Northern and central Chile still free of emerging flaviviruses in mosquitoes (Diptera: Culicidae).

Geographic isolation and strict control limits in border areas have kept Chile free from various pathogens, including Flavivirus. However, the scenario is changing mainly due to climate change, the reintroduction of more aggressive mosquitoes, and the great wave of migration of people from endemic countries in recent years. Hence, it is necessary to surveillance mosquitoes to anticipate a possible outbreak in the population and take action to control it. This study aimed to investigate the presence of Flavivirus RNA by molecular tools with consensus primers in mosquitoes collected in the extreme north and central Chile. From 2019 to 2021, a prospective study was carried out in localities of Northern and part of Central Chile. Larvae, pupae, and adults of mosquitoes were collected in rural and urban sites in each locality. The collected samples were pooled by species and geographical location and tested using RT-PCR and RT-qPCR to determine presence of Flavivirus. 3085 specimens were collected, the most abundant specie Culex quinquefasciatus in the North and Aedes (Ochlerotatus) albifasciatus in the Center of Chile. Both genera are associated with Flavivirus transmission. However, PCR and RT-PCR did not detect Flavivirus RNA in the mosquitoes studied. These negative results indicate we are still a free Flavivirus country, which is reaffirmed by the non-existence of endemic human cases. Despite this, routine surveillance of mosquitoes and the pathogens they carry is highly recommended to evaluate each area-specific risk of vector-borne transmission.

The emergence of Dirofilaria repens in a non-endemic area influenced by climate change: dynamics of transmission using a mathematical model.

Dirofilaria repens is a nematode affecting domestic and wild canids, transmitted by several species of mosquitoes of different genera. It usually causes a non-pathogenic subcutaneous infection in dogs and is the principal agent of human dirofilariasis in the Old World. The geographic distribution of D. repens is changing rapidly, and several factors contribute to the spread of the infection to non-endemic areas. A mathematical model for transmission of Dirofilaria spp. was built, using a system of ordinary differential equations that consider the interactions between reservoirs, vectors, and humans. The transmission simulations of D. repens were carried out considering a projection in time, with intervals of 15 and 100 years. For the dynamics of the vector, seasonal variations were presented as series with quarter periodicity during the year. The results of the simulations highlight the peak of contagions in the reservoir and in humans, a product of the action of the vector when it remains active throughout the year. A 300% infection increase in the reservoir was observed during the first decade and remains present in the population with a representative number of cases. When the vector maintains its density and infectivity during the year, the incidence of the infection in humans increases. Accumulated cases amount to 45 per 100,000 inhabitants, which corresponds to a cumulative incidence of 0.05%, in 85 years. This indicates that early prevention of infection in canids would significantly reduce the disease, also reducing the number of accumulated cases of human dirofilariasis by D. repens. The interaction between the simulations generated by the model highlights the sensitivity of the epidemiological curve to the periodicity of seasonality, reaffirming the hypothesis of the probability of movement of the zoonotic disease to non-endemic areas, due to climate change.

Simulation Model for Hashimoto Autoimmune Thyroiditis Disease.

Hashimoto thyroiditis (HT) is a pathology that often causes a gradual thyroid insufficiency in affected patients due to the autoimmune destruction of this gland. The cellular immune response mediated by T helper lymphocytes TH1 and TH17 can induce the HT disease. In this pathologic condition, there is an imbalance between the TH17 and Treg lymphocytes as well as a gut microbiota dysfunction. The objective of this work was to describe the interactions of the cell subpopulations that participate in HT. To achieve this goal, we generated a mathematical model that allowed the simulation of different scenarios for the dynamic interaction between thyroid cells, the immune system, and the gut microbiota. We used a hypothetical-deductive design of mathematical modeling based on a system of ordinary differential equations, where the state variables are the TH1, TH17, and Treg lymphocytes, the thyrocytes, and the bacteria from gut microbiota. This work generated a compartmental model of the cellular immune response occurring in the thyroid gland. It was observed that TH1 and TH17 lymphocytes could increase the immune cells' activity, as well as activate effector cells directly and trigger the apoptosis and inflammation processes of healthy thyrocytes indirectly. Likewise, the model showed that a reduction in Treg lymphocytes could increase the activity of TH17 lymphocytes when an imbalance of the gut microbiota composition occurred. The numerical results highlight the TH1, TH17, and bacterial balance of the gut microbiota activities as important factors for the development of HT disease.

Histone Methyltransferases Useful in Gastric Cancer Research.

Gastric cancer (GC) is one of the most frequent tumors in the world. Stomach adenocarcinoma is a heterogeneous tumor, turning the prognosis prediction and patients' clinical management difficult. Some diagnosis tests for GC are been development using knowledge based in polymorphisms, somatic copy number alteration (SCNA) and aberrant histone methylation. This last event, a posttranslational modification that occurs at the chromatin level, is an important epigenetic alteration seen in several tumors including stomach adenocarcinoma. Histone methyltransferases (HMT) are the proteins responsible for the methylation in specific amino acids residues of histones tails. Here, were presented several HMTs that could be relating to GC process. We use public data from 440 patients with stomach adenocarcinoma. We evaluated the alterations as SCNAs, mutations, and genes expression level of HMTs in these aforementioned samples. As results, it was identified the 10 HMTs most altered (up to 30%) in stomach adenocarcinoma samples, which are the PRDM14, PRDM9, SUV39H2, NSD2, SMYD5, SETDB1, PRDM12, SUV39H1, NSD3, and EHMT2 genes. The PRDM9 gene is among most mutated and amplified HMTs within the data set studied. PRDM14 is downregulated in 79% of the samples and the SUV39H2 gene is down expressed in patients with recurred/progressed disease. Several HMTs are altered in many cancers. It is important to generate a genetic atlas of alterations of cancer-related genes to improve the understanding of tumorigenesis events and to propose novel tools of diagnosis and prognosis for the cancer control.