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Three key elements are the drivers of Aedes -borne disease: mosquito infestation, virus circulating, and susceptible human population. However, information on these aspects is not easily available in low- and middle-income countries. We analysed data on factors that influence one or more of those elements to study the first chikungunya epidemic in Rio de Janeiro city in 2016. Using spatio-temporal models, under the Bayesian framework, we estimated the association of those factors with chikungunya reported cases by neighbourhood and week. To estimate the minimum temperature effect in a non-linear fashion, we used a transfer function considering an instantaneous effect and propagation of a proportion of such effect to future times. The sociodevelopment index and the proportion of green areas (areas with agriculture, swamps and shoals, tree and shrub cover, and woody-grass cover) were included in the model with time-varying coefficients, allowing us to explore how their associations with the number of cases change throughout the epidemic. There were 13627 chikungunya cases in the study period. The sociodevelopment index presented the strongest association, inversely related to the risk of cases. Such association was more pronounced in the first weeks, indicating that socioeconomically vulnerable neighbourhoods were affected first and hardest by the epidemic. The proportion of green areas effect was null for most weeks. The temperature was directly associated with the risk of chikungunya for most neighbourhoods, with different decaying patterns. The temperature effect persisted longer where the epidemic was concentrated. In such locations, interventions should be designed to be continuous and to work in the long term. We observed that the role of the covariates changes over time. Therefore, time-varying coefficients should be widely incorporated when modelling Aedes -borne diseases. Our model contributed to the understanding of the spatio-temporal dynamics of an urban Aedes- borne disease introduction in a tropical metropolitan city.

As essential components of gene expression networks, transcription factors regulate neural circuit assembly. The homeobox transcription factor encoding gene, gs homeobox 1 ( gsx1 ), is expressed in the developing visual system; however, no studies have examined its role in visual system formation. In zebrafish, retinal ganglion cell (RGC) axons that transmit visual information to the brain terminate in ten arborization fields (AFs) in the optic tectum (TeO), pretectum (Pr), and thalamus. Pretectal AFs (AF1-AF9) mediate distinct visual behaviors, yet we understand less about their development compared to AF10 in the TeO. Using gsx1 zebrafish mutants, immunohistochemistry, and transgenic lines, we observed that gsx1 is required for vesicular glutamate transporter, Tg(slc17a6b : DsRed) , expression in the Pr, but not overall neuron number. gsx1 mutants have normal eye morphology, yet they exhibit impaired visual ability during prey capture. RGC axon volume in the gsx1 mutant Pr and TeO is reduced, and AF7 that is active during feeding is missing which is consistent with reduced hunting performance. Timed laser ablation of Tg(slc17a6b : DsRed) -positive cells reveals that they are necessary for AF7 formation. This work is the first to implicate gsx1 in establishing cell identity and functional neural circuits in the visual system.

Dicarboxylic fatty acids are generated in the liver and kidney in a minor pathway called fatty acid ω-oxidation. The effects of consuming dicarboxylic fatty acids as an alternative source of dietary fat have not been explored. Here, we fed dodecanedioic acid, a 12-carbon dicarboxylic (DC12), to mice at 20% of daily caloric intake for 9 weeks. DC12 increased metabolic rate, reduced body fat, reduced liver fat, and improved glucose tolerance. We observed DC12-specific breakdown products in liver, kidney, muscle, heart, and brain, indicating that oral DC12 escaped first-pass liver metabolism and was utilized by many tissues. In tissues expressing the \"a\" isoform of acyl-CoA oxidase-1 (ACOX1), a key peroxisomal fatty acid oxidation enzyme, DC12 was chain shortened to the TCA cycle intermediate succinyl-CoA. In tissues with low peroxisomal fatty acid oxidation capacity, DC12 was oxidized by mitochondria. In vitro, DC12 was catabolized even by adipose tissue and was not stored intracellularly. We conclude that DC12 and other dicarboxylic acids may be useful for combatting obesity and for treating metabolic disorders.

This in-vitro study aimed to analyse the effect of brushing and different brushing parameters (kind of toothpaste, kind of toothbrush, brushing force) on erosive tooth wear of primary bovine enamel and dentin. Specimens were prepared from primary bovine enamel or dentin (each group n = 12) and cyclically eroded (6 × 60 s/d, citric acid, pH 2.4) and brushed with children’s toothbrushes (2 × 15 s/d) over 5 days. The brushing parameters under investigation were: toothpaste (fluoridated, fluoride-free), toothbrush (manual; rotating-oscillating and sonic, each at two different activation modes) and brushing force (1 N, 2 N). Specimens that were only eroded and not brushed served as controls. Enamel and dentin wear was quantified using widefield confocal microscopy. Statistical analysis was performed using three- and one-way ANOVAs followed by Scheffe’s (enamel) or Tamhane’s (dentin) post-hoc tests (p < 0.05). Brushing with the fluoridated toothpaste was able to significantly reduce erosive wear in enamel (by 15 to 37%, 6 of 10 groups) and in dentin (by 58 to 72%, all groups), while brushing with the fluoride-free toothpaste was not different from the controls. Considering the kind of toothpaste and brushing force, slight differences between the toothbrushes were observed in enamel, but not in dentin. Within the same toothbrush and activation mode, almost no differences between 1 and 2 N brushing force were detected. In conclusion, erosive tooth wear on primary bovine dental hard tissue mainly depends on the kind of toothpaste, rather than on the kind of toothbrush and the brushing force.

We hypothesized that the double hit conferred by sex and diagnosis increases the risk for internalizing disorders in adolescent females with autism spectrum disorder (ASD). In a sample of 32 adolescents with ASD and 32 controls, we examined the effects of sex, diagnostic factors, and developmental stages on depression and anxiety. A 3-way interaction revealed that females with ASD exhibited greater depressive symptoms than males with ASD and female controls particularly during early adolescence; therefore, females with ASD might have a unique combination of genetic, hormonal, and psychosocial vulnerabilities that heighten their risk for depression during early adolescence. Additionally, the ASD group reported high levels of separation anxiety and panic in late adolescence, possibly indicating atypical development of independence.

HIV-HCV coinfected individuals are often more deprived than the general population. However, deprivation is difficult to measure, often relying on aggregate data which does not capture individual heterogeneity. We developed an individual-level deprivation index for HIV-HCV co-infected persons that encapsulated social, material, and lifestyle factors. We estimated an individual-level deprivation index with data from the Canadian Coinfection Cohort, a national prospective cohort study. We used a predetermined process to select 9 out of 19 dichotomous variables at baseline visit to include in the deprivation model: income >$1500/month; education >high school; employment; identifying as gay or bisexual; Indigenous status; injection drug use in last 6 months; injection drug use ever; past incarceration, and past psychiatric hospitalization. We fitted an item response theory model with: severity parameters (how likely an item was reported), discriminatory parameters, (how well a variable distinguished index levels), and an individual parameter (the index). We considered two models: a simple one with no provincial variation and a hierarchical model by province. The Widely Applicable Information Criterion (WAIC) was used to compare the fitted models. To showcase a potential utility of the proposed index, we evaluated with logistic regression the association of the index with non-attendance to a second clinic visit (as a proxy for disengagement) and using WAIC compared it to a model containing all the individual parameters that compose the index as covariates. We analyzed 1547 complete cases of 1842 enrolled participants. According to the WAIC the hierarchical model provided a better fit when compared to the model that does not consider the individual's province. Values of the index were similarly distributed across the provinces. Overall, past incarceration, education, and unemployment had the highest discriminatory parameters. However, in each province different components of the index were associated with being deprived reflecting local epidemiology. For example, Saskatchewan had the highest severity parameter for Indigenous status while Quebec the lowest. For the secondary analysis, 457 (30%) failed to attend a second visit. A one-unit increase in the index was associated with 17% increased odds (95% credible interval, 2% to 34%) of not attending a second visit. The model with just the index performed better than the model with all the components as covariates in terms of WAIC. We estimated an individual-level deprivation index in the Canadian Coinfection cohort. The index identified deprivation profiles across different provinces. This index and the methodology used may be useful in studying health and treatment outcomes that are influenced by social disparities in co-infected Canadians. The methodological approach described can be used in other studies with similar characteristics.

Zika, a viral disease transmitted to humans by Aedes mosquitoes, emerged in the Americas in 2015, causing large-scale epidemics. Colombia alone reported over 72,000 Zika cases between 2015 and 2016. Using national surveillance data from 1121 municipalities over 70 weeks, we identified sociodemographic and environmental factors associated with Zika’s emergence, re-emergence, persistence, and transmission intensity in Colombia. We fitted a zero-state Markov-switching model under the Bayesian framework, assuming Zika switched between periods of presence and absence according to spatially and temporally varying probabilities of emergence/re-emergence (from absence to presence) and persistence (from presence to presence). These probabilities were assumed to follow a series of mixed multiple logistic regressions. When Zika was present, assuming that the cases follow a negative binomial distribution, we estimated the transmission intensity rate. Our results indicate that Zika emerged/re-emerged sooner and that transmission was intensified in municipalities that were more densely populated, at lower altitudes and/or with less vegetation cover. Warmer temperatures and less weekly-accumulated rain were also associated with Zika emergence. Zika cases persisted for longer in more densely populated areas with more cases reported in the previous week. Overall, population density, elevation, and temperature were identified as the main contributors to the first Zika epidemic in Colombia. We also estimated the probability of Zika presence by municipality and week, and the results suggest that the disease circulated undetected by the surveillance system on many occasions. Our results offer insights into priority areas for public health interventions against emerging and re-emerging Aedes -borne diseases.

This in vitro study aimed to analyse the effect of various children’s toothpastes on erosive tooth wear of primary bovine enamel and dentin. Enamel and dentin specimens (n = 12) were cyclically eroded (6 × 60 s/d, citric acid, pH 2.4) and brushed (2 × 15 s/d, 2 N) over 5 days. Nine fluoride toothpastes (500 to 1450 ppm) and eight toothpastes containing no fluoride or other active ingredients (hydroxyapatite and/or xylitol) were tested. Unbrushed specimens served as control. Tissue loss was quantified using widefield confocal microscopy and statistically analysed using two-way and one-way ANOVAs followed by Scheffe’s (enamel) or Tamhane’s (dentin) post-hoc tests (p < 0.05). Only one fluoride toothpaste (1400 ppm) was able to reduce erosive wear of enamel significantly by 15% compared to the control (p adj.  = 0.002). All fluoridated toothpastes reduced dentin surface loss significantly by 32 to 69% compared to the control (p adj.  ≤ 0.001), while fluoride-free toothpastes were unable to reduce dentin loss significantly (p adj.  ≥ 0.971). Most fluoridated toothpastes caused less erosive wear compared to fluoride-free toothpastes. Children toothpastes containing fluoride were more effective in reducing erosive wear compared to toothpastes containing no fluoride or other active ingredients.