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This report presents a case of endocarditis due to Haemophilus segnis, which represents a speciation difficulty for the routine laboratory. In this study, a molecular approach provided speciation, which was confirmed phenotypically by a reference laboratory. The use of molecular genotypic analysis is an additional strategy in the investigation of endocarditis. It has applications not only in isolate identification but also in primary detection of infection, particularly in patients whose blood is culture negative by conventional methodologies. [ABSTRACT FROM AUTHOR]

Bifidobacteria are commonly encountered members of the human gut microbiota that possess the enzymatic machinery necessary for the metabolism of certain plant-derived, complex carbohydrates. In the current study we describe differential growth profiles elicited by a panel of 21 newly isolated Bifidobacterium pseudocatenulatum strains on various plant-derived glycans. Using a combination of gene-trait matching and comparative genome analysis, we identified two distinct xylanases responsible for the degradation of xylan. Furthermore, three distinct extracellular α-amylases were shown to be involved in starch degradation by certain strains of B. pseudocatenulatum . Biochemical characterization showed that all three α-amylases can cleave the related substrates amylose, amylopectin, maltodextrin, glycogen and starch. The genes encoding these enzymes are variably found in the species B. pseudocatenulatum , therefore constituting a strain-specific adaptation to the gut environment as these glycans constitute common plant-derived carbohydrates present in the human diet. Overall, our study provides insights into the metabolism of these common dietary carbohydrates by a human-derived bifidobacterial species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sanchez-Gallardo, Bottacini, Friess, Esteban-Torres, Somers, Moore, McAuliffe, Cotter and van Sinderen.)

There is large potential to increase cycling participation worldwide. Participation in cycling is associated with lower risk of mortality from any cause, and incidence of cardiovascular disease and type 2 diabetes, as well as positive mental health and well-being. The largest potential for health gains likely to come from increasing participation amongst those who do not currently cycle regularly, rather than encouraging those who already cycle regularly to cycle more. Replacing car journeys with cycling can lead to reductions in air pollution emissions and lower pollutant exposure to the general population. Important gaps and uncertainties in the existing evidence base include: the extent to which the health benefits associated with cycling participation are fully causal due to the observational nature of much of the existing evidence base; the real-world economic cost-benefits of pragmatic interventions to increase cycling participation; and the most effective (combination of) approaches to increase cycling participation. To address these uncertainties, large-scale, long-term randomised controlled trials are needed to: evaluate the effectiveness, and cost-effectiveness, of (combinations of) intervention approaches to induce sustained long-term increases in cycling participation in terms of increases in numbers of people cycling regularly and number of cycling journeys undertaken, across a range of population demographic groups; establish the effects of such interventions on relevant outcomes related to health and wellbeing, economic productivity and wider societal impacts; and provide more robust quantification of potential harms of increasing cycling participation, such as collision risks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The nature of the Cycle Nation Project meant that the funders, British Cycling and HSBC UK, were intimately involved as representatives in this review. All analysis was performed by the authors without input from British Cycling or HSBC UK., (© 2023 Logan, Somers, Baker, Connell, Gray, Kelly, McIntosh, Welsh, Gray and Gill.)

Alzheimer's disease CSF biomarkers 42 amino acid long amyloid-β peptide (Aβ1-42), total tau protein (T-tau), and tau protein phosphorylated at threonine 181 (P-tau181) are considered surrogate biomarkers of Alzheimer's disease pathology, and significantly improve diagnostic accuracy. Their ability to reflect neuropathological changes later in the disease course is not well characterized. This study aimed to assess the potential of CSF biomarkers measured in mid to late stage Alzheimer's disease to reflect post-mortem neuropathological changes. Individuals were selected from two autopsy cohorts of Alzheimer's disease patients in Antwerp and Amsterdam. Neuropathological diagnosis was performed according to the updated consensus National Institute on Aging-Alzheimer's Association guidelines, which includes quantification of amyloid-β plaque, neurofibrillary tangle, and neuritic plaque load. CSF samples were analysed for Aβ1-42, T-tau, and P-tau181 by ELISA. One hundred and fourteen cases of pure definite Alzheimer's disease were included in the study (mean age 74 years, disease duration 6 years at CSF sampling, 50% females). Median interval between CSF sampling and death was 1 year. We found no association between Aβ1-42 and Alzheimer's disease neuropathological change profile. In contrast, an association of P-tau181 and T-tau with Alzheimer's disease neuropathological change profile was observed. P-tau181 was associated with all three individual Montine scores, and the associations became stronger and more significant as the interval between lumbar puncture and death increased. T-tau was also associated with all three Montine scores, but in individuals with longer intervals from lumbar puncture to death only. Stratification of the cohort according to APOE ε4 carrier status revealed that the associations applied mostly to APOE ε4 non-carriers. Our data suggest that similar to what has been reported for Aβ1-42, plateau levels of P-tau181 and T-tau are reached during the disease course, albeit at later disease stages, reducing the potential of tau biomarkers to monitor Alzheimer's disease pathology as the disease progresses. As a consequence, CSF biomarkers, which are performant for clinical diagnosis of early Alzheimer's disease, may not be well suited for staging or monitoring Alzheimer's disease pathology as it progresses through later stages., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Cycle Nation Project (CNP) aimed to develop, test the feasibility of and optimize a multi-component individual-/social-level workplace-based intervention to increase cycling among office staff at a multinational bank (HSBC UK). To do this, we first explored barriers to cycling in a nationally-representative survey of UK adults, then undertook focus groups with bank employees to understand any context-specific barriers and ways in which these might be overcome. These activities led to identification of 10 individual-level, two social-level, and five organizational-level modifiable factors, which were mapped to candidate intervention components previously identified in a scoping review of cycling initiatives. Interviews with HSBC UK managers then explored the practicality of implementing the candidate intervention components in bank offices. The resultant pilot CNP intervention included 32 core components across six intervention functions (education, persuasion, incentivisation, training, environmental restructuring, enablement). Participants received a loan bike for 12-weeks (or their own bike serviced), and a 9-week cycle training course (condensed to 6 weeks for those already confident in basic cycling skills), including interactive information sharing activities, behavior change techniques (e.g., weekly goal setting), bike maintenance training, practical off-road cycling skill games and on-road group rides. Sessions were delivered by trained bank staff members who were experienced cyclists. The CNP pilot intervention was delivered across three sites with 68 participants. It was completed in two sites (the third site was stopped due to COVID-19) and was feasible and acceptable to both women and men and across different ethnicities. In addition, the CNP intervention was successful (at least in the short term) in increasing cycling by 3 rides/week on average, and improving perceptions of safety, vitality, confidence, and motivation to cycle. Following minor modifications, the long-term effectiveness and cost-effectiveness of the CNP intervention should be tested in a full-scale randomized controlled trial., Competing Interests: The nature of the co-design of the Cycle Nation Project intervention meant that the funders, British Cycling and HSBC UK, were intimately involved in the design and delivery of the intervention, and representatives from both organizations are authors on the paper. All data analysis was performed by researchers at the University of Glasgow without input from British Cycling or HSBC UK. Authors SB and JP were employed by British Cycling, and authors SR and LH are employees of HSBC UK. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Connell, Logan, Somers, Baker, Broadfield, Bunn, Harper, Kelly, McIntosh, Pell, Puttnam, Robson, Gill and Gray.)

Background. Responding to rising oncology therapy costs, multiple value frameworks are emerging. However, input from economists in their design and conceptualization has been limited, and no existing framework has been developed using preference weightings as legitimate indicators of value. This article outlines use of the nominal group technique to identify valued treatment attributes (such as treatment inconvenience) and contextual considerations (such as current life expectancy) to inform the design of a discrete choice experiment to develop a preference weighted value framework for future decision makers. Methods. Three focus groups were conducted in 2017 with cancer patients, oncology physicians, and nurses. Using the nominal group technique, participants identified and prioritized cancer therapy treatment and delivery attributes as well as contextual issues considered when choosing treatment options. Results. Focus groups with patients ( n = 8), physicians ( n = 6), and nurses ( n = 10) identified 30 treatment attributes and contextual considerations. Therapy health gains was the first priority across all groups. Treatment burden/inconvenience to patients and their families and quality of evidence were prioritized treatment attributes alongside preferences for resource use and cost (to patients and society) attributes. The groups also demonstrated that contextual considerations when choosing treatment varied across the stakeholders. Patients prioritized existence of alternative treatments and oncologist/center reputation while nurses focused on administration harms, communication, and treatment innovation. The physicians did not prioritize any contextual issues in their top rankings. Conclusions. The study demonstrates that beyond health gains, there are treatment attributes and contextual considerations that are highly prioritized across stakeholder groups. These represent important candidates for inclusion in a discrete choice experiment seeking to provide weighted preferences for a value framework for oncology treatment that goes beyond health outcomes., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The following authors are employed by the sponsor: Prof Briggs, Dr Susan Chimonas, Anna Kaltenboeck, and Dr Peter Bach.

