Emotional Value of Fear Memory and the Role of the Ventral Hippocampus in Systems Consolidation.

Recent studies have explored the circuitry involving the ventral hippocampus (vHPC), the amygdala, and the prefrontal cortex, a pathway mainly activated to store contextual information efficiently. Lesions in the vHPC impair remote memory, but not in the short term. However, how the vHPC is affected by distinct memory strength or its role in systems consolidation has not yet been elucidated. Here, we investigated how distinct training intensities, with strong or weak contextual fear conditioning, affect activation of the dorsal hippocampus (dHPC) and the vHPC. We found that the time course of memory consolidation differs in fear memories of different training intensities in both the dHPC and vHPC. Our results also indicate that memory generalization happens alongside greater activation of the vHPC, and these processes occur faster with stronger fear memories. The vHPC is required for the expression of remote fear memory and may control contextual fear generalization, a view corroborated by the fact that inactivation of the vHPC suppresses generalized fear expression, making memory more precise again. Systems consolidation occurs concomitantly with greater activation of the vHPC, which is accelerated in stronger fear memories. These findings lead us to propose that greater activation of the vHPC could be used as a marker for memory generalization.

Second-line treatment strategies for RAS wild-type colorectal cancer: A systematic review and Network Meta-analysis (NMA).

BACKGROUND: The optimal strategy for second-line (IIL) treatment in KRAS wt metastatic colorectal cancer (mCRC) is not determined yet. METHODS: A random-effect NMA of phase II/III RCTs was conducted to evaluate IIL treatment for all-RAS wt mCRC, comparing anti-EGFR or anti-VEGF, and chemotherapy (CT). RESULTS: Overall, 11 RCTs (3613 patients) were included. In KRAS wt patients, PFS was improved with anti-VEGF (HR 0.43) and anti-EGFR (HR 0.63) vs CT. However, anti-VEGF based therapy had the highest likelihood of being ranked as the best treatment in terms of PFS (SUCRA 99.3%) and OS (SUCRA 99.4%). Bevacizumab-based treatment is most likely to be the best treatment in terms of PFS (SUCRA 89.1%) and OS (SUCRA 86.7%). CONCLUSIONS: Second line treatment with anti-VEGF and anti-EGFR improved PFS in mCRC patients, however, anti-VEGF based therapy, particularly CT plus bevacizumab, is the best treatment according to SUCRA in terms of PFS and OS.

Use of 2D and co-culture cell models to assess the toxicity of zein nanoparticles loading insect repellents icaridin and geraniol.

After the latest dengue and Zika outbreaks, the fight against mosquito vectors has become an emerging area of research. One tool for this combat is repellents; however, these products are composed of different toxic agents. Botanical compounds with repellent potential are an alternative; however these compounds are highly volatile. Thus, the present study aimed to synthesize zein-based polymeric nanoparticles as an efficient carrier system for the sustained release of the repellents icaridin and geraniol and evaluate the toxicity of these nanorepellents comparing two different cell models. In vitro tests were carried out due to current Brazilian legislation prohibiting animal testing for cosmetics (current classification of repellents). The cytotoxicity and genotoxicity of the nanoparticles were evaluated in 2D and co-culture cell models (A549/lung epithelium, HaCaT/keratinocytes, HT-29/intestinal epithelium, and THP-1/peripheral blood monocytes). Cell viability by mitochondrial activity, cell membrane integrity, damage to genetic material, and expression of genes involved in the allergic/inflammatory system were evaluated. The results of cytotoxicity evaluation showed cell viability above 70% in both cell models. No differences were observed in genotoxicity assessment between cells exposed to nanorepellents and controls. In contrast, gene expression analysis showed increased cytokine expression for the emulsion compounds in 2D cell cultures compared to co-cultures. These findings open perspectives that zein-based nanorepellents have potential applications due to the reduced toxicity observed when the compounds are encapsulated and emerge as an alternative for arbovirus control. In addition, the study demonstrated that depending on the analysis, different results might be observed when comparing 2D and co-culture cell models to evaluate the toxicity of new nanosystems.

