Green endoscopy: British Society of Gastroenterology (BSG), Joint Accreditation Group (JAG) and Centre for Sustainable Health (CSH) joint consensus on practical measures for environmental sustainability in endoscopy.

GI endoscopy is highly resource-intensive with a significant contribution to greenhouse gas (GHG) emissions and waste generation. Sustainable endoscopy in the context of climate change is now the focus of mainstream discussions between endoscopy providers, units and professional societies. In addition to broader global challenges, there are some specific measures relevant to endoscopy units and their practices, which could significantly reduce environmental impact. Awareness of these issues and guidance on practical interventions to mitigate the carbon footprint of GI endoscopy are lacking. In this consensus, we discuss practical measures to reduce the impact of endoscopy on the environment applicable to endoscopy units and practitioners. Adoption of these measures will facilitate and promote new practices and the evolution of a more sustainable specialty.

Activin A causes endothelial dysfunction of mouse aorta and human aortic cells.

Preeclampsia is a multisystem hypertensive disorder of pregnancy that remains one of the leading causes of maternal and perinatal morbidity and mortality worldwide. The widespread maternal endothelial dysfunction that underlies preeclampsia is thought to arise from excessive placental production of various factors combined with enhanced oxidative stress. While previous studies have reported elevated activin A in women diagnosed with preeclampsia, whether activin A can cause vascular dysfunction has not yet been thoroughly investigated. Here, we demonstrated that different subtypes of activin A receptors were localised to the endothelial and smooth muscle cells of mouse and human aortae. Then, the aorta of healthy female C57Bl6J mice (n = 8) were incubated for 24 h in various concentrations of recombinant activin A to mimic early pregnancy (5 ng/mL), late pregnancy (20 ng/mL) and preeclampsia (50 ng/mL). Vascular reactivity as assessed by wire myography revealed that only the preeclamptic level of activin A impaired agonist-mediated endothelium-dependent relaxation by reducing the vasodilator prostanoid contribution to relaxation. However, agonist-mediated endothelium-independent mechanisms were unaffected. Further investigations carried out on human aortic endothelial cells suggested that the impairment of aorta relaxation could also be driven by increased endothelial cell permeability, and decreased cell viability, adherence and proliferation. This is the first direct evidence to show that activin A can induce endothelial dysfunction in whole blood vessels, suggesting that at high circulating levels it may contribute to the widespread endothelial dysfunction in women with preeclampsia.

A supramolecular host for phosphatidylglycerol (PG) lipids with antibacterial activity.

Lipids fulfill a variety of important physiological functions, such as energy storage, providing a hydrophobic barrier, and signal transduction. Despite this plethora of biological roles, lipids are rarely considered a potential target for medical applications. Here, we report a set of neutral small molecules that contain boronic acid and urea functionalities to selectively recognize the bacterial lipid phosphatidylglycerol (PG). The affinity and selectivity was determined using 1H NMR titrations and a liposome-based Alizarin Red S assay. Minimum inhibitory concentrations (MIC) were determined to assess antibacterial activity. The most potent compounds display an association constant with PG in liposomes of at least 5 × 103 M-1, function as antibacterial agents against Gram-positive bacteria (MIC = 12.5-25 µM), and show little hemolytic activity. Mode of action studies suggest that the boronic acids bind to the headgroup of the PG lipids, which leads to a change in membrane fluidity and ultimately causes membrane depolarization and cell death.

Modifiable predictors of breastfeeding status and duration at 6 and 12 months postpartum.

