The burden of neglected tropical diseases in Ethiopia, and opportunities for integrated control and elimination

Background: Neglected tropical diseases (NTDs) are a group of chronic parasitic diseases and related conditions that are the most common diseases among the 2·7 billion people globally living on less than US$2 per day. In response to the growing challenge of NTDs, Ethiopia is preparing to launch a NTD Master Plan. The purpose of this review is to underscore the burden of NTDs in Ethiopia, highlight the state of current interventions, and suggest ways forward. Results: This review indicates that NTDs are significant public health problems in Ethiopia. From the analysis reported here, Ethiopia stands out for having the largest number of NTD cases following Nigeria and the Democratic Republic of Congo. Ethiopia is estimated to have the highest burden of trachoma, podoconiosis and cutaneous leishmaniasis in sub-Saharan Africa (SSA), the second highest burden in terms of ascariasis, leprosy and visceral leishmaniasis, and the third highest burden of hookworm. Infections such as schistosomiasis, trichuriasis, lymphatic filariasis and rabies are also common. A third of Ethiopians are infected with ascariasis, one quarter is infected with trichuriasis and one in eight Ethiopians lives with hookworm or is infected with trachoma. However, despite these high burdens of infection, the control of most NTDs in Ethiopia is in its infancy. In terms of NTD control achievements, Ethiopia reached the leprosy elimination target of 1 case/10,000 population in 1999. No cases of human African trypanosomiasis have been reported since 1984. Guinea worm eradication is in its final phase. The Onchocerciasis Control Program has been making steady progress since 2001. A national blindness survey was conducted in 2006 and the trachoma program has kicked off in some regions. Lymphatic Filariasis, podoconiosis and rabies mapping are underway. Conclusion: Ethiopia bears a significant burden of NTDs compared to other SSA countries. To achieve success in integrated control of NTDs, integrated mapping, rapid scale up of interventions and operational research into co implementation of intervention packages will be crucial

Identifying Critical Non-Catalytic Residues that Modulate Protein Kinase A Activity

Distal interactions between discrete elements of an enzyme are critical for communication and ultimately for regulation. However, identifying the components of such interactions has remained elusive due to the delicate nature of these contacts. Protein kinases are a prime example of an enzyme with multiple regulatory sites that are spatially separate, yet communicate extensively for tight regulation of activity. Kinase misregulation has been directly linked to a variety of cancers, underscoring the necessity for understanding intramolecular kinase regulation.A genetic screen was developed to identify suppressor mutations that restored catalytic activity in vivo from two kinase-dead Protein Kinase A mutants in S. cerevisiae. The residues defined by the suppressors provide new insights into kinase regulation. Many of the acquired mutations were distal to the nucleotide binding pocket, highlighting the relationship of spatially dispersed residues in regulation.The suppressor residues provide new insights into kinase regulation, including allosteric effects on catalytic elements and altered protein-protein interactions. The suppressor mutations identified in this study also share overlap with mutations identified from an identical screen in the yeast PKA homolog Tpk2, demonstrating functional conservation for some residues. Some mutations were independently isolated several times at the same sites. These sites are in agreement with sites previously identified from multiple cancer data sets as areas where acquired somatic mutations led to cancer progression and drug resistance. This method provides a valuable tool for identifying residues involved in kinase activity and for studying kinase misregulation in disease states

The Mothers and Children’s Environmental Health (MOCEH) study

The MOCEH study is a prospective hospital- and community-based cohort study designed to collect information related to environmental exposures (chemical, biological, nutritional, physical, and psychosocial) during pregnancy and childhood and to examine how exposure to environmental pollutants affects growth, development, and disease. The MOCEH network includes one coordinating center, four local centers responsible for recruiting pregnant women, and four evaluation centers (a nutrition center, bio-repository center, neurocognitive development center, and environment assessment center). At the local centers, trained nurses interview the participants to gather information regarding their demographic and socioeconomic characteristics, complications related to the current gestation period, health behaviors and environmental factors. These centers also collect samples of blood, placenta, urine, and breast milk. Environmental hygienists measure each participant’s level of exposure to indoor and outdoor pollutants during the pre- and postnatal periods. The participants are followed up through delivery and until the child is 5 years of age. The MOCEH study plans to recruit 1,500 pregnant women between 2006 and 2010 and to perform follow-up studies on their children. We expect this study to provide evidence to support the hypothesis that the gestational environment has an effect on the development of diseases during adulthood. We also expect the study results to enable evaluation of latency and age-specific susceptibility to exposure to hazardous environmental pollutants, evaluation of growth retardation focused on environmental and genetic risk factors, selection of target environmental diseases in children, development of an environmental health index, and establishment of a national policy for improving the health of pregnant women and their children

Podoconiosis, trachomatous trichiasis and cataract in northern Ethiopia: a comparative cross-sectional study

Background: Rural populations in low-income countries commonly suffer from the co-morbidity of neglected tropical diseases (NTDs). Podoconiosis, trachomatous trichiasis (both NTDs) and cataract are common causes of morbidity among subsistence farmers in the highlands of northern Ethiopia. We explored whether podoconiosis was associated with cataract or trachomatous trichiasis (TT) among this population. Methods: A comparative cross-sectional study was conducted in East Gojam region, Amhara, Ethiopia in May 2016 . Data were collected from patients previously identified as having podoconiosis and from matched healthy neighbourhood controls. Information on socio- demographic factors, clinical factors and past medical history were collected by an interview-administered questionnaire. Clinical examination involved grading of podoconiosis by examination of both legs, measurement of visual acuity, direct ophthalmoscopy of dilated pupils to grade cataract, and eyelid and corneal examination to grade trachoma. Multiple logistic regression was conducted to estimate independent association and correlates of podoconiosis, TT and cataract. Findings: A total of 700 participants were included in this study; 350 podoconiosis patients and 350 healthy neighbourhood controls. The prevalence of TT was higher among podoconiosis patients than controls (65 (18.6%) vs 43 (12.3%)) with an adjusted odds ratio (OR) 1.55 (95% Confidence Interval (CI) 1.12 - 2.11), p=0.05. There was no significant difference in 3 prevalence of cataract between the two populations with an adjusted OR 0.83 (95% CI 0.55-1.38), p=0.37. Mean best visual acuity was 0.59 (SD +/- 0.06) in podoconiosis cases compared to 0.44 (SD +/- 0.04) in controls, p=< 0.001. The proportion of patients classified as blind was higher in podoconiosis cases compared with healthy controls; 5.6% vs 2.0%; adjusted OR 2.63 (1.08-6.39), P = 0.03. Conclusions Individuals with podoconiosis have a higher burden of TT and worse visual acuity than their matched healthy neighbourhood controls. Further research into the environmental and biological reasons for this co-morbidity is required. A shared approach to managing these two NTDs within the same population could be beneficial

Perioperative mortality after hemiarthroplasty related to fixation method: A study based on the Australian Orthopaedic Association National Joint Replacement Registry

Background and purpose: The appropriate fixation method for hemiarthroplasty of the hip as it relates to implant survivorship and patient mortality is a matter of ongoing debate. We examined the influence of fixation method on revision rate and mortality.----- ----- Methods: We analyzed approximately 25,000 hemiarthroplasty cases from the AOA National Joint Replacement Registry. Deaths at 1 day, 1 week, 1 month, and 1 year were compared for all patients and among subgroups based on implant type.----- ----- Results: Patients treated with cemented monoblock hemiarthroplasty had a 1.7-times higher day-1 mortality compared to uncemented monoblock components (p < 0.001). This finding was reversed by 1 week, 1 month, and 1 year after surgery (p < 0.001). Modular hemiarthroplasties did not reveal a difference in mortality between fixation methods at any time point.----- ----- Interpretation: This study shows lower (or similar) overall mortality with cemented hemiarthroplasty of the hip

A Novel Genetic Screen Implicates Elm1 in the Inactivation of the Yeast Transcription Factor SBF

BACKGROUND: Despite extensive large scale analyses of expression and protein-protein interactions (PPI) in the model organism Saccharomyces cerevisiae, over a thousand yeast genes remain uncharacterized. We have developed a novel strategy in yeast that directly combines genetics with proteomics in the same screen to assign function to proteins based on the observation of genetic perturbations of sentinel protein interactions (GePPI). As proof of principle of the GePPI screen, we applied it to identify proteins involved in the regulation of an important yeast cell cycle transcription factor, SBF that activates gene expression during G1 and S phase. METHODOLOGY/PRINCIPLE FINDINGS: The principle of GePPI is that if a protein is involved in a pathway of interest, deletion of the corresponding gene will result in perturbation of sentinel PPIs that report on the activity of the pathway. We created a fluorescent protein-fragment complementation assay (PCA) to detect the interaction between Cdc28 and Swi4, which leads to the inactivation of SBF. The PCA signal was quantified by microscopy and image analysis in deletion strains corresponding to 25 candidate genes that are periodically expressed during the cell cycle and are substrates of Cdc28. We showed that the serine-threonine kinase Elm1 plays a role in the inactivation of SBF and that phosphorylation of Elm1 by Cdc28 may be a mechanism to inactivate Elm1 upon completion of mitosis. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that GePPI is an effective strategy to directly link proteins of known or unknown function to a specific biological pathway of interest. The ease in generating PCA assays for any protein interaction and the availability of the yeast deletion strain collection allows GePPI to be applied to any cellular network. In addition, the high degree of conservation between yeast and mammalian proteins and pathways suggest GePPI could be used to generate insight into human disease

Minimally invasive and computer-navigated total hip arthroplasty: a qualitative and systematic review of the literature

ABSTRACT: BACKGROUND: Both minimally invasive surgery (MIS) and computer-assisted surgery (CAS) for total hip arthroplasty (THA) have gained popularity in recent years. We conducted a qualitative and systematic review to assess the effectiveness of MIS, CAS and computer-assisted MIS for THA. METHODS: An extensive computerised literature search of PubMed, Medline, Embase and OVIDSP was conducted. Both randomised clinical trials and controlled clinical trials on the effectiveness of MIS, CAS and computer-assisted MIS for THA were included. Methodological quality was independently assessed by two reviewers. Effect estimates were calculated and a best-evidence synthesis was performed. RESULTS: Four high-quality and 14 medium-quality studies with MIS THA as study contrast, and three high-quality and four medium-quality studies with CAS THA as study contrast were included. No studies with computer-assisted MIS for THA as study contrast were identified. Strong evidence was found for a decrease in operative time and intraoperative blood loss for MIS THA, with no difference in complication rates and risk for acetabular outliers. Strong evidence exists that there is no difference in physical functioning, measured either by questionnaires or by gait analysis. Moderate evidence was found for a shorter length of hospital stay after MIS THA. Conflicting evidence was found for a positive effect of MIS THA on pain in the early postoperative period, but that effect diminished after three months postoperatively. Strong evidence was found for an increase in operative time for CAS THA, and limited evidence was found for a decrease in intraoperative blood loss. Furthermore, strong evidence was found for no difference in complication rates, as well as for a significantly lower risk for acetabular outliers. CONCLUSIONS: The results indicate that MIS THA is a safe surgical procedure, without increases in operative time, blood loss, operative complication rates and component malposition rates. However, the beneficial effect of MIS THA on functional recovery has to be proven. The results also indicate that CAS THA, though resulting in an increase in operative time, may have a positive effect on operative blood loss and operative complication rates. More importantly, the use of CAS results in better positioning of acetabular component of the prosthesis

Adaptive Melanin Response of the Soil Fungus Aspergillus niger to UV Radiation Stress at “Evolution Canyon”, Mount Carmel, Israel

BACKGROUND:Adaptation is an evolutionary process in which traits in a population are tailored by natural selection to better meet the challenges presented by the local environment. The major discussion relating to natural selection concerns the portraying of the cause and effect relationship between a presumably adaptive trait and selection agents generating it. Therefore, it is necessary to identify trait(s) that evolve in direct response to selection, enhancing the organism's fitness. "Evolution Canyon" (EC) in Israel mirrors a microcosmic evolutionary system across life and is ideal to study natural selection and local adaptation under sharply, microclimatically divergent environments. The south-facing, tropical, sunny and xeric "African" slope (AS) receives 200%-800% higher solar radiation than the north-facing, temperate, shady and mesic "European" slope (ES), 200 meters apart. Thus, solar ultraviolet radiation (UVR) is a major selection agent in EC influencing the organism-environment interaction. Melanin is a trait postulated to have evolved for UV-screening in microorganisms. Here we investigate the cause and effect relationship between differential UVR on the opposing slopes of EC and the conidial melanin concentration of the filamentous soil fungus Aspergillus niger. We test the working hypothesis that the AS strains exhibit higher melanin content than strains from the ES resulting in higher UV resistance. METHODOLOGY/PRINCIPAL FINDINGS:We measured conidial melanin concentration of 80 strains from the EC using a spectrophotometer. The results indicated that mean conidial melanin concentration of AS strains were threefold higher than ES strains and the former resisted UVA irradiation better than the latter. Comparisons of melanin in the conidia of A. niger strains from sunny and shady microniches on the predominantly sunny AS and predominantly shady ES indicated that shady conditions on the AS have no influence on the selection on melanin; in contrast, the sunny strains from the ES displayed higher melanin concentrations. CONCLUSIONS/SIGNIFICANCE:We conclude that melanin in A. niger is an adaptive trait against UVR generated by natural selection

Accuracy of biplane x-ray imaging combined with model-based tracking for measuring in-vivo patellofemoral joint motion

<p>Abstract</p> <p>Background</p> <p>Accurately measuring <it>in-vivo</it> motion of the knee's patellofemoral (PF) joint is challenging. Conventional measurement techniques have largely been unable to accurately measure three-dimensional, <it>in-vivo</it> motion of the patella during dynamic activities. The purpose of this study was to assess the accuracy of a new model-based technique for measuring PF joint motion.</p> <p>Methods</p> <p>To assess the accuracy of this technique, we implanted tantalum beads into the femur and patella of three cadaveric knee specimens and then recorded dynamic biplane radiographic images while manually flexing and extending the specimen. The position of the femur and patella were measured from the biplane images using both the model-based tracking system and a validated dynamic radiostereometric analysis (RSA) technique. Model-based tracking was compared to dynamic RSA by computing measures of bias, precision, and overall dynamic accuracy of four clinically-relevant kinematic parameters (patellar shift, flexion, tilt, and rotation).</p> <p>Results</p> <p>The model-based tracking technique results were in excellent agreement with the RSA technique. Overall dynamic accuracy indicated errors of less than 0.395 mm for patellar shift, 0.875° for flexion, 0.863° for tilt, and 0.877° for rotation.</p> <p>Conclusion</p> <p>This model-based tracking technique is a non-invasive method for accurately measuring dynamic PF joint motion under <it>in-vivo</it> conditions. The technique is sufficiently accurate in measuring clinically relevant changes in PF joint motion following conservative or surgical treatment.</p