α'-Selective Selenium-catalyzed Allylic C-H Amination of Enol Derivatives.

A transition metal-free Se-catalyzed C-H amination protocol for α'-amination of enol derivatives has been developed. This reaction can be used to functionalize a wide variety of oxygen- and halogen-substituted alkenes spanning a vast range of nucleophilicities, giving α'-aminated enol derivatives with high regioselectivity. Amination of E/Z mixtures of alkenes proceeds stereoconvergently to give the (Z)-enol derivatives exclusively. Mechanistic studies revealed that the relative reactivity and α'-regioselectivity of these transformations is determined by substantial resonance donation to the heteroatom-bound carbon in the transition state. These products participate in traditional reactions of enol derivatives, allowing for efficient functionalization of both α- and α'-positions from a single enol derivative with high diastereocontrol.

Effects of seeking compensation on the psychological health and recovery of injured patients: the role of stress vulnerability and injury-related disability.

BACKGROUND: Seeking compensation has been shown to have an adverse effect on the psychological health and recovery of injured patients, however, this effect requires clarification. METHODS: A total of 2019 adults sustaining a traffic injury were recruited. Of these, 709 (35.1%) lodged a compensation claim. Interviews occurred at 1-, 6- and 12-month post-injury. Outcomes were psychological distress (posttraumatic stress (PTS) and depressive symptoms) and health-related functioning (HrF) (quality of life measured by EQ-5D-3L and disability by WHODAS) over 12-months post-injury. Covariates included individual stress vulnerability (preinjury, injury-related factors). RESULTS: Compared with non-compensation participants, compensation groups had higher stress vulnerability (more severe injuries and negative reactions) and poorer baseline outcomes (psychological health and HrF). After adjustment, we found an effect of compensation on HrF [ß-0.09 (-0.11 to -0.07), p < 0.001] and PTS [ß = 0.36 (0.16 to 0.56), p = 0.0003], but not on depression [ß = -0.07 (-0.42 to 0.28), p = 0.7]. Both groups improved over time. Vulnerable individuals (ß = 1.23, p < 0.001) and those with poorer baseline outcomes (PTS: ß = 0.06, p = 0.002; HrF: ß = -1.07, p < 0.001) were more likely to lodge a claim. In turn, higher stress vulnerability, poor baseline outcomes and claiming compensation were associated with long-term psychological distress and HrF. Nevertheless, concurrent HrF in the model fully accounted for the compensation effect on psychological distress (ß = -0.14, p = 0.27), but not vice versa. CONCLUSIONS: This study provides convincing evidence that seeking compensation is not necessarily harmful to psychological health. The person's stress vulnerability and injury-related disability emerge as major risk factors of long-term psychological distress, requiring a whole-systems approach to address the problem.

Hydrogel Matrix-Grafted Impedimetric Aptasensors for the Detection of Diclofenac.

Driven by the growing concern about the release of untreated emerging pollutants and the need for determining small amounts of these pollutants present in the environment, novel biosensors dedicated to molecular recognition are developed. We have designed biosensors using a novel class of grafted polymers, surface-attached hydrogel thin films, on conductive transducers as a biocompatible matrix for biomolecule immobilization. We showed that they can be dedicated to the molecular recognition of diclofenac (DCL). The immobilization of the aptamer onto surface-attached hydrogel thin films by covalent attachment provides a biodegradable shelter, providing the aptamer with excellent environments to preserve its active and functional structure while allowing the detection of DCL. The grafting of the aptamer is obtained using the formation of amide bonds via the activation of carboxylic acid groups of the poly(acrylic acid) hydrogel thin film. For improved sensitivity and higher stability of the sensor, a high density of the immobilized aptamer is enabled. The aptamer-modified electrode was then incubated with DCL solutions at different concentrations. The performances of the aptasensor were investigated by electrochemical impedance spectroscopy. The change in charge-transfer resistance was found to be linear with DCL concentration in the 30 pM to 1 µM range. The detection limit was calculated to be 0.02 nM. The improvement of the limit of detection can be mainly attributed to the three-dimensional environment of the hydrogel matrix which improves the grafting density of the aptamer and the affinity of the aptamer to DCL.

