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Background Influenza remains a major threat to public health. Live-attenuated influenza vaccines (LAIV) have been shown to be effective, particularly in children. Follicular T helper (TFH) cells provide B-cell help and are crucial for generating long-term humoral immunity. However the role of TFH cells in LAIV-induced immune responses is unknown. Methods We collected tonsils, plasma, and saliva samples from children and adults receiving LAIV prior to tonsillectomy. We measured influenza-specific TFH-cell responses after LAIV by flow cytometry and immunohistochemistry. Systemic and local antibody responses were analysed by hemagglutination inhibition assay and enzyme-linked immunosorbent assay. Results We report that LAIV induced early (3–7 days post-vaccination) activation of tonsillar follicles and influenza-specific TFH-cell (CXCR5+CD57+CD4+ T cell) responses in children, and to a lesser extent in adults. Serological analyses showed that LAIV elicited rapid (day 14) and long-term (up to 1 year post-vaccination) antibody responses (hemagglutination inhibition, influenza-specific IgG) in children, but not adults. There was an inverse correlation between pre-existing influenza-specific salivary IgA concentrations and tonsillar TFH-cell responses, and a positive correlation between tonsillar TFH-cell and systemic IgG induction after LAIV. Conclusions Our data, taken together, demonstrate an important role of tonsillar TFH cells in LAIV-induced immunity in humans., Live attenuated influenza vaccine induces rapid influenza-specific tonsillar TFH-cell and antibody responses in children, but is less potent in adults. The magnitude of influenza-specific TFH-cell responses inversely correlated with pre-existing salivary IgA, and directly associated with post-vaccination antibody fold-induction.

Influenza vaccination often results in a large percentage of low responders, especially in high-risk groups. As a first line of defense, natural killer (NK) cells play a crucial role in the fight against infections. However, their implication with regard to vaccine responsiveness is insufficiently assessed. Therefore, this study aimed at the validation of essential NK cell features potentially associated with differential vaccine responsiveness with a special focus on NKG2C- and/or CD57-expressing NK cells considered to harbor memory-like functions. To this end, 16 healthy volunteers were vaccinated with an adjuvanted pandemic influenza vaccine. Vaccine responders and low responders were classified according to their hemagglutination inhibition antibody titers. A majority of responders displayed enhanced frequencies of NKG2C-expressing NK cells 7- or 14-days post-vaccination as compared to low responders, whereas the expression of CD57 was not differentially modulated. The NK cell cytotoxic potential was found to be confined to CD56dimCD16+ NKG2C-expressing NK cells in the responders but not in the low responders, which was further confirmed by stochastic neighbor embedding analysis. The presented study is the first of its kind that ascribes CD56dimCD16+ NKG2C-expressing NK cells a crucial role in biasing adaptive immune responses upon influenza vaccination and suggests NKG2C as a potential biomarker in predicting pandemic influenza vaccine responsiveness.

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Introduction: The peri-orbital contusion (PC) is a common injury in day to day surgical casualties. It is a common injury observed in patients who are in an unconscious state following head injuries. The aim of the study is to describe characteristics of PC and understand its relationship with associated injuries, especially with facial injuries and intracranial injuries. Methods: This retrospective study reviewed the medico-legal examination forms (MLEF) of 67 inward patients in Teaching Hospital, Karapitiya and District General Hospital, Matara with peri-orbital contusions following trauma during a period of six months from January 2020 to June 2020. Results: A total number of 67 patients were included with 81% being male patients. The commonest soft tissue injuries around the PCs were abrasions (n=39, 71%) and 25 (38%) of the study sample had fractures of the skull. The majority (n=22, 88%) of them had fractures of facial bones followed by vault and basal skull fractures. The majority of PCs (45%) were blue in colour and only 8% were red. The red colour was observed only in PCs of less than 24 hours. The main cause for PC was due to direct blow to the eye while the rest (n=29, 45%) were due to the indirect blow. A higher incidence of fracture of the head was observed in assaults (39%). Conclusions: The commonest cause for the black eye in the study sample was the direct blow with a blunt force in an assault. The red colour was observed in PC of less than 24 hours duration. The PC had not caused major injuries to the eye but there was frequent involvement of facial bone fractures.

Summary: Outer membrane vesicles (OMV) were first described approximately 50 years ago, and for many years were considered to be an artefact of bacterial growth. Since that initial discovery, it has become evident that OMVs are produced by almost all Gram-negative bacteria as part of their normal growth in addition to driving pathogenesis within the host. More recently, the identification of membrane vesicle (MV) production by some Gram-positive bacteria, parasites, fungi, mycobacteria and infected host cells has significantly broadened the field of MV production and emphasised their importance to pathogenesis. In this review we will focus on discussing recent advances in the field of bacterial membrane vesicle biogenesis and the mechanisms whereby they modulate immunity and contribute to pathogenesis. We will highlight findings identifying the contribution of extracellular vesicles produced by Gram-positive bacteria, fungi, parasites and infected host cells in mediating pathogenesis in addition to the functions of MVs produced by commensal bacteria. Finally, we discuss recent progress in the development of bacterial MVs as novel vaccines capable of mediating cellular and humoral immune responses.

Background We analyzed the impact of the anti-T-cell agents basiliximab and antithymocyte globulins (ATG) on antibody and cell-mediated immune responses after influenza vaccination in solid-organ transplant recipients. Methods 71 kidney and heart transplant recipients (basiliximab [ n = 43] and ATG [ n = 28]) received the trivalent influenza vaccine. Antibody responses were measured at baseline and 6 weeks post-vaccination by hemagglutination inhibition assay; T-cell responses were measured by IFN-γ ELISpot assays and intracellular cytokine staining (ICS); and influenza-specific memory B-cell (MBC) responses were evaluated using ELISpot. Results Median time of vaccination from transplantation was 29 months (IQR 8–73). Post-vaccination seroconversion rates were 26.8% for H1N1, 34.1% for H3N2 and 4.9% for influenza B in the basiliximab group and 35.7% for H1N1, 42.9% for H3N2 and 14.3% for influenza B in the ATG group ( p = 0.44, p = 0.61, and p = 0.21, respectively). The number of influenza-specific IFN-γ-producing cells increased significantly after vaccination (from 35 to 67.5 SFC/10 6 PBMC, p = 0.0007), but no differences between treatment groups were observed ( p = 0.88). Median number of IgG-MBC did not increase after vaccination (H1N1, p = 0.94; H3N2 p = 0.34; B, p = 0.79), irrespective of the type of anti-T-cell therapy. Conclusions After influenza vaccination, a significant increase in antibody and T-cell immune responses but not in MBC responses was observed in transplant recipients. Immune responses were not significantly different between groups that received basiliximab or ATG.

Child abuse is a complex problem. It is sensitive in nature and requires a comprehensive police investigation. Police officers are at the forefront of this issue and hence it is important that they have optimal skills when investigating cases of suspected child abuse. This article evaluates the effectiveness of a short-term, 6-hour, child protection training provided to 39 Sri Lankan police officers (37 female). The effectiveness of the program was assessed using a scale at pre- and post-program. The results indicated that the training significantly increased participants’ knowledge on aspects of child abuse. However, the program did not significantly affect their attitudes about child abuse or their perceived skill in managing cases of abuse. Qualitative feedback from the participants and their superior officers, obtained during a group discussion, indicated that the training had been effective and the learning outcomes had been achieved. This article makes recommendations for improving the child protection services in middle-income countries such as Sri Lanka, in terms of multiphasic and comprehensive training for police officers.

Healthcare workers (HCW) were prioritized for vaccination during the 2009 influenza A(H1N1)pdm09 pandemic. We conducted a clinical trial in October 2009 where 237 HCWs were immunized with a AS03-adjuvanted A(H1N1)pdm09 monovalent vaccine. In the current study, we analyzed the homologous and cross-reactive H1N1 humoral responses using prototype vaccine strains dating back to 1977 by the haemagglutinin inhibition (HI), single radial hemolysis SRH), antibody secreting cell (ASC) and memory B cell (MBC) assays. The cellular responses were assessed by interferon-γ (IFN-γ) ELISPOT and by intracellular staining (ICS) for the Th1 cytokines IFN-γ, interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α). All assays were performed using blood samples obtained prior to (day 0) and 7, 14 and 21 d post-pandemic vaccination, except for ASC (day 7) and ICS (days 0 and 21). Vaccination elicited rapid HI, SRH and ASC responses against A(H1N1)pdm09 which cross reacted with seasonal H1N1 strains. MBC responses were detected against the homologous and seasonal H1N1 strains before vaccination and were boosted 2 weeks post-vaccination. An increase in cellular responses as determined by IFN-γ ELISPOT and ICS were observed 1–3 weeks after vaccination. Collectively, our data show that the AS03-adjuvanted A(H1N1)pdm09 vaccine induced rapid cellular and humoral responses against the vaccine strain and the response cross-reacted against prototype H1N1 strains dating back to 1977. publishedVersion

Early Violence Prevention (EVP) programs are a concept alien to policy makers of the Early Childhood Care and Education in Sri Lanka, even though Sri Lanka as a has country experienced violence for almost fourt decades. This study explores the perceived preschool teacher practices pertaining to EVP (preventing/minimizing aggressive behaviors and promoting prosocial behaviors) within Sri Lankan preschool teachers using a survey (n = 275) and a semi structured interviews (n = 23). The results conveyed that Sri Lankan preschool teacher recognize such practices as a necessity and seemed to be practicing a wide spectrum of behaviors. These could be categorized on several dimensions: telling/teaching vs. doing activities, individual focused vs. group/social, authoritative/instructive vs. democratic, child initiated good practices vs. bad practices. Practices could also be categorized into religious activities, activities with emphasis on silence, praise, techniques to prevent discrimination, techniques to divert attention, socially focused, direct conflict management, instructional emphasis, empowering the children, moral and teacher initiated action. These activities were carried out using stories, puppets and role-plays. The study also provides recommendations to policy developers in the context of culture sensitive early violence prevention practices for Sri Lankan preschool children.

In this paper we present the work in progress of WireMe IoT development platform, a simple way to deploy IoT systems in an intuitive approach. WireMe platforms' simplified software and hardware modules enables users to deploy personalized web interface and program their hardware modules to achieve their home automation tasks without having deep technical knowledge in either of the above domains, with the help of visual programming. Apart from that, advanced users may extend this approach with the framework provided so that they can build their hardware and software modules to support our WireMe IoT platform as well. With this platform, kids can learn to build programming logics and learn about programming with code generation as well as people can build their typical IoT automation systems to monitor and control their IoT modules.

Adolescence is a time of change and transition, specifically in the context of interpersonal relationships with significant adults in their lives. Adolescence is also a period in which vastly reflects growing psychological and emotional independence from adults and proximity and dependence to peers. Therefore, adolescents often must negotiate and establish relationships with adults under less than optimal conditions. Thus, nature and quality of relationship interactions between teachers and adolescents are fundamental to understanding adolescent psychosocial wellbeing. A particular concern lies with the adolescents who do not enjoy positive, supportive relationships with their teachers. Such adolescents are often at risk for academic and psychosocial problems. The present study explores Sri Lankan adolescents’ perceived relationship interactions with their teachers and its impact on their psychosocial wellbeing, using in depth interviews. The findings provide specific components pertaining to strong positive relationships such as empathy, warmth, sense of comfort, guidance, provision of financial assistance when in need and confidentiality. However, adolescents also mentioned teachers as figures detrimental to their wellbeing.

The present study explored the Sri Lankan pre/school teachers’ (n = 365) knowledge, and perceived skills of child protection against their general attitudes pertaining to violence/ abuse as well as their specific attitudes pertaining corporal punishment using a four point rating scale. Results conveyed that while teachers’ knowledge and perceived skills of child protection was high, teacher who favored corporal punishment as an acceptable mode of disciplinary strategy had higher knowledge (M = 32.1, S.D = 3.02) than those who did not (M = 31.29; S.D = 2.97), t(363) = 2.634, p = .009. Based on its findings, the study offers recommendation for teacher trainers and child protection practitioners.

This study explores the Sri Lankan students’ perceptions of their school counselors and counseling services available to them. It comprises of two phases involving data collected through in-depth interviews (n = 10) and semi-structured interviews using a survey questionnaire (n = 126). The data were collected during two measurement points.Findings convey that the students did not provide positive evaluations of school counseling services during both phases, depicting the reluctance to access it due to several key factors. They are: social stigma associated with accessing counseling services, location of the counseling room, misperceptions pertaining to its aims and objectives, ignorance, and lack of time. The study provides suggestions and recommendations for policy makers, teacher educators and school counselors with the broad aim of improving the quality of the school counseling services in Sri Lanka.

Annually, influenza virus infection has a large socioeconomic burden on society, with 500 000 fatal cases globally [1–3]. The World Health Organization estimates that 20% of children are infected with influenza virus each year, and they are the main source of spread of the virus and have a high burden of the disease [4]. Vaccination is the cornerstone of prophylaxis and is recommended for high-risk patients. The trivalent inactivated influenza vaccine (TIV) is safe and provides protection but may not be the optimal vaccine for young children, owing to their lack of previous infection. Since 2003, the cold-adapted live attenuated influenza vaccine (LAIV), administered as a nasal spray, has been approved in the United States for individuals aged 2–49 years. The vaccine was licensed in Europe in 2012 (for individuals aged 2–17 years) and was implemented in the British childhood vaccination campaign, beginning in 2013 [5]. In June 2014, the Advisory Committee on Immunization Practices preferentially recommended LAIV in healthy children 2–8 years old when it is immediately available [6]. Despite many years on the market, there are no established correlates of protection for LAIV. Efficacy studies and observational data suggest that the LAIV provides higher levels of protection than TIV in children [7–11]. The hemagglutination inhibition (HI) titer is widely used as a surrogate correlate of protection after TIV receipt; however, the cutoff titer of 1:40 is based on adult trials. There is debate on both the protective HI level in children and the fact that an HI titer underestimates the protection obtained by LAIV [12–14]. Cellular immunity may be a better measure of protective immunity after LAIV in children [15]. CD4+ T cells have the ability to act as effector cells and to direct and generate specific memory CD4+ and CD8+ T-cell subsets with diverse functions [16–18]. Animal and human studies have demonstrated protective cellular immunity after LAIV [10, 19–21]. Therefore, the duration and quality of the immune response in humans after LAIV needs to be studied. We conducted a pediatric clinical trial to elucidate the immunological mechanisms induced by LAIV, with emphasis on the long-term, strain-specific cellular immune responses. Our study is unique, as we obtained sequential blood samples from young children up to 1 year after vaccination, allowing us to compare and analyze serum and cellular responses in the same child. Our results indicate that LAIV induces long-term humoral and cellular immune responses in children and that priming is important in determining the magnitude of the response.

Conceptions of mental illness are often decided by the socio-cultural background and other socio-demographic factors. The aim of the present study was to assess the perceived knowledge, attitudes and perceived behaviors pertaining to mental illness within the Sri Lankan public. In order to achieve this aim, 167 participants (Females = 97; Males = 70) from 17districts in Sri Lanka were given a survey questionnaire to assess their knowledge, attitudes and perceived practices towards PwMI. The results conveyed that in general participants had high to moderate knowledge, were open minded, displayed pro-integrated attitudes and high to moderate sensitivity towards PwMI. Results also conveyed that there is a positive relationship among knowledge, attitudes, and perceived behaviors towards PwMI.

Guillain-Barre syndrome (GBS) is the commonest cause of acute flaccid paralysis in Sri Lanka. Annual incidence of GBS in Sri Lanka is not known. The aim of this study was to find out the incidence of GBS in administrative district of Galle, Sri Lanka based on hospital records. Method: We conducted a retrospective analytical study to find out the incidence and epidemiological patterns of GBS in patients admitted to Teaching Hospital Galle (THG). We scrutinized the case notes of all the patients categorized G 61.0 of 10th Edition of International Classification of Diseases Classification, from 1995 through 2000. The cases fulfilling NINCDS criteria for GBS were included in the study. We excluded the patients referred from other districts for calculation of the incidence of GBS in Galle. Official population statistics and the regional rainfall recorded in the meteorological department were used for analysis. Results: There were 114 patients fulfilling the inclusion criteria over the study period. Seventysix patients were from Galle District and 54% were males. The age distribution showed a bimodal pattern with peak incidence in 10-19 age group and a smaller peak in 30-39 age group. Number of cases from Galle District reported in years 1995 to 2000 was 8, 16, 15, 18, 8 and 11 respectively. This is equivalent to a crude incidence of 0.8, 1.6, 1.5, 1.8, 0.8 and 1.1 per /100,000 population for each year respectively considering the mean population of 1.04 million. Mean crude incidence for the study period was 1.26 per 100000. Seasonal variation with clustering following high rainfall was seen in years 1996, 1997 and 1998. Identified preceding illnesses recorded in the notes were upper respiratory tract infection in 22.7%, diarrhoea in 14%, varicella in 8% and non-specific viral infection in 14%. Conclusion: The mean incidence of GBS in Galle District is 1.26 per 100,000 population with a range of 0.8 to 1.8 over the study period. The age distribution and seasonal variation are different from those reported from many other countries. The clinical features and preceding illness were similar to those described in other series.

We report a young female with multifocal motor neuropathy (MMN) who had unusually rapid progression involving both distal and proximal weakness, which responded dramatically to treatment, without any relapses up to now.

Very few studies have explored young children’s aggressive behaviors in collective cultures or in South Asian contexts. The present study reconnoitres in depth; the nature, types, prevalence and antecedents of aggressive behaviors displayed by Sri Lankan preschool children. The study was carried out in two phases using a mixed method; 1. Preschool teacher interviews (N = 23) with teachers from 14 varied preschool contexts in Sri Lanka, and 2. Observations of aggressive behaviors of 16 preschool children displaying prominent overt, and relational aggression from four varied preschool communities selected from a group of 135 children. Findings of this study make important contributions to aggressive behaviors within Sri Lankan preschool children and discuss them in the back drop of global research findings. Findings also provide new information regarding the manner in which aggression was expressed by the observed group of preschool children, labeled as ‘playful aggressive parodies’ by the author.

Academic achievement or (academic) performance is the outcome of education — the extent to which a student, teacher or institution has achieved their educational goals. Academic achievement generally refers to how well a student is accomplishing his or her tasks and studies. The most well-known indicator of academic achievement is the student’s ‘score’ for their classes and overall tenure. Many variables affect the academic achievement of the student i.e. Meta cognition, executive function, intelligence etc. The present study will investigate the relation between Meta cognition, executive function, intelligence and academic achievement. For this purpose a sample of 100 students (6th to 8th) was selected and data was collected.

Outer membrane vesicles were first described approximately 50 years ago and for many years were considered to be an artifact of bacterial growth. Since that initial discovery, it has become evident that outer membrane vesicles are produced by almost all Gram-negative bacteria as part of their normal growth in addition to driving pathogenesis within the host. More recently, the identification of membrane vesicle (MV) production by some Gram-positive bacteria, parasites, fungi, mycobacteria and infected host cells has significantly broadened the field of MV research and emphasized their importance to pathogenesis. In this review, we will focus on discussing recent advances in the field of bacterial MV biogenesis and the mechanisms whereby they modulate immunity and contribute to pathogenesis. We will highlight findings identifying the contribution of extracellular vesicles produced by Gram-positive bacteria, fungi, parasites, and infected host cells in mediating pathogenesis in addition to the functions of MVs produced by commensal bacteria. Finally, we will discuss recent progress in the development of bacterial MVs as novel vaccines capable of mediating cellular and humoral immune responses.

The aim of the present study is to explore Sri Lankan adolescents’ relationships with their parents, siblings and peers. To investigate this aspect a semi-structured interview schedule was used to interview 10 adolescents (6 girls and 4 boys aged at 15 to 18 years) from varied socioeconomic backgrounds, belonging to varied communities (sports clubs, plantation sector, urban, rural) . The results conveyed that parents, siblings and peers had an impact on the psychosocial wellbeing of the studied adolescents. However, positive relationships with parents, siblings and peers did not seem to be the only influence on adolescent wellbeing. Adolescents in the study who reported abusive and neglecting experiences from parents also reported well-being and attributed it to multitude of other factors.

Please cite this paper as: Svindland et al. (2012) A study of Chitosan and c-di-GMP as mucosal adjuvants for intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses 10.1111/irv.12056000(000), 000–000. Background Highly pathogenic avian influenza A/H5N1 virus remains a potential pandemic threat, and it is essential to continue vaccine development against this subtype. A local mucosal immune response in the upper respiratory tract may stop influenza transmission. It is therefore important to develop effective intranasal pandemic influenza vaccines that induce mucosal immunity at the site of viral entry. Objectives We evaluated the humoral and cellular immune responses of two promising mucosal adjuvants (Chitosan and c-di-GMP) for intranasal influenza H5N1 vaccine in a murine model. Furthermore, we evaluated the concept of co-adjuvanting an experimental adjuvant (c-di-GMP) with chitosan. Methods BALB/c mice were intranasally immunised with two doses of subunit NIBRG-14 (H5N1) vaccine (7·5, 1·5 or 0·3 μg haemagglutinin (HA) adjuvanted with chitosan (CSN), c-di-GMP or both adjuvants. Results All adjuvant formulations improved the serum and local antibody responses, with the highest responses observed in the 7·5 μg HA CSN and c-di-GMP-adjuvanted groups. The c-di-GMP provided dose sparing with protective single radial haemolysis (SRH), and haemagglutination inhibition (HI) antibody responses found in the 0·3 μg HA group. CSN elicited a Th2 response, whereas c-di-GMP induced higher frequencies of virus-specific CD4+ T cells producing one or more Th1 cytokines (IFN-γ+, IL-2+, TNF-α+). A combination of the two adjuvants demonstrated effectiveness at 7·5 μg HA and triggered a more balanced Th cytokine profile. Conclusion These data show that combining adjuvants can modulate the Th response and in combination with ongoing studies of adjuvanted intranasal vaccines will dictate the way forward for optimal mucosal influenza vaccines.

Background. We conducted a clinical trial in October 2009 to evaluate the immunogenicity of the AS03adjuvanted influenza vaccine (pH1N1 vaccine) in health care workers (HCWs) (www.clinicaltrials.gov, NCT01003288). By 2 weeks after vaccination, 97% had protective hemagglutinin inhibition (HI) titers (≥40) however, 16% were low responders (LR) and failed to maintain a protective response 90 days after vaccination. Methods. We analyzed the humoral responses (HI, antibody-secreting cell [ASC], and serum immunoglobulin G [IgG]) in 15 LRs and 25 control HCWs. Twelve LRs were revaccinated with the pH1N1 vaccine, and 7 were subsequently vaccinated with the 2010 seasonal trivalent influenza vaccine. We conducted a long-term analysis of the humoral and CD4 + T-helper (Th) 1 responses. Results. The LRs had a slower HI antibody response than the control HCWs, with protective antibody titers not reached until 2 weeks after vaccination in the majority of the participants. The LRs also had significantly lower IgG ASCs at day 7 and HA1-specific serum IgG responses at day 21, compared with the control HCWs. Revaccination with the pH1N1 vaccine elicited rapid HI antibody, ASC, memory B cell, and multifunctional CD4 + Th1 cell responses. Conclusion. This study shows that revaccination of low-responding HCWs with the pH1N1 vaccine is required for maintaining long-term protection.

Background. Vaccination is the best measure to protect the population against a potential influenza H5N1 pandemic, but 2 doses of vaccine are needed to elicit protective immune responses. An immunological marker for H5N1 vaccine effectiveness is needed for early identification of the best vaccine candidate. Methods. We conducted a phase I clinical trial of a virosomal H5N1 vaccine adjuvanted with Matrix M. Sixty adult volunteers were vaccinated intramuscularly with 2 doses of either 30 μg hemagglutinin (HA) alone or with 1.5, 7.5, or 30 μg HA and Matrix M adjuvant (50 μg). The humoral response was measured by the hemagglutination inhibition (HI), microneutralization (MN), and single radial hemolysis (SRH) assays, and the CD4 + T-helper 1 (Th1)–cell response was measured by intracellular staining for the cytokines interleukin 2, interferon γ, and tumor necrosis factor α. Results. The adjuvanted vaccine effectively induced CD4 + Th1-cell responses, and the frequency of influenzaspecific Th1 cells after the first vaccine dose predicted subsequent HI, MN, and SRH seroprotective responses after the second vaccination. Conclusions. These results support early identification of Th1-cell responses as a predictive biomarker for an efficient vaccine response, which could have great implications for early identification of persons with low or no response to vaccine when evaluating future pandemic influenza vaccines. Clinical Trials Registration. NCT00868218.

Background Despite the chronicity of psoriasis, most systematic reviews focus on short-term treatment. Methods The systematic search strategy and results from the German Psoriasis Guidelines were adapted. To update the data a literature search in Medline, Embase and the Cochrane Library was conducted. The proportion of participants achieving ≥75% decrease in Psoriasis Area and Severity Index (PASI) as well as Dermatology Life Quality Index (DLQI) reduction at different time points were assessed. Trials were summarized with respect to time periods and study designs. Suitable trials were included in a meta-analysis. Particular attention was paid to statistical approaches of handling dropouts. Results A total of 33 articles including 27 trials totaling 6575 patients with active treatment were included in the systematic review. Seven randomized controlled trials were eligible for the meta-analysis. Over a 24 week treatment period infliximab [risk difference (RD) 78%, 95% confidence interval (CI) 72–83%] and ustekinumab 90 mg every 12 weeks (RD 77%, 95% CI 71–83%) were the most efficacious treatments. Adalimumab (RD: 60%, 95% CI 45–74%) showed results within the range of different etanercept dosages (etanercept 50 mg once weekly: RD 62%, 95% CI, 52–72%), (etanercept 25 mg twice weekly: RD 45%, 95% CI 34–56%), (etanercept 50 mg twice weekly: RD 56%, 95% CI 49–62%) and (etanercept 50 mg twice weekly until week 12, then 25 mg twice weekly: RD 50%, 95% CI 42–57%). After 24 weeks a decrease in efficacy for inflximab, adalimumab and etanercept was observed. Conclusions More sufficient data is required to draw reliable conclusions in extended long-term treatment and head-to-head comparisons are necessary.

Forearm median motor conduction velocity (FMCV) is reduced in carpal tunnel syndrome (CTS). The aim of this study was to investigate the association of FMCV with age and severity of median nerve compression. Forearm median motor conduction velocity and median nerve motor distal latencies were measured in 312 CTS hands. Forearm median motor conduction velocity correlated negatively with age. This correlation persisted in the subgroups of hands with severe and less severe CTS. Forearm median motor conduction velocity correlated negatively with the degree of compression (as measured by median nerve motor distal latencies). This correlation persisted in subgroup of hands with severe CTS but not in less severe ones. Multiple regression analysis comparing the influence of age and median nerve motor distal latencies on FMCV showed higher standardized coefficients (beta) value for age than for median nerve motor distal latencies, suggesting a greater influence for age. The beta value for age is higher in severe group than in less severe group, suggesting that age has higher influence on FMCV in severe group. The degree of compression influences FMCV in hands with severe CTS but not in hands with less severe CTS. This difference in severe and less severe CTS may be because of the differences in the underlying pathophysiological processes in the 2 entities.

Please cite this paper as: Svindland et al. The mucosal and systemic immune responses elicited by a chitosan-adjuvanted intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses DOI:10.1111/j.1750-2659.2011.00271.x. Background Development of influenza vaccines that induce mucosal immunity has been highlighted by the World Health Organisation as a priority (Vaccine 2005;23:1529). Dose-sparing strategies and an efficient mass-vaccination regime will be paramount to reduce the morbidity and mortality of a future H5N1 pandemic. Objectives This study has investigated the immune response and the dose-sparing potential of a chitosan-adjuvanted intranasal H5N1 (RG-14) subunit (SU) vaccine in a mouse model. Methods Groups of mice were intranasally immunised once or twice with a chitosan (5 mg/ml)-adjuvanted SU vaccine [7·5, 15 or 30 μg haemagglutinin (HA)] or with a non-adjuvanted SU vaccine (30 μg HA). For comparison, another group of mice were intranasally immunised with a whole H5N1 (RG-14) virus (WV) vaccine (15 μg HA), and the control group consisted of unimmunised mice. Results The chitosan-adjuvanted SU vaccine induced an immune response superior to that of the non-adjuvanted SU vaccine. Compared with the non-adjuvanted SU group, the chitosan-adjuvanted SU vaccine elicited higher numbers of influenza-specific antibody-secreting cells (ASCs), higher concentrations of local and systemic antibodies and correspondingly an improved haemagglutination inhibition (HI) and single radial haemolysis (SRH) response against both the homologous vaccine strain and drifted H5 strains. We measured a mixed T-helper 1/T-helper 2 cytokine response in the chitosan-adjuvanted SU groups, and these groups had an increased percentage of virus-specific CD4+ T cells producing two Thelper 1 (Th1) cytokines simultaneously compared with the non-adjuvanted SU group. Overall, the WV vaccine induced higher antibody concentrations in sera and an HI and SRH response similar to that of the chitosan-adjuvanted SU vaccine. Furthermore, the WV vaccine formulation showed a stronger bias towards a T-helper 1 profile than the SU vaccine and elicited the highest frequencies of CD4+ Th1 cells simultaneously secreting three different cytokines (INFγ+, IL2+ and INFα+). As expected, two immunisations gave a better immune response than one in all groups. The control group had very low or not detectable results in the performed immunoassays. Conclusion The cross-clade serum reactivity, improved B- and T-cell responses and dose-sparing potential of chitosan show that a chitosan-adjuvanted intranasal influenza vaccine is a promising candidate vaccine for further preclinical development.

