Neutrophil-derived CCL3 is essential for the rapid recruitment of dendritic cells to the site of Leishmania major inoculation in resistant mice.

Neutrophils are rapidly and massively recruited to sites of microbial infection, where they can influence the recruitment of dendritic cells. Here, we have analyzed the role of neutrophil released chemokines in the early recruitment of dendritic cells (DCs) in an experimental model of Leishmania major infection. We show in vitro, as well as during infection, that the parasite induced the expression of CCL3 selectively in neutrophils from L. major resistant mice. Neutrophil-secreted CCL3 was critical in chemotaxis of immature DCs, an effect lost upon CCL3 neutralisation. Depletion of neutrophils prior to infection, as well as pharmacological or genetic inhibition of CCL3, resulted in a significant decrease in DC recruitment at the site of parasite inoculation. Decreased DC recruitment in CCL3(-/-) mice was corrected by the transfer of wild type neutrophils at the time of infection. The early release of CCL3 by neutrophils was further shown to have a transient impact on the development of a protective immune response. Altogether, we identified a novel role for neutrophil-secreted CCL3 in the first wave of DC recruitment to the site of infection with L. major, suggesting that the selective release of neutrophil-secreted chemokines may regulate the development of immune response to pathogens.

High proportion of wrongly identified methicillin-resistant Staphylococcus aureus carriers by use of a rapid commercial PCR assay due to presence of staphylococcal cassette chromosome element lacking the mecA gene.

During a 9-month period, 217 patients were newly diagnosed as methicillin-resistant Staphylococcus aureus (MRSA) carriers by using a commercial rapid PCR-based test (GeneXpert). However, no MRSA was recovered by culturing the second swab in 61 of these patients. Further analyses showed that 28 (12.9%) of the patients harbored S. aureus isolates with a staphylococcal cassette chromosome element lacking the mecA gene and were thus incorrectly determined to be MRSA carriers.

Rapid diagnostic tests for the home-based management of malaria, in a high-transmission area.

Rapid diagnostic tests (RDT) are sometimes recommended to improve the home-based management of malaria. The accuracy of an RDT for the detection of clinical malaria and the presence of malarial parasites has recently been evaluated in a high-transmission area of southern Mali. During the same study, the cost-effectiveness of a 'test-and-treat' strategy for the home-based management of malaria (based on an artemisinin-combination therapy) was compared with that of a 'treat-all' strategy. Overall, 301 patients, of all ages, each of whom had been considered a presumptive case of uncomplicated malaria by a village healthworker, were checked with a commercial RDT (Paracheck-Pf). The sensitivity, specificity, and positive and negative predictive values of this test, compared with the results of microscopy and two different definitions of clinical malaria, were then determined. The RDT was found to be 82.9% sensitive (with a 95% confidence interval of 78.0%-87.1%) and 78.9% (63.9%-89.7%) specific compared with the detection of parasites by microscopy. In the detection of clinical malaria, it was 95.2% (91.3%-97.6%) sensitive and 57.4% (48.2%-66.2%) specific compared with a general practitioner's diagnosis of the disease, and 100.0% (94.5%-100.0%) sensitive but only 30.2% (24.8%-36.2%) specific when compared against the fulfillment of the World Health Organization's (2003) research criteria for uncomplicated malaria. Among children aged 0-5 years, the cost of the 'test-and-treat' strategy, per episode, was about twice that of the 'treat-all' (U.S.$1.0. v. U.S.$0.5). In older subjects, however, the two strategies were equally costly (approximately U.S.$2/episode). In conclusion, for children aged 0-5 years in a high-transmission area of sub-Saharan Africa, use of the RDT was not cost-effective compared with the presumptive treatment of malaria with an ACT. In older patients, use of the RDT did not reduce costs. The question remains whether either of the strategies investigated can be made affordable for the affected population.

Viremic blood donor found by a rapid screening method in a season of high human parvovirus B19 activity in Niterói, Rio de Janeiro, Brazil

Erythrovirus B19 infection is usually benign but may have serious consequences in patients with hemolytic anemia (transient aplastic crisis), immunodeficiency (in whom persistent infection can lead to chronic bone marrow failure with anemia), or who are in the first or second trimester of gestation (spontaneous abortion, hydrops fetalis, and fetal death). Being non-enveloped, B19 resists most inactivation methods and can be transmitted by transfusion. B19 is difficult to cultivate and native virus is usually obtained from viremic blood. As specific antibodies may be absent, and there is no reliable immunological method for antigen detection, hybridization or polymerase chain reaction are needed for detecting viremia. A rapid method, gel hemagglutination (Diamed ID-Parvovirus B19 Antigen Test), can disclose highly viremic donations, whose elimination lessens the viral burden in pooled blood products and may even render them non-infectious. In order to obtain native antigen and to determine the frequency of viremic donors, we applied this test to blood donors in a period of high viral activity in our community. Positive or indeterminate results were re-tested by dot-blot hybridization. We tested 472 donors in 1998 and 831 ones in 1999. One viremic donor was found in 1999. We suggest that in periods of high community viral activity the gel hemagglutination test may be useful in avoiding highly viremic blood being added to plasma pools or directly transfused to patients under risk.

Microfluidic processor allows rapid HER2 immunohistochemistry of breast carcinomas and significantly reduces ambiguous (2+) read-outs.

Biomarker analysis is playing an essential role in cancer diagnosis, prognosis, and prediction. Quantitative assessment of immunohistochemical biomarker expression on tumor tissues is of clinical relevance when deciding targeted treatments for cancer patients. Here, we report a microfluidic tissue processor that permits accurate quantification of the expression of biomarkers on tissue sections, enabled by the ultra-rapid and uniform fluidic exchange of the device. An important clinical biomarker for invasive breast cancer is human epidermal growth factor receptor 2 [(HER2), also known as neu], a transmembrane tyrosine kinase that connotes adverse prognostic information for the patients concerned and serves as a target for personalized treatment using the humanized antibody trastuzumab. Unfortunately, when using state-of-the-art methods, the intensity of an immunohistochemical signal is not proportional to the extent of biomarker expression, causing ambiguous outcomes. Using our device, we performed tests on 76 invasive breast carcinoma cases expressing various levels of HER2. We eliminated more than 90% of the ambiguous results (n = 27), correctly assigning cases to the amplification status as assessed by in situ hybridization controls, whereas the concordance for HER2-negative (n = 31) and -positive (n = 18) cases was 100%. Our results demonstrate the clinical potential of microfluidics for accurate biomarker expression analysis. We anticipate our technique will be a diagnostic tool that will provide better and more reliable data, onto which future treatment regimes can be based.

Rapid Diagnostic Test-Based Management of Malaria: An Effectiveness Study in Papua New Guinean Infants With Plasmodium falciparum and Plasmodium vivax Malaria.

Background. In malaria-endemic areas it is recommended that febrile children be tested for malaria by rapid diagnostic test (RDT) or blood slide (BS) and receive effective malaria treatment only if results are positive. However, RDTs are known to perform less well for Plasmodium vivax. We evaluated the safety of withholding antimalarial drugs from young Papua New Guinean children with negative RDT results in areas with high levels of both Plasmodium falciparum and P. vivax infections. Methods. longitudinal prospective study of children aged 3-27 months visiting outpatient clinics for fever. RDT was administered at first visit. RDT and microscopy were performed if children returned because of persistent symptoms. Outcomes were rates of reattendance and occurrence of severe illnesses. Results. Of 5670 febrile episodes, 3942 (70%) involved a negative RDT result. In 133 cases (3.4%), the children reattended the clinic within 7 days for fever, of whom 29 (0.7%) were parasitemic by RDT or microscopy. Of children who reattended, 24 (0.7%) presented with a severe illness: 2 had lower respiratory tract infections (LRTIs) with low-density P. vivax on BS; 2 received a diagnosis of P. vivax malaria on the basis of RDT but BSs were negative; 16 had LRTIs; 3 had alternative diagnoses. Of these 24, 22 were cured at day 28. Two children died of illnesses other than malaria and were RDT and BS negative at the initial and subsequent visits. Conclusion. Treatment for malaria based on RDT results is safe and feasible even in infants living in areas with moderate to high endemicity for both P. falciparum and P. vivax infections.

Pulmonary artery pressure and cardiac function in children and adolescents after rapid ascent to 3,450 m.

High-altitude destinations are visited by increasing numbers of children and adolescents. High-altitude hypoxia triggers pulmonary hypertension that in turn may have adverse effects on cardiac function and may induce life-threatening high-altitude pulmonary edema (HAPE), but there are limited data in this young population. We, therefore, assessed in 118 nonacclimatized healthy children and adolescents (mean ± SD; age: 11 ± 2 yr) the effects of rapid ascent to high altitude on pulmonary artery pressure and right and left ventricular function by echocardiography. Pulmonary artery pressure was estimated by measuring the systolic right ventricular to right atrial pressure gradient. The echocardiography was performed at low altitude and 40 h after rapid ascent to 3,450 m. Pulmonary artery pressure was more than twofold higher at high than at low altitude (35 ± 11 vs. 16 ± 3 mmHg; P < 0.0001), and there existed a wide variability of pulmonary artery pressure at high altitude with an estimated upper 95% limit of 52 mmHg. Moreover, pulmonary artery pressure and its altitude-induced increase were inversely related to age, resulting in an almost twofold larger increase in the 6- to 9- than in the 14- to 16-yr-old participants (24 ± 12 vs. 13 ± 8 mmHg; P = 0.004). Even in children with the most severe altitude-induced pulmonary hypertension, right ventricular systolic function did not decrease, but increased, and none of the children developed HAPE. HAPE appears to be a rare event in this young population after rapid ascent to this altitude at which major tourist destinations are located.

Impact of a smoking ban in public places: a rapid assessment in the Seychelles.

Background We assessed the impact of a smoking ban in hospitality venues in the Seychelles 9 months after legislation was implemented. Methods Survey officers observed compliance with the smoking ban in 38 most popular hospitality venues and administered a structured questionnaire to two customers, two workers and one manager in each venue. Results Virtually no customers or workers were seen smoking in the indoor premises. Patrons, workers and managers largely supported the ban. The personnel of the hospitality venues reported that most smokers had no difficulty refraining from smoking. However, a third of workers did not systematically request customers to stop smoking and half of them did not report adequate training. Workers reported improved health. No substantial change in the number of customers was noted. Conclusion A ban on public smoking was generally well implemented in hospitality venues but some less than optimal findings suggest the need for adequate training of workers and strengthened enforcement measures. The simple and inexpensive methodology used in this rapid survey may be a useful approach to evaluate the implementation and impact of clean air policy in low and middle-income countries.

A Rapid Mapping Study of Smoking Projects and Services Targeted at People Living on Low Income and/or Minority Ethnic Groups

This is a study concerned with community based services aimed at smokers living on a low income and/or black and minority ethnic groups.

Rapid review of brief interventions to prevent or reduce obesity in adults and children

The results of, and recommendations from, a rapid review of the literature assessing the effectiveness of brief interventions as a possible approach to the management of obesity

Substance Misuse Among People Over 55 - Perspectives from the Community and Voluntary sector in Belfast

The Belfast Health Development Unit (BHDU) was established as a Ministerial priority in March 2010, co-locating staff from The Public Health Agency (PHA), Belfast Health and Social Care Trust (BHSCT) and Belfast City Council (BCC). One of the strategic priorities for the BHDU is: an integrated approach to planning and delivery of services for older people in the city.The PHA and the BHDU had identified a need to examine the extent of substance misuse issues within the older population of the city of Belfast and to explore early intervention programmes targeting this population. It is envisioned that this piece of work will inform and support the Belfast Healthy Ageing Strategic Partnership on older people and its multi-sectoral action plan and will influence the work and priorities of the Belfast Strategic Partnership and its constituent stakeholders in taking drug and alcohol work forward in Belfast.The aim of this research was to review knowledge, awareness and evidence of the impact of substance misuse on the older population (aged 55+) and to review good practice in reducing substance related harm within this population which has been done by undertaking a review of available research, data and information sources. However, the main focus of the research involved consulting with a broad range of community and voluntary sector organisations working in the Belfast area to assess their views and perceptions of the prevalence and extent of substance misuse within the older population and the services currently in place to address this issue.�

Evaluation of rapid alternative methods for drug susceptibility testing in clinical isolates of Mycobacterium tuberculosis

A study was carried out to compare the performance of a commercial method (MGIT) and four inexpensive drug susceptibility methods: nitrate reductase assay (NRA), microscopic observation drug susceptibility (MODS) assay, MTT test, and broth microdilution method (BMM). A total of 64 clinical isolates of Mycobacterium tuberculosis were studied. The Lowenstein-Jensen proportion method (PM) was used as gold standard. MGIT, NRA, MODS, and MTT results were available on an average of less than 10 days, whereas BMM results could be reported in about 20 days. Most of the evaluated tests showed excellent performance for isoniazid and rifampicin, with sensitivity and specificity values > 90%. With most of the assays, sensitivity for ethambutol was low (62-87%) whereas for streptomycin, sensitivity values ranged from 84 to 100%; NRA-discrepancies were associated with cultures with a low proportion of EMB-resistant organisms while most discrepancies with quantitative tests (MMT and BMM) were seen with isolates whose minimal inhibitory concentrations fell close the cutoff. MGIT is reliable but still expensive. NRA is the most inexpensive and easiest method to perform without changing the organization of the routine PM laboratory performance. While MODS, MTT, and BMM, have the disadvantage from the point of view of biosafety, they offer the possibility of detecting partial resistant strains. This study shows a very good level of agreement of the four low-cost methods compared to the PM for rapid detection of isoniazid, rifampicin and streptomycin resistance (Kappa values > 0.8); more standardization is needed for ethambutol.

Bamford rapid reviews

The Bamford review of mental health and learning disabilities identified the need for research to help with service and policy development in a number of areas. We worked with key stakeholders, gaining significant input from service users and carers along with professionals and researchers, to agree five top priorities. Research reviews were funded by HSC R&D Division, Public Health Agency (PHA) to set out current knowledge about policies and care services relevant to Children and Young People; Patient Outcomes; Intellectual Disability; Psychological Therapies and Primary Care.The reviews which can be accessed below will serve as accessible, high quality sources of up-to-date knowledge for commissioners, policy-makers, academics and providers of health or social care services as well as service users. We hope that the reviews will help to inform future development and delivery of Mental Health and Intellectual Disability services and so achieve the best outcomes for service users and their families. The reviews have also identified a number of important areas for further research.A Call for research proposals�to these areas is announced today. Further information on this Call can be found by clicking hereA further Rapid review in personality disorders has been commissioned in conjunction with HSCB and DHSSPS and is now available to download here.

Extensive remodeling of DC function by rapid maturation-induced transcriptional silencing.

The activation, or maturation, of dendritic cells (DCs) is crucial for the initiation of adaptive T-cell mediated immune responses. Research on the molecular mechanisms implicated in DC maturation has focused primarily on inducible gene-expression events promoting the acquisition of new functions, such as cytokine production and enhanced T-cell-stimulatory capacity. In contrast, mechanisms that modulate DC function by inducing widespread gene-silencing remain poorly understood. Yet the termination of key functions is known to be critical for the function of activated DCs. Genome-wide analysis of activation-induced histone deacetylation, combined with genome-wide quantification of activation-induced silencing of nascent transcription, led us to identify a novel inducible transcriptional-repression pathway that makes major contributions to the DC-maturation process. This silencing response is a rapid primary event distinct from repression mechanisms known to operate at later stages of DC maturation. The repressed genes function in pivotal processes--including antigen-presentation, extracellular signal detection, intracellular signal transduction and lipid-mediator biosynthesis--underscoring the central contribution of the silencing mechanism to rapid reshaping of DC function. Interestingly, promoters of the repressed genes exhibit a surprisingly high frequency of PU.1-occupied sites, suggesting a novel role for this lineage-specific transcription factor in marking genes poised for inducible repression.