Series of M-MOF-184 (M = Mg, Co, Ni, Zn, Cu, Fe) Metal-Organic Frameworks for Catalysis Cycloaddition of CO2.

In light of the chemical exploitation of CO2, new reusable materials for efficiently catalyzing the cycloaddition of CO2 and epoxides under moderate conditions are needed. Herein, a new series of isostructural metal-organic frameworks (MOFs) M2(EDOB) [EDOB4- = 4,4'-(ethyne-1,2-diyl)bis(2-oxidobenzoate), M = Mg, Ni, Co, Zn, Cu, Fe], known as M-MOF-184, analogous to a well-studied MOF-74 structure, were synthesized and fully characterized. The M-MOF-184 (M = Mg, Co, Ni, Zn) frameworks exhibit accessible mesopore channels (24 Å) and high porosity. Among them, Mg-MOF-184 demonstrated the most upper surface area (>4000 m2 g-1) in any reported MOF-74-type frameworks. Furthermore, Co-MOF-184 revealed the highest CO2 uptake (73 cm3 g-1, at 298 K), and Zn-MOF-184 showed the highest catalytic activity upon the cycloaddition of CO2 (96% conversion, 86% selectivity, and 82% yield) under mild conditions (1 atm CO2, 80 °C, 6 h, and solvent-free). Notably, the catalytic performance of Zn-MOF-184 outperformed that of the original M-MOF-74 (M = Mg, Co, Zn) materials and various Zn-based MOFs. To evaluate the acidity and basicity of a series of M-MOF-184 (M = Mg, Co, Ni, Zn) frameworks, the interaction of these MOFs with acetonitrile vapor was investigated by vapor adsorption and ATR-FTIR spectroscopy measurements. As such, Zn-MOF-184 showed the strongest Lewis acidity derived by Zn cations, which was correlated to the highest catalytic activity upon the cycloaddition of CO2. Interestingly, the 2-oxidobenzoate anions from Co-MOF-184 showed the strongest basicity among the series, which was associated with the highest saturated acetonitrile uptake (544 cm3 g-1 at 298 K). Our findings suggest that the integration of Lewis acidic and basic sites, high surface area, and large accessible pores into the framework can facilitate the CO2 fixation reaction.

Outcomes after traffic injury: mental health comorbidity and relationship with pain interference.

BACKGROUND: Mental health symptoms, like depressive mood (DM) and post-traumatic stress (PTS), and pain interference (PI) with daily functioning often co-occur following traffic injury and their comorbidity can complicate recovery. This study aimed to map the course and overlapping trajectories of mental health symptoms, and associations with PI in a traffic injury population. METHODS: In total, 2019 adults sustaining minor-to-moderate traffic injury were recruited within 28 days post-injury and assessed using phone interviews at 1, 6 and 12-months post-injury. Trajectories of DM, PTS and PI were established and relationships between DM, PTS and PI trajectories were explored using dual trajectory modelling. Bio-psychosocial predictors (e.g. pre-injury health, catastrophizing, acute distress, quality of life, social support) of mental health trajectories were investigated. RESULTS: Up to five typical post-trauma trajectories were identified for DM, PTS and PI. Most people were in a resilient mental health trajectory (over 60%, DM or PTS), or in a chronic PI trajectory (almost 60%) 12 months post-injury. While recovery/resilient mental health trajectories were strongly interrelated (73.4% joint probability and > 94% conditional probabilities), DM/PTS comorbidity in chronic trajectories was not straightforward, suggesting a possibly asymmetric relationship. That is, persistent DM was more likely associated with persistent PTS (90.4%), than vice versa (31.9%), with a 22.5% probability that persistent PTS was associated with none or milder depression (i.e. following a recovery/resilient DM trajectory). An asymmetrical relationship was also found between mental health and PI. The majority of those with persistent PI were likely to be in a recovery/resilient DM/PTS trajectory (almost 70%), but those in a non-resilient DM/PTS trajectory showed a high risk of persistent PI. Predictors of non-resilient mental health trajectories included poorer pre-injury health and social support, and shared factors like acute psychological distress and pain catastrophizing. CONCLUSIONS: Strong interrelations were confirmed between mental health symptoms and PI following traffic injury. However, persistent DM was more strongly linked to persistent PTS, than vice versa. Persistent PI was only linked with persistent DM/PTS in vulnerable subgroups. Early psychiatric/psychological interventions should target elevated psychological distress and negative appraisals in vulnerable individuals, to reduce long-term mental health morbidity/comorbidity and PI. TRIAL REGISTRATION: ACTRN12613000889752.

A Series of Metal-Organic Frameworks for Selective CO2 Capture and Catalytic Oxidative Carboxylation of Olefins.

Three new lanthanide-based metal-organic frameworks (Ln-MOFs), namely MOF-590, -591, and -592 constructed from a tetratopic linker, benzoimidephenanthroline tetracarboxylic acid (H4BIPA-TC), were synthesized under solvothermal conditions and fully characterized. All of the new MOFs exhibit three-dimensional frameworks, which adopt unprecedented topologies in MOF field. Gas adsorption measurements of MOF-591 and -592 revealed good adsorption of CO2 (low pressure, at room temperature) and moderate CO2 selectivity over N2 and CH4. Consequently, breakthrough experiments illustrated the separation of CO2 from binary mixture of CO2 and N2 with the use of MOF-592. Accordingly, MOF-592 revealed the selective CO2 capture effectively without any loss in performance after three cycles. Moreover, MOF-590, -591, and -592 showed to be catalytically active in the oxidative carboxylation of styrene and CO2 for a one-pot synthesis of styrene carbonate under mild conditions (1 atm CO2, 80 °C, and without solvent). Among the new materials, MOF-590 revealed a remarkable efficiency with exceptional conversion (96%), selectivity (95%), and yield (91%).

Depressive mood in adults with spinal cord injury as they transition from an inpatient to a community setting: secondary analyses from a clinical trial.

STUDY DESIGN: Prospective cohort controlled trial design. OBJECTIVES: (i) To investigate mood benefits of adding group cognitive behaviour therapy (group-CBT) to standard spinal cord injury (SCI) inpatient rehabilitation (SR) that included access to antidepressant medication and individually delivered CBT on demand. (ii) To determine whether those with elevated depressive mood during inpatient rehabilitation significantly improve. SETTING: SCI rehabilitation and community settings in New South Wales, Australia. METHODS: Participants included 50 adults with SCI who completed SCI rehabilitation that included group-CBT compared with 38 participants who also completed SCI rehabilitation that did not contain group-CBT. Comprehensive assessment occurred after admission, within 2 weeks of discharge and 12 months post-injury. Multivariate repeated measures analyses were conducted to examine differences between groups and over time. RESULTS: The addition of group-CBT to SR did not result in significant improvement in mood. However, participants with clinically elevated depressive mood assessed during inpatient rehabilitation experienced significant reductions in depressive mood when assessed in the community regardless of CBT dosage. Anxiety correlated with mood while no sociodemographic/injury factors correlated with mood at any time period except education level. CONCLUSION: There were no mood advantages over time of adding group-CBT to inpatient SCI rehabilitation that contains individually delivered CBT on demand and access to antidepressant medication. However, findings showed those with elevated depressive mood during inpatient rehabilitation significantly improved when assessed in the community; however, their levels of depressive mood remain high. Future research should investigate the efficacy of providing individual preferences for managing depression in people with SCI.

