Blood-Brain Barrier Disruption And Lesion Localisation In Experimental Autoimmune Encephalomyelitis With Predominant Cerebellar And Brainstem Involvement

The role of the blood-brain barrier (BBB) in determining lesion distribution was assessed in an atypical model of experimental autoimmune encephalomyelitis (EAE) induced in C3H/HeJ mice by immunisation with peptide 190-209 of myelin proteolipid protein, which can result in two distinct types of EAE, each with distinct lesion distribution. Areas of the BBB showing constitutively greater permeability in naive mice did not correlate with the lesion distribution in EAE. BBB disruption occurred only in sites of inflammatory cell infiltration. Irrespective of the clinical type, the BBB was disrupted in the cerebellum and brainstem. Pertussis toxin had no effect on lesion distribution. Thus, lesion distribution is not influenced solely by BBB permeability

Chemokines and Chemokine Receptors: Potential Therapeutic Targets in Multiple Sclerosis

Multiple sclerosis (MS) is a common inflammatory and demyelinating disease of the central nervous system (CNS), which causes progressive neurological disability. The disease is characterised pathologically by destruction of the myelin sheaths, which surround nerve fibres in the CNS. It is believed that this tissue damage in the brain and spinal cord of MS patients is caused by an inflammatory response that is initiated when autoreactive T cells, specific for myelin antigens, cross the blood-brain barrier and detect their antigen within the CNS. As a result, most therapies to date have been immunosuppressive and/or anti-inflammatory in nature, targeting the process involved in activation and migration of leukocytes and promotion of the immune response. Over the last decade, a family of chemotactic cytokines called chemokines, have been found to be involved in the trafficking of leukocytes in both the normal and pathological states. The expression of these chemokines and their receptors is increased during the acute phase of MS and also in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). As a result, these chemokines have become an emerging focus for research into novel therapeutics for EAE and ultimately MS. This review will briefly describe the structure and function of chemokines and their receptors, before discussing the latest advances in developing pharmacological agents to block the effects of chemokines involved in promoting the inflammatory response in EAE and MS

Seroprevalence of measles and rubella antibodies in vaccinated and unvaccinated infants in the Lao People’s Democratic Republic

Background Even though measles vaccination was introduced in the Lao PDR in 1984, coverage rates remain consistently low and outbreaks continue to occur frequently. This study was performed to investigate the seroprevalence of measles and rubella antibodies in vaccinated and unvaccinated children from Central Lao PDR. Methods Antibody titres of 1090 children aged 8–29 months who were vaccinated at different levels of the health care system were assessed by ELISA. Bivariate and multivariable analyses were performed to identify factors affecting seropositivity against measles and rubella. Results Among the vaccinated children, 67.5% in Vientiane Province and 76.4% in Bolikhamxay Province were double positive/borderline for measles and rubella IgG. A high proportion of unvaccinated children at both study sites (24.4% and 38.4%) were positive/borderline for measles and/or rubella. Time since vaccination <180 days, more than two siblings, and a mother who is a farmer/labourer were negatively associated with seropositivity. Conclusions A high prevalence of measles and rubella antibodies was found in unvaccinated children, indicating widespread circulation of both viruses and underreporting of cases. The high proportion of vaccinated children still susceptible to measles suggests problems with vaccine immunogenicity, emphasizing the need for regular evaluations of vaccine efficacy and management

Epidemiological, clinical and laboratory characteristics of the measles resurgence in the Republic of Serbia in 2014-2015

The Republic of Serbia is a country with ongoing endemic transmission of measles. The aim of this study is to summarize the main characteristics of the measles resurgence that occurred in Serbia in 2014-2015. The national surveillance data on measles was analysed in relation to the clinical, epidemiological and laboratory data. Between November 2014 and December 2015 a measles resurgence with 420 cases was observed in Serbia. Measles virus was initially introduced by and spread among citizens of Bosnia and Herzegovina with temporary residence in Serbia, before spreading to the resident population. Of the 223 patients with available medical records, 173 (77.6%) were unvaccinated. The overall measles incidence during the outbreak was 5.8/100.000. The highest age-specific incidence rate was recorded in children aged lt = 4 years (25.9/100.000), but most cases (67.9%) were gt = 20 years old. Hospitalization rate was high (32.9%) and included two cases of encephalitis associated with measles. In total, 42 health-care workers and 22 related cases including hospitalized patients (n = 13) contracted measles. The overall percentage of laboratory confirmed cases was 81.7% (n = 343/420). All measles virus sequences except one (D9) belonged to genotype D8, suggesting interruption of transmission after the previous outbreak in 2010-2011 caused by genotype D4 viruses. The growing number of adult patients as compared to previous epidemics, suggests an urgent need for supplementary immunization activities targeting susceptible health care workers, unvaccinated or incompletely vaccinated adults as well as people without vaccination records. The comprehensive investigation of the 2014/2015 measles resurgence will contribute to decisions about appropriate countermeasures to stop the future measles resurgences in Serbia

Varicella zoster and fever rash surveillance in Lao People’s Democratic Republic

Background In Lao PDR, the epidemiology of varicella infection is uncertain, since it is not a notifiable disease and VZV outbreaks are rarely reported as fever/rash (F/R) diseases. Methods We estimated the seroprevalence of VZV (IgG ELISA) in different age cohorts (9 months to 46 years; N = 3139) and investigated VZV and 6 other viruses in patients during F/R outbreaks and in an ad hoc sentinel site in the context of the national reporting system (IgM ELISA, PCR). Results At least 80% of the sampled population had evidence of VZV infection before the age of 15. The largest increase in seroprevalence occurred between the age groups 1 to 5 and 6 to 7 year-olds. A VZV outbreak (clade 2) also occurred in this age group mostly during the first year of primary school (median age 6 years, interquartile range 4.0–7.5). During a dengue outbreak, 6% had varicella. At our F/R sentinel site, 14% of children with viral etiology were laboratory diagnosed as varicella and among others, a sizeable number of measles (N = 12) and rubella cases (N = 25) was detected compared to those reported for the whole country (N = 56 and 45), highlighting nationwide a large challenge of underreporting or misdiagnosis of these notifiable diseases because of lack of diagnostic laboratory capacity. Conclusion We recommend strengthening the clinical and laboratory diagnosis of VZV, measles and rubella, the surveillance and reporting of notifiable F/R diseases by retraining of healthcare workers and by setting up sentinel sites and enhancing laboratory capacity

FHL2 inhibits the activated osteoclast in a TRAF6-dependent manner

TNF receptor–associated factor 6 (TRAF6) associates with the cytoplasmic domain of receptor activator of NF-κB (RANK). This event is central to normal osteoclastogenesis. We discovered that TRAF6 also interacts with FHL2 (four and a half LIM domain 2), a LIM domain–only protein that functions as a transcriptional coactivator or corepressor in a cell-type–specific manner. FHL2 mRNA and protein are undetectable in marrow macrophages and increase pari passu with osteoclast differentiation in vitro. FHL2 inhibits TRAF6-induced NF-κB activity in wild-type osteoclast precursors and, in keeping with its role as a suppressor of TRAF6-mediated RANK signaling, TRAF6/RANK association is enhanced in FHL2(–/–) osteoclasts. FHL2 overexpression delays RANK ligand–induced (RANKL-induced) osteoclast formation and cytoskeletal organization. Interestingly, osteoclast-residing FHL2 is not detectable in naive wild-type mice, in vivo, but is abundant in those treated with RANKL and following induction of inflammatory arthritis. Reflecting increased RANKL sensitivity, osteoclasts generated from FHL2(–/–) mice reach maturation and optimally organize their cytoskeleton earlier than their wild-type counterparts. As a consequence, FHL2(–/–) osteoclasts are hyperresorptive, and mice lacking the protein undergo enhanced RANKL and inflammatory arthritis–stimulated bone loss. FHL2 is, therefore, an antiosteoclastogenic molecule exerting its effect by attenuating TRAF6-mediated RANK signaling

Hepatitis B virus in the Lao People’s Democratic Republic: a cross sectional serosurvey in different cohorts

Background Despite hepatitis B vaccination at birth and at 6, 10 and 14 weeks of age, hepatitis B virus (HBV) infection continues to be endemic in the Lao People’s Democratic Republic (PDR). We carried out a cross-sectional serological study in infants, pre-school children, school pupils and pregnant women to determine their burden of disease, risk of infection and vaccination status. Methods A total of 2471 participants between 9 months and 46 years old were recruited from urban (Vientiane Capital, Luang Prabang), semi-urban (Boulhikhamxai and Savannakhet) and remote rural areas (Huaphan). All sera were tested for anti-HBs and anti-HBc. Sera testing positive for anti-HBc alone were further tested for the presence of HBsAg. Results A low prevalence of HBsAg (0.5%) was detected among infants from Vientiane and Luang Prabang, indicating some success of the vaccination policy. However, only 65.6% had protective anti-HBs antibodies, suggesting that vaccination coverage or responses remain sub-optimal, even in these urban populations. In pre-school children from remote areas in Huaphan, 21.2% were positive for anti-HBc antibodies, and 4.6% were for HBsAg positive, showing that a significant proportion of children in these rural regions have early exposure to HBV. In pre-school children with 3 documented HBV vaccinations, only 17.0% (15/55) were serologically protected. Among school-children from semi-urban regions of Luang Prabang, Boulhikhamxai and Savannakhet provinces, those below the age of 9 who were born after HBV vaccine introduction had anti-HBc and HBsAg prevalence of 11.7% and 4.1%, respectively. The prevalence increased to 19.4% and 7.8% of 10–14 year olds and to 27% and 10.2% of 15–19 year olds. Pregnant women from Luang Prabang and Vientiane had very high anti-HBc and HBsAg prevalence (49.5% and 8.2%), indicating high exposure and risk of onward vertical transmission to the unborn infant. Conclusions Overall, the results demonstrate a dramatic deficiency in vaccination coverage and vaccine responses and/or documentation within the regions of Lao PDR studied, which included urbanized areas with better health care access. Timely and effective hepatitis B vaccination coverage is needed in Lao PDR

Measles situation in Serbia in an era of measles elimination (2007-2009)

Following the introduction of measles immunization in Serbia in 1971, measles outbreaks were recorded every 3 to 5 years until 1997. The outbreak in 1997 with 4000 cases was the last large outbreak in Serbia. In 2007, an outbreak with 191 laboratory confirmed or epidemiologically linked cases was reported in Vojvodina. In 2008 and 2009, only 3 cases were confirmed. From 2007-2009, measles infections were most frequently detected in the Roma population but also in non-immunized or partially immunized persons from the general population

What motivates general practitioners to change practice behaviour? A qualitative study of audit and feedback group sessions in Dutch general practice

Objectives Adopting an attributional perspective, the current article investigates how audit and feedback group sessions contribute to general practitioners’ (GPs) motivation to change their practice behaviour to improve care. We focus on the contributions of the audit and feedback itself (content) and the group discussion (process). Methods Four focus groups, comprising a total of 39 participating Dutch GPs, discussed and compared audit and feedback of their practices. The focus groups were analysed thematically. Results Audit and feedback contributed to GPs’ motivation to change in two ways: by raising awareness about aspects of their current care practice and by providing indications of the possible impact of change. For these contributions to play out, the audit and feedback should be reliable and valid, specific, recent and recurrent and concern GPs’ own practices or practices within their own influence sphere. Care behaviour attributed to external, uncontrollable or unstable causes would not induce change. The added value of the group is twofold as well: group discussion contributed to GPs’ motivation to change by providing a frame of reference and by affording insights that participants would not have been able to achieve on their own. Conclusions In audit and feedback group sessions, both audit and feedback information and group discussion can valuably contribute to GPs’ motivation to change care practice behaviour. Peer interaction can positively contribute to explore alternative practices and avenues for improvement. Local or regional peer meetings would be beneficial in facilitating reflection and discussion. An important avenue for future studies is to explore the contribution of audit and feedback and small-group discussion to actual practice change

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript