Carriers Of Disease Research Articles

Pan-Genome-Wide Association Study of Serotype 19A Pneumococci Identifies Disease-Associated Genes.

Despite the widespread implementation of pneumococcal vaccines, hypervirulent Streptococcus pneumoniae serotype 19A is endemic worldwide. It is still unclear whether specific genetic elements contribute to complex pathogenicity of serotype 19A isolates. We performed a large-scale pan-genome-wide association study (pan-GWAS) of 1,292 serotype 19A isolates sampled from patients with invasive disease and asymptomatic carriers. To address the underlying disease-associated genotypes, a comprehensive analysis using three methods (Scoary, a linear mixed model, and random forest) was performed to compare disease and carriage isolates to identify genes consistently associated with disease phenotype. By using three pan-GWAS methods, we found consensus on statistically significant associations between genotypes and disease phenotypes (disease or carriage), with a subset of 30 consistently significant disease-associated genes. The results of functional annotation revealed that these disease-associated genes had diverse predicted functions, including those that participated in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. Our findings suggest the multifactorial pathogenicity nature of this hypervirulent serotype and provide important evidence for the design of novel protein-based vaccines to prevent and control pneumococcal disease. IMPORTANCE It is important to understand the genetic and pathogenic characteristics of S. pneumoniae serotype 19A, which may provide important information for the prevention and treatment of pneumococcal disease. This global large-sample pan-GWAS study has identified a subset of 30 consistently significant disease-associated genes that are involved in mobile genetic elements, antibiotic resistance, virulence, and cellular metabolism. These findings suggest the multifactorial pathogenicity nature of hypervirulent S. pneumoniae serotype 19A isolates and provide implications for the design of novel protein-based vaccines.

P-746 Carrier Screening analysis in more than 20.000 patients. Is complete analysis important vs genotyping analysis?

Abstract Study question How comprehensive gene sequencing analysis impacts on carrier screening (CS) results and couple risk reduction? Summary answer Comprehensive genetic sequencing analysis facilitates more accurate carrier rates and provides better information for final panel design and partner risk reduction. What is known already Since CS began in the 1970s, it has helped millions of couples at risk of affected offspring affected by genetic diseases.From the first panels for Ashkenazi Jewish to today’s pan-ethnic CS panels, genetic testing has improved from analysis of a few known pathogenic variants to full sequence analysis. The American College of Medical Genetics and Genomics (ACMG) published Standards and Guidelines for the Interpretation of Sequence Variants in 2015, providing an important tool for full sequence analysis for CS. CS analyses can report only already known mutations (genotyping) or screen for all variants with ACMG-guidelines and laboratory experience (full sequencing). Study design, size, duration This study includes 20774 patients screened with an expanded carrier screening panel of 301 genes, including autosomal recessive (AR) and X-linked (XL) disorders by next-generation sequencing (NGS). ACMG guidelines for variant interpretation were followed in 13954 patients and only pathogenic and likely pathogenic variants were reported. 6820 patients were analyzed with genotyping analysis. 15758 matching analyses were performed for couples and gamete donors. The study has been conducted between August 2018 and December 2022. Participants/materials, setting, methods DNA was extracted from saliva and blood samples and sequenced. The data obtained were processed by means of computer tools. The carrier frequency (CFR) was obtained from the full sequencing analyses. The observed CFRs was compared with the expected CFRs obtained from databases and literature.To define its similarity a range of +-25% was accepted as similar CFR. For matching analyses, high at-risk couples were divided for autosomal recessive diseases(both carriers) and X-linked diseases (female carriers). Main results and the role of chance For the 301 genes analyzed, 34%(103) had a similar CF than the expected one and, more importantly, 65%(198) showed different CFR. In some cases this difference is due to the lack of complete information on the CFR on bibliography and databases like the CFR associated a diseases with more than one gene associated or genes related with more than one disease, some of which with low clinical implications, usually underdiagnosed. One of the genes on which the CFR was not similar to the expected was SMN1. For this well-known gene, related to spinal muscular atrophy, the CFR was higher than expected, probably due to the analysis of the variants c.*3 + 80T>G(p.?),c.*211_*212del(p.?) that indicate a higher risk of 0 + 2 configuration. The patients with these variants and 2 SMN1-exon8 copies are at higher risk to be silent carriers, but they may not be carriers. For the 15758 performed, if one or both patients were analyzed by genotyping analysis, 3,6% (432/12055 matchings) identified had high risk of affected offspring for autosomal or X-Linked recessive diseases. When both patients were analyzed by sequencing, 6% (223/3703 matchings) were identified at high risk of affected offspring of the diseases analyzed allowing a higher identification of couples at risk. Limitations, reasons for caution The analysis was performed on 301 genes, in order to have a better understanding of CFR for panel designs or patients genetic counseling, a larger cohort of genes should be taken into account, these results show the importance of complete analysis to assess the carrier risks. Wider implications of the findings It is important to have wider genetic databases for CFR but also for variant pathogenicity in order to have better results on CFR analyses and panel designs, in order to provide proper genetic counseling to patients looking to improve the chances of healthy offspring. Trial registration number Not applicable

EFFECTS OF CHEMICAL PESTICIDES ON HUMAN HEALTH

The industrialization of agriculture has made natural ecosystems more chemically burdened. Agrochemicals known as pesticides. Use of pesticides is common in controlling weeds and insect infestation in agricultural fields as well as a variety of pests and disease carriers such as mosquitoes, ticks, rodents, and mice in homes, workplaces, shopping centers, and public areas their exposure through numerous pathways such as residues in food and drinking water, inhalation, ingestion, eye, and dermal contact. Although these risks can have short-term effects e.g., skin and eye irritation, headaches, dizziness, and nausea, or long-term effects e.g., cancer, asthma, infertility, allergy, Parkinson’s disease, and birth defects on human health. It is challenging to determine the risks because of the interaction of many variables, including the duration and intensity of exposure, the type of pesticide (in terms of toxicity and persistence), and the environmental characteristics of the affected areas.

Barriers with Valve Mechanisms Are Predicted to Protect Crops from Slug Carriers of Rat Lungworm Disease.

Angiostrongyliasis (Rat Lungworm disease) is an emerging parasitic disease caused by the ingestion of gastropods infected with the neurotropic nematode Angiostrongylus cantonensis. The reduction of crop infestation with infected slug carriers may vary widely by protection method. We explored the application of barriers with valve mechanisms, whereby selective directional forces caused a greater number of slugs to exit than enter the protected plot, leading to decreased slug population densities at a steady state. Using field data, we constructed predictive models to estimate slug population densities at a steady state in protected plots with (1) no valve effect, (2) a valve effect, (3) no valve effect with a single breach of the barrier, (4) a valve effect with a single breach of the barrier, (5) a valve effect with a constant breach of the barrier, and (6) a repelling effect. For all scenarios, plots protected using a barrier with a valve effect had consistently lower slug densities at a steady state. Our findings support the use of barriers with valve mechanisms under different conditions, and potentially in combination with other interventions to reduce the contamination of crops by slug carriers of A. cantonensis. Improving barriers extends beyond disease mitigation to economic and cultural impacts on the local farmer and consumer communities.

Identifikasi Cemaran Mikroba pada Jajanan Bakso di Kota Majene

High microbial contamination in food is an indicator of hygiene that determines the health of food for consumption. Meatballs are a very popular snack in Majene City. Apart from their delicious taste, meatballs also have a relatively cheap price, so they have always been a popular snack alternative. The high nutritional content in meatballs can be a medium for the growth of bacteria so meatballs can be carriers of disease. The aims of this study were to determine the total number of bacterial contaminants and identify the coliform in meatballs at Majene City. The study used a quantitative descriptive method with a sample of 10 traders. The test carried out was culturing bacteria on NA (Nutrient Agar) media to calculate the total number of microbes in meatballs using the Total Plate Count (TPC) method and EMBA (Eosin Methylene Blue Agar) media to determine the presence of coliform bacteria in the sample then continued with gram staining test. The results of the study showed that 3 samples were found on NA media which had microbial contamination levels exceeding the threshold specified in SNI (Indonesian National Standard) 3818:2014 where the highest amount allowed was 1 × 105 cfu/g. Samples that exceeded the threshold namely sample A was 1.33 × 106 cfu/g; sample C was 1.06 × 105 cfu/g; and sample G was 5.8 × 106 cfu/g. There were 5 samples that tested positive for coliform, namely samples A, B, C, D, and G

Multi-ethnic Imputation System (MI-System): A genotype imputation server for high-dimensional data

ObjectiveGenotype imputation is a commonly used technique that infers un-typed variants into a study’s genotype data, allowing better identification of causal variants in disease studies. However, due to overrepresentation of Caucasian studies, there’s a lack of understanding of genetic basis of health-outcomes in other ethnic populations. Therefore, facilitating imputation of missing key-predictor-variants that can potentially improve a risk health-outcome prediction model, specifically for Asian ancestry, is of utmost relevance. MethodsWe aimed to construct an imputation and analysis web-platform, that primarily facilitates, but is not limited to genotype imputation on East-Asians. The goal is to provide a collaborative imputation platform for researchers in the public domain towards rapidly and efficiently conducting accurate genotype imputation. ResultsWe present an online genotype imputation platform, Multi-ethnic Imputation System (MI-System) (https://misystem.cgm.ntu.edu.tw/), that offers users 3 established pipelines, SHAPEIT2-IMPUTE2, SHAPEIT4-IMPUTE5, and Beagle5.1 for conducting imputation analyses. In addition to 1000 Genomes and Hapmap3, a new customized Taiwan Biobank (TWB) reference panel, specifically created for Taiwanese-Chinese ancestry is provided. MI-System further offers functions to create customized reference panels to be used for imputation, conduct quality control, split whole genome data into chromosomes, and convert genome builds. ConclusionUsers can upload their genotype data and perform imputation with minimum effort and resources. The utility functions further can be utilized to preprocess user uploaded data with easy clicks. MI-System potentially contributes to Asian-population genetics research, while eliminating the requirement for high performing computational resources and bioinformatics expertise. It will enable an increased pace of research and provide a knowledge-base for genetic carriers of complex diseases, therefore greatly enhancing patient-driven research. Statement of significanceMulti-ethnic Imputation System (MI-System), primarily facilitates, but is not limited to, imputation on East-Asians, through 3 established prephasing-imputation pipelines, SHAPEIT2-IMPUTE2, SHAPEIT4-IMPUTE5, and Beagle5.1, where users can upload their genotype data and perform imputation and other utility functions with minimum effort and resources. A new customized Taiwan Biobank (TWB) reference panel, specifically created for Taiwanese-Chinese ancestry is provided. Utility functions include (a) create customized reference panels, (b) conduct quality control, (c) split whole genome data into chromosomes, and (d) convert genome builds. Users can also combine 2 reference panels using the system and use combined panels as reference to conduct imputation using MI-System.

Large eddy simulation of sneeze plumes and particles in a poorly ventilated outdoor air condition: A case study of the University of Houston main campus

Since the outbreak of the COVID-19 pandemic, many previous studies using computational fluid dynamics (CFD) have focused on the dynamics of air masses, which are believed to be the carriers of respiratory diseases, in enclosed indoor environments. Although outdoor air may seem to provide smaller exposure risks, it may not necessarily offer adequate ventilation that varies with different micro-climate settings. To comprehensively assess the fluid dynamics in outdoor environments and the efficiency of outdoor ventilation, we simulated the outdoor transmission of a sneeze plume in “hot spots” or areas in which the air is not quickly ventilated. We began by simulating the airflow over buildings at the University of Houston using an OpenFOAM computational fluid dynamics solver that utilized the 2019 seasonal atmospheric velocity profile from an on-site station. Next, we calculated the length of time an existing fluid is replaced by new fresh air in the domain by defining a new variable and selecting the hot spots. Finally, we conducted a large-eddy simulation of a sneeze in outdoor conditions and then simulated a sneeze plume and particles in a hot spot. The results show that fresh incoming air takes as long as 1000 s to ventilate the hot spot area in some specific regions on campus. We also found that even the slightest upward wind causes a sneeze plume to dissipate almost instantaneously at lower elevations. However, downward wind provides a stable condition for the plume, and forward wind can carry a plume even beyond six feet, the recommended social distance for preventing infection. Additionally, the simulation of sneeze droplets shows that the majority of the particles adhered to the ground or body immediately, and airborne particles can be transported more than six feet, even in a minimal amount of ambient air.

Language disorders in patients with striatal lesions: Deciphering the role of the striatum in language performance

The classical neural model of language refers to a cortical network involving frontal, parietal and temporal regions. However, patients with subcortical lesions of the striatum have language difficulties. We investigated whether the striatum is directly involved in language or whether its role in decision-making has an indirect effect on language performance, by testing carriers of Huntington's disease (HD) mutations and controls. HD is a genetic neurodegenerative disease primarily affecting the striatum and causing language disorders. We asked carriers of the HD mutation in the premanifest (before clinical diagnosis) and early disease stages, and controls to perform two discrimination tasks, one involving linguistic and the other non-linguistic stimuli. We used the hierarchical drift diffusion model (HDDM) to analyze the participants' responses and to assess the decision and non-decision parameters separately. We hypothesized that any language deficits related to decision-making impairments would be reflected in the decision parameters of linguistic and non-linguistic tasks. We also assessed the relative contributions of both HDDM decision and non-decision parameters to the participants' behavioral data (response time and discriminability). Finally, we investigated whether the decision and non-decision parameters of the HDDM were correlated with brain atrophy.The HDDM analysis showed that patients with early HD have impaired decision parameters relative to controls, regardless of the task. In both tasks, decision parameters better explained the variance of response time and discriminability performance than non-decision parameters. In the linguistic task, decision parameters were positively correlated with gray matter volume in the ventral striatum and putamen, whereas non-decision parameters were not.Language impairment in patients with striatal atrophy is better explained by a deficit of decision-making than by a deficit of core linguistic processing. These results suggest that the striatum is involved in language through the modulation of decision-making, presumably by regulating the process of choice between linguistic alternatives.

Abstract 5768: Genetic screening in a tertiary medical center identifies carriers of cancer predisposition diseases that would be missed by clinical guidelines

Abstract Two inherited autosomal dominant cancer predisposition conditions - BRCA related hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) - are termed Centers for Disease Control and Prevention Tier 1 (CDCT1) genetic conditions, for which early identification and intervention have a positive impact on public health. Selection of individuals for genetic testing for these conditions is based on personal and family history. The goal of this study was to evaluate whether screening in a tertiary medical center using exome sequencing could efficiently identify carriers of HBOC and LS and to determine the frequency of incremental carriers identified outside of traditional clinical practice guidelines. Participants from three geographically diverse Mayo Clinic practices in the USA (Rochester MN, Phoenix AZ, Jacksonville FL) consented to clinical “Exome+” sequencing (Helix, San Mateo, CA; Mayo GeneGuide, Rochester, MN) in the TAPESTRY study (NCT05212428), which links sequencing data with electronic health records and the return of CDCT1 genetic findings. For this study we focused on two inherited cancer predisposition conditions: BRCA-related HBOC (BRCA1 and BRCA2) and LS (MLH1, MSH2, MSH6, PMS2 and EPCAM). Detailed chart review to collect demographic information, personal and family history, and assessment of clinical practice guidelines for genetic evaluation (National Cancer Control Network 2021). To date, 44,306 patients have enrolled and sequenced in TAPESTRY. Annotation and interpretation of all variants in 7 genes for HBOC and LS resulted in identification of 550 carriers (prevalence 1.24%) which included 387 with HBOC (27.2% BRCA1, 42.8% BRCA2) and 163 with LS (12.3% MSH6, 8.8% PMS2, 4.5% MLH1, 3.8% MSH2 and 0.2% EPCAM). Demographics of the cohort included: 62.7% female, mean age 55.2 years, non-white race 9.6% and 3.8% Hispanic/Latino ethnicity. A personal history of cancer was present in 46.4% of test positive patients, including 22.5% of HBOC patients with breast or ovarian cancer and 20.9% of LS patients with colorectal or uterine cancer. More than half of the patients (52.1%) were newly diagnosed with HBOC and LS based on the results of this study. Overall, 39.2% of HBOC/LS carriers identified through Exome+ sequencing did not satisfy NCCN criteria for genetic evaluation, this was higher for LS (56.2%) compared to HBOC (32%). Amongst those newly diagnosed with HBOC/LS (n=286), NCCN criteria were not satisfied in 60% of cases (78% for LS and 51% for HBOC). Of the pathogenic germline variant carriers who met NCCN guidelines for testing, 34.2% were not aware of their diagnosis prior to participation in this study. Our results emphasize the need for wide genomic screening for CDCT1 cancer predisposition syndromes. Such screening could identify at-risk carriers of HBOC and LS, who would not otherwise be identified through clinical practice guidelines. Citation Format: Emily Gay, Niloy Jewel Samadder, Michelle L. Bublitz, Melanie M. Peterson, Tammy A. Wilson, Lorelei A. Bandel, Sebastian M. Armasu, Robert A. Vierkant, Matthew J. Ferber, Eric W. Klee, Nicholas B. Larson, Teresa M. Kruisselbrink, Timothy B. Curry, Jan B. Egan, Jennifer L. Kemppainen, Jessa S. Bidwell, Jennifer L. Anderson, Tammy M. McAllister, T'Nita S. Walker, Katie L. Kunze, Vanda Lindpere, Michael A. Golafshar, Margaret Klint, Richard J. Presutti, William V. Bobo, Aleksander Sekulic, Jolene M. Summer Bolster, Cheryl L. Willman, Konstantinos N. Lazaridis. Genetic screening in a tertiary medical center identifies carriers of cancer predisposition diseases that would be missed by clinical guidelines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5768.

Impact of Indication for Oocyte and Embryo Reception on Reproductive and Obstetric Outcomes

Objectives: This study aimed to assess if the indication for oocyte reception (OR) or embryo reception (ER) impacts the reproductive and obstetric outcomes by evaluating our experience at a tertiary fertility centre and by performing a literature review on this subject. Several previous studies have reported that, in contrast to other types of fertility treatment, the indication for OR/ER seems to have little impact on the outcomes. However, the compared indication groups vary considerably between these studies, and some data indicates worse outcomes in patients who developed premature ovarian insufficiency (POI) due to Turner syndrome or treatment with chemotherapy/radiotherapy. Design: A retrospective analysis of all cases of OR/ER at a tertiary fertility centre from 2001 until 2020 was conducted. We analysed 584 cycles from 194 individual patients. A literature review on the impact of indication on reproductive or obstetric outcomes of OR/ER was performed using the following databases: PubMed/MEDLINE, Embase, and the Cochrane Library. A total of 27 studies were included and analysed. Participants, Setting, Methods: For the retrospective analysis, patients were divided into three major indication groups: failure of autologous assisted reproductive technology, POI, and genetic disease carrier. To assess reproductive outcomes, we determined pregnancy rate, implantation rate, miscarriage rate, and live birth rate. For comparing obstetric outcomes, we reviewed the term of birth, mode of delivery, and birthweight. Outcomes were compared using Fisher’s exact test, χ² test, and one-way ANOVA utilizing the GraphPad tool. Results: There were no significant differences in reproductive and obstetric outcomes between the three major indication groups in our population, in line with the findings reported by existing literature. Data on impaired reproductive outcomes in patients with POI after chemotherapy/radiotherapy are conflicting. Obstetrically, these patients are at higher risk of preterm birth and possibly also low birthweight, especially after abdomino-pelvic or total body irradiation. For patients with POI due to Turner syndrome, most data suggest similar pregnancy rates but a higher rate of pregnancy loss, and obstetrically an increased risk of hypertensive disorders and caesarean section. Limitations: The small number of patients in the retrospective analysis resulted in low statistical power when evaluating differences between smaller subgroups. There were some missing data on the occurrence of complications during pregnancy. Our analysis covers a period of 20 years, during which several technological innovations have also been made. Conclusions: Our study shows that the important heterogeneity in couples treated with OR/ER does not significantly impact their reproductive or obstetric outcomes, except for POI due to Turner syndrome or treatment with chemotherapy/radiotherapy, where there seems to be an important uterine/endometrial component that cannot be entirely overcome by providing a healthy oocyte.

Ovarian endometrioma increases the embryo aneuploid rate: an analysis of 7092 biopsied blastocysts from fertile monogenetic disease carriers

BackgroundEndometriosis affects many reproductive aged patients with fertility decline and poor outcomes of assisted reproductive treatments, mainly by decreased ovarian reserve and lower fertilization and implantation rates. In recent decade, altered oocyte microenvironments and abnormal spindle organization have been reported to be critical to oocyte chromosomal segregation, organization and aneuploid formation. However, clinical evidences are still limited on whether endometriosis influences oocyte and embryo development. We aimed to figure out the impact of endometrioma on embryo aneuploid formation.MethodThis retrospective cohort study included 1,021 patients (7,092 biopsied embryos) from January 2012 to December 2020. Fertile patients without a history of miscarriage who underwent PGT-M treatment with aneuploid screening were included. Patients with ovarian endometrioma were defined as the study group, while patients without endometriosis were defined as the control group. All demographic, controlled ovarian stimulation treatment and aneuploid screening data were recorded and compared.ResultsThe incidence of endometrioma in our study population was 6.5%. There were 7,092 embryos biopsied in total, with 308 embryos in the study group and 6,784 embryos in the control groups. The demographic characteristics were comparable between the two groups except the basal FSH level (6.02 IU/L vs. 5.52 IU/L, p = 0.012). The euploid rate of the study group was significantly lower than that of the control group (52.6% vs. 61.8%, p = 0.012), while the oocyte maturation, fertilization, usable embryo and blastocyst formation rates were comparable. Adjusted for basal FSH level, starting stimulating gonadotropin dosage, total gonadotropin dosage and FSH level on hCG day, euploid rate was still negatively related to endometrioma status.ConclusionsEndometrioma status disturbs oocyte and embryo development. For infertile patients with endometrioma who require assisted reproductive treatment, pre-treatment is necessary to improve treatment outcomes.Trial registrationNot applicable.

Resilient and social health service network design to reduce the effect of COVID-19 outbreak.

With the severe outbreak of the novel coronavirus (COVID-19), researchers are motivated to develop efficient methods to face related issues. The present study aims to design a resilient health system to offer medical services to COVID-19 patients and prevent further disease outbreaks by social distancing, resiliency, cost, and commuting distance as decisive factors. It incorporated three novel resiliency measures (i.e., health facility criticality, patient dissatisfaction level, and dispersion of suspicious people) to promote the designed health network against potential infectious disease threats. Also, it introduced a novel hybrid uncertainty programming to resolve a mixed degree of the inherent uncertainty in the multi-objective problem, and it adopted an interactive fuzzy approach to address it. The actual data obtained from a case study in Tehran province in Iran proved the strong performance of the presented model. The findings show that the optimum use of medical centers' potential and the corresponding decisions result in a more resilient health system and cost reduction. A further outbreak of the COVID-19 pandemic is also prevented by shortening the commuting distance for patients and avoiding the increasing congestion in the medical centers. Also, the managerial insights show that establishing and evenly distributing camps and quarantine stations within the community and designing an efficient network for patients with different symptoms result in the optimum use of the potential capacity of medical centers and a decrease in the rate of bed shortage in the hospitals. Another insight drawn is that an efficient allocation of the suspect and definite cases to the nearest screening and care centers makes it possible to prevent the disease carriers from commuting within the community and increase the coronavirus transmission rate.

Transcriptome Profiling of Rhipicephalus annulatus Reveals Differential Gene Expression of Metabolic Detoxifying Enzymes in Response to Acaricide Treatment.

Ticks are hematophagous ectoparasites of economic consequence by virtue of being carriers of infectious diseases that affect livestock and other sectors of the agricultural industry. A widely prevalent tick species, Rhipicephalus (Boophilus) annulatus, has been recognized as a prime vector of tick-borne diseases in South Indian regions. Over time, the use of chemical acaricides for tick control has promoted the evolution of resistance to these widely used compounds through metabolic detoxification. Identifying the genes related to this detoxification is extremely important, as it could help detect valid insecticide targets and develop novel strategies for effective insect control. We performed an RNA-sequencing analysis of acaricide-treated and untreated R. (B.) annulatus and mapped the detoxification genes expressed due to acaricide exposure. Our results provided high-quality RNA-sequenced data of untreated and amitraz-treated R. (B.) annulatus, and then the data were assembled into contigs and clustered into 50,591 and 71,711 uni-gene sequences, respectively. The expression levels of the detoxification genes across different developmental stages of R. (B.) annulatu identified 16,635 transcripts as upregulated and 15,539 transcripts as downregulated. The annotations of the differentially expressed genes (DEGs) revealed the significant expression of 70 detoxification genes in response to the amitraz treatment. The qRT-PCR revealed significant differences in the gene expression levels across different life stages of R. (B.) annulatus.

Abundance and Condition of Populations of Small Mammals as Carriers of Natural Focal Human Diseases in the Karelia North-East Ladoga

Summing up the results of the long-term studies of population ecology and dynamics of small mammals for more than half a century (1966–2018). Small mammals are involved in the formation and functioning of natural-focil of human vector-borne diseases common in the North-Eastern Ladoga region. Encephalitis and tularemia circulate intensively in the Ladoga region under conditions of intensive anthropogenic transformation of taiga ecosystems. Local landscapes belong to the subzone of the middle taiga forests. Most of the studied species of small mammals are located in the northern periphery of this area. Here representatives of the native taiga fauna of Micromammalia constantly experience powerful anthropogenic pressure, which leads to a decrease in their abundance and correlation of the species. Of the total amount of 22 species of small mammals collected here, Sorex araneus and Myodes glareolus dominate. Next, the species prevalent (according to the degree of predominant species) in the counts are Microtus agrestis, Sorex minutus and Sorex caecutiens. Other species are relatively rare and appear in smaller numbers. Myodes glareolus has main role in the feeding of ticks and, accordingly, in the circulation of infections in nature, the differentiated contribution of individual intrapopulation groups in maintaining the number of vectors and the activity of pathogens. Shrews are important for the development of the larval stages of the tick. In the research area, were recorded total index of trap catch of abundance of small animals with trap lines from 0.34 to 18.5 individuals per 100 snap traps-nights (average of 7.8 ind.) and with pitfall traps recorded from 2.7 to 25.4 individuals per 10 ditch-nights (average of 14 ind.). This indicates that the studied area has smaller amount of mammals compared to other regions in Southern Europe. Nevertheless, the studies determine a rather tense epidemic situation in the studied area. Population of small mammals of boreal ecosystem steadily affect the mass feeding of carriers of natural focal infections.

Farmers’ Perception towards Agricultural Pesticides and Associated Human Health Impact in Misrak Badawacho Woreda, Ethiopia

Pesticides are applied to control weeds and insect infestation in agricultural fields and various pests and disease carriers. As the modes of action for pesticides are not species-specific, concerns have been raised about risks associated with their exposure through various routes. The main objective of this study was to assess farmers’ perception towards agricultural pesticides and associated human health impact in Misrak Badawacho Woreda, Ethiopia. Community-based cross-sectional study was used to assess farmers’ perception towards agricultural pesticides and associated human health impact. Systematic random sampling technique was used to select study subjects. Structured questionnaires were used to collect data. Data were entered and analyzed using SPSS 20. Descriptive statistics were used during this study. About 361 study subjects completed the questionnaires. Among the studies subjects (81%) of them were males and 19% were females. The results showed that commonly applied pesticides comprised of herbicides (55%), fungicides (28%), Veterinary control (14%) and insecticides (3%). About 54% of the farm workers were used normal clothe, 17% were used boots,11% were used eye glass, 8% were used handkerchief, 3% were used mask and 2% were used Cotton during pesticide application. From total study subjects 38% do not follow instructions during pesticide application and 55% reuse pesticide containers for storing food and water in the home. Majority (93%) reported that they had suffered from pesticide-related health signs and symptoms during or after application of pesticides. Itching and skin irritation was the common symptom (74%) followed by headache (68%) during pesticide application. Generally the Farm workers had poor handling practices during pesticide application. Therefore continuous pesticide training programs for workers could be implemented.

Methods and means for managing moisture supply regimes during original potato seed growing in the context of global climate change

Obtaining high-quality seed material in soil-climatic zones favorable for the production of original and elite potato seed production requires placing production on clean phytosanitary territories in the high-mountainous, North-Western and Arctic regions of the Russian Federation, where there is a minimum number of carriers of potato diseases, moderate temperatures, and a sufficient level of moisture supply to plants. The statistics of weather observations show a steady increase in average air temperatures, as well as an increase in the amount of average annual precipitation with uneven precipitation. In intensive technologies used for the production of potato seeds, there is a significant over compaction of the surface and subsurface horizons of the soil, which leads to a deterioration in the moisture supply regime for plants, which significantly affects the yield and quality of seed material. The solution of this problem requires the improvement of technological methods and technical means used during potato seed production.

Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers

Genetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, the cell-specific effect of variants in these genes is not fully understood. Here, we perform single-nucleus RNA-sequencing (snRNA-seq) on nearly 300,000 nuclei from the parietal cortex of AD autosomal dominant (APP and PSEN1) and risk-modifying variant (APOE, TREM2 and MS4A) carriers. Within individual cell types, we capture genes commonly dysregulated across variant groups. However, specific transcriptional states are more prevalent within variant carriers. TREM2 oligodendrocytes show a dysregulated autophagy-lysosomal pathway, MS4A microglia have dysregulated complement cascade genes, and APOEε4 inhibitory neurons display signs of ferroptosis. All cell types have enriched states in autosomal dominant carriers. We leverage differential expression and single-nucleus ATAC-seq to map GWAS signals to effector cell types including the NCK2 signal to neurons in addition to the initially proposed microglia. Overall, our results provide insights into the transcriptional diversity resulting from AD genetic architecture and cellular heterogeneity. The data can be explored on the online browser (http://web.hararilab.org/SNARE/).

Oocytes Development in Ixodid Tick of the Genus Dermacentor

Introduction. Ixodid ticks are the carriers of many infectious and parasitic diseases. Transmissible tick-borne diseases include borreliosis, viral encephalitis, anaplasmosis, ehrlichiosis and babesiosis, they can be dangerous for both humans and animals. Since the forest areas stopped being treated with pesticides, the reproduction of ixodid ticks became almost unregulated, and their population is constantly growing. In addition, ixodid ticks, the carriers of a number of dangerous anthropozoonosis, have high fecundity.Therefore, the aim of the study was to investigate the process of ectoparasites development, specifically, the dynamics of the oocytes maturation process in ixodid ticks of the genus Dermacentor. Materials and methods. The ixodid ticks of the genus Dermacentor were the object of the study. The study was conducted on the basis of the Chair “Parasitology and Veterinary-Sanitary Expertise, Anatomy and Pathoanatomy named after Prof. S. N. Nikolsky” and the Scientific-Diagnostic and Medical Veterinary Center of the Federal State Budgetary Educational Institution of Higher Education "Stavropol State Agrarian University", as well as on the basis of veterinary clinics "Veterinary Center named after Pirogov” of the individual entrepreneur Zaichenko. The reproductive system of females served the material for the research. The females were treated and filled into paraffin according to the routine histological technique, afterwards the sections of 5-7 µm. thick were made. For routine examination, histological sections were stained with hematoxylin and eosin, as well as by Mallory staining method. Microscopic examination of the histological sections of female ticks was carried out using the Olympus BX53 microscope (Japan) at 4×, 20×, 40×, 100× magnification.Results. The macroscopic examination of female ixodid ticks of the genus Dermacentor showed that ovary is an azygos, horseshoe-shaped organ to which oocytes are attached. It was observed that oocytes develop asynchronously. Immature oocytes predominated mostly in the distal part of the ovary, while mature — in the proximal. The oocytes of this species of tick are classified by five main stages of maturation and are described based on the cytoplasm external view, the presence of the germinal vesicle, the presence of yolk granules and the chorion formation, and the morphometric data. The process of oocytes maturation at different stages is not linear. During vitellogenesis, the active and verified dynamics of growth is recorded from I to V stage of oocytes development the increase of their size by 55 times is observed.Discussion and conclusions. In female ticks of the genus Dermacentor, maturation of oocytes goes through 5 stages. The process of oocytes maturation at different stages is not linear, since both mitotic and meiotic processes occur simultaneously in the ovary. At the same time, in the oocytes development the active verified dynamics of growth is recorded.

Clinical studies of the repellent effectiveness of the new veterinary drug Okvet

Mosquitoes are one of the most common dipteran insects and are carriers of dangerous vector-borne diseases. An important role of reservoirs of ectoparasites belongs to dogs. The domestic dog is close to the person. The problem of maintaining the health of the dog and reducing the risk of human infection in conditions of high density of blood-sucking insects can be solved by the use of repellent sprays for animals. Recently, synthetic pyrethroids have been used as effective insecticides. We have conducted clinical studies to study the effectiveness of the repellent action of the new veterinary drug "Okvet" insect-acaricidal spray on dogs. The use of the spray was carried out during the period of mosquito activity, depending on the time of day in the Republic of Armenia. The study involved 22 clinically healthy dogs aged 1.5 to 9 years of both sexes. According to the results of clinical studies, it was found that the repellent effect of the veterinary drug "Okvet" applied to dogs individually, once, while preventing bites of dipterous flying insects according to the presented doses, rules and application techniques, the drug "Okvet" showed a high efficiency of the repellent effect in the conditions of farms in Ararat area within 3 days. During the physical examination, no side effects from the use of the drug "Okvet" were revealed.

Exploring the barriers to and facilitators of implementing CanRisk in primary care: a qualitative thematic framework analysis.

The CanRisk tool enables the collection of risk factor information and calculation of estimated future breast cancer risks based on the multifactorial Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model. Despite BOADICEA being recommended in National Institute for Health and Care Excellence (NICE) guidelines and CanRisk being freely available for use, the CanRisk tool has not yet been widely implemented in primary care. To explore the barriers to and facilitators of the implementation of the CanRisk tool in primary care. A multi-methods study was conducted with primary care practitioners (PCPs) in the East of England. Participants used the CanRisk tool to complete two vignette-based case studies; semi-structured interviews gained feedback about the tool; and questionnaires collected demographic details and information about the structural characteristics of the practices. Sixteen PCPs (eight GPs and eight nurses) completed the study. The main barriers to implementation included: time needed to complete the tool; competing priorities; IT infrastructure; and PCPs' lack of confidence and knowledge to use the tool. Main facilitators included: easy navigation of the tool; its potential clinical impact; and the increasing availability of and expectation to use risk prediction tools. There is now a greater understanding of the barriers and facilitators that exist when using CanRisk in primary care. The study has highlighted that future implementation activities should focus on reducing the time needed to complete a CanRisk calculation, integrating the CanRisk tool into existing IT infrastructure, and identifying appropriate contexts in which to conduct a CanRisk calculation. PCPs may also benefit from information about cancer risk assessment and CanRisk-specific training.