Определение содержания тетрациклина в молоке методом капиллярного электрофореза

Mentalizing, i.e. the process of inferring another person's mental state, is thought to be primarily subserved by three brain regions, the VMPFC (ventromedial prefrontal cortex), precuneus and TPJ (temporo-parietal junction). However, it is still unclear what the exact roles of these regions in mentalizing are. Here, we compare activity within, and functional connectivity between, the VMPFC, precuneus and TPJ during two different mentalizing tasks. Specifically, we examine whether inferring another person's emotion (“emotion mentalizing”) and inferring another person's intention (“intention mentalizing”) activate similar or distinct subregions within the VMPFC, precuneus and TPJ, and whether these different kinds of mentalizing are associated with different patterns of functional connectivity between these regions. Our results indicate that emotion mentalizing and intention mentalizing activate partly distinct subregions of the right and left TPJ that can be spatially separated across participants. These subregions also showed different patterns of functional connectivity with the VMPFC: a more anterior region of the right and left TPJ, which was more strongly activated during emotion mentalizing, showed stronger functional connectivity with the VMPFC, particularly during emotion mentalizing, than a more posterior region that was more strongly activated during intention mentalizing. Critically, this double dissociation became evident only when the fine-scale distribution of activity within activated regions was analysed, and despite the fact that there was also a significant overlap of activity during the two tasks. Our findings provide first evidence that different neural modules might have evolved within the TPJ that show distinct patterns of functional connectivity and might subserve slightly different subfunctions of mentalizing

Plasmodium knowlesi Genome Sequences from Clinical Isolates Reveal Extensive Genomic Dimorphism.

Plasmodium knowlesi is a newly described zoonosis that causes malaria in the human population that can be severe and fatal. The study of P. knowlesi parasites from human clinical isolates is relatively new and, in order to obtain maximum information from patient sample collections, we explored the possibility of generating P. knowlesi genome sequences from archived clinical isolates. Our patient sample collection consisted of frozen whole blood samples that contained excessive human DNA contamination and, in that form, were not suitable for parasite genome sequencing. We developed a method to reduce the amount of human DNA in the thawed blood samples in preparation for high throughput parasite genome sequencing using Illumina HiSeq and MiSeq sequencing platforms. Seven of fifteen samples processed had sufficiently pure P. knowlesi DNA for whole genome sequencing. The reads were mapped to the P. knowlesi H strain reference genome and an average mapping of 90% was obtained. Genes with low coverage were removed leaving 4623 genes for subsequent analyses. Previously we identified a DNA sequence dimorphism on a small fragment of the P. knowlesi normocyte binding protein xa gene on chromosome 14. We used the genome data to assemble full-length Pknbpxa sequences and discovered that the dimorphism extended along the gene. An in-house algorithm was developed to detect SNP sites co-associating with the dimorphism. More than half of the P. knowlesi genome was dimorphic, involving genes on all chromosomes and suggesting that two distinct types of P. knowlesi infect the human population in Sarawak, Malaysian Borneo. We use P. knowlesi clinical samples to demonstrate that Plasmodium DNA from archived patient samples can produce high quality genome data. We show that analyses, of even small numbers of difficult clinical malaria isolates, can generate comprehensive genomic information that will improve our understanding of malaria parasite diversity and pathobiology

Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region

Influence of Biopsy Technique on Molecular Genetic Tumor Characterization in Non-Small Cell Lung Cancer—The Prospective, Randomized, Single-Blinded, Multicenter PROFILER Study Protocol

The detection of molecular alterations is crucial for the individualized treatment of advanced non-small cell lung cancer (NSCLC). Missing targetable alterations may have a major impact on patient’s progression free and overall survival. Although laboratory testing for molecular alterations has continued to improve; little is known about how biopsy technique affects the detection rate of different mutations. In the retrospective study detection rate of epidermal growth factor (EGFR) mutations in tissue extracted by bronchoscopic cryobiopsy (CB was significantly higher compared to other standard biopsy techniques. This prospective, randomized, multicenter, single blinded study evaluates the accuracy of molecular genetic characterization of NSCLC for different cell sampling techniques. Key inclusion criteria are suspected lung cancer or the suspected relapse of known NSCLC that is bronchoscopically visible. Patients will be randomized, either to have a CB or a bronchoscopic forceps biopsy (FB). If indicated, a transbronchial needle aspiration (TBNA) of suspect lymph nodes will be performed. Blood liquid biopsy will be taken before tissue biopsy. The primary endpoint is the detection rate of molecular genetic alterations in NSCLC, using CB and FB. Secondary endpoints are differences in the combined detection of molecular genetic alterations between FB and CB, TBNA and liquid biopsy. This trial plans to recruit 540 patients, with 178 evaluable patients per study cohort. A histopathological and molecular genetic evaluation will be performed by the affiliated pathology departments of the national network for genomic medicine in lung cancer (nNGM), Germany. We will compare the diagnostic value of solid tumor tissue, lymph node cells and liquid biopsy for the molecular genetic characterization of NSCLC. This reflects a real world clinical setting, with potential direct impact on both treatment and survival

Clinical Characteristics and Neonatal Outcomes of Pregnant Patients With COVID-19: A Systematic Review

Background and Objective: Coronavirus disease 2019 (COVID-19) characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created serious concerns about its potential adverse effects. There are limited data on clinical, radiological, and neonatal outcomes of pregnant women with COVID-19 pneumonia. This study aimed to assess clinical manifestations and neonatal outcomes of pregnant women with COVID-19. Methods: We conducted a systematic article search of PubMed, EMBASE, Scopus, Google Scholar, and Web of Science for studies that discussed pregnant patients with confirmed COVID-19 between January 1, 2020, and April 20, 2020, with no restriction on language. Articles were independently evaluated by two expert authors. We included all retrospective studies that reported the clinical features and outcomes of pregnant patients with COVID-19. Results: Forty-seven articles were assessed for eligibility; 13 articles met the inclusion criteria for the systematic review. Data is reported for 235 pregnant women with COVID-19. The age range of patients was 25�40 years, and the gestational age ranged from 8 to 40 weeks plus 6 days. Clinical characteristics were fever 138/235 (58.72%), cough 111/235 (47.23%), and sore throat 21/235 (8.93%). One hundred fifty six out of 235 (66.38%) pregnant women had cesarean section, and 79 (33.62%) had a vaginal delivery. All the patients showed lung abnormalities in CT scan images, and none of the patients died. Neutrophil cell count, C-reactive protein (CRP) concentration, ALT, and AST were increased but lymphocyte count and albumin levels were decreased. Amniotic fluid, neonatal throat swab, and breastmilk samples were taken to test for SARS-CoV-2 but all found negativ results. Recent published evidence showed the possibility of vertical transmission up to 30%, and neonatal death up to 2.5%. Pre-eclampsia, fetal distress, PROM, pre-mature delivery were the major complications of pregnant women with COVID-19. Conclusions: Our study findings show that the clinical, laboratory and radiological characteristics of pregnant women with COVID-19 were similar to those of the general populations. The possibility of vertical transmission cannot be ignored but C-section should not be routinely recommended anymore according to latest evidences and, in any case, decisions should be taken after proper discussion with the family. Future studies are needed to confirm or refute these findings with a larger number of sample sizes and a long-term follow-up period. © Copyright © 2020 Islam, Poly, Walther, Yang, Wang, Hsieh, Atique, Salmani, Alsinglawi, Lin, Jian and Jack Li

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Mapping disparities in education across low- and middle-income countries

Educational attainment is an important social determinant of maternal, newborn, and child health1–3. As a tool for promoting gender equity, it has gained increasing traction in popular media, international aid strategies, and global agenda-setting4–6. The global health agenda is increasingly focused on evidence of precision public health, which illustrates the subnational distribution of disease and illness7,8; however, an agenda focused on future equity must integrate comparable evidence on the distribution of social determinants of health9–11. Here we expand on the available precision SDG evidence by estimating the subnational distribution of educational attainment, including the proportions of individuals who have completed key levels of schooling, across all low- and middle-income countries from 2000 to 2017. Previous analyses have focused on geographical disparities in average attainment across Africa or for specific countries, but—to our knowledge—no analysis has examined the subnational proportions of individuals who completed specific levels of education across all low- and middle-income countries12–14. By geolocating subnational data for more than 184 million person-years across 528 data sources, we precisely identify inequalities across geography as well as within populations

The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990�2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: The burden of inflammatory bowel disease (IBD) is rising globally, with substantial variation in levels and trends of disease in different countries and regions. Understanding these geographical differences is crucial for formulating effective strategies for preventing and treating IBD. We report the prevalence, mortality, and overall burden of IBD in 195 countries and territories between 1990 and 2017, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Methods: We modelled mortality due to IBD using a standard Cause of Death Ensemble model including data mainly from vital registrations. To estimate the non-fatal burden, we used data presented in primary studies, hospital discharges, and claims data, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to ensure consistency between measures. Mortality, prevalence, years of life lost (YLLs) due to premature death, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were estimated. All of the estimates were reported as numbers and rates per 100 000 population, with 95 uncertainty intervals (UI). Findings: In 2017, there were 6·8 million (95 UI 6·4�7·3) cases of IBD globally. The age-standardised prevalence rate increased from 79·5 (75·9�83·5) per 100 000 population in 1990 to 84·3 (79·2�89·9) per 100 000 population in 2017. The age-standardised death rate decreased from 0·61 (0·55�0·69) per 100 000 population in 1990 to 0·51 (0·42�0·54) per 100 000 population in 2017. At the GBD regional level, the highest age-standardised prevalence rate in 2017 occurred in high-income North America (422·0 398·7�446·1 per 100 000) and the lowest age-standardised prevalence rates were observed in the Caribbean (6·7 6·3�7·2 per 100 000 population). High Socio-demographic Index (SDI) locations had the highest age-standardised prevalence rate, while low SDI regions had the lowest age-standardised prevalence rate. At the national level, the USA had the highest age-standardised prevalence rate (464·5 438·6�490·9 per 100 000 population), followed by the UK (449·6 420·6�481·6 per 100 000). Vanuatu had the highest age-standardised death rate in 2017 (1·8 0·8�3·2 per 100 000 population) and Singapore had the lowest (0·08 0·06�0·14 per 100 000 population). The total YLDs attributed to IBD almost doubled over the study period, from 0·56 million (0·39�0·77) in 1990 to 1·02 million (0·71�1·38) in 2017. The age-standardised rate of DALYs decreased from 26·5 (21·0�33·0) per 100 000 population in 1990 to 23·2 (19·1�27·8) per 100 000 population in 2017. Interpretation: The prevalence of IBD increased substantially in many regions from 1990 to 2017, which might pose a substantial social and economic burden on governments and health systems in the coming years. Our findings can be useful for policy makers developing strategies to tackle IBD, including the education of specialised personnel to address the burden of this complex disease. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background The burden of inflammatory bowel disease (IBD) is rising globally, with substantial variation in levels and trends of disease in different countries and regions. Understanding these geographical differences is crucial for formulating effective strategies for preventing and treating IBD. We report the prevalence, mortality, and overall burden of IBD in 195 countries and territories between 1990 and 2017, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Methods We modelled mortality due to IBD using a standard Cause of Death Ensemble model including data mainly from vital registrations. To estimate the non-fatal burden, we used data presented in primary studies, hospital discharges, and claims data, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to ensure consistency between measures. Mortality, prevalence, years of life lost (YLLs) due to premature death, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were estimated. All of the estimates were reported as numbers and rates per 100 000 population, with 95% uncertainty intervals (UI). Findings In 2017, there were 6.8 million (95% UI 6.4-7.3) cases of IBD globally. The age-standardised prevalence rate increased from 79.5 (75.9-83.5) per 100 000 population in 1990 to 84.3 (79.2-89.9) per 100 000 population in 2017. The age-standardised death rate decreased from 0.61 (0.55-0.69) per 100 000 population in 1990 to 0.51 (0.42-0.54) per 100 000 population in 2017. At the GBD regional level, the highest age-standardised prevalence rate in 2017 occurred in high-income North America (422.0 [398.7-446.1] per 100 000) and the lowest age-standardised prevalence rates were observed in the Caribbean (6.7 [6.3-7.2] per 100 000 population). High Sociodemographic Index (SDI) locations had the highest age-standardised prevalence rate, while low SDI regions had the lowest age-standardised prevalence rate. At the national level, the USA had the highest age-standardised prevalence rate (464.5 [438.6-490.9] per 100 000 population), followed by the UK (449.6 [420.6-481.6] per 100 000). Vanuatu had the highest age-standardised death rate in 2017 (1.8 [0.8-3.2] per 100 000 population) and Singapore had the lowest (0.08 [0.06-0.14] per 100 000 population). The total YLDs attributed to IBD almost doubled over the study period, from 0.56 million (0.39-0.77) in 1990 to 1.02 million (0.71-1.38) in 2017. The age-standardised rate of DALYs decreased from 26.5 (21.0-33.0) per 100 000 population in 1990 to 23.2 (19.1-27.8) per 100 000 population in 2017. Interpretation The prevalence of IBD increased substantially in many regions from 1990 to 2017, which might pose a substantial social and economic burden on governments and health systems in the coming years. Our findings can be useful for policy makers developing strategies to tackle IBD, including the education of specialised personnel to address the burden of this complex disease. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe