The Rediscovery of a Relict Unlocks the First Global Phylogeny of Whip Spiders (Amblypygi).

Asymmetrical rates of cladogenesis and extinction abound in the tree of life, resulting in numerous minute clades that are dwarfed by larger sister groups. Such taxa are commonly regarded as phylogenetic relicts or "living fossils" when they exhibit an ancient first appearance in the fossil record and prolonged external morphological stasis, particularly in comparison to their more diversified sister groups. Due to their special status, various phylogenetic relicts tend to be well-studied and prioritized for conservation. A notable exception to this trend is found within Amblypygi ("whip spiders"), a visually striking order of functionally hexapodous arachnids that are notable for their antenniform first walking leg pair (the eponymous "whips"). Paleoamblypygi, the putative sister group to the remaining Amblypygi, is known from Late Carboniferous and Eocene deposits but is survived by a single living species, Paracharon caecusHansen (1921), that was last collected in 1899. Due to the absence of genomic sequence-grade tissue for this vital taxon, there is no global molecular phylogeny for Amblypygi to date, nor a fossil-calibrated estimation of divergences within the group. Here, we report a previously unknown species of Paleoamblypygi from a cave site in Colombia. Capitalizing upon this discovery, we generated the first molecular phylogeny of Amblypygi, integrating ultraconserved element sequencing with legacy Sanger datasets and including described extant genera. To quantify the impact of sampling Paleoamblypygi on divergence time estimation, we performed in silico experiments with pruning of Paracharon. We demonstrate that the omission of relicts has a significant impact on the accuracy of node dating approaches that outweighs the impact of excluding ingroup fossils, which bears upon the ancestral range reconstruction for the group. Our results underscore the imperative for biodiversity discovery efforts in elucidating the phylogenetic relationships of "dark taxa," and especially phylogenetic relicts in tropical and subtropical habitats. The lack of reciprocal monophyly for Charontidae and Charinidae leads us to subsume them into one family, Charontidae, new synonymy.

Frequency of Deleterious Germline Variants in HER2-Low Breast Cancer Patients Using a Hereditary Multipanel Gene Testing.

HER2-Low is defined as low levels of HER2 expression, based on a score of 1+ on immunohistochemical (IHC) assay or as an IHC score of 2+ and negative results on in situ hybridization (ISH or FISH). They are a heterogeneous population of breast cancers that vary in prognosis and sensitivity to systemic treatments. The frequency and clinical characteristics of pathogenic germline variants (PGVs) in HER2-Low breast cancer (BC) patients is not defined. We analyzed results from patients with BC who underwent multi-gene panel testing (MGPT) (maximum 145 genes) between 2018-2019. We reclassified HER-2 status accordingly. Relationships between the variables of interest were assessed by adopting the proportional regression Cox models. Of a total of 167 BC patients who underwent MGPT, half were hormone-receptor-positive. The median age was 45 years. About two thirds of the patients were in the earlier stage of BC. A total of 57% of the cases were reclassified as HER-2-negative or -Low. PGVs were found in 19% of the patients overall, as follows: seven BRCA1, four BRCA2, two ATM, one ATR, two CFTR, three CHEK2, one FANCA, one MERTK, one MLH1, three MUTYH, one RAD50, three RAD51C, one RECQL4, and two TP53 mutations. In HER2-Low, 26.5% of the patients had PGVs, and in the overall cohort, this was 19.8%. In conclusion, differences in the prevalence of deleterious germline mutations in HER2-Low BC patients compared to non-HER2-Low BC patients were identified. Similar alterations in BRCA were observed in this group of patients compared to the overall cohort. Germline genetic tests should be evaluated in larger cohorts of patients with HER2-Low status to better address the findings.

Complete phylogeny of Micrathena spiders suggests multiple dispersal events among Neotropical rainforests, islands and landmasses, and indicates that Andean orogeny promotes speciation.

