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Background Plasmodium vivax represents the most geographically widespread human malaria parasite affecting civilian and military populations in endemic areas. Targeting the pre-erythrocytic (PE) stage of the parasite life cycle is especially appealing for developing P. vivax vaccines as it would prevent disease and transmission. Here, naturally acquired immunity to a panel of P. vivax PE antigens was explored, which may facilitate vaccine development and lead to a better understanding of naturally acquired PE immunity. Methods Twelve P. vivax PE antigens orthologous to a panel of P. falciparum antigens previously identified as highly immunogenic in protected subjects after immunization with radiation attenuated sporozoites (RAS) were used for evaluation of humoral and cellular immunity by ELISA and IFN-γ ELISpot. Samples from P. vivax infected individuals (n = 76) from a low endemic malaria region in the Peruvian Amazon Basin were used. Results In those clinical samples, all PE antigens evaluated showed positive IgG antibody reactivity with a variable prevalence of 58–99% in recently P. vivax diagnosed patients. The magnitude of the IgG antibody response against PE antigens was lower compared with blood stage antigens MSP1 and DBP-II, although antibody levels persisted better for PE antigens (average decrease of 6% for PE antigens and 43% for MSP1, p < 0.05). Higher IgG antibodies was associated with one or more previous malaria episodes only for blood stage antigens (p < 0.001). High IgG responders across PE and blood stage antigens showed significantly lower parasitaemia compared to low IgG responders (median 1,921 vs 4,663 par/µl, p < 0.05). In a subgroup of volunteers (n = 17),positive IFN-γ T cell response by ELISPOT was observed in 35% vs 9–35% against blood stage MSP1 and PE antigens, respectively, but no correlation with IgG responses . Conclusions These results demonstrate clear humoral and T cell responses against P. vivax PE antigens in individuals naturally infected with P. vivax. These data identify novel attractive PE antigens suitable for use in the potential development and selection of new malaria vaccine candidates which can be used as a part of malaria prevention strategies in civilian and military populations living in P. vivax endemic areas.

Background A major concern in malaria vaccine development is genetic polymorphisms typically observed among Plasmodium isolates in different geographical areas across the world. Highly polymorphic regions have been observed in Plasmodium falciparum and Plasmodium vivax antigenic surface proteins such as Circumsporozoite protein (CSP), Duffy-binding protein (DBP), Merozoite surface protein-1 (MSP-1), Apical membrane antigen-1 (AMA-1) and Thrombospondin related anonymous protein (TRAP). Methods Genetic variability was assessed in important polymorphic regions of various vaccine candidate antigens in P. vivax among 106 isolates from the Amazon Region of Loreto, Peru. In addition, genetic diversity determined in Peruvian isolates was compared to population studies from various geographical locations worldwide. Results The structured diversity found in P. vivax populations did not show a geographic pattern and haplotypes from all gene candidates were distributed worldwide. In addition, evidence of balancing selection was found in polymorphic regions of the trap, dbp and ama-1 genes. Conclusions It is important to have a good representation of the haplotypes circulating worldwide when implementing a vaccine, regardless of the geographic region of deployment since selective pressure plays an important role in structuring antigen diversity.

The \"Social Security Center No.102\" has a deficiency in customer service, which has caused problems such as low user satisfaction, bad reputation, long waiting times for answers and loss of customers. The objective of this project is to demonstrate that the design and implementation of a virtual assistant (Chatbot) optimizes the service to users of the organization. As for the design of the method, the research is considered mixed, applied and technological; and depending on the level of research, it is descriptive, explanatory, cross-sectional, non-experimental and field. A stratified population sample of 380 people was considered, to whom a \"questionnaire\" type data collection instrument was applied, consisting of 4 sections and 24 items. Based on the results obtained, it was shown that the Chatbot improved efficiency by 64.4% and effectiveness by 63.1% in the provision of customer service to users.

Complex marine–terrestrial interactions characterize Chilean fjords, where benthic communities influence the distribution of organic matter (OM). We examined spatial and seasonal changes in the hydrography, sediment conditions and soft-bottom macrobenthic, meiobenthic, and total microbial biomass in a glacial Patagonian fjord (Martinez Channel, Chile). The transport of a high load of glacial mineral and particulate OM to the fjord in the austral summer coincided with low total live benthic biomass. Multivariate analysis evidenced temporal-related macrofaunal groups influenced by the different environments produced by the advection of sediment transport and terrestrial OM from the Baker River, Chile. The relationships between density/biomass and respiration versus body size varied considerably with distance from major riverine inputs, but the slopes of density size spectra and normalized biomass size spectra were less negative in summer than in winter. Occasional large-scale advective processes in the water column affected sediment conditions and removed surface macrofauna, influencing the slope and intercept of the regression models. In the outer fjord, lateral advection and subsequent sedimentation of terrestrial OM contributed a significant fraction to total OM sediments (<14.76%). Stable carbon isotopes measured in benthic organisms suggest that benthic communities in the inner fjord may assimilate a significant fraction of terrestrial OM via heterotrophic bacteria in contrast to the minor input of terrestrial OM in the outer fjord.