BACKGROUND: Breastfeeding practices are determined by complex multilevel factors. This study assessed pregnant women's knowledge of breastfeeding and intention to breastfeed and investigated modifiable predictors for breastfeeding status (exclusive or any breastfeeding) and duration at 6 and 12 months postpartum. MATERIALS AND METHODS: Longitudinal data were extracted from a trial in Sydney, Australia, 2017-19. Women (n = 1155) were recruited from antenatal clinics and followed up for telephone interviews at baseline (third trimester), then at 6 and 12 months postpartum. Data collected included mothers' demographics; knowledge of breastfeeding and intention to breastfeed; work status; support from caregivers; breastfeeding environment; breastfeeding status and duration. Multiple logistic and Cox regression models were built to identify predictors for breastfeeding. RESULTS: At baseline, most mothers knew the recommendation to exclusively breastfeed until 6 months (66%) and the benefits (65%). The modifiable predictors for breastfeeding duration at 12 months included the following: mothers' knowledge of the recommendation (adjusted hazard ratio (AHR) 0.73, 95% confidence interval (CI) 0.60-0.90) and the benefits of exclusive breastfeeding (AHR 0.68, 95% CI 0.55-0.82), intention to meet the recommendation (AHR 0.76, 95% CI 0.63-0.93), and intention to breastfeed for two years (AHR 0.38, 95% CI 0.27-0.52) measured at baseline; mothers not working or studying (AHR 0.70, 95% CI 0.55-0.89), having support from other caregivers (AHR 0.64, 95% CI 0.43-0.96), and having breastfeeding women around (AHR 0.80, 95% CI 0.65-0.98) measured at 6 months. CONCLUSIONS: Support for women to meet the breastfeeding recommendations should commence during pregnancy and focus on breastfeeding education and enabling environments.

A Real-Time, Plate-Based BRET Assay for Detection of cGMP in Primary Cells.

Cyclic guanosine monophosphate (cGMP) is a second messenger involved in the regulation of numerous physiological processes. The modulation of cGMP is important in many diseases, but reliably assaying cGMP in live cells in a plate-based format with temporal resolution is challenging. The Förster/fluorescence resonance energy transfer (FRET)-based biosensor cGES-DE5 has a high temporal resolution and high selectivity for cGMP over cAMP, so we converted it to use bioluminescence resonance energy transfer (BRET), which is more compatible with plate-based assays. This BRET variant, called CYGYEL (cyclic GMP sensor using YFP-PDE5-Rluc8), was cloned into a lentiviral vector for use across different mammalian cell types. CYGYEL was characterised in HEK293T cells using the nitric oxide donor diethylamine NONOate (DEA), where it was shown to be dynamic, reversible, and able to detect cGMP with or without the use of phosphodiesterase inhibitors. In human primary vascular endothelial and smooth muscle cells, CYGYEL successfully detected cGMP mediated through either soluble or particulate guanylate cyclase using DEA or C-type natriuretic peptide, respectively. Notably, CYGYEL detected differences in kinetics and strength of signal both between ligands and between cell types. CYGYEL remained selective for cGMP over cAMP, but this selectivity was reduced compared to cGES-DE5. CYGYEL streamlines the process of cGMP detection in plate-based assays and can be used to detect cGMP activity across a range of cell types.

Engagement, satisfaction, retention and behavioural outcomes of linguistically diverse mothers and infants participating in an Australian early obesity prevention trial.

BACKGROUND: Early obesity prevention research interventions in Australia generally expect participants to be able to communicate in English, but do not account for other languages. This study aimed to investigate engagement, satisfaction, retention and behavioural outcomes of linguistically diverse participants from a mainstream early childhood obesity prevention trial. METHODS: Healthy Beginnings is a nurse-led intervention based in Sydney, supporting families with optimal infant feeding and active play via telephone. This secondary analysis assessed participant engagement in the nurse telephone calls (call completions), satisfaction and behavioural outcomes (6- and 12-month survey data) and retention (survey completions), in the first year of life according to participants' language spoken at home (English or other language). RESULTS: Of 1155 mothers, 533 (46%) spoke a language other than English at home. Significantly fewer mothers speaking a language other than English completed the 6-month survey (79%) compared to those speaking English (84%), yet mothers speaking a language other than English who completed the program were more satisfied with the program overall. Significantly fewer mothers speaking a language other than English completed the final four nurse calls (of six) (56%-65%) compared to those speaking English (70%-80%). Adjusted odds ratios showed selected behavioural outcomes were significantly more positive for participants speaking English at home. CONCLUSIONS: Healthy Beginnings trial participants who spoke a language other than English at home had less favourable engagement, retention and behavioural outcomes compared to those who spoke English. So what? Early obesity prevention interventions should consider cultural adaptations to improve engagement and effectiveness among culturally and linguistically diverse families.

