Th17 cells in inflammation and autoimmunity.

T helper 17 (Th17), a distinct subset of CD4(+) T cells with IL-17 as their major cytokine, orchestrate the pathogenesis of inflammatory and autoimmune diseases. Dysregulated Th17 cells contribute to inflammatory and autoimmune diseases. Candidate biologics are in development for targeting IL-17, IL-17 receptors or IL-17 pathways. Several drugs that impact the IL-17 pathway are already in clinical trials for the treatment of autoimmune diseases. In this review we provide evidence for the role of Th17 cells in immune-mediated diseases. An understanding of the role of Th17 in these conditions will provide important insights and unravel novel targets for therapeutic intervention.

Regulatory T cells in systemic lupus erythematosus (SLE); role of peptide tolerance.

Regulatory T cells play an important role in the maintenance and regulation of immune tolerance and in the prevention of autoimmunity. Recent studies have demonstrated a deficiency in number and function of regulatory T cells in lupus and other autoimmune diseases. This may contribute to immune dysregulations and a defect in self-tolerance mechanisms. How to balance and "reset" the immune response from harmful pro-inflammatory to beneficial anti-inflammatory is the current strategy of the research. In this regard, several studies have been performed with various peptides, drugs, steroids and epigenetic agents to induce or modify regulatory cells and some measure of success has been achieved in the animal model of SLE and with lupus patient cells. Challenges ahead include the heterogeneous nature, phenotype and function of regulatory cells and the difficulties in manipulation of regulatory function in healthy versus diseased states. In this review, we will provide some recent findings indicating challenges and potential benefits of targeting of regulatory T cells in lupus.

Using formative research to develop MNCH programme in urban slums in Bangladesh: experiences from MANOSHI, BRAC.

BACKGROUND: MANOSHI, an integrated community-based package of essential Maternal, Neonatal and Child Health (MNCH) services is being implemented by BRAC in the urban slums of Bangladesh since 2007. The objective of the formative research done during the inception phase was to understand the context and existing resources available in the slums, to reduce uncertainty about anticipated effects, and develop and refine the intervention components. METHODS: Data were collected during Jan-Sept 2007 in one of the earliest sites of programme intervention in the Dhaka metropolitan area. A conceptual framework guided data collection at different stages. Besides exploring slum characteristics, studies were done to map existing MNCH service providing facilities and providers, explore existing MNCH-related practices, and make an inventory of community networks/groups with a stake in MNCH service provision. Also, initial perception and expectations regarding the community delivery centres launched by the programme was explored. Transect walk, observation, pile sorting, informal and focus group discussions, in-depth interviews, case studies, network analysis and small quantitative surveys were done to collect data. RESULTS: Findings reveal that though there are various MNCH services and providers available in the slums, their capacity to provide rational and quality services is questionable. Community has superficial knowledge of MNCH care and services, but this is inadequate to facilitate the optimal survival of mothers and neonates. Due to economic hardships, the slum community mainly relies on cheap informal sector for health care. Cultural beliefs and practices also reinforce this behaviour including home delivery without skilled assistance. Men and women differed in their perception of pregnancy and delivery: men were more concerned with expenses while women expressed fear of the whole process, including delivering at hospitals. People expected 'one-stop' MNCH services from the community delivery centres by skilled personnel. Social support network for health was poor compared to other networks. Referral linkages to higher facilities were inadequate, fragmentary, and disorganised. CONCLUSIONS: Findings from formative research reduced contextual uncertainty about existing MNCH resources and care in the slum. It informed MANOSHI to build up an intervention which is relevant and responsive to the felt needs of the slum population.

Malaria prevalence in endemic districts of Bangladesh.

BACKGROUND: Following the 1971 ban of DDT in Bangladesh, malaria cases have increased steadily. Malaria persists as a major health problem in the thirteen south-eastern and north-eastern districts of Bangladesh. At present the national malaria control program, largely supported by the Global Fund for AIDS, Tuberculosis and Malaria (GFATM), provides interventions including advocacy at community level, Insecticide Treated Net (ITN) distribution, introduction of Rapid Diagnostic Tests (RDT) and combination therapy with Coartem. It is imperative, therefore, that baseline data on malaria prevalence and other malaria indicators are collected to assess the effectiveness of the interventions and rationalize the prevention and control efforts. The objective of this study was to obtain this baseline on the prevalence of malaria and bed net use in the thirteen malaria endemic districts of Bangladesh. METHODS AND PRINCIPAL FINDINGS: In 2007, BRAC and ICDDR,B carried out a malaria prevalence survey in thirteen malaria endemic districts of Bangladesh. A multi-stage cluster sampling technique was used and 9750 blood samples were collected. Rapid Diagnostic Tests (RDT) were used for the diagnosis of malaria. The weighted average malaria prevalence in the thirteen endemic districts was 3.97%. In five south-eastern districts weighted average malaria prevalence rate was 6.00% and in the eight north-eastern districts weighted average malaria prevalence rate was (0.40%). The highest malaria prevalence was observed in Khagrachari district. The majority of the cases (90.18%) were P. falciparum infections. Malaria morbidity rates in five south-eastern districts was 2.94%. In eight north-eastern districts, morbidity was 0.07%. CONCLUSION AND SIGNIFICANCE: Bangladesh has hypoendemic malaria with P. falciparum the dominant parasite species. The malaria situation in the five north-eastern districts of Bangladesh in particular warrants urgent attention. Detailed maps of the baseline malaria prevalence and summaries of the data collected are provided along with the survey results in full, in a supplemental information.

Spatial malaria epidemiology in Bangladeshi highlands.

BACKGROUND: Malaria is a major public health burden in the south-eastern part of Bangladesh, particularly in the Chittagong Hill Tracts region. In 2007, BRAC and ICDDR,B carried out a malaria prevalence survey in the endemic regions including the Khagrachari District. METHODS: This study was done to detect clusters of malaria and identify the geographic risk factors. Thirty mauzas (the lowest administrative unit/bigger than village in Bangladesh that has polygon boundary) from the area were selected for the survey using probability proportional to size (PPS) sampling. Twenty-five households within each mauza were then randomly selected for screening, with a GPS point being recorded at each household. Rapid diagnostic tests were used to diagnose malaria. RESULTS: The average malaria prevalence in the District was 15.47% (n = 750). SaTScan detected five geographic clusters of malaria, one of which was highly significant (p = 0.001). Malaria cases were significantly associated with proximity to water bodies and forests. CONCLUSION: The data presented in this paper are the first step to understanding malaria in southeastern Bangladesh from a micro-geographic perspective. The study results suggest that there are 'malaria hot-spots' in the study area. The government of Bangladesh and non-governmental organizations involved in malaria control should consider these results when planning malaria control measures. In particular, malaria maps should be updated on a regular basis as new data become available.

Knowledge on the transmission, prevention and treatment of malaria among two endemic populations of Bangladesh and their health-seeking behaviour.

BACKGROUND: Data on sociological and behavioural aspects of malaria, which is essential for an evidence-based design of prevention and control programmes, is lacking in Bangladesh. This paper attempts to fill this knowledge gap by using data from a population-based prevalence survey conducted during July to November 2007, in 13 endemic districts of Bangladesh. METHODS: A two-stage cluster sampling technique was used to select study respondents randomly from 30 mauzas in each district for the socio-behavioural inquiry (n = 9,750). A pre-tested, semi-structured questionnaire was used to collect data in face-to-face interview by trained interviewers, after obtaining informed consent. RESULTS: The overall malaria prevalence rate in the 13 endemic districts was found to be 3.1% by the Rapid Diagnostic Test 'FalciVax' (P. falciparum 2.73%, P. vivax 0.16% and mixed infection 0.19%), with highest concentration in the three hill districts (11%). Findings revealed superficial knowledge on malaria transmission, prevention and treatment by the respondents. Poverty and level of schooling were found as important determinants of malaria knowledge and practices. Allopathic treatment was uniformly advocated, but the 'know-do' gap became especially evident when in practice majority of the ill persons either did not seek any treatment (31%) or practiced self-treatment (12%). Of those who sought treatment, the majority went to the village doctors and drugstore salespeople (around 40%). Also, there was a delay beyond twenty-four hours in beginning treatment of malaria-like fever in more than half of the instances. In the survey, gender divide in knowledge and health-seeking behaviour was observed disfavouring women. There was also a geographical divide between the high endemic south-eastern area and the low-endemicnorth-eastern area, the former being disadvantaged with respect to different aspects of malaria studied. CONCLUSION: The respondents in this study lacked comprehensive knowledge on different aspects of malaria, which was influenced by level of poverty and education. A gender and geographical divide in knowledge was observed disfavouring women and south-eastern area respectively. They preferred allopathic treatment for malaria, although a substantial proportion did not seek any treatment or sought self-treatment for malaria-like fever. Delay in seeking care was common. The implications of these findings for programme development are discussed.

Surface texture and composition of titanium brushed with toothpaste slurries of different pHs.

OBJECTIVES: This in vitro study characterized the surface texture and composition of titanium brushed with toothpaste slurries of different pHs, and thereby elucidated mechanochemical interactions between the metal and abrasive material in dentifrice. METHODS: Two fluoride-free toothpastes, which contained crystalline CaHPO(4).2H(2)O and amorphous SiO(2) particles as abrasive, were mixed with acidic buffers to provide slurries of pH 6.8 and 4.8. Specimens were cast from CP Ti, mirror-polished, and then toothbrushed at 120strokes/min for 350,400 strokes under a load of 2.45N. Specimen surfaces were characterized by means of SPM and EPMA. The obtained data were compared with the already reported results of water-diluted alkaline slurries. SPM data of each paste were analyzed using one-way ANOVA, followed by post hoc Tukey test. RESULTS: Irrespective of toothpaste, neutral slurries, as with alkaline slurries, yielded a chemically altered surface with rough texture, whereas acidic slurries formed a chemically clean surface with relatively smooth texture. Mechanochemical polishing effect might be mainly responsible for the cleanness and smoothness. SIGNIFICANCE: Acidic slurry-induced smooth surface may minimize plaque formation. However, the augmentation of released titanium ions may be adverse to the human body. For evaluation of toothpaste abrasion effects on titanium, paste slurry pH should be taken into account.

Effect of toothbrushing on titanium surface: an approach to understanding surface properties of brushed titanium.

OBJECTIVES: This in vitro study aimed to characterize the surface morphology and composition of tooth-brushed titanium casting and thereby to elucidate interactions between the metal and abrasive material in dentifrice. METHODS: Specimens were cast from CP Ti ingots and then mirror-finished. Two fluoride-free toothpastes containing crystalline CaHPO4.2H2O and amorphous SiO2 particles as abrasive were slurried with distilled water (15 g/30 mL). While toothbrushes were reciprocated at 120 strokes/min for 350,400 strokes, the specimens were brushed with the respective slurries under a load of 2.45 N. The brushed and non-brushed surfaces were characterized by means of SPM, EPMA, and XPS. SPM data were analyzed using one-way ANOVA, followed by post hoc Tukey test (p<0.01). RESULTS: Irrespective of toothpastes, toothbrushing had a significant influence on surface roughness. The CaHPO4.2H2O-containing paste produced much rougher surface than the SiO2-containing paste. Both the surfaces were chemically altered due to reactions with the respective abrasive materials. Abrading chips had dimensions of micron to submicron order. A number of chips were attached to abrasive particles. SIGNIFICANCE: The alterations of surface morphology and composition may affect biological responses of titanium in the oral environment. Dentifrice with lower abrasivity might be advisable for daily oral hygiene practice of patients with dental titanium devices.

Surface composition and texture of titanium polished with colloidal silica suspension and chromic oxide slurry.

CP titanium was polished with a colloidal silica suspension and chromic oxide slurry under low and high pressures. The polished surfaces were characterized by means of EPMA and XPS. Irrespective of polishing pressure, colloidal silica suspension successfully created a mirror-like surface that was clean at EPMA level. However, XPS detected a small amount of silicon on the outermost surface. On the other hand, chromic oxide slurry under high pressure yielded a very uneven surface with numerous scratches. The EPMA and XPS results suggested the presence of chromium-containing species in the polished surface, which might include hydroxides as well as oxides. In addition, the level of oxygen concentration was noticeably raised, which probably resulted from the increase of surface oxide film thickness or the extension of oxide-to-metal transition zone.

Surface properties of electrochemically buffed titanium casting.

Electrochemical buffing, a combined process of electrochemical and mechanical polishing, was applied to titanium casting. Mixture of alpha-Al2O3 suspension (average grain diameter of 5 microm) and 5% KNO3 solution was used as abrasive slurry. Specimen and experimental wheel buff were respectively connected to the positive and negative poles of a DC source, whose potential ratings ranged from 0 V (MEP) to 10 V (ECB10). Surface roughness, hardness, color, and cleanness were investigated. ECB10 surface produced a gold color and attained a mirror finish, as its roughness value was only one-quarter that of MEP. High amount of aluminum was present in MEP surface. Its bond state entirely differed from that of alpha-Al2O3, hence indicating surface alteration due to chemical reactions with the abrasive material. At higher potentials, reaction products might be dissolved anodically, so that the surface was chemically clean to some extent. The surface also became rich in OH-.