The Neotropical region is the most diverse on the planet, largely owing to its mosaic of tropical rainforests. Multiple tectonic and climatic processes have been hypothesized to contribute to generating this diversity, including Andean orogeny, the closure of the Isthmus of Panama, the GAARlandia land bridge and historical connections among currently isolated forests. Micrathena spiders are diverse and widespread in the region, and thus a complete phylogeny of this genus allows the testing of hypotheses at multiple scales. We estimated a complete, dated phylogeny using morphological data for 117 Micrathena species and molecular data of up to five genes for a subset of 79 species. Employing eventc-based approaches and biogeographic stochastic mapping while considering phylogenetic uncertainty, we estimated ancestral distributions, the timing and direction of dispersal events and diversification rates among areas. The phylogeny is generally robust, with uncertainty in the position of some of the species lacking sequences. Micrathena started diversifying around 25 Ma. Andean cloud forests show the highest in-situ speciation, while the Amazon is the major dispersal source for adjacent areas. The Dry Diagonal generated few species and is a sink of diversity. Species exchange between Central and South America involved approximately 23 dispersal events and started ~20 Ma, which is consistent with a Miocene age for the Isthmus of Panama closure. We inferred four dispersal events from Central America to the Antilles in the last 20 Myr, indicating the spiders did not reach the islands through the GAARlandia land bridge. We identified important species exchange routes among the Amazon, Andean cloud forests and Atlantic forests during the Plio-Pleistocene. Sampling all species of the genus was fundamental to the conclusions above, especially in identifying the Andean forests as the area that generated the majority of species. This highlights the importance of complete taxonomic sampling in biogeographic studies.

Remote intensive management to improve antiplatelet adherence in acute myocardial infarction: a secondary analysis of the randomized controlled IMMACULATE trial.

This study aim to investigate if remote intensive coaching for the first 6 months post-AMI will improve adherence to the twice-a-day antiplatelet medication, ticagrelor. Between July 8, 2015, to March 29, 2019, AMI patients were randomly assigned to remote intensive management (RIM) or standard care (SC). RIM participants underwent 6 months of weekly then two-weekly consultations to review medication side effects and medication adherence coaching by a centralized nurse practitioner team, whereas SC participants received usual cardiologist face-to-face consultations. Adherence to ticagrelor were determined using pill counting and serial platelet reactivity measurements for 12 months. A total of 149 (49.5%) of participants were randomized to RIM and 152 (50.5%) to SC. Adherence to ticagrelor was similar between RIM and SC group at 1 month (94.4 ± 0.7% vs. 93.6±14.7%, p = 0.537), 6 months (91.0±14.6% vs. 90.6±14.8%, p = 0.832) and 12 months (87.4±17.0% vs. 89.8±12.5%, p = 0.688). There was also no significant difference in platelet reactivity between the RIM and SC groups at 1 month (251AU*min [212-328] vs. 267AU*min [208-351], p = 0.399), 6 months (239AU*min [165-308] vs. 235AU*min [171-346], p = 0.610) and 12 months (249AU*min [177-432] vs. 259AU*min [182-360], p = 0.678). Sensitivity analysis did not demonstrate any association of ticagrelor adherence with bleeding events and major adverse cardiovascular events. RIM, comprising 6 months of intensive coaching by nurse practitioners, did not improve adherence to the twice-a-day medication ticagrelor compared with SC among patients with AMI. A gradual decline in ticagrelor adherence over 12 months was observed despite 6 months of intensive coaching.

Perillyl alcohol reduces parasite sequestration and cerebrovascular dysfunction during experimental cerebral malaria.

Cerebral malaria (CM) is a severe immunovasculopathy which presents high mortality rate (15-20%), despite the availability of artemisinin-based therapy. More effective immunomodulatory and/or antiparasitic therapies are urgently needed. Experimental Cerebral Malaria (ECM) in mice is used to elucidate aspects involved in this pathology since manifests many of the neurological features of CM. In the present study, we evaluated the potential mechanisms involved in the protection afforded by perillyl alcohol (POH) in mouse strains susceptible to CM caused by Plasmodium berghei ANKA (PbA) infection through intranasal preventive treatment. Additionally, to evaluate the interaction of POH with the cerebral endothelium using an in vitro model of human brain endothelial cells (HBEC). Pharmacokinetic approaches demonstrated constant and prolonged levels of POH in the plasma and brain after a single intranasal dose. Treatment with POH effectively prevented vascular dysfunction. Furthermore, treatment with POH reduced the endothelial cell permeability and PbA s in the brain and spleen. Finally, POH treatment decreased the accumulation of macrophages and T and B cells in the spleen and downregulated the expression of endothelial adhesion molecules (ICAM-1, VCAM-1, and CD36) in the brain. POH is a potent monoterpene that prevents cerebrovascular dysfunction in vivo and in vitro, decreases parasite sequestration, and modulates different processes related to the activation, permeability, and integrity of the blood brain barrier (BBB), thereby preventing cerebral oedema and inflammatory infiltrates.

Immunomodulation through vaccination as a promising therapeutic strategy to mitigate malaria-related neurocognitive sequelae.

Malaria, an ancient infectious parasitic disease, is caused by protozoa of the genus Plasmodium, whose erythrocytic cycle is accompanied by fever, headache, sweating and chills and a systemic inflammation that can progress to severe forms of disease, including cerebral malaria. Approximately 25% of survivors of this syndrome develop sequelae that may include neurological, neurocognitive, behavioral alterations and poor school performance. Furthermore, some outcomes have also been recorded following episodes of non-severe malaria, which correspond to the most common clinical form of the disease worldwide. There is a body of evidence that neuroinflammation, due to systemic inflammation, plays an important role in the neuropathogenesis of malaria culminating in these cognitive dysfunctions. Preclinical studies suggest that vaccination with type 2 immune response elicitors, such as the tetanus-diphtheria (Td) vaccine, may exert a beneficial immunomodulatory effect by alleviating neuroinflammation. In this viewpoint article, vaccination is proposed as a therapy approach to revert or mitigate neurocognitive deficits associated with malaria.

Changes in oxygen delivery during experimental models of cerebral malaria.

Cerebral malaria (CM) is a severe manifestation of malaria that commonly occurs in children and is hallmarked by neurologic symptoms and significant Plasmodium falciparum parasitemia. It is currently hypothesized that cerebral hypoperfusion from impaired microvascular oxygen transport secondary to parasitic occlusion of the microvasculature is responsible for cerebral ischemia and thus disease severity. Animal models to study CM, are known as experimental cerebral malaria (ECM), and include the C57BL/6J infected with Plasmodium berghei ANKA (PbA), which is ECM-susceptible, and BALB/c infected with PbA, which is ECM-resistant. Here we sought to investigate whether changes in oxygen (O2) delivery, O2 flux, and O2 utilization are altered in both these models of ECM using phosphorescence quenching microscopy (PQM) and direct measurement of microvascular hemodynamics using the cranial window preparation. Animal groups used for investigation consisted of ECM-susceptible C57BL/6 (Infected, n = 14) and ECM-resistant BALB/c (Infected, n = 9) mice. Uninfected C57BL/6 (n = 6) and BALB/c (n = 6) mice were included as uninfected controls. Control animals were manipulated in the exact same way as the infected mice (except for the infection itself). C57BL/6 ECM animals at day 6 of infection were divided into two cohorts: Early-stage ECM, presenting mild to moderate drops in body temperature (>34 < 36 °C) and Late-stage ECM, showing marked drops in body temperature (<33 °C). Data taken from new experiments conducted with these animal models were analyzed using a general linear mixed model. We constructed three general linear mixed models, one for total O2 content, another for total O2 delivery, and the third for total O2 content as a function of convective flow. We found that in both the ECM-susceptible C57BL/6J model and ECM-resistant BALB/c model of CM, convective and diffusive O2 flux along with pial hemodynamics are impaired. We further show that concomitant changes in p50 (oxygen partial pressure for 50% hemoglobin saturation), only 5 mmHg in the case of late-stage CM C57BL/6J mice, and O2 diffusion result in insufficient O2 transport by the pial microcirculation, and that both these changes are required for late-stage disease. In summary, we found impaired O2 transport and O2 affinity in late-stage ECM, but only the former in either early-stage ECM and ECM-resistant strains.