Forelimb myology of armadillos (Xenarthra: Cingulata, Chlamyphoridae): Anatomical correlates with fossorial ability.

Descriptions of myology reflect adaptations of the post-cranium and are essential for understanding the functional morphology of animal limbs. Armadillos (Cingulata) are the most species-rich group of the basal superorder Xenarthra, which is evident by their various lifestyles (subterranean vs. terrestrial) and levels of fossoriality (fossorial vs. semi-fossorial). While there have been several studies on limb bone proportions in numerous armadillos, limb myology has been reported for a limited number of species. Many of these descriptions need updating, and detailed quantitative muscle data are available only for nine-banded armadillos. The main objective of this study is to assess the forelimb myology of the pichi (Zaedyus pichiy), screaming hairy (Chaetophractus vellerosus), large hairy (Chaetophractus villosus), and pink fairy (Chlamyphorus truncatus) armadillos with comparisons to previous observations to specify muscle traits that indicate scratch-digging specializations in cingulates. Several myological features are variable among the species studied, including the origin of m. trapezius pars cervicalis, presence of a distinct m. rhomboideus profundus and m. omotransversarius, and number of heads present for m. triceps brachii and m. flexor digitorum profundus, all of which can be associated with variability in their respective habitats and functional habits. These traits are consistently observed in the members of the Euphractinae, whereas they are slightly divergent (i.e., reduced complexity) in the pink fairy armadillo despite a similar distribution of muscle mass in the limb retractors, elbow extensors, and carpal/digital flexors across species. The ecomorphology observed here among cingulates also confirms their recent reorganization into separate families and subfamilies.

Low Referral Rates for Genetic Assessment of Patients With Multiple Adenomas in United Kingdom Bowel Cancer Screening Programs.

BACKGROUND: Approximately 1 in 20 cases of colorectal cancer are caused by monogenic syndromes. Published guidelines recommend that patients with 10 or more adenomas be referred for genetic testing, based on evidence that colorectal cancer risk is associated with adenoma multiplicity. OBJECTIVE: The aim of this study was to determine adherence to guidelines on referral for genetic screening in patients with 10 or more adenomas. DESIGN: A cross-sectional study was performed of prospectively collected data from the UK Bowel Cancer Screening Programme between May 2007 and June 2018. Only histologically confirmed adenomas were included. Clinicopathological data were recorded from patient records, and referrals to clinical genetics services were ascertained. SETTING: Data were obtained from 3 centers in London, United Kingdom. PATIENTS: A total of 17,450 subjects underwent colonoscopy following an abnormal fecal occult blood test. MAIN OUTCOME MEASURES: We quantified patients with 10 or more adenomas and the proportion referred for genetic screening. RESULTS: The adenoma detection rate was 50.6% among 17,450 patients who underwent colonoscopy (8831 had 1 or more adenomas). Three hundred forty-seven patients (2.0%) had 10 or more adenomas. Patients with 10 or more adenomas were more likely to be male than those with fewer than 10 adenomas (76.9% vs 53.4%; p < 0.0001). A family history was collected in 37.8% of the multiple adenoma population. Of 347 patients with 10 or more adenomas, 28 (8.1%) were referred for genetic assessment. LIMITATIONS: All 3 screening centers were in a single city. No genetic outcome data were available to permit analysis of actual rates of inherited cancer syndromes in this population. CONCLUSIONS: In this study, almost 1 in 50 patients had 10 or more adenomas. Despite guidelines advising genetic testing in this group, referral rates are low. A referral pathway and management strategies should be established to address this patient population. See Video Abstract at http://links.lww.com/DCR/B630. TASAS BAJAS DE DERIVACIN PARA LA EVALUACIN GENTICA DE PACIENTES CON ADENOMAS MLTIPLES EN LOS PROGRAMAS DE DETECCIN DEL CNCER DE INTESTINO DEL REINO UNIDO: ANTECEDENTES:Aproximadamente uno de cada veinte casos de cáncer colorrectal son causados por síndromes monogénicos. Las pautas publicadas recomiendan que los pacientes con diez o más adenomas sean derivados para pruebas genéticas, basándose en la evidencia de que el riesgo de cáncer colorrectal está asociado con la multiplicidad de adenomas.OBJETIVO:El objetivo de este estudio fue determinar la adherencia a las guías de derivación para cribado genético en pacientes con diez o más adenomas.DISEÑO:Se realizó un estudio transversal de datos recolectados prospectivamente del Programa de Detección de Cáncer de Intestino del Reino Unido entre mayo de 2007 y junio de 2018. Solo se incluyeron los adenomas confirmados histológicamente. Los datos clínico-patológicos se registraron a partir de los registros de los pacientes y se determinaron las derivaciones a los servicios de genética clínica.AJUSTE ENTORNO CLINICO:Los datos se obtuvieron de tres centros en Londres, Reino Unido.PACIENTES:Un total de 17.450 17450 sujetos pacientes se sometieron a una colonoscopia después de una prueba de sangre oculta en heces anormal positiva.PRINCIPALES MEDIDAS DE RESULTADO VOLARACION:cuantificamos los pacientes con diez o más adenomas y la proporción remitida para cribado genético.RESULTADOS:La tasa de detección de adenomas fue del 50,6% entre 17.450 17450 pacientes que se sometieron a colonoscopia (8.831 8831 tenían uno o más adenomas). 347 pacientes (2,0%) tenían 10 o más adenomas. Los pacientes con 10 o más adenomas tenían más probabilidades de ser hombres que aquellos con menos de 10 adenomas (76,9% frente versus a 53,4%; p <0,0001). Se recogieron antecedentes familiares en el 37,8% de la población de adenomas múltiples. De 347 pacientes con 10 o más adenomas, 28 (8,1%) fueron remitidos para evaluación genética.LIMITACIONES:Los tres centros de detección se encontraban en una sola ciudad. No se disponía de datos de resultados genéticos que permitieran el análisis de las tasas reales de síndromes de cáncer hereditario en esta población.CONCLUSIONES:En este estudio, casi uno de cada cincuenta pacientes tenía diez o más adenomas. A pesar de las pautas que recomiendan las pruebas genéticas en este grupo, las tasas de derivación son bajas. Se debe establecer una vía de derivación y estrategias de manejo para abordar esta población de pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B630.

The process of culturally adapting the Healthy Beginnings early obesity prevention program for Arabic and Chinese mothers in Australia.

BACKGROUND: Behavioural interventions for the early prevention of childhood obesity mostly focus on English-speaking populations in high-income countries. Cultural adaptation is an emerging strategy for implementing evidence-based interventions among different populations and regions. This paper describes the initial process of culturally adapting Healthy Beginnings, an evidence-based early childhood obesity prevention program, for Arabic and Chinese speaking migrant mothers and infants in Sydney, Australia. METHODS: The cultural adaptation process followed the Stages of Cultural Adaptation theoretical model and is reported using the Framework for Reporting Adaptations and Modifications-Enhanced. We first established the adaptation rationale, then considered program underpinnings and the core components for effectiveness. To inform adaptations, we reviewed the scientific literature and engaged stakeholders. Consultations included focus groups with 24 Arabic and 22 Chinese speaking migrant mothers and interviews with 20 health professionals. With input from project partners, bi-cultural staff and community organisations, findings informed cultural adaptations to the content and delivery features of the Healthy Beginnings program. RESULTS: Program structure and delivery mode were retained to preserve fidelity (i.e. staged nurse calls with key program messages addressing modifiable obesity-related behaviours: infant feeding, active play, sedentary behaviours and sleep). Qualitative analysis of focus group and interview data resulted in descriptive themes concerning cultural practices and beliefs related to infant obesity-related behaviours and perceptions of child weight among Arabic and Chinese speaking mothers. Based on the literature and local study findings, cultural adaptations were made to recruitment approaches, staffing (bi-cultural nurses and project staff) and program content (modified call scripts and culturally adapted written health promotion materials). CONCLUSIONS: This cultural adaptation of Healthy Beginnings followed an established process model and resulted in a program with enhanced relevance and accessibility among Arabic and Chinese speaking migrant mothers. This work will inform the future cultural adaptation stages: testing, refining, and trialling the culturally adapted Healthy Beginnings program to assess acceptability, feasibility and effectiveness.

Ethnic inequalities in older adults bowel cancer awareness: findings from a community survey conducted in an ethnically diverse region in England.

BACKGROUND: To date, research exploring the public's awareness of bowel cancer has taken place with predominantly white populations. To enhance our understanding of how bowel cancer awareness varies between ethnic groups, and inform the development of targeted interventions, we conducted a questionnaire study across three ethnically diverse regions in Greater London, England. METHODS: Data were collected using an adapted version of the bowel cancer awareness measure. Eligible adults were individuals, aged 60+ years, who were eligible for screening. Participants were recruited and surveyed, verbally, by staff working at 40 community pharmacies in Northwest London, the Harrow Somali association, and St. Mark's Bowel Cancer Screening Centre. Associations between risk factor, symptom and screening awareness scores and ethnicity were assessed using multivariate regression. RESULTS: 1013 adults, aged 60+ years, completed the questionnaire; half were of a Black, Asian or Minority ethnic group background (n = 507; 50.0%). Participants recognised a mean average of 4.27 of 9 symptoms and 3.99 of 10 risk factors. Symptom awareness was significantly lower among all ethnic minority groups (all p's < 0.05), while risk factor awareness was lower for Afro-Caribbean and Somali adults, specifically (both p's < 0.05). One in three adults (n = 722; 29.7%) did not know there is a Bowel Cancer Screening Programme. Bowel screening awareness was particularly low among Afro-Caribbean and Somali adults (both p's < 0.05). CONCLUSION: Awareness of bowel cancer symptoms, risk factors and screening varies by ethnicity. Interventions should be targeted towards specific groups for whom awareness of screening and risk factors is low.

Feasibility of a culturally adapted early childhood obesity prevention program among migrant mothers in Australia: a mixed methods evaluation.

INTRODUCTION: Healthy Beginnings is an established nurse-led early childhood obesity prevention program that promotes healthy infant feeding practices and active play in the early years of life. To improve engagement with culturally and linguistically diverse populations, the Healthy Beginnings program delivered by telephone was culturally adapted and implemented with Arabic- and Chinese-speaking mothers in Sydney, Australia. The cultural adaptation process has been published separately. In this article, we aimed to evaluate the feasibility of the culturally adapted program. METHODS: In 2018-2019, the culturally adapted Healthy Beginnings program was implemented with Arabic- and Chinese-speaking women recruited from antenatal clinics in Sydney. At four staged timepoints (from third trimester until 6 months of age), mothers were sent culturally adapted health promotion booklets and text messages and offered four support calls from bi-cultural child and family health nurses in Arabic and Chinese. A mixed methods evaluation included a) baseline and 6-month telephone surveys, followed by b) semi-structured follow-up interviews with a subset of participating mothers and program delivery staff. Main outcomes of this feasibility study were reach (recruitment and retention), intervention dose delivered (number of nurse support calls completed) and acceptability (appropriateness based on cognitive and emotional responses). RESULTS: At recruitment, 176 mothers were eligible and consented to participate. Of 163 mothers who completed the baseline survey, 95% completed the program (n = 8 withdrew) and 83% completed the 6-month survey (n = 70 Arabic- and n = 65 Chinese-speaking mothers). Most mothers (n = 127, 78%) completed at least one nurse support call. The qualitative analysis of follow-up interviews with 42 mothers (22 Arabic- and 20 Chinese-speaking mothers) and 10 program delivery staff highlighted the perceived value of the program and the positive role of bi-cultural nurses and in-language resources. Mothers who completed more nurse support calls generally expressed greater acceptability. CONCLUSIONS: The culturally adapted Healthy Beginnings program was feasible to deliver and acceptable to Arabic- and Chinese-speaking mothers. Our results highlight the importance of in-language resources and individualised bi-cultural nurse support by telephone for supporting culturally and linguistically diverse migrant families with infant feeding and active play. These findings support the potential for program refinements and progression to an effectiveness trial.

