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Lyme disease (LD) cases have been on the rise throughout the United States, costing the healthcare system up to $1.3 billion per year, and making LD one of the greatest threats to public health. Factors influencing the number of LD cases range from environmental to system-level variables, but little is known about the influence of vegetation (canopy, understory, and ground cover) and human behavioral risk on LD cases and exposure to infected ticks. We determined the influence of various risk factors on the risk of exposure to infected ticks on 22 different walkways using multinomial logistic regression. The model classifies the walkways into high-risk and low-risk categories with 90% accuracy, in which the understory, human risk, and number of rodents are significant indicators. These factors should be managed to control the risk of transmission of LD to humans.

Precision medicine has emerged as a transformative approach aimed at tailoring treatment to individual patients, moving away from the traditional one-size-fits-all model. However, Clinical decision support systems encounter challenges, particularly in terms of data aspects. In response, our study proposes a data-driven framework rooted in Simon’s decision-making model. This framework leverages advanced technologies such as artificial intelligence and data analytics to enhance clinical decision-making in precision medicine. By addressing limitations and integrating AI and analytics, our study contributes to the advancement of optimal clinical decision-making practices in precision healthcare.

The innovation inherent to employing expanded polystyrene (EPS) beads lies in its transformative impact on traditional concrete practices. Through the incorporation of EPS beads in concrete mixtures, a novel approach emerges that significantly alters the material’s characteristics, and opens up new avenues for construction and design. Studying the shear behavior of RC beams made with EPS beads is essential for advancing knowledge, improving design practices, ensuring structural integrity, and promoting the effective and responsible use of innovative materials in construction. This research experimentally investigated the effect of using EPS beads and pozzolana aggregate (PA) on the shear behavior of the RC beams. A total of 27 simply supported rectangular beams were cast, using three novel distinct mix designs, and were subjected to two-point load testing until failure. These three mixes were categorized as follows: a control mix, a mix with only EPS, and a mix with EPS, along with an additive. The ultimate failure load was experimentally recorded for all specimens, and the influence of the temperature (300 °C and 600 °C) on the RC beams made with EPS was examined. The findings revealed a reduction in the concrete compressive strength and density in the beams containing EPS and EPS with superplasticizers of (21.7%, 24.9%) and (11.3%, 16.2%), respectively. Additionally, EPS played a significant role in diminishing the ultimate shear capacity of the beams, compared to the control beams, by about 19.4%. However, the addition of a superplasticizer along with the EPS helped to maintain the beam capacity, to some extent. Conversely, the beams exposed to a temperature of 300 °C exhibited an almost similar capacity to that of the control beams without heating. Nevertheless, at 600 °C, the beams displayed a noticeable decrease in the ultimate load capacity, compared to the unheated control beams.

Reinforced concrete corbels were examined in this study for the cracking behavior and strength evaluation, focusing on defects typically found in these structures. A total of 11 corbel specimens were tested, including healthy specimens (HS), specimens with lower concrete strength (LC), specimens with less reinforcement ratio (LR), and specimens with more concrete cover than specifications (MC). The HS specimens were designed using the ACI conventional method. The specimens were tested under static loading conditions, and the actual strengths along with the crack patterns were determined. In the experimental tests, the shear capacity of the HS specimens was 28.18% and 57.95% higher than the LR and LC specimens, respectively. Similarly, the moment capacity of the HS specimens was 25% and 57.52% greater than the LR and LC specimens, respectively. However, in the case of the built-up sections, the shear capacity of the HS specimens was 9.91% and 37.51% higher than the LR and LC specimens, respectively. Likewise, the moment capacity of the HS specimens was 39.91% and 14.30% higher than the LR and LC specimens, respectively. Moreover, a detailed nonlinear finite element model (FEM) was developed using ABAQUS, and a more user-friendly strut and tie model (STM) was investigated toward its suitability to assess the strengths of the corbels with construction defects. The results from FEM and STM were compared. It was found that the FEM results were in close agreement with their experimental counterparts.

The aim of this study is to investigate the therapeutic potential of higher doses of PU-91, quercetin, or in combination on transmitochondrial cybrid cell lines with various mtDNA haplogroups derived from patients with age-related macular degeneration (AMD), glaucoma (Glc), keratoconus (KC), and normal (NL) individuals. Cybrids were treated with PU-91 (P) (200 µM) alone, quercetin (Q) (20 µM) alone, or a combination of PU-91 and quercetin (P+Q) for 48 h. Cellular metabolism and the intracellular levels of reactive oxygen species (ROS) were measured by MTT and H2DCFDA assays, respectively. Quantitative real-time PCR was performed to measure the expression levels of genes associated with mitochondrial biogenesis, antioxidant enzymes, inflammation, apoptosis, and senescence pathways. PU-91(P) (i) improves cellular metabolism in AMD cybrids, (ii) decreases ROS production in AMD cybrids, and (iii) downregulates the expression of LMNB1 in AMD cybrids. Combination treatment of PU-91 plus quercetin (P+Q) (i) improves cellular metabolism in AMD, (ii) induces higher expression levels of TFAM, SOD2, IL6, and BAX in AMD cybrids, and (iii) upregulates CDKN1A genes expression in all disease cybrids. Our study demonstrated that the P+Q combination improves cellular metabolism and mitochondrial biogenesis in AMD cybrids, but senescence is greatly exacerbated in all cybrids regardless of disease type by the P+Q combined treatment.

Heating, ventilation, and air conditioning (HVAC) systems play a crucial role in either increasing or decreasing the risk of airborne disease transmission. High ventilation, for instance, is a common method used to control and reduce the infection risk of airborne diseases such as COVID-19. On the other hand, high ventilation will increase energy consumption and cost. This paper proposes an optimal HVAC controller to assess the trade-off between energy consumption and indoor infection risk of COVID-19. To achieve this goal, a nonlinear model predictive controller (NMPC) is designed to control the HVAC systems of a university building to minimize the risk of COVID-19 transmission while reducing building energy consumption. The NMPC controller uses dynamic models to predict future outputs while meeting system constraints. To this end, a set of dynamic physics-based models are created to capture heat transfer and conservation of mass, which are used in the NMPC controller. Then, the developed models are experimentally validated by conducting experiments in the ETLC building at the University of Alberta, Canada. A classroom in the building is equipped with a number of sensors to measure indoor and outdoor environmental parameters such as temperature, relative humidity, and CO2 concentration. The validation results show that the model can predict room temperature and CO2 concentration by 0.8%, and 2.4% mean absolute average errors, respectively. Based on the validated models, the NMPC controller is designed to calculate the optimal airflow and supply air temperature for every 15 min. The results for real case studies show that the NMPC controller can reduce the infection risk of COVID-19 transmission below 1% while reducing energy consumption by 55% when compared to the existing building controller.

Mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is the most unearthed peptide encoded by mitochondrial DNA (mtDNA). It is an important regulator of the nuclear genome during times of stress because it promotes an adaptive stress response to maintain cellular homeostasis. Identifying MOTS-c specific binding partners may aid in deciphering the complex web of mitochondrial and nuclear-encoded signals. Mitochondrial damage and dysfunction have been linked to aging and the accelerated cell death associated with many types of retinal degenerations. Furthermore, research on MOTS-c ability to revive oxidatively stressed RPE cells has revealed a significant protective role for the molecule. Evidence suggests that senescent cells play a role in the development of age-related retinal disorders. This review examines the links between MOTS-c, mitochondria, and age-related diseases of the retina. Moreover, the untapped potential of MOTS-c as a treatment for glaucoma, diabetic retinopathy, and age-related macular degeneration is reviewed.

