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PLoS currents [journal]
- A summary case report on the health impacts and response to the pakistan floods of 2010. [Journal Article]
- PLoS Curr 2013.
In July 2010, Pakistan suffered nationwide floods after unprecedented monsoon rains overwhelmed the Indus basin. The ensuing floods claimed 1985 lives, injured 2946 people and affected over 20.2 million people. Seventy-eight out of 121 districts were affected and at one stage one-fifth of the country's land was inundated with water. Indiscriminate damage was caused to housing, educational and health facilities, communication networks, power plants and grids, irrigation channels, agricultural land and livestock. Over 37 million medical consultations were reported within one year of the floods with acute respiratory infection, skin diseases, acute diarrhoea and suspected malaria forming the most common presentations. Rescue and relief operations were organised through the National Disaster Management Authority and a UN Cluster Approach was adopted for providing humanitarian assistance. The Office for the Coordination of Humanitarian Affairs (OCHA) played a pivotal role in coordinating relief efforts between cluster groups and providing communication platforms for identifying gaps and sharing information. This paper attempts to collate information available in the public domain into a summary report based on key principles described by Kulling et al. (2010) on health crisis reporting.
On 11 August 2012, twin earthquakes measured 6.3 and 6.4 on the Richter scale hit three towns (Ahar, Varzaqan, and Heris) in East Azerbaijan Province, Iran resulting in tragic loss of three hundred lives and leaving thousands of injured. The aim of the present study was to report the spinal injuries during recent earthquake in northwest Iran, its consequences and management. Of the 923 hospitalized patients, 26 (2.8%) had neurosurgical complications. The imaging and clinical data of the patients were retrospectively studied regarding the anatomical location of the injury, the severity of spinal injury and associated neurological deficit. To further analyze the findings, Magerl (AO) and Frankel's classifications were used. The injuries without any fracture were considered as minor spinal injuries. The mean age of the patients was 44.54±22.52 (range: 5-88) years. We detected a total of 38 vertebral injuries including 24 major (63.15%) and 14 minor injuries (36.85%). The most common injuries were observed in the lumbar spine (19 injuries, 50%). The 24 major injuries chiefly included Magerl type A (14 injuries, 58.3%). According to the Frankel's classification, majority of the patients (88.46%) had no neurological deficit. In this study, three patients had nerve injuries. In conclusion, the number and proportion of spinal fractures patients in the recent twin earthquakes, northwest Iran was limited and caused less nerve injuries compared to the previous similar disasters. This might be due to the milder earthquake consequences since the incident happened in the middle of the day when men were working their fields. Potential complications in patients traumatized in earthquake incidents should be monitored for and early assessment of the neurological function is required to prioritize care for the victims.
- Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model. [Journal Article]
- PLoS Curr 2013.
Metabolic dysfunction and mitochondrial involvement are recognised as part of the pathology in Huntington's Disease (HD). Post-mortem examinations of the striatum from end-stage HD patients have shown a decrease in the in vitro activity of complexes II, III and IV of the electron transport system (ETS). In different models of HD, evidence of enzyme defects have been reported in complex II and complex IV using enzyme assays. However, such assays are highly variable and results have been inconsistent. We investigated the integrated ETS function ex vivo using a sensitive high-resolution respirometric (HRR) method. The O2 flux in a whole-cell sample combined with the addition of mitochondrial substrates, uncouplers and inhibitors enabled us to accurately quantitate the function of individual mitochondrial complexes in intact mitochondria, while retaining mitochondrial regulation and compensatory mechanisms. We used HRR to examine the mitochondrial function in striata from 12-week old R6/2 mice expressing exon 1 of human HTT with 130 CAG repeats. A significant reduction in complex II and complex IV flux control ratios was found in the R6/2 mouse striatum at 12 weeks of age compared to controls, confirming previous findings obtained with spectrophotometric enzyme assays.
Multicopper blue proteins, composed of several repetitive copper-binding domains similar to one-domain cupredoxin-like proteins, were found in almost all organisms. They are classified into the three different groups, based on their two-, three- or six-domain organization. We found orthologs of chordate six-domain copper-binding proteins in animals, plants, bacteria and archea. The phylogenetic analysis of 183 multicopper blue proteins and their copper-binding sites comparison make us think that all the modern six-domain blue proteins have originated from the common ancestral six-domain protein in the process of gene duplication and copper-binding sites loss as a result of amino acid substitutions.
- Proof of concept of the ability of the kinect to quantify upper extremity function in dystrophinopathy. [Journal Article]
- PLoS Curr 2013.