[Comparative analysis of refractive and topographic changes after eye muscle surgery]. / Vergleichende Analyse der Refraktions- und Topographieveränderungen nach Augenmuskeloperationen.

BACKGROUND: The question of whether refractive or topographic changes are to be expected after eye muscle surgery is largely unanswered. MATERIALS AND METHODS: Results of pre- and postoperative objective refraction, Pentacam (Oculus, Menlo Park, CA, USA), and visual acuity tests of 229 eyes are included in the present analysis. The examinations took place preoperatively, on the first postoperative day, and after 3 months. RESULTS: After surgery on one or two extraocular recti muscle, there are significant changes in the cylinder (p < 0.001) on the first postoperative day, although values returned to normal after 3 months. Similar changes also appeared in combined operations of extraocular and oblique muscles. CONCLUSION: The authors postulate that extensive patient education with regard to temporary changes in the cylinder is necessary, particularly when the extraocular muscles are involved, and that additional refraction and topography control can be useful postoperatively if visual rehabilitation is inadequate.

The External Morphology of Mythimna (Pseudaletia) sequax (Lepidoptera: Noctuidae).

Mythimna (Pseudaletia) sequax Franclemont, 1951 (Lepidoptera: Noctuidade) is the most important armyworm in the American tropics and subtropics. In this study, we describe the external morphology of the immatures and adults, based on larvae fed on quicuio grass (Pennisetum clandestinum Hochst. ex Chiov - Poaceae). The external morphology of the eggs, larvae, pupae, and adults is described and illustrated. Important taxonomic structures of the larvae are described, including hypopharynx, spinneret, and mandible. Adult structures that allow the differentiation of the species, such as male genitalia and scent brushes, are also described. The results are compared and discussed based on morph functionality and with publications on the congeneric species.

Overlooked South American noctuid species: revalidation of Feltia llanoi stat. rev. and redescription of Feltia brachystria (Lepidoptera: Noctuidae).

Feltia llanoi (Köhler, 1953) stat. rev. and its hitherto senior subjective synonym Feltia brachystria (Hampson, 1903) are two species of noctuid moths with unusual broadly bipectinate antenna and restricted distribution in central eastern Argentina, southern Brazil, and Uruguay. Examination of the type of specimens and further material from several collections indicates that these names are not synonyms, but valid species, and reveal the occurrence of F. llanoistat. rev. in Brazil. Therefore, F. llanoistat. rev. and F. brachystria are redescribed and the former name is reinstated to species, including taxonomic comments, illustration of some characters of taxonomic importance, and of structures of the male and female genitalia. The species are compared with similar-looking and supposedly closely related species, such as F. chilensis (Hampson, 1903), F. carolia (Schaus, 1929), and F. gypaetina (Guenée, 1852). Additionally, in order to stabilize nomenclature, a lectotype for F. llanoistat. rev. is designated, and Agrotis daguerrei Köhler, 1961 is here recognized as a junior subjective synonym of F. llanoistat. rev. (syn. nov.).

Feltia submontana (Noctuidae, Noctuinae): Redescription, Taxonomy, Life Cycle, and Spatial Distribution of a Neglected South American Potential Pest Species.

Feltia submontana (Köhler, 1961) is redescribed based on specimens from Northwestern Argentina and Central and Southeastern Brazil. Taxonomic comments, photographs of the adults, characters of taxonomic importance, and illustrations of structures of the labial palpus, legs, and male and female genitalia are provided. The species is compared with similar-looking and supposedly closely related species, such as F. hispidula (Guenée, 1852) and F. lilacina (Zerny, 1916). The species, originally described for Argentina, is reported for Brazil for the first time. Most Brazilian specimens come from the "Cerrado" but also from Southeastern Atlantic Forests. The life cycle of F. submontana specimens collected in Planaltina, Distrito Federal, Brazil, is described; the species probably has only a single generation per year and imagines are on the wing in the late autumn and early winter months; the last instar prepupa and pupa pass through aestival diapause. The abundance of F. submontana relative to other species of Agrotis Ochsenheimer, 1816, and Feltia Walker, 1856, in the above-cited locality is accessed through 4 years of standardized collecting with light trap; the species is the second most abundant species of these genera in the area, with about one fifth of the captures, second only to A. ipsilon (Hufnagel, 1766), with about two thirds of the captures, and about two times more abundant than F. subterranea (Fabricius, 1794); the latter two are regarded as important pest species in South America.

Invasive slug Meghimatium pictum (Stoliczka, 1873) infected by Angiostrongylus costaricensis Morera & Céspedes, 1971, and the possible risk of human infection associated with grape consumption.

Many molluscs may be infected with angiostrongylid larvae. Following the histopathological diagnosis of abdominal angiostrongyliasis in a grape farmer from southern Brazil, molluscs in the area were investigated. During a nocturnal search, 245 specimens of slugs were collected and identified as the invasive Chinese slug Meghimatium pictum. Angiostrongylus costaricensis worms were recovered from mice that were experimentally infected with larvae obtained from 11 (4.5%) of the molluscs. This study presents the first report of M. pictum being identified as an intermediate host for A. costaricensis. Most of the slugs were collected from grape plants, which suggests that transmission may be associated with grape consumption.

Where and when? How phenological patterns of armyworm moths (Lepidoptera: Noctuidae) change along a latitudinal gradient in Brazil.

The phenological patterns exhibited by different organisms are known as adaptive responses to the cyclical environmental conditions. However, only a limited number of researches explore which factors are responsible for these phenological patterns in pest species. In the current study, abundance patterns were studied in the phenology of three Spodoptera Guenée, 1852 species, along the 29° latitudinal gradient in South America. The goal was to test whether widely distributed and abundant crop pest species would exhibit different phenological responses to seasonal meteorological variables and host plant availability. To test this, 13 light traps were set up in Brazil to collect adult Spodoptera samples at the time of the new moon, every month, from June 2015 to May 2016. The time of occurrence and intensity of the phenology were determined for each species, employing circular statistics. Both metrics revealed significant variations among the different species, as well as the factors associated with them. Latitude was found to affect the period of occurrence in Spodoptera cosmioides (Walker, 1858) and Spodoptera albula (Walker, 1857), whereas in Spodoptera frugiperda (J. E. Smith, 1797) its effect was evident only in the intensity of its phenology. Further, both meteorological variables and host plant availability in the sampling sites produced predictive models to account for the phenological patterns expressed. These findings suggest that different species of Spodoptera exhibit different adaptive strategies in their life cycles in response to environmental conditions, thus necessitating specific management practices regarding their seasonal population fluctuation.

Spodoptera marima: a New Synonym of Spodoptera ornithogalli (Lepidoptera: Noctuidae), with Notes on Adult Morphology, Host Plant Use and Genetic Variation Along Its Geographic Range.

Spodoptera marima (Schaus, 1904) and Spodoptera ornithogalli (Guenée, 1852) are noctuid moths recognized for their economic importance in the New World. Historically, they have been considered cryptic species, being supposedly differentiated from each other by the absence of sexual dimorphism in S. marima, subtle differences in coloration on the hindwings and scale tufts of the ovipositor and the shape of male valva. The species are allopatric: North and Central America for S. ornithogalli and South America for S. marima. Previous phylogenetic studies using multilocus DNA sequences including a few specimens of S. marima suggested these species merge into a single clade. Here, we performed a comparative analysis to elucidate further their taxonomic status, using specimens of S. marima from various localities in Brazil. These species were recovered in the phylogenetic analysis as consistently mixed with each other in a major well-supported clade within Spodoptera. The existence of a spatial pattern for genetic structure was not clearly supported when two biogeographic regions (Neotropics and Neartic) were taken in separation; however, an individual-level isolation by distance was significant. The morphological characters traditionally used to differentiate the species were also not consistent. Therefore, we now consider S. marima a new junior synonym of S. ornithogalli. Results on host plant use demonstrated that it is a polyphagous species using more than 200 plants, which may mediate phenotypic variation along its geographical range.

Bone metastases in biliary cancers: A multicenter retrospective survey.

•Natural history of biliary cancers metastatic to bone•The role of skeletal events in patients with biliary cancer•Biliary cancer and bone metastases: role of bisphosphonates.

Three-dimensional surface models of the facial soft tissues acquired with a low-cost scanner.

Although there has been an increase in three-dimensional (3D) scanning methods available on the market, they are generally expensive. The DI3D system is considered a good scanner for the acquisition of soft tissue surface images. The Microsoft Kinect scanner is a much more affordable alternative for acquiring 3D models. The aim of this study was to determine whether the precision and accuracy of Kinect are similar to those of DI3D. To verify the accuracy, 10 patients were scanned with both methods The models of each patient acquired from the two scanners were superimposed using a surface-to-surface registration technique, and the distances between the models were recorded for 10 different anatomical regions of interest. For the evaluation of precision, one patient was scanned 11 different times with the Kinect scanner, and these models were compared using the same superimposition method. It was found that the average difference between the two methods was 0.3±2.03mm. The assessment of reproducibility showed an average difference between the images taken with Kinect of 0.1±0.6mm (P<0.05, one-sample t-test). Thus, Kinect showed good precision and reasonable accuracy, and appears to be an interesting and promising resource for facial analysis.

The use of γ-rays analysis by HPGe detector to assess the gross alpha and beta activities in waters.

This paper describes an alternative method for evaluating gross alpha and beta radioactivity in waters by using γ-rays analysis performed with hyper-pure germanium detector (HPGe). Several gamma emissions related to α and ß- decays were used to provide the activity concentration data due to natural radionuclides commonly present in waters like 40K and those belonging to the 238U and 232Th decay series. The most suitable gamma emissions related to ß- decays were 214Bi (1120.29 keV, 238U series) and 208Tl (583.19 keV, 232Th series) as the equation in activity concentration yielded values compatible to those generated by the formula taking into account the detection efficiency. The absence of isolated and intense γ-rays peaks associated to α decays limited the choice to 226Ra (186.21 keV, 238U series) and 224Ra (240.99 keV, 232Th series). In these cases, it was adopted appropriate correction factors involving the absolute intensities and specific activities for avoiding the interferences of other γ-rays energies. The critical level of detection across the 186-1461 keV energy region corresponded to 0.010, 0.023, 0.038, 0.086, and 0.042 Bq/L, respectively, for 226Ra, 224Ra, 208Tl, 214Bi and 40K. It is much lower than the WHO guideline reference value for gross alpha (0.5 Bq/L) and beta (1.0 Bq/L) in waters. The method applicability was checked by the analysis of groundwater samples from different aquifer systems occurring in the Brazilian states of São Paulo, Minas Gerais and Mato Grosso do Sul. The waters exhibit very different chemical composition and the samples with the highest radioactivity levels were those associated with lithotypes possessing enhanced uranium and thorium levels. The technique allowed directly discard the 40K contribution to the gross beta activity as potassium is an essential element for humans.

Morphological Characterization of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae: Heliothinae).

The cotton bollworm Helicoverpa armigera (Hübner) is a widespread lepidopteran pest found in various crops worldwide. This highly polyphagous species, commonly found both in the Old and New World, has caused significant economic damage as an invasive agricultural pest in Brazil since 2013. The goal of the present study is to provide a detailed morphological assessment of adults and immature stages of H. armigera, as this species is often confused with H. zea (Boddie), a congeneric species that is native to the New World. The biology data were acquired during four full life cycles, and observations on general behavior, nocturnal habits of larvae and adults, and sensitivity of larvae to humidity were recorded. Larval chaetotaxy differs between the first and the remaining instars, which bear L2 on the meso- and metathorax and L3 on A3 through A6, along with conspicuous chalazae and longitudinal bands. Important morphological characters of this species include the following: eggs with four micropylar openings, lined with 12 cells arranged in the shape of a rosette; pupa adecticous and obtect, with prominent spiracles; adults with the distal antennomere striate. Adults exhibit sexual dimorphism in the number of setae on the frenulum and spines on the prothoracic leg. Illustrations of the critical morphological features of this species are provided.