This paper aims to investigate the effect of using different configurations of near-surface mounted carbon-fiber-reinforced polymer (NSM-CFRP) strips on the shear strength of strengthened and rehabilitated reinforced concrete (RC) T-beams with different internal shear stirrup spacing. The internal shear stirrup spacing was 50 and 150 mm. The NSM-CFRP strips were at an inclination of 45° and spaced at 75 and 150 mm. A total of eight beams were tested in this study: two beams without NSM-CFRP as control beams for the purpose of comparison; three beams were strengthened by NSM-CFRP; and three beams were rehabilitated by NSM-CFRP. The experimental shear capacities were compared with the theoretical values predicted by the ACI 440.2R-17. The results indicated that the use of NSM-CFRP strips enhanced the shear capacity for all beams compared to their corresponding control beams. The enhancements in the shear capacity increased with the decrease in the spacing of the internal shear stirrups and NSM-CFRP strips. The ACI 440.2R-17 was conservative in predicting the theoretical shear capacities.

The ubiquitin-proteasome pathway (UPP) is the major proteolytic system in the cytosol and nucleus of all eukaryotic cells. The role of proteasome inhibitors (PIs) as critical agents for regulating cancer cell death has been established. Aziridine derivatives are well-known alkylating agents employed against cancer. However, to the best of our knowledge, aziridine derivatives showing inhibitory activity towards proteasome have never been described before. Herein we report a new class of selective and nonPIs bearing an aziridine ring as a core structure. In vitro cell-based assays (two leukemia cell lines) also displayed anti-proliferative activity for some compounds. In silico studies indicated non-covalent binding mode and drug-likeness for these derivatives. Taken together, these results are promising for developing more potent PIs.

MOTS-c, a 16 amino acid mitochondrial derived peptide, is encoded from the 12S rRNA region of the mitochondrial genome. Under stress conditions, MOTS-c translocates to the nucleus where it regulates a wide range of genes in response to metabolic dysfunction. It is colocalized to mitochondria in various tissues and is found in plasma, but the levels decline with age. Since MOTS-c has important cellular functions as well as a possible hormonal role, it has been shown to have beneficial effects on age-related diseases including Diabetes, Cardiovascular diseases, Osteoporosis, postmenopausal obesity and Alzheimer. Aging is characterized by gradual loss of (mitochondrial) metabolic balance, decreased muscle homeostasis and eventual diminished physical capability, which potentially can be reversed with MOTS-c treatment. This review examines the latest findings on biological effects of MOTS-c as a nuclear regulatory peptide and focuses on the role of MOTS-c in aging and age-related disorders, including mechanisms of action and therapeutic potential.

The chemotherapy of tumors is frequently limited by the development of resistance and severe side effects. Phytochemicals may offer promising candidates to meet the urgent requirement for new anticancer drugs. We screened 69 phytochemicals, and focused on gedunin to analyze its molecular modes of action. Pearson test-base correlation analyses of the log10IC50 values of 55 tumor cell lines of the National Cancer Institute (NCI), USA, for gedunin with those of 91 standard anticancer agents revealed statistically significant relationships to all 10 tested microtubule inhibitors. Thus, we hypothesized that gedunin may be a novel microtubule inhibitor. Confocal microscopy, cell cycle measurements, and molecular docking in silico substantiated our assumption. Agglomerative cluster analyses and the heat map generation of proteomic data revealed a subset of 40 out of 3171 proteins, the expression of which significantly correlated with sensitivity or resistance for the NCI cell line panel to gedunin. This indicates the complexity of gedunin’s activity against cancer cells, underscoring the value of network pharmacological techniques for the investigation of the molecular modes of drug action. Finally, we correlated the transcriptome-wide mRNA expression of known drug resistance mechanism (ABC transporter, oncogenes, tumor suppressors) log10IC50 values for gedunin. We did not find significant correlations, indicating that gedunin’s anticancer activity might not be hampered by classical drug resistance mechanisms. In conclusion, gedunin is a novel microtubule-inhibiting drug candidate which is not involved in multidrug resistance mechanisms such as other clinically established mitotic spindle poisons.

We assessed the potential negative effects of bacteriostatic and bactericidal antibiotics on the AMD cybrid cell lines (K, U and J haplogroups). AMD cybrid cells were created and cultured in 96-well plates and treated with tetracycline (TETRA) and ciprofloxacin (CPFX) for 24 h. Reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔψM), cellular metabolism and ratio of apoptotic cells were measured using H2DCFDA, JC1, MTT and flow cytometry assays, respectively. Expression of genes of antioxidant enzymes, and pro-inflammatory and pro-apoptotic pathways were evaluated by quantitative real-time PCR (qRT-PCR). Higher ROS levels were found in U haplogroup cybrids when treated with CPFX 60 µg/mL concentrations, lower ΔψM of all haplogroups by CPFX 120 µg/mL, diminished cellular metabolism in all cybrids with CPFX 120 µg/mL, and higher ratio of dead cells in K and J cybrids. CPFX 120 µg/mL induced overexpression of IL-33, CASP-3 and CASP-9 in all cybrids, upregulation of TGF-β1 and SOD2 in U and J cybrids, respectively, along with decreased expression of IL-6 in J cybrids. TETRA 120 µg/mL induced decreased ROS levels in U and J cybrids, increased cellular metabolism of treated U cybrids, higher ratio of dead cells in K and J cybrids and declined ΔψM via all TETRA concentrations in all haplogroups. TETRA 120 µg/mL caused upregulation of IL-6 and CASP-3 genes in all cybrids, higher CASP-7 gene expression in K and U cybrids and downregulation of the SOD3 gene in K and U cybrids. Clinically relevant dosages of ciprofloxacin and tetracycline have potential adverse impacts on AMD cybrids possessing K, J and U mtDNA haplogroups in vitro.

Direct oral anticoagulants (DOACs) apixaban and rivaroxaban are broadly used in the management of venous thromboembolism (VTE). Although not routinely required, measurement of their plasma concentration is advised for an increasing number of indications. Due to the lack of therapeutic ranges, current guidelines recommend reporting DOAC plasma levels together with expected levels from previous pivotal studies. The aim of this study was to assess DOAC level variation in a large VTE patient population. Drug concentrations determined by measurement of the anti-Xa-activity using drug-specific calibrators in citrated plasma samples from patients on rivaroxaban (n = 1471) or apixaban (n = 725) were analyzed. Observed 5th–95th percentile ranges of apixaban peak/trough levels (63–299/13–114 ng/mL for 5 mg, 37–161/7–68 ng/mL for 2.5 mg twice daily) were similar to previously reported mass-spectrometry-based reference data, and 10th–90th percentile ranges of rivaroxaban peak/trough levels (98–367/8–55 ng/mL for 20 mg, 51–211/5–27 ng/mL for 10 mg once daily) were even narrower. Age and drug levels correlated weakly (r ≤ 0.330). Drug levels measured repeatedly in subgroups of patients showed a strong correlation (r ≥ 0.773). In conclusion, anti-Xa-activity-based measurement of apixaban and rivaroxaban yields reliable results. However, the paucity of levels off-range underlines the need for evidence-based thresholds to better assist clinical decision making.

Alginate is a hydrocolloid from algae, specifically brown algae, which is a group that includes many of the seaweeds, like kelps and an extracellular polymer of some bacteria. Sodium alginate is one of the best-known members of the hydrogel group. The hydrogel is a water-swollen and cross-linked polymeric network produced by the simple reaction of one or more monomers. It has a linear (unbranched) structure based on d-mannuronic and l-guluronic acids. The placement of these monomers depending on the source of its production is alternating, sequential and random. The same arrangement of monomers can affect the physical and chemical properties of this polysaccharide. This polyuronide has a wide range of applications in various industries including the food industry, medicine, tissue engineering, wastewater treatment, the pharmaceutical industry and fuel. It is generally recognized as safe when used in accordance with good manufacturing or feeding practice. This review discusses its application in addition to its structural, physical, and chemical properties.

The main protease (Mpro or 3CLpro) in coronaviruses represents a promising specific drug target as it is essential for the cleavage of the virus polypeptide and has a unique cleavage site that does not exist in human host proteases. In this study, we explored potential natural pan-coronavirus drugs using in vitro and in silico approaches and three coronavirus main proteases as treatment targets. The PyRx program was used to screen 39,442 natural-product-like compounds from the ZINC database and 121 preselected phytochemicals from medicinal plants with known antiviral activity. After assessment with Lipinski’s rule of five, molecular docking was performed for the top 33 compounds of both libraries. Enzymatic assays were applied for the top candidates from both in silico approaches to test their ability to inhibit SARS-CoV-2 Mpro. The four compounds (hypericin, rosmarinic acid, isorhamnetin, and luteolin) that most efficiently inhibited SARS-CoV-2 Mpro in vitro were further tested for their efficacy in inhibiting Mpro of SARS-CoV-1 and MERS-CoV. Microscale thermophoresis was performed to determine dissociation constant (Kd) values to validate the binding of these active compounds to recombinant Mpro proteins of SARS-CoV-2, SARS-CoV-1, and MERS-CoV. The cytotoxicity of hypericin, rosmarinic acid, isorhamnetin, and luteolin was assessed in human diploid MRC-5 lung fibroblasts using the resazurin cell viability assay to determine their therapeutic indices. Sequence alignment of Mpro of SARS-CoV-2 demonstrated 96.08%, 50.83%, 49.17%, 48.51%, 44.04%, and 41.06% similarity to Mpro of other human-pathogenic coronaviruses (SARS-CoV-1, MERS-CoV, HCoV-NL63, HCoV-OC43, HCoV-HKU1, and HCoV-229E, respectively). Molecular docking showed that 12 out of 121 compounds were bound to SARS-CoV-2 Mpro at the same binding site as the control inhibitor, GC376. Enzyme inhibition assays revealed that hypericin, rosmarinic acid, isorhamnetin, and luteolin inhibited Mpro of SARS-CoV-2, while hypericin and isorhamnetin inhibited Mpro of SARS-CoV-1; hypericin showed inhibitory effects toward Mpro of MERS-CoV. Microscale thermophoresis confirmed the binding of these compounds to Mpro with high affinity. Resazurin assays showed that rosmarinic acid and luteolin were not cytotoxic toward MRC-5 cells, whereas hypericin and isorhamnetin were slightly cytotoxic. We demonstrated that hypericin represents a potential novel pan-anti-coronaviral agent by binding to and inhibiting Mpro of several human-pathogenic coronaviruses. Moreover, isorhamnetin showed inhibitory effects toward SARS-CoV-2 and SARS-CoV-1 Mpro, indicating that this compound may have some pan-coronaviral potential. Luteolin had inhibitory effects against SARS-CoV-2 Mpro.

This paper investigates the effect of using near-surface mounted carbon fiber-reinforced polymer (NSM-CFRP) on the shear strengthening of rectangle beams with low strength concrete (f′c = 17 MPa), medium strength concrete (f′c = 32 MPa), and high strength concrete (f′c = 47 MPa). The experimental program was performed by installing NSM-CFRP strips vertically in three different configurations: aligned with the internal stirrups, one vertical NSM-CFRP strip between every two internal stirrups, and two vertical NSM-CFRP strips between every two internal stirrups. All tested beams were simply supported beams and tested under a three-point loading test. The experimental results were compared with the theoretical capacities that were calculated according to the ACI 440.2R-17 and finite element analysis (FEA) that was conducted using ABAQUS software to simulate the behavior of all beams. The experimental results indicated that using NSM-CFRP limited the failure mode of all beams to pure shear failure with no debonding or rapture of the carbon strips. Moreover, the use of NSM-CFRP proved its efficiency by increasing the shear capacity of all beams by a range of 4% to 66%, in which the best enhancement was recorded for the case of using two unaligned NSM-CFRP strips. In general, the experimental shear capacities increased with the increase in the compressive strength of all beams. On the other hand, the ACI 440.2R-17 was conservative in predicting the theoretical shear capacities, and the FEA results agreed well with the experimental results.

Along with the increased competition in production and service areas, many organizations attempt to provide their products at a lower price and higher quality. On the other hand, consideration of environmental criteria in the conventional supplier selection methodologies is required for companies trying to promote green supply chain management (GSCM). In this regard, a multi-criteria decision-making (MCDM) technique based on analytic hierarchy process (AHP) and fuzzy technique for order of preference by similarity to ideal solution (TOPSIS) is used to evaluate and rate the suppliers. Then, considering the resource constraint, weight of criteria and a rank of suppliers are taken into account in a multi-objective mixed-integer linear programming (MOMILP) to determine the optimum order quantity of each supplier under uncertain conditions. To deal with the uncertain multi-objectiveness of the proposed model, a robust goal programming (RGP) approach based on Shannon entropy is applied. The offered methodology is applied to a real case study from a green service food manufacturing company in Iran in order to verify its applicability with a sensitivity analysis performed on different uncertainty levels. Furthermore, the threshold of robustness worthiness (TRW) is studied by applying different budgets of uncertainty for the green service food manufacturing company. Finally, a discussion and conclusion on the applicability of the methodology is provided, and an outlook to future research projects is given.

Coagulation factor XIII (FXIII) is a protransglutaminase which plays an important role in clot stabilization and composition by cross-linking the α- and γ-chains of fibrin and increasing the resistance of the clot to mechanical and proteolytic challenges. In this study, we selected six DNA aptamers specific for activated FXIII (FXIIIa) and investigated the functional characterization of FXIIIa after aptamer binding. One of these aptamers, named FA12, efficiently captures FXIIIa even in the presence of zymogenic FXIII subunits. Furthermore, this aptamer inhibits the incorporation of FXIII and α2-antiplasmin (α2AP) into fibrin(ogen) with IC50-values of 38 nM and 17 nM, respectively. In addition to FA12, also another aptamer, FA2, demonstrated significant effects in plasma-based thromboelastometry (rotational thromboelastometry analysis, ROTEM)-analysis where spiking of the aptamers into plasma decreased clot stiffness and elasticity (p < 0.0001). The structure–function correlations determined by combining modeling/docking strategies with quantitative in vitro assays revealed spatial overlap of the FA12 binding site with the binding sites of two FXIII substrates, fibrinogen and α2AP, while FA2 binding sites only overlap those of fibrinogen. Taken together, these features especially render the aptamer FA12 as an interesting candidate molecule for the development of FXIIIa-targeting therapeutic strategies and diagnostic assays.

Antibiotic producers have mainly been isolated from soil, which often has led to the rediscovery of known compounds. In this study, we identified the freshwater snail Physa acuta as an unexplored source for new antibiotic producers. The bacterial diversity associated with the snail was characterized by a metagenomic approach using cultivation-independent high-throughput sequencing. Although Actinobacteria represented only 2% of the bacterial community, the focus was laid on the isolation of the genus Streptomyces due to its potential to produce antibiotics. Three Streptomyces strains (7NS1, 7NS2 and 7NS3) were isolated from P. acuta, and the antimicrobial activity of the crude extracts were tested against a selection of Gram-positive and Gram-negative bacteria and fungi. 7NS3 showed the strongest activity against Gram-positive bacteria and, thus, was selected for genome sequencing and a phylogenomic analysis. 7NS3 represents a novel Streptomyces species, which was deposited as Streptomyces sp. DSM 110735 at the Leibniz Institute-German Collection of Microorganisms and Cell Cultures (DSMZ). Bioassay-guided high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS) analyses of crude extract fractions resulted in the detection of four compounds, one of which matched the compound characteristics of emycin A, an angucycline-like aromatic polyketide. Genome mining studies based on the whole-genome sequence of 7NS3 resulted in the identification of a gene cluster potentially coding for emycin A biosynthesis. Our study demonstrates that freshwater snails like P. acuta can represent promising reservoirs for the isolation of new antibiotic-producing actinobacterial species.

Cancer therapy is still a huge challenge, as especially chemotherapy shows several drawbacks like low specificity to tumor cells, rapid elimination of drugs, high toxicity and lack of aqueous solubility. The combination of molecular imprinting technology with magnetic nanoparticles provides a new class of smart hybrids, i.e., magnetic molecularly imprinted polymers (MMIPs) to overcome limitations in current cancer therapy. The application of these complexes is gaining more interest in therapy, due to their favorable properties, namely, the ability to be guided and to generate slight hyperthermia with an appropriate external magnetic field, alongside the high selectivity and loading capacity of imprinted polymers toward a template molecule. In cancer therapy, using the MMIPs as smart-drug-delivery robots can be a promising alternative to conventional direct administered chemotherapy, aiming to enhance drug accumulation/penetration into the tumors while fewer side effects on the other organs. Overview: In this review, we state the necessity of further studies to translate the anticancer drug-delivery systems into clinical applications with high efficiency. This work relates to the latest state of MMIPs as smart-drug-delivery systems aiming to be used in chemotherapy. The application of computational modeling toward selecting the optimum imprinting interaction partners is stated. The preparation methods employed in these works are summarized and their attainment in drug-loading capacity, release behavior and cytotoxicity toward cancer cells in the manner of in vitro and in vivo studies are stated. As an essential issue toward the development of a body-friendly system, the biocompatibility and toxicity of the developed drug-delivery systems are discussed. We conclude with the promising perspectives in this emerging field. Areas covered: Last ten years of publications (till June 2020) in magnetic molecularly imprinted polymeric nanoparticles for application as smart-drug-delivery systems in chemotherapy.

Circulating microRNAs (miRNAs) have been implicated in several pathologies including type 1 diabetes. In the present study, we aimed to identify circulating miRNAs affected by disease duration in children with recent onset type 1 diabetes. Forty children and adolescents from the Danish Remission Phase Cohort were followed with blood samples drawn at 1, 3, 6, 12, and 60 months after diagnosis. Pancreatic autoantibodies were measured at each visit. Cytokines were measured only the first year. miRNA expression profiling was performed by RT-qPCR. The effect of disease duration was analyzed by mixed models for repeated measurements adjusted for sex and age. Eight miRNAs (hsa-miR-10b-5p, hsa-miR-17-5p, hsa-miR-30e-5p, hsa-miR-93-5p, hsa-miR-99a-5p, hsa-miR-125b-5p, hsa-miR-423-3p, and hsa-miR-497-5p) were found to significantly change in expression (adjusted p-value < 0.05) with disease progression. Three pancreatic autoantibodies, ICA, IA-2A, and GAD65A, and four cytokines, IL-4, IL-10, IL-21, and IL-22, were associated with the miRNAs at different time points. Pathway analysis revealed associations with various immune-mediated signaling pathways. Eight miRNAs that were involved in immunological pathways changed expression levels during the first five years after diagnosis and were associated with variations in cytokine and pancreatic antibodies, suggesting a possible effect on the immunological processes in the early phase of the disease.

Lyme disease (LD) cases have been on the rise throughout the United States, costing the healthcare system up to $1.3 billion per year, and making LD one of the greatest threats to public health. Factors influencing the number of LD cases range from environmental to system-level variables, but little is known about the influence of vegetation (canopy, understory, and ground cover) and human behavioral risk on LD cases and exposure to infected ticks. We determined the influence of various risk factors on the risk of exposure to infected ticks on 22 different walkways using multinomial logistic regression. The model classifies the walkways into high-risk and low-risk categories with 90% accuracy, in which the understory, human risk, and number of rodents are significant indicators. These factors should be managed to control the risk of transmission of LD to humans.