Knowledge sharing in virtual communities of practice of family caregivers of people with Alzheimer's.

INTRODUCTION: Knowledge sharing can only happen in the context of a trusting and supportive environment, such as evolves in communities of practice and their virtual equivalent, virtual communities of practice. The main objective of this study was to understand knowledge sharing between participants in a virtual community of practice of caregivers of people with Alzheimer's. METHODS: The authors designed their own mobile application, and two virtual communities of practice were created independently and differentiated by how they were moderated: one by an expert caregiver and the other by three health professionals. 38 caregivers and four moderators were involved in the study, which ran between July 2017 and April 2018. A total of 1925 messages were exchanged within the two communities and used as data in the study. Message data was analysed using LINKS (Leveraging Internet Networks for knowledge sharing). RESULTS: Participants were more motivated to acquire knowledge related to caring for the person with Alzheimer's rather than caring for themselves. The purpose of the messages was to inform others about the sender and not to seek answers. It seems that the interaction was more to socialise and to feel heard, than to gain information. Face to face meetings appear to have accelerated community development. On nearly every parameter, behaviour was significantly different in the two communities, reflecting the importance of the character of the moderator. Caring for oneself was a much stronger theme in the community that included health professionals. Experiential knowledge sharing was particularly strong in the group led by a caregiver. DISCUSSION: Caregivers adapted the virtual community of practice to their own needs and mainly shared social knowledge. This focus on social support, which seems to be more valued by the caregivers than information about the disease, was not an expected pattern. Virtual communities of practice where peers count on each other, function more as a support group, whereas those moderated by health professionals function more as a place to go to acquire information. The level of interactivity points to such communities being important for knowledge sharing not mere knowledge transfer.

Sensory Processing Assessment and Feedback in the Treatment of Complex Developmental Trauma.

This study explored the impact of a sensory processing assessment, recommendations and feedback process on the functioning at school and after-hours environments of children who had been traumatised by abuse. A mixed methods design (Schoonenboom & Johnson, 2017) was utilized incorporating pre (12 months prior) and post (four to eight months after the report) repeated child focused measure, alongside thematic analysis of participants qualitative survey feedback. The methodology included two stages: firstly, an occupational therapy assessment of young people referred by Own Organisation clinicians for a sensory processing assessment and secondly, an evaluation was conducted of the impact of occupational therapy on the young person's behaviour and their carers. The study found significant improvement in family life and relationships as well as a reduction in impairment as evidenced by decreases in HoNOSCA scores across problems with family life and relationships, non-accidental self-injury, problems with emotional and related symptoms, poor school attendance and on the social subscale. These findings were supported by clinician participant reports. A sensory processing assessment provided young people, their carers and teachers with information which contributed to environmental adaptations. These environmental adaptations were associated with improved functioning and behaviour of young people impacted by child abuse. It is recommended future research attempt to replicate and extend our understanding of how sensory processing assessments and interventions can increase children's wellbeing. Supplementary Information: The online version contains supplementary material available at 10.1007/s40653-023-00607-0.

Initial experience using middle meningeal artery embolisation for patients with recurrent and high-recurrence-risk chronic subdural haematoma.

Recurrence rates following surgical management of chronic subdural haematoma (CSDH) range from 5 to 33 %. There is growing evidence which suggests middle meningeal artery embolisation (MMAe) may reduce recurrence rates when used as surgical adjunct or standalone treatment. In this study we described our experience of this new procedure in the our UK institution. Patients with recurrent CSDH or CSDH at high risk of recurrence were selected for MMAe on a case-by-case basis following MDT discussion. A departmental database was used to identify patients treated. 26 CSDH were embolised in 20 patients; 9 CSDH were de-novo and 17 were recurrent. 10/26 CSDH were treated with MMAe only. No procedural mortality, access site or thrombo-embolic complications occurred. One patient experienced symptomatic collection growth 12 h following MMAe and required surgical drainage. 15 (75 %) of patients were living at home at follow-up (mean 14 months). On imaging follow-up 15/18 showed CSDH volume reduction or resolution, 1/18 remained stable requiring no further treatment, 2/18 patients suffered recurrent CSDH requiring treatment. In both recurrent cases incomplete embolisation was noted on procedural imaging (posterior division of MMA not embolised). Persistent posterior MMA division filling was significantly associated with collection recurrence (p = 0.002). Our results suggest MMAe as a stand-alone or adjuvant therapy can be performed safely in a UK neuroscience setting and is associated with high rates of symptomatic CSDH size reduction or resolution in problematic CSDH that have either recurred or are prone to recurrence.

Obesity medications: A narrative review of current and emerging agents.

The aim of this narrative review is to synthesize the available data describing the efficacy and safety of medications approved for obesity management and to provide an overview of upcoming agents in development. A literature search of PubMed, Medline, and Embase databases identified relevant articles describing medications approved in the U.S., Australia, U.K., and/or Europe. Papers were selected based on relevance and originality, with phase 3 clinical trials and meta-analyses preferentially included. Six medications are widely approved for long-term weight management in conjunction with lifestyle interventions in people with body mass index (BMI) ≥30 â€‹kg/m2 or BMI ≥27 â€‹kg/m2 and at least one medical condition related to excess weight. Compared with lifestyle interventions alone, all medications approved for obesity management are more effective for long-term weight loss and improvements in cardiometabolic risk factors. Older obesity medications are associated with mean weight losses in the range of 5-10%. The new generation of agents, including the injectable incretin analogues semaglutide and tirzepatide are associated with sustained mean weight reductions of 15-20%, along with substantial benefits on a range of health outcomes. Several novel agents are under development, with multi-hormone receptor agonists and oral formulations likely to become available in the coming years. As effective treatment options expand, cost and availability will need to be addressed to enable equitable access to treatment. Other important challenges for clinical practice and research include the need for long-term strategies to prevent and manage weight regain and loss of lean muscle and bone mineral density.

Validation of actigraphy sleep metrics in children aged 8 to 16 years: considerations for device type, placement and algorithms.

BACKGROUND: Actigraphy is often used to measure sleep in pediatric populations, despite little confirmatory evidence of the accuracy of existing sleep/wake algorithms. The aim of this study was to determine the performance of 11 sleep algorithms in relation to overnight polysomnography in children and adolescents. METHODS: One hundred thirty-seven participants aged 8-16 years wore two Actigraph wGT3X-BT (wrist, waist) and three Axivity AX3 (wrist, back, thigh) accelerometers over 24-h. Gold standard measures of sleep were obtained using polysomnography (PSG; Embletta MPRPG, ST + Proxy and TX Proxy) in the home environment, overnight. Epoch by epoch comparisons of the Sadeh (two algorithms), Cole-Kripke (three algorithms), Tudor-Locke (four algorithms), Count-Scaled (CS), and HDCZA algorithms were undertaken. Mean differences from PSG values were calculated for various sleep outcomes. RESULTS: Overall, sensitivities were high (mean ± SD: 91.8%, ± 5.6%) and specificities moderate (63.8% ± 13.8%), with the HDCZA algorithm performing the best overall in terms of specificity (87.5% ± 1.3%) and accuracy (86.4% ± 0.9%). Sleep outcome measures were more accurately measured by devices worn at the wrist than the hip, thigh or lower back, with the exception of sleep efficiency where the reverse was true. The CS algorithm provided consistently accurate measures of sleep onset: the mean (95%CI) difference at the wrist with Axivity was 2 min (-6; -14,) and the offset was 10 min (5, -19). Several algorithms provided accurate measures of sleep quantity at the wrist, showing differences with PSG of just 1-18 min a night for sleep period time and 5-22 min for total sleep time. Accuracy was generally higher for sleep efficiency than for frequency of night wakings or wake after sleep onset. The CS algorithm was more accurate at assessing sleep period time, with narrower 95% limits of agreement compared to the HDCZA (CS:-165 to 172 min; HDCZA: -212 to 250 min). CONCLUSION: Although the performance of existing count-based sleep algorithms varies markedly, wrist-worn devices provide more accurate measures of most sleep measures compared to other sites. Overall, the HDZCA algorithm showed the greatest accuracy, although the most appropriate algorithm depends on the sleep measure of focus.

Cancer risk-factor and symptom awareness among adults with intellectual disabilities, paid and unpaid carers, and healthcare practitioners: a scoping review.

BACKGROUND: The physical health of people with intellectual disabilities (ID) has been identified as an area of ongoing concern and priority. Research has increasingly focused on cancer, with studies indicating that people with ID are at an increased risk of cancer and of mortality, compared with the general population. This review aims to systematically identify and synthesise the published academic literature exploring cancer risk-factor and symptom awareness among people with IDs, carers and healthcare professionals. METHODS: In line with Arksey and O'Malley's (2005) framework for scoping reviews, five incremental stages were followed: (1) identifying research question, (2) identifying relevant studies, (3) study selection, (4) extracting and charting of data, and (5) collating, summarising and reporting results. Findings were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews (PRISMA-Scr). RESULTS: The search strategy identified 352 records, 16 records met all eligibility criteria and were included for review. The studies address a range of areas including knowledge and awareness of cancer risk-factors and symptoms and interventions to promote awareness of cancer. CONCLUSIONS: Cancer risk-factor and symptom awareness is low among adults with ID, paid and unpaid carers and healthcare practitioners (HCPs). Theoretically underpinned, co-designed tools and interventions to improve awareness are lacking. There is uncertainty surrounding how to best support people with ID in raising cancer awareness, even within the professional healthcare environment. There is a predominance of research on breast cancer awareness. Future studies focusing on other cancers are needed to build a complete picture of awareness among adults with IDs, paid and unpaid carers, and HCPs.

Comparative evaluation of Luminex based assays for detection of SARS-CoV-2 antibodies in a transplantation laboratory.

BACKGROUND: Detection of SARS-CoV-2 antibodies is essential in establishing the parameters of an individual's immune response to COVID-19, from both natural infection and vaccination. Despite this, there is currently limited clinical guidance or recommendations for serological methods for their measurement. Here, we evaluate and compare four Luminex-based assays for the multiplex detection of IgG SARS-CoV-2 antibodies. METHODS: The four assays tested were Magnetic Luminex Assay, MULTICOV-AB Assay, Luminex xMAP SARS-CoV-2 Multi-Antigen IgG Assay and LABScreen COVID Plus Assay. Each assay's ability to detect antibodies to SARS-CoV-2 Spike (S), Nucleocapsid (N) and Spike-Receptor Binding Domain (RBD) was evaluated using 50 test samples (25 positive, 25 negative), previously tested by a widely used ELISA technique. RESULTS: The MULTICOV-AB Assay had the highest clinical performance detecting antibodies to S trimer and RBD in 100% (n = 25) of known positive samples. Both the Magnetic Luminex Assay and LABScreen COVID Plus Assay showed significant diagnostic accuracy with sensitivities of 90% and 88% respectively. The Luminex xMAP SARS-CoV-2 Multi-Antigen IgG Assay demonstrated limited detection of antibodies to the S antigen resulting in a sensitivity of 68%. CONCLUSION: Luminex-based assays provide a suitable serological method for multiplex detection of SARS-CoV-2 specific antibodies, with each assay able to detect antibodies to a minimum of 3 different SARS-CoV-2 antigens. Assay comparison identified there is moderate performance variability between manufacturers and further inter-assay variation of antibodies detected to different SARS-CoV-2 antigens.

An Ambulatory Pathway for the Investigation of Patients with Suspected Pulmonary Embolism.

Aims The aim of this project was to provide an ambulatory pathway for diagnosis and management of patients with suspected Pulmonary Embolism (PE) with "low-risk" features. Methods A structured algorithm for the management of suspected PE was designed and implemented in April 2021. This involved the development of local guidelines to identify those "low-risk" patients with suspected PE, through the use of modified sPESI and Hestia criteria. This pathway was audited monthly to establish effect on admission and hospital length of stay. Results 51 CT PAs were performed by the Emergency Department in April 2021. Total number of CT confirmed PEs in April was 7(11%). 12 "low-risk" patients with suspected PE were identified and placed on the "Ambulatory Suspected Pulmonary Embolism Pathway". One (8.3%) patient on this pathway had a confirmed PE. Patients placed on this pathway spent significantly less time in the Emergency Department and in hospital with greater satisfaction by physicians using this pathway. Conclusion This pathway has succeeded in significantly decreasing length of stay both in the ED and in hospital for patients with suspected and confirmed PE.

Comparison of circulating total sFLT-1 to placental-specific sFLT-1 e15a in women with suspected preeclampsia.

INTRODUCTION: Soluble fms-like tyrosine kinase 1 (sFLT-1), a circulating anti-angiogenic factor that binds and antagonizes placental growth factor (PlGF), appears key to preeclamptic pathophysiology. Two main sFLT-1 splice variants exist: sFLT-1 e15a and sFLT-1 i13. Total sFLT-1/PlGF ratios are increasingly used clinically; we explore whether using placental-specific sFLT-1 e15a improves test performance compared with total sFLT-1 in preeclampsia diagnosis. METHODS: Consent was obtained for serum sampling from 96 women with suspected preeclampsia. Total sFLT-1 and PlGF were quantified using the B.R.A.H.M.S Kryptor Compact Plus automated immunoassay platform, and sFLT-1 e15a by custom enzyme-linked immunosorbent assay. Test performance was then assessed by subsequent diagnosis. RESULTS: Of 96 participants, 32 did not develop preeclampsia, 32 had early-onset (<34 weeks') disease and 32 had late-onset (≥34 weeks') disease. In those with preeclampsia, median sFLT-1 and sFLT-1 e15a were significantly increased (7361.0 vs 2463.0 pg/mL, and 946.6 vs 305.4 ng/mL respectively; p < 0.001 for both), and PlGF significantly reduced (43.5 vs 154.4 pg/mL; p < 0.001) compared to those without preeclampsia. Those with early-onset, compared to late-onset, preeclampsia chiefly had lower median PlGF levels (16.0 vs 57.3; p < 0.001), which contributed to higher sFLT-1/PlGF and sFLT-1 e15a/PlGF ratios (830.1 vs 86.7, and 109258.9 vs 12608.7 respectively; p < 0.001 for both). DISCUSSION: sFLT-1 e15a performs comparably to total sFLT-1 in women with suspected preeclampsia, however with higher translational burden. Our results support the expanding clinical use of the sFLT-1/PlGF ratio in suspected preeclampsia, particularly early-onset, to assist with disease diagnosis.

Pre-exposure prophylaxis awareness, acceptability and potential stigma among medical and non-medical clinic staff in methadone treatment settings in northern New Jersey: The key role of non-medical staff in enhancing HIV prevention.

BACKGROUND: HIV prevention is needed among people who use drugs (PWUD) due to mixing sex and drugs, selling/trading sex, and/or injecting drugs. Pre-exposure prophylaxis (PrEP) is an extremely effective biomedical HIV prevention strategy, but uptake remains low among communities most in need of HIV prevention, including PWUD. Previous studies have found that providers are less willing to prescribe PrEP to PWUD, yet PWUD express high levels of PrEP acceptance. More research is needed to understand how people who provide substance use treatment services think about PrEP to maximize this biomedical prevention strategy. METHODS: The study conducted semistructured interviews with 29 staff members in two methadone clinic settings in urban northern New Jersey. Staff members included medical providers, methadone counselors, intake coordinators, front desk staff, lab technicians, security guards, and administrative/leadership personnel. RESULTS: All staff recognized the need for HIV prevention among their patient populations, but most were either unaware of PrEP or unfamiliar with its purpose and how it works. Medical providers were more likely to have some PrEP knowledge in comparison to counselors and other staff, but the former largely did not have in-depth knowledge. Among those familiar with PrEP, many confused PrEP with HIV medication, as Truvada was the only FDA-approved PrEP at the time of the study. About half of participants expressed clear support for PrEP, while the other half expressed mixed or negative attitudes related to HIV, sexual behavior, and mistrust of the medication. Both the positive and negative perceptions entailed stigmatizing elements. RECOMMENDATIONS: Due to patients' frequent interactions with non-medical staff (e.g., front desk staff, lab technicians, etc.), all staff, not only medical personnel, should be aware of PrEP and comfortable discussing it to foster well-informed, nonjudgmental conversations about HIV prevention with patients. PrEP education should specifically address HIV and sexual-related stigma, as even positive perceptions of PrEP may entail stigmatizing elements.

Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease.

Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.

Simplified sperm testing devices: a possible tool to overcome lack of accessibility and inconsistency in male factor infertility diagnosis. An opportunity for low- and middle- income countries.

BACKGROUND: Manual semen assessment (MSA) is a key component in a male's fertility assessment. Clinicians rely on it to make diagnostic and treatment decisions. When performed manually, this routine laboratory test is prone to variability due to human intervention which can lead to misdiagnosis and consequently over- or under- treatment. For standardisation, continuous training, quality control (QC) programs and pricy Computer-Assisted Sperm Analysis (CASA) systems have been proposed, yet, without resolving intra- and inter-laboratory variability. In response, promising simplified sperm testing devices, able to provide cost-effective point-of-care male infertility diagnosis are prospected as a plausible solution to resolve variability and increase access to sperm testing. MATERIALS AND METHODS: A throughout literature research for semen testing, sperm analysis, smart-phone assisted semen analysis, 'at-home' semen testing, male infertility, infertility in developing countries, infertility in low- and middle-income countries (LMIC) and quantitative sperm analysis was performed. A total of 14 articles, specific to 'at-home' simplified sperm assessment, were included to treat the core subject. RESULTS: Continuous training and consistent QC, are sine qua none conditions to achieve accurate and comparable MSA. Compliance does not rule-out variability, nevertheless. Emerging simplified sperm assessment devices are an actual alternative to resolve the lack of standardisation and accessibility to sperm analysis. YO ® , SEEM ® , and ExSeed ® are commercially available, user-friendly smartphone-based devices which can accurately measure volume, sperm concentration (millions/ml) and total motile sperm count. More broadly, by cost-effectiveness, availability, accuracy and convenient application, these devices could effectively select patients for first-line artificial reproduction treatments such as intrauterine insemination. CONCLUSIONS: Accuracy and cost-effectiveness make smart-phone based sperm testing devices a practical and realistic solution to overcome variability in MSA. Importantly, these tools represent an actual opportunity to standardise and improve male subfertility diagnosis and treatment, especially in LMIC. However, before clinical application is possible, guidelines, further testing with special attention on accuracy in washed sperm, availability, cost-benefit and reliability are required.

Correlates of PrEP Uptake Among Young Sexual Minority Men and Transgender Women in New York City: The Need to Reframe "Risk" Messaging and Normalize Preventative Health.

Pre-exposure prophylaxis (PrEP) is an effective form of HIV prevention, but young sexual minority men face myriad barriers to PrEP uptake. Participants (n = 202) completed a survey on healthcare experiences and beliefs about HIV and PrEP. While 98% of the sample knew about PrEP, only 23.2% reported currently taking PrEP. Participants were more likely to be taking PrEP if they received PrEP information from a healthcare provider and endorsed STI-related risk compensation. Conversely, PrEP uptake was less likely among those with concerns about medication use and adherence. While there were no racial/ethnic differences in PrEP uptake, there were differences in correlates of PrEP use for White participants and participants of color. To facilitate PrEP uptake, clinicians should provide PrEP education and screen all patients for PrEP candidacy. Additionally, public health messaging must reframe HIV "risk", highlight benefits of STI testing, and emphasize the importance of preventive healthcare for SMM.

Novel homozygous variant in BMP1 associated with a rare osteogenesis imperfecta phenotype.

Osteogenesis imperfecta (OI) is characterized by bone fragility and increased fracture susceptibility. BMP1 variants have been reported in the rare OI type XIII, specifically referred to herein as BMP1-associated autosomal recessive (AR) OI. We report the clinical presentation and diagnostic evaluation of a patient found to have a novel homozygous variant in BMP1. We also provide an overview of reported BMP1 variants to date, with discussion focusing on the use of bisphosphonate therapy in these patients. A 7-year-old male with speech and motor delay sustained five bilateral tibial fractures with minimal trauma since age 2.5 years. At age 6, he developed severe back pain after a fall. Diffuse spinal osteopenia and multiple vertebral compression fractures (VCF) at T9, L1, L3, and L5 were identified. Total hip BMD was generous (adjusted Z-score* = 1.76), and femoral neck BMD was high (adjusted Z-score* = 2.67). VCFs precluded assessment of lumbar spine BMD. Genetic analysis identified a homozygous missense variant in exon 4 of BMP1 (c.C505T; p.Arg169Cys). Unlike most forms of OI, patients with BMP1-associated AR OI may have normal or paradoxically increased BMD, making BMD and fracture risk correlation difficult. While bisphosphonates (BP) may help reduce recurrent fractures and provide symptomatic relief, the broad phenotypic spectrum and underlying bone pathology, often in the setting of increased BMD, complicate management. HR-pQCT assessment of bone microarchitecture and quality may aid in the decision of BP therapy and subsequent monitoring. Evidence is limited with respect to the effectiveness of BP in this rare form of OI. *Z-score was adjusted for height Z-score.

Sulforaphane Bioavailability and Effects on Blood Pressure in Women with Pregnancy Hypertension.

Sulforaphane, an isothiocyanate found in cruciferous vegetables such as broccoli, shows promise as an adjuvant therapy for preeclampsia. To inform future clinical trials, we set out to determine the bioavailability of sulforaphane in non-pregnant and preeclamptic women. In six healthy female volunteers, we performed a crossover trial to compare the bioavailability of sulforaphane and metabolites afforded by an activated and non-activated broccoli extract preparation. We then undertook a dose escalation study of the activated broccoli extract in 12 women with pregnancy hypertension. In non-pregnant women, an equivalent dose of activated broccoli extract gave higher levels of sulforaphane and metabolites than a non-activated extract (p < 0.0001) and greater area under the curve (AUC) (3559 nM vs. 2172 nM, p = 0.03). Compared to non-pregnant women, in women with preeclampsia, the same dose of activated extract gave lower levels of total metabolites (p < 0.000) and AUC (3559 nM vs. 1653 nM, p = 0.007). Doubling the dose of the activated extract in women with preeclampsia doubled levels of sulforaphane and metabolites (p = 0.02) and AUC (1653 nM vs. 3333 nM, p = 0.02). In women with preeclampsia, activated broccoli extract was associated with modest decreases in diastolic blood pressure (p = 0.05) and circulating levels of sFlt-1 (p = 0.0002). A myrosinase-activated sulforaphane formulation affords better sulforaphane bioavailability than a non-activated formulation. Higher doses of sulforaphane are required to achieve likely effective doses in pregnant women than in non-pregnant women. Sulforaphane may improve endothelial function and blood pressure in women with pregnancy hypertension.

Proceedings of a workshop to discuss the epidemiology of invasive Haemophilus influenzae disease with emphasis on serotype a and b in the Americas, 2019.

On March 9, 2019, a one-day workshop titled "The current epidemiology of invasive Haemophilus influenzae disease in the Americas", jointly organized by the Public Health Agency of Canada (PHAC), the Canadian Institute of Health Research (CIHR), and the National Research Council Canada (NRC), brought together experts in the epidemiology and surveillance of invasive Haemophilus influenzae (Hi) disease from the Pan American Health Organization (PAHO) and its five regional reference laboratories in South America, USA, and Canada in Ottawa, Ontario, Canada. This workshop built upon recommendations of previous related workshops and incorporated updated data.

Comparison of polysaccharide glycoconjugates as candidate vaccines to combat Clostridiodes (Clostridium) difficile.

Two known Clostridiodes (Clostridium) difficile surface antigens, a lipoteichoic acid (LTA) and a polysaccharide (PS-II) were isolated and purified in order to prepare glycoconjugate vaccines to the carrier protein human serum albumin utilising a reductive amination strategy. Mice and rabbits were immunized with a prime and two boost strategy and the resulting sera were examined for their ability to recognise the purified homologous antigens and subsequently killed whole cells of C. difficile strains and other Clostridia species. Immunisation derived antisera from rabbits and mice, recognised all strains of C. difficile vegetative cells examined, with generally similar titers from animals that received the LTA or the PS-II conjugates. Sera raised to the LTA conjugates were able to recognise other Clostridia species C. butyricum, C. bifermentans and C. subterminale whereas sera raised to the PS-II conjugates were not. These LTA and PS-II sera recognised live cells in an immunofluorescence assay and were also able to recognise the spore form of the bacterium. This study has confirmed that the LTA and PS-II polysaccharides are both highly conserved surface polymers of C. difficile that are easily accessible to the immune system and as such may have potential as vaccine antigens or as targets for therapeutics to combat C. difficile infection.

Sulforaphane improves vascular reactivity in mouse and human arteries after "preeclamptic-like" injury.

INTRODUCTION: The widespread maternal endothelial dysfunction that underlies the manifestations of preeclampsia is thought to arise from excessive placental production of antiangiogenic factors and enhanced oxidative stress. Therefore, we assessed whether the natural antioxidant sulforaphane could improve vascular function. METHODS: Cell viability of human umbilical vein endothelial cells (HUVECs) was assessed after 24 or 48 h in normoxia (20% O2) or hypoxia (1% O2) with or without sulforaphane. To model vascular dysfunction associated with preeclampsia, mouse mesenteric arteries were incubated in trophoblast conditioned media (TCM), and human omental arteries incubated in preeclamptic explant media (PEM) with or without sulforaphane. Both media are rich in antiangiogenic compounds associated with preeclampsia. TCM was generated from primary cytotrophoblast cells from term placentae of normotensive, while PEM was generated from explants from preeclamptic women. Reactivity was assessed by wire myography. sulforaphane's actions as a vasodilator were also investigated. RESULTS: Under conditions of hypoxia, sulforaphane improved HUVEC viability. In mouse mesenteric arteries, sulforaphane reduced contraction evoked by potassium (p < 0.001), phenylephrine and endothelin 1 (all p < 0.001). Sulforaphane also inhibited Ca2+-induced contraction (p = 0.014). Sulforaphane prevented TCM-induced augmentation of phenylephrine and angiotensin II-mediated contraction of mouse mesenteric arteries. In human omental arteries, sulforaphane induced vasodilation (p < 0.001), and prevented PEM-induced endothelial dysfunction by restoring arterial sensitivity to the endothelium-dependent vasodilator bradykinin (p = 0.008). DISCUSSION: Sulforaphane causes relaxation in arteries and protects against arterial dysfunction induced by placental-derived antiangiogenic factors, which are known to contribute to the preeclampsia.