Lymphatic filariasis epidemiology in Samoa in 2018: Geographic clustering and higher antigen prevalence in older age groups

BackgroundSamoa conducted eight nationwide rounds of mass drug administration (MDA) for lymphatic filariasis (LF) between 1999 and 2011, and two targeted rounds in 2015 and 2017 in North West Upolu (NWU), one of three evaluation units (EUs). Transmission Assessment Surveys (TAS) were conducted in 2013 (failed in NWU) and 2017 (all three EUs failed). In 2018, Samoa was the first in the world to distribute nationwide triple-drug MDA using ivermectin, diethylcarbamazine, and albendazole. Surveillance and Monitoring to Eliminate LF and Scabies from Samoa (SaMELFS Samoa) is an operational research program designed to evaluate the effectiveness of triple-drug MDA on LF transmission and scabies prevalence in Samoa, and to compare the usefulness of different indicators of LF transmission. This paper reports results from the 2018 baseline survey and aims to i) investigate antigen (Ag) prevalence and spatial epidemiology, including geographic clustering; ii) compare Ag prevalence between two different age groups (5–9 years versus ≥10 years) as indicators of areas of ongoing transmission; and iii) assess the prevalence of limb lymphedema in those aged ≥15 years.MethodsA community-based cluster survey was conducted in 30 randomly selected and five purposively selected clusters (primary sampling units, PSUs), each comprising one or two villages. Participants were recruited through household surveys (age ≥5 years) and convenience surveys (age 5–9 years). Alere Filariasis Test Strips (FTS) were used to detect Ag, and prevalence was adjusted for survey design and standardized for age and gender. Adjusted Ag prevalence was estimated for each age group (5–9, ≥10, and all ages ≥5 years) for random and purposive PSUs, and by region. Intraclass correlation (ICC) was used to quantify clustering at regions, PSUs, and households.ResultsA total of 3940 persons were included (1942 children aged 5–9 years, 1998 persons aged ≥10 years). Adjusted Ag prevalence in all ages ≥5 years in randomly and purposively selected PSUs were 4.0% (95% CI 2.8–5.6%) and 10.0% (95% CI 7.4–13.4%), respectively. In random PSUs, Ag prevalence was lower in those aged 5–9 years (1.3%, 95% CI 0.8–2.1%) than ≥10 years (4.7%, 95% CI 3.1–7.0%), and poorly correlated at the PSU level (R-square = 0.1459). Adjusted Ag prevalence in PSUs ranged from 0% to 10.3% (95% CI 5.9–17.6%) in randomly selected and 3.8% (95% CI 1.3–10.8%) to 20.0% (95% CI 15.3–25.8%) in purposively selected PSUs. ICC for Ag-positive individuals was higher at households (0.46) compared to PSUs (0.18) and regions (0.01).ConclusionsOur study confirmed ongoing transmission of LF in Samoa, in accordance with the 2017 TAS results. Ag prevalence varied significantly between PSUs, and there was poor correlation between prevalence in 5–9 year-olds and older ages, who had threefold higher prevalence. Sampling older age groups would provide more accurate estimates of overall prevalence, and be more sensitive for identifying residual hotspots. Higher prevalence in purposively selected PSUs shows local knowledge can help identify at least some hotspots.     

Identification of bacteria in culture negative and polymerase chain reaction (PCR) positive intraocular specimen from patients with infectious endopthalmitis

A novel Denaturing High-Performance Liquid Chromatography (dHPLC)-based technique allows rapid high-resolution analysis of PCR products. We show the application of this PCR/dHPLC approach for direct detection and identification of bacterium from the Eubacterial PCR amplified products of aqueous and vitreous aspirates from patients with endopthalmitis and to differentially identify the culture negative cases and initiate appropriate therapy. The aim of this study is to identify culture negative PCR positive cases by the application of PCR based DNA sequencing. A total of 116 intraocular specimens were subjected for the study. Sixty-nine different bacteria were identified using dHPLC based DNA sequencing of which predominant ones were Gram-positive bacteria and cannot be cultured by conventional methods. Forty eight different bacteria detected in this study is being reported for the first time in infectious endopthalmitis.     

The human ubiquitin C promoter drives selective expression in principal neurons in the brain of a transgenic mouse line

The specificity of promoters used to drive the expression of proteins of interest is a crucial determinant of transgenesis. Numerous strategies have been developed to restrict expression on a certain cell population. On the other hand it has also remained challenging to obtain ubiquitous expression of transgenes which is needed for example to generate recombination reporter mice or to induce expression by recombination mediated excision of STOP-cassettes. We have generated transgenic mice with the expression of nuclear β-galactosidase driven by the human ubiquitin C promoter thought to mediate ubiquitous expression. However, in the brains of these transgenic mice the expression of the transgene was strikingly limited to principal neurons, while no expression was detected in interneurons or glial cells. These results indicate that the human ubiquitin C promoter might be useful to selectively target projections neurons of the brain.     

