Electrochemistry at nanoscale electrodes : individual single-walled carbon nanotubes (SWNTs) and SWNT-templated metal nanowires

Individual nanowires (NWs) and native single-walled carbon nanotubes (SWNTs) can be readily used as well-defined nanoscale electrodes (NSEs) for voltammetric analysis. Here, the simple photolithography-free fabrication of submillimeter long Au, Pt, and Pd NWs, with sub-100 nm heights, by templated electrodeposition onto ultralong flow-aligned SWNTs is demonstrated. Both individual Au NWs and SWNTs are employed as NSEs for electron-transfer (ET) kinetic quantification, using cyclic voltammetry (CV), in conjunction with a microcapillary-based electrochemical method. A small capillary with internal diameter in the range 30–70 μm, filled with solution containing a redox-active mediator (FcTMA+ ((trimethylammonium)methylferrocene), Fe(CN)64–, or hydrazine) is positioned above the NSE, so that the solution meniscus completes an electrochemical cell. A 3D finite-element model, faithfully reproducing the experimental geometry, is used to both analyze the experimental CVs and derive the rate of heterogeneous ET, using Butler–Volmer kinetics. For a 70 nm height Au NW, intrinsic rate constants, k0, up to ca. 1 cm s–1 can be resolved. Using the same experimental configuration the electrochemistry of individual SWNTs can also be accessed. For FcTMA+/2+ electrolysis the simulated ET kinetic parameters yield very fast ET kinetics (k0 > 2 ± 1 cm s–1). Some deviation between the experimental voltammetry and the idealized model is noted, suggesting that double-layer effects may influence ET at the nanoscale

An observational study on the expression levels of MDM2 and MDMX proteins, and associated effects on P53 in a series of human liposarcomas

Background: Inactivation of wild type P53 by its main cellular inhibitors (MDM2 and MDMX) is a well recognised feature of tumour formation in liposarcomas. MDM2 over-expression has been detected in approximately 80% of liposarcomas but only limited information is available about MDMX over-expression. To date, we are not aware of any study that has described the patterns of MDM2 and MDMX co-expression in liposarcomas. Such information has become more pertinent as various novel MDM2 and/or MDMX single and dual affinity antagonist compounds are emerging as an alternative approach for potential targeted therapeutic strategies. Methods. We analysed a case series of 61 fully characterized liposarcomas of various sub-types by immunohistochemistry, to assess the expression levels of P53, MDM2 and MDMX, simultaneously. P53 sequencing was performed in all cases that expressed P53 protein in 10% or more of cells to rule out mutation-related over-expression. Results: 50 cases over-expressed MDM2 and 42 of these co-expressed MDMX at varying relative levels. The relative expression levels of the two proteins with respect to each other were subtype-dependent. This apparently affected the detected levels of P53 directly in two distinct patterns. Diminished levels of P53 were observed when MDM2 was significantly higher in relation to MDMX, suggesting a dominant role for MDM2 in the degradation of P53. Higher levels of P53 were noted with increasing MDMX levels suggesting an interaction between MDM2 and MDMX that resulted in a reduced efficiency of MDM2 in degrading P53. Of the 26 cases of liposarcoma with elevated P53 expression, 5 were found to have a somatic mutation in the P53 gene. Conclusions: The results suggest that complex dynamic interactions between MDM2 and MDMX proteins may directly affect the cellular levels of P53. This therefore suggests that careful characterization of both these markers will be necessary in tumours when considering in vivo evaluation of novel blocker compounds for MDM proteins, as a therapeutic strategy to restore wild type P53 function

Effect of Soil pH on Emergence and Survival of \u3ci\u3eAustrodanthonia\u3c/i\u3e spp.

We evaluated the effects of soil acidity on seedling emergence and seedling persistence of several ecotypes of Austrodanthonia spp. collected from the Central, Southern and Monaro Tablelands of New South Wales (NSW) in southern temperate Australia. A pot experiment was conducted outdoors to identify the most promising material tolerant to soil acidity for domestication. In the experiment, 183 ecotypes and two commercial cultivars of Austrodanthonia were grown in pots at three levels of pHCa (3.9, 4.4 and 5.3). The pH treatments were achieved by adding either aluminium sulphate or lime to an acid earthy sandy loam soil collected from a grazing farm. Seedling emergence and persistence were recorded for 170 days after sowing (DAS). Establishment of all lines was severely reduced by soil acidity. At pH 3.9, average seedling emergence over all lines was 11%, whereas, at higher pH (pH 4.4 and 5.3) emergence was about 72%. Of the seeds sown, survival at 170 DAS was, on average, less than 1% at pH 3.9, compared with 25% at pH 4.4 and 5.3. Further investigations on species/ecotypes, particularly those favoured at low soil pH, should provide a useful basis for selection programmes

The Effect of Electronic Paramagnetism on Nuclear Magnetic Resonance Frequencies in Metals

Observations on the shifts of nuclear resonances in metals (Id {sup 7}, Na {sup 23}, Ou {sup 63}, Be {sup 9}, Fe {sup 207}, A1 {sup 27} and Oa {sup 69}) due to free electron paramagnetism; comparison with theoretical values

Preferences for sexual health services among middle-aged and older adults in the UK: a discrete choice experiment

OBJECTIVES: Sexual health is an integral part of well-being. However, the sexual health needs and desires of middle-aged and older adults have been largely disregarded. Therefore, this study aimed to understand the sexual health service preferences of adults aged 45 and older to improve the accessibility of sexual health services in the UK. METHODS: The formative stage of the discrete choice experiment (DCE) followed three steps: concept elicitation, refining and implementation. The attributes and levels were determined through 22 semistructured interviews during the concept elicitation, followed by pilot testing for refining the survey. Qualtrics XM, with conjoint project features, was implemented as the DCE survey platform. We used a random parameter logit model to estimate the relative importance (RI) of each attribute and preference for each attribute level. We also used a latent class model to explore groups of participants with similar preferences. RESULTS: In total, 200 responses were included for analysis. The demographic breakdown included 62.5% females, 35.5% people with disabilities and 26.0% identifying as a sexual minority. The median age was 53. Preferences for using sexual health services were mainly influenced by the mode of delivery (RI 32%), location (RI 18%) and cost (RI 16%). Participants showed a preference for face-to-face interactions at sexual health clinics and displayed a willingness to pay for private services. Extra support and the consultation style played minor roles in their decision-making process. No differences in preferences were identified among disabled people. However, sexual minorities expressed their preferences for conventional messaging. CONCLUSIONS: Our study revealed that middle-aged and older individuals prioritise sexual health services offering face-to-face consultations, emphasising a preference to attend sexual health clinics over cost. Aligning service delivery with these preferences has the potential to significantly improve the accessibility and uptake of sexual health services for adults aged 45 and older in the UK

In utero exposure to transient ischemia-hypoxemia promotes long-term neurodevelopmental abnormalities in male rat offspring

The impact of transient ischemic-hypoxemic insults on the developing fetal brain is poorly understood despite evidence suggesting an association with neurodevelopmental disorders such as schizophrenia and autism. To address this, we designed an aberrant uterine hypercontractility paradigm with oxytocin to better assess the consequences of acute, but transient, placental ischemia-hypoxemia in term pregnant rats. Using MRI, we confirmed that oxytocin-induced aberrant uterine hypercontractility substantially compromised uteroplacental perfusion. This was supported by the observation of oxidative stress and increased lactate concentration in the fetal brain. Genes related to oxidative stress pathways were significantly upregulated in male, but not female, offspring 1 hour after oxytocin-induced placental ischemia-hypoxemia. Persistent upregulation of select mitochondrial electron transport chain complex proteins in the anterior cingulate cortex of adolescent male offspring suggested that this sex-specific effect was enduring. Functionally, offspring exposed to oxytocin-induced uterine hypercontractility showed male-specific abnormalities in social behavior with associated region-specific changes in gene expression and functional cortical connectivity. Our findings, therefore, indicate that even transient but severe placental ischemia-hypoxemia could be detrimental to the developing brain and point to a possible mitochondrial link between intrauterine asphyxia and neurodevelopmental disorders

Oxytocin-induced birth causes sex-specific behavioral and brain connectivity changes in developing rat offspring

Despite six decades of the use of exogenous oxytocin for management of labor, little is known about its effects on the developing brain. Motivated by controversial reports suggesting a link between oxytocin use during labor and autism spectrum disorders (ASDs), we employed our recently validated rat model for labor induction with oxytocin to address this important concern. Using a combination of molecular biological, behavioral, and neuroimaging assays, we show that induced birth with oxytocin leads to sex-specific disruption of oxytocinergic signaling in the developing brain, decreased communicative ability of pups, reduced empathy-like behaviors especially in male offspring, and widespread sex-dependent changes in functional cortical connectivity. Contrary to our hypothesis, social behavior, typically impaired in ASDs, was largely preserved. Collectively, our foundational studies provide nuanced insights into the neurodevelopmental impact of birth induction with oxytocin and set the stage for mechanistic investigations in animal models and prospective longitudinal clinical studies

Co-creating inclusive sexual health services for middle-aged and older adults, including disabled people, in England: an innovative participatory approach within the field of sexual health

Background: Middle-aged and older adults, including disabled people, are rarely engaged in helping to develop sexual health services to meet their needs. We used co-creation as a promising participatory strategy to develop ideas to inform more inclusive sexual health services for middle-aged and older adults in England. Methods: During April and May 2023, we recruited participants to take part in our co-creation workshops and interviews. The research team partnered with active community leaders with lived experience to co-design and co-organise sessions. Discussion topics were developed iteratively, centred on participant input, to ensure the sessions were accessible and appropriate for the focus population. Implementation of the co-creation workshops and one-to-one interviews was evaluated by gathering community facilitators’ reflections on how they felt about their experience as facilitators and the success of the workshops. Reflections: Overall, co-creation activities are well-accepted and highly valuable means to engage middle-aged and older adults. We are identifying three strengths and four challenges worth noting. As for strengths, they entail: (1) shared informed decision-making; (2) co-leadership for conducting the research activities; and (3) importance of co-facilitation; and for challenges: (1) ensuring the venue/information is accessible to all; (2) recruitment of middle-aged and older adults for a stigmatised research topic; (3) need more time for co-creation sessions to make sure equal opportunity to contribute; and (4) integrating co-creation into existing community activities. Conclusion: Co-creation is crucial for inclusive health services, but underexplored in sexual health research involving middle-aged, older and disabled individuals. This study emphasises shared ownership, which enables the offering of practical guidance for researchers and healthcare professionals

Safety assessment of inhaled xylitol in mice and healthy volunteers

BACKGROUND: Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in mice and human volunteers. METHODS: This was a prospective cohort study of C57Bl/6 mice in an animal laboratory and healthy human volunteers at the clinical research center of a university hospital. Mice underwent a baseline methacholine challenge, exposure to either aerosolized saline or xylitol (5% solution) for 150 minutes and then a follow-up methacholine challenge. The saline and xylitol exposures were repeated after eosinophilic airway inflammation was induced by sensitization and inhalational challenge to ovalbumin. Normal human volunteers underwent exposures to aerosolized saline (10 ml) and xylitol, with spirometry performed at baseline and after inhalation of 1, 5, and 10 ml. Serum osmolarity and electrolytes were measured at baseline and after the last exposure. A respiratory symptom questionnaire was administered at baseline, after the last exposure, and five days after exposure. In another group of normal volunteers, bronchoalveolar lavage (BAL) was done 20 minutes and 3 hours after aerosolized xylitol exposure for levels of inflammatory markers. RESULTS: In naïve mice, methacholine responsiveness was unchanged after exposures to xylitol compared to inhaled saline (p = 0.49). There was no significant increase in Penh in antigen-challenged mice after xylitol exposure (p = 0.38). There was no change in airway cellular response after xylitol exposure in naïve and antigen-challenged mice. In normal volunteers, there was no change in FEV1 after xylitol exposures compared with baseline as well as normal saline exposure (p = 0.19). Safety laboratory values were also unchanged. The only adverse effect reported was stuffy nose by half of the subjects during the 10 ml xylitol exposure, which promptly resolved after exposure completion. BAL cytokine levels were below the detection limits after xylitol exposure in normal volunteers. CONCLUSIONS: Inhalation of aerosolized iso-osmotic xylitol was well-tolerated by naïve and atopic mice, and by healthy human volunteers