Myasthenia Gravis : en retrospektiv journalstudie ved Ullevål universitetssykehus i 2005

Myasthenia Gravis: a retrospective study of case records at Ullevål University Hospital in 2005 Medical student Hilde Teigen Andås Medical student Tahira R. Ahmad Guidance by Chantal ME Tallaksen Department of Neurology, UUH Background Myasthenia gravis (MG) is an autoimmune neurological disease caused by a disturbance in the neuromuscular transmission. The most frequent type is associated with the presence of antibodies to the acetylcholine receptor (AChR) in the neuromuscular junction (80-85% of the cases). The world prevalence of MG is estimated to be between 8-15/100 000. Objectives and hypothesis Our main objectives were to establish the prevalence of myasthenia gravis at Ullevål University Hospital in August 2005, and to examine how various factors influence the course of the disease; > age at onset > severity at onset > antibodies > treatment We also wanted to confirm in our hospital population that 1. MG most frequently affects fertile women 2. The older group of patients have a more severe illness 3. Elders have better effect of treatment Design A study of case records. Data and methodology Myasthenia gravis is diagnosed in the hospital at the department of neurology. This implies that all patients with MG at some time have been examined at a hospital. We searched the hospital’s archives for MG patients the last 15 years using the ICD-10 and ICD-9 criteria’s. We found a total of 150 patients. After examining the case records we could include 80 patients who were still alive and had a verified MG in our study. We divided our patient material in two groups, group I with disease onset under 50 years, group II with disease onset after 50 years. It is important to be aware that our data might be insufficient because of faulty case records. The data was registered in Microsoft Excel and made anonymous. The statistical analysis was preformed using SSPS. Results There are twice as many women than men in our material. In group I (56% of the patients) 32% were men and 67% were women. Men had a milder condition, but there wasn’t a clear difference between the women. 81% of the patients had documented elevated AChR antibodies. There was no significant difference in respect of antibodies between group 1 and 2. 60% of the patients were thymectomized, with no difference between men and women. All men and 80% of the women in group 1 were thymectomized, compared to 20% and 31% in group 2. Discussion The prevalence of MG in our population at August 1st 2005 was 10.5/100 000. All our hypotheses were verified in our material. 81% of the patients had positive AChR antibodies, which concurs with literature. 20 % (6) of the women diagnosed before 50 years of age were not thymectomized. Eight patients diagnosed after the age of fifty were thymectomized. This is higher than expected, but six of these had a thymoma. Our study confirms current literature reports about MG patients, particularly the differences between the patients with early and late onset. The hospital reports were unfortunately often insufficient to study these differences in details, and more detailed studies (without anonymity) would be necessary to further examine these differences

El procés de desistiment de les persones empresonades : obstacles i suports

La voluntat d'aconseguir els millors resultats en les polítiques de reinserció és compartida tant per les persones que lideren les institucions de rehabilitació com pels equips que fan recerca en aquesta matèria. Aquest treball pretén contribuir-hi analitzant el procés de transició entre la presó i la vida en llibertat. Enfront els enfocaments que consideren que la predisposició inicial -antecedents personals, familiars i d'entorn- és el principal factor que explica la continuïtat o el cessament de l'activitat delictiva d'una persona, la recerca que aquí es presenta parteix de la premissa que, en el decurs de la vida adulta, existeixen nous esdeveniments que expliquen la trajectòria futura. En aquest sentit, es presta especial atenció als mecanismes de transició entre la presó i la vida en llibertat i, particularment, al paper que aquests juguen en els processos de desistiment del delicte.La voluntad de conseguir mejores resultados en las políticas de reinserción es compartida tanto por las personas que lideran las instituciones de rehabilitación como por los equipos que investigan en esta materia. Este trabajo pretende contribuir a esta voluntad analizando el proceso de transición entre la cárcel y la vida en libertad. Frente a los enfoques que consideren que la predisposición inicial -antecedentes personales, familiares y de entorno- es el principal factor que explica la continuidad o el cese de la actividad delictiva de una persona, la investigación que aquí se presenta parte de la premisa que, en el transcurso de la vida adulta, existen nuevos acontecimientos que explican la trayectoria futura. En consecuencia, se presta especial atención a los mecanismos de transición entre la prisión y la vida en libertad y, particularmente, al papel que estos juegan en los procesos de desistimiento del delito

Genetic Polymorphism of UDP-Glucuronosyltransferase

Genetic polymorphism is referred to the discontinuous interspecies genetic variability among individuals having distinct alleles on a particular locus. Genetic polymorphism of genes encoding drug-metabolizing enzymes constitutes individual’s susceptibility to drugs, affirmed by having discrete allelic frequencies by the individual, strengthening the concept of precision medicine. To combat with toxic consequences of drugs, the polymorphic genes associated with xenobiotic metabolism must be studied. Up to 70% xenobiotic elimination is believed to be dependent on UDP-glucuronosyltransferase (UGT), an enzyme encoded by polymorphic UGT1A and UGT2B genes. Both bimodal and trimodal distribution patterns of UGT have been reported in various human populations studied. Genetic polymorphisms of UGT may even lead to truncated and shorter gene with grossly diminished enzymatic activity. The extent of phenotypic alteration inflicted by genetic polymorphisms depends on its nature and position on gene locus. The different isoforms of UGT superfamily differ from each other regarding substrate specificity and selectivity. The incidence of genetic polymorphisms and associated altered gene functions results in inter-individual variability in metabolic clearance and elimination of drugs. Hence, the critical interaction between genetics and biotransformation of drugs has recently been the focus of pharmacology research

Role of fertilization regime on soil carbon sequestration and crop yield in a maize-cowpea intercropping system on low fertility soils

Achieving food security through intensive agricultural practices on low fertility soils is challenging as crop productivity is increasingly curtailed by the loss of soil structural stability and rapid depletion of soil organic carbon (SOC). As such, the conversion from traditional mono-cropping to legume-cereal intercropping, especially with integrated fertilization, may increase crop yields with the least ecological footprint. We set up a 2-year field experiment in a split-plot design with cowpea-maize monoculture and intercropping under different organic-inorganic fertilization regimes, including no fertilization (control), organic input only (compost), chemical input only (NPK), and multi-nutrient enriched compost (NPKEC). We observed that intercropped maize had a significantly higher biomass yield compared to the corresponding monoculture when fertilized with NPKEC fertilizer. However, cowpea biomass yield differences between monoculture and intercropped plots were comparable under all fertilization regimes. In contrast, the grain yield advantage of both maize and cowpea was significantly enhanced under the intercropping system compared to monoculture, with NPKEC showing the most significant effect among all fertilization regimes. When comparing the relative contribution of the fertilization regime to SOC, the NPKEC fertilizer provided the highest SOC-sequestration (0.30 Mg C/ha yr−1). At the same time, the effect of the cropping system on C-sequestration showed that intercropping provided the highest C-sequestration (0.17 Mg C/ha yr−1) compared to monocultures of both crops. Although compost application significantly increased mineral associated (MAOC) and particulate associated organic carbon (PAOC) concentrations compared to unfertilized control plots, NPKEC fertilization with intercropping system was the most effective combination causing the greatest increase of both soil C pools over time. Based on redundancy analysis (RDA), the positive association of MAOC and PAOC with C-sequestration suggests the importance of both organic fractions as primary C reservoirs conducting SOC storage. Importantly, although compost alone in association with intercropping had a lower C-sequestration, it was associated to a better soil structure as confirmed by its positive relationship with macro-and micro-aggregation, water stable aggregates (WSA), and mean weight diameter (MDA). Overall, our results indicate the importance of restoring soil structure in degraded soils through appropriate land management solutions, such as stoichiometrically balanced fertilization practices (NPKEC) and crop diversification (intercropping), in order to achieve significant gains in SOC storage and, ultimately, improve crop productivity

A comprehensive review on Gossypium hirsutum resistance against cotton leaf curl virus

Cotton (Gossypium hirsutum L.) is a significant fiber crop. Being a major contributor to the textile industry requires continuous care and attention. Cotton is subjected to various biotic and abiotic constraints. Among these, biotic factors including cotton leaf curl virus (CLCuV) are dominant. CLCuV is a notorious disease of cotton and is acquired, carried, and transmitted by the whitefly (Bemisia tabaci). A cotton plant affected with CLCuV may show a wide range of symptoms such as yellowing of leaves, thickening of veins, upward or downward curling, formation of enations, and stunted growth. Though there are many efforts to protect the crop from CLCuV, long-term results are not yet obtained as CLCuV strains are capable of mutating and overcoming plant resistance. However, systemic-induced resistance using a gene-based approach remained effective until new virulent strains of CLCuV (like Cotton Leaf Curl Burewala Virus and others) came into existence. Disease control by biological means and the development of CLCuV-resistant cotton varieties are in progress. In this review, we first discussed in detail the evolution of cotton and CLCuV strains, the transmission mechanism of CLCuV, the genetic architecture of CLCuV vectors, and the use of pathogen and nonpathogen-based approaches to control CLCuD. Next, we delineate the uses of cutting-edge technologies like genome editing (with a special focus on CRISPR-Cas), next-generation technologies, and their application in cotton genomics and speed breeding to develop CLCuD resistant cotton germplasm in a short time. Finally, we delve into the current obstacles related to cotton genome editing and explore forthcoming pathways for enhancing precision in genome editing through the utilization of advanced genome editing technologies. These endeavors aim to enhance cotton’s resilience against CLCuD

Identification of surface proteins in Enterococcus faecalis V583

<p>Abstract</p> <p>Background</p> <p>Surface proteins are a key to a deeper understanding of the behaviour of Gram-positive bacteria interacting with the human gastro-intestinal tract. Such proteins contribute to cell wall synthesis and maintenance and are important for interactions between the bacterial cell and the human host. Since they are exposed and may play roles in pathogenicity, surface proteins are interesting targets for drug design.</p> <p>Results</p> <p>Using methods based on proteolytic "shaving" of bacterial cells and subsequent mass spectrometry-based protein identification, we have identified surface-located proteins in <it>Enterococcus faecalis </it>V583. In total 69 unique proteins were identified, few of which have been identified and characterized previously. 33 of these proteins are predicted to be cytoplasmic, whereas the other 36 are predicted to have surface locations (31) or to be secreted (5). Lipid-anchored proteins were the most dominant among the identified surface proteins. The seemingly most abundant surface proteins included a membrane protein with a potentially shedded extracellular sulfatase domain that could act on the sulfate groups in mucin and a lipid-anchored fumarate reductase that could contribute to generation of reactive oxygen species.</p> <p>Conclusions</p> <p>The present proteome analysis gives an experimental impression of the protein landscape on the cell surface of the pathogenic bacterium <it>E. faecalis</it>. The 36 identified secreted (5) and surface (31) proteins included several proteins involved in cell wall synthesis, pheromone-regulated processes, and transport of solutes, as well as proteins with unknown function. These proteins stand out as interesting targets for further investigation of the interaction between <it>E. faecalis </it>and its environment.</p

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050

Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached$8. 8 trillion (95% uncertainty interval UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total,$40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this,$13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and$1.4 billion was repurposed from existing health projects. $3.1 billion (22.4$2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7$1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd