Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR). OBJECTIVES: We sought to perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality of life of patients with perennial or seasonal AR. METHODS: The investigators searched 4 electronic bibliographic databases and 3 clinical trials databases for randomized controlled trials (1) assessing adult patients with seasonal or perennial AR and (2) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. The investigators performed random-effects meta-analyses of mean differences for each medication and outcome. The investigators assessed evidence certainty using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: This review included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate, and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the Total Nasal Symptom Score and Rhinoconjunctivitis Quality-of-Life Questionnaire. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of Total Ocular Symptom Score. Overall, evidence certainty was considered "high" in 6 of 46 analyses, "moderate" in 23 of 46 analyses, and "low"/"very low" in 17 of 46 analyses. CONCLUSIONS: Most intranasal medications are effective in improving rhinitis symptoms and quality of life. However, there are relevant differences in the associated evidence certainty.

Implementation impact assessment of Uber System on mortality from traffic injuries in Brazilian capitals.

The rapid expansion of Uber System and e-hailing apps has been transforming the logistics network and urban mobility around the world. The present work aims at evaluating the impact of Uber System on the traffic injury mortality (TI) in implementation in Brazilian capitals. A quasi-experimental design of interrupted time series was used. The monthly mortality rates for TI standardized by age were analised. The date of availability of Uber app, specific to each capital, was considered as the start date. Data from the Brazilian Mortality Information System and the Brazilian Institute of Geography and Statistics were used. For the data analysis from interrupted time series design, ARIMA with transfer function were fitted. In 95,6% (n=25) of Brazilian capitals, there was no impact of Uber System implementation, twelve months after the start of its activities, on mortality from traffic injuries. A reduction in mortality from this cause was observed after the System was implemented in Belo Horizonte e Rio de Janeiro. The impact was progressive and continuous on TI mortality in both. More studies are needed to establish the factors associated with the inequalities observed in the impact of the Uber System implementation between different locations and the heterogeneity of effects.

Stem cell-conditioned medium improves methylation patterns and quality of caprine preantral follicles.

This study investigated the methylation patterns of H3K4me3 and H3K9me3, as well as the mRNA expression of genes encoding the epigenetic regulators KDM1AX1, KDM1AX2, and KDM3A in goat preantral follicles developed in vivo (Uncultured control) or after in vitro culture for 7 days in either the absence (α-MEM+) or presence of conditioned medium (α-MEM+ + CM) from Wharton's jelly mesenchymal stem cells (WJ-MSCs). In the in vivo setting, all follicular categories exhibited similar H3K4me3 and H3K9me3 patterns, and transcripts of KDM1AX1, KDM1AX2, and KDM3A were detected in all samples. During in vitro culture, α-MEM+ + CM enhanced several important aspects. It increased the percentage of normal growing follicles, oocyte diameters across all categories, stromal cell density, and the H3K4me3 methylation pattern in preantral follicles. Simultaneously, it decreased the levels of reduced thiols and reactive oxygen species in the spent media, diminished the presence of lipofuscin aggresomes, lowered granulosa cell apoptotic rates, and reduced the H3K9me3 methylation pattern in preantral follicles. In conclusion, the findings from this study provide compelling evidence that supplementing the in vitro culture medium (α-MEM+) with CM from WJ-MSCs has a protective effect on goat preantral follicles. Notably, CM supplementation preserved follicular survival, as evidenced by enhanced follicular and oocyte growth and increased stromal cell density when compared to the standard culture conditions in the α-MEM+ medium. Furthermore, CM reduced oxidative stress and apoptosis and promoted alterations in H3K4me3 and H3K9me3 patterns.

Contact tracing management of a measles case in a paediatric hospital: experience of the local public health unit, Portugal, January 2024.

In January 2024, a child was diagnosed with measles in a paediatric hospital in Lisbon. Of 123 contacts, 39 (32%) were not fully immunised, presenting a risk for a potential outbreak. The public health unit initiated control measures and identified challenges during the response, such as the lack of interoperability between information systems and accessing vaccination records. The lessons learned prompted changes to national contact tracing procedures for measles, further strengthening Portugal's preparedness.

Redox imbalance induces remodeling of glucose metabolism in Rhipicephalus microplus embryonic cell line.

Carbohydrate metabolism not only functions in supplying cellular energy but also has an important role in maintaining physiological homeostasis and in preventing oxidative damage caused by reactive oxygen species. Previously, we showed that arthropod embryonic cell lines have high tolerance to H2O2 exposure. Here, we describe that Rhipicephalus microplus tick embryonic cell line (BME26) employs an adaptive glucose metabolism mechanism that confers tolerance to hydrogen peroxide at concentrations too high for other organisms. This adaptive mechanism sustained by glucose metabolism remodeling promotes cell survival and redox balance in BME26 cell line after millimolar H2O2 exposure. The present work shows that this tick cell line could tolerate high H2O2 concentrations by initiating a carbohydrate-related adaptive response. We demonstrate that gluconeogenesis was induced as a compensation strategy that involved, among other molecules, the metabolic enzymes NADP-ICDH, G6PDH, and PEPCK. We also found that this phenomenon was coupled to glycogen accumulation and glucose uptake, supporting the pentose phosphate pathway to sustain NADPH production and leading to cell survival and proliferation. Our findings suggest that the described response is not atypical, being also observed in cancer cells, which highlights the importance of this model to all proliferative cells. We propose that these results will be useful in generating basic biological information to support the development of new strategies for disease treatment and parasite control.

Trimethylation profile of histones H3 lysine 4 and 9 in late preantral and early antral caprine follicles grown in vivo versus in vitro in the presence of anethole.

This study assessed the histones methylation profile (H3K4me3 and H3K9me3) in late preantral (PA) and early antral (EA) caprine follicles grown in vivo and in vitro, and the anethole effect during in vitro culture of PA follicles. Uncultured in vivo-grown follicles (PA, n = 64; EA, n = 73) were used as controls to assess the methylation profile and genes' expression related to apoptosis cascade (BAX, proapoptotic; BCL2, antiapoptotic), steroidogenesis (CYP17, CYP19A1), and demethylation (KDM1AX1, KDM1AX2, KDM3A). The isolated PA follicles (n = 174) were cultured in vitro for 6 days in α-MEM+ in either absence (control) or presence of anethole. After culture, EA follicles were evaluated for methylation, mRNA abundance, and morphometry. Follicle diameter increased after culture, regardless of treatment. The methylation profile and the mRNA abundance were similar between in vivo-grown PA and EA follicles. Anethole treatment led to higher H3K4me3 fluorescence intensity in EA follicles. The mRNA abundances of BAX, CYP17, and CYP19A1 were higher, and BCL2 and KDM3A were lower in in vitro-grown EA follicles than in vivo-grown follicles. In conclusion, in vitro follicle culture affected H3K4me3 fluorescence intensity, mRNA abundance of apoptotic genes, and steroidogenic and demethylase enzymes compared with in vivo-grown follicles.

What to expect from primary inferior oblique overaction after esotropia surgery : Primary inferior oblique overaction in esotropia.

BACKGROUND: Overelevation in adduction is common in patients with primary esotropia. This study evaluates the variation in ocular motility pattern in patients with primary inferior oblique (IO) muscle overaction after esotropia surgery. METHODS: The medical records of consecutive patients who underwent surgery for infantile, partially accommodative, and basic esotropia over eleven years and had at least one year of follow-up were reviewed. Patients with primary inferior oblique muscle overaction (IOOA) presented at baseline or during follow-up were selected and divided according to the first surgery performed concurrently with horizontal rectus surgery: without IO recession (NO-recess), with unilateral IO recession (UNIL-recess), and with bilateral IO recession (BIL-recess). The success (version normalisation or at least 2 points upgrade in severity scale [0-4] in the operated eye), recurrence rates, and the evolution of the non-operated IO muscles were evaluated. RESULTS: One hundred and ten patients were included - 53 NO-recess, 26 UNIL-recess, and 31 BIL-recess. Medial rectus muscle posterior fixation sutures surgery (PFS) was performed in 88.2% of patients for esotropia. A recession with graded anterior transposition was the weakening IO procedure. In the NO-recess group, 28 (52.8%) patients normalised their mild IOOA after PFS surgery alone. In the UNI-recess group, the success rate was 88.5%, with 16 (61.5%) patients showing worsened IO muscle of the fellow eye, which prompted additional surgery in 10 patients. In the BIL-recess group, all 31 patients improved the adduction pattern of the operated eye for an 80.6% success rate (6 improved marginally). CONCLUSION: Graded anterior transposition of the inferior oblique muscle effectively normalises versions. However, it's frequent for a contralateral overaction to become manifest after unilateral IO surgery.

