Impact of an addiction medicine consult service on patients admitted to the hospital with injection drug use-associated infective endocarditis

Background: The addition of an addiction medicine consult service has been shown to improve mortality and decrease hospital costs but its impact on the proportion of patients discharged against medical advice (DAMA) and in-hospital initiation of medication for opioid use disorder (MOUD) has not been examined. Methods: A retrospective before-after cohort study was performed at an urban, academic medical center between January 1, 2015 and November 1, 2019. We included adult patients with infective endocarditis and injection drug use determined by admitting diagnosis ICD-9 or ICD-10 codes or documentation within the history section of electronic health recordEHR. Our institution implemented a formal addiction medicine consult service on July 1, 2018. We determined the proportion of patients DAMA and the proportion of patients started on MOUD among patients in the pre-intervention (i.e. hospitalized before July 1, 2018) and intervention (i.e. hospitalized July 1, 2018 or after) groups. Results: A total of 171 patients among hospitalized patients with injection drug use-associated infective endocarditis were included with 119 patients in the pre-intervention group and 52 patients in the intervention group. There was no statistically significant difference in patients DAMA [19% vs 15%, absolute risk difference 4.6% (95% confidence interval -8.6% to 17.7%)] between the intervention and pre-intervention groups. However, there was an increase in the proportion of inpatient MOUD initiation in the intervention group compared to the pre-intervention group [56% vs 21%, absolute risk difference 35% (95% confidence interval 19% to 50%)]. Conclusions: The initiation of an addiction medicine consult service was associated with a higher proportion of MOUD initiation but there was no statistically significant association with the proportion of patients DAMA

In Vivo Targeting of Alveolar Macrophages Via RAFT-Based Glycopolymers

Targeting cell populations via endogenous carbohydrate receptors is an appealing approach for drug delivery. However, to be effective, this strategy requires the production of high affinity carbohydrate ligands capable of engaging with specific cell-surface lectins. To develop materials that exhibit high affinity towards these receptors, we synthesized glycopolymers displaying pendent carbohydrate moieties from carbohydrate-functionalized monomer precursors via reversible addition-fragmentation chain transfer (RAFT) polymerization. These glycopolymers were fluorescently labeled and used to determine macrophage-specific targeting both in vitro and in vivo. Mannose- and N-acetylglucosamine-containing glycopolymers were shown to specifically target mouse bone marrow-derived macrophages (BMDMs) in vitro in a dose-dependent manner as compared to a galactose-containing glycopolymer (30- and 19-fold higher uptake, respectively). In addition, upon macrophage differentiation, the mannose glycopolymer exhibited enhanced uptake in M2-polarized macrophages, an anti-inflammatory macrophage phenotype prevalent in injured tissue. This carbohydrate-specific uptake was retained in vivo, as alveolar macrophages demonstrated 6-fold higher internalization of mannose glycopolymer, as compared to galactose, following intratracheal administration in mice. We have shown the successful synthesis of a class of functional RAFT glycopolymers capable of macrophage-type specific uptake both in vitro and in vivo , with significant implications for the design of future targeted drug delivery systems

Stomatal pore size and density in mangrove leaves and artificial leaves: effects on leaf water isotopic enrichment during transpiration

We tested the hypothesis that the previously observed low isotopic enrichment of mangrove leaf water is caused by larger stomatal pores and lower densities compared with freshwater plants. First, we measured and compared pore size and density in mangroves, transitional and freshwater species in South Florida. We pooled this data with other reports encompassing 14 mangrove species and 134 freshwater species and tested for differences in pore size and density between mangroves and freshwater plants. Second, we built artificial leaves having different pore size and density and determined whether there were isotopic differences in their water after transpiration. Both the local survey and pooled data showed that mangrove leaves have significantly larger stomatal pores with lower densities compared with freshwater plants. Isotope enrichment of water from artificial leaves having larger less dense pores was lower than those having smaller and denser pores. Stomatal pore size and density has an effect on leaf water isotopic enrichment amongst other factors. Pore size and density probably affects key components of the Peclet ratio such as the distance advective flow of water must travel to the evaporative surface and the cross-sectional area of advective flow. These components, in turn, affect leaf water isotopic enrichment. Results from the artificial leaf experiment also mimic a recent finding that effective path length scales to the inverse of transpiration in real leaves. The implications of these findings further our understanding of leaf water isotope ratios and are important in applications of stable isotopes in the study of paleoclimate and atmospheric processes

In vivo targeting of alveolar macrophages via RAFT-based glycopolymers

Targeting cell populations via endogenous carbohydrate receptors is an appealing approach for drug delivery. However, to be effective, this strategy requires the production of high affinity carbohydrate ligands capable of engaging with specific cell-surface lectins. To develop materials that exhibit high affinity towards these receptors, we synthesized glycopolymers displaying pendant carbohydrate moieties from carbohydrate-functionalized monomer precursors via reversible addition-fragmentation chain transfer (RAFT) polymerization. These glycopolymers were fluorescently labeled and used to determine macrophage-specific targeting both in vitro and in vivo. Mannose- and N-acetylglucosamine-containing glycopolymers were shown to specifically target mouse bone marrow-derived macrophages (BMDMs) in vitro in a dose-dependent manner as compared to a galactose-containing glycopolymer (30- and 19-fold higher uptake, respectively). In addition, upon macrophage differentiation, the mannose glycopolymer exhibited enhanced uptake in M2-polarized macrophages, an anti-inflammatory macrophage phenotype prevalent in injured tissue. This carbohydrate-specific uptake was retained in vivo, as alveolar macrophages demonstrated 6-fold higher internalization of mannose glycopolymer, as compared to galactose, following intratracheal administration in mice. We have shown the successful synthesis of a class of functional RAFT glycopolymers capable of macrophage-type specific uptake both in vitro and in vivo, with significant implications for the design of future targeted drug delivery systems

Rewriting desire: the construction of sexual identity in literary and legal discourse in postcolonial Ireland

The failure of the legal imaginary to reflect sexual difference in the opening decades of the postcolonial Irish state led to what in psychoanalytical terms may be described as the creation of socially abjected groups. Lesbians and gay men were numbered among such groups. The failure of official discourse to contemplate sexual difference as an integral part of Irish national identity was a residue of the Irish colonial experi- ence. The association of Ireland with the female in colonial discourse led the Irish revolutionary elite to propagate a myth of hypermasculinity. This strategy had farreaching consequences for the manner in which matters of sexual difference were to be treated in the postcolonial era. The exclusion of sexually dissident voices from official discourse did not stifle attempts at the levels of literary discourse and pressure group politics to voice alternative desires which were deemed antithetical to the heterosexual Irish state. The growth of alternative narratives of sexual identity led to a gradual transformation of the legal and cultural construction of homosexuality in Ireland. This demonstrates the power of narrative strategies to counter a dominant discourse of blindness to sexual difference and reflects a link between the cultural and legal constructions of sexual identity

Non-viral gene delivery strategies for gene therapy: a “ménage à trois” among nucleic acids, materials, and the biological environment

Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription-translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors