Simultaneous in vivo positron emission tomography and magnetic resonance imaging

Positron emission tomography (PET) and magnetic resonance imaging (MRI) are widely used in vivo imaging technologies with both clinical and biomedical research applications. The strengths of MRI include high-resolution, high-contrast morphologic imaging of soft tissues; the ability to image physiologic parameters such as diffusion and changes in oxygenation level resulting from neuronal stimulation; and the measurement of metabolites using chemical shift imaging. PET images the distribution of biologically targeted radiotracers with high sensitivity, but images generally lack anatomic context and are of lower spatial resolution. Integration of these technologies permits the acquisition of temporally correlated data showing the distribution of PET radiotracers and MRI contrast agents or MR-detectable metabolites, with registration to the underlying anatomy. An MRI-compatible PET scanner has been built for biomedical research applications that allows data from both modalities to be acquired simultaneously. Experiments demonstrate no effect of the MRI system on the spatial resolution of the PET system and <10% reduction in the fraction of radioactive decay events detected by the PET scanner inside the MRI. The signal-to-noise ratio and uniformity of the MR images, with the exception of one particular pulse sequence, were little affected by the presence of the PET scanner. In vivo simultaneous PET and MRI studies were performed in mice. Proof-of-principle in vivo MR spectroscopy and functional MRI experiments were also demonstrated with the combined scanner

Traumatic lumbar Spondylolisthesis: Case Report

Only few cases of traumatic spondylolisthesis (from the cranial to lumbosacral joint) have been reported to date. Recovery of neurological function is dependent on the time of decompression and stabilization. We highlight the paramount importance that the time past between injury and surgical decompression have on neurological recovery and implant durability. Authors present the case of a 26 years old patient who suffered a motor crash 10 days ago before admission in our institution for cauda equina syndrome (L5 level). He also presented abdominal trauma with left kidney contusion, spleen contusion, thoracic contusion and left fibular fracture. X-ray and MRI examinations of the lumbosacral spine revealed grade 3 of spondylolistesis (60% anterior dislocation L5 - S1, intervertebral disc and posterior ligaments laceration, severe compression of the dural sac and dural laceration with CSF leakage through the posterior muscular mass). Surgery performed 14 days after the injury consisted in a posterior approach with L5 laminectomy, dural decompression and duroplasty with fascia lata, segmental reduction and stabilization with transpedicular screws, L5-S1 discectomy and anterior intervertebral grafting with two tricortical iliac crest grafts. Posterior lumbar interbody fusion was carried out using titanium screws (Solas system). Decompression, reduction with L5, S1 pedicular screw fixation, L5 – S1 disc excision and anterior intervertebral grafting with two tricortical iliac crest grafts is an appropriate surgical technique wich offer a good stabilization and fine functional recovering

On Optimal Coverage of a Tree with Multiple Robots

We study the algorithmic problem of optimally covering a tree with $k$ mobile robots. The tree is known to all robots, and our goal is to assign a walk to each robot in such a way that the union of these walks covers the whole tree. We assume that the edges have the same length, and that traveling along an edge takes a unit of time. Two objective functions are considered: the cover time and the cover length. The cover time is the maximum time a robot needs to finish its assigned walk and the cover length is the sum of the lengths of all the walks. We also consider a variant in which the robots must rendezvous periodically at the same vertex in at most a certain number of moves. We show that the problem is different for the two cost functions. For the cover time minimization problem, we prove that the problem is NP-hard when $k$ is part of the input, regardless of whether periodic rendezvous are required or not. For the cover length minimization problem, we show that it can be solved in polynomial time when periodic rendezvous are not required, and it is NP-hard otherwise

Bioengineering bacterial encapsulin nanocompartments as targeted drug delivery system

The development of Drug Delivery Systems (DDS) has led to increasingly efficient therapies for the treatment and detection of various diseases. DDS use a range of nanoscale delivery platforms produced from polymeric of inorganic materials, such as micelles, and metal and polymeric nanoparticles, but their variant chemical composition make alterations to their size, shape, or structures inherently complex. Genetically encoded protein nanocages are highly promising DDS candidates because of their modular composition, ease of recombinant production in a range of hosts, control over assembly and loading of cargo molecules and biodegradability. One example of naturally occurring nanocompartments are encapsulins, recently discovered bacterial organelles that have been shown to be reprogrammable as nanobioreactors and vaccine candidates. Here we report the design and application of a targeted DDS platform based on the Thermotoga maritima encapsulin reprogrammed to display an antibody mimic protein called Designed Ankyrin repeat protein (DARPin) on the outer surface and to encapsulate a cytotoxic payload. The DARPin9.29 chosen in this study specifically binds to human epidermal growth factor receptor 2 (HER2) on breast cancer cells, as demonstrated in an in vitro cell culture model. The encapsulin-based DDS is assembled in one step in vivo by co-expressing the encapsulin-DARPin9.29 fusion protein with an engineered flavin-binding protein mini-singlet oxygen generator (MiniSOG), from a single plasmid in Escherichia coli. Purified encapsulin-DARPin_miniSOG nanocompartments bind specifically to HER2 positive breast cancer cells and trigger apoptosis, indicating that the system is functional and specific. The DDS is modular and has the potential to form the basis of a multi-receptor targeted system by utilising the DARPin screening libraries, allowing use of new DARPins of known specificities, and through the proven flexibility of the encapsulin cargo loading mechanism, allowing selection of cargo proteins of choice

