Promoting labour market inclusion of the chronically ill: a scoping review of Scandinavian countries' efforts.

OBJECTIVES: This article is a scoping review of efforts in labour market inclusion of the chronically ill in the Scandinavian countries, a research area that has received much political as well as research attention in recent years. The aim of the review was to identify promising strategies and the need for further research. METHODS: Six electronic databases were searched for literature published between 2015 and 2020. We included peer-reviewed articles that studied the effect of measures, aimed at the workplace or at the individual, that are intended to increase participation. Our search resulted in 2718 articles; our screening procedures resulted in 47 included articles. RESULTS: Among the included studies, musculoskeletal problems (17 articles) and mental health problems (29 articles) were the most frequent chronic conditions. Multimodal occupational rehabilitation programmes directed towards the individual employee were the most frequent interventions (30 articles). Return to work (24 articles) and sickness absence (12 articles) were the most common outcomes. About half (25 articles) of the included studies reported a positive impact of the intervention on work inclusion of the chronically ill. CONCLUSIONS: Our review found little evidence of how government programmes directed towards the supply side of the labour market succeed in including the chronically ill. Our review further indicated that multidisciplinary workplace interventions have a substantial effect. We also identified a significant lack of research on the effect of various governmental policies and programmes, including local health, work and welfare services, and limited coordination and cooperation between health and work services professions.

Role of TaqMan array card in determining causative organisms of acute febrile illness in hospitalized patients.

BACKGROUND: Acute febrile illness (AFI) is a prevalent disease in developing countries that is difficult to diagnose due to the diversity of infectious organisms and the poor quality of clinical diagnosis. TaqMan array card (TAC) can detect up to 35 AFI-associated organisms in 1.5 h, addressing diagnostic demands. In this study, we aimed to evaluate the role of TAC in determining the causative organisms in hospitalized AFI patients. METHODS: The study had a cross-sectional design and enrolled 120 admitted patients with persistent fever for three or more days from the medicine ward of Chittagong Medical College Hospital (CMCH) and Bangladesh Institute of Tropical and Infectious Diseases Hospital (BITID). Blood samples were collected and then subjected to automated BacT/Alert blood culture, microbial culture, TAC assay, and typhoid/paratyphoid test. RESULTS: The total number of study participants was 120, among them 48 (40%) samples showed a positive result in TAC card, 29 (24.16%) were TP positive and nine (7.51%) were culture positive. The number of organisms detected by the TAC card was 13 bacteria, three viruses, one protozoan, and one fungus. The sensitivity and specificity of the TAC assay for different bacterial pathogen compared to blood culture was 44.44%, and 90.99%, respectively. In contrast, the TP test had a sensitivity and specificity of 100% and 80%, respectively, compared to the blood culture test. CONCLUSION: TAC can be a handful tool for detecting multiple organisms in AFI with high specificity which can facilitate early diagnosis of different pathogens contributing to AFI.

A cross-sector systematic review and synthesis of knowledge on telemedicine interventions in chronic wound management-Implications from a system perspective.

Based on initially identified needs for further telemedicine (TM) and chronic wound management research, the objective of this article is twofold: to conduct a systematic review of existing knowledge on TM interventions in chronic wound management-including barriers and opportunities-across the specialist and primary care sectors, and to incorporate the review findings into a system framework that can be further developed and validated through empirical data. We conclude that there is a pressing need for broader and more comprehensive empirical explorations into quality improvement and integration of TM in chronic wound management, including using system frameworks that can capture cross-sector system perspectives and associated implications. Of practical consideration, we suggest that the design and execution of TM improvement interventions and associated research projects should be conducted in close cooperation with managers and practitioners knowledgeable about barriers and opportunities that can influence the implementation of important interventions within chronic wound management.

Pharmacodynamics of Piperacillin-Tazobactam/Amikacin Combination versus Meropenem against Extended-Spectrum ß-Lactamase-Producing Escherichia coli in a Hollow Fiber Infection Model.

Carbapenems are recommended for the treatment of urosepsis caused by extended-spectrum ß-lactamase (ESBL)-producing, multidrug-resistant Escherichia coli; however, due to selection of carbapenem resistance, there is an increasing interest in alternative treatment regimens including the use of ß-lactam-aminoglycoside combinations. We compared the pharmacodynamic activity of piperacillin-tazobactam and amikacin as mono and combination therapy versus meropenem monotherapy against extended-spectrum ß-lactamase (ESBL)-producing, piperacillin-tazobactam resistant E. coli using a dynamic hollow fiber infection model (HFIM) over 7 days. Broth-microdilution was performed to determine the MIC of E. coli isolates. Whole genome sequencing was conducted. Four E. coli isolates were tested in HFIM with an initial inoculum of ~107 CFU/mL. Dosing regimens tested were piperacillin-tazobactam 4.5 g, 6-hourly, plus amikacin 30 mg/kg, 24-hourly, as combination therapy, and piperacillin-tazobactam 4.5 g, 6-hourly, amikacin 30 mg/kg, 24-hourly, and meropenem 1 g, 8-hourly, each as monotherapy. We observed that piperacillin-tazobactam and amikacin monotherapy demonstrated initial rapid bacterial killing but then led to amplification of resistant subpopulations. The piperacillin-tazobactam/amikacin combination and meropenem experiments both attained a rapid bacterial killing (~4-5 log10) within 24 h and did not result in any emergence of resistant subpopulations. Genome sequencing demonstrated that all ESBL-producing E. coli clinical isolates carried multiple antibiotic resistance genes including blaCTX-M-15, blaOXA-1, blaEC, blaTEM-1, and aac(6')-Ib-cr. These results suggest that the combination of piperacillin-tazobactam/amikacin may have a potential role as a carbapenem-sparing regimen, which should be tested in future urosepsis clinical trials.

Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial.

BACKGROUND: Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings. METHODS: We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110. FINDINGS: 41 344 children were vaccinated in April-May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI -12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed. INTERPRETATION: Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses. FUNDING: The study was funded by the Bill & Melinda Gates Foundation.

Pharmacodynamic evaluation of piperacillin/tazobactam versus meropenem against extended-spectrum ß-lactamase-producing and non-producing Escherichia coli clinical isolates in a hollow-fibre infection model.

BACKGROUND: Urosepsis caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. Carbapenems are commonly recommended for the treatment of ESBL infections; however, to minimize the emergence of carbapenem resistance, interest in alternative treatments has heightened. OBJECTIVES: This study compared pharmacodynamics of piperacillin/tazobactam versus meropenem against ESBL-producing and non-producing E. coli clinical isolates. METHODS: E. coli isolates, obtained from national reference laboratory in Bangladesh, were characterized by phenotypic tests, WGS, susceptibility tests and mutant frequency analysis. Three ESBL-producing and two non-producing E. coli were exposed to piperacillin/tazobactam (4.5 g, every 6 h and every 8 h, 30 min infusion) and meropenem (1 g, every 8 h, 30 min infusion) in a hollow-fibre infection model over 7 days. RESULTS: Piperacillin/tazobactam regimens attained ∼4-5 log10 cfu/mL bacterial killing within 24 h and prevented resistance emergence over the experiment against ESBL-producing and non-producing E. coli. However, compared with 8 hourly meropenem, the 6 hourly piperacillin/tazobactam attained ∼1 log10 lower bacterial kill against one of three ESBL-producing E. coli (CTAP#173) but comparable killing for the other two ESBL-producing (CTAP#168 and CTAP#169) and two non-producing E. coli (CTAP#179 and CTAP#180). The 6 hourly piperacillin/tazobactam regimen attained ∼1 log10 greater bacterial kill compared with the 8 hourly regimen against CTAP#168 and CTAP#179 at 24 h. CONCLUSIONS: Our study suggests piperacillin/tazobactam may be a potential alternative to carbapenems to treat urosepsis caused by ESBL-producing E. coli, although clinical trials with robust design are needed to confirm non-inferiority of outcome.

A review of the impact of environmental factors and pollutants on covid-19 transmission.

The coronavirus disease (COVID-19) caused an unprecedented loss of life with colossal social and economic fallout over 237 countries and territories worldwide. Environmental conditions played a significant role in spreading the virus. Despite the availability of literature, the consecutive waves of COVID-19 in all geographical conditions create the necessity of reviewing the impact of environmental factors on it. This study synthesized and reviewed the findings of 110 previously published articles on meteorological factors and COVID-19 transmission. This study aimed to identify the diversified impacts of meteorological factors on the spread of infection and suggests future research. Temperature, rainfall, air quality, sunshine, wind speed, air pollution, and humidity were found as investigated frequently. Correlation and regression analysis have been widely used in previous studies. Most of the literature showed that temperature and humidity have a favorable relationship with the spread of COVID-19. On the other hand, 20 articles stated no relationship with humidity, and nine were revealed the negative effect of temperature. The daily number of COVID-19 confirmed cases increased by 4.86% for every 1 °C increase in temperature. Sunlight was also found as a significant factor in 10 studies. Moreover, increasing COVID-19 incidence appeared to be associated with increased air pollution, particularly PM10, PM2.5, and O3 concentrations. Studies also indicated a negative relation between the air quality index and the COVID-19 cases. This review determined environmental variables' complex and contradictory effects on COVID-19 transmission. Hence it becomes essential to include environmental parameters into epidemiological models and controlled laboratory experiments to draw more precious results.

Etiology of Diarrhea Requiring Hospitalization in Bangladesh by Quantitative Polymerase Chain Reaction, 2014-2018.

BACKGROUND: Diarrhea remains a major public health problem and characterization of its etiology is needed to prioritize interventions. However, most data are from single-site studies of children. We tested samples from participants of any age from 11 geographically diverse hospitals in Bangladesh to describe pathogen-specific burdens of diarrhea. METHODS: We utilized 2 existing diarrhea surveillance systems: a Nationwide network at 10 sentinel hospitals and at the icddr,b hospital. We tested stools from enrolled participants and nondiarrheal controls for enteropathogens using quantitative polymerase chain reaction and calculated pathogen-specific attributable fractions (AFs) of diarrhea. RESULTS: We analyzed 5516 patients with diarrhea and 735 controls. Overall, rotavirus had the highest attributable burden of diarrhea (Nationwide AF, 17.7%; 95% confidence interval [CI], 14.3-20.9%; icddr,b AF, 39.9%; 38.0-41.8%), followed by adenovirus 40/41 (Nationwide AF, 17.9%; 95% CI: 13.9-21.9%; icddr,b AF, 16.6%; 95% CI, 14.4-19.4%) and Vibrio cholerae (Nationwide AF, 10.2%; 95% CI, 9.1-11.3%; icddr,b AF, 13.3%; 95% CI: 11.9-15.1%). Rotavirus was the leading pathogen in children <5 years and was consistent across the sites (coefficient of variation = 56.3%). Adenovirus 40/41 was the second leading pathogen in both children and adults. Vibrio cholerae was the leading pathogen in individuals >5 years old, but was more geographically variable (coefficient of variation = 71.5%). Other attributable pathogens included astrovirus, norovirus, Shigella, Salmonella, ETEC, sapovirus, and typical EPEC. CONCLUSIONS: Rotavirus, adenovirus 40/41, and V. cholerae were the leading etiologies of infectious diarrhea requiring hospitalization in Bangladesh. Other pathogens were important in certain age groups or sites.

Evaluating Complex Health and Social Care Program Using Multi-Criteria Decision Analysis: A Case Study of "Better Together in Amsterdam North".

OBJECTIVES: Multi-criteria decision analysis (MCDA) has been recommended to support policy making in healthcare. However, practical applications of MCDA are sparse. One potential use for MCDA is for the evaluation of programs for complex and vulnerable patients. These complex patients benefit from integrated care programs that span healthcare and social care and aim to improve more than just health outcomes. MCDA can evaluate programs that aim to improve broader outcomes because it allows the evaluation of multiple outcomes alongside each other. In this study, we evaluate an innovative integrated care program in the Netherlands using MCDA. METHODS: We used an innovative MCDA framework with broad outcomes of health, well-being, and cost to evaluate the Better Together in Amsterdam North (BSiN) program using preferences of patients, partners, providers, payers, and policy makers in the Netherlands. BSiN provides case management support for a period of 6 months. Seven outcomes that previous research has deemed important to complex patients were measured, including physical functioning and social relationships and participation. RESULTS: We find that the program improved the overall MCDA score marginally, and, thus, after 6 and after 12 months, BSiN was preferred to usual care by all stakeholders. BSiN was preferred to usual care, mostly owing to improvements in psychological well-being and social relationships and participation. CONCLUSIONS: The integrated healthcare and social care program BSiN in the Netherlands was preferred to usual care according to an MCDA evaluation. MCDA seems a useful method to evaluate complex programs with benefits beyond health.

Effectiveness of protected areas in reducing deforestation and forest fragmentation in Bangladesh.

The establishment of protected areas has been considered a tool to battle deforestation in densely populated countries like Bangladesh. Since 2000, Bangladesh's Forest Department has declared about 41 protected areas. However, before more land is designated as a protected area, it is important to know how effective existing protected areas are in achieving conservation goals. Unfortunately, the determination of the conservation effectiveness of protected areas, such as their capacity to reduce deforestation and forest fragmentation over a considerable period at high temporal frequency (e.g., yearly), is still unavailable despite some known methods being available, for example, the System for the Integrated Assessment of Protected Areas. In this study, we processed and analyzed the Hansen dataset from 2000 to 2018 to produce yearly forest/non-forest maps of four protected areas in Bangladesh and used these maps, with a matching method, to estimate the effectiveness of protected area in reducing deforestation after controlling for potential hidden bias. We also analyzed the forest fragmentation scenario over the same time frame. The forest cover change results from 2010 to 2018 revealed a large-scale deforestation pattern in areas adjacent to the protected area boundary of Chunati Wildlife Sanctuary (CWS) and Baroiyadhala National Park-Hazarikhil Wildlife Sanctuary (together B-HWS). Using a propensity score matching (PSM) approach with a caliper of 0.25, we found that B-HWS was the best performing of the studied protected areas, and that 37% of forest pixels in B-HWS would have been deforested in 2018 if they had not been brought under protection in 2010. Similarly, the estimated avoided deforestation rates were approximately 21% and 4% for CWS and Dudpukuria-Dhopachari Wildlife Sanctuary, respectively. Despite an improvement in deforestation scenarios, during the period 2010-2018, for all protected areas, the forest fragmentation scenarios were exacerbated both inside their boundaries and in adjacent unprotected areas. Therefore, it remains questionable whether protected areas can ultimately maintain the integrity of conservation.

Pharmacodynamic evaluation of intermittent versus extended and continuous infusions of piperacillin/tazobactam in a hollow-fibre infection model against Klebsiella pneumoniae.

OBJECTIVES: To compare bacterial killing and the emergence of resistance to piperacillin/tazobactam, administered by intermittent versus prolonged infusion (i.e. extended or continuous), for ceftriaxone-resistant Klebsiella pneumoniae clinical isolates in an in vitro dynamic hollow-fibre infection model (HFIM). METHODS: K. pneumoniae 68 (Kp68; MIC = 8 mg/L, producing SHV-106 and DHA-1) and K. pneumoniae 69 (Kp69; MIC = 1 mg/L, producing CTX-M-14) were studied in the HFIM over 7 days (initial inoculum ~107 cfu/mL). Six piperacillin/tazobactam dosing regimens for Kp68 (4/0.5 g 8 hourly as 0.5 and 4 h infusions, 12/1.5 g/24 h continuous infusion, 4/0.5 g 6 hourly as 0.5 and 3 h infusions and 16/2 g/24 h continuous infusion) and three piperacillin/tazobactam dosing regimens for Kp69 (4/0.5 g 8 hourly as 0.5 and 4 h infusions and 12/1.5 g/24 h continuous infusion) were simulated (piperacillin clearance = 14 L/h, creatinine clearance = 100 mL/min). Total and resistant populations and MICs were quantified/determined. RESULTS: For Kp68, all simulated dosing regimens exhibited approximately 4 log10 of bacterial killing at 8 h followed by regrowth to approximately 1011 cfu/mL within 24 h. The MICs for resistant subpopulations exceeded 256 mg/L at 72 h. Similarly, for Kp69, all simulated dosing regimens exhibited approximately 4 log10 of bacterial killing over 8 h; however, only the continuous infusion prevented bacterial regrowth. CONCLUSIONS: Compared with intermittent infusion, prolonged infusion did not increase initial bacterial killing and suppression of regrowth of plasmid-mediated AmpC- and ESBL-producing K. pneumoniae. However, continuous infusion may suppress regrowth of some ESBL-producing susceptible K. pneumoniae, although more data are warranted to confirm this observation.

Evaluation of integrated care services in Catalonia: population-based and service-based real-life deployment protocols.

BACKGROUND: Comprehensive assessment of integrated care deployment constitutes a major challenge to ensure quality, sustainability and transferability of both healthcare policies and services in the transition toward a coordinated service delivery scenario. To this end, the manuscript articulates four different protocols aiming at assessing large-scale implementation of integrated care, which are being developed within the umbrella of the regional project Nextcare (2016-2019), undertaken to foster innovation in technologically-supported services for chronic multimorbid patients in Catalonia (ES) (7.5 M inhabitants). Whereas one of the assessment protocols is designed to evaluate population-based deployment of care coordination at regional level during the period 2011-2017, the other three are service-based protocols addressing: i) Home hospitalization; ii) Prehabilitation for major surgery; and, iii) Community-based interventions for frail elderly chronic patients. All three services have demonstrated efficacy and potential for health value generation. They reflect different implementation maturity levels. While full coverage of the entire urban health district of Barcelona-Esquerra (520 k inhabitants) is the main aim of home hospitalization, demonstration of sustainability at Hospital Clinic of Barcelona constitutes the core goal of the prehabilitation service. Likewise, full coverage of integrated care services addressed to frail chronic patients is aimed at the city of Badalona (216 k inhabitants). METHODS: The population-based analysis, as well as the three service-based protocols, follow observational and experimental study designs using a non-randomized intervention group (integrated care) compared with a control group (usual care) with a propensity score matching method. Evaluation of cost-effectiveness of the interventions using a Quadruple aim approach is a central outcome in all protocols. Moreover, multi-criteria decision analysis is explored as an innovative method for health delivery assessment. The following additional dimensions will also be addressed: i) Determinants of sustainability and scalability of the services; ii) Assessment of the technological support; iii) Enhanced health risk assessment; and, iv) Factors modulating service transferability. DISCUSSION: The current study offers a unique opportunity to undertake a comprehensive assessment of integrated care fostering deployment of services at regional level. The study outcomes will contribute refining service workflows, improving health risk assessment and generating recommendations for service selection. TRIALS REGISTRATION: NCT03130283 (date released 04/06/2018), NCT03768050 (date released 12/05/2018), NCT03767387 (date released 12/05/2018).

Strengthening the evidence-base of integrated care for people with multi-morbidity in Europe using Multi-Criteria Decision Analysis (MCDA).

BACKGROUND: Evaluation of integrated care programmes for individuals with multi-morbidity requires a broader evaluation framework and a broader definition of added value than is common in cost-utility analysis. This is possible through the use of Multi-Criteria Decision Analysis (MCDA). METHODS AND RESULTS: This paper presents the seven steps of an MCDA to evaluate 17 different integrated care programmes for individuals with multi-morbidity in 8 European countries participating in the 4-year, EU-funded SELFIE project. In step one, qualitative research was undertaken to better understand the decision-context of these programmes. The programmes faced decisions related to their sustainability in terms of reimbursement, continuation, extension, and/or wider implementation. In step two, a uniform set of decision criteria was defined in terms of outcomes measured across the 17 programmes: physical functioning, psychological well-being, social relationships and participation, enjoyment of life, resilience, person-centeredness, continuity of care, and total health and social care costs. These were supplemented by programme-type specific outcomes. Step three presents the quasi-experimental studies designed to measure the performance of the programmes on the decision criteria. Step four gives details of the methods (Discrete Choice Experiment, Swing Weighting) to determine the relative importance of the decision criteria among five stakeholder groups per country. An example in step five illustrates the value-based method of MCDA by which the performance of the programmes on each decision criterion is combined with the weight of the respective criterion to derive an overall value score. Step six describes how we deal with uncertainty and introduces the Conditional Multi-Attribute Acceptability Curve. Step seven addresses the interpretation of results in stakeholder workshops. DISCUSSION: By discussing our solutions to the challenges involved in creating a uniform MCDA approach for the evaluation of different programmes, this paper provides guidance to future evaluations and stimulates debate on how to evaluate integrated care for multi-morbidity.

Development of a Label-Free Immunosensor for Clusterin Detection as an Alzheimer's Biomarker.

Clusterin (CLU) has been associated with the clinical progression of Alzheimer's disease (AD) and described as a potential AD biomarker in blood plasma. Due to the enormous attention given to cerebrospinal fluid (CSF) biomarkers for the past couple of decades, recently found blood-based AD biomarkers like CLU have not yet been reported for biosensors. Herein, we report the electrochemical detection of CLU for the first time using a screen-printed carbon electrode (SPCE) modified with 1-pyrenebutyric acid N-hydroxysuccinimide ester (Pyr-NHS) and decorated with specific anti-CLU antibody fragments. This bifunctional linker molecule contains succinylimide ester to bind protein at one end while its pyrene moiety attaches to the carbon surface by means of π-π stacking. Cyclic voltammetric and square wave voltammetric studies showed the limit of detection down to 1 pg/mL and a linear concentration range of 1-100 pg/mL with good sensitivity. Detection of CLU in spiked human plasma was demonstrated with satisfactory recovery percentages to that of the calibration data. The proposed method facilitates the cost-effective and viable production of label-free point-of-care devices for the clinical diagnosis of AD.

Ethnic variation in inflammatory profile in tuberculosis.

Distinct phylogenetic lineages of Mycobacterium tuberculosis (MTB) cause disease in patients of particular genetic ancestry, and elicit different patterns of cytokine and chemokine secretion when cultured with human macrophages in vitro. Circulating and antigen-stimulated concentrations of these inflammatory mediators might therefore be expected to vary significantly between tuberculosis patients of different ethnic origin. Studies to characterise such variation, and to determine whether it relates to host or bacillary factors, have not been conducted. We therefore compared circulating and antigen-stimulated concentrations of 43 inflammatory mediators and 14 haematological parameters (inflammatory profile) in 45 pulmonary tuberculosis patients of African ancestry vs. 83 patients of Eurasian ancestry in London, UK, and investigated the influence of bacillary and host genotype on these profiles. Despite having similar demographic and clinical characteristics, patients of differing ancestry exhibited distinct inflammatory profiles at presentation: those of African ancestry had lower neutrophil counts, lower serum concentrations of CCL2, CCL11 and vitamin D binding protein (DBP) but higher serum CCL5 concentrations and higher antigen-stimulated IL-1 receptor antagonist and IL-12 secretion. These differences associated with ethnic variation in host DBP genotype, but not with ethnic variation in MTB strain. Ethnic differences in inflammatory profile became more marked following initiation of antimicrobial therapy, and immunological correlates of speed of elimination of MTB from the sputum differed between patients of African vs. Eurasian ancestry. Our study demonstrates a hitherto unappreciated degree of ethnic heterogeneity in inflammatory profile in tuberculosis patients that associates primarily with ethnic variation in host, rather than bacillary, genotype. Candidate immunodiagnostics and immunological biomarkers of response to antimicrobial therapy should be derived and validated in tuberculosis patients of different ethnic origin.

Tridax procumbens flavonoids promote osteoblast differentiation and bone formation.

BACKGROUND: Tridax procumbens flavonoids (TPFs) are well known for their medicinal properties among local natives. Besides traditionally used for dropsy, anemia, arthritis, gout, asthma, ulcer, piles, and urinary problems, it is also used in treating gastric problems, body pain, and rheumatic pains of joints. TPFs have been reported to increase osteogenic functioning in mesenchymal stem cells. Our previous study showed that TPFs were significantly suppressed the RANKL-induced differentiation of osteoclasts and bone resorption. However, the effects of TPFs to promote osteoblasts differentiation and bone formation remain unclear. TPFs were isolated from Tridax procumbens and investigated for their effects on osteoblasts differentiation and bone formation by using primary mouse calvarial osteoblasts. RESULTS: TPFs promoted osteoblast differentiation in a dose-dependent manner demonstrated by up-regulation of alkaline phosphatase and osteocalcin. TPFs also upregulated osteoblast differentiation related genes, including osteocalcin, osterix, and Runx2 in primary osteoblasts. TPFs treated primary osteoblast cells showed significant upregulation of bone morphogenetic proteins (BMPs) including Bmp-2, Bmp-4, and Bmp-7. Addition of noggin, a BMP specific-antagonist, inhibited TPFs induced upregulation of the osteocalcin, osterix, and Runx2. CONCLUSION: Our findings point towards the induction of osteoblast differentiation by TPFs and suggested that TPFs could be a potential anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis.

Flavonoids isolated from Tridax procumbens (TPF) inhibit osteoclasts differentiation and bone resorption.

BACKGROUND: The Tridax procumbens flavonoids (TPF), are well known for their medicinal properties among local natives. The TPF are traditionally used for dropsy, anaemia, arthritis, gout, asthma, ulcer, piles, and urinary problems. It also used in treating gastric problems, body pain, and rheumatic pains of joints. The TPF have been reported to increase osteogenic functioning in mesenchymal stem cells. However, their effects on osteoclastogenesis remain unclear. The TPF isolated from T. procumbens and investigated the effects of the TPF inhibit on osteoclast differentiation and bone resorption activities using primary osteoclastic cells. Osteoclast formation was assessed by counting the number of tartrate resistant acid phosphatase (TRAP) positive multinucleated cells and by measuring both TRAP activities. RESULTS: The TPF significantly suppressed the RANKL-induced differentiation of osteoclasts and the formation of pits in primary osteoclastic cells. The TPF also decreased the expression of mRNAs related to osteoclast differentiation, including Trap, Cathepsin K, Mmp-9, and Mmp-13 in primary osteoclastic cells. The treatment of primary osteoclastic cells with the TPF decreased Cathepsin K, Mmp-9, and Mmp-13 proteins expression in primary osteoclastic cells. CONCLUSION: These results indicated that TPF inhibit osteoclastogenesis and pits formation activities. Our results suggest that the TPF could be a potential anti-bone resorptic agent to treat patients with bone loss-associated diseases such as osteoporosis.

Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment.

Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.

Microchip capillary electrophoresis based electroanalysis of triazine herbicides.

The number of pesticides used in agriculture is increasing steadily, leading to contamination of soil and drinking water. Herein, we present a microfluidic platform to detect the extent of contamination in soil samples. A microchip capillary electrophoresis system with in-channel electrodes was fabricated for label-free electroanalytical detection of triazine herbicides. The sample mixture contained three representative triazines: simazine, atrazine and ametryn. The electropherogram for each individual injection of simazine, atrazine and ametryn showed peaks at 58, 66 and 72 s whereas a mixture of them showed distinct peaks at 59, 67 and 71 s respectively. The technique as such may prove to be a useful qualitative and quantitative tool for the similar environmental pollutants.