Re-introduction of vivax malaria in a temperate area (Moscow region, Russia): a geographic investigation.

BACKGROUND: Between 1999 and 2008 Russia experienced a flare-up of transmission of vivax malaria following its massive importation with more than 500 autochthonous cases in European Russia, the Moscow region being the most affected. The outbreak waned soon after a decrease in importation in mid-2000s and strengthening the control measures. Compared with other post-eradication epidemics in Europe this one was unprecedented by its extension and duration. METHODS: The aim of this study is to identify geographical determinants of transmission. The degree of favourability of climate for vivax malaria was assessed by measuring the sum of effective temperatures and duration of season of effective infectivity using data from 22 weather stations. For geospatial analysis, the locations of each of 405 autochthonous cases detected in Moscow region have been ascertained. A MaxEnt method was used for modelling the territorial differentiation of Moscow region according to the suitability of infection re-emergence based on the statistically valid relationships between the distribution of autochthonous cases and environmental and climatic factors. RESULTS: In 1999-2004, in the beginning of the outbreak, meteorological conditions were extremely favourable for malaria in 1999, 2001 and 2002, especially within the borders of the city of Moscow and its immediate surroundings. The greatest number of cases occurred at the northwestern periphery of the city and in the adjoining rural areas. A significant role was played by rural construction activities attracting migrant labour, vegetation density and landscape division. A cut-off altitude of 200 m was observed, though the factor of altitude did not play a significant role at lower altitudes. Most likely, the urban heat island additionally amplified malaria re-introduction. CONCLUSION: The malariogenic potential in relation to vivax malaria was high in Moscow region, albeit heterogeneous. It is in Moscow that the most favourable conditions exist for vivax malaria re-introduction in the case of a renewed importation. This recent event of large-scale re-introduction of vivax malaria in a temperate area can serve as a case study for further research.

Evaluation of ground glass nodules.

PURPOSE OF REVIEW: Ground glass nodules (GGNs) represent an indolent subset of lung nodules including preinvasive nonsmall-cell lung cancer associated with a favorable prognosis and low risk for progression. Increased performance of screening cat-scan (CT) for high-risk patients has identified an increasing number of GGNs. The management of these nodules is founded mostly on single institution data and currently no universally accepted recommendations help guide clinicians managing these patients. RECENT FINDINGS: The solid component within a GGN is the key determinant of prognosis and is best defined by evaluating nodule density on mediastinal windows of a chest CT. When a GGN is small (<3 cm), associated with minimal change in size (<25% growth per year), and there is no demonstration of a significant solid component on mediastinal windows (<2 mm in diameter), patients can be safely observed with serially imaging. These imaging features also help distinguish patients that may harbor early-stage lung cancers that benefit from local treatment options. SUMMARY: The majority of GGNs do not undergo significant progression during surveillance. Evidence of nodule progression on interval imaging may be a trigger for consideration of a local treatment option such as surgical resection. Large prospective studies are needed in the United States to validate the more robust data derived from Asian studies to help formulate formal recommendations for surveillance and treatment. Future improvements in imaging and the molecular characterization of these GGNs may further refine which patients are at risk for progression.

Natural-focal diseases: mapping experience in Russia.

BACKGROUND: Natural-focal diseases constitute a serious hazard for human health. Agents and vectors of such diseases belong to natural landscapes. The aim of this study is to identify the diversity and geography of natural-focal diseases in Russia and to develop cartographic approaches for their mapping, including mathematical-cartographical modeling. Russian medico-geographical mapping of natural-focal diseases is highly developed regionally and locally but extremely limited at the national level. To solve this problem, a scientific team of the Faculty of Geography at Lomonosov Moscow State University has developed and implemented a project of a medico-geographical Atlas of Russia "Natural-Focal Diseases". METHODS: The mapping is based on medical statistics data. The Atlas contains a series of maps on disease incidence, long-term dynamics of disease morbidity, etc. In addition, other materials available to the authors were used: mapping of the natural environment, field data, archival materials, analyzed satellite images, etc. The maps are processed using ArcGIS (ESRI) software application. Different methods of rendering of mapped phenomena are used (geographical ranges, diagrams, choropleth maps etc.). RESULTS: A series of analytical, integrated, and synthetic maps shows disease incidence in the population at both the national and regional levels for the last 15 years. Maps of the mean annual morbidity of certain infections and maps of morbidity dynamics and nosological profiles allow for a detailed analysis of the situation for each of 83 administrative units of the Russian Federation. The degree of epidemic hazard in Russia by natural-focal diseases is reflected in a synthetic medico-geographical map that shows the degree of epidemic risks due to such diseases in Russia and allows one to estimate the risk of disease manifestation in a given region. CONCLUSIONS: This is the first attempt at aggregation and public presentation of diverse and multifaceted information about natural-focal diseases in Russia. Taken in entirety, the maps that have been prepared for the Atlas will enable researchers to evaluate the stability of epidemic manifestation of individual diseases and the susceptibility of a given territory to disease transmission. The results can be used for sanitary monitoring and disease prevention.

Spatial and temporal patterns of haemorrhagic fever with renal syndrome (HFRS) and the impact of environmental drivers in a border area of the Russian Far East.

AIMS: Haemorrhagic fever with renal syndrome (HFRS) is a significant zoonotic disease transmitted by rodents. The distribution of HFRS in the European part of Russia has been studied quite well; however, much less is known about the endemic area in the Russian Far East. The mutual influence of the epidemic situation in the border regions and the possibility of cross-border transmission of infection remain poorly understood. This study aims to identify the spatiotemporal hot spots of the incidence and the impact of environmental drivers on the HFRS distribution in the Russian Far East. METHODS AND RESULTS: A two-scale study design was performed. Kulldorf's spatial scan statistic was used to conduct spatiotemporal analysis at a regional scale from 2000 to 2020. In addition, an ecological niche model based on maximum entropy was applied to analyse the contribution of various factors and identify spatial favourability at the local scale. One spatiotemporal cluster that existed from 2002 to 2011 and located in the border area and one pure temporal cluster from 2004 to 2007 were revealed. The best suitability for orthohantavirus persistence was found along rivers, including those at the Chinese-Russian border, and was mainly explained by land cover, NDVI (as an indicator of vegetation density and greenness) and elevation. CONCLUSIONS: Despite the stable incidence in recent years in, targeted prevention strategies are still needed due to the high potential for HRFS distribution in the southeast of the Russian Far East.

Spatial patterns of West Nile virus distribution in the Volgograd region of Russia, a territory with long-existing foci.

Southern Russia remains affected by West Nile virus (WNV). In the current study, we identified the spatial determinants of WNV distribution in an area with endemic virus transmission, with special reference to the urban settings, by mapping probable points of human infection acquisition and points of virus detection in mosquitoes, ticks, birds, and mammals during 1999-2016. The suitability of thermal conditions for extrinsic virus replication was assessed based on the approach of degree-day summation and their changes were estimated by linear trend analysis. A generalized linear model was used to analyze the year-to-year variation of human cases versus thermal conditions. Environmental suitability was determined by ecological niche modelling using MaxEnt software. Human population density was used as an offset to correct for possible bias. Spatial analysis of virus detection in the environment showed significant contributions from surface temperature, altitude, and distance from water bodies. When indicators of location and mobility of the human population were included, the relative impact of factors changed, with roads becoming most important. When the points of probable human case infection were added, the percentage of leading factors changed only slightly. The urban environment significantly increased the epidemic potential of the territory and created quite favorable conditions for virus circulation. The private building sector with low-storey houses and garden plots located in the suburbs provided a connection between urban and rural transmission cycles.

Identification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach.

1,4-Dioxane (1,4-DX) is an environmental contaminant found in drinking water throughout the United States. Although it is a suspected liver carcinogen, there is no federal or state maximum contaminant level for 1,4-DX in drinking water. Very little is known about the mechanisms by which this chemical elicits liver carcinogenicity. In the present study, female BDF-1 mice were exposed to 1,4-DX (0, 50, 500, and 5,000mg/L) in their drinking water for 1 or 4 weeks, to explore the toxic effects. Histopathological studies and a multi-omics approach (transcriptomics and metabolomics) were performed to investigate potential mechanisms of toxicity. Immunohistochemical analysis of the liver revealed increased H2AXγ-positive hepatocytes (a marker of DNA double-strand breaks), and an expansion of precholangiocytes (reflecting both DNA damage and repair mechanisms) after exposure. Liver transcriptomics revealed 1,4-DX-induced perturbations in signaling pathways predicted to impact the oxidative stress response, detoxification, and DNA damage. Liver, kidney, feces, and urine metabolomic profiling revealed no effect of 1,4-DX exposure, and bile acid quantification in liver and feces similarly showed no effect of exposure. We speculate that the results may be reflective of DNA damage being counterbalanced by the repair response, with the net result being a null overall effect on the systemic biochemistry of the exposed mice. Our results show a novel approach for the investigation of environmental chemicals that do not elicit cell death but have activated the repair systems in response to 1,4-DX exposure.

Sex Differences in Colon Cancer Metabolism Reveal A Novel Subphenotype.

Women have a lower incidence of colorectal cancer (CRC) than men, however, they have a higher incidence of right-sided colon cancer (RCC). This is of concern as patients with RCC have the poorest clinical outcomes among all CRC patients. Aberrant metabolism is a known hallmark and therapeutic target for cancer. We propose that metabolic subphenotypes exist between CRCs due to intertumoral molecular and genomic variation, and differences in environmental milieu of the colon which vary between the sexes. Metabolomics analysis of patient colon tumors (n = 197) and normal tissues (n = 39) revealed sex-specific metabolic subphenotypes dependent on anatomic location. Tumors from women with RCC were nutrient-deplete, showing enhanced energy production to fuel asparagine synthesis and amino acid uptake. The clinical importance of our findings were further investigated in an independent data set from The Cancer Genomic Atlas, and demonstrated that high asparagine synthetase (ASNS) expression correlated with poorer survival for women. This is the first study to show a unique, nutrient-deplete metabolic subphenotype in women with RCC, with implications for tumor progression and outcomes in CRC patients.

Molecular Pathway Analysis Indicates a Distinct Metabolic Phenotype in Women With Right-Sided Colon Cancer.

Colon cancer is the third most commonly diagnosed cancer in the United States. Recent reports have shown that the location of the primary tumor is of clinical importance. Patients with right-sided colon cancers (RCCs) (tumors arising between the cecum and proximal transverse colon) have poorer clinical outcomes than those with left-sided colon cancers (LCCs) (tumors arising between the distal transverse colon and sigmoid colon, excluding the rectum). Interestingly, women have a lower incidence of colon cancer than men, but have a higher propensity for RCC. The reason for this difference is not known; however, identification of sex-specific differences in gene expression by tumor anatomical location in the colon could provide further insight. Moreover, it could reveal important predictive markers for response to various treatments. This study provides a comprehensive bioinformatic analysis of various genes and molecular pathways that correlated with sex and anatomical location of colon cancers using four publicly available annotated data sets housed in the National Center for Biotechnology Information's Gene Expression Omnibus. We identified differentially expressed genes in tumor tissues from women with RCC, which showed attenuated energy and nutrient metabolism when compared with women with LCC. Specifically, we showed the downregulation of 5' AMP-activated protein kinase alpha subunit (AMPKα) and anti-tumor immune responses in women with RCC. This difference was not seen when comparing tumor tissues from men with RCC to men with LCC. Therefore, women with RCC may have a specific metabolic and immune phenotype which accounts for differences in prognosis and treatment response.

Tumor Tissue-Specific Biomarkers of Colorectal Cancer by Anatomic Location and Stage.

The progress in the discovery and validation of metabolite biomarkers for the detection of colorectal cancer (CRC) has been hampered by the lack of reproducibility between study cohorts. The majority of discovery-phase biomarker studies have used patient blood samples to identify disease-related metabolites, but this pre-validation phase is confounded by non-specific disease influences on the metabolome. We therefore propose that metabolite biomarker discovery would have greater success and higher reproducibility for CRC if the discovery phase was conducted in tumor tissues, to find metabolites that have higher specificity to the metabolic consequences of the disease, that are then validated in blood samples. This would thereby eliminate any non-tumor and/or body response effects to the disease. In this study, we performed comprehensive untargeted metabolomics analyses on normal (adjacent) colon and tumor tissues from CRC patients, revealing tumor tissue-specific biomarkers (n = 39/group). We identified 28 highly discriminatory tumor tissue metabolite biomarkers of CRC by orthogonal partial least-squares discriminant analysis (OPLS-DA) and univariate analyses (VIP > 1.5, p < 0.05). A stepwise selection procedure was used to identify nine metabolites that were the most predictive of CRC with areas under the curve (AUCs) of >0.96, using various models. We further identified five biomarkers that were specific to the anatomic location of tumors in the colon (n = 236). The combination of these five metabolites (S-adenosyl-L-homocysteine, formylmethionine, fucose 1-phosphate, lactate, and phenylalanine) demonstrated high differentiative capability for left- and right-sided colon cancers at stage I by internal cross-validation (AUC = 0.804, 95% confidence interval, CI 0.670-0.940). This study thus revealed nine discriminatory biomarkers of CRC that are now poised for external validation in a future independent cohort of samples. We also discovered a discrete metabolic signature to determine the anatomic location of the tumor at the earliest stage, thus potentially providing clinicians a means to identify individuals that could be triaged for additional screening regimens.

Effects of Climate Change and Heterogeneity of Local Climates оn the Development of Malaria Parasite (Plasmodium vivax) in Moscow Megacity Region.

The article presents the results of a spatio-temporal analysis of the changes of the favorability of climatic conditions for the transmission of vivax malaria in the Moscow megacity and its surroundings during the period from 1977 to 2016. Using the historical temperature records at urban and rural weather stations, we calculated the key indicators of climate favorability for malaria transmission, viz. the sum of effective temperatures, the duration of the season of effective infectiveness, and a new integral index of climate favorability. We demonstrated a dramatic increase of all three indicators, which accelerated after 1984, and a high spatial heterogeneity among them. Due to the urban heat island effect, the degree of climatic favorability is especially high in the densely urbanized areas of Moscow megacity compared with the suburban and rural areas. Climatic conditions for vivax malaria in Moscow are better now than before. The season of effective infectiveness continues in the central part of the city for 25 days longer, and the integral index of climate favorability is 85% higher in comparison to mean values over the rural surroundings. The study contains an alert regarding the risk of malaria resurgence in the Moscow region in the case of the sufficient importation of cases from abroad.