Ecology meets reproductive medicine in HIV prevention: the case for geography-informed approaches for bacterial vaginosis in Africa.

Purpose Of Review: Women in Africa bear the burden of the HIV epidemic, which has been associated with the high prevalence of bacterial vaginosis (BV) in the region. However, little progress has been made in finding an effective cure for BV. Drawing on advances in microbiome-directed therapies for gastrointestinal disorders, similar live-biotherapeutic based approaches for BV treatment are being evaluated.

Genetic labeling of embryonically-born dentate granule neurons in young mice using the Penk mouse line.

The dentate gyrus (DG) of the hippocampus is a mosaic of dentate granule neurons (DGNs) accumulated throughout life. While many studies focused on the morpho-functional properties of adult-born DGNs, much less is known about DGNs generated during development, and in particular those born during embryogenesis. One of the main reasons for this gap is the lack of methods available to specifically label and manipulate embryonically-born DGNs.

Genomically informed small-molecule drugs overcome resistance to a sustained-release formulation of an engineered death receptor agonist in patient-derived tumor models.

Extrinsic pathway agonists have failed repeatedly in the clinic for three core reasons: Inefficient ligand-induced receptor multimerization, poor pharmacokinetic properties, and tumor intrinsic resistance. Here, we address these factors by (i) using a highly potent death receptor agonist (DRA), (ii) developing an injectable depot for sustained DRA delivery, and (iii) leveraging a CRISPR-Cas9 knockout screen in DRA-resistant colorectal cancer (CRC) cells to identify functional drivers of resistance. Pharmacological blockade of XIAP and BCL-X by targeted small-molecule drugs strongly enhanced the antitumor activity of DRA in CRC cell lines.

Fusion-mediated chromosomal instability promotes aneuploidy patterns that resemble human tumors.

Oncogenesis is considered to result from chromosomal instability, in addition to oncogene and tumor-suppressor alterations. Intermediate to aneuploidy and chromosomal instability, genome doubling is a frequent event in tumor development but the mechanisms driving tetraploidization and its impact remain unexplored. Cell fusion, one of the pathways to tetraploidy, is a physiological process involved in mesenchymal cell differentiation.

Erratum: Organocatalyzed synthesis of fluorinated poly(aryl thioethers).

A correction to this article has been published and is linked from the HTML version of this article.

Catalysis as an Enabling Science for Sustainable Polymers.

The replacement of current petroleum-based plastics with sustainable alternatives is a crucial but formidable challenge for the modern society. Catalysis presents an enabling tool to facilitate the development of sustainable polymers. This review provides a system-level analysis of sustainable polymers and outlines key criteria with respect to the feedstocks the polymers are derived from, the manner in which the polymers are generated, and the end-of-use options.

Organocatalyzed synthesis of fluorinated poly(aryl thioethers).

The preparation of high-performance fluorinated poly(aryl thioethers) has received little attention compared to the corresponding poly(aryl ethers), despite the excellent physical properties displayed by many polysulfides. Herein, we report a highly efficient route to fluorinated poly(aryl thioethers) via an organocatalyzed nucleophilic aromatic substitution of silyl-protected dithiols. This approach requires low catalyst loadings, proceeds rapidly at room temperature, and is effective for many different perfluorinated or highly activated aryl monomers.

Broad Spectrum Macromolecular Antimicrobials with Biofilm Disruption Capability and In Vivo Efficacy.

In this study, antimicrobial polymers are synthesized by the organocatalytic ring-opening polymerization of an eight-membered heterocyclic carbonate monomer that is subsequently quaternized with methyl iodide. These polymers demonstrate activity against clinically relevant Gram-positive Staphylococcus epidermidis and Staphylococcus aureus, Gram-negative Escherichia coli and Pseudomonas aeruginosa, and fungus Candida albicans with fast killing kinetics. Importantly, the polymer efficiently inhibits biofilm growth and lyses existing biofilm, leading to a reduction in biomass and cell viability.

Highly potent antimicrobial polyionenes with rapid killing kinetics, skin biocompatibility and in vivo bactericidal activity.

Effective antimicrobial agents are important arsenals in our perennial fight against communicable diseases, hospital-acquired and surgical site multidrug-resistant infections. In this study, we devise a strategy for the development of highly efficacious and skin compatible yet inexpensive water-soluble macromolecular antimicrobial polyionenes by employing a catalyst-free, polyaddition polymerization using commercially available monomers. A series of antimicrobial polyionenes are prepared through a simple polyaddition reaction with both polymer-forming reaction and charge installation occurring simultaneously.

Expanding the Cationic Polycarbonate Platform: Attachment of Sulfonium Moieties by Postpolymerization Ring Opening of Epoxides.