Background: Changing population demographics and technology developments have resulted in growing interest in the potential of consumer-facing digital health. In the United Kingdom, a £37 million (US $49 million) national digital health program delivering assisted living lifestyles at scale (dallas) aimed to deploy such technologies at scale. However, little is known about how consumers value such digital health opportunities., Objective: This study explored consumers' perspectives on the potential value of digital health technologies, particularly mobile health (mHealth), to promote well-being by examining their willingness-to-pay (WTP) for such health solutions., Methods: A contingent valuation study involving a UK-wide survey that asked participants to report open-ended absolute and marginal WTP or willingness-to-accept for the gain or loss of a hypothetical mHealth app, Healthy Connections., Results: A UK-representative cohort (n=1697) and a dallas-like (representative of dallas intervention communities) cohort (n=305) were surveyed. Positive absolute and marginal WTP valuations of the app were identified across both cohorts (absolute WTP: UK-representative cohort £196 or US $258 and dallas-like cohort £162 or US $214; marginal WTP: UK-representative cohort £160 or US $211 and dallas-like cohort £151 or US $199). Among both cohorts, there was a high prevalence of zeros for both the absolute WTP (UK-representative cohort: 467/1697, 27.52% and dallas-like cohort: 95/305, 31.15%) and marginal WTP (UK-representative cohort: 487/1697, 28.70% and dallas-like cohort: 99/305, 32.5%). In both cohorts, better general health, previous amount spent on health apps (UK-representative cohort 0.64, 95% CI 0.27 to 1.01; dallas-like cohort: 1.27, 95% CI 0.32 to 2.23), and age had a significant (P>.00) association with WTP (UK-representative cohort: -0.1, 95% CI -0.02 to -0.01; dallas-like cohort: -0.02, 95% CI -0.03 to -0.01), with younger participants willing to pay more for the app. In the UK-representative cohort, as expected, higher WTP was positively associated with income up to £30,000 or US $39,642 (0.21, 95% CI 0.14 to 0.4) and increased spending on existing phone and internet services (0.52, 95% CI 0.30 to 0.74). The amount spent on existing health apps was shown to be a positive indicator of WTP across cohorts, although the effect was marginal (UK-representative cohort 0.01, 95% CI 0.01 to 0.01; dallas-like cohort 0.01, 95% CI 0.01 to 0.02)., Conclusions: This study demonstrates that consumers value mHealth solutions that promote well-being, social connectivity, and health care control, but it is not universally embraced. For mHealth to achieve its potential, apps need to be tailored to user accessibility and health needs, and more understanding of what hinders frequent users of digital technologies and those with long-term conditions is required. This novel application of WTP in a digital health context demonstrates an economic argument for investing in upskilling the population to promote access and expedite uptake and utilization of such digital health and well-being apps., (©Camilla Somers, Eleanor Grieve, Marilyn Lennon, Matt-Mouley Bouamrane, Frances S Mair, Emma McIntosh. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 17.01.2019.)