The effects of periodized concurrent and aerobic training on oxidative stress parameters, endothelial function and immune response in sedentary male individuals of middle age

The vascular endothelium plays a key role in arterial wall homeostasis by preventing atherosclerotic plaque formation. A primary causal factor of endothelial dysfunction is the reactive oxygen species. Aerobic exercise is ascribed as an important adjuvant therapy in endothelium‐dependent cardiovascular disease. However, little is known about the effects of concurrent (aerobic + strength) training on that. For a comparison of the effects of aerobic and concurrent physical training on endothelial function, oxidative stress parameters and the immunoinflammatory activity of monocytes/macrophages, 20 adult male volunteers of middle age were divided into a concurrent training (CT) programme group and an aerobic training group. The glutathione disulphide to glutathione ratio (GSSG/GSH) and plasma lipoperoxide (LPO) levels, as well as flow‐mediated dilation (FMD), monocyte/macrophage functional activity (zymosan phagocytosis), body lipid profiles, aerobic capacity (maximal oxygen uptake) and strength parameters (one‐repetition maximum test), were measured before and after the exercise training programmes. The CT exhibited reduced acute effects of exercise on the GSSG/GSH ratio, plasma LPO levels and zymosan phagocytosis. The CT also displayed improved lipid profiles, glycaemic control, maximal oxygen uptake and one‐repetition maximum test values. In both the aerobic training and the CT, training improved the acute responses to exercise, as inferred from a decrease in the GSSG/GSH ratios. The aerobic sessions did not alter basal levels of plasma LPO or macrophage phagocytic activity but improved FMD values as well as lipid profiles and glycaemic control. In summary, both training programmes improve systemic redox status and antioxidant defences. However, the aerobic training was more efficient in improving FMD in the individuals studied. Copyright © 2011 John Wiley & Sons, Ltd.     

53BP1 and MDC1 foci formation in HT-1080 cells for low- and high-LET microbeam irradiations

An improved assessment of the biological effects and related risks of low doses of ionizing radiation is currently an important issue in radiation biology. Irradiations using microbeams are particularly well suited for precise and localized dose depositions, whereas recombinant cell lines with fluorescent proteins allow the live observation of radiation-induced foci. Living cells of the fibrosarcoma cell line HT-1080 stably expressing 53BP1 or full-length reconstituted MDC1 fused to Green Fluorescent Protein (GFP) were irradiated with protons and α-particles of linear energy transfers (LETs) of 15 and 75 keV/μm, respectively. Using a microbeam, the irradiations were carried out in line patterns, which facilitated the discrimination between undefined background and radiation-induced foci. As expected, foci formation and respective kinetics from α-particle irradiations with a high LET of 75 keV/μm could be detected in a reliable manner by both fusion proteins, as reported previously. Colocalization of γ-H2AX foci confirmed the DSB nature of the detected foci. As a novel result, the application of protons with low LET of 15 keV/μm generated 53BP1- and MDC1-mediated foci of almost equal size and slightly different kinetics. This new data expands the capability of 53BP1 and wild-type MDC1 on visible foci formation in living cells after irradiation with low-LET particles. Furthermore, the kinetics in HT-1080 cells for α-particle irradiation show a delay of about 20 s for 53BP1 foci detection compared to wild-type MDC1, confirming the hierarchical assembly of both proteins. Preliminary data for proton irradiations are shown and also these indicate a delay for 53BP1 versus MDC1.     

Protein myozap — a late addition to the molecular ensembles of various kinds of adherens junctions

The protein myozap, a polypeptide of 54 kDa, has recently been identified as a component of the cytoplasmic plaques of the composite junctions (areae compositae) in the myocardiac intercalated disks and of the adherens junctions (AJs) in vascular endothelia. Now we report that using very sensitive new antibodies and drastic localization methods, we have also identified this protein as a component of the AJ plaques in simple and complex epithelia, in the adluminal cell layer of the transitional epithelium of the urinary tract and in certain cell layers of diverse stratified epithelia, including gingiva, tongue, pharynx and esophagus, cervix, vagina and epidermis. Myozap has not been identified in desmosomal and tight junction plaques. We have also detected protein myozap in AJ structures of carcinomas. The discovery of a novel major protein in AJ plaques now calls for re-examinations of molecular interactions in AJ formation and maintenance and also offers a new marker for diagnostic immunocytochemistry. We also discuss the need for progressive unravelling, extractive treatments and buffer rinses of sections and cultured cells to reveal obscured or masked antigens, before definitive negative conclusions in immunohistochemistry can be made.     

Cassava: constraints to production and the transfer of biotechnology to African laboratories

Knowledge and technology transfer to African institutes is an important objective to help achieve the United Nations Millennium Development Goals. Plant biotechnology in particular enables innovative advances in agriculture and industry, offering new prospects to promote the integration and dissemination of improved crops and their derivatives from developing countries into local markets and the global economy. There is also the need to broaden our knowledge and understanding of cassava as a staple food crop. Cassava (Manihot esculenta Crantz) is a vital source of calories for approximately 500 million people living in developing countries. Unfortunately, it is subject to numerous biotic and abiotic stresses that impact on production, consumption, marketability and also local and country economics. To date, improvements to cassava have been led via conventional plant breeding programmes, but with advances in molecular-assisted breeding and plant biotechnology new tools are being developed to hasten the generation of improved farmer-preferred cultivars. In this review, we report on the current constraints to cassava production and knowledge acquisition in Africa, including a case study discussing the opportunities and challenges of a technology transfer programme established between the Mikocheni Agricultural Research Institute in Tanzania and Europe-based researchers. The establishment of cassava biotechnology platform(s) should promote research capabilities in African institutions and allow scientists autonomy to adapt cassava to suit local agro-ecosystems, ultimately serving to develop a sustainable biotechnology infrastructure in African countries.     

Estimation of human circadian phase via a multi-channel ambulatory monitoring system and a multiple regression model

Reliable detection of circadian phase in humans using noninvasive ambulatory measurements in real-life conditions is challenging and still an unsolved problem. The masking effects of everyday behavior and environmental input such as physical activity and light on the measured variables need to be considered critically. Here, we aimed at developing techniques for estimating circadian phase with the lowest subject burden possible, that is, without the need of constant routine (CR) laboratory conditions or without measuring the standard circadian markers, (rectal) core body temperature (CBT), and melatonin levels. In this validation study, subjects (N = 16) wore multi-channel ambulatory monitoring devices and went about their daily routine for 1 week. The devices measured a large number of physiological, behavioral, and environmental variables, including CBT, skin temperatures, cardiovascular and respiratory function, movement/posture, ambient temperature, and the spectral composition and intensity of light received at eye level. Sleep diaries were logged electronically. After the ambulatory phase, subjects underwent a 32-h CR procedure in the laboratory for measuring unmasked circadian phase based on the "midpoint" of the salivary melatonin profile. To overcome the complex masking effects of confounding variables during ambulatory measurements, multiple regression techniques were applied in combination with the cross-validation approach to subject-independent prediction of circadian phase. The most accurate estimate of circadian phase was achieved using skin temperatures, irradiance for ambient light in the blue spectral band, and motion acceleration as predictors with lags of up to 24 h. Multiple regression showed statistically significant improvement of variance of prediction error over the traditional approaches to determining circadian phase based on single predictors (motion acceleration or sleep log), although CBT was intentionally not included as the predictor. Compared to CBT alone, our method resulted in a 40% smaller range of prediction errors and a nonsignificant reduction of error variance. The proposed noninvasive measurement method could find applications in sleep medicine or in other domains where knowing the exact endogenous circadian phase is important (e.g., for the timing of light therapy).     

The BapF protein from Pseudomonas aeruginosa is a β-peptidyl aminopeptidase

A gene encoding a so far uncharacterized β-peptidyl aminopeptidase from the opportunistic human pathogen Pseudomonas aeruginosa PAO1 was cloned and actively expressed in the heterologue host Escherichia coli. The gene was identified in the genome sequence by its homology to the S58 family of peptidases. The sequence revealed an open reading frame of 1,101 bp with a deduced amino acid sequence of 366 amino acids. The gene was amplified by PCR, ligated into pET22b(+) and was successfully expressed in E. coli BL21 (DE3). It was shown that the enzyme consists of two polypeptides (α- and β-subunit), which are processed from the precursor. The enzyme is specific for N-terminal β-alanyl dipeptides (β-Ala-Xaa). BapF hydrolyses efficiently β-alanine at the N-terminal position, including H-β³hAla-pNA, H–D-β³hAla-pNA and β-Ala-l-His (l-carnosine). d- and l-alaninamide were also hydrolysed by the enzyme.     

A mathematical model to design a lignocellulosic biofuel supply chain system with a case study based on a region in Central Texas

This study formulates a model to maximize the profit of a lignocellulosic biofuel supply chain ranging from feedstock suppliers to biofuel customers. The model deals with a time-staged, multi-commodity, production/distribution system, prescribing facility locations and capacities, technologies, and material flows. A case study based on a region in Central Texas demonstrates application of the proposed model to design the most profitable biofuel supply chain under each of several scenarios. A sensitivity analysis identifies that ethanol (ETOH) price is the most significant factor in the economic viability of a lignocellulosic biofuel supply chain.