Postpolymerization modification is a critical strategy for the development of functional polycarbonate scaffolds for medicinal applications. To expand the scope of available postpolymerization functionalization methods, polycarbonates containing pendant thioether groups were synthesized by organocatalyzed ring-opening polymerization. The thioether group allowed for the postpolymerization ring-opening of functional epoxides, affording a wide variety of sulfonium-functionalized A-B diblock and A-B-A triblock polycarbonate copolymers.

All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth.

Gastric carcinoma is the third leading cause of cancer-related death worldwide. This cancer, most of the time metastatic, is essentially treated by surgery associated with conventional chemotherapy, and has a poor prognosis. The existence of cancer stem cells (CSC) expressing CD44 and a high aldehyde dehydrogenase (ALDH) activity has recently been demonstrated in gastric carcinoma and has opened new perspectives to develop targeted therapy.

Reduced variability and execution time to reach a target with a needle GPS system: Comparison between physicians, residents and nurse anaesthetists.

Ultrasound (US) guided needle positioning is safer than anatomical landmark techniques for central venous access. Hand-eye coordination and execution time depend on the professional's ability, previous training and personal skills. Needle guidance positioning systems (GPS) may theoretically reduce execution time and facilitate needle positioning in specific targets, thus improving patient comfort and safety.

BIOBRAD Study: The Search for Biomarkers of Bradykinin-Mediated Angio-Oedema Attacks.

Background: The aetiology of angio-oedema (AE) is difficult to determine; however, it is essential in emergency situations when two major contexts may be present: mast cell-mediated AE and bradykinin-mediated AE. Different forms of AE are currently distinguished based on clinical criteria (spontaneous duration of the attack, presence of concomitant or late-appearing superficial urticaria, history of atopy, and others), but specific biomarkers could improve patient management.

Objective: In this prospective study, potential biomarkers have been identified, and their statistical characteristics were examined.

Trypanosoma brucei gambiense Infections in Mice Lead to Tropism to the Reproductive Organs, and Horizontal and Vertical Transmission.

Trypanosoma brucei gambiense, transmitted by the tsetse fly, is the main causative agent of Human African trypanosomosis in West Africa and poses a significant health risk to 70 million people. Disease progression varies depending on host immunity, but usually begins with a haemo-lymphatic phase, followed by parasite invasion of the central nervous system. In the current study, the tropism of T.

Melt-processable dynamic-covalent poly(hemiaminal) organogels as scaffolds for UV-induced polymerization.

Hemiaminal poly(ethylene glycol) (PEG)-based organogels are formulated in polymerizable solvents. The dynamic-covalent nature of the solvent-H-bonded hemiaminal crosslinks, together with the modification of the crosslinking density of the organogels allows for temperature-dependent viscoelastic control. The shape of uncured gels can be permanently retained by templated UV-curing of the solvent, offering great promise for complex manufacturing, printing, sealants, and materials repair.

Precision synthesis of poly(ionic liquid)-based block copolymers by cobalt-mediated radical polymerization and preliminary study of their self-assembling properties.

A poly(ionic liquid)-based block copolymer (PIL BCP), namely, poly(vinyl acetate)-b-poly(N-vinyl-3-butylimidazolium bromide), PVAc-b-PVBuImBr, is synthesized by sequential cobalt-mediated radical polymerization (CMRP). A PVAc precursor is first prepared at 30 °C in bulk by CMRP of VAc, using bis(acetylacetonato)cobalt(II), Co(acac)2, and a radical source (V-70). Growth of PVBuImBr from PVAc-Co(acac)2 is accomplished by CMRP in DMF/MeOH (2:1, v/v).

N-Heterocyclic carbenes (NHCs) as organocatalysts and structural components in metal-free polymer synthesis.

The chemistry of N-heterocyclic carbenes (NHCs) has witnessed tremendous development in the past two decades: NHCs have not only become versatile ligands for transition metals, but have also emerged as powerful organic catalysts in molecular chemistry and, more recently, in metal-free polymer synthesis. To understand the success of NHCs, this review first presents the electronic properties of NHCs, their main synthetic methods, their handling, and their reactivity. Their ability to activate key functional groups (e.

Lattice stability and formation energies of intrinsic defects in Mg2Si and Mg2Ge via first principles simulations.

We report an ab initio study of the semiconducting Mg(2)X (with X = Si, Ge) compounds and in particular we analyze the formation energies of the different point defects with the aim of understanding the intrinsic doping mechanisms. We find that the formation energy of Mg(2)Ge is 50% larger than that of Mg(2)Si, in agreement with the experimental tendency. From a study of the stability and the electronic properties of the most stable defects, taking into account the growth conditions, we show that the main cause of the n doping in these materials comes from interstitial magnesium defects.

Imidazolium hydrogen carbonates versus imidazolium carboxylates as organic precatalysts for N-heterocyclic carbene catalyzed reactions.

Imidazolium-2-carboxylates (NHC-CO(2) adducts, 3) and (benz)imidazolium hydrogen carbonates ([NHC(H)][HCO(3)], 4) were independently employed as organic precatalysts for various molecular N-heterocyclic carbene (NHC) catalyzed reactions. NHC-CO(2) adducts were obtained by carboxylation in THF of related free NHCs (2), while the synthesis of [NHC(H)][HCO(3)] precursors was directly achieved by anion metathesis of imidazolium halides (1) using potassium hydrogen carbonate (KHCO(3)) in methanolic solution, without the need for the prior preparation of free carbenes. Thermogravimetric analysis (TGA) and TGA coupled with mass spectrometry (TGA-MS) of most [NHC(H)][HCO(3)] precursors 4 showed a degradation profile in stages, with either a concomitant or a stepwise release of H(2)O and CO(2), between 108 and 280 °C, depending on the nature of the azolium and substituents.

A beat-by-beat, on-line, cardiovascular index, CARDEAN, to assess circulatory responses to surgery: a randomized clinical trial during spine surgery.

Automated assessment of circulatory response to surgical stimuli is unsolved. Would detection of cardiac baroreflex inhibition assess adequacy of intra-operative anti-nociception upon incision, as performed on-line on a beat-by-beat basis by a cardiovascular index, CARDEAN™? 18 ASA I-II patients undergoing spinal disc repair were studied, in a prospective randomized single-blinded trial (observational study). During infusion of propofol to maintain bispectral index between 40 and 60, patients were allocated to receive an effect site target-controlled infusion of remifentanil at Ce = 2 or 4 ng ml(-1).

Imidazol(in)ium hydrogen carbonates as a genuine source of N-heterocyclic carbenes (NHCs): applications to the facile preparation of NHC metal complexes and to NHC-organocatalyzed molecular and macromolecular syntheses.

Anion metathesis of imidazol(in)ium chlorides with KHCO(3) afforded an easy one step access to air stable imidazol(in)ium hydrogen carbonates, denoted as [NHC(H)][HCO(3)]. In solution, these compounds were found to be in equilibrium with their corresponding imidazol(in)ium carboxylates, referred to as N-heterocyclic carbene (NHC)-CO(2) adducts. The [NHC(H)][HCO(3)] salts were next shown to behave as masked NHCs, allowing for the NHC moiety to be readily transferred to both organic and organometallic substrates, without the need for dry and oxygen-free conditions.

[Normobaric hyperoxia therapy for patients with traumatic brain injury].

Cerebral ischaemia plays a major role in the outcome of brain-injured patients. Because brain oxygenation can be assessed at bedside using intra-parenchymal devices, there has been a growing interest about whether therapeutic hyperoxia could be beneficial for severely head-injured patients. Normobaric hyperoxia increases brain oxygenation and may improve glucose-lactate metabolism in brain regions at risk for ischaemia.

Reduced brain edema and functional deficits after treatment of diffuse traumatic brain injury by carbamylated erythropoietin derivative.

Objective: To investigate the effects of carbamylated erythropoietin, a modified erythropoietin lacking erythropoietic activity, on brain edema and functional recovery in a model of diffuse traumatic brain injury.

Design: Adult male Wistar rats.

Setting: Neurosciences and physiology laboratories.

Development and physico-chemical characterization of a liposomal formulation of istaroxime.

Istaroxime, an investigational new drug that targets defective Ca(2+) cycling without compromising cardiac efficiency, may represent a promising and safe treatment of both acute and chronic heart failure. Even though the compound demonstrated good tolerability in a phase I/II safety study, symptoms related to the gastro-intestinal tract and pain at the injection site were reported as the most frequent side effects. The aim of this study was to encapsulate istaroxime in a drug delivery system (DDS) that could minimize the pain perceived upon administration.

The impact of erythropoietin on short-term changes in phosphorylation of brain protein kinases in a rat model of traumatic brain injury.

We found that recombinant human erythropoietin (rhEPO) reduced significantly the development of brain edema in a rat model of diffuse traumatic brain injury (TBI) (impact-acceleration model). In this study, we investigated the molecular and intracellular changes potentially involved in these immediate effects. Brain tissue nitric oxide (NO) synthesis, phosphorylation level of two protein kinases (extracellular-regulated kinase (ERK)-1/-2 and Akt), and brain water content were measured 1 (H1) and 2 h (H2) after insult.