Managing pain and fatigue in people with spinal cord injury: a randomized controlled trial feasibility study examining the efficacy of massage therapy.

STUDY DESIGN: A randomized controlled trial (RCT). OBJECTIVES: To determine the efficacy of massage therapy (MT) as a treatment that could be implemented to reduce pain and fatigue in people with chronic spinal cord injury (SCI). SETTING: Laboratory setting in Sydney, Australia. METHODS: Participants included 40 people with SCI living in the community who were randomly assigned into one of two RCT arms: MT (Swedish massage to upper body) or an active concurrent control (guided imagery (GI) relaxation). All participants received 30 min once a week of either massage or GI over 5 consecutive weeks. In addition to sociodemographic and injury factors, assessments and reliable measures including the short-form McGill Pain Questionnaire and Chalder's Fatigue Scale were validated. RESULTS: Chronic pain and fatigue were significantly reduced in the massage group when assessed at the end of 5 weeks (P<0.05), with large effect sizes. Interestingly, GI was as effective as MT in reducing pain and fatigue. Pain scores were reduced significantly over time in both MT and GI groups (P=0.049 and P=0.032, respectively). Total fatigue scores were also reduced in both MT and GI groups (P=0004 and P=0.037, respectively.)Conclusions:Massage and GI are both active treatments that provide potential clinical benefits for adults with SCI. Future research should clarify the role of massage and GI in managing pain and fatigue in SCI and assess outcomes into the longer-term.

Poroelastic indentation of mechanically confined hydrogel layers.

We report on the poroelastic indentation response of hydrogel thin films geometrically confined within contacts with rigid spherical probes of radii in the millimeter range. Poly(PEGMA) (poly(ethylene glycol) methyl ether methacrylate), poly(DMA) (dimethylacrylamide) and poly(NIPAM) (N-isopropylacrylamide) gel films with thickness less than 15 µm were grafted onto glass substrates using a thiol-ene click chemistry route. Changes in the indentation depth under constant applied load were monitored over time as a function of the film thickness and the radius of curvature of the probe using an interferometric method. In addition, shear properties of the indented films were measured using a lateral contact method. In the case of poly(PEGMA) films, we show that poroelastic indentation behavior is adequately described within the framework of an approximate contact model derived within the limits of confined contact geometries. This model provides simple scaling laws for the characteristic poroelastic time and the equilibrium indentation depth. Conversely, deviations from this model are evidenced for poly(DMA) and poly(NIPAM) films. From lateral contact experiments, these deviations are found to result from strong changes in the shear properties as a result of glass transition (poly(DMA)) or phase separation (poly(NIPAM)) phenomena induced by the drainage of the confined films squeezed between the rigid substrates.

Influence of neurological lesion level on heart rate variability and fatigue in adults with spinal cord injury.

STUDY DESIGN: Group cohort design. OBJECTIVES: To determine the influence of spinal cord injury (SCI) and neurological level on heart rate variability (HRV) and associations with fatigue. SETTING: SCI rehabilitation outpatient and community settings in New South Wales, Australia. METHODS: Participants included 45 adults with SCI living in the community and 44 able-bodied controls. Socio-demographic, neurological injury, psychological, HRV and eye blink variables were assessed. Multivariate analysis of variance and post hoc protected t-tests were used to determine differences in HRV and fatigue as a function of the neurological level. Pearson's correlation analysis was used to determine the relationships between these factors. RESULTS: Participants with SCI had significantly reduced sympathetic activity. Those with tetraplegia had lowered sympathetic activity compared with those with paraplegia and able-bodied controls. Neither were differences in parasympathetic activity found between groups nor were there any significant differences found for the time domain or non-linear domains. Higher levels of fatigue were found in the SCI sample, and participants with tetraplegia had higher fatigue levels compared with those with paraplegia. Fatigued participants were more likely to have altered autonomic function-that is, reduced sympathetic activity. CONCLUSIONS: Higher levels of neurological impairment in people with SCI are more likely to result in disordered cardiovascular control involving reduced sympathetic activity, whereas elevated fatigue was found to be associated with increased sympathetic dysfunction. Findings highlight the need to address risks associated with this dysfunction, such as improved HRV and fatigue screening for people with SCI and improved education on cardiovascular risk factors.