Strong Pinning in High Temperature Superconductors

Detailed measurements of the critical current density jc of YBa2Cu3O7 films grown by pulsed laser deposition reveal the increase of jc as function of the filmthickness. Both this thickness dependence and the field dependence of the critical current are consistently described using a generalization of the theory of strong pinning of Ovchinnikov and Ivlev [Phys. Rev. B 43, 8024 (1991)]. From the model, we deduce values of the defect density (10^21 m^-3) and the elementary pinning force, which are in good agreement with the generally accepted values for Y2O3-inclusions. In the absence of clear evidence that the critical current is determined by linear defects or modulations of the film thickness, our model provides an alternative explanation for the rather universal field dependence of the critical current density found in YBa2Cu3O7 films deposited by different methods.Comment: 11 pages; 8 Figures; Published Phys. Rev. B 66, 024523 (2002

Surgical management of symptomatic spinal cord and intracerebral cavernomas in a multiple cavernomas case

Multiple cavernous malformations are associated with familial cases and are present in 10-20% of all cavernoma cases. 5% of cavernomas are located intramedullary and of these only 10% present multiple cavernomas. With the availability of echo gradient MRI the cases of multiple cavernomas are diagnosed earlier and it is not rare that it uncovers multiple cavernomas in cases where only a single lesion can be identified on regular MRI sequences. We present the case of a 55 years old woman presented with a two years history of mild backache, followed by progressive lower legs motor deficit and urinary retention. The spine MRI showed an intramedullary T2/3 lesion and the cerebral MRI established the diagnosis of multiple cavernomas. One year after the intramedullary cavernoma was operated with success, she developed generalized seizures and a new cerebral MRI showed bleeding and volume growth of one right temporal pole cavernoma. The cerebral lesion was resected successfully and the patient was discharged free of seizures. This familial type multiple cavernomas cases should be screened and followed with repeated brain and spine MRI’s every year

El ferro, la llaminadura i el verí dels bacteris

El ferro és vital per a gairebé tots els organismes vius, atès el paper crucial que té en nombrosos processos biològics. Però, en concentracions inadequades, aquest element és un verí per a qualsevol cèl·lula. Per això, els éssers vius disposen de mecanismes que en controlen la concentració. Així, els vertebrats tenen sistemes que segresten ferro per evitar-ne l'efecte deleteri. A més, el segrest té un altre efecte positiu per a aquests animals, ja que el ferro no estarà disponible per al desenvolupament dels bacteris patògens que els puguin infectar. Com a resposta, els patògens bacterians han desenvolupat diverses estratègies de captura del ferro segrestat

Neuro-immune signatures in chronic low back pain subtypes

We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine, and Gulf War Illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18 kDa translocator protein, which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple etiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct “neuroinflammatory signatures”. To further explore this hypothesis, we tested whether neuroinflammatory signal can characterize putative etiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. “radicular” vs. “axial” back pain). Fifty-four chronic low back pain patients, twenty-six with axial back pain (43.7 ± 16.6 y.o. [mean±SD]) and twenty-eight with radicular back pain (48.3 ± 13.2 y.o.), underwent PET/MRI with [11C]PBR28, a second-generation radioligand for the 18 kDa translocator protein. [11C]PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the [11C]PBR28 data 1) to functionally localize the primary somatosensory cortex back and leg subregions and 2) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of “fibromyalgianess” (i.e. the degree of pain centralization, or “nociplastic pain”). Furthermore, statistical mediation models were employed to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, [11C]PBR28 PET signal and functional connectivity to the thalamus were: 1) higher in radicular compared to axial back pain patients, 2) positively correlated with each other and 3) positively correlated with fibromyalgianess scores, across groups. Finally, 4) fibromyalgianess mediated the association between [11C]PBR28 PET signal and primary somatosensory cortex-thalamus connectivity across groups. Our findings support the existence of “neuroinflammatory signatures” that are accompanied by neurophysiological changes, and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about inter-individual variability in neuro-immune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches