through Formation of the ß-Cyclodextrin-Curcumin Inclusion Complex.

Molecular adsorption to the nanoparticle surface may switch the colloidal interactions from repulsive to attractive and promote nanoparticle agglomeration. If the nanoparticles are magnetic, then their agglomerates exhibit a much stronger response to external magnetic fields than individual nanoparticles. Coupling between adsorption, agglomeration, and magnetism allows a synergy between the high specific area of nanoparticles (∼100 m2/g) and their easy guidance or separation by magnetic fields. This yet poorly explored concept is believed to overcome severe restrictions for several biomedical applications of magnetic nanoparticles related to their poor magnetic remote control. In this paper, we test this concept using curcumin (CUR) binding (adsorption) to ß-cyclodextrin (ßCD)-coated iron oxide nanoparticles (IONP). CUR adsorption is governed by host-guest hydrophobic interactions with ßCD through the formation of 1:1 and, possibly, 2:1 ßCD:CUR inclusion complexes on the IONP surface. A 2:1 stoichiometry is supposed to promote IONP primary agglomeration, facilitating the formation of the secondary needle-like agglomerates under external magnetic fields and their magneto-microfluidic separation. The efficiency of these field-induced processes increases with CUR concentration and ßCD surface density, while their relatively short timescale (<5 min) is compatible with magnetic drug delivery application.

Adsorption of Organic Dyes on Magnetic Iron Oxide Nanoparticles. Part II: Field-Induced Nanoparticle Agglomeration and Magnetic Separation.

This paper (part II) is devoted to the effect of molecular adsorption on the surface of magnetic iron oxide nanoparticles (IONP) on the enhancement of their (secondary) field-induced agglomeration and magnetic separation. Experimentally, we use Methylene Blue (MB) cationic dye adsorption on citrate-coated maghemite nanoparticles to provoke primary agglomeration of IONP in the absence of the field. The secondary agglomeration is manifested through the appearance of needlelike micron-sized agglomerates in the presence of an applied magnetic field. With the increasing amount of adsorbed MB molecules, the size of the field-induced agglomerates increases and the magnetic separation on a magnetized micropillar becomes more efficient. These effects are mainly governed by the ratio of magnetic-to-thermal energy α, suspension supersaturation Δ0, and Brownian diffusivity Deff of primary agglomerates. The three parameters (α, Δ0, and Deff) are implicitly related to the surface coverage θ of IONP by MB molecules through the hydrodynamic size of primary agglomerates exponentially increasing with θ. Experiments and developed theoretical models allow quantitative evaluation of the θ effect on the efficiency of the secondary agglomeration and magnetic separation.

Kinetics of field-induced phase separation of a magnetic colloid under rotating magnetic fields.

This paper is focused on the experimental and theoretical study of the phase separation of a magnetic nanoparticle suspension under rotating magnetic fields in a frequency range, 5 Hz ≤ ν ≤ 25 Hz, relevant for several biomedical applications. The phase separation is manifested through the appearance of needle-like dense particle aggregates synchronously rotating with the field. Their size progressively increases with time due to the absorption of individual nanoparticles (aggregate growth) and coalescence with neighboring aggregates. The aggregate growth is enhanced by the convection of nanoparticles toward rotating aggregates. The maximal aggregate length, Lmax ∝ ν-2, is limited by fragmentation arising as a result of their collisions. Experimentally, the aggregate growth and coalescence occur at a similar timescale, ∼1 min, weakly dependent on the field frequency. The proposed theoretical model provides a semi-quantitative agreement with the experiments on the average aggregate size, aggregation timescale, and size distribution function without any adjustable parameter.

Muscle parameters estimation based on biplanar radiography.