Anti-infective immunoadhesins from plants.

Immunoadhesins are recombinant proteins that combine the ligand-binding region of a receptor or adhesion molecule with immunoglobulin constant domains. All FDA-approved immunoadhesins are designed to modulate the interaction of a human receptor with its normal ligand, such as Etanercept (Enbrel(®) ), which interferes with the binding of tumour necrosis factor (TNF) to the TNF-alpha receptor and is used to treat inflammatory diseases such as rheumatoid arthritis. Like antibodies, immunoadhesins have long circulating half-lives, are readily purified by affinity-based methods and have the avidity advantages conferred by bivalency. Immunoadhesins that incorporate normal cellular receptors for viruses or bacterial toxins hold great, but as yet unrealized, potential for treating infectious disease. As decoy receptors, immunoadhesins have potential advantages over pathogen-targeted monoclonal antibodies. Planet Biotechnology has specialized in developing anti-infective immunoadhesins using plant expression systems. An immunoadhesin incorporating the cellular receptor for anthrax toxin, CMG2, potently blocks toxin activity in vitro and protects animals against inhalational anthrax. An immunoadhesin based on the receptor for human rhinovirus, ICAM-1, potently blocks infection of human cells by one of the major causes of the common cold. An immunoadhesin targeting the MERS coronavirus is in an early stage of development. We describe here the unique challenges involved in designing and developing immunoadhesins targeting infectious diseases in the hope of inspiring further research into this promising class of drugs.

Submicrometric Films of Surface-Attached Polymer Network with Temperature-Responsive Properties.

Temperature-responsive properties of surface-attached poly(N-isopropylacrylamide) (PNIPAM) network films with well-controlled chemistry are investigated. The synthesis consists of cross-linking and grafting preformed ene-reactive polymer chains through thiol-ene click chemistry. The formation of surface-attached and cross-linked polymer films has the advantage of being well-controlled without any caution of no-oxygen atmosphere or addition of initiators. PNIPAM hydrogel films with same cross-link density are synthesized on a wide range of thickness, from nanometers to micrometers. The swelling-collapse transition with temperature is studied by using ellipsometry, neutron reflectivity, and atomic force microscopy as complementary surface-probing techniques. Sharp and high amplitude temperature-induced phase transition is observed for all submicrometric PNIPAM hydrogel films. For temperature above LCST, surface-attached PNIPAM hydrogels collapse similarly but without complete expulsion of water. For temperature below LCST, the swelling of PNIPAM hydrogels depends on the film thickness. It is shown that the swelling is strongly affected by the surface attachment for ultrathin films below ∼150 nm. For thicker films above 150 nm (to micrometers), surface-attached polymer networks with the same cross-link density swell equally. The density profile of the hydrogel films in the direction normal to the substrate is confronted with in-plane topography of the free surface. It results that the free interface width is much larger than the roughness of the hydrogel film, suggesting pendant chains at the free surface.

Factors predicting resilience in people with spinal cord injury during transition from inpatient rehabilitation to the community.