Individuals with dystrophinopathy lose upper extremity strength in proximal muscles followed by those more distal. Current upper extremity evaluation tools fail to fully capture changes in upper extremity strength and function across the disease spectrum as they tend to focus solely on distal ability. The Kinect by Microsoft is a gaming interface that can gather positional information about an individual's upper extremity movement which can be used to determine functional reaching volume, velocity of movement, and rate of fatigue while playing an engaging video game. The purpose of this study was to determine the feasibility of using the Kinect platform to assess upper extremity function in individuals with dystrophinopathy across the spectrum of abilities.Investigators developed a proof-of-concept device, ACTIVE (Abilities Captured Through Interactive Video Evaluation), to measure functional reaching volume, movement velocity, and rate of fatigue. Five subjects with dystrophinopathy and 5 normal controls were tested using ACTIVE during one testing session. A single subject with dystrophinopathy was simultaneously tested with ACTIVE and a marker-based motion analysis system to establish preliminary validity of measurements.ACTIVE proof-of-concept ranked the upper extremity abilities of subjects with dystrophinopathy by Brooke score, and also differentiated them from performance of normal controls for the functional reaching volume and velocity tests. Preliminary test-retest reliability of the ACTIVE for 2 sequential trials was excellent for functional reaching volume (ICC=0.986, p<0.001) and velocity trials (ICC=0.963, p<0.001).The data from our pilot study with ACTIVE proof-of-concept demonstrates that newly available gaming technology has potential to be used to create a low-cost, widely-accessible and functional upper extremity outcome measure for use with children and adults with dystrophinopathy.
- Effects of the Pimelic Diphenylamide Histone Deacetylase Inhibitor HDACi 4b on the R6/2 and N171-82Q Mouse Models of Huntington's Disease. [Journal Article]
- PLoS Curr 2013.
This report represents a detailed description of experiments designed to replicate and extend the findings of a published study on the effects of treating the R6/2 Huntington's disease (HD) mouse model with ~300 CAG repeats using the pimelic diphenylamide histone deacetylase (HDAC) inhibitor, HDACi 4b (Thomas et al., 2008). In addition to testing the R6/2 mice, similar experiments examined the effects of the drug on a second transgenic HD mouse model, the N171-82Q mice. As in the original study, the drug was delivered in the drinking water. In the present study we tested larger groups of mice than in the original study. The results indicated that we were unable to replicate the significant behavioral effects of oral HDACi 4b treatment in the R6/2 mice. There were however, non-significant trends for the treated R6/2 mice to be less affected on some of the measures and there were instances of phenotype progression being delayed in these treated mice. In contrast, we did replicate the protection from striatal atrophy in the R6/2 mice. We also did not observe any beneficial effects of HDACi 4b treatment in the N171-82Q mice. Although the behavioral procedures were replicated and an automated activity assessment was added, there were several unexpected complications in terms of solubility of the drug, CAG repeat length differences and gender differences in progression of the phenotype that could have affected outcomes. Clearly more studies will have to be performed using other methods of delivery as well as assessing effects in more slowly progressing HD models to better evaluate the effects of this HDAC inhibitor.
- Use of the Afirma® Gene Expression Classifier for Preoperative Identification of Benign Thyroid Nodules with Indeterminate Fine Needle Aspiration Cytopathology. [JOURNAL ARTICLE]
- PLoS Curr 2013.
Ruling out malignancy in thyroid nodules historically depended on thyroid resection and histopathological evaluation until fine needle aspiration (FNA) biopsy was introduced into the United States in the 1970's. Thyroid FNA biopsy identified a majority of thyroid nodules as benign, obviating the need for surgery in over half of the patients. However, 15%-30% of thyroid FNAs have indeterminate cytology that still requires operation, even though most of these operated nodules prove to be benign post-operatively. In order to predict which cytologically indeterminate thyroid nodules are benign and to potentially avoid surgery on these nodules, a recently described commercially available Gene Expression Classifier (GEC) test (Afirma®, Veracyte, Inc., South San Francisco, CA) has been developed that can be run on the FNA sample. This paper reviews the published literature and technology assessments/guidelines by independent parties and professional groups regarding the clinical utility as well as the analytic and clinical validity of the Afirma GEC.
- A Method to Produce and Purify Full-Length Recombinant Alpha Dystroglycan: Analysis of N- and O-Linked Monosaccharide Composition in CHO Cells with or without LARGE Overexpression. [Journal Article]
- PLoS Curr 2013.
α dystroglycan (αDG) is part of the dystrophin-associated glycoprotein (DAG) complex, a series of cytoskeletal, transmembrane, and membrane-associated proteins that serve to link the extracellular matrix (ECM) surrounding individual skeletal myofibers to the intracellular F-actin cytoskeleton. Glycosylation and ECM protein binding to αDG are regulated by a number of genes that, when defective, give rise to congenital or limb-girdle forms of muscular dystrophy termed dystroglycanopathies. One such dystroglycanopathy gene is LARGE. Here, we describe a method to produce and purify full-length, furin-resistant, recombinant αDG from CHO cells and CHO cells overexpressing LARGE (CHO-LARGE). In addition, we analyze the O- and N-linked monosaccharide composition of such proteins. αDG purified from CHO-LARGE cells had increased molar content of xylose and fucose relative to CHO, while no significant changes were found in N-linked monosaccharides. Glucuronic acid could not be quantified by the methods used. These studies describe a method to produce and purify the milligram amounts of αDG needed for certain biochemical methods, including monosaccharide analysis. Key words: Dystroglycan, muscular dystrophy, xylose, fucose, laminin, LARGE Correspondence: Paul.Martin@nationwidechildrens.org.
- The use of systematic reviews and other research evidence in disasters and related areas: preliminary report of a needs assessment survey. [Journal Article]
- PLoS Curr 2013.
This paper presents the initial data analysis for a survey to identify the attitudes towards systematic reviews and research of those involved in the humanitarian response to natural disasters and other crises; their priorities for evidence, and their preferences for accessing this information.Snowballing sampling techniques were used to recruit participants who identified themselves as humanitarian aid workers, with or without experience in providing funding to aid agencies. An online questionnaire with both quantitative and qualitative questions was made available to participants using a variety of e-mail lists. Quantitative responses from 85 participants to a selection of questions were descriptively analysed using SPSS.Findings indicated that respondents had positive opinions about systematic reviews and using research evidence when planning and responding to disasters. Seventy participants answered the question on the usefulness of reviews before, during and after disasters and, of these, 83% said that systematic reviews are useful in disasters, and the remaining 17% said they did not know. No-one selected the option that systematic reviews are not useful. The most preferred format for access to systematic reviews was the whole reviews, supplemented by comments from experts in the humanitarian sector (61%), 33% choose access to the full review, 20% choose the summary of reviews and 50% choose summary of reviews plus context-specific information. Inadequate access was the most commonly reported barrier to the use of systematic reviews (70%). This was followed by the lack of time to use reviews (59%) and insufficient knowledge about reviews (49%). Respondents selected scientific evidence as the most preferred type of evidence for influencing their decisions (80%), 11% ranked personal experience highest, 6% said their organisation's usual practice, 1% said anecdotal evidence and 1% said intuition would be their first choice. 69% of participants "strongly agreed" that evidence from systematic reviews could have a positive role in humanitarian interventions and a further 29% "agreed" with the same statement. 66% thought they would like to access them when a natural disaster is not known to be imminent, compared to 34% who said that they would not wish to access systematic reviews at such a time. 70% would like to access systematic reviews during the period of prediction that a disaster will happen Conclusion: These preliminary findings from the Evidence Aid survey emphasise the need for "global" evidence but also the need that this be supplemented by local and context-specific knowledge. Systematic reviews could play a central role in improving the effectiveness of humanitarian aid in the planning, delivery and recovery phases of a disaster. Keywords: Evidence base, humanitarian planning, delivery and recovery, systematic review.
- Public health surveillance after the 2010 haiti earthquake: the experience of médecins sans frontières. [Journal Article]
- PLoS Curr 2013.
Background In January 2010, Haiti was struck by a powerful earthquake, killing and wounding hundreds of thousands and leaving millions homeless. In order to better understand the severity of the crisis, and to provide early warning of epidemics or deteriorations in the health status of the population, Médecins Sans Frontières established surveillance for infections of epidemic potential and for death rates and malnutrition prevalence. Methods Trends in infections of epidemic potential were detected through passive surveillance at health facilities serving as sentinel sites. Active community surveillance of death rates and malnutrition prevalence was established through weekly home visits. Results There were 102,054 consultations at the 15 reporting sites during the 26 week period of operation. Acute respiratory infections, acute watery diarrhoea and malaria/fever of unknown origin accounted for the majority of proportional morbidity among the diseases under surveillance. Several alerts were triggered through the detection of immediately notifiable diseases and increasing trends in some conditions. Crude and under-5 death rates, and acute malnutrition prevalence, were below emergency thresholds. Conclusion Disease surveillance after disasters should include an alert and response component, requiring investment of resources in informal networks that improve sensitivity to alerts as well as on the more common systems of data collection, compilation and analysis. Information sharing between partners is necessary to strengthen early warning systems. Community-based surveillance of mortality and malnutrition is feasible but requires careful implementation and validation.