Intravenous whole blood transfusion results in faster recovery of vascular integrity and increased survival in experimental cerebral malaria.

BACKGROUND: Cerebral malaria is a lethal complication of Plasmodium falciparum infections in need of better therapies. Previous work in murine experimental cerebral malaria (ECM) indicated that the combination of artemether plus intraperitoneal whole blood improved vascular integrity and increased survival compared to artemether alone. However, the effects of blood or plasma transfusion administered via the intravenous route have not previously been evaluated in ECM. OBJECTIVES: To evaluate the effects of intravenous whole blood compared to intravenous plasma on hematological parameters, vascular integrity, and survival in artemether-treated ECM. METHODS: Mice with late-stage ECM received artemether alone or in combination with whole blood or plasma administered via the jugular vein. The outcome measures were hematocrit and platelets; plasma angiopoietin 1, angiopoietin 2, and haptoglobin; blood-brain barrier permeability; and survival. FINDINGS: Survival increased from 54% with artemether alone to 90% with the combination of artemether and intravenous whole blood. Intravenous plasma lowered survival to 18%. Intravenous transfusion provided fast and pronounced recoveries of hematocrit, platelets, angiopoietins levels and blood brain barrier integrity. MAIN CONCLUSIONS: The outcome of artemether-treated ECM was improved by intravenous whole blood but worsened by intravenous plasma. Compared to prior studies of transfusion via the intraperitoneal route, intravenous administration was more efficacious.

Perillyl alcohol modulates activation, permeability and integrity of human brain endothelial cells induced by Plasmodium falciparum.

BACKGROUND: Cerebral malaria (CM) is a severe immunovasculopathy caused for Plasmodium falciparum infection, which is characterised by the sequestration of parasitised red blood cells (pRBCs) in brain microvessels. Previous studies have shown that some terpenes, such as perillyl alcohol (POH), exhibit a marked efficacy in preventing cerebrovascular inflammation, breakdown of the brain-blood barrier (BBB) and brain leucocyte accumulation in experimental CM models. OBJECTIVE: To analyse the effects of POH on the endothelium using human brain endothelial cell (HBEC) monolayers co-cultured with pRBCs. METHODOLOGY: The loss of tight junction proteins (TJPs) and features of endothelial activation, such as ICAM-1 and VCAM-1 expression were evaluated by quantitative immunofluorescence. Microvesicle (MV) release by HBEC upon stimulation by P. falciparum was evaluated by flow cytometry. Finally, the capacity of POH to revert P. falciparum-induced HBEC monolayer permeability was examined by monitoring trans-endothelial electrical resistance (TEER). FINDINGS: POH significantly prevented pRBCs-induced endothelial adhesion molecule (ICAM-1, VCAM-1) upregulation and MV release by HBEC, improved their trans-endothelial resistance, and restored their distribution of TJPs such as VE-cadherin, Occludin, and JAM-A. CONCLUSIONS: POH is a potent monoterpene that is efficient in preventing P. falciparum-pRBCs-induced changes in HBEC, namely their activation, increased permeability and alterations of integrity, all parameters of relevance to CM pathogenesis.

Increased Neutrophil Percentage and Neutrophil-T Cell Ratio Precedes Clinical Onset of Experimental Cerebral Malaria.