STUDY DESIGN: This is a longitudinal design study. OBJECTIVES: The objective of this study was to determine factors that predict resilience in people with spinal cord injury (SCI) at discharge from inpatient rehabilitation and after reintegration into the community 6 months post discharge. SETTING: This study was conducted in SCI rehabilitation units and the community in New South Wales, Australia. METHODS: Participants included 88 adults with SCI admitted over almost 3 years into three SCI Units in Sydney. Standardized self-report and clinician-based measures were used. Longitudinal assessment occurred up to 6 months post discharge. Sociodemographic, injury and psychological variables were assessed at admission, before discharge and 6 months post discharge. Standard multiple regression was used to determine factors that predict resilience at discharge from hospital and 6 months post discharge. RESULTS: Almost 70% of the participants were classified as resilient at discharge and 66% after 6 months of living in the community. Multiple factors significantly predicted resilience at discharge and 6 months post discharge, including self-efficacy, low levels of negative mood and lower functional independence, whereas social support and low severity of secondary conditions trended to significance. Demographic and injury variables did not contribute significantly. CONCLUSION: Self-efficacy and low levels of negative mood states strongly contribute to resilience. The determination of these predictors will assist in improving rehabilitation programs to strengthen the resilience of people with SCI. However, given that 40-44% of the variance in resilience was explained by the group of factors entered, future longitudinal research is needed to determine not only whether resilience correlates but also whether these associations change over time.

Developing an algorithm capable of discriminating depressed mood in people with spinal cord injury.

STUDY DESIGN: Cross-section design. OBJECTIVES: The development of reliable screen technology for predicting those at risk of depression in the long-term remains a challenge. The objective of this research was to determine factors that classify correctly adults with spinal cord injury (SCI) with depressed mood and to develop a diagnostic algorithm that could be applied for prediction of depressed mood in the long-term. SETTING: SCI rehabilitation unit, rehabilitation outpatient clinic and Australian community. METHODS: Participants included 107 adults with SCI. The assessment regimen included demographic and injury variables, negative mood states, pain intensity, health-related quality of life and self-efficacy. Participants were divided into those with 'normal' mood versus those with elevated depressed mood. Discriminant function analysis (DFA) was then used to isolate factors that in combination, best classify the presence or absence of depressed mood. RESULTS: At the time of assessment, 24 participants (22.4%) had elevated depressed mood. DFA identified six factors that discriminated between those with depressed mood (P<0.01) and those with normal mood, explaining 61% of the variance. Factors consisted of pain intensity, mental health, emotional and social functioning, self-efficacy and fatigue. DFA correctly classified 91.7% (n=22 of 24) of those with depressed mood and 95.2% (n=79 of 83) of those without. Demographic, injury and physical health function variables were not found to discriminate depressed mood. CONCLUSION: Clinical implications of applying a diagnostic algorithm for detecting depression in adults with SCI are discussed. Prospective research is needed to test the predictive efficacy of the algorithm.

Injectable hydrogels based on alginates grafted with LCST side-chains of different chemistry.

A homologous series of thermoassociating copolymers was prepared by grafting onto alginates different amounts of three different temperature responsive polymers: poly(N-isopropylacrylamide), poly(di(ethylene glycol)methacrylate) and poly(ethylene oxide-co-propylene oxide). From a large set of analytical techniques combining rheology, calorimetry, NMR and SAXS, the relevant parameters controlling the sol/gel transition and the gel properties, mainly the degree of entanglement of macromolecules and the fraction of responsive stickers, were highlighted and interpreted objectively by considering the particularities of the phase diagrams of LCST polymers. Complementary analyses were implemented to investigate adhesiveness, injectabilty, gel swelling and molecular release in physiological environment of thermogelling formulations. In particular, it is shown that steady shear experiments allow to predict the injection forces by taking into account the characteristics of the system (syringe and needle), and that the rapid gelation of the formulations when they are heated at 37 °C delays the release of small molecules into the environment. The overall set of data is discussed in the framework of scaling relations in order to draw quantitative guidelines for the design of injectable thermoresponsive hydrogels.

The seroprevalence of toxocariasis and related risk factors in children in Ho Chi Minh City, Vietnam: results from a school-based cross-sectional study.