Motivation and Knowledge of Portuguese Community Pharmacists Towards the Reporting of Suspected Adverse Reactions to Medicines: A Cross-Sectional Survey.

The close contact between patients and community pharmacists, along with the extensive geographical distribution of pharmacies in Portugal, offer exceptional conditions to detect and report adverse drug reactions (ADR). This study aimed to evaluate the motivation and knowledge of spontaneous reporting of ADR by community pharmacists of Porto, Portugal. Secondly, we aimed to generate real-world evidence on the main factors determining ADR report and at raising potential alternatives to the current reporting procedure in community pharmacy. We performed a descriptive, cross-sectional, observational, anonymous web survey-based study. Between April and July 2021, a web survey was implemented, targeting community pharmacists in the Porto district, Portugal. We validated 217 surveys from pharmacists. Regular notifiers seem to be more familiarised than non-regular notifiers with the Portuguese Pharmacovigilance System (PPS), with the Portal RAM for reporting suspected ADR, and with the update of the concept of ADR. Moreover, regular notifiers seem to be more proactive with their care in questioning patients about ADR and have more self-knowledge to identify suspected ADR. Conversely, non-regular notifiers, seem to be more reluctant to be judged by their ADR reporting activities. Respondents suggested to simplify and optimise the reporting process (31% of the suggestions), or to integrate a reporting platform into the pharmacy's software (27%). This study identified opportunities to promote the ADR reporting process by community pharmacists, namely receiving feedback from the PPS on the reported case and its regulatory implications, implementing training programs in pharmacovigilance, and creating solutions to simplify the reporting process.

Expression of chronic pain genes in apical periodontitis tissues.

AIM: To evaluate the expression of genes involved in chronic pain conditions in apical periodontitis (AP) tissues. METHODOLOGY: An electronic search was performed in Scopus and MEDLINE (via PubMed) databases to identify articles (n = 173) related to genes involved in chronic pain conditions. Full-text reviews of the selected articles allowed the prioritization of 16 genes to be investigated with regards to their expression in AP tissues. Periapical lesions (n = 42) were collected during surgical endodontic procedures and processed for mRNA extraction and investigation of target genes via RT-qPCR. Healthy periodontal ligament tissues obtained from third molar extractions were used as controls. Relative levels of target gene expression in AP and control tissues were normalized to GAPDH expression and compared using the 2-ΔΔCt method. Data analysis was performed using the Mann-Whitney U test with a statistical significance threshold set at p < .05. RESULTS: mRNA expression levels of MMP9, TIMP1, TNFA, CAMK4 and COMT were significantly increased in AP tissue samples compared with controls (p < .05). Positive correlations were observed between the expression of TIMP1 with COMT and CAMK4, TNFA with TIMP1 and CAMK4, COMT with CAMK4. CONCLUSIONS: This study confirms the upregulation of MMP9, TIMP1, TNFA in AP tissues and reports for the first time, the expression of CAMK4 and COMT as suggestive of their involvement in AP pathogenesis.

Sequential time-window learning with approximate Bayesian computation: an application to epidemic forecasting.

The long duration of the COVID-19 pandemic allowed for multiple bursts in the infection and death rates, the so-called epidemic waves. This complex behavior is no longer tractable by simple compartmental model and requires more sophisticated mathematical techniques for analyzing epidemic data and generating reliable forecasts. In this work, we propose a framework for analyzing complex dynamical systems by dividing the data in consecutive time-windows to be separately analyzed. We fit parameters for each time-window through an approximate Bayesian computation (ABC) algorithm, and the posterior distribution of parameters obtained for one window is used as the prior distribution for the next window. This Bayesian learning approach is tested with data on COVID-19 cases in multiple countries and is shown to improve ABC performance and to produce good short-term forecasting. Supplementary Information: The online version contains supplementary material available at 10.1007/s11071-022-07865-x.

A comprehensive review of adverse events to drugs used in COVID-19 patients: Recent clinical evidence.

BACKGROUND: Since the breakthrough of the pandemic, several drugs have been used to treat COVID-19 patients. This review aims to gather information on adverse events (AE) related to most drugs used in this context. METHODS: We performed a literature search to find articles that contained information about AE in COVID-19 patients. We analysed and reviewed the most relevant studies in the Medline (via PubMed), Scopus and Web of Science. The most frequent AE identified were grouped in our qualitative analysis by System Organ Class (SOC), the highest level of the MedDRA medical terminology for each of the drugs studied. RESULTS: The most frequent SOCs among the included drugs are investigations (n = 7 drugs); skin and subcutaneous tissue disorders (n = 5 drugs); and nervous system disorders, infections and infestations, gastrointestinal disorders, hepatobiliary disorders, and metabolism and nutrition disorders (n = 4 drugs). Other SOCs also emerged, such as general disorders and administration site conditions, renal and urinary disorders, vascular disorders and cardiac disorders (n = 3 drugs). Less frequent SOC were eye disorders, respiratory, thoracic and mediastinal disorders, musculoskeletal and connective tissue disorders, and immune system disorders (n = 2 drugs). Psychiatric disorders, and injury, poisoning and procedural complications were also reported (n = 1 drug). CONCLUSIONS: Some SOCs seem to be more frequent than others among the COVID-19 drugs included, although neither of the studies included reported causality analysis. For that purpose, further clinical studies with robust methodologies, as randomised controlled trials, should be designed and performed.

How in vitro maturation changes the proteome of ovine cumulus-oocyte complexes?

The present study evaluated the effects of in vitro maturation (IVM) on the proteome of cumulus-oocyte complexes (COCs) from ewes. Extracted COC proteins were analyzed by LC-MS/MS. Differences in protein abundances (p < 0.05) and functional enrichments in immature versus in vitro-matured COCs were evaluated using bioinformatics tools. There were 2550 proteins identified in the COCs, with 89 and 87 proteins exclusive to immature and mature COCs, respectively. IVM caused downregulation of 84 and upregulation of 34 proteins. Major upregulated proteins in mature COCs were dopey_N domain-containing protein, structural maintenance of chromosomes protein, ubiquitin-like modifier-activating enzyme 2. Main downregulated proteins in mature COCs were immunoglobulin heavy constant mu, inter-alpha-trypsin inhibitor heavy chain 2, alpha-2-macroglobulin. Proteins exclusive to mature COCs and upregulated after IVM related to immune response, complement cascade, vesicle-mediated transport, cell cycle, and extracellular matrix organization. Proteins of immature COCs and downregulated after IVM were linked to metabolic processes, immune response, and complement cascade. KEGG pathways and miRNA-regulated genes attributed to downregulated and mature COC proteins related to complement and coagulation cascades, metabolism, humoral response, and B cell-mediated immunity. Thus, IVM influenced the ovine COC proteome. This knowledge supports the future development of efficient IVM protocols for Ovis aries.

Prevalence and factors associated with excessive and severe daytime sleepiness among healthcare university students in the Brazilian Midwest.