Over the last quarter century, increasing honey bee colony losses motivated standardized large-scale surveys of managed honey bees ( Apis mellifera ), particularly in Europe and the United States. Here we present the first large-scale standardized survey of colony losses of managed honey bees and stingless bees across Latin America. Overall, 1736 beekeepers and 165 meliponiculturists participated in the 2-year survey (2016–2017 and 2017–2018). On average, 30.4% of honey bee colonies and 39.6% of stingless bee colonies were lost per year across the region. Summer losses were higher than winter losses in stingless bees (30.9% and 22.2%, respectively) but not in honey bees (18.8% and 20.6%, respectively). Colony loss increased with operation size during the summer in both honey bees and stingless bees and decreased with operation size during the winter in stingless bees. Furthermore, losses differed significantly between countries and across years for both beekeepers and meliponiculturists. Overall, winter losses of honey bee colonies in Latin America (20.6%) position this region between Europe (12.5%) and the United States (40.4%). These results highlight the magnitude of bee colony losses occurring in the region and suggest difficulties in maintaining overall colony health and economic survival for beekeepers and meliponiculturists.

This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4 + T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4 + T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4 + T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4 + T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.

N 6 -methyladenosine (m 6 A) is the most abundant internal modification described in eukaryotic mRNA and several viral RNA including human respiratory syncytial virus (HRSV). Here, we evaluated the impact of m 6 A writers, erasers and readers on HRSV genomic RNA accumulation and inclusion bodies assembly during viral replication. We observed that the METTL3/METTL14 m 6 A writer complex plays a negative role in HRSV protein synthesis and viral titers, while m 6 A erasers FTO and ALKBH5 had the opposite effect. We also observed that m 6 A readers YTHDF1-3 bind to the viral genomic RNA inducing a decrease in its intracellular levels and thus, inhibiting viral replication. Finally, we observed that overexpression of YTHDFs proteins caused a decrease in the size of inclusion bodies (IBs), accompanied by an increase in their number. METTL3 knockdown cells showed an opposite effect indicating that the dynamics of IBs assembly and coalescence are strongly affected by m 6 A readers in a mechanism dependent on m 6 A writers. Taken together, our results demonstrated that the m 6 A modification negatively affects HRSV replication, possibly through a mechanism involving the assembly of inclusion bodies, the main factories of viral genomic RNA synthesis.

Web-based cognitive behavioral therapy (wb-CBT) is a scalable way to reach distressed university students. Guided wb-CBT is typically superior to self-guided wb-CBT over short follow-up periods, but evidence is less clear over longer periods. This study aimed to compare short-term (3 months) and longer-term (12 months) aggregate effects of guided and self-guided wb-CBT versus treatment as usual (TAU) in a randomized controlled trial of Colombian and Mexican university students and carry out an initially unplanned secondary analysis of the role of differential predicted compliance in explaining these differences. The 1319 participants, recruited either through email and social media outreach invitations or from waiting lists of campus mental health clinics, were undergraduates (1038/1319, 78.7% female) with clinically significant baseline anxiety (Generalized Anxiety Disorder-7 score≥10) or depression (Patient Health Questionnaire-9 score≥10). The intervention arms comprised guided wb-CBT with weekly asynchronous written human feedback, self-guided wb-CBT with the same content as the guided modality, and TAU as provided at each university. The prespecified primary outcome was joint remission (Generalized Anxiety Disorder-7 score=0-4 and Patient Health Questionnaire-9 score=0-4). The secondary outcome was joint symptom reduction (mean scores on the Patient Health Questionnaire Anxiety and Depression Scale) at 3 and 12 months after randomization. As reported previously, 3-month outcomes were significantly better with guided wb-CBT than self-guided wb-CBT (P=.02) or TAU (P=.02). However, subsequent follow-up showed that 12-month joint remission (adjusted risk differences=6.0-6.5, SE 0.4-0.5, and P<.001 to P=.007; adjusted mean differences=2.70-2.69, SE 0.7-0.8, and P<.001 to P=.001) was significantly better with self-guided wb-CBT than with the other interventions. Participants randomly assigned to the guided wb-CBT arm spent twice as many minutes logged on as those in the self-guided wb-CBT arm in the first 12 weeks (mean 12.5, SD 36.9 vs 5.9, SD 27.7; χ =107.1, P<.001), whereas participants in the self-guided wb-CBT arm spent twice as many minutes logged on as those in the guided wb-CBT arm in weeks 13 to 52 (mean 0.4, SD 7.5 vs 0.2, SD 4.4; χ =10.5, P=.001). Subgroup analysis showed that this longer-term superiority of self-guided wb-CBT was confined to the 40% (528/1319) of participants with high predicted self-guided wb-CBT compliance beyond 3 months based on a counterfactual nested cross-validated machine learning model. The 12-month outcome differences were nonsignificant across arms among other participants (all P>.05). The results have important practical implications for precision intervention targeting to maximize longer-term wb-CBT benefits. Future research needs to investigate strategies to increase sustained guided wb-CBT use once guidance ends. ClinicalTrials.gov NCT04780542; https://www.clinicaltrials.gov/study/NCT04780542. RR2-10.1186/s13063-022-06255-3.

During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3–5 years old and headache in 6–17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac® was safe and well tolerated in children and adolescents, with different safety patterns according to age.