BACKGROUND: Children are especially vulnerable to Toxocara infection and its severe complications; however, there have not been any published data on the disease prevalence and treatment effectiveness in the population of Vietnamese children. This study was conducted to determine the prevalence of toxocariasis and explore factors associated with Toxocara infection in children aged 3-15 y in Ho Chi Minh City, Vietnam. METHODS: We conducted a cross-sectional study using a multistage cluster sampling approach in public schools. Blood samples were collected, and toxocariasis cases were confirmed, based on a history of contact with dogs/cats and positive anti-Toxocara antibody detection via ELISA. We calculated the percentage of seropositive children across gender, grade levels, districts and caregiver education. Multiple regression models were employed to identify potential risk factors. RESULTS: Anti-Toxocara antibodies were found in 14.2% of the 986 children studied. Significant variations in seropositivity were observed across grade levels, districts and caregiver education levels. Multivariable analysis identified caregiver education, contact with dogs/cats and improper handling of pet feces as seropositivity risk factors. CONCLUSION: This was the first community-based prevalence study of toxocariasis in a pediatric population in Vietnam. Implementation of preventive measures such as public education, routine fecal examinations and chemotherapeutic treatment of animals is highly recommended.

Food Insecurity and Hearing Loss Are Interrelated: A Cross-Sectional Population-Based Study.

OBJECTIVES: We aimed to assess whether objectively measured hearing loss and self-perceived hearing handicap in adults are independently associated with food insecurity, and vice versa. DESIGN: Cross-sectional population-based study. POPULATION: 2,500 participants aged 50+ years from the Blue Mountains Hearing Study, with both complete pure-tone audiometry data and information on food security status. MEASUREMENTS: The pure-tone average of frequencies 0.5, 1.0, 2.0 and 4.0 kHz (PTA0.5-4KHz) >25 dB HL in the better ear, established the presence of hearing loss. Self-perceived hearing handicap was assessed by administering the Hearing Handicap Inventory for Elderly Screening (HHIE-S total scores of ≥8 indicates hearing handicap). A 12-item food security survey was administered, comprising statements related to individual and household food situations. RESULTS: Food insecurity was reported by 12.8% of study participants. After adjusting for all potential confounders, any self-perceived hearing handicap significantly increased the likelihood of participants reporting food insecurity by 94% (p<0.0001). Participants reporting any, mild or severe self-perceived hearing handicap had around 2-fold greater odds of experiencing food insecurity. Objectively measured hearing loss did not significantly influence the food security status of study participants. Conversely, food insecurity was significantly associated with both objectively measured hearing loss and self-perceived hearing handicap: multivariate-adjusted OR 1.37 (95% CI 1.01-1.88) and OR 1.83 (95% CI 1.40-2.39), respectively. CONCLUSIONS: Food insecurity was an important social determinant of hearing health among community-dwelling adults. Conversely, participants with a significant self-perceived hearing handicap were more likely to experience food insecurity. These findings add to our understanding of the substantial public health impact of both food insecurity and hearing loss and may highlight areas for future intervention.

Sol/gel transition of thermoresponsive Hyaluronan: From liquids to elastic and sticky materials.

Thermoassociating copolymers were prepared by grafting temperature responsive poly(N-isopropylacrylamide-stat-N-tert-butylacrylamide) telomers onto hyaluronan. By varying the composition of LCST side chains, from 50 to 100 wt% of NIPAM units, it is shown that the sol/gel transition of entangled solutions can be accurately controlled in the range of 10 to 35 °C with an abrupt transition and reversible properties. Complementary experiments, performed by DSC and NMR, demonstrate the close relationship between thermoassociation of LCST grafts, forming microdomains of low mobility, and macroscopic properties. Moreover, by performing tack experiments during heating we demonstrate that hyaluronan formulations abruptly switch from a weak adhesive viscous behavior to an elastic adhesive profile in the gel regime. As LCST side-chains form concentrated micro-domains of low mobility, physical gels can resist to dissociation above their sol/gel transition for relatively long periods when immersed in excess physiological medium. The thermoassociative behavior of these copolymers, whose properties can be finely tuned in order to form sticky gels at body temperature, clearly demonstrates their potential in biomedical applications such as injectable gels for drug delivery or tissue engineering.

A Factor H-Fc fusion protein increases complement-mediated opsonophagocytosis and killing of community associated methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus employs a multitude of immune-evasive tactics to circumvent host defenses including the complement system, a component of innate immunity central to controlling bacterial infections. With antibiotic resistance becoming increasingly common, there is a dire need for novel therapies. Previously, we have shown that S. aureus binds the complement regulator factor H (FH) via surface protein SdrE to inhibit complement. To address the need for novel therapeutics and take advantage of the FH:SdrE interaction, we examined the effect of a fusion protein comprised of the SdrE-interacting domain of FH coupled with IgG Fc on complement-mediated opsonophagocytosis and bacterial killing of community associated methicillin-resistant S. aureus. S. aureus bound significantly more FH-Fc compared to Fc-control proteins and FH-Fc competed with serum FH for S. aureus binding. FH-Fc treatment increased C3-fragment opsonization of S. aureus for both C3b and iC3b, and boosted generation of the anaphylatoxin C5a. In 5 and 10% serum, FH-Fc treatment significantly increased S. aureus killing by polymorphonuclear cells. This anti-staphylococcal effect was evident in 75% (3/4) of clinical isolates tested. This study demonstrates that FH-Fc fusion proteins have the potential to mitigate the protective effects of bound serum FH rendering S. aureus more vulnerable to the host immune system. Thus, we report the promise of virulence-factor-targeted fusion-proteins as an avenue for prospective anti-staphylococcal therapeutic development.

An optimized Factor H-Fc fusion protein against multidrug-resistant Neisseria gonorrhoeae.

Novel therapeutics against the global threat of multidrug-resistant Neisseria gonorrhoeae are urgently needed. Gonococci evade killing by complement by binding factor H (FH), a key inhibitor of the alternative pathway. FH comprises 20 short consensus repeat (SCR) domains organized as a single chain. Gonococci bind FH through domains 6 and 7, and C-terminal domains 18 through 20. Previously, we showed that a chimeric protein comprising (from the N- to C-terminus) FH domains 18-20 (containing a point mutation in domain 19 to prevent lysis of host cells) fused to human IgG1 Fc (called FH*/Fc1) killed gonococci in a complement-dependent manner and reduced the duration and bacterial burden in the mouse vaginal colonization model of gonorrhea. Considering the N. gonorrhoeae-binding FH domains 18-20 are C-terminal in native FH, we reasoned that positioning Fc N-terminal to FH* (Fc1/FH*) would improve binding and bactericidal activity. Although both molecules bound gonococci similarly, Fc1/FH* displayed a 5-fold lower IC50 (the concentration required for 50% killing in complement-dependent bactericidal assays) than FH*/Fc1. To further increase complement activation, we replaced human IgG1 Fc in Fc1/FH* with Fc from human IgG3, the most potent complement-activating IgG subclass, to obtain Fc3/FH*. Bactericidal activity was further increased ~2.3-fold in Fc3/FH* compared to Fc1/FH*. Fc3/FH* killed (defined by <50% survival) 45/45 (100%) diverse PorB1B-expessing gonococci, but only 2/15 PorB1A-expressing isolates, in a complement-dependent manner. Decreased Fc3/FH* binding accounted for the limited activity against PorB1A strains. Fc3/FH* was efficacious against all four tested PorB1B gonococcal strains in the mouse vaginal colonization model when administered at a dose of 5 µg intravaginally, daily. Furthermore, Fc3/FH* retained bactericidal activity when reconstituted following lyophilization or spray-drying, suggesting feasibility for formulation into intravaginal rings. In conclusion, Fc3/FH* represents a promising prophylactic immunotherapeutic against multidrug-resistant gonococci.