The present study aimed to determine the prevalence of, and factors associated with excessive and severe daytime sleepiness in healthcare university students. A cross-sectional university-based study was conducted with 1,779 students from a university located in the Brazilian Midwest State of Goiás, Brazil, in 2018. Daytime sleepiness was assessed using the Epworth Sleepiness Scale (ESS) and classified as excessive daytime sleepiness (EDS; cut-off ESS score ≥10) and severe EDS (S-EDS; cut-off ESS score ≥16). Associated factors included sociodemographic, behavioural, academic, nutritional status, and sleep-related and perceived health characteristics. Poisson regression was used for the data analysis. The mean (SD) age of the sample was 22.5 (3.84) years. The prevalence of EDS was 54.4% (95% confidence interval [CI] 51.9-56.1) and S-EDS was 10.0% (95% CI 9.2-11.7). After adjustment, a higher probability of occurrence of EDS was found among women (prevalence ratio [PR] 1.37, 95% CI 1.24-1.53), younger students (PR 1.23, 95% CI 1.07-1.42), those who were studying medicine (PR 1.14, 95% CI 1.02-1.28), with poor sleep quality (PR 1.29, 95% CI 1.17-1.43), and among those who reported constant loss of sleep due to internet use (PR 1.14, 95% CI 1.02-1.27). After adjustment, the highest probability of occurrence of S-EDS was found among women (PR 1.72, 95% CI 1.22-2.43), among those with poor sleep quality (PR 2.17, 95% CI 1.54-3.08), and medical students (PR 1.39, 95% CI 1.01-1.90). In conclusion, there was a high prevalence of daytime sleepiness among healthcare university students, especially among medical students and women.

Seroprevalence of Epstein-Barr virus and cytomegalovirus infections in Presidente Figueiredo, Amazonas, Brazil.

Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections affect around 95% of the world's population. In Brazil, there are few epidemiological reports related to EBV and CMV infection, especially in the western Amazon region. This study aimed to estimate the seroprevalence of EBV and CMV infection in individuals residents in Presidente Figueiredo, Amazonas, Brazil. Blood samples of 443 individuals were tested for the presence of anti-EBV and anti-CMV IgG antibodies through an enzyme-linked immunosorbent assay. EBV (95.9%; 95% CI: 0.94;0.98), CMV (96.8%; 95% CI: 0.95;0.98) and CMV/EBV (93%;95% CI: 0.91-0.95) coinfection were highly prevalent in the study population. Children (1 to 5 years) not attending school were less susceptible to EBV (OR 0.15; 95% CI: 0.05-0.52; p = 0.017) and CMV infections (OR 0.05; 95% CI: 0.02 - 0.17; p < 0.0001). Teenagers at high school showed increased susceptibility to CMV infection (OR 4.65; 95%CI: 1.43-15.08; p = .013) and EBV/CMV co-infection (OR 3.04; 95%CI: 1.44-6.45; p = 0.005). The seroprevalence of CMV and EBV infections were preeminent and tend to increase with age in the study population. Either attendance to a daycare facility or primary school before the age of 5 years may increase the susceptibility to EBV or CMV infection.

Global proteomic analysis of preimplantational ovine embryos produced in vitro.

The present study was conducted to characterize the major proteome of preimplantation (D6) ovine embryos produced in vitro. COCs were aspirated from antral follicles (2-6 mm), matured and fertilized in vitro and cultured until day six. Proteins were extracted separately from three pools of 45 embryos and separately run in SDS-PAGE. Proteins from each pool were individually subjected to in-gel digestion followed by LC-MS/MS. Three 'raw files' and protein lists were produced by Pattern Lab software, but only proteins present in all three lists were used for the bioinformatics analyses. There were 2,262 proteins identified in the 6-day-old ovine embryos, including albumin, zona pellucida glycoprotein 2, 3 and 4, peptidyl arginine deiminase 6, actin cytoplasmic 1, gamma-actin 1, pyruvate kinase, heat shock protein 90 and protein disulfide isomerase, among others. Major biological processes linked to the sheep embryo proteome were translation, protein transport and protein stabilization, and molecular functions, defined as ATP binding, oxygen carrier activity and oxygen binding. There were 42 enriched functional clusters according to the 2,147 genes (UniProt database). Ten selected clusters with potential association with embryo development included translation, structural constituent of ribosomes, ribosomes, nucleosomes, structural constituent of the cytoskeleton, microtubule-based process, translation initiation factor activity, regulation of translational initiation, cell body and nucleotide biosynthetic process. The most representative KEEG pathways were ribosome, oxidative phosphorylation, glutathione metabolism, gap junction, mineral absorption, DNA replication and cGMP-PKG signalling pathway. Analyses of functional clusters clearly showed differences associated with the proteome of preimplantation (D6) sheep embryos generated after in vitro fertilization in comparison with in vivo counterparts (Sanchez et al., 2021; https://doi.org/10.1111/rda.13897), confirming that the quality of in vitro derived blastocysts are unlike those produced in vivo. The present study portrays the first comprehensive overview of the proteome of preimplantational ovine embryos grown in vitro.