Teamworking in endoscopy: a human factors toolkit for the COVID-19 era.

BACKGROUND: Endoscopy services have had to rapidly adapt their working practices in response to COVID-19. As recovery of endoscopy services proceeds, our workforce faces numerous challenges that can impair effective teamworking. We designed and developed a novel toolkit to support teamworking in endoscopy during the pandemic. METHODS: A human factors model was developed to understand the impact of COVID-19 on endoscopy teams. From this, we identified a set of key teamworking goals, which informed the development of a toolkit to support several team processes. The toolkit was refined following expert input and refinement over a 6-week period. RESULTS: The toolkit consists of four cognitive aids that can be used to support team huddles, briefings, and debriefs, alongside techniques to optimize endoscopic nontechnical skills across the patient-procedure pathway. We describe the processes that local endoscopy units can employ to implement this toolkit. CONCLUSION: A toolkit of cognitive aids, based on human factors principles, may be useful in supporting teams, helping them adapt to working safely in the era of COVID-19.

Use of a GP-endorsed non-participant reminder letter to promote uptake of bowel scope screening: A randomised controlled trial in a hard-to-reach population.

Previous research suggests that sending non-participants a reminder letter, 1 year after their initial invitation, can improve coverage for bowel scope screening (BSS), also known as flexible sigmoidoscopy screening. We hypothesised that adding a general practitioner's (GPs) endorsement to the reminder letter could improve coverage even further. We conducted a randomised controlled trial in North West London, UK. Participants were screening-eligible men and women who had not responded to their initial BSS invitation at least 12 months prior to the trial period. Eligible adults were randomised in a 1:1 ratio to receive either a GP-endorsed reminder letter, or a standard reminder letter from June to August 2019. Logistic regression models were used to test the effect of the GP endorsement on attendance at BSS, adjusting for sex, clinical commissioning group, and local area socioeconomic deprivation. In total, 1200 participants were enrolled into the study and randomised to either the control (n = 600) or the intervention (n = 600) group. Those who received the GP-endorsed reminder letter were only slightly more likely to attend BSS than those who received the standard reminder letter (4% vs. 3%); this difference was not statistically significant (Adjusted OR = 1.30; 95% CI: 0.69, 2.43). Adding a GP-endorsement to the annual reminder letter did not have an effect on attendance at BSS. One possible explanation for this is that the endorsement used was not personalised enough. Future research should examine stronger GP-endorsements or other methods to promote uptake.

Is Self-Compassion Selfish? The Development of Self-Compassion, Empathy, and Prosocial Behavior in Adolescence.

Both self-compassion and empathy have been theorized to promote prosociality in youth, but there is little longitudinal data examining this possibility. We assessed self-compassion, empathy, and peer-rated prosociality yearly, in a cohort of 2,078 youth across 17 schools (M age at T1 = 14.65 years; 49.2% female), as they progressed from Grade 9-12. We utilized multi-level modeling to predict prosocial behavior, nested within students, classes, and schools. We found that self-compassion and empathy uniquely predicted peer-rated prosocial behavior. However, only empathy predicted increases in prosocial behavior across time. While self-compassion is not selfish, it does not appear to facilitate the development of kindness toward adolescent peers. Self-compassion may help to buffer against possible negative effects of empathic distress.

