We also discuss the role of FDG-PET/CT in the diagnosis and monitoring of these diseases.Advanced imaging techniques may enable early diagnosis and monitoring of therapy in various rheumatic diseases. To prevent irreversible tissue damage, inflammatory rheumatic disease must be diagnosed and treated in pre-clinical stages, requiring highly sensitive detection techniques. Positron emission tomography (PET) provides highly sensitive, quantitative imaging at a molecular level, revealing the important pathophysiological processes underlying inflammation. This review provides an overview of the current utility of  Timely diagnosis and early effective treatment can improve the outcome of various inflammatory rheumatic diseases . To enab18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in the diagnosis and monitoring of inflammatory rheumatic diseases is discussed.Because diagnosis and assessment of disease activity at subclinical stages are increasingly important, nuclear imaging techniques are becoming more widely used. In this review, the potential role of Increased ‘aerobic glycolysis’ in cancer cells, originally described by Otto Warburg, provides a growth advantage to tumor cells. With the imbalance in the growth of capillaries and cancer cells, cancer cells become hypoxic. The transcription factor hypoxia-inducible factor 1α (HIF1α) mediates cancer cell metabolism and shifts cancer cells into oxygen conservation mode, aerobic glycolysis, so that the reduced oxygen consumption saves cancer cells from anoxic death; that is, HIF1α regulates the expression of glucose transporters, hexokinase, and other factors in cancer cells .FDG is used to trace glucose metabolism. Many cancer cells showed elevated expression of glucose transporters and hexokinase. Most cancer cells are FDG-avid, and a fusion imaging technique combining PET/CT, which provides information on both anatomy and glucose metabolism, has improved the diagnostic accuracy and is now widely used in oncology.in vivo inflammation model. More recently, Matsui and colleagues [in vitro experiments, Matsui and colleagues suggested that the cell types responsible for FDG uptake are activated macrophages and proliferating fibroblasts in the presence of cytokine stimulation and under hypoxic circumstances within a joint. The FDG uptake by inflammatory tissue, such as arthritis lesions, seems to reflect the inflammatory activity accurately. Such studies have strongly encouraged the clinical application of FDG-PET/CT for rheumatic diseases.FDG uptake is not limited to cancer cells; uptake may also occur in various inflammatory cells. Elevated FDG uptake by activated macrophages and by newly formed granulation tissue was demonstrated by Kubota and colleagues ,7 in thelleagues  reportedTypical FDG-PET/CT images of rheumatoid arthritis (RA) are shown in Figure Beckers and colleagues  reportedmax, and the mean number of joints per patient with high FDG uptake were all significantly lower for patients in clinical remission. In all patients in remission, however, increased FDG uptake was still observed in one or more joints, suggesting subclinical disease activity.Recently, several studies have indicated that subclinical disease is present during clinical remission and may be related to progression of joint damage . Owing tBesides its ability to detect and monitor subclinical disease, PET may have prognostic power. Recently, FDG changes in inflamed hand joints after 2 weeks of infliximab treatment were correlated with DAS28 joint scores at 14 to 22 weeks of treatment . In contComparison of semiquantitative PET data with US data and clinical findings  revealedOver the last few years, hybrid PET-CT and PET-MRI have become available. Combining PET with CT has helped place pathophysiologic PET information in its anatomic context . Thus, hTypical FDG-PET/CT images of spondyloarthritis (SpA) are shown in Figure max was significantly higher at the enthesis of the lumbar spinous process, pubic symphysis, and ischial tuberosity in patients with SpA than in patients with RA. Lumbar spinous processes and ischial tuberosities appeared more frequently via PET/CT than MRI in patients with SpA. The authors concluded that PET/CT represents an alternative modality to identifying enthesitis and will likely contribute to the early diagnosis of SpA.Taniguchi and colleagues  evaluateStrobel and colleagues  evaluatemax in the SIJ was greater than in patients with PMR or RA. No significant difference in vertebral scores was observed among groups. PET/CT findings thus can distinguish SpA from RA and PMR and are useful for the early diagnosis of sacroiliitis.We used FDG-PET/CT to compare SUVs in various joints in 53 patients with SpA, polymyalgia rheumatica (PMR), and RA . In patiVijayant and colleagues  evaluateTypical FDG-PET/CT images of PMR are shown in Figure Moosig and colleagues  quantifiBlockmans and colleagues  investigWhereas Blockmans and colleagues  analyzedmax for ischial tuberosities was significantly higher than in patients with SpA or RA, and those in the greater trochanter and spinous processes were also significantly higher than in patients with RA.We also used FDG-PET/CT to compare SUVs in various joints in 53 patients with SpA, PMR, and RA . In patiFurthermore, we compared PET/CT findings in a large number of PMR cases with those in patients with elderly-onset RA (EORA), which is extremely difficult to distinguish from PMR. We observed no significant difference in FDG uptake in the shoulders or hips. However, specific uptake patterns were observed in each group: circular and linear uptake patterns around the humeral head in EORA and focal and nonlinear uptake patterns in PMR. Moreover, focal uptake at the front of the hip joint, indicating iliopectineal bursitis, tended to be limited to the PMR group. The sensitivity and specificity for PMR diagnosis were very high at 92.6% and 90.0%, respectively, when at least three of the five items, including findings characteristic of shoulder and iliopectineal bursitis, FDG uptake in ischial tuberosities and spinal spinous processes, and lack of FDG uptake in the wrists, were satisfied. FDG-PET/CT may be useful for the detection of PMR lesions, which are difficult to identify by using other methods.max, in the bone marrow, spleen, and lymph nodes. The only correlation with laboratory data was between lactate dehydrogenase and spleen SUV. In conclusion, FDG-PET/CT is useful for long-term assessment of AOSD activity in individual patients. However, PET/CT findings alone are not sufficient to make a differential diagnosis of AOSD versus malignant lymphoma.Typical FDG-PET/CT images of adult-onset Still’s disease (AOSD) are shown in Figure Typical FDG PET/CT images of relapsing polychondritis (RPC) are shown in Figure IgG4-related disease (IgG4-RD) is a systemic disorder associated with lesions characterized by mass formation in multiple specific organs. This disorder comprises Mikulicz’s disease, autoimmune pancreatitis (AIP), hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, lymphadenopathy, retroperitoneal fibrosis, and inflammatory pseudotumour . The comShigekawa and colleagues  noted thEbbo and colleagues  evaluateIn addition, we evaluated the utility of FDG-PET/CT in eight patients with IgG4-RD . AlthougTypical FDG-PET/CT images of large-vessel vasculitis (LVV) are shown in Figure max and PET scores of the aortic wall, as well as aortic wall thickness (W) and its ratio with respect to aortic radius (W/R) by contrast-enhanced CT, and compared pre-treatment and post-treatment values. Of 124 patients who were hospitalized because of advanced age and IUO, 10.5% had LVV, and more than half had non-specific symptoms. Compared with control subjects, patients with LVV showed significantly higher aortic wall SUVmax, higher PET scores as revealed by FDG-PET/CT, and increased aortic wall thicknesses as revealed by contrast-enhanced CT. In conclusion, LVV is an important cause of IUO with non-specific symptoms in older patients. Imaging examination comprising contrast-enhanced CT and FDG-PET/CT is useful for early diagnosis and early treatment evaluation of LVV, as it detects amelioration of aortic wall thickening.We also studied the usefulness of FDG-PET/CT and contrast-enhanced CT in early diagnosis and treatment follow-up of patients with LVV presenting as elderly-onset inflammation of unknown origin (IUO) . For quaNotably, FDG-PET/CT may be negative for old lesions even if the arterial stricture is severe. Lesions in which the inflammatory activity has already subsided may not be appropriate for evaluation by FDG-PET; in such cases, morphological imaging such as MRI or contrast-enhanced CT may be used. Again, LVV should be diagnosed in the early phase with FDG-PET/CT to prevent stricture formation.Wegener’s granulomatosis (WG), namely granulomatosis with polyangiitis, is a relatively rare disease characterized by granulomatous necrotizing vasculitis. In the first evaluation of FDG-PET/CT imaging for the diagnosis and monitoring of WG , we retrOwada and colleagues  examinedOn the other hand, Tanaka and colleagues  also conFDG-PET images do detect reductions in metabolism and treatment-related changes in the volume of pannus that are not detectable with conventional imaging . In 2006max in 12 large joints and clinical parameters in 22 patients with RA before and after treatment with biologics. The results showed positive correlations of ΔSUV with ΔDAS28, ΔDAS28-CRP, and ΔTJC in large joints before and after treatment, suggesting the usefulness of PET in evaluating treatment responses [Recently, Okamura and colleagues  investigesponses .A number of studies have examined the ability of PET to accurately indicate treatment outcomes compared with MRI. Before and during treatment with non-steroidal anti-inflammatory drugs, prednisone, or methotrexate, changes in joint uptake of FDG, as revealed by PET, were strongly correlated with synovial volume upon MRI in patients with RA ,53.The first study simultaneously investigating PET, MRI, and US in patients with RA showed that changes in SUVs in RA-affected knees after initiation of anti-TNF therapy were also correlated with changes in MRI parameters and serum CRP and metalloproteinase-3 levels but not with changes in synovial thickness as measured via US .max correlating to the clinical improvement in the patient. FDG-PET also appears to be a sensitive tool in the early assessment of treatment response, especially when using quantitative information.Vijayant and colleagues  evaluateTypical FDG-PET/CT images of PMR are shown in Figure Moosig and colleagues  quantifiBlockmans and colleagues  investigTypical FDG-PET/CT images of AOSD are shown in Figure Typical FDG PET/CT images of RPC are shown in Figure Ebbo and colleagues  evaluateTypical FDG-PET/CT images of LVV are shown in Figure From a systematic review on FDG-PET/CT in patients with LVV, Treglia and colleagues  concludeWe also studied the usefulness of FDG-PET/CT and contrast-enhanced CT in early diagnosis and treatment follow-up of patients with LVV . PET scoWe retrospectively analyzed 13 FDG-PET/CT images obtained from eight patients with WG. All active lesions showed decreased FDG uptake after treatment . Ozmen a89Zr or 124I by using good manufacturing procedures have been established, and therefore these radiopharmaceuticals are being investigated for clinical use. Immuno-PET is expected to become an option as a non-invasive diagnostic tool providing ‘comprehensive immunohistochemical staining in vivo’ [The development of non-invasive imaging techniques using monoclonal antibodies (mAbs) is a quickly evolving field. Immuno-PET uses positron-emitting isotopes to track the localization of mAbs with excellent image quality. Procedures for labeling mAbs with in vivo’ . TherefoIt is sometimes difficult to distinguish between RA and other rheumatic diseases such as SpA and PMR, which lack specific serum markers; PET may be useful for differentiating among these conditions. Moreover, no specific serum markers exist for AOSD, making its differentiation from other rheumatic diseases occasionally difficult. However, the finding of FDG accumulation in the bone marrow, spleen, lymph nodes, and joints in this condition is useful. It should be acknowledged, however, that differentiation of AOSD from malignant lymphomas is sometimes difficult. As for RPC, it is possible to identify asymptomatic chondritis by using PET and readily identify the distribution of the lesions. With respect to IgG4-RD, the diagnostic yield can be increased by recognizing the characteristic distribution of the lesions in this disease by using PET combined with the absence of a significant inflammatory response. In addition, LVV can be cited in the differential diagnosis as a cause of IUO in older patients who present with non-specific symptoms only; PET is useful for early diagnosis of this condition, and early therapeutic intervention may prevent stenotic lesions. With regard to WG (granulomatosis with polyangiitis (GPA)), PET is useful for the evaluation of active lesions, therapeutic monitoring, and identification of biopsy sites. As for inflammatory myopathy, whereas one report suggests the limited usefulness of PET because of its low sensitivity, another report suggests that PET provides useful information for determining the appropriate biopsy sites.FDG-PET/CT can provide information on active inflammatory lesions. It is a very sensitive but non-specific imaging modality. The distribution patterns of inflammatory foci sometimes suggest specific disease. In general, if FDG-PET/CT imaging is used appropriately, it may provide very helpful information for accurate diagnosis. In addition, FDG-PET/CT is very sensitive for monitoring disease activity. It could be applied to the prediction of therapeutic response, but further studies are required. FDG-PET/CT is a promising imaging modality for rheumatic diseases.


Maternal mortality is of global public health concern and >99 % of maternal deaths occur in less developed countries. The common causes of direct maternal death are hemorrhage, sepsis and pre-eclampsia/eclampsia. In Pakistan, pre-eclampsia/eclampsia deaths represents one-third of maternal deaths reported at the tertiary care hospital settings. This study explored community perceptions, and traditional management practices about pre-eclampsia/eclampsia.N = 173); and 7 with husbands/fathers-in-law (N = 65). The data were transcribed verbatim in Sindhi and Urdu, then analyzed for emerging themes and sub-themes using NVivo version 10 software.A qualitative study was conducted in Sindh Province of Pakistan from February to July 2012. Twenty-six focus groups were conducted, 19 with women of reproductive age/mothers-in-law (Pre-eclampsia in pregnancy was not recognized as a disease and there was no name in the local languages to describe this. Women however, knew about high blood pressure and were aware they can develop it during pregnancy. It was widely believed that stress and weakness caused high blood pressure in pregnancy and it caused symptoms of headache. The perception of high blood pressure was not based on measurement but on symptoms. Self-medication was often used for headaches associated with high blood pressure. They were also awareness that severely high blood pressure could result in death.Community-based participatory health education strategies are recommended to dispel myths and misperceptions regarding pre-eclampsia and eclampsia. The educational initiatives should include information on the presentation, progression of illness, danger signs associated with pregnancy, and appropriate treatment. The hypertensive disorders of pregnancy (HDP), particularly pre-eclampsia and eclampsia are among the top three leading causes of maternal mortality globally , 2. Pre-The secondary analysis of the World Health Organization Global Survey on maternal and perinatal health revealed socio-demographic variables , as well as, clinical variables  as the highest risk factors for pre-eclampsia in low-and-middle income countries .Pakistan is the sixth most populous country in the world. A recent systematic analysis of global mortality ranked Pakistan as the country with the third highest burden of maternal, fetal and child mortality , 9. AccoEclampsia is responsible for 34 % of maternal deaths in women admitted to a tertiary care hospital in Pakistan . ClinicaThis study was conducted as part of the formative research of a large community-based research trial - Community Level Interventions for Pre-eclampsia  in Sindh province, Pakistan (NCT01911494) . The objA qualitative study was undertaken between February to July 2012, as part of a large multi-country study, the detailed methods are described elsewhere . This stData were collected through focus group discussions (FGDs) , with woThe FGD guides were translated into Sindhi and Urdu languages, and pilot tested for comprehension, cultural sensitivity, and duration. To respect local preferences of participants, FGDs were held separately for women and men at local venues. Data saturation was reached through 26 FGDs .All discussions were transcribed into Sindhi and Urdu languages. Stringent data quality control measures were followed. These included random observations of FGDs, 20 %  verification of the content of manual transcripts by audio-recording review, and fortnightly debriefing sessions with moderators and transcribers. In addition, the moderators recoded a self-reflection after each session to describe their thoughts and impressions to better contextualize the data, as well as, to protect against self-bias. A thematic analysis (combining an inductive and deductive approach) was used with the assistance of NVivo version 10 software . All responses were coded to relevant nodes, which were later categorized into hierarchy of tree-nodes.Subsequently, emerging themes and sub-themes were drawn from the tree nodes , Karachi Pakistan, National Bioethics Committee of Pakistan and Clinical Research Ethics Board of University of British Columbia, Vancouver Canada (H12-00132).Twenty-six focus groups were conducted: 19 with women of reproductive age/mothers-in-law; and 7 with husbands/fathers-in-law  were not possible given logistic and resource limitations; as a result, it is possible that some participants did not feel comfortable to actively participate despite encouragement by the moderator. Combined focus groups were held for women of reproductive age and mothers-in-law, therefore some women were hesitant to speak-up. Similarly, group sessions for husbands and fathers-in-law were combined. The combined focus groups may have impeded open dialogue because potential cultural barrier whereby young people are unlikely to oppose senior members of the community.This qualitative study provides insights of community’s understanding of pre-eclampsia ascribed as general symptoms, and less specific to clinical conditions. There were mixed opinions regarding the causes of the hypertension in pregnancy and a poor understanding regarding the connection between pregnancy, hypertension and seizures.Community-based participatory health education strategies are highly recommended to address myths and misperceptions about danger signs of pregnancy in Pakistan. Dissemination of knowledge to the wider community would likely challenge traditional beliefs, customs and practices; therefore behavior change communication would be very useful strategies to implement at community settings. Education should be integrated into training programs for community health workers to improve their knowledge base and facilitate community awareness in rural Pakistan.


To determine, in areas supported by BRAC, Bangladesh i) the pre-diagnosis and pre-treatment attrition among presumptive and confirmed Multi-Drug Resistant Tuberculosis (MDR-TB) patients and ii) factors associated with attrition.This was a retrospective cohort study involving record review. Presumptive MDR-TB patients from peripheral microscopy centres serving 60% of the total population of Bangladesh were included in the study. Attrition and turnaround time for MDR-TB diagnosis by Xpert MTB/RIF and treatment initiation were calculated between July 2012 and June 2014.Of 836 presumptive MDR-TB patients referred from 398 peripheral microscopy centres, 161 MDR-TB patients were diagnosed. The number of diagnosed MDR-TB patients was less than country estimates of MDR-TB patients (2000 cases) during the study period. Among those referred, pre-diagnosis and pre-treatment attrition was 17% and 21% respectively. Median turnaround time for MDR-TB testing, result receipt and treatment initiation was four, zero and five days respectively. Farmers  and daily wage laborers  had twice the risk of having pre-diagnosis attrition. Poor record-keeping and unreliable upkeep of presumptive MDR-TB patient databases were identified as challenges at the peripheral microscopy centres.There was a low proportion of pre-diagnosis and pre-treatment attrition in patients with presumptive and confirmed MDR-TB under programmatic conditions. However, the recording and reporting system did not detect all presumptive MDR-TB patients, highlighting the need to improve the system in order to prevent morbidity, mortality and transmission of MDR-TB in the community. Despite progress in the detection of Multi-Drug Resistant/Rifampicin Resistant Tuberculosis (MDR/RR-TB) cases, major diagnostic gaps remain: 55% of reported TB patients estimated to have MDR-TB were not detected in 2013 [Timely identification of MDR-TB cases and prompt initiation of treatment are crucial to prevent the transmission of disease and reduce related high morbidity and mortality . StudiesBangladesh is one of the 27 high burden countries for MDR-TB . The NatAccording to Bangladesh NTP policy, all presumptive MDR-TB cases should be tested by Xpert MTB/ RIF. However, out of an estimated 4700 MDR-TB patients in 2013, NTP Bangladesh diagnosed only 1024 MDR/RR TB cases and only 684 MDR–TB patients enrolled for treatment in 2013 [This operational research was conducted i) to determine the pre-diagnosis and pre-treatment attrition among presumptive and confirmed MDR/RR-TB patients and ii) to study factors associated with attrition, in areas supported by BRAC in Bangladesh, between July 2012 and June 2014.Ethics approval was obtained from the Bangladesh Medical Research Council (BMRC), Dhaka and the Ethics Advisory Group, International Union Against Tuberculosis and Lung Disease, Paris, France. As this study involved collection of routine programme data, informed consent from the patients was waived by the ethics committee.This was a retrospective cohort study involving record review of presumptive MDR-TB patients.Bangladesh is situated in the north-eastern part of South Asia. It has a population of over 150 million and administratively it is divided in seven divisions, 64 districts, 488 sub-districts (upazilas) and 4,466 unions . BangladIn collaboration with the NTP, this study was carried out in 42 districts and one city corporation area of Sylhet covered by BRAC. BRAC supports a population of 93 million which is approximately 60% of the Bangladeshi population. These areas contain 398 microscopy laboratories, 18 Xpert MTB/RIF laboratories including the Regional TB Reference Laboratory (RTRL), the National TB Reference Laboratory (NTRL), and Chest Diseases Hospitals and National Institute of Diseases of the Chest and Hospital (NIDCH) of Dhaka plus some other specialized hospitals.The criteria used to identify presumptive MDR-TB in the NTP are (any one): i) new case—treatment failure, ii) retreatment case—treatment failure, iii) symptomatic contacts of confirmed MDR-TB cases, iv) new cases who didn’t convert smear by three months, v) Category II patients who did not convert smear by four months, vi) any treatment relapse, vii) any return after default, viii) all TB-HIV co-infected patients at the start of TB treatment, and ix) others .All presumptive MDR-TB patients from peripheral microscopy laboratories, except some areas where piloting of sample referral is going on, are referred to nearest Xpert MTB/RIF laboratory for MDR-TB testing. If diagnosed as MDR-TB, then patients are counseled to get admitted at the nearest MDR-TB treatment facilities. MDR-TB treatment is initiated with the detection of MDR/RR-TB as per the national algorithm. BRAC also provides social support in terms of financial support throughout the MDR-TB diagnosis and treatment cascade in Bangladesh.All presumptive MDR-TB patients, who were referred from BRAC’s peripheral microscopy centres to Xpert MTB/RIF laboratories under areas supported by BRAC between July 2012 and June 2014, were included in the study.The following operational definitions were used in the study: pre-diagnosis attrition applies to any presumptive MDR-TB patient who was not tested within 30 days from the date when the patient was declared “presumptive MDR-TB” based on microscopy laboratory test; and pre-treatment attrition applies to any confirmed MDR-TB patient who was not enrolled for treatment within 30 days from the date of diagnosis based on the Xpert MTB/RIF result.A list of presumptive DR-TB patients, who were referred, was prepared from the presumptive MDR-TB register at peripheral microscopy centres. Data for this cohort were collected through a structured proforma from presumptive DR-TB registers, TB treatment cards, Xpert MTB/RIF register and MDR-TB treatment cards. Data were validated from different sources wherever possible. Data variables included age, sex, occupation, TB disease type, TB registration number, criterion for presumptive MDR-TB, name of the peripheral microscopy lab, name of the reference or Xpert MTB/RIF laboratory and DR-TB registration number. We also collected the following: date of declaration as presumptive MDR-TB, date of MDR-TB test result if done, and date of registration for MDR-TB treatment, if it was initiated.We used EpiData software for data entry and analysis . Descriptive statistics  were used to describe the data. Relative risks (RR) and Chi- square tests were used to determine factors associated with attrition. A P value <0.05 was considered statistically significant.A total of 836 presumptive MDR-TB patients were identified and included in the analysis. The diagnosis and treatment cascade is shown in Pre-diagnosis attrition was found in 139 (16.6%) patients . Among tThe number of MDR-TB cases diagnosed and referred for DR-TB treatment among the cohort was 161 (19.3%). Of those, 110 (68.3%) were male, the mean (SD) age was 35 (17) years, 29 (18%) were farmers and all were pulmonary cases. Pre-treatment attrition was seen in 33 (20.5%) patients . Among tUnivariate analysis of socio-demographic factors showed that farmers  and daily wage laborers  had twice the risk of having pre-diagnosis attrition when compared to employed patients. Extra-pulmonary TB patients also had twice the risk of having pre-diagnosis attrition when compared to pulmonary TB patients, but this difference was not statistically significant. No factors were found to be significantly associated with pre-treatment attrition.In BRAC supported areas of the Bangladesh NTP, both pre-diagnostic attrition and pre-treatment attrition were low (≤ 21%) among presumptive MDR-TB patients referred from the peripheral microscopy centres. The NTP performance in referring presumptive MDR-TB patients has been improving over time from July 2012 to June 2014 and this was an encouraging finding.In Bangladesh about 83% patients referred for Xpert MTB/RIF testing were actually tested as compared to 10% in Tanzania , 40% in The median turnaround times throughout the diagnosis and treatment pathway were satisfactory in Bangladesh, especially when compared to other settings: four days for Xpert MTB/RIF testing, same day for Xpert MTB/RIF results given to the patients, and five days from confirmation of MDR-TB diagnosis to treatment initiation. In the Delhi study, for example, these median TATs were nine, five and 37 days respectively . Median We acknowledge some limitations in this study. The diagnosed number of MDR-TB patients was less than the country estimates of MDR-TB patients (2000 cases) during the study period. In our study, only cases referred from microscopy centres were included, whereas in other studies some of the presumptive MDR-TB cases might come directly from other sources. Also, overlapping (BRAC and non BRAC) of services is possible even in BRAC supported areas. Moreover, it is highly likely that not all presumptive MDR-TB were being identified.During the study, a register of presumptive MDR-TB patients was not found in several peripheral microscopy laboratories and proper documentation of presumptive MDR-TB patients was not recorded, especially between June–Dec 2012 when PMDT was being implemented. Over time, this situation has improved, yet, there is further room for improvement. Poor update of the list of presumptive MDR-TB patients in peripheral microscopy laboratory centers was also common. There were several cases in which baseline data as well as dates were incompletely entered in records. It is hypothesized that referred patients who returned with Xpert MTB/RIF results were more likely entered retrospectively into the registers. Therefore, a selection bias was likely introduced during the study which may have led to an underestimation of attrition, especially pre-diagnosis attrition.Actual eligible referrals were not identified by the investigators. Only those identified by the programme were included as the denominator in the cohort. Many referrals were not included in the denominator because of absence of baseline data. These are inherent limitations of a record review study. Health system factors, particularly relating to the recording and registration of presumptive and confirmed tuberculosis cases, were found to be important contributors to pre-treatment loss to follow-up in several studies . It willDespite these limitations, our study has several strengths. This was the first study in Bangladesh to identify attrition in the diagnostic and treatment pathway of PMDT services and describe the diagnosis and treatment cascade. A-major strength of this study is that data were collected from a large area of the country (representing 60% of the population) under programmatic conditions and, thus, they are likely to be representative of the PMDT activities countrywide. A standard and strict attrition criterion of 30 days was uniformly followed for each referral. This was not the case in previous studies from other settings. Some operational challenges identified are specific to the region, though are likely to be encountered in other low and middle income countries. Data were quality assured and robust and STROBE guidelines were followed .Mere implementation of molecular diagnostic tests won’t suffice unless operational issues related to PMDT at field level are addressed. There is a need to improve the recording and reporting of presumptive MDR-TB cases at each level. A cohort-wise analysis of patients from identification to testing to treatment initiation must be routinely carried out and qualitative methods should be also considered. An improved mechanism for tracking referrals from presumptive diagnosis to treatment commencement should be developed.The MDR-TB diagnosis and treatment pathway is costly and long, even in settings where health care and diagnostic tests are provided free of charge at the point of delivery. Reducing costs and time for patients might improve retention in care . In BangFurther studies are recommended to assess implementation of systems-wide interventions to improve identification, tracking, and ultimately treatment of MDR TB patients to minimize further infections.In conclusion, low pre-diagnosis and pre-treatment attrition was found among MDR-TB patients under programmatic conditions in a large area of Bangladesh. However, several operational gaps were identified; especially low overall MDR-TB case detection, and several weaknesses in the existing reporting and recording system which highlight the urgent need for action to prevent MDRTB associated morbidity and mortality and community transmission of resistant TB strains.