Newly emerging data suggest that several neutrophil defense mechanisms may play a role in both aggravating and protecting against malaria. These exciting findings suggest that the balance of these cells in the host body may have an impact on the pathogenesis of malaria. To fully understand the role of neutrophils in severe forms of malaria, such as cerebral malaria (CM), it is critical to gain a comprehensive understanding of their behavior and functions. This study investigated the dynamics of neutrophil and T cell responses in C57BL/6 and BALB/c mice infected with Plasmodium berghei ANKA, murine models of experimental cerebral malaria (ECM) and non-cerebral experimental malaria, respectively. The results demonstrated an increase in neutrophil percentage and neutrophil-T cell ratios in the spleen and blood before the development of clinical signs of ECM, which is a phenomenon not observed in the non-susceptible model of cerebral malaria. Furthermore, despite the development of distinct forms of malaria in the two strains of infected animals, parasitemia levels showed equivalent increases throughout the infection period evaluated. These findings suggest that the neutrophil percentage and neutrophil-T cell ratios may be valuable predictive tools for assessing the dynamics and composition of immune responses involved in the determinism of ECM development, thus contributing to the advancing of our understanding of its pathogenesis.

Chromosome diversity in Buthidae and Chactidae scorpions from Brazilian fauna: Diploid number and distribution of repetitive DNA sequences.

In this work, we analyzed cytogenetically eight Chactidae and Buthidae, including the localization of repetitive DNA sequences. The chactids possess monocentric chromosomes and the highest diploid numbers (2n=50 in Brotheas amazonicus, 2n=36 in Chactopsis amazonica, 2n=30 in Neochactas sp.) when compared with buthids (2n=10 in Tityus bahiensis, 2n=14 in Tityus apiacas and Tityus metuendus, 2n=18 in Tityus aba, 2n=26 in Ischnotelson peruassu). The localization of rDNA genes and (TTAGG)n sequences exhibited a conserved pattern of two terminal/subterminal ribosomal cistrons and terminal telomere signals. However, the comparison between the data of C-banding, DAPI after FISH and Cot-DNA fraction indicated a variable quantity and distribution of these regions, as follow: (i) positive heterochromatin and Cot-DNA signals (B. amazonicus and I. peruassu), (ii) small blocks of heterochromatin with large Cot-DNA signals (T. metuendus), (iii) positive heterochromatic regions and absence of Cot-DNA signals (T. aba and T. apiacas), and (iv) negative heterochromatin and Cot-DNA signals (T. bahiensis). Therefore, our results revealed that there still is not a clear relation between quantity of heterochromatin and presence of monocentric or holocentric chromosomes and occurrence of chromosomal rearrangements, indicating that repetitive regions in scorpions must be analyzed using different cytogenetic approaches.

Chemical management of aquatic macrophytes under simulated floodplain condition in mesocosms.

Floating natives (Eichhornia crassipes and Pistia stratiotes) and emergent exotic invasives (Hedychium coronarium and Urochloa arrecta) macrophytes grow as aquatic weeds in both natural and artificial floodplain areas in Brazil, where the chemical control should be researched. The herbicides glyphosate and saflufenacil, alone or mixed, were tested for weed control under simulated floodplain condition in mesocosms. Glyphosate (1,440 g ha-1), saflufenacil (120 g ha-1), or glyphosate (1,440 g ha-1) + saflufenacil (42, 84, and 168 g ha-1) were applied firstly; and 75 days after treatment (DAT), glyphosate (1,680 g ha-1) was applied as a follow-up treatment to control plant regrowth. An herbicide-free check was also used. Echhinornia crassipes was the species most susceptible to the different herbicides. Saflufenacil alone presented the lowest control on the macrophytes (≤45%) from 7 to 75 DAT, and in most cases they presented high regrowth rates, i.e., this herbicide was the least effective treatment in reducing the dry mass production of the macrophyte community. Glyphosate alone presented low efficacy to control H. coronarium (30-65%), but for the other macrophytes, it presented control peaks ≥90%, maintaining control levels ≥50% until 75 DAT. Glyphosate + saflufenacil, regardless rate of saflufenacil, caused similar damage to glyphosate in E. crassipes and P. stratiotes; however, in U. arrecta it caused 20-30% less injury. In contrast, these treatments provided the best control of H. coronarium. The complementary application of glyphosate was essential to improve the level of control of the first application, after plant regrowth.