The Novel Small-molecule Annexin-A1 Mimetic, Compound 17b, Elicits Vasoprotective Actions in Streptozotocin-induced Diabetic Mice.

The formyl peptide receptor (FPR) family are a group of G-protein coupled receptors that play an important role in the regulation of inflammatory processes. It is well-established that activation of FPRs can have cardioprotective properties. Recently, more stable small-molecule FPR1/2 agonists have been described, including both Compound 17b (Cmpd17b) and Compound 43 (Cmpd43). Both agonists activate a range of signals downstream of FPR1/2 activation in human-engineered FPR-expressing cells, including ERK1/2 and Akt. Importantly, Cmpd17b (but not Cmpd43) favours bias away from intracellular Ca2+ mobilisation in this context, which has been associated with greater cardioprotection in response to Cmpd17b over Cmpd43. However, it is unknown whether these FPR agonists impact vascular physiology and/or elicit vasoprotective effects in the context of diabetes. First, we localized FPR1 and FPR2 receptors predominantly in vascular smooth muscle cells in the aortae of male C57BL/6 mice. We then analysed the vascular effects of Cmpd17b and Cmpd43 on the aorta using wire-myography. Cmpd17b but not Cmpd43 evoked a concentration-dependent relaxation of the mouse aorta. Removal of the endothelium or blockade of endothelium-derived relaxing factors using pharmacological inhibitors had no effect on Cmpd17b-evoked relaxation, demonstrating that its direct vasodilator actions were endothelium-independent. In aortae primed with elevated K+ concentration, increasing concentrations of CaCl2 evoked concentration-dependent contraction that is abolished by Cmpd17b, suggesting the involvement of the inhibition of Ca2+ mobilisation via voltage-gated calcium channels. Treatment with Cmpd17b for eight weeks reversed endothelial dysfunction in STZ-induced diabetic aorta through the upregulation of vasodilator prostanoids. Our data indicate that Cmpd17b is a direct endothelium-independent vasodilator, and a vasoprotective molecule in the context of diabetes.

Measuring Sulforaphane and Its Metabolites in Human Plasma: A High Throughput Method.

(1) Background: There is increasing understanding of the potential health benefits of cruciferous vegetables. In particular sulforaphane (SFN), found in broccoli, and its metabolites sulforaphane-glutathione (SFN-GSH), sulforaphane-cysteine (SFN-Cys), sulforaphane cysteine-glycine (SFN-CG) and sulforaphane-N-acetyl-cysteine (SFN-NAC) have potent antioxidant effects that may offer therapeutic value. Clinical investigation of sulforaphane as a therapeutic antioxidant requires a sensitive and high throughput process for quantification of sulforaphane and metabolites; (2) Methods: We collected plasma samples from healthy human volunteers before and for eight hours after consumption of a commercial broccoli extract supplement rich in sulforaphane. A rapid and sensitive method for quantification of sulforaphane and its metabolites in human plasma using Liquid Chromatography-Mass Spectrometry (LC-MS) has been developed; (3) Results: The LC-MS analytical method was validated at concentrations ranging between 3.9 nM and 1000 nM for SFN-GSH, SFN-CG, SFN-Cys and SFN-NAC and between 7.8 nM and 1000 nM in human plasma for SFN. The method displayed good accuracy (1.85%-14.8% bias) and reproducibility (below 9.53 %RSD) including low concentrations 3.9 nM and 7.8 nM. Four SFN metabolites quantitation was achieved using external standard calibration and in SFN quantitation, SFN-d8 internal standardization was used. The reported method can accurately quantify sulforaphane and its metabolites at low concentrations in plasma; (4) Conclusions: We have established a time- and cost-efficient method of measuring sulforaphane and its metabolites in human plasma suitable for high throughput application to clinical trials.

Optimising bowel preparation before colonoscopy.

A clean colon is required for a colonoscopy to be effective. Therefore, patients undergo a bowel preparation in advance of the procedure to clear the colon. Typically, this involves drinking 2 litres of polyethylene glycol or macrogol (PEG) solution, but dislike of the taste or having to drink such a large volume causes some patients not to adhere to this regimen. To address this, a PEG solution has been developed that requires patients to drink only 1 litre of bowel preparation in two flavours. The hope is this will increase patient adherence.

From pregnancy to cardiovascular disease: Lessons from relaxin-deficient animals to understand relaxin actions in the vascular system.

Early maternal vascular adaptations to pregnancy are predominantly driven by changes in vascular tone, reactivity, and remodeling. Failure of the maternal systemic vasculature to adapt sufficiently can lead to serious complications of pregnancy. The hormone relaxin is widely recognized for its contribution to the essential renal and systemic hemodynamic adaptations in early pregnancy through direct actions on the maternal vasculature. Studies in relaxin gene knockout mice revealed that endogenous relaxin is not only a "pregnancy hormone" but has pleiotropic actions in various tissues in males and non-pregnant females. There is strong interest in relaxin's actions in the vasculature and its utility in the treatment of vascular diseases. Relaxin treatment in rodents for 2-5 days or acute intravenous injection enhances endothelium-dependent relaxation and decreases myogenic tone in resistance arteries. These vascular actions are prolonged, even in the absence of circulating relaxin, and are underpinned by the production of endothelium-derived relaxing factors including nitric oxide, endothelium-derived hyperpolarization, and prostacyclin. Relaxin is also capable of remodeling the vascular wall in a variety of blood vessels in disease conditions. Lessons learned in pregnancy research have aided studies investigating the potential therapeutic potential of relaxin in cardiovascular disease.

Side-Chain Protonation States of a Fluorescent Arginine.

An arginine derivative with a fluorescent side-chain, Boc-Arg(Nap)-OH, was prepared by palladium(0)-catalyzed coupling of Boc-Arg-OH with a 4-bromonaphthalimide. The presence of the fluorophore lowers the pKa of the side-chain guanidinium group by several orders of magnitude, to 9.0 (±0.1), allowing the derivative to access an electrically neutral protonation state that is not generally available to arginine itself. Computational modeling (DFT) predicts that protonation takes place at the side-chain C═N atom that bears the fluorophore. Calculated electronic absorptions for the protonated (356 nm) and neutral species (440 nm) are in good agreement with experiment. When irradiated with light, excited-state proton transfer (ESPT) occurs from cationic side-chains to suitably basic solvents, resulting in fluorescence emission from the neutral species. Arg(Nap) can be incorporated into peptides with sterically accessible N-termini using specially adapted conditions of solid-phase peptide synthesis.

Targeting the vascular dysfunction: Potential treatments for preeclampsia.

Preeclampsia is a pregnancy-specific disorder, primarily characterized by new-onset hypertension in combination with a variety of other maternal or fetal signs. The pathophysiological mechanisms underlying the disease are still not entirely clear. Systemic maternal vascular dysfunction underlies the clinical features of preeclampsia. It is a result of oxidative stress and the actions of excessive anti-angiogenic factors, such as soluble fms-like tyrosine kinase, soluble endoglin, and activin A, released by a dysfunctional placenta. The vascular dysfunction then leads to impaired regulation and secretion of relaxation factors and an increase in sensitivity/production of constrictors. This results in a more constricted vasculature rather than the relaxed vasodilated state associated with normal pregnancy. Currently, the only effective "treatment" for preeclampsia is delivery of the placenta and therefore the baby. Often, this means a preterm delivery to save the life of the mother, with all the attendant risks and burdens associated with fetal prematurity. To lessen this burden, there is a pressing need for more effective treatments that target the maternal vascular dysfunction that underlies the hypertension. This review details the vascular effects of key drugs undergoing clinical assessment as potential treatments for women with preeclampsia.