Grafting a chromophore on AMD070 analogues for CXCR4 bioimaging: Chemical synthesis and in vitro assessment of the inhibition properties of the CXCR4 receptor.

Thank to their particular pharmacokinetics, the use of small organic molecules can be a very promising alternative to macromolecular targeting biomolecules (i.e. antibodies, peptides…) for specific imaging of tumours.

Use of an Artificial Intelligence Device for Evaluating Blood Loss in Complex Major Orthopaedic Surgery Procedures.

Background: An artificial intelligence algorithm that analyzes the pulse oximeter waveform in the fingertip can be used to determine the compensatory reserve index (CRI) in trauma patients. This measurement shows the remaining cardiovascular capacity and is known to be more specific and sensitive in detecting blood loss than are routine vital signs. We hypothesized that the CRI measurement could predict loss of reserve cardiovascular capacity in patients undergoing major orthopaedic surgery, and therefore could help in their management.

Selective synthesis of an elusive -functional bis-cyclam and study of its inhibition of the CXCR4 chemokine receptor.

This article presents the controlled synthesis of a rare example of ,'-linked bis-cyclam architecture in mild conditions through the "bis-aminal" route previously used for the advantageous synthesis of cyclam, - and -functional cyclams and ,'-bis-cyclams. Two synthetic pathways were explored with the smart design of α,β-unsaturated ketones or alkyl halides bis-cyclizing agents. The first led to the isolation of a key intermediate for the future design of -functionalized bis-cyclams, whereas the second allowed the preparation of the targeted ,'-xylylene-bis-cyclam under mild conditions with decent yield.

Enhanced macromolecular substance extravasation through the blood-brain barrier via acoustic bubble-cell interactions.

The blood-brain barrier (BBB) maintains brain homeostasis, regulates influx and efflux transport, and provides protection to the brain tissue. Ultrasound (US) and microbubble (MB)-mediated blood-brain barrier opening is an effective and safe technique for drug delivery in-vitro and in-vivo. However, the exact mechanism underlying this technique is still not fully elucidated.

Delivery of Anticancer Drugs Using Microbubble-Assisted Ultrasound in a 3D Spheroid Model.

Tumor spheroids are promising three-dimensional (3D) tumor models for the evaluation of drug delivery methods. The design of noninvasive and targeted drug methods is required to improve the intratumoral bioavailability of chemotherapeutic drugs and reduce their adverse off-target effects. Among such methods, microbubble-assisted ultrasound (MB-assisted US) is an innovative modality for noninvasive targeted drug delivery.

A Phosphine Oxide-Functionalized Cyclam as a Specific Copper(II) Chelator.

Although cyclam-based ligands are among the strongest copper(II) chelators available, they also usually present good affinity for other divalent cations [Zn(II), Ni(II), and Co(II)], with no copper(II)-specific cyclam ligands having been described so far. As such a property is highly desirable in a wide range of applications, we present herein two novel phosphine oxide-appended cyclam ligands that could be efficiently synthesized through Kabachnik-Fields type reactions on protected cyclam precursors. Their copper(II) coordination properties were closely studied by different physicochemical techniques [electron paramagnetic resonance (EPR) and ultraviolet-visible (UV-vis) spectroscopies, X-ray diffraction, and potentiometry].

Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review.

Tumor spheroids as well as multicellular tumor spheroids (MCTSs) are promising 3D in vitro tumor models for drug screening, drug design, drug targeting, drug toxicity, and validation of drug delivery methods. These models partly reflect the tridimensional architecture of tumors, their heterogeneity and their microenvironment, which can alter the intratumoral biodistribution, pharmacokinetics, and pharmacodynamics of drugs. The present review first focuses on current spheroid formation methods and then on in vitro investigations exploiting spheroids and MCTS for designing and validating acoustically mediated drug therapies.

Highly inert Cu(II) complexes of -aryl bifunctional cyclam-picolinates with remarkable Cu-labelling and biodistribution.

Cyclam-picolinate chelators were functionalized click chemistry with an additional carboxyl group for subsequent bioconjugation to antibodies or for the modification of the overall charge of the corresponding Cu-radiocomplexes. The -aryl functionalization strategy developed here preserves the chemical properties of the radiocomplexes whilst deeply enhancing their applications within nuclear medicine.

Flaviviridae and mitochondria: Everything you always wanted to know about their relationship but were afraid to ask.

Infections with Flaviviridae constitute a major public health concern, especially considering the limited availability of prophylactic and therapeutic treatments. Most notably, the recent emergence of Zika virus in the Americas was associated with the dramatic increase of severe symptoms such as congenital microcephaly, while hepatitis C virus causes the death of approximately 300,000 individuals annually. Flaviviridae have evolved to hijack cellular organelles and to favor their replication, often via divergent molecular mechanisms.

[Flaviviridae and mitochondria: Everything you always wanted to know about their relationship but were afraid to ask].

Infections with Flaviviridae constitute a major public health concern, especially considering the limited availability of prophylactic and therapeutic treatments. Most notably, the recent emergence of Zika virus in the Americas was associated with the dramatic increase of severe symptoms such as congenital microcephaly, while hepatitis C virus causes the death of approximately 300,000 individuals annually. Flaviviridae have evolved to hijack cellular organelles and to favor their replication, often by divergent molecular mechanisms.

Cobalt-chromium femoral components developed scratches and released metal debris in simulated wear whereas ceramic femoral components did not.

Aims: The aims of this study were to evaluate wear on the surface of cobalt-chromium (CoCr) femoral components used in total knee arthroplasty (TKA) and compare the wear of these components with that of ceramic femoral components.

Methods: Optical profilometry was used to evaluate surface roughness and to examine the features created by the wear process in a knee wear simulator. We developed a method of measuring surface changes on five CoCr femoral components and quantifying the loss of material from the articular surface during the wear process.

Valosin-containing protein ATPase activity regulates the morphogenesis of Zika virus replication organelles and virus-induced cell death.

With no available therapies, infections with Zika virus (ZIKV) constitute a major public health concern as they can lead to congenital microcephaly. In order to generate an intracellular environment favourable to viral replication, ZIKV induces endomembrane remodelling and the morphogenesis of replication factories via enigmatic mechanisms. In this study, we identified the AAA+ type ATPase valosin-containing protein (VCP) as a cellular interaction partner of ZIKV non-structural protein 4B (NS4B).

Targeted Disruption of Lats1 and Lats2 in Mice Impairs Adrenal Cortex Development and Alters Adrenocortical Cell Fate.

It has recently been shown that the loss of the Hippo signaling effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in adrenocortical steroidogenic cells impairs the postnatal maintenance of the adrenal gland. To further explore the role of Hippo signaling in mouse adrenocortical cells, we conditionally deleted the key Hippo kinases large tumor suppressor homolog kinases 1 and -2 (Lats1 and Lats2, two kinases that antagonize YAP and TAZ transcriptional co-regulatory activity) in steroidogenic cells using an Nr5a1-cre strain (Lats1flox/flox;Lats2flox/flox;Nr5a1-cre). We report here that developing adrenocortical cells adopt characteristics of myofibroblasts in both male and female Lats1flox/flox;Lats2flox/flox;Nr5a1-cre mice, resulting in a loss of steroidogenic gene expression, adrenal failure and death by 2 to 3 weeks of age.

[F]ML-10 PET imaging fails to assess early response to neoadjuvant chemotherapy in a preclinical model of triple negative breast cancer.

Purpose: Pathological complete response to the neoadjuvant therapy (NAT) for triple negative breast cancer (TNBC) is predictive of prolonged patient survival. Methods for early evaluation of NAT efficiency are still needed, in order to rapidly adjust the therapeutic strategy in case of initial non-response. One option for this is molecular imaging of apoptosis induced by chemotherapy.

Enhanced adhesion of plasma-sprayed commercially pure titanium porous coatings to polished Mg-PSZ ceramic substrates.

The purpose of this study was to evaluate the suitability of a plasma sprayed titanium porous coating on polished magnesia-stabilized zirconia (Mg-PSZ) ceramic surfaces. We hypothesized that diffusion bonding was responsible for the adhesion of the coating to the ceramic substrate. Mg-PSZ tensile test coupons were vibratory polished (roughness Sa = 0.

Phase Transformation and Roughening in Artificially Aged and Retrieved Zirconia-Toughened Alumina Femoral Heads.

Background: Zirconia-toughened alumina (ZTA) used in hip arthroplasty contains yttria-stabilized zirconia (Y-TZP) as a toughening agent. However, Y-TZP is well known to degrade in vivo from tetragonal to monoclinic phase transformation. The stability of never-implanted ZTA femoral heads was evaluated in a severe artificial aging test, with retrieved ZTA heads also evaluated for clinical relevance.

Retrieved Magnesia-Stabilized Zirconia Femoral Heads Exhibit Minimal Roughening and Abrasive Potential.

Background: The degradation of ceramic femoral heads made of yttria-stabilized zirconia (Y-TZP) because of tetragonal-to-monoclinic phase transformation in vivo is well-described, whereas magnesia-stabilized zirconia (Mg-PSZ) ceramics resist phase transformation in a warm aqueous environment. The purpose of this study was to evaluate phase transformation, changes in surface topography, and roughness parameters, including changes in surface polarity and abrasiveness, among retrieved zirconia femoral heads.

Methods: A total of 69 Y-TZP and 86 Mg-PSZ-retrieved femoral heads were examined, with 5 never-implanted heads of each type as controls.

Comparing those diagnosed early versus late in their HIV infection: implications for public health.

Routine HIV surveillance cannot distinguish between recent and older infections: HIV-positive individuals reported soon or long after infection are both considered new diagnoses from a surveillance perspective, notwithstanding the time since infection. This lack of specificity makes it difficult to understand the jurisdiction-specific trends in HIV epidemiology needed for prevention planning. Previous efforts have been made to discern such timing of infection, but these methodologies are not easily applied in a public health setting.

Community-based, nurse-led post-exposure prophylaxis: results and implications.

HIV medications can be used as post-exposure prophylaxis to efficaciously prevent an HIV-negative person who has come into contact with HIV from becoming HIV-positive. Traditionally, these medications have been available in emergency departments, which have constituted a barrier for the members of many minority groups who are greatly affected by HIV transmission (i.e.

Counselling about HIV serological status disclosure: nursing practice or law enforcement? a Foucauldian reflection.

Recently, focus groups and qualitative interviews with nurses who provide frontline care for persons living with HIV highlighted the contentiousness surrounding the seemingly innocuous activity of counselling clients about HIV-status disclosure, hereafter disclosure counselling. These empirical studies highlighted that while some nurses felt they should instruct clients to disclose their HIV-positive status if HIV transmission were possible, other nurses were equally adamant that such counselling was outside the nursing scope of practice. A review of these opposing perceptions about disclosure counselling, including an examination of the empirical evidence which supports each point, revealed that the dichotomous arguments needed to be nuanced.

Overviewing a Nurse-Led, Community-Based HIV PEP Program: Applying the Extant Literature in Frontline Practice.

This clinical concept paper overviews a program to facilitate access to postexposure prophylaxis (PEP) for gay, bisexual, and other men who have sex with men. The project, which was a collaborative initiative involving the local School of Nursing, public health unit, AIDS service organization, hospital-based HIV clinic, and an outpatient pharmacy, was implemented to circumvent common barriers to care identified in the literature. In this project, persons who present to one of the two participating clinics after having come, or likely having come, into contact with HIV within the previous 72 hr, are offered rapid HIV testing, also known as point-of-care (POC) testing, to rule out existing HIV infection, and provided with a follow-up appointment booked at the HIV clinic.

HIV criminal prosecutions and public health: an examination of the empirical research.

Objectives: To review the extant literature on HIV criminal laws, and to determine the impact of these laws on public health practice.

Methods: The available research on this topic was obtained and reviewed.

Results: The extant literature addressed three main topics: people's awareness of HIV criminal laws; people's perceptions of HIV criminal laws; and the potential effects of HIV criminal laws on people's sexual, HIV-status disclosure and healthcare-seeking practices.

Diamond-like carbon coatings enhance scratch resistance of bearing surfaces for use in joint arthroplasty: hard substrates outperform soft.

The purpose of this study was to test the hypotheses that diamond-like carbon (DLC) coatings will enhance the scratch resistance of a bearing surface in joint arthroplasty, and that a hard ceramic substrate will further enhance scratch resistance by reducing plastic deformation. We tested these hypotheses by applying a hard DLC coating to medical-grade cobalt chromium alloy (CoCr) and magnesia-stabilized zirconia (Mg-PSZ) femoral heads and performing scratch tests to determine the loads required to cause cohesive and adhesive fracture of the coating. Scratch tracks of DLC-coated and noncoated heads were then scanned by optical profilometry to determine scratch depth, width, and pile-up (raised edges), as measures of susceptibility to scratching.

Annexin-I expression modulates drug resistance in tumor cells.

The use of anti-cancer chemotherapy often leads to the rise of multidrug-resistant (MDR) tumors. We have previously reported the overexpression of a 40kDa protein (P-40) in several MDR tumor cell lines. In this report we describe the cloning of a 1.