Objective: Approximately one-quarter of military personnel who deployed to combat stations sustained one or more blast-related, closed-head injuries. Blast injuries result from the detonation of an explosive device. The mechanisms associated with blast exposure that give rise to traumatic brain injury (TBI), and place military personnel at high risk for chronic symptoms of post-concussive disorder (PCD), post-traumatic stress disorder (PTSD), and depression are not elucidated.Methods: To investigate the mechanisms of persistent blast-related symptoms, we examined expression profiles of transcripts across the genome to determine the role of gene activity in chronic symptoms following blast-TBI. Active duty military personnel with (1) a medical record of a blast-TBI that occurred during deployment (n = 19) were compared to control participants without TBI (n = 17). Controls were matched to cases on demographic factors including age, gender, and race, and also in diagnoses of sleep disturbance, and symptoms of PTSD and depression. Due to the high number of PCD symptoms in the TBI+ group, we did not match on this variable. Using expression profiles of transcripts in microarray platform in peripheral samples of whole blood, significantly differentially expressed gene lists were generated. Statistical threshold is based on criteria of 1.5 magnitude fold-change (up or down) and p-values with multiple test correction .Results: There were 34 transcripts in 29 genes that were differentially regulated in blast-TBI participants compared to controls. Up-regulated genes included epithelial cell transforming sequence and zinc finger proteins, which are necessary for astrocyte differentiation following injury. Tensin-1, which has been implicated in neuronal recovery in pre-clinical TBI models, was down-regulated in blast-TBI participants. Protein ubiquitination genes, such as epidermal growth factor receptor, were also down-regulated and identified as the central regulators in the gene network determined by interaction pathway analysis.Conclusion: In this study, we identified a gene-expression pathway of delayed neuronal recovery in military personnel a blast-TBI and chronic symptoms. Future work is needed to determine if therapeutic agents that regulate these pathways may provide novel treatments for chronic blast-TBI-related symptoms. Improvised explosive devices (IEDs) have induced blast traumatic brain injuries (TBI) in approximately one-quarter of military personnel deployed to combat stations in Operations Enduring Freedom and Iraqi Freedom . In addiClinical studies report differential gene expression following TBI; however, these studies do not include blast-TBI, and most use post-mortem, neuronal tissue samples obtained from severe TBI patients –10. StudAlthough pre-clinical models are not in agreement in the preferential models of blast-TBI, there is definitive evidence linking blast-TBIs to neuronal function changes . Blast-TTherefore, we suggest that central neuronal recovery mechanisms may be detected in the periphery through whole blood samples obtained from military personnel with a history of blast-TBI who are seeking care for chronic symptoms. To further investigate this postulation, we enrolled military personnel with medically documented blast-TBI, as well as controls without TBI. Instruments and a clinical evaluation were undertaken to determine current symptoms of PCD, PTSD, depression, and sleep disturbance. Differentially expressed genes related to blast-TBI were obtained by comparing military personnel with blast-TBI to matched controls without TBI using a whole-genome approach that eliminates any biased selection of biological targets. We addressed the possible impact of PTSD, depression, and sleep disturbance on gene-expression through group matching, on diagnoses of sleep disturbance, and symptom severity of PTSD and depression. This approach may provide a minimally invasive opportunity to investigate the gene-expression pathways that contribute to blast-TBI pathology in military personnel. We expect this line of research to ultimately inform pharmacological agents to better treat military personnel with chronic symptoms and deficits following a blast-TBI.This study was an observational assessment of U.S. military personnel at the Madigan Army Medical Center who had been deployed within the previous 18 months. Exclusion criteria included (1) no history of drug or alcohol abuse in the previous year and (2) no current medical condition that required substantial treatments , or a severe psychiatric condition . Subjects with neurological disorders other than headaches, e.g., multiple sclerosis, seizure disorders, and a history of stroke, were excluded. Subjects with blast-TBI were identified by having a blast-TBI documented in their medical record. Blast-TBI cases did not require a pre-specified severity of PCD symptoms. Controls neither have a medical history of any TBI in their records nor report a TBI when asked. Controls were matched to blast-cases as much as possible on critical variables that would have influenced gene-expression including the following: age, gender, race/ethnicity, and diagnoses of sleep disorder, and symptom severity of PTSD and depression. The medical record was used to determine the number and type of prescribed medications that military personnel were prescribed. This study was approved by the institutional review board at the Madigan Army Medical Center, and informed consent was obtained from each individual prior to any baseline measurements.The case history of TBI was extracted from medical records of the 117 military personnel enrolled in a larger observational study. Clinical information obtained includes the following: type of injury, diagnosis of TBI that includes severity, loss of consciousness, and time since the TBI. To be a blast-TBI case, the participant must also have reported sustaining a TBI through administration of the warrior administered retrospective casualty assessment tool (WARCAT) . A negatr = 0.88–0.93)  was used to measure PCD symptom severity. The NSI is a 22-item measure designed to evaluate self-reported post-concussion symptoms . The NSI requires the test taker to rate the presence/severity of each symptom on a 5-point scale . A total score is obtained by summing the ratings for the 22 items (range = 0–88). The NSI has a high-internal consistency  and reliability (88–0.93) . This inSymptoms of PTSD were assessed by the PTSD checklist military version (PCL-M), resulting in a score between 0 and 80, with higher numbers indicating the greatest severity . The quiBlood samples were collected in PAXgene blood RNA tubes and processed with PAXgene™ Blood RNA Kits  for RNA extraction according to the manufacturer’s instruction. Quality and quantity of extracted RNA were evaluated with the NanoDrop DN-1000 spectrophotometer  and the Agilent Bioanalyzer 2100 eukaryotic total RNA Nano assay . The 260/280 ratio ranged 2.03–2.34 and the RNA integrity numbers (RIN) were >7.0 in all samples.Purified RNAs (100 ng) were amplified, fluorescently labeled, and hybridized to Affymetrix GeneChip Human Gene U133 Plus 2.0 Arrays , which contain more than 54,000 probes representing thousands of specific gene coding regions. After thorough washing, the raw data were obtained by laser scanning imaging. All RNA preparation and transcriptome assays were undertaken in the NINR laboratory based on manufacturer’s protocols.t-tests. A priori p-values <0.05 were considered significant.Descriptive statistics for all demographic and clinical variables were calculated using SPSS Statistics  Tables  and 2. C2 transformation, and probe-set summarization were performed on gene-expression intensity values. Multi-way analysis of variance (ANOVA) mixed models were constructed for differential expressions for both the blast-TBI + PCD (N = 19) and control (N = 17) groups. Since samples were processed on different dates, batch correction was applied. Pair-wise comparisons were made by setting the contrast between blast-TBI and control groups. Significant differentially expressed gene lists were generated based on criteria of 1.5 magnitude fold-change (up or down), and p-values corrected for false discovery rate (FDR < 0.05) using the step-up Benjamini–Hochberg method.Microarray data were analyzed for a total of 36 participants for gene-expression profiles using Partek Genomics Suite software . The probe-level robust multichip average background correction, quantile normalization, logInteractive pathway analysis (IPA)  was performed on differentially expressed genes to identify gene interactions and networks associated with biological functions.Clinical variables were compared using ANOVA models for continuous variables, and chi-square for categorical data. Although our data were small in sample size, it met the assumptions of the tests we used, including ANOVA. Bonferroni corrections were used to adjust for multiple comparisons.N = 19) was group matched to a control group (N = 17) to ensure that the groups did not differ on any demographic  or clinical characteristics . There was no difference in the total number of military personnel taking any prescribed medication, or the type of medications, the most common being serotonin reuptake inhibitors (SSRIs), anti-hypertensive, and prazosin. The mean ages of the blast-TBI and control groups were 32.0 and 30.9 years, respectively. The sample was male, primarily Caucasian, and demonstrated high rates of comorbid symptoms of sleep disorders, depression, and PTSD. The blast-TBI group reported a far greater severity of PCD symptoms compared to controls.The demographic and clinical characteristics of the 36 participants used in this analysis are described in Table All 19 participants in the TBI group experienced a blast injury, and 84.25% had a loss of consciousness following the blast-TBI. By medical diagnosis in theater, approximately 78.95% had a mild blast-TBI, and 21.05% of the sample was diagnosed with a moderate blast-TBI. In this sample, a brain contusion was reported to have occurred at the time of the blast in 36.84% of the sample, and all were determined to be mild in severity. More than half of the sample had more than one blast-TBI (52.6%), and approximately one-third had (38.8%) three or more blast-TBIs. The time since TBI varied, with 3–6 months, 6–12 months, and more than 12 months having elapsed for 15.8, 31.6, and 52.7% of the group, respectively.p-value of 0.05, and adjustment for multiple comparisons.The breakdown of the 22 components of the NSI for both the blast group and control group are shown in Table MARCH8, −1.6123 fold-change), tensin-1 , tripartite motif containing 58 , Kruppel-like factor 1 , WNK lysine deficient protein kinase 1 , ankyrin1 , and epidermal growth factor receptor . Differentially expressed gene pathways are shown in the network figure  as well as tripartite motif containing 58 (TRIM58) in military personnel with blast-TBI suggest that adequate functionality of the ubiquitin proteasome is essential for recovery from blast-TBI. Protein ubiquitination protects neurons from the detrimental impact of accumulating reactive oxygen, nitrogen species, and free release of zinc initiates  8, E3 ubiquitin protein ligase (nitiates  by initinitiates . In factnitiates –31, withnitiates .Pre-clinical models link blast-TBIs to the activation of the autonomous nervous system and the neuroendocrine–immune system, suggesting that neuronal pathology results from the over-activation of multiple biological systems . For exaTherefore, reduction in the expression of this gene suggests that this process is down-regulated and may contribute to chronic neurological symptoms and impairments in military personnel with a blast-TBI. This assertion is further supported by pre-clinical models that link down-regulation in protein ubiquitination genes to poor neuronal repair , greaterWe also report reduced expression of TNS1, a gene that is pivotal to neuronal recovery following a TBI, which works in coordination with protein ubiquitination genes. Thus, our finding of a reduction in TNS1 in conjunction with reductions in protein ubiquitination genes leads us to question if a down-regulation in these genes may compromise neuronal recovery following blast-TBI, resulting in chronic neurological symptoms and deficits. Increases in the activity of TNS1 are linked to a risk for the onset of cancer and allergy induced asthma , 42. In Axonal injury and degeneration, whether primary or secondary, contribute to the morbidity and mortality risks following TBI, which is shaped in part by the EGFR pathway through the activation of astrocytes. Astrocytes promote neuronal survival through potentiation of collateral synapses, migration of neuronal progenitor cells, and differentiation of glial progenitor cells following TBI , 45. EGFAlthough many of the genes that were significantly different in the blast-TBI group compared to controls related to neuronal compromise, a number of genes were not. One such gene was up-regulation of MLF1 interacting protein, a gene that suppresses cancer cell progression , as wellOur findings are limited by the cross-sectional nature of the study in a relatively small sample of military personnel. Additional larger studies are required to confirm our findings. Additionally, our design did not allow for randomization. To combat this limitation, we matched controls to blast-TBI participants on diagnoses of sleep disturbance and symptom severity of PTSD and depression. Although this allowed for isolation of gene expression changes more related to blast-TBI, the heterogeneity of symptoms of PCD and times since the blast event were issues that we were not able to address with the current design. In addition, without a third comparison group with a TBI not related to blast, we are unable to be certain that our findings are related to blast-TBI. We were limited in not including a clinician administered diagnostic tool to determine diagnoses of PTSD and depression, which is an issue in this group of patients who often present with complex symptoms that may be psychosomatic in nature. We report high rates of comorbidity in PCD, PTSD, and depression symptoms, as well as perceived health declines , and greTaken together, the identification of down-regulation in protein ubiquitination and mediation of this pathway in gene expression, as well as down-regulation of EGFR and TNS1, suggest involvement of these gene-expression pathways in chronic TBI pathology. Both of these gene-pathways protect neurons from secondary injuries following TBI and are highly specific to neurons , 54, andNo author has any conflicts of interest to disclose. The opinions and assertions in this manuscript are those of the authors and do not necessarily represent those of the Department of the Army, Department of Defense, U.S. Government, or the Center for Neuroscience and Regenerative Medicine.