Disease-modifying treatment trials are increasingly advanced to the prodromal or preclinical phase of Alzheimer's disease (AD), and inclusion criteria are based on biomarkers rather than clinical symptoms. Therefore, it is of great interest to determine which biomarkers should be combined to accurately predict conversion from mild cognitive impairment (MCI) to AD dementia. However, up to date, only few studies performed a complete A/T/N subject characterization using each of the CSF and imaging markers, or they only investigated long-term (≥ 2 years) prognosis. This study aimed to investigate the association between cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), amyloid- and 18 F-FDG positron emission tomography (PET) measures at baseline, in relation to cognitive changes and conversion to AD dementia over a short-term (12-month) period. We included 13 healthy controls, 49 MCI and 16 AD dementia patients with a clinical-based diagnosis and a complete A/T/N characterization at baseline. Global cortical amyloid-β (Aβ) burden was quantified using the 18 F-AV45 standardized uptake value ratio (SUVR) with two different reference regions (cerebellar grey and subcortical white matter), whereas metabolism was assessed based on 18 F-FDG SUVR. CSF measures included Aβ 1-42 , Aβ 1-40 , T-tau, P-tau 181 , and their ratios, and MRI markers included hippocampal volumes (HV), white matter hyperintensities, and cortical grey matter volumes. Cognitive functioning was measured by MMSE and RBANS index scores. All statistical analyses were corrected for age, sex, education, and APOE ε4 genotype. As a result, faster cognitive decline was most strongly associated with hypometabolism (posterior cingulate) and smaller hippocampal volume (e.g., Δstory recall: β = +0.43 [p < 0.001] and + 0.37 [p = 0.005], resp.) at baseline. In addition, faster cognitive decline was significantly associated with higher baseline Aβ burden only if SUVR was referenced to the subcortical white matter (e.g., Δstory recall: β = -0.28 [p = 0.020]). Patients with MCI converted to AD dementia at an annual rate of 31%, which could be best predicted by combining neuropsychological testing (visuospatial construction skills) with either MRI-based HV or 18 F-FDG-PET. Combining all three markers resulted in 96% specificity and 92% sensitivity. Neither amyloid-PET nor CSF biomarkers could discriminate short-term converters from non-converters., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Beginning in the elementary school years, there are differences among children on how they perceive their competence in physical activity (PA). Children's competence perceptions may influence their affective reactions to PA. A crucial question is how to motivate children who hold low competence perceptions to enhance their enjoyment and PA involvement. Because parents play critical roles in children's development and socialization, social support from parents can be an important factor to complement teachers' effort to enhance children's enjoyment and PA involvement. In this research we identified the associations among children's beliefs about parental social support, perceived competence, and enjoyment in school PA., Methods: Three hundred and twenty children (9-11 years old) participated in a two-wave study. At the first wave, children completed questionnaires measuring their beliefs about parental social support, perceived competence, and enjoyment in school PA; they reported their enjoyment again 8 months later at the second wave., Results: Both concurrent and longitudinal analyses revealed that beliefs about parental social support were important factors associated with children's enjoyment in school PA, especially among girls with low competence perceptions., Conclusion: Family socialization factors should be taken into consideration. The efficacy of individual and community-level strategies should be included and evaluated when designing effective intervention strategies that enhance children's PA in school.

Increased brain uptake of 18 F-AV45 visualized by PET is a key biomarker for Alzheimer disease (AD). The SUV ratio (SUVR) is widely used for quantification, but is subject to variability based on choice of reference region and changes in cerebral blood flow. Here we validate the SUVR method against the gold standard volume of distribution (V T ) to assess cross-sectional differences in plaque load. Methods: Dynamic 60-min 18 F-AV45 (291 ± 67 MBq) and 1-min 15 O-H 2 O (370 MBq) scans were obtained in 35 age-matched elderly subjects, including 10 probable AD, 15 amnestic mild cognitive impairment (aMCI), and 10 cognitively healthy controls (HCs). 18 F-AV45 V T was determined from 2-tissue-compartment modeling using a metabolite-corrected plasma input function. Static SUVR was calculated at 50-60 min after injection, using either cerebellar gray matter (SUVR CB ) or whole subcortical white matter (SUVR WM ) as the reference. Additionally, whole cerebellum, pons, centrum semiovale, and a composite region were examined as alternative references. Blood flow was quantified by 15 O-H 2 O SUV. Data are presented as mean ± SEM. Results: There was rapid metabolization of 18 F-AV45, with only 35% of unchanged parent remaining at 10 min. Compared with V T , differences in cortical Aβ load between aMCI and AD were overestimated by SUVR WM (+4% ± 2%) and underestimated by SUVR CB (-10% ± 2%). V T correlated better with SUVR WM (Pearson r: from 0.63 for posterior cingulate to 0.89 for precuneus, P < 0.0001) than with SUVR CB (Pearson r: from 0.51 for temporal lobe [ P = 0.002] to 0.82 for precuneus [ P < 0.0001]) in all tested regions. Correlation results for the alternative references were in between those for CB and WM. 15 O-H 2 O data showed that blood flow was decreased in AD compared with aMCI in cortical regions (-5% ± 1%) and in the reference regions (CB, -9% ± 8%; WM, -8% ± 8%). Conclusion: Increased brain uptake of 18 F-AV45 assessed by the simplified static SUVR protocol does not truly reflect Aβ load. However, SUVR WM is better correlated with V T and more closely reflects V T differences between aMCI and AD than SUVR CB ., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ 1-42 , t-tau, and p-tau 181 overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-tau rel ), may improve differential dementia diagnosis. The goal of this study is to investigate if p-tau rel can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis., Methods: The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls. A substantial subset of the patients was pathology-confirmed. CSF levels of Aβ 1-42 , t-tau, p-tau 181 , and p-tau rel were determined with commercially available single-analyte enzyme-linked immunosorbent assay (ELISA) kits. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analyses, and area under the curve (AUC) values were compared using DeLong tests., Results: The diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. The addition of p-tau rel to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-tau rel increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-tau rel when differentiating between AD or non-AD dementias and controls., Conclusions: The addition of p-tau rel to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias.

Although the core cerebrospinal fluid Alzheimer's disease (AD) biomarkers amyloid-β (Aβ 1-42 ) and tau show a high diagnostic accuracy, there are still limitations due to overlap in the biomarker levels with other neurodegenerative and dementia disorders. During Aβ 1-42 production and clearance in the brain, several other Aβ peptides and amyloid precursor protein fragments are formed that could potentially serve as biomarkers for this ongoing disease process. Therefore, this review will present the current status of the findings for amyloid precursor protein and Aβ peptide isoforms in AD and clinically related disorders. In conclusion, adding new Aβ isoforms to the AD biomarker panel may improve early differential diagnostic accuracy and increase the cerebrospinal fluid biomarker concordance with AD neuropathological findings in the brain.

Pasture-based livestock systems are often associated with losses of reactive forms of nitrogen (N) to the environment. Research has focused on losses to air and water due to the health, economic and environmental impacts of reactive N. Di-nitrogen (N2) emissions are still poorly characterized, both in terms of the processes involved and their magnitude, due to financial and methodological constraints. Relatively few studies have focused on quantifying N2 losses in vivo and fewer still have examined the relative contribution of the different N2 emission processes, particularly in grazed pastures. We used a combination of a high (15)N isotopic enrichment of applied N with a high precision of determination of (15)N isotopic enrichment by isotope-ratio mass spectrometry to measure N2 emissions in the field. We report that 55.8 g N m(-2) (95%, CI 38 to 77 g m(-2)) was emitted as N2 by the process of co-denitrification in pastoral soils over 123 days following urine deposition (100 g N m(-2)), compared to only 1.1 g N m(-2) (0.4 to 2.8 g m(-2)) from denitrification. This study provides strong evidence for co-denitrification as a major N2 production pathway, which has significant implications for understanding the N budgets of pastoral ecosystems.

Background: Non-volitional sex (NVS) in young people continues to be a major public health problem with long-term negative health outcomes. For the first time, the prevalence of different types of NVS and associated factors are compared between young people with same-sex sexual activities and those who have not., Methods: We obtained data from 10,401 young women and men (aged 12 to 25 years) who participated in a population study on sexual health, the Netherlands. We calculated and compared the prevalence of six types of NVS between women who had sex with men (yWSM) or women (yWSW), and men who had sex with women (yMSW) or men (yMSM). In sexually experienced participants (n = 5986) logistic regression analyses were applied to assess associations with NVS by assault or penetration. Analyses were weighted to represent the Dutch population., Results: The prevalence of NVS ranged from 1% to 61%, depending on type. Prevalence was higher for young women (any: 40.6%) than men (any: 20.4%), and highest for yMSM and yWSW. Prevalence of NVS by assault or penetration was related to a range of socio-demographic, behavioral and social factors, which were largely similar regardless of sex or same-sex-experiences. The NVS perpetrators were in over 70% of cases known to the victim; 1 in 4 cases of NVS by penetration were accompanied by violence., Conclusion: A substantial proportion of young people in the Netherlands have experienced NVS. Medical professionals, educators and caregivers should integrate services to continue to address NVS by targeting young people's multifaceted risk profiles and evidenced based interventions for doing so are needed.

The effectiveness of chemical amendment of pig slurry to ameliorate phosphorus (P) losses in runoff is well studied, but research mainly has concentrated only on the runoff pathway. The aims of this study were to investigate changes to leachate nutrient losses, soil properties and greenhouse gas (GHG) emissions due to the chemical amendment of pig slurry spread at 19 kg total phosphorus (TP), 90 kg total nitrogen (TN), and 180 kg total carbon (TC) ha(-1). The amendments examined were: (1) commercial grade liquid alum (8% Al2O3) applied at a rate of 0.88:1 [Al:TP], (2) commercial-grade liquid ferric chloride (38% FeCl3) applied at a rate of 0.89:1 [Fe:TP] and (3) commercial-grade liquid poly-aluminium chloride (PAC) (10% Al2O3) applied at a rate of 0.72:1 [Al:TP]. Columns filled with sieved soil were incubated for 8 mo at 10 °C and were leached with 160 mL (19 mm) distilled water wk(-1). All amendments reduced the Morgan's phosphorus and water extractable P content of the soil to that of the soil-only treatment, indicating that they have the ability to reduce P loss in leachate following slurry application. There were no significant differences between treatments for nitrogen (N) or carbon (C) in leachate or soil, indicating no deleterious impact on reactive N emissions or soil C cycling. Chemical amendment posed no significant change to GHG emissions from pig slurry, and in the cases of alum and PAC, reduced cumulative N2O and CO2 losses. Chemical amendment of land applied pig slurry can reduce P in runoff without any negative impact on nutrient leaching and GHG emissions. Future work must be conducted to ascertain if more significant reductions in GHG emissions are possible with chemical amendments., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Hospital HIV care and public sexual health care (a Sexual Health Care Centre) services were integrated to provide sexual health counselling and sexually transmitted infections (STIs) testing and treatment (sexual health care) to larger numbers of HIV patients. Services, need and usage were assessed using a patient perspective, which is a key factor for the success of service integration., Methods: The study design was a one-group pre-test and post-test comparison of 447 HIV-infected heterosexual individuals and men who have sex with men (MSM) attending a hospital-based HIV centre serving the southern region of the Netherlands. The intervention offered comprehensive sexual health care using an integrated care approach. The main outcomes were intervention uptake, patients' pre-test care needs (n=254), and quality rating., Results: Pre intervention, 43% of the patients wanted to discuss sexual health (51% MSM; 30% heterosexuals). Of these patients, 12% to 35% reported regular coverage, and up to 25% never discussed sexual health topics at their HIV care visits. Of the patients, 24% used our intervention. Usage was higher among patients who previously expressed a need to discuss sexual health. Most patients who used the integrated services were new users of public health services. STIs were detected in 13% of MSM and in none of the heterosexuals. The quality of care was rated good., Conclusions: The HIV patients in our study generally considered sexual health important, but the regular counselling and testing at the HIV care visit was insufficient. The integration of public health and hospital services benefited both care sectors and their patients by addressing sexual health questions, detecting STIs, and conducting partner notification. Successful sexual health care uptake requires increased awareness among patients about their care options as well as a cultural shift among care providers.

Infection by RNA viruses is detected by the host through Toll-like receptors or RIG-I-like receptors. Toll-like receptors and RIG-I-like receptors signal through the adaptors MyD88 and MAVS, respectively, to induce type I IFNs (IFN-I) and other antiviral molecules, which are thought to be essential for activating the adaptive immune system. We investigated the role of these adaptors in innate and adaptive immune responses against respiratory syncytial virus (RSV), a common human pathogen. Deletion of Mavs abolished the induction of IFN-I and other proinflammatory cytokines by RSV. Genome-wide expression profiling in the lung showed that the vast majority of RSV-induced genes depended on MAVS. Although Myd88 deficiency did not affect most RSV-induced genes, mice lacking both adaptors harbored a higher and more prolonged viral load and exhibited more severe pulmonary disease than those lacking either adaptor alone. Surprisingly, Myd88(-/-)Mavs(-/-) mice were able to activate a subset of pulmonary dendritic cells that traffic to the draining lymph node in response to RSV. These mice subsequently mounted a normal cytotoxic T-lymphocyte response and demonstrated delayed but effective viral clearance. These results provide an example of a normal and effective adaptive immune response in the absence of innate immunity mediated by MAVS and MyD88.

To define the prevalence and correlates of grief-related symptoms among long-term care staff who care for patients near the end of life, a cross-sectional survey was conducted at six Program of All-inclusive Care for the Elderly (PACE) organizations that provide long-term care in the home and in institutions. All clinical and non-clinical program staff were surveyed to examine the prevalence of 20 grief-related symptoms and assess current sources of bereavement support, as well as willingness to use additional sources of support. Surveys were completed by 203/236 staff (86%), who described a wide variety of symptoms they attributed to the death of one of their patients in the past month. Most staff (147/203; 72%) reported at least one symptom. Staff with more symptoms had experienced more patient deaths in the past month (Spearman rho = 0.20, P = 0.007), had worked for a longer time at a PACE organization (Spearman rho = 0.16, P = 0.031), and reported a closer and longer relationship with the last patient who died (Spearman rho = 0.32, P < 0.001; rho = 0.24, P = 0.001). Although staff identified several informal sources of bereavement support (mean 2.3 sources, range 0-6), almost all (n = 194; 96%) said they would use additional support services if they were offered. These community-based long-term care staff experience a variety of symptoms attributable to the deaths of their patients, and would welcome additional sources of bereavement support.

In an effort to reduce teen pregnancy, schools are purchasing a program called "Baby Think It Over," a computerized infant simulator intended to provide a realistic infant care experience. However, little empirical, especially experimental, program effectiveness data exist. This study determined if the program changed participants' attitudes toward parenting, as well as sexual and contraceptive behaviors linked to avoidance of teen pregnancy. Development of measurement tools was a part of the purpose. The study also asked teen-agers, through narrative questions, about their conscious perceptions of the baby's utility and impact. Participants included experimental (n = 151) and control (n = 62) groups of primarily White, middle class, suburban high school' students (mean age = 16.2). The quasi-experimental portion of the study failed to reveal a statistically significant effect. Narrative data revealed several positive and notable program effects.

Fibroblasts have cell surface sites that mediate the assembly of fibronectin (Fn) into the extracellular matrix. Treatment of fibroblasts with kinase inhibitors (ML-7, H7, HA1004, calphostin C, and staurosporine) resulted in the rapid decrease in the binding of 125I-labeled plasma Fn and iodinated amino-terminal fragments of Fn. The dose responses of the four inhibitors suggest that the target kinase is protein kinase C (PKC) rather than the cyclic AMP- or cyclic GMP-dependent kinases. Three different fibroblastic cells were similarly affected. The inhibition was rapid and reversible and could not be overcome by increasing concentrations of Fn. Treatment of fibroblasts with phorbol esters and other agents that activate PKC resulted in increased amounts of 125I-labeled Fn binding to the cell surface. These results imply that Fn matrix assembly is modulated by PKC-mediated phosphorylation.

Ovoperoxidase, the enzyme that hardens the sea urchin fertilization envelope, is inserted into the assembling extracellular matrix through the action of an intermediary protein, proteoliaisin (PLN). The domain structure of PLN, a large, rod-shaped protein that binds to ovoperoxidase and the vitelline layer, was examined by limited proteolytic cleavage. Purified proteolytic fragments of PLN were tested for their ability to bind ovoperoxidase, inhibit the binding of 125I-PLN to the vitelline layer, or act as substrates for the hardening reaction. Based on these results, the vitelline layer-binding domain can be placed near the amino terminus, followed by the binding site for ovoperoxidase; the distal two-thirds of the protein contain sites for ovoperoxidase-catalyzed dityrosine formation. The pentapeptide GRGDS (but not RGD) inhibited PLN-vitelline layer binding half-maximally at 0.2 mM. Moreover, PLN promoted adhesion of bovine aortic endothelial cells to plastic dishes, a process inhibited by GRGDS. Thus PLN is a new member of the adhesive protein family, the function of which is to coordinate the morphogenesis of a specific, rapidly assembled extracellular matrix.