Synthesis of a Select Group of Proteins by Neisseria Gonorrhoeae in Response to Thermal Stress

We report the thermal conditions that induce the heat shock response in Neisseria gonorrhoeae. Under conditions of thermal stress, Neisseria gonorrhoeae synthesizes heat shock proteins (hsps), which differ quantitatively from conventionally studied gonococcal proteins. Gonococci accelerate the rate of synthesis of the hsps as early as 5 min after the appropriate stimulus is applied, with synthesis continuing for 30 min, as demonstrated by in vivo labeling experiments with L-[35S]methionine. Two of the gonococcal hsps are immunologically cross-reactive with the hsps of Escherichia coli, DnaK and GroEL, as demonstrated by Western blot (immunoblot) analysis. Ten hsps can be identified on two-dimensional autoradiograms of whole gonococci (total protein). Four hsps can be identified on two-dimensional autoradiograms of 1% N-lauroylsarcosine (sodium salt) (Sarkosyl)-insoluble membrane fractions. Two of the hsps from the 1% Sarkosyl-insoluble fraction are found exclusively in this fraction, suggesting that they are membrane proteins. The identification of this group of proteins will facilitate further study of the function of these proteins and provide insight into the possible role of hsps in disease pathogenesis

Chronic Recurrent Multifocal Osteomyelitis (CRMO):advancing the diagnosis

BackgroundChronic recurrent multifocal osteomyelitis (CRMO) is a little known inflammatory bone disease occurring primarily in children and adolescents. Delays in referral and diagnosis may lead to prolonged courses of antibiotics with in-patient care, unnecessary radiation exposure from multiple plain radiographs or bone scans and repeated surgery including bone biopsies.Children (aged < 18 years) diagnosed with CRMO between January 2005 and December 2012, reviewed at Bristol Royal Hospital for Children were included and all available data collected. Information regarding CRMO was sent to all orthopaedic surgeons in the region in 2009.The aim of the study was to examine the features of the cohort, to examine the length of time to diagnosis and to explore the criteria used for diagnosis with and without biopsy.FindingsOver an 8 year period, 41 patients were diagnosed with CRMO. Symptom onset occurred at a median of 9 years of age and time to diagnosis had a median of 15 months (range 0 - 92). Correlation coefficient analysis for time to diagnosis by year showed statistical significance with a decreasing trend. From the cohort data, diagnostic criteria were developed; applied retrospectively, 34 (83%) children may have been diagnosed using the criteria, without a biopsy.ConclusionsThe data suggest that increasing knowledge of this condition may shorten time to diagnosis. Use of the Bristol diagnostic criteria by an experienced clinician may obviate the need for biopsy in some patients

COMPLEMENT FACTOR B IS A DETERMINANT OF BOTH METABOLIC AND CARDIOVASCULAR FEATURES OF METABOLIC SYNDROME

CFB (complement factor B) is elevated in adipose tissue and serum from patients with type 2 diabetes mellitus and cardiovascular disease, but the causal relationship to disease pathogenesis is unclear. Cfb is also elevated in adipose tissue and serum of the spontaneously hypertensive rat, a well-characterized model of metabolic syndrome. To establish the role of CFB in metabolic syndrome, we knocked out the Cfb gene in the spontaneously hypertensive rat. Cfb−/− rats showed improved glucose tolerance and insulin sensitivity, redistribution of visceral to subcutaneous fat, increased adipocyte mitochondrial respiration, and marked changes in gene expression. Cfb−/− rats also had lower blood pressure, increased ejection fraction and fractional shortening, and reduced left ventricular mass. These changes in metabolism and gene expression, in adipose tissue and left ventricle, suggest new adipose tissue-intrinsic and blood pressure-independent mechanisms for insulin resistance and cardiac hypertrophy in the spontaneously hypertensive rat. In silico analysis of the human CFB locus revealed 2 cis-regulated expression quantitative trait loci for CFB expression significantly associated with visceral fat, circulating triglycerides and hypertension in genome-wide association studies. Together, these data demonstrate a key role for CFB in the development of spontaneously hypertensive rat metabolic syndrome phenotypes and of related traits in humans and indicate the potential for CFB as a novel target for treatment of cardiometabolic disease

The jigsaw puzzle of chronic non-bacterial osteomyelitis:are anti-IL7 therapies the next piece?

[No abstract

How acceptable is adolescent self-consent for the HPV vaccination: Findings from a qualitative study in south-west England

BackgroundHuman Papillomavirus (HPV) vaccination programmes have the potential to reduce the incidence of cervical cancer. The preferred age for HPV vaccination is 12–13 years for optimal benefit. The legal framework in England allows adolescents to be vaccinated without parental consent if they are assessed as competent. A ‘South West Template Pathway on Self Consent for School Aged Immunisations’ was developed to improve uptake of immunisations in south-west England.Study aimTo examine how acceptable the new procedures are to the young women, parents and carers, school staff and immunisation nurses involved.MethodsThe research was undertaken in two local authorities in south-west England during the 2017/18 and 2018/19 programme years. Semi-structured digitally recorded interviews were undertaken with 53 participants: one health service manager, three immunisation nurses, five staff at alternative education providers, three staff at mainstream schools, 19 young women and 22 parents. All recordings were transcribed verbatim and thematic analysis was undertaken, assisted by NVivo software.ResultsMost participants were not fully aware of the legal framework that enables a young person to self-consent to vaccination. There was a strong presumption that parents should make decisions affecting the health of their children. The preferred age at which the HPV vaccination is administered (12–13 years) contributed to reluctance in endorsing self-consent which was thought to have the potential to break down trust between parents and school staff, and within families. In practice, formal self-consent was rare.ConclusionUnresolved issues in relation to adolescent self-consent include public and professional perceptions of young people’s rights and abilities to take responsibility for decisions affecting their health, and concerns about the impact of self-consent on relationships both within families and between professionals and the families they serve

Implementing new consent procedures for the schools-based HPV vaccination programme:a qualitative study

Background. The English schools-based human papillomavirus (HPV) programme was offered to young women aged 12-13 years. High coverage was achieved, but variations in uptake across local authorities were apparent. The requirement for written parental consent acted as a barrier to some young women with the potential to exacerbate health inequities.Objectives. To consider the practicalities and implications of implementing new consent procedures for the schools-based HPV vaccination programme.Design. Qualitative study.Settings. Two local authority areas in the south-west of England with relatively lower uptake of the HPV vaccination programme.Participants. The 53 participants included: the immunisation programme manager, three immunisation nurses, three members of staff in mainstream schools, five members of staff in alternative education provider settings, 19 young women, and 22 parents.Methods. Digitally recorded, semi-structured interviews were undertaken. All transcripts were fully transcribed and anonymised. Thematic analysis was undertaken, assisted by the Framework approach to data management.Results. The new consent processes for the HPV vaccination generally worked well. Telephoning parents on the day of the vaccination session was viewed as an acceptable and effective way to reach parents. Adolescent self-consent was rarely undertaken. This can be explained partially by the relative success in gaining parental verbal consent but concerns about disrupting relationships - between healthcare professionals, parents and school staff, or within families – made professionals reluctant to administer the vaccine without some form of parental consent. For young women with special educational needs and disabilities the consent process relied upon close communication between school staff and parents. Other young women whose access to the vaccine, or consent options, were unclear or problematic included: those who were registered with a school but attended an alternative setting for part of their timetable; those educated at home; those in the care of the local authority or living with a foster family, and; young people with gender dysphoria.Conclusions. Expanding the consent procedures for the schools-based HPV vaccination programme to include parental telephone consent was broadly welcomed by the immunisation nurses, parents, and young women in our study. The requirement for young women to confirm that they had discussed vaccination with their parents, and that vaccination would not cause difficulties at home, meant adolescent self-consent was rare in this age-group. Greater understanding of the barriers to uptake outside of the mainstream school-based sessions is needed to further address inequalities in uptake

Secondary analyses to test the impact on inequalities and uptake of the schools-based human papillomavirus (HPV) vaccination programme by stage of implementation of a new consent policy in the south-west of England

Objectives To test the impact on inequalities and uptake of the schools-based human papillomavirus (HPV) vaccination programme by stage of implementation of a new policy providing additional opportunities to consent.Setting Two local authorities in the south-west of England.Participants Young women (n=7129) routinely eligible for HPV vaccination aged 12–13 years during the intervention period (2017/2018 to 2018/2019 programme years).Interventions Local policy change that included additional opportunities to provide consent (parental verbal consent and adolescent self-consent).Outcomes Secondary analyses of cross-sectional intervention data were undertaken to examine uptake by: (1) receipt of parental written consent forms and; (2) percentage of unvaccinated young women by stage of implementation.Results During the intervention period, 6341 (89.0%) eligible young women initiated the HPV vaccination series. Parental written consent forms were less likely to be returned where young women attended alternative education provider settings (p<0.001), belonged to non-white British ethnic groups (p<0.01) or more deprived quintiles (p<0.001). Implementation of parental verbal consent and adolescent self-consent reduced the percentage of unvaccinated young women from 21.3% to 16.5% (risk difference: 4.8%). The effect was greater for young women belonging to the most deprived compared with the least deprived quintile (risk difference: 7.4% vs 2.3%, p<0.001), and for young women classified as Unknown ethnic category compared with white British young women (6.7% vs 4.2%, p<0.001). No difference was found for non-white British young women (5.4%, p<0.21).Conclusions Local policy change to consent procedures that allowed parents to consent verbally and adolescents to self-consent overcame some of the barriers to vaccination of young women belonging to families less likely to respond to paper-based methods of gaining consent and at greater risk of developing cervical cancer.Trial registration number 49 086 105