The evaluation of muscle and joint forces in vivo is still a challenge. Musculo-Skeletal (musculo-skeletal) models are used to compute forces based on movement analysis. Most of them are built from a scaled-generic model based on cadaver measurements, which provides a low level of personalization, or from Magnetic Resonance Images, which provide a personalized model in lying position. This study proposed an original two steps method to access a subject-specific musculo-skeletal model in 30 min, which is based solely on biplanar X-Rays. First, the subject-specific 3D geometry of bones and skin envelopes were reconstructed from biplanar X-Rays radiography. Then, 2200 corresponding control points were identified between a reference model and the subject-specific X-Rays model. Finally, the shape of 21 lower limb muscles was estimated using a non-linear transformation between the control points in order to fit the muscle shape of the reference model to the X-Rays model. Twelfth musculo-skeletal models were reconstructed and compared to their reference. The muscle volume was not accurately estimated with a standard deviation (SD) ranging from 10 to 68%. However, this method provided an accurate estimation the muscle line of action with a SD of the length difference lower than 2% and a positioning error lower than 20 mm. The moment arm was also well estimated with SD lower than 15% for most muscle, which was significantly better than scaled-generic model for most muscle. This method open the way to a quick modeling method for gait analysis based on biplanar radiography.

Influence of the overall stiffness of a load-bearing porous titanium implant on bone ingrowth in critical-size mandibular bone defects in sheep.

The aim of this work was to assess the influence of reduction of the apparent mechanical properties of fully load-bearing porous titanium implants used in mandibular bone defects. Segmental 18mm long bone defects were created bilaterally in the lower jaws of adult ewes. One group of 6 ewes (group A) was treated with load-bearing 'rigid' (high stiffness) porous implants on the right side, and with control on the left side. A second group of 6 ewes (group B) was treated with 'flexible' porous and control implants exhibiting apparent mechanical properties ten times lower than the rigid implants. The mechanical behavior of the reconstructed hemi-mandibles was assessed by cantilever testing and bone ingrowth into the segmental defects was assessed by BV/TV measurement within the implant using micro-CT 12 weeks after implantation. A significantly higher rigidity was identified for porous implants compared with control implants at the anterior interface in group B. BV/TV of porous implants was significantly higher than that of control implants in group A. BV/TV differences were significant between porous and control implants in group B and were homogeneous along the main axis. Significantly higher BV/TV was identified in most sub-volumes of group B porous implants compared with group A. This work highlights the critical importance of the tuning of scaffolds to promote bone ingrowth with reference to the local strains occurring within the porous scaffold, which in this application was achieved using fully load-bearing low-stiffness porous titanium implants.

Differential thyroid hormone sensitivity of fast cycling progenitors in the neurogenic niches of tadpoles and juvenile frogs.

Adult neurogenesis occurs in neural stem cell (NSC) niches where slow cycling stem cells give rise to faster cycling progenitors. In the adult mouse NSC niche thyroid hormone, T3, and its receptor TRα act as a neurogenic switch promoting progenitor cell cycle completion and neuronal differentiation. Little is known about whether and how T3 controls proliferation of differentially cycling cells during xenopus neurogenesis. To address this question, we first used Sox3 as a marker of stem cell and progenitor populations and then applied pulse-chase EdU/IdU incorporation experiments to identify Sox3-expressing slow cycling (NSC) and fast cycling progenitor cells. We focused on the lateral ventricle of Xenopus laevis and two distinct stages of development: late embryonic development (pre-metamorphic) and juvenile frogs (post-metamorphic). These stages were selected for their relatively stable thyroid hormone availability, either side of the major dynamic phase represented by metamorphosis. TRα expression was found in both pre and post-metamorphic neurogenic regions. However, exogenous T3 treatment only increased proliferation of the fast cycling Sox3+ cell population in post-metamorphic juveniles, having no detectable effect on proliferation in pre-metamorphic tadpoles. We hypothesised that the resistance of proliferative cells to exogenous T3 in pre-metamorphic tadpoles could be related to T3 inactivation by the inactivating Deiodinase 3 enzyme. Expression of dio3 was widespread in the tadpole neurogenic niche, but not in the juvenile neurogenic niche. Use of a T3-reporter transgenic line showed that in juveniles, T3 had a direct transcriptional effect on rapid cycling progenitors. Thus, the fast cycling progenitor cells in the neurogenic niche of tadpoles and juvenile frogs respond differentially to T3 as a function of developmental stage.

Reliable femoral frame construction based on MRI dedicated to muscles position follow-up.

In vivo follow-up of muscle shape variation represents a challenge when evaluating muscle development due to disease or treatment. Recent developments in muscles reconstruction techniques indicate MRI as a clinical tool for the follow-up of the thigh muscles. The comparison of 3D muscles shape from two different sequences is not easy because there is no common frame. This study proposes an innovative method for the reconstruction of a reliable femoral frame based on the femoral head and both condyles centers. In order to robustify the definition of condylar spheres, an original method was developed to combine the estimation of diameters of both condyles from the lateral antero-posterior distance and the estimation of the spheres center from an optimization process. The influence of spacing between MR slices and of origin positions was studied. For all axes, the proposed method presented an angular error lower than 1° with spacing between slice of 10 mm and the optimal position of the origin was identified at 56 % of the distance between the femoral head center and the barycenter of both condyles. The high reliability of this method provides a robust frame for clinical follow-up based on MRI .

Alcohol, cigarette, and illegal substance consumption among medical students: a cross-sectional survey.

This study investigated addictive substance use by French medical students. A cross-sectional survey was distributed to 255 participants randomly selected from 1,021 second- to sixth-year medical students. Questionnaires were self-administered and included questions on sociodemographic characteristics, mental health, and alcohol (The Alcohol Use Disorders Identification Test [AUDIT test]), tobacco (Fagerstrom test), and illegal substance consumption (Cannabis Abuse Screening Test [CAST test]). The AUDIT scores indicated that 11% of the study participants were at risk for addiction and 21% were high-risk users. Tobacco dependence was strong or very strong for 12% of the participants. The CAST score showed that 5% of cannabis users needed health care services. Cannabis users were also more likely than non-users to fail their medical school examinations (89% vs. 39%, p<.01). One quarter of medical student participants (n=41) had used other illegal drugs, and 10% of study participants had considered committing suicide during the previous 12 months. Psychoactive substance consumption by French medical students requires preventive measures, screening, and health care services.

[Clinical case of the month. An unusual sepsis]. / Un sepsis mystérieux.

Lemierre's syndrome is a rare, but significant pathology to recognize. It most often affects young patients in good health; a late diagnosis can be fatal. It consists in an anaerobic septicemia (usually, Fusobacterium necrophorum) originating from a suppurative thrombophlebitis of the internal jugular vein. Infection occurs during a common sore throat and spreads by contiguity. The clinical presentation is a sepsis with pulmonary embolisations, but other sites of dissemination can also occur. Treatment consists of prolonged intravenous antibiotherapy associated with supportive therapy, if needed. Anticoagulation remains controversial. The outcome is favorable in most cases provided diagnosis and treatment are early; mortality however remains significant, around 5%.

Description and variability of temporal venous vascularization: clinical relevance in temporoparietal free flap technique.

The few studies on the venous vascularization of the temporal area indicate a high variability among individuals. The preoperative knowledge of the venous vascularization of the temporal area is critical for microsurgical reconstruction, such as temporoparietal fascia free flap, and especially in understanding the anatomy of the veins for flap survival. Therefore, we conducted an anatomic study to confirm the classification of Legre et al. and a radiologic study to examine the venous network of the temporal area. We found three frequent patterns of the temporal venous network: (1) Type I (the most common), with a predominant temporal vein; (2) Type II, with a predominant posterior auricular vein; (3) Type III, when both veins were equally important. Because of this great variability, the use of a temporal flap for reconstruction of the head and neck should be restricted, and the examination of venous vascularization appears to be necessary before surgery. Here, we report a three-dimensional description of the venous temporal vascularization by computer tomography, which is particularly useful before temporoparietal flaps.

Is thyroid hormone signaling relevant for vertebrate embryogenesis?

Classically, thyroid hormones (THs) have been primarily associated with postembryonic development (Tata, 1968), notably metamorphosis in anuran amphibians and flat fish. This period is parallel to the perinatal period in man and many marked developmental transitions in other species. As amply described in other chapters, metamorphosis is characterized by a peak of thyroxine (T(4)) and triiodothyronine (T(3)) that is synchronous with the metamorphic climax. In contrast, the developmental period that characterizes embryonic development prior to the significant production of TH by the endogenous thyroid gland has received little attention. Furthermore, the prevailing concepts of TH physiology during this period have been framed by two observations in amphibians and mammals: first, TRs are expressed, while circulating TH levels are much lower than those during metamorphosis and, second, extrapolating from the knowledge largely obtained from in vitro models, in the absence of TH, the aporeceptor represses target gene transcription during premetamorphic development. We propose to revisit both concepts in the light of accumulating data, first, on TH availability both in eggs and in embryos and, second, on the increasing knowledge of the complexity of TR and TH control of transcription.