Perception of health-related quality of life, sleep quality and sleepiness index in an educational environment at a dental school in Southeast Brazil.

INTRODUCTION: University entrance is often associated with changes in quality of life, individuals' cognitive and physical behavior. The present study aimed to evaluate health-related quality of life (HRQoL), sleep quality and sleepiness index in dentistry students at a university in Southeast Brazil, in different semesters of their course. MATERIALS AND METHODS: Samples were obtained from 55 students from the dentistry course at the Federal University of Alfenas (UNIFAL-MG). For collecting information, validated SF-36 questionnaires (Medical Outcomes Study 36-item Short-Form Health Survey), namely, Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), were used as instruments in an educational environment. The relationship between the association of demographic factors and academic performance with SF-36, PSQI and ESS was assessed with an alpha of 0.05. RESULTS: The worst HRQoL parameters reported by the participants were observed in the domains of body pain, vitality, general health perception, and limitations due to emotional and social aspects when associated with the investigated variables. Regarding the relative sleep quality index, differences in the PSQI domains were observed when related to demographic factors and academic performance. There was no significant difference in the sleepiness index of these students according to the mean values of the ESS domains. CONCLUSION: The SF-36, PSQI and ESS questionnaires indicated that it is a reliable instrument for measuring the impact of quality of life on dentistry students. In addition, dentistry students of UNIFAL-MG had poor indicators of quality of life associated with health and an inadequate index of quality of sleep.

Effect of fine-scale habitat differences on algal colonisation in a coral-dominated subtropical reef.

Maintaining the coexistence of algae and corals depends on the interactions between them. We investigated these interactions to assess: (1) recruitment patterns of algal turfs over time in dead areas on live corals; (2) the influence of fine-scale differences in coral-dominated environments on algal colonisation; (3) the influence of coral as a substrate for algal recruitment; (4) the invasion potential of algal turf on live coral tissue. This study compared algal colonisation directly on dead or damaged coral areas with algal colonisation on recruitment plates in coral-dominated or -free areas at 23, 154, and 230 days. We also monitored coral colonies over 1.5 years. Filamentous and articulated coralline algae were primarily evident in the early colonisation, reaching stability after 154 days. On a fine scale, the coral-dominated environment showed an increase in number of algal species and coverage. However, coral substrate was selective, with fewer species recruited to this substrate compared to the artificial plates. Furthermore, the competitive dynamics between corals and algal turfs did not result in a winner over time. Thus, algal turf colonisation was influenced not only by coral substrate but also by the reef environment on a fine scale.

A Novel Theoretical Probabilistic Model for Opportunistic Routing with Applications in Energy Consumption for WSNs.

This paper proposes a new theoretical stochastic model based on an abstraction of the opportunistic model for opportunistic networks. The model is capable of systematically computing the network parameters, such as the number of possible routes, the probability of successful transmission, the expected number of broadcast transmissions, and the expected number of receptions. The usual theoretical stochastic model explored in the methodologies available in the literature is based on Markov chains, and the main novelty of this paper is the employment of a percolation stochastic model, whose main benefit is to obtain the network parameters directly. Additionally, the proposed approach is capable to deal with values of probability specified by bounded intervals or by a density function. The model is validated via Monte Carlo simulations, and a computational toolbox (R-packet) is provided to make the reproduction of the results presented in the paper easier. The technique is illustrated through a numerical example where the proposed model is applied to compute the energy consumption when transmitting a packet via an opportunistic network.

Is stronger better? Influence of a strength phase followed by a hypertrophy phase on muscular adaptations in resistance-trained men.

Although used by resistance-trained individuals, it is unknown if increasing muscle strength prior to hypertrophy training leads to greater muscle growth and strength gains. We investigated muscle thickness and maximum strength in 26 resistance-trained men who were randomly assigned to either: STHT, consisted in a 3-week strength-oriented training period (4x1-3 repetition maximum [RM]) prior to a 5-week hypertrophy-oriented period (4x8-12RM), or HT, which comprised an 8-week hypertrophy-oriented training period. Vastus lateralis muscle thickness, and back squat and leg-press 1-RM were assessed at pre, third week, and after 8 weeks of training. When pre-to-post changes are compared, STHT induced greater muscle growth (p = 0.049; 95%CI = 0.15-3.2%; d = 0.81) and strength gains in the back squat (p = 0.015; 95%CI = 1.5-13%; d = 1.05) and leg-press 45° (p = 0.044; 95%CI = 0.16-9.9%; d = 0.79) compared to HT. Our results support the use of a period to increase muscle strength prior to an HT to increase muscle thickness and maximum strength in resistance-trained men.

Chloroquine and mefloquine resistance profiles are not related to the circumsporozoite protein (CSP) VK210 subtypes in field isolates of Plasmodium vivax from Manaus, Brazilian Amazon.

BACKGROUND: The central repetitive region (CRR) of the Plasmodium vivax circumsporozoite surface protein (CSP) is composed of a repetitive sequence that is characterised by three variants: VK210, VK247 and P. vivax-like. The most important challenge in the treatment of P. vivax infection is the possibility of differential response based on the parasite genotype. OBJECTIVES: To characterise the CSP variants in P. vivax isolates from individuals residing in a malaria-endemic region in Brazil and to profile these variants based on sensitivity to chloroquine and mefloquine. METHODS: The CSP variants were determined by sequencing and the sensitivity of the P. vivax isolates to chloroquine and mefloquine was determined by Deli-test. FINDINGS: Although five different allele sizes were amplified, the sequencing results showed that all of the isolates belonged to the VK210 variant. However, we observed substantial genetic diversity in the CRR, resulting in the identification of 10 different VK210 subtypes. The frequency of isolates that were resistant to chloroquine and mefloquine was 11.8 and 23.8%, respectively. However, we did not observe any difference in the frequency of the resistant isolates belonging to the VK210 subtypes. MAIN CONCLUSION: The VK210 variant is the most frequently observed in the studied region and there is significant genetic variability in the CRR of the P. vivax CSP. Moreover, the antimalarial drug sensitivity profiles of the isolates does not seem to be related to the VK210 subtypes.

Ischemic Preconditioning Improves Strength Endurance Performance.

Carvalho, L and Barroso, R. Ischemic preconditioning improves strength endurance performance. J Strength Cond Res 33(12): 3332-3337, 2019-Ischemic preconditioning (IPC) has been used to improve performances in aerobic and anaerobic activities. However, a few studies aimed at observing the effects of IPC on resistance training. The purpose of this study is to examine the effects of IPC on the number of repetitions performed during high-load resistance training. We also aimed at investigating blood lactate concentration and muscle activation in an attempt to understand the physiological mechanisms that may be caused by IPC. Ten resistance-trained participants performed four 5-minute cycles of either IPC (250 mm Hg) or Placebo (10 mm Hg) before performing a single set to failure of knee extension exercise with 85% of 1 repetition maximum. We also assessed muscle activation during the set (EMGRMS), median power frequency (EMGMPF), and blood lactate concentration before, 3, 7, and 11 minutes after (peak value was identified and used to calculate delta to prevalues, Δlactate). Data are presented as mean, 90% confidence intervals (CIs), and were analyzed with paired t-test. The level of significance was set at p < 0.05. Participants performed on average 3.9 repetitions (90% CI = 2.4-5.4; p = 0.01), which is ∼20%, more in the IPC condition. There were no significant differences between IPC and Placebo for EMGMPF (5.0%; 90% CI = -5.2 to 15; p = 0.50), EMGRMS (4.5%; 90% CI = -8.8 to 17; p = 0.78), and Δlactate (44%; 90% CI = 11-144; p = 0.16). Our results demonstrate the effect of IPC just on the number of repetitions performed in high-load resistance exercise compared with the Placebo condition.

Mechanisms of karyotype evolution in the Brazilian scorpions of the subfamily Centruroidinae (Buthidae).

The recently-revised subfamily Centruroidinae is part of the New World clade of buthid scorpions. In this study, we analyzed the cytogenetic characteristics of nine of the 10 Brazilian centruroidines, and one undescribed species of the genus Ischnotelson, using a phylogenetic approach to determine the chromosomal rearrangements responsible for the differentiation of karyotypes among the species. The cytogenetic data recorded in the present study supported the new taxonomic arrangement of the Centruroidinae, with all the species of the same genus sharing the same or similar diploid numbers, i.e., 2n = 20 or 22 in Troglorhopalurus lacrau and T. translucidus, 2n = 25 or 26 in Ischnotelson sp., I. guanambiensis and I. peruassu, and 2n = 28 in Jaguajir agamemnon, J. pintoi and J. rochae. The karyotype modelling in the ChromEvol software indicated 2n = 18 as the ancestral diploid number of the Centruroidinae. The differentiation of karyotypes among the centruroidine genera was based on increasing chromosome numbers resulting from progressive fission events. These changes probably occurred prior to the diversification of the genera Ischnotelson, Jaguajir, Physoctonus and Rhopalurus, and appear to have played a more important role in karyotype evolution at the intergeneric level than the interspecific one. However, the observed increase in diploid numbers was not accompanied by changes in the number or location of ribosomal genes or telomeric sequences. The identification of meiotic cells in female specimens also allowed us to discuss the mechanisms of achiasmatic meiosis in scorpions.

Synthesis and molecular modelling studies of pyrimidinones and pyrrolo[3,4-d]-pyrimidinodiones as new antiplasmodial compounds.

BACKGROUND Malaria is responsible for 429,000 deaths per year worldwide, and more than 200 million cases were reported in 2015. Increasing parasite resistance has imposed restrictions to the currently available antimalarial drugs. Thus, the search for new, effective and safe antimalarial drugs is crucial. Heterocyclic compounds, such as dihydropyrimidinones (DHPM), synthesised via the Biginelli multicomponent reaction, as well as bicyclic compounds synthesised from DHPMs, have emerged as potential antimalarial candidates in the last few years. METHODS Thirty compounds were synthesised employing the Biginelli multicomponent reaction and subsequent one-pot substitution/cyclisation protocol; the compounds were then evaluated in vitro against chloroquine-resistant Plasmodium falciparum parasites (W2 strain). Drug cytotoxicity in baseline kidney African Green Monkey cells (BGM) was also evaluated. The most active in vitro compounds were evaluated against P. berghei parasites in mice. Additionally, we performed an in silico target fishing approach with the most active compounds, aiming to shed some light into the mechanism at a molecular level. RESULTS The synthetic route chosen was effective, leading to products with high purity and yields ranging from 10-84%. Three out of the 30 compounds tested were identified as active against the parasite and presented low toxicity. The in silico study suggested that among all the molecular targets identified by our target fishing approach, Protein Kinase 3 (PK5) and Glycogen Synthase Kinase 3ß (GSK-3ß) are the most likely molecular targets for the synthesised compounds. CONCLUSIONS We were able to easily obtain a collection of heterocyclic compounds with in vitro anti-P. falciparum activity that can be used as scaffolds for the design and development of new antiplasmodial drugs.