Impact of new consent procedures on uptake of the schools-based Human Papillomavirus (HPV) vaccination programme

BACKGROUND: Local policy change initiating new consent procedures was introduced during 2017–2018 for the human papillomavirus (HPV) vaccination programme year in two local authorities in the south–west of England. This study aims to assess impact on uptake and inequalities. METHODS: Publicly available aggregate and individual-level routine data were retrieved for the programme years 2015–2016 to 2018–2019. Statistical analyses were undertaken to show: (i) change in uptake in intervention local authorities in comparison to matched local authorities and (ii) change in uptake overall, and by local authority, school type, ethnicity and deprivation. RESULTS: Aggregate data showed uptake in Local Authority One increased from 76.3% to 82.5% in the post-intervention period (risk difference: 6.2% P = 0.17), with a difference-in-differences effect of 11.5% (P = 0.03). There was no evidence for a difference-in-differences effect in Local Authority Two (P = 0.76). Individual-level data showed overall uptake increased post-intervention (risk difference: +1.1%, P = 0.05), and for young women attending school in Local Authority One (risk difference: 2.3%, P < 0.01). No strong evidence for change by school category, ethnic group and deprivation was found. CONCLUSION: Implementation of new consent procedures can improve and overcome trends for decreasing uptake among matched local authorities. However, no evidence for reduction in inequalities was found. IMPLICATIONS AND DISCUSSION: The new consent procedures increased uptake in one of the intervention sites and appeared to overcome trends for decreasing uptake in matched sites. There are issues in relation to the quality of data which require addressing

Influence of commissioned provider type and deprivation score on uptake of the childhood flu immunization

BACKGROUND: Since 2015/16 the UK seasonal influenza immunization programme has included children aged 5 and 6 years. In the South West of England school-based providers, GPs or community pharmacies were commissioned to deliver the vaccine depending on the locality. We aimed to assess variation in vaccine uptake in relation to the type of commissioned provider, and levels of socioeconomic deprivation.METHODS: Data from the South West of England (2015-16 season) were analysed using multilevel logistic regression to assess variation in vaccine uptake by type of commissioned provider, allowing for clustering of children within delivery sites.RESULTS: Overall uptake in 5 and 6 year olds was 34.3% (37 555/109 404). Vaccine uptake was highest when commissioned through school-based programmes 50.2% (9983/19 867) and lowest when commissioned through pharmacies, 23.1% (4269/18 479). Delivery through schools resulted in less variation by site and equal uptake across age groups, in contrast to GP and pharmacy delivery for which uptake was lower among 6 year olds. Vaccine uptake decreased with increasing levels of deprivation across all types of commissioned provider.CONCLUSION: School-based programmes achieve the highest and most consistent rates of childhood influenza vaccination. Interventions are still needed to promote more equitable uptake of the childhood influenza vaccine.</p

Efficacy of pamidronate in children with chronic non-bacterial osteitis using whole body MRI as a marker of disease activity

Background: To study the response to pamidronate using whole body magnetic resonance imaging (WB-MRI) in children with chronic non-bacterial osteitis (CNO) in a tertiary health centre. Methods: The medical records of children under the age of sixteen with a diagnosis of chronic non-bacterial osteitis between 2005 and 2018 were reviewed. All those who were treated with pamidronate were included and relevant data was collected. Response to therapy was determined based on the status of lesions on WB- MRI. Results: Forty six patients were included in the study. Pre- and post-treatment WB-MRI was available in forty patients. Cumulative lesions pre-treatment were 150 and reduced to 45 (30%) post-treatment. Seventeen patients (42.5%) had a good response with complete resolution of all lesions and nine patients (22.5%) worsened during or following treatment with pamidronate. Vertebral disease had a good response and 82.3% of the lesions resolved completely. Conclusion: Our study describes the experience with pamidronate in a tertiary health centre using WB-MRI as a marker of disease activity. Pamidronate was well tolerated in our cohort and treatment response was fairly good. Significance and innovation: 1. Bisphosphonates can be used in the treatment of CNO when response to NSAIDs is suboptimal. 2. In the presence of spinal or mandibular lesions bisphosphonates were used as first line. 3. Treatment was escalated to a TNF blocker when response to bisphosphonates was suboptimal.</p