Development of sheep secondary follicles and preservation of aromatase and metalloproteinases 2 and 9 after vitrification and in vitro culture.

The cryopreservation of secondary follicles (SF) is a promising alternative to preserve the reproductive potential both in humans and animals in situations in which the transplantation of ovarian tissue is not possible. The objective of the present study was cryopreserved SF isolated sheep. Beyond follicular morphology, viability and development, we investigated proteins related to steroidogenic function and basement membrane remodeling [metalloproteinases 2 (MMP-2) and 9 (MMP-9)] in fresh SF (FSF) and vitrified SF (VSF) followed by in vitro culture for 6 (D6) or 12 days (D12). The percentage of intact follicles, follicular and oocyte diameter of the VSF were lower than FSF on both days of culture (P < 0.05). The VSF viability was statistically reduced from D6 (95.5%) to D12 (77.3%) but did not differ from the FSF on both days (D6:96.2% to D12:86.5%). Antrum formation in the VSF (D6: 59.13%; D12: 79.56%) was significantly lower than the FSF (D6: 79.61%; D12: 92.23%). However, an increase in this percentage was observed from D6 to D12 in both groups. Aromatase showed stronger labeling on FSF D6 and VSF D12 compared to other treatments (P < 0.05). MMP-2 showed a similar pattern of labeling in FSF D6 and VSF D12, similarly to that observed in FSF D12 and VSF D6. MMP-9 was similar in FSF and VSF cultivated for 6 and 12 days. In conclusion, VSF are able to grow and develop during 12 days of in vitro culture and showed evidence of preservation of steroidogenic function and remodeling of the basement membrane.

SINDy-SA framework: enhancing nonlinear system identification with sensitivity analysis.

Machine learning methods have revolutionized studies in several areas of knowledge, helping to understand and extract information from experimental data. Recently, these data-driven methods have also been used to discover structures of mathematical models. The sparse identification of nonlinear dynamics (SINDy) method has been proposed with the aim of identifying nonlinear dynamical systems, assuming that the equations have only a few important terms that govern the dynamics. By defining a library of possible terms, the SINDy approach solves a sparse regression problem by eliminating terms whose coefficients are smaller than a threshold. However, the choice of this threshold is decisive for the correct identification of the model structure. In this work, we build on the SINDy method by integrating it with a global sensitivity analysis (SA) technique that allows to hierarchize terms according to their importance in relation to the desired quantity of interest, thus circumventing the need to define the SINDy threshold. The proposed SINDy-SA framework also includes the formulation of different experimental settings, recalibration of each identified model, and the use of model selection techniques to select the best and most parsimonious model. We investigate the use of the proposed SINDy-SA framework in a variety of applications. We also compare the results against the original SINDy method. The results demonstrate that the SINDy-SA framework is a promising methodology to accurately identify interpretable data-driven models. Supplementary Information: The online version contains supplementary material available at 10.1007/s11071-022-07755-2.

Framework for enhancing the estimation of model parameters for data with a high level of uncertainty.

Reliable data are essential to obtain adequate simulations for forecasting the dynamics of epidemics. In this context, several political, economic, and social factors may cause inconsistencies in the reported data, which reflect the capacity for realistic simulations and predictions. In the case of COVID-19, for example, such uncertainties are mainly motivated by large-scale underreporting of cases due to reduced testing capacity in some locations. In order to mitigate the effects of noise in the data used to estimate parameters of models, we propose strategies capable of improving the ability to predict the spread of the diseases. Using a compartmental model in a COVID-19 study case, we show that the regularization of data by means of Gaussian process regression can reduce the variability of successive forecasts, improving predictive ability. We also present the advantages of adopting parameters of compartmental models that vary over time, in detriment to the usual approach with constant values.

Evidence for Middle Miocene origin and morphological evolutionary stasis in a Barbacenia Inselberg clade (Velloziaceae).

Atlantic Forest Inselbergs (AFI) and Campos Rupestres (CR) are mountains and highlands of eastern South America, relatively poorly studied and highly threatened, which display extraordinary levels of plant endemism and richness. In spite of their geographical and environmental differences, the origin of the flora of CR and AFI are likely linked to each other, because several plant clades are distributed across both ecosystems. In addition to these studies, little has been investigated about the historical biogeographical connections between AFI and CR and most evolutionary studies are restricted to CR. Barbacenia (Velloziaceae) is widely spread and nearly endemic to the AFI and CR outcrops and thus represent an ideal system to study the biogeographical connections between CR and AFI. Besides, given the remarkable diversity of Barbacenia in CR compared to AFI, it appears that different factors were important drivers in the diversification of Barbacenia lineages, likely leading to different patterns of morphological diversification. Here, we integrate phylogenetic, biogeographic and morphological approaches to: (i) address whether AFI species of Barbacenia are monophyletic and thus a single colonization of AFI can be inferred; (ii) understand the timing and geographical origin of CR and AFI clades; (iii) compare morphological diversity between Barbacenia from AFI and CR under the hypothesis that these two systems have experienced similar levels of morphological diversification during their evolutionary history. To this end, we presented a phylogeny inferred using plastid (atpB-rbcL, trnH-psbA and trnL-trnF) and nuclear (ITS) markers and a complete sampling of AFI Barbacenia, estimated divergence times, reconstructed the ancestral areas of Barbacenia clades and compared their morphological diversity based on a dataset of 16 characters. Our results provided evidence for a diversification of Barbacenia from the Middle Miocene to Pleistocene, as suggested in previous studies. We suggest that stepping-stone dispersal across mountaintops in interplay with paleovegetation dynamics during the global Miocene cooling and Pleistocene climatic oscillations may played an important role in the range expansion of modern AFI Barbacenia lineages. Finally, our results also showed a significant differences in morphological diversity between AFI and CR clades, suggesting a long-term morphological stasis in AFI species.

Glucose metabolomic profile during embryogenesis in the tick Rhipicephalus microplus.

INTRODUCTION: Metabolomic approaches can assess the actual state of an organism's energy metabolism during a specific morphological event, providing a more accurate insight into the correlations between physiology and metabolic regulation. METHODS: The study of the metabolomic profile aim to identify the largest possible number of biomolecules in a certain organism or specific structures. For this purpose, mass spectrometry (MS) and chromatography have been used in the present study. OBJECTIVES: In this context, the aim of the present work is to evaluate the glucose metabolomic profile during embryogenesis in Rhipicephalus microplus tick, investigating the dynamics of nutrient utilization during tick embryo formation, as well as the control of glucose metabolism. RESULTS: We show that glycogen reserves are preferentially mobilized to sustain the energy-intensive process of embryogenesis. Subsequently, the increase in concentration of specific amino acids indicates that protein degradation would provide carbons to fuel gluconeogenesis, supplying the embryo with sufficient glucose and glycogen during development. CONCLUSION: Altogether, these results demonstrated the presence of a very refined catabolic and anabolic control during embryogenesis in R. microplus tick, suggesting the pronounced gluconeogenesis as a strategy to secure embryo development. Moreover, this research contributes to the understanding of the mechanisms that control glucose metabolism during tick embryogenesis and may aid the identification of putative targets for novel chemical or immunological control methods, which are essential to improve the prevention of tick infestations.