BACKGROUND This pilot study compared a monophasic hyaluronic acid dermal filler with a biphasic filler for the correction of nasolabial folds. METHODS Participant- and assessor-blinded, randomized clinical trial involving participants with moderate to severe nasolabial folds. Split-face design comparing a monophase hyaluronic acid (HA) filler (mono-HA) with a biphasic HA filler (bi-HA). Injection with touch-up after 1 month. Wrinkle improvement was measured before and after injection and after 1, 2, 4, and 7 months, using the Wrinkle Severity Rating Scale and the Global Aesthetic Improvement Scale as outcome criteria. An optional treatment was offered at the end of the study, with participants allowed to choose one of the products. OBJECTIVE Evaluation of efficacy and safety of both products. RESULTS Both products showed immediate, good results after injection and touch-up and demonstrated good durability over time. Participant preference for optional treatment at the end of the study favoured mono-HA. Both products were well tolerated, without serious adverse events. CONCLUSION The effect after injection of mono-HA and bi-HA is generally comparable, although there was a trend in favor of mono-HA. Materials and funding for this study were provided by Teoxane, Geneva, Switzerland.

Background The development of evidence based guidelines is a demanding and time consuming process. Therefore it is important to share the knowledge and discuss the structure of these guidelines in detail. Objectives To present a method report on the development process of the European evidence based guidelines on the systemic treatment of psoriasis vulgaris with the aim to offer guidance to other guidelines groups with lesser experience and to critically appraise the methodology of the guidelines development process. Methods The guidelines are based on the previously evaluated literature from three European national evidence based guidelines and an additional systematic search and evaluation of new literature. Further steps included a structured consensus conference and a DELPHI procedure to develop the recommendations, as well as several internal and external reviews. All steps were coordinated by the Division of evidence based medicine in cooperation with a group of methodologists. Results A total of 114 studies were included, serving as base for the efficacy chapters of the intervention. The recommendations, based on the efficacy and the level of evidence of the included studies were discussed and finally consented by the guidelines group. After subsequent reviews the guidelines were presented to the European Dermatology Forum, European Academy of Dermatology and Venereology and Union Europeenne des Medicins Specialistes for approval and published in October 2009. Conclusion The development of European evidence based guidelines requires a coordinated structure which can be achieved by the integration of an experienced group of methodologists. Nevertheless further improvements are imaginable and might be considered for an update or other European evidence based guidelines.

Persistent infection with HPV 16 and 18 has been causally associated with the development of cervical cancer and its precursor lesions as well as with other carcinomas and their precursors, e.g. some vulvar and vaginal cancers. Furthermore HPV 6 and 11 are responsible for anogenital condylomata acuminata in more than 90% of cases. With the recently developed prophylactic bivalent (HPV 16 and 18) and quadrivalent (HPV 6, 11, 16 and 18) vaccines, it is possible to prevent infection of the cervical epithelium and other squamous epithelia, the development of premalignant lesions and, in the case of the quadrivalent vaccine, the development of condylomata acuminata. The following paper represents a summary of the full-text version of the German evidence-based Guidelines, including all evidence-based recommendations regarding the safety as well as the efficacy of the vaccines in preventing CIN, VIN/VaIN, genital warts and other HPV-associated lesions.

Porphyromonas gingivalis strains W50 and ATCC 33277 were shown to bind to cultured human fibroblast (MRC-5) cells using flow cytometry. As the concentration of P. gingivalis strain W50 cells was increased relative to the concentration of MRC-5 cells, the number of W50 cells bound per MRC-5 cell increased, as did the percentage of MRC-5 cells with bacteria bound. However, this relationship was only seen for P. gingivalis strain ATCC 33277 at low cell concentrations: at high bacterial cell concentrations strain ATCC 33277 auto-aggregated and binding to the MRC-5 cells decreased. Strain W50 was therefore chosen to study the role of the surface proteinase-adhesin complexes (RgpA-Kgp complexes) in binding to MRC-5 cells. P. gingivalis W50 cells treated with an inhibitor of the RgpA-Kgp complexes exhibited reduced binding to MRC-5 cells. The purified active and proteinase-inactive RgpA-Kgp complexes competitively inhibited binding of W50 to MRC-5 cells, and isogenic mutants of W50 lacking RgpA/B and Kgp displayed reduced binding. P. gingivalis W50 mutant cells lacking Kgp exhibited the lowest binding to MRC-5 cells, suggesting an important role for this proteinase and its associated adhesins in binding to fibroblasts.

Rationale Evidence-based guidelines can make a substantial contribution to improving medical care. However, it is important to ensure that guidelines are: (1) developed in areas in which they are needed the most; and (2) translated effectively into everyday clinical practice. Objectives To evaluate the need for guidelines in the treatment of psoriasis vulgaris, the success of the dissemination activities undertaken to date, and the potential benefits of educational interventions in encouraging guideline compliance. Methods All dermatologists working in the Berlin-Brandenburg region of Germany were invited to attend a workshop on the psoriasis treatment guidelines. Participants could take part in a survey examining the general need for psoriasis guidelines and the success of previous dissemination activities. Results A total of 42% of survey participants had not received a copy of the guidelines prior to the workshop. Of those who had received a copy, only 15% had studied the guidelines in detail. In total, 76% of survey participants felt that physicians' low levels of confidence in administering systemic treatments had resulted in these treatment options being used less frequently than they should. Seventy-nine per cent of survey participants believed that the guidelines would be helpful in improving physicians' confidence and ultimately lead to an increased use of systemic treatments. Conclusion The results of the present study indicate that there is a great need for guidelines on the treatment of psoriasis vulgaris in Germany, especially in light of dermatologists' low levels of confidence administering systemic treatments. Strategies for broad dissemination are essential for proper guideline implementation.

By using fluorescence microscopy, fluorescently labeled Porphyromonas gingivalis W50 was shown to adhere to oral epithelial (KB) cells as discrete cells or small cell aggregates, whereas P. gingivalis ATCC 33277 bound as large cell aggregates. Flow cytometric analysis showed that for P. gingivalis W50 there was a logarithmic relationship between the bacterial cell ratio (BCR), that is the number of bacterial cells to KB cells, and the percentage of KB cells with W50 cells attached. This percentage of KB cells with W50 attached reached a plateau of ∼84% cells at a BCR of 500:1. In contrast, a quadratic relationship was observed between BCR and the percentage of KB cells with P. gingivalis ATCC 33277 attached, reaching a maximum of 47% at a BCR of 100:1 but decreasing to 7% at a BCR of 1,000:1. The lower binding of ATCC 33277 at high cell concentrations was attributed to autoaggregation. P. gingivalis W50 cells treated with an inhibitor ( N α- p -tosyl- l -lysine chloromethyl ketone [TLCK]) of its RgpA-Kgp proteinase-adhesin complex exhibited significantly reduced binding to KB cells than to untreated cells, suggesting a role for proteinase activity in binding to KB cells. Competitive inhibition with purified proteinase-active and TLCK-inactivated RgpA-Kgp complex significantly decreased the adherence of P. gingivalis W50 cells to KB cells. Furthermore, isogenic mutants of P. gingivalis W50 lacking the kgp gene product, but not the rgpA or rgpB gene products, exhibited significantly decreased adherence to KB cells compared to the wild type.

The contributions of three proteinase genes ( rgpA , rgpB , and kgp ) to the virulence of Porphyromonas gingivalis W50 were investigated in the murine periodontitis model. Mice were orally inoculated with eight doses (1 × 10 10 cells per dose) of rgpA , rgpB , kgp , rgpA rgpB , or rgpA rgpB kgp isogenic mutants, and the level of alveolar bone loss, immune response induced, and number of bacterial cells per half maxilla were compared with those of animals inoculated with wild-type P. gingivalis . The kgp , rgpB , rgpA rgpB , and rgpA rgpB kgp isogenic mutants induced significantly ( P < 0.05) less bone loss than the rgpA isogenic mutant and the wild type did, and the virulence of the rgpA isogenic mutant and the wild type were not significantly different. Mice inoculated with the wild type or the rgpA isogenic mutant exhibited significantly ( P < 0.01) more P. gingivalis cells per half maxilla than mice inoculated with rgpB , kgp , rgpA rgpB , and rgpA rgpB kgp isogenic mutants or nonchallenged mice did, as determined using real-time PCR. A significant positive correlation was found between the number of P. gingivalis cells detected per half maxilla and the amount of alveolar bone loss induced. Enzyme-linked immunosorbent assay results showed that each isogenic mutant and the wild type induced a predominant P. gingivalis antigen-specific immunoglobulin G3 (IgG3) response. Furthermore, the kgp and rgpA rgpB kgp isogenic mutants induced significantly ( P < 0.05) lower IgG3 antibody responses than the responses induced by the wild type or the rgpA , rgpB , and rgpA rgpB isogenic mutants. The results suggest that the order in which the proteinases contribute to the virulence of P. gingivalis in the murine periodontitis model is Kgp ≥ RgpB ≫ RgpA.

Highly pathogenic avian influenza H5N1 infection remains a public health threat and vaccination is the best measure of limiting the impact of a potential pandemic. Mucosal vaccines have the advantage of eliciting immune responses at the site of viral entry, thereby preventing infection as well as further viral transmission. In this study, we assessed the protective efficacy of hemagglutinin (HA) from the A/Indonesia/05/05 (H5N1) strain of influenza virus that was produced by transient expression in plants. The plant-derived vaccine, in combination with the mucosal adjuvant (3′,5′)-cyclic dimeric guanylic acid (c-di-GMP) was used for intranasal immunization of mice and ferrets, before challenge with a lethal dose of the A/Indonesia/05/05 (H5N1) virus. Mice vaccinated with 15 μg or 5 μg of adjuvanted HA survived the viral challenge, while all control mice died within 10 d of challenge. Vaccinated animals elicited serum hemagglutination inhibition, IgG and IgA antibody titers. In the ferret challenge study, all animals vaccinated with the adjuvanted plant vaccine survived the lethal viral challenge, while 50% of the control animals died. In both the mouse and ferret models, the vaccinated animals were better protected from weight loss and body temperature changes associated with H5N1 infection compared with the non-vaccinated controls. Furthermore, the systemic spread of the virus was lower in the vaccinated animals compared with the controls. Results presented here suggest that the plant-produced HA-based influenza vaccine adjuvanted with c-di-GMP is a promising vaccine/adjuvant combination for the development of new mucosal influenza vaccines. publishedVersion