Reaction types such as hydrolysis, transfer, addition, elimination, isomerization, hydride transfer and electron transfer have been included in the reaction classification, RLCP. This database includes information related to ligand molecules on the enzyme structures in the PDB data, classified in terms of cofactors, substrates, products and intermediates, which are also necessary to elucidate the catalytic mechanisms. Recently, the database system was updated. The 3D structures of active sites for each PDB entry can be viewed using Jmol or Rasmol software. Moreover, sequence search systems of two types were developed for the EzCatDB database: EzCat-BLAST and EzCat-FORTE. EzCat-BLAST is suitable for quick searches, adopting the BLAST algorithm, whereas EzCat-FORTE is more suitable for detecting remote homologues, adopting the algorithm for FORTE protein structure prediction software. Another system, EzMetAct, is also available to searching for major active-site structures in EzCatDB, for which PDB-formatted queries can be searched.The EzCatDB database ( The ‘basic reaction’ group includes reaction types, which can be related to the primary number of E.C. numbers : A reaction that adds a group to a double bond. This reaction is an inverse reaction of ‘addition reaction’ described above.Elimination reaction (eliminative double-bond formation): A reaction that eliminates a group from a moiety that consists of a single bond, in which the single bond can be converted to a double-bonded atoms. This reaction usually involves a Schiff-base bond, in which a carbonyl group is replaced by a Schiff-base bond, and vice versa; alternatively, an external/internal aldimine group is converted on the active sites of pyridoxal 5′-phosphate-dependent enzymes.Exchange of double-bonded atoms: A reaction that replaces double bond to its adjacent bond.Shift of the double-bond position (or isomerization): A reaction that shifts the position of a Hydride transfer: A major redox reaction that catalyzes transfer of one proton and two electrons between substrate/intermediate and cofactor such as NAD(H) and NADP(H). This reaction is distinct from the electron transfer described below.Electron transfer: A major redox reaction that catalyzes transfer of an electron, usually between heavy metals or sulfur atoms that are involved in redox reactions.As described earlier in the literature , the rea numbers . At the  numbers . Since tdouble bond, whereas elimination reaction (b) removes a group from a single bond, leading to formation of a new double bond. Reaction (c) replaces double-bonded atoms (examples: C=O to C=N and vice versa). Isomerization in our definition (d) catalyzes shifts of the position of double bonds. For example, triose phosphate isomerase  catalyzes two consecutive isomerization reactions, in which a shift of the double-bond position occurs twice. In the case of mandelate racemase , it also catalyzes two consecutive isomerization reactions. During the two reactions, a proton is removed from one side, forming an enolic intermediate, in the first isomerization, and another proton is attached from the opposite side in the second isomerization. Consequently, these two isomerization reactions complete the racemization. On the other hand, reaction types such as hydride transfer (e) and electron transfer (f) are major redox reactions. In the future, other redox reactions such as oxidation can be included in the RLCP reaction classification. Although the original RLCP site page (URL: http://ezcatdb.cbrc.jp/EzCatDB/RLCP/index.html) is hierarchic, the table of the whole reaction classification can be viewed at the RLCP overview site (URL: http://ezcatdb.cbrc.jp/EzCatDB/overview/reaction.html).Reaction types such as addition (a), elimination (b), exchange of double-bonded atoms (c) and isomerization (d) involve double bonds, in contrast to hydrolysis and transfer reactions that involve nucleophilic substitutions. Addition reaction (a) adds a group to a For each entry of EzCatDB, annotation of ligand molecules bound to the enzyme structures in the corresponding PDB entries  was perfSince the first release of this database, various improvements have been made in EzCatDB . The maiThe 3D structures of active sites for each PDB data can be viewed using Jmol  or RasmoSequence search systems of two types, EzCat-BLAST and EzCat-FORTE, were developed for different uses for the EzCatDB database. EzCat-BLAST is suitable for quick searches, adopting the BLAST algorithm ,16, wherFor the EzCat-BLAST system, sequence data of the UniProtKB and corresponding PDB data registered in the EzCatDB, which are assigned with manually annotated active-site residue information, are clustered using BLASTClust software (with 70% sequence identity threshold and 3% coverage), which is also a part of the BLAST package ,16, so tIn the EzCat-FORTE system, the position-specific scoring matrix (PSSM) is pre-calculated for each representative sequence that contains active-site information, according to the method for FORTE that was developed originally for protein structure prediction ,18. WhenCurrently, 1413 representative sequences from 871 EzCatDB entries are available for EzCat-BLAST and EzCat-FORTE. These representative sequences can be prepared semi-automatically.Another system, EzMetAct, is also available to search for major active-site structures in EzCatDB, for which PDB-formatted queries can be searched . AnalysiTaken together, these three systems are expected to be extremely helpful and convenient for searching for EzCatDB entries.http://ezcatdb.cbrc.jp/EzCatDB/DL/index.html. The general help page for this database is also available at http://ezcatdb.cbrc.jp/EzCatDB/ezcat.html.The EzCatDB enzyme reaction database was updated substantially. The recent developments include three novel search systems, two sequence search systems, EzCat-BLAST and EzCat-FORTE, and an active-site structure search system, EzMetAct. Using these systems, the database is expected to become more useful and convenient for users. In addition to other databases such as UniProtKB , PDBsum


AbstractBird tracking - GPS tracking of Lesser Black-backed Gulls and Herring Gulls breeding at the southern North Sea coast is described, a species occurrence dataset published by the Research Institute for Nature and Forest (INBO). The dataset (version 5.5) contains close to 2.5 million occurrences, recorded by 101 GPS trackers mounted on 75 Lesser Black-backed Gulls and 26 Herring Gulls breeding at the Belgian and Dutch coast. The trackers were developed by the University of Amsterdam Bird Tracking System . These automatically record and transmit bird movements, which allows us and others to study their habitat use and migration behaviour in great detail. Our bird tracking network is operational since 2013. It is funded for LifeWatch by the Hercules Foundation and maintained in collaboration with UvA-BiTS and the Flanders Marine Institute (VLIZ). The recorded data are periodically released in bulk as open data (http://dataset.inbo.be/bird-tracking-gull-occurrences), and are also accessible through CartoDB and the Global Biodiversity Information Facility (GBIF).In this data paper,  The project builds upon the extensive knowledge the INBO has acquired over the last 15 years when studying in particular postnuptial migration, as well as mate and site fidelity of large gulls, by means of sightings of colour-marked individuals ringed in Belgium and via individual-based life-history studies by UGent and UA. The data collected through this bird tracking network allows to study the migration patterns and habitat use of the gulls in more detail. Furthermore, they are no longer biased towards locations where observers can see colour-ringed birds. To allow greater use of the data beyond our research questions, all data are published as open data.As part of our terrestrial and marine observatory for LifeWatch , Larusargentatus (Herring Gull)The tracked birds breed at the southern North Sea coast in three colonies, located in the ports of Zeebrugge (Belgium), Ostend (Belgium) and Vlissingen-Oost (the Netherlands). During the breeding season, their foraging range includes the west of Belgium and the Netherlands, northern France, the North Sea, and the English Channel. The Lesser Black-backed Gulls migrate south in winter, mainly hibernating in the south of Spain, Portugal, and North Africa Figure .PageBreak10° to 60° latitude, -25° to 10° longitudeDate range: 2013-05-17 to 2015-09-02Formation periods: breeding season 2013Formation periods: migration/wintering season 2013-2014Formation periods: breeding season 2014Formation periods: migration/wintering season 2014-2015Formation periods: breeding season 2015The birds were trapped and tagged at or near their breeding colony at the southern North Sea coast.PageBreak51.341 latitude, 3.182 longitude) at sites that are not used for port activities and on rooftops. The first Herring Gulls (HG) nested here in 1987, followed by the first breeding record of Lesser Black-backed Gull (LBBG) in 1991. In the 1990s, the number of breeding pairs strongly increased, with a maximum of 2,336 pairs of HG and 4,760 pairs of LBBG in 2011 (LBBG and HG (Vulpesvulpes). In the period 2000–2010, Zeebrugge hosted on average 91% of all large gulls in Belgium. This proportion decreased to 33% in 2015 , breeding started in 1993. Here the the numbers of breeding pairs are still increasing with a maximum of 505 pairs of HG and 551 pairs of LBBG in 2015 (data INBO). In Ostend most gulls breed on rooftops both in industrial areas and in the town itself.In the colony of Ostend  is located in the industrial port area near Vlissingen. Here the gulls nest on the grassy grounds that are not yet in use for port activities. LBBG started breeding in 1984, and the area is now the second biggest colony of LBBG in the southwestern part of the Netherlands. The numbers of breeding pairs increased from a few hundred in the second part of the nineties to 5,220 pairs in 2011. HG started breeding in 1977 (5–10 pairs) with a maximum of 4,353 pairs in 2008  and a feather sample to determine the sex. The e Figure .The number of tagged birds and their trap location per year are:HG nesting on the roof of the Vismijn in Ostend and 22 LBBG nesting in the port of Zeebrugge.2013: 5 HG and 24 LBBG nesting in the port of Zeebrugge, and 3 HG feeding on the Visserskaai in Ostend .2014: 8 HB nesting on the roof of the Vismijn in Ostend, 1 HG nesting on the roof of the Vismijn in Ostend, 13 LBBG nesting in the port of Zeebrugge, and 16 LBBG nesting in Vlissingen-Oost.2015: 9 UvA-BiTS, http://www.uva-bits.nl). The system has been described in detail in PageBreakbuilt-in tri-axial accelerometer as well. The system allows us to remotely set or change a measurement interval per tracker: the actual interval between measurements is provided in samplingEffort as secondsSinceLastOccurrence.The birds are tracked with the University of Amsterdam Bird Tracking System  will thus not be found in the dataset. At the time of publication most individuals (88%) were tracked for more than 10 days and 41% for more than 100 days .The data are stored on the tracker, until these can be transmitted automatically and wireless to a base station using the built-in ZigBee transceiver with whip antenna. This receiver is also used to receive new measurement settings. The spatial range for this communication is restricted to the location of the base station (or antenna network), which is placed near the colony. Data cannot be retrieved from birds that do not return to the colony with the base station. For 3 of the 101 birds fitted with trackers no data were obtained and their UvA-BiTS , which is accessible to the involved researchers only. We periodically export the tracking data to CartoDB for visualization purposes , removing test records and flagging outliers.Data received by the base stations are automatically harvested, post-processed, and stored in a central PostgreSQL database at PageBreakoccurrences/mapping/dwc-occurrence.sql). The dataset is documented, published via our IPT (http://dataset.inbo.be/bird-tracking-gull-occurrences), and registered with the Global Biodiversity Information System (http://www.gbif.org/dataset/83e20573-f7dd-4852-9159-21566e1e691e). Issues or remarks regarding the data or this procedure can be reported at https://github.com/LifeWatchINBO/data-publication/tree/master/datasets/bird-tracking-gull-occurrencesTo create the Darwin Core Archive, we extract the data from the database and standardize these to Darwin Core using an SQL query  and standardization to Darwin Core (https://github.com/LifeWatchINBO/data-publication/blob/master/datasets/bird-tracking-gull-occurrences/mapping/dwc-occurrence.sql) are publicly documented.See the section PageBreakResearcher captures bird, takes biometrics, attaches GPS tracker, and releases bird.Researcher sets a measurement scheme, which can be updated anytime.GPS tracker records data.GPS tracker automatically receives new measurement settings and transmits recorded data when a connection can be established with the base station at the colony.UvA-BiTS.Recorded data are automatically harvested, post-processed, and stored in a central PostgreSQL database at INBO team periodically exports tracking data to CartoDB and makes these publicly accessible.LifeWatch INBO team periodically (re)publishes data as a Darwin Core Archive, registered with GBIF.LifeWatch Data stream stops when bird no longer returns to colony or if GPS tracker no longer functions .Object name: Bird tracking - GPS tracking of Lesser Black-backed Gulls and Herring Gulls breeding at the southern North Sea coastFormat name: Darwin Core Archive formatFormat version: 1.0Character encoding: UTF-8Language: EnglishLicense: http://creativecommons.org/publicdomain/zero/1.0/Usage norms: http://www.inbo.be/en/norms-for-data-usePublication date: 2014-06-18Distribution: http://dataset.inbo.be/bird-tracking-gull-occurrencesDOI: http://doi.org/10.15468/02omlyhttp://creativecommons.org/publicdomain/zero/1.0/). We would appreciate however, if you read and follow these norms for data use (http://www.inbo.be/en/norms-for-data-use) and provide a link to the original dataset (http://doi.org/10.15468/02omly) whenever possible. If you use these data for a scientific paper, please cite the dataset following the applicable citation norms and/PageBreakor consider us for co-authorship. We are always interested to know how you have used or visualized the data, or to provide more information, so please contact us via the contact information provided in the metadata, opendata@inbo.be or https://twitter.com/LifeWatchINBO.To allow anyone to use this dataset, we have released the data to the public domain under a Creative Commons Zero waiver (https://inbo.cartodb.com/u/lifewatch), where users can query the data using SQL via the CartoDB API or download these in various formats . Two tables are of use: bird_tracking, containing all occurrence data and bird_tracking_devices, containing information on the GPS trackers and individual birds. Note that these tables are not standardized to Darwin Core, contain flagged outliers (omitted from the standardized dataset) and include data from other bird species. For more info, see https://github.com/LifeWatchINBO/bird-tracking/blob/master/cartodb/README.mdAll our public bird tracking data are also available through CartoDB , bird biometrics data measured during tagging , life history data , as well as growth data of chicks.PageBreakBird tracking networkhttp://www.herculesstichting.be/in_English/), with additional funding from the Research Foundation Flanders (FWO) to Wendt Müller and Luc Lens and Interreg Natura People (EFRO) through the Province of West Flanders.This bird tracking network is funded for LifeWatch by the Hercules Foundation (http://www.lifewatch.be/en/gps-tracking-network-large-birds


Genomic features of whole genome sequences emerging from various sequencing and annotation projects are represented and stored in several formats. Amongst these formats, the GFF  has emerged as a widely accepted, portable and successfully used flat file format for genome annotation storage. With an increasing interest in genome annotation projects and secondary and meta-analysis, there is a need for efficient tools to extract sequences of interests from GFF files.We have developed GFF-Ex to automate feature-based extraction of sequences from a GFF file. In addition to automated sequence extraction of the features described within a feature file, GFF-Ex also assigns boundaries for the features , which are not explicitly specified in the GFF format, and exports the corresponding primary sequence information into predefined feature specific output files. GFF-Ex package consists of several UNIX Shell and PERL scripts.http://bioinfo.icgeb.res.in/gff.Compared to other available GFF parsers, GFF-Ex is a simpler tool, which permits sequence retrieval based on additional inferred features. GFF-Ex can also be integrated with any genome annotation or analysis pipeline. GFF-Ex is freely available at  GFF represents genome feature data in a tab-delimited table, single feature per line, making it ideal for use with various data analysis pipelines. Currently, the scientific communities are becoming more and more reliant on these information for secondary analysis and laboratory experiments too, which has resulted in a growing need for efficient tools to extract desirable sequences based on annotations[Technical advancements in the field of high-throughput DNA sequencing,2, the eotations. This mohttp://bioinfo.icgeb.res.in/gff/) is a collection of various modules developed using Shell and PERL string parsing scripts. The current version of GFF-Ex  equipped with an installation file, copies program scripts to the user specified installation directory. The package also includes few example files and a README file to help users install and execute GFF-Ex. GFF-Ex is robust and adaptable towards future integrations of the GFF-Ex plug-ins. The software enables GFF-Ex users to pass input arguments and parameters as a single command statement, along with invoking GFF-Ex. This helps GFF-Ex to switch to the specified modules/plug-ins without taking much of kernel time. For an input file size of about 500 MB, the CPU time between invocation and termination of GFF-Ex is 2 m2.305 s. The current GFF-Ex architecture is suitable for transparent integration with various sequencing data analysis pipelines, meeting the requirements of researchers handling large datasets. To evaluate the GFF-Ex performance with other publicly available stand-alone parsers, we have performed comparison with functions of few parsers performing similar tasks. We compared GFF-Ex with other publicly available stand-alone gff parsers (accessed on 27-02-2013), namely, Sanger Institute GFF Perl modules[GFF-Ex . “COLx” plugin exports feature based coordinates from specified columns and translates them into sequences using GFF-Ex. Another plug-in “FETx” (http://bioinfo.icgeb.res.in/gff/gffdownloads/FETx.tar.gz) is a plugin for feature extraction, which extracts sequences on the basis of user-specified custom features declared in the input GFF annotation file. Keeping in mind the growing rates of genomic data and GFF files, the next version of GFF-Ex (under development) shall be made compatible with high performance clustered nodes.GFF-Ex is freely available from With the rapid advancements and automation of sequencing projects, the interests of scientific groups involve studies and experimental designs that make use of sequencing and GFF annotations. Handling large datasets to parse desirable information, especially sequence files, have always been an important and complex startup step in such studies. GFF-Ex is a reliable GFF parsing tool, which integrates with various applications and pipelines requiring large volumes of sequence extraction from GFF files, based on customized or GFF defined annotations.Project Name: GFF-Ex (A genome feature extraction package)Project home page:http://bioinfo.icgeb.res.in/gff/Operating system(s): UNIXProgramming Language: PERL and UNIX ShellLicense: NAAny restrictions to use by non-academics: None.The authors declare that they have no competing interests.DG and AR conceptualized development of the package. DG guided AR to develop the package; AR and DG tested the package. DG and AR wrote and approve the manuscript.


Shewanella oneidensis MR-1 is a facultative anaerobe that respires using a variety of inorganic and organic compounds. MR-1 is also capable of utilizing extracellular solid materials, including anodes in microbial fuel cells (MFCs), as electron acceptors, thereby enabling electricity generation. As MFCs have the potential to generate electricity from biomass waste and wastewater, MR-1 has been extensively studied to identify the molecular systems that are involved in electricity generation in MFCs. These studies have demonstrated the importance of extracellular electron-transfer (EET) pathways that electrically connect the quinone pool in the cytoplasmic membrane to extracellular electron acceptors. Electricity generation is also dependent on intracellular catabolic pathways that oxidize electron donors, such as lactate, and regulatory systems that control the expression of genes encoding the components of catabolic and electron-transfer pathways. In addition, recent findings suggest that cell-surface polymers, e.g., exopolysaccharides, and secreted chemicals, which function as electron shuttles, are also involved in electricity generation. Despite these advances in our knowledge on the EET processes in MR-1, further efforts are necessary to fully understand the underlying intra- and extracellular molecular systems for electricity generation in MFCs. We suggest that investigating how MR-1 coordinates these systems to efficiently transfer electrons to electrodes and conserve electrochemical energy for cell proliferation is important for establishing the biological basis for MFCs. Microbial fuel cells (MFCs) are devices that use living microbes as catalysts for the conversion of fuels, such as organic compounds, into electricity . In MFCsProteobacteria, mediate the transfer of electrons to anodes  pathways), and are therefore able to use electrodes as terminal electron acceptors for respiration  in MR-1 critical for electricity generation in MFCs have been identified. Intracellular catabolic pathways that produce reducing equivalents  have also been extensively studied in this species. In addition, several studies have analyzed the transcriptional regulatory systems that control catabolic and electron-transfer pathways in MR-1. In this article, we summarize the current knowledge on catabolic and regulatory systems in S. oneidensis MR-1 , across the inner membrane (IM) and outer membrane (OM), to extracellularly located insoluble electron acceptors. Genetic and biochemical studies have identified five primary protein components, CymA, MtrA, MtrB, MtrC, and OmcA, comprising the EET pathway in In the Mtr pathway, EET is initiated by the transfer of electrons from the IM quinone pool to IM-anchored CymA (SO_4591). CymA is a tetraheme c-type cytochrome belonging to the NapC/NirT protein family and consists of a short N-terminal region that is anchored in the IM and a long C-terminal region that protrudes into the periplasm , 2000. TmtrB-deletion strain, but is localized in the OM fraction in wild-type MR-1, indicating that MtrB supports the in vivo localization of MtrA to the OM, although MtrA per se is a soluble protein (MtrA (SO_1777) is regarded as a key protein for electron transfer to OM c-type cytochromes (OM-cyts), such as MtrC and OmcA, based on its periplasmic localization and biochemical association with MtrB and MtrC . MtrB S. Evidenc protein .mtrC and omcA and severely impaired in a mtrC/omcA double-knockout mutant  oxides (omcA-deletion mutant to reduce MnO2 (2O3) than MtrC. Furthermore, MtrC appears to play a dominant role in electron-transfer reactions to electrodes, whereas OmcA plays a preferential role in the attachment of cells to solid surfaces (The OM-cyts OmcA (SO_1779) and MtrC (SO_1778) contain 10 heme-binding sites and serve as the terminal reductases for extracellular electron acceptors in the Mtr pathway , 2004. Tt mutant . In addi) oxides , and theuce MnO2 . Howeversurfaces .fccA and stc (cctA) exhibits substantial growth deficiencies on ferric iron and other soluble electron acceptors. These observations suggest that the periplasmic cytochrome pool, which mainly consists of STC and FccA, plays important roles in mediating electron transfer from CymA to OM-cyts in the Mtr pathway.Although many studies have demonstrated that OmcA and the MtrCAB complex play key roles in the Mtr pathway, it is not yet fully understood how electrons are transferred from IM-anchored CymA across the periplasmic space, which has an average distance of 23.5 nm, to the OM components of this pathway . One posShewanella spp. secrete flavins, including riboflavin and flavin mononucleotide (FMN), which function as electron shuttles for MET. Notably, however, Studies have indicated that electrons are transferred from OM-cyts to electrodes via two pathways, direct electron transfer (DET) and mediated electron transfer (MET) pathways . In DET,Although MR-1 appears to utilize both DET and MET pathways, several lines of evidence indicate that soluble flavins are indispensable for EET under physiological conditions. For instance, The X-ray crystal structures of two OM-cyts, MtrF (MtrC homolog) and OmcA, have been resolved to date , and havomcA-mtrCAB; the mtr genes) are organized in a cluster and oriented in the same direction  at 1:1:1 stoichiometry  have been identified in the upstream regions of omcA and mtrC  receptor protein (CRP) and adenylate cyclase (CyaC) are essential for the transcriptional activation of the mtr genes , fumarate (fccA), nitrate (nap), and DMSO (dms), under anaerobic conditions (mtr genes (omcA and mtrCAB), and demonstrated that CRP directly regulates the expression of these genes by binding to the upstream regions of omcA and mtrC  binds to the deleted region and negatively regulates the expression of omcA  regulatory system and has been well characterized functionally in E. coli. The E. coli Arc system consists of ArcA and the sensor histidine kinase ArcB, which acts as an indirect oxygen sensor by sensing the redox state of ubiquinone and menaquinone , and Fur may be involved in the transcriptional regulation of the aquinone . Studies E. coli , 2013. Gand mtrC .Fumarate nitrate-reduction regulator (Fnr) is another transcriptional regulator that is reported to influence the expression of the mtr genes. In E. coli, Fnr functions as a sensory protein for environmental oxygen levels by directly reacting with oxygen through a 4Fe–4S cluster  and Mn(IV) oxides, indicating that, unlike CRP, Fnr only plays a minor role in regulation of the Mtr pathway. cluster . Cruz-Gaferric uptake regulator (Fur) and intracellular iron levels affect expression of the mtr genes and the EET activity of Shewanella spp. Fur acts as a sensor for intracellular iron levels in many Gram-negative bacteria, including E. coli and Shewanella (2+) and regulates the transcription of many genes, including those related to iron uptake and homeostasis -reducing conditions, suggesting that the intracellular iron concentration is a key determinant of the expression levels of the mtr genes. Furthermore, mtr homologs in S. piezotolerans WP3 by directly binding to the upstream region of an omcA homolog (swp3277). In MR-1, the deletion of the fur gene decreases mtr-gene expression, and a putative Fur-binding site is located upstream of omcA  in the culture supernatant, along with decreased levels of FMN and riboflavin. Since UshA was located to the periplasmic space and was shown to catalyze the hydrolysis of FAD to FMN  that appear to be involved in the reduction of solid Fe(III) oxides and electricity generation in MFCs. MtrC and OmcA were also shown to be required for not only the EET activity of MR-1 cells, but also for the conductivity of nanowires  and other biofilm-related components are also reported to influence the EET activity of MR-1. For example, D- or L-lactate stereoisomers under both aerobic and anaerobic conditions (D- and L-lactate dehydrogenases (D- and L-LDH) that use oxidized quinones as electron acceptors  consisting of a putative lactate permease gene [lldP (SO_1522)] and candidate LDH genes for oxidative lactate utilization (dld-II (SO_1521)] is a distant homolog of FAD-dependent LDH in yeast, whereas L-LDH is predicted to be comprised three subunits encoded by lldEGF (SO_1520 to SO_1518). Genetic and biochemical characterization confirmed that dld-II and lldEFG encode functional D- and L-LDHs, respectively  is required for L-lactate utilization by MR-1, although the regulatory mechanisms, including the role of LlpR, in the transcription of LDH genes have not yet been determined.Carbon catabolism is comprised a series of enzymatic reactions, in which reducing equivalents, such as NADH, formate, and reduced quinones, are produced from the oxidation of organic matter. The generated reducing equivalents must be removed from the cell for the catabolic reactions to proceed. In MR-1, these reducing equivalents are utilized for the transfer electrons to extracellular electron acceptors via the EET pathway. As can be seen from the main catabolic pathways in MR-1 Figure , this stnditions . In manycceptors . Althouglization . The putectively . Althougbacteria . Notably2, because the pyruvate produced from lactate is completely oxidized into CO2 (aceEFG (SO_0424 to SO_0426)] and/or pyruvate formate-lyase [pflB (SO_2912)], resulting in the formation of acetyl-CoA and CO2 or formate, respectively (pta (SO_2916)] and acetate kinase [ackA (SO_2915)], where ATP is synthesized by substrate-level phosphorylation (ack- and pta-deletion mutants of MR-1 are unable to grow on lactate as the sole electron donor and fumarate or Fe(III) citrate as the electron acceptor  is also not encoded in the genome, MR-1 is unable to catabolize glucose. Although MR-1 has a complete set of genes encoding the phosphoenolpyruvate (PEP):glucose phosphotransferase system , it is known that this system does not support growth on glucose via the ED pathway, as this glycolytic pathway cannot produce a sufficient amount of PEP for the phosphotransferase reaction  and glucokinase (glk) genes of Zymomonas mobilis allowed MR-1 to generate current using glucose as the electron donor in MFC , are not sufficiently expressed under anaerobic conditions , isocitrate dehydrogenase (icdA), succinate dehydrogenase (sdhABCD), and malate dehydrogenase (mdh, E. coli, including acnA and sdhABCD, are regulated by Fur and the related small RNA, RyhB (Several studies have indicated that the regulatory systems for the TCA cycle genes of y system . Under aase mdh, . Howeverase mdh, . It has NA, RyhB , the corNA, RyhB . FurtherMR-1 is an extensively studied model organism for understanding the genetics and biochemistry of bacterial EET and electricity generation in MFCs. Current knowledge on the mechanisms by which bacteria generate electricity in MFCs has largely been obtained from studies performed on MR-1. As described in this article, studies have revealed that many cellular components that are directly and/or indirectly involved in bacterial electricity generation have been identified. However, relatively limited information is available concerning how these components cooperatively work for efficiently generating electricity and conserving energy. As available evidence suggests that the EET pathway is regulated by the level of cAMP, which is an indicator of the cellular energetic states , the EETThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Mass spectrometry (MS) is a very sensitive and specific method for protein identification, biomarker discovery, and biomarker validation. Protein identification is commonly carried out by comparing MS data with public databases. However, with the development of high throughput and accurate genomic sequencing technology, public databases are being overwhelmed with new entries from different species every day. The application of these databases can also be problematic due to factors such as size, specificity, and unharmonized annotation of the molecules of interest. Current databases representing liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based searches focus on enzyme digestion patterns and sequence information and consequently, important functional information can be missed within the search output. Protein variants displaying similar sequence homology can interfere with database identification when only certain homologues are examined. In addition, recombinant DNA technology can result in products that may not be accurately annotated in public databases. Curated databases, which focus on the molecule of interest with clearer functional annotation and sequence information, are necessary for accurate protein identification and validation. Here, four cases of curated database application have been explored and summarized.Escherichia coli (E. coli) flagella (H antigen) database produced for MS-H, a new H-typing technique. Clearly annotating the proteins of interest was essential for highly accurate, specific, and sensitive sequence identification, and searching against public databases resulted in inaccurate identification of the sequence of interest, while combining the curated database with a public database reduced both the confidence and sequence coverage of the protein search.The four presented curated databases were constructed with clear goals regarding application and have proven very useful for targeted protein identification and biomarker application in different fields. They include a sheeppox virus database created for accurate identification of proteins with strong antigenicity, a custom database containing clearly annotated protein variants such as tau transcript variant 2 for accurate biomarker identification, a sheep-hamster chimeric prion protein (PrP) database constructed for assay development of prion diseases, and a custom Curated protein sequence databases incorporating clear annotations are very useful for accurate protein identification and fit-for-purpose application through MS-based biomarker validation. The maturity of modern genomic sequencing technology has seen genomic databases being generated for more and more species and public databases growing larger every day. Owing to advanced instrumentation and powerful search engines, this mounting comprehensiveness and the refinement of databases have benefited mass spectrometry (MS)-based protein identification and biomarker discovery. However, despite improvement in these areas, MS-based protein characterization using public databases has not yet been perfected for all species. For instance, annotation of individual genes and their related protein products has not been standardized. As the setup of sequence-focused protein identification by MS is primarily based on post-proteolytic enzyme-digested peptides, much important annotation information, including the functions of proteins, can be ignored by the applied search engine . It has In this paper, four projects spanning six years at the National Microbiology Laboratory in Canada, involving curated database creation and application for the purpose of biomarker identification and validation, are presented. All MS-based protein identification was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS) detection and a Mascot database search algorithm. All the curated databases are presented in FASTA file format in Additional file http://www.poxvirus.org/index.asp?bhcp=1), a more accurate identification was obtained (i.e. the “sheeppox virus protein”) with higher confidence (Mascot score = 1039) based on 80 peptide matches  protein bands derived from sheeppox virus . A westeThe second project employed MS to detect a protein with transcript variants. Microtubule-associated protein tau (or simply “tau”) has several variant forms ,11; examMesocricetus auratus) and sheep (Ovis aries)] represented only the third and fourth hits, respectively. In order to accurately identify the chimeric protein, a curated database called “PrpSheep-Hamster” was created to accurately annotate and identify the protein , where low levels of infectious prion can be detected in human cerebral spinal fluid . When thin Table . Indeed,in Table . This siE. coli flagellar serotyping. As there are 53 flagellar serotypes in E. coli bacteria, serotyping by way of antigen-antibody agglutination reactions is a costly and tedious process [E. coli flagellar database representing all serotypes was created as a FASTA file, using sequence data obtained from this public database of NCBInr. The custom database was used to successfully identify all examined flagella H types from reference E. coli strains [The fourth project highlights the ability of both MS and curated protein database to supplement traditional  process ,15. In rWith the growing comprehensiveness of many species’ genomes and the maturity of MS-based technology, biomarker application and validation are being applied more and more for use in disease diagnosis and improvements of conventional bio-assay methods. From the above cases, it is evident that curated databases are very useful for accurate, specific, and consistent identification and confirmation of proteins and biomarkers of interest. Moreover, clearly annotated, fit-for-purpose databases prove extremely useful for high quality and standardized method development and validation using MS-based technology. Due to the sophistication of MS instrumentation and specific software requirements, together with variations in protein expression and posttranslational modifications, detection of analogous proteins through MS remains complicated. This paper will hopefully serve as an example and reminder for all MS users, especially those performing specific and/or “non-mainstream” research and applications, recombinant DNA technology quality control, and targeted biomarker identification and validation, to use curated fit-for-purpose databases in order to consistently and accurately identify MS data.All the databases are available in the Additional file LC-MS/MS: Liquid-chromatography tandem mass spectrometry; MS: Mass spectrometry; MSDB: Mass spectrometry database; NCBInr: National Centre of Biotechnology Information Non-Redundant; PBR: Poxvirus Bioinformatics Resource Centre; PrP: Prion protein; Pup: Prokaryotic ubiquitin-like protein; RT-QuIC: Real-time quaking-induced conversion; SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis.The authors declare that they have no competing interests.E. coli flagella database and was responsible for critical writing of the manuscript. SM was responsible for mass spectrometry runs and database maintenance. SB was responsible for managing the poxvirus project and critical writing of the paper. TRB contributed to the design of the poxvirus project. GW was responsible for managing the E. coli flagellar typing project. JKD was responsible for managing the tau-2 and prion protein detection project, as well as critical writing of the paper. All authors read and approved the final manuscript.KC was responsible for preparing tryptic digest samples, collecting the data, and drafting the manuscript. AMS updated the Contains four individual databases in FASTA file format.Click here for fileSheeppox Virus-band A-MSDB search.Click here for fileSheeppox Virus-band A-PBRdb search.Click here for fileTau-2 NCBInr DB search.Click here for fileTau-2 custom DB search.Click here for fileSh-Ha Chimeric PrP-NCBInr DB search.Click here for fileSh-Ha PrP-custom DB search.Click here for fileH37-NCBInr DB search.Click here for fileH37-E coli-flagellar DB search.Click here for file


Large randomized trials have failed to show a beneficial effect of statin treatment in chronic HF. The investigators tried to evaluate the long-term effects of statin therapy in patients with new onset heart failure (HF) following acute myocardial infarction (AMI).Between January 2008 and December 2011, a total of 13,616 AMI patients were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) which was a prospective, multi-center, nationwide, web-based database of AMI in Korea. From this database, we studied 1,055 patients with AMI who had newly developed severe acute HF [left ventricular ejection fraction ≤ 40%] and were discharged alive. The patients were divided into two groups, a statin group (n = 756) and a no-statin group (n = 299). We investigated the one-year major adverse cardiovascular events (MACEs), including all-cause mortality, MI, and any revascularization of each group. We then performed a propensity-score matched analysis.p = 0.47). Propensity-score matching yielded 256 pairs, and in that population we observed comparable results in terms of MACEs  and mortality . Cox-regression analysis revealed that statin therapy was not an independent predictor for occurrence of a MACE  or all-cause mortality .In the original cohort, one-year MACEs were similar between the two groups (16.5% vs. 14.7% in the statin or no-statin groups; Statin therapy was not associated with a reduction in the long-term occurrence of MACEs or mortality in survivors of AMI with severe acute HF in this retrospective cohort study. The 3-hydroxy-3-methylglutaryl coenzyme-A inhibitors or statins are widely used, and statin therapy has been shown to reduce adverse cardiovascular (CV) events and all-cause mortality in atherosclerotic coronary artery disease ,2. HowevOur study was conducted according to the ethical guidelines of the 1975 Declaration of Helsinki, as revised in 2000. The study protocol was approved by the institutional review board of all centers, and the approval number was 05–49 of Chonnam National University Hospital. Participating sites are listed in an appendix. Given the retrospective design of the project, this institutional review board waived the need for consent. The study was conducted using the format recommended by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines .The Korea Acute Myocardial Infarction Registry (KAMIR) was developed to establish a standardized practice guideline for AMI patients in Korea. The KAMIR was a prospective, multi-center nationwide web-based database supported by the Korean Society of Cardiology that collects precise data with regard to demographic characteristics, treatment strategies in the emergency room, detailed angiographic findings, in-hospital medications, and the clinical outcomes of AMI patients. The detailed was described in previously . It begaThis is a retrospective observational pooled analysis of nationwide registry data. Between January 2008 and December 2011, a total of 13,616 AMI patients were enrolled in the KAMIR registry. As shown in All of the definitions of the clinical outcomes in this study were based on the recommendations of Academic Research Consortium . The prit-test (2-sided) and Chi-square test or Fisher's exact test were used, respectively. An unadjusted Cox proportional-hazards model was used to evaluate the association between statin treatment and clinical outcomes and to calculate hazard ratios (HR) with 95% confidence intervals (CI). The cumulative MACE and mortality rates were estimated using the Kaplan-Meier method with the log rank test, and the time-dependent effect of statin therapy as a covariate on clinical outcomes was analyzed using a Cox proportional hazards regression model.All descriptive data are expressed as the mean ± SEM. To compare continuous and categorical variables between groups, Student’s To overcome differences in baseline characteristics and discharge medications between the two groups and to minimize any selection bias, we performed a propensity-score matched analysis, which yielded 256 well-matched pairs. Briefly, the propensity-score of each patient, which indicated the estimated probability of receiving statin treatment, was calculated from the equation of a logistic regression model. Variables included in the logistic regression model used to deduce the propensity-score were age; gender; body mass index; systolic and diastolic blood pressure; heart rate; hypertension; diabetes mellitus; dyslipidemia; family history of heart disease; smoking history; specific medical history, including coronary artery disease, cerebrovascular accident, peripheral artery disease, and statin use before index admission; and lipid profiles, including total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein cholesterol. The c-statistic for the propensity score derivation was 0.85. Analyses were carried out using SPSS for Windows, version 19.0 .p = 0.72). In Angiographic results, lesion characteristics showed more severe in the statin group, but pre-procedural Thrombolysis in Myocardial Infarction score; pre-procedural lesion stenosis; and implanted stent number, diameter, and length were not significantly different between the two groups . The intensities of statin therapy were also not an independent predictor of MACEs or all-cause mortality , and the same tendency was observed in the propensity score-matched populations.The statins prescribed at discharge and the intensities of statin therapy are demonstrated in In this registry-based observational study, we found that long-term statin therapy did not reduce one-year MACEs or all-cause mortality in patients with AMI complicated by severe acute HF. Additionally, neither the type nor the intensity of statin therapy affected the one-year clinical outcomes of enrolled patients.p < 0.01), and after adjustment for various confounding factors, the relative risk of all-cause mortality was lower in patients belonging to the group that received statin therapy  [p < 0.01). Statin therapy has also been shown to independently reduce HF re-admissions  and death from HF  [Although all of the patients in our study suffered from new onset acute HF, the results of our study are comparable to other prospective randomized controlled trials, such as Controlled Rosuvastatin Multinational Trial in HF trial (CORONA) or GISSI-Heart Failure trial (GISSI-HF), that enrolled patients with chronic systolic HF ,8. In co < 0.01) . In addi < 0.01) . However10. Coenzyme Q10 is a key element in mitochondrial oxidative phosphorylation, and its depletion has been reported to be associated with increased mortality [et al. demonstrated that neither statin (rosuvastatin) nor coenzyme Q10 is an independent prognostic factor in patients with HF [Recent clinical studies have suggested that the potential benefits of statins in HF patients can be partially explained by their lipid-independent pleiotropic effects. These pleiotropic effects include stabilizing atherosclerotic plaques, improving endothelial function, and alleviating vascular oxidation and inflammation . On the ortality ,21, but  with HF .According to the latest guidelines for dyslipidemia management, there is no obvious evidence that supports a beneficial effect of statin therapy in patients with New York Heart Association (NYHA) class II-IV HF ,24. AddiOur study had a number of limitations. First, it was a retrospective, observational study based on a registry data. There was a lack of data that cannot be ignored although we encouraged to fill-up the missing values. Undetected selection bias may remain despite our cautious use of propensity-score matching with excluding patients with missing data. We could not controlled non-cardiac related medications and other patients' condition such as nutritional status or life style because of inherent limitations of registry data. Second, the number of patients participating in this study was relatively small. Third, there was the possibility of including patients with pre-existing non-ischemic HF despite of our careful review. Fourth, we have no detailed follow-up data with regard to lipid profiles or echocardiographic parameters of registered patients. Finally, we were not able to acquire safety information for the statins prescribed to the patients, such as the incidence rates of serious adverse effects or compliance data. Despite these drawbacks, we are able to present some negative evidence with regard to statin therapy in patients with MI complicated by severe acute ischemic HF. We also found that the type of statin and intensity of statin therapy did not exert an influence on clinical outcomes.In conclusion, statin therapy had no significant effect on the one-year incidence of MACEs or mortality in survivors with acute severe ischemic HF following AMI.The Korea Acute Myocardial Infarction Registry (KAMIR) was approved by the institutional review board (IRB) at each participating center .S1 Table(DOC)Click here for additional data file.