Browsing by Author "Diethelm-Varela, Benjamin"

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    Contribution of Two-Dose Vaccination Toward the Reduction of COVID-19 Cases, ICU Hospitalizations and Deaths in Chile Assessed Through Explanatory Generalized Additive Models for Location, Scale, and Shape
    (2022) Reyes, Humberto; Diethelm-Varela, Benjamin; Mendez Vejar, Constanza; Rebolledo-Zelada, Diego; Lillo-Dapremont, Bastián; Muñoz, Sergio R.; Bueno, Susan M.; González, Pablo A.; Kalergis, Alexis
    Objectives: To assess the impact of the initial two-dose-schedule mass vaccination campaign in Chile toward reducing adverse epidemiological outcomes due to SARS-CoV-2 infection. Methods: Publicly available epidemiological data ranging from 3 February 2021 to 30 September 2021 were used to construct GAMLSS models that explain the beneficial effect of up to two doses of vaccination on the following COVID-19-related outcomes: new cases per day, daily active cases, daily occupied ICU beds and daily deaths. Results: Administered first and second vaccine doses, and the statistical interaction between the two, are strong, statistically significant predictors for COVID-19-related new cases per day (R2 = 0.847), daily active cases (R2 = 0.903), ICU hospitalizations (R2 = 0.767), and deaths (R2 = 0.827). Conclusion: Our models stress the importance of completing vaccination schedules to reduce the adverse outcomes during the pandemic. Future work will continue to assess the influence of vaccines, including booster doses, as the pandemic progresses, and new variants emerge. Policy Implications: This work highlights the importance of attaining full (two-dose) vaccination status and reinforces the notion that a second dose provides increased non-additive protection. The trends we observed may also support the inclusion of booster doses in vaccination plans. These insights could contribute to guiding other countries in their vaccination campaigns.
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    Design of benzimidazoles, benzoxazoles, benzothiazoles and thiazolopyridines as leukotriene A4 hydrolase inhibitors through 3D-QSAR, docking and molecular dynamics
    (2023) Lorca, Marcos; Faundez, Mario; Pessoa-Mahana, C. David; Recabarren-Gajardo, Gonzalo; Diethelm-Varela, Benjamin; Millan, Daniela; Celik, Ismail; Mellado, Marco; Araque, Ileana; Mella, Jaime; Romero-Parra, Javier
    Human leukotriene A4 hydrolase enzyme (LTA4H) catalyses the biotransformation of the inactive precursor leukotriene A4 (LTA4) to the bioactive Leukotriene B4 (LTB4), which causes many inflammatory responses in the human body. Therefore, the selective inhibition of this enzyme becomes a useful strategy for the treatment of several illnesses such as asthma, allergic rhinitis, cardiovascular diseases, and cancer. Herein we report a 3D-QSAR/ /CoMFA and CoMSIA study on a series of 47 benzimidazoles, benzoxazoles, benzothiazoles and thiazolopyridines reported as potent LTA4H inhibitors. Good statistical parameters were obtained for the best model (q2 = 0.568, r2 ncv = 0.891 and r2 test = 0.851). A new series of 10 compounds capable of inhibiting leukotriene A4 hydrolase with high potency was presented. All designed inhibitors showed low IC50 in nano- and sub-nanomolar ranges, when they were evaluated in 3D-QSAR models. Subsequently, the designed molecules, as well as the least and most active compounds were subjected to docking and molecular dynamics studies into LTA4H. In conclusion, we summarised a thorough structure-activity relationship (SAR) of LTA4H inhibitors of heterocyclic structure. These models can be used for the rational proposal of new inhibitors.
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    Effect of biomedical complications on very and extremely preterm children's language
    (2023) Varela-Moraga, Virginia; Diethelm-Varela, Benjamin; Perez-Pereira, Miguel
    IntroductionVery and extremely preterm children have been found to show delays in the development of language in early years. In some investigations, however, a rigorous control of biomedical complications, such as Periventricular Leukomalacia (PVL), Intraventricular Hemorrhage (IVH) or Bronchopulmonary Dysplasia (BPD), does not always exist. For that reason, a confounding effect of low gestational age and biomedical complications may lead to erroneous conclusions about the effect of gestational age. MethodsIn this investigation we compare language development [use of words, sentence complexity and mean length of the three longest utterances (MLU3)] of three groups of Chilean children at 24 months of age (corrected age for preterm children). The first group was composed of 42 healthy full-term children (Full term group: FT), the second group of 60 preterm children born below 32 gestational weeks without medical complications (low risk preterm group: LRPT), and the third group was composed of 64 children below 32 gestational weeks who had medical complications (High risk preterm group: HRPT). The three groups were similar in terms of gender distribution, maternal education, and socio-economic environment. The instrument used to assess language was the Communicative Development Inventories (CDI). In addition, the Ages and Stages Questionnaire-3 (ASQ-3) was also used to assess other developmental dimensions. ResultsThe results indicate that HRPT and LRPT children obtained significantly lower results than the FT group in the three language measures obtained through the CDI. No significant differences were observed between the HRPT and the LRPT groups, although the HRPT obtained the lowest results in the three CDI measures. The results obtained through the administration of the ASQ-3 confirm the delay of both preterm groups in communicative development when compared to the FT group. No significant differences between the FT and the PT groups were observed in gross motor, fine motor and problem solving dimensions of the ASQ-3. The LRPT group obtained results that were significantly higher than those of the FT group and the HRPT group in gross motor development. DiscussionThese results seem to indicate that the area of language development is particularly influenced by very or extremely low gestational age.
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    Federation of Clinical Immunology Societies Goes South 2021: advanced course on molecular and cellular translational immunology
    (2022) Diethelm-Varela, Benjamin; Reyes, Antonia; Rosenstein, Yvonne; Kalil, Jorge; Hill, Marcelo; Docena, Guillermo; Anegon, Ignacio; Gonzalez, Pablo A.; Kalergis, Alexis M.
    The Federation of Clinical Immunology Societies (FOCIS) regularly organizes scientific meetings to foster advances in immunology. A new event of this type is FOCIS Goes South, a course and workshop organized by FOCIS Centers of Excellence (FCEs) from across Latin America, which consists of a course on advanced immunology, a flow cytometry workshop and seminars on cutting-edge research in autoimmunity, tolerance, cancer, infectious diseases and vaccines. Due to the COVID-19 pandemic, the second version of FOCIS Goes South, hosted by the Millennium Institute on Immunology and Immunotherapy in Chile, took place virtually from 15 to 18 November 2021, with more than 950 registered participants. The present article summarizes the key findings and insights discussed at FOCIS Goes South 2021.
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    Inter-Laboratory Comparison of qPCR Assays for Piscirickettsia salmonis in Atlantic Salmon (Salmo salar L.) in 11 Chilean Laboratories
    (2024) Pena, Andrea; Rozas-Serri, Marco; Gardner, Ian A.; Diethelm-Varela, Benjamin; Anguita, Carla; Jerez, Carlos Navarro; Mardones, Fernando O.
    Real-time PCR (qPCR) testing is an essential component of early detection surveillance systems for Piscirickettsia salmonis infection in Atlantic salmon farms in Chile. Currently, all 11 laboratories in the authorised diagnostic laboratory network use assays based on published protocols. Compared with other P. salmonis qPCR assays, these assays have the advantage of targeting two different genes, that is, the 16S ribosomal gene and the internal transcribed spacer (ITS), potentially allowing for higher diagnostic accuracy. However, variation and lack of harmonisation of qPCR testing systems (e.g., primers/probe, RNA/DNA as target, extraction methods, etc.) may contribute to among-laboratory variation in qPCR results and an increased frequency of false-negative and false-positive results. The purpose of the ring trial reported herein was to compare qPCR results from 11 laboratories in Chile routinely testing Atlantic salmon for P. salmonis as part of a national control program. The panel of 14 samples included duplicates of three concentrations of P. salmonis in a homogenised head kidney, LF89 and EM90 bacteria and two negative controls (blank and a suspension of Flavobacterium psychrophilum). The sample order was randomised across labs, samples were tested blinded and analysed without knowledge of the source lab. Of the laboratories, 8 (72.7%) had at least one incorrect result out of 14 tested samples. Low-concentration samples (Ct of about 30) were more often incorrectly classified by reverse transcription-qPCR (RT-qPCR) (3/6 labs) than by qPCR (0/5). Six (54.5%) labs had at least one false-positive result indicating that cross-contamination was likely during sample processing. Affected laboratories are advised to conduct internal investigations to confirm the causes of false-positive results and recommendations for design and implementation of future ring trials are discussed.