Uncovered Diversity of a Predominantly Andean Butterfly Clade in the Brazilian Atlantic Forest: a Revision of the Genus Praepedaliodes Forster (Lepidoptera: Nymphalidae, Satyrinae, Satyrini).

The genus Praepedaliodes Forster, 1964, the only representative of the mega-diverse mostly Andean Pedaliodes complex lineage in the Brazilian Atlantic Forest, is revised. Prior to this study, four species were known, P. phanias (Hewitson, 1862), P. granulata (Butler, 1868), P. amussis (Thieme, 1905) and P. exul (Thieme, 1905). Here, a further six are described, all from SE Brazil, expanding to 10 the number of species in this genus. Lectotypes are designated for P. phanias, P. granulata and P. amussis. The genus is most diverse in the Serra da Mantiqueira (São Paulo, Rio de Janeiro, Minas Gerais) and in the Serra Geral (Paraná, Santa Catarina) with seven species occurring in both ranges. Praepedaliodes phanias is the most widespread species and the only one found in the western part of the Atlantic Forest; only this species and P. duartei Dias, Dolibaina & Pyrcz n. sp. occurring to near sea level. Other species, P. zaccae Dolibaina, Dias & Pyrcz n. sp., P. francinii Freitas & Pyrcz n. sp., P. sequeirae Pyrcz, Dias & Dolbaina n. sp., P. landryi Pyrcz & Freitas n. sp. and P. pawlaki Pyrcz & Boyer n. sp. are strictly montane and the highest species richness is reached at 1400-1800 m. One species, P. sequeirae n. sp., is a narrow endemic found only at timberline in the Agulhas Negras massif above 2300 m. Immature stages are described for two species, P. phanias and P. landryi n. sp. Molecular data (barcode region of cytochrome oxidase, subunit I) and adult morphology, including male and female genitalia, support the genus as monophyletic, belonging to a predominantly Andean clade of the Pedaliodes Butler, 1867 complex. Morphological evidences, in particular female genitalia comparative analysis, indicate the genera Physcopedaliodes Forster, 1964 and Panyapedaliodes Forster, 1964 as possibly the closest relatives to Praepedaliodes. Molecular data are inconclusive in this respect.

The effect of age and carbohydrate and protein sources on digestibility, fecal microbiota, fermentation products, fecal IgA, and immunological blood parameters in dogs.

The present study compared the effects of diets formulated with fibers of different fermentability and protein sources of animal or vegetable origins on old and adult dogs. The experiment was organized in a 3 (diets) × 2 (ages) factorial arrangement, totaling 6 treatments. Thirty-six Beagle dogs were used (18 old dogs [10.2 ± 1.0 yr] and 18 young adult dogs [2.6 ± 0.9 yr]), with 6 dogs per treatment. Three diets with similar compositions were used: a nonfermentable insoluble fiber source (sugarcane fiber) and chicken byproduct meal (nonfermentable fiber [NFF] diet), a fermentable fiber source (beet pulp) and chicken byproduct meal (fermentable fiber [FF] diet), and soybean meal as a protein and fiber source (soybean meal [SM] diet). Data were evaluated using the MIXED procedure and considering the effects and interactions of block, animal, diets, and age. Means were compared using Tukey's test ( < 0.05). Age × diet interactions were evaluated when < 0.1. Old dogs had a reduced coefficient of total tract apparent digestibility of DM, which was explained by the age and diet interaction of CP and fat digestibility that was lower for old than for adult dogs fed the FF diet ( < 0.05). The SM diet obtained higher DM, OM, CP, and fiber digestibility compared with the NFF diet ( < 0.05). The feces of dogs fed the NFF diet had increased DM content ( < 0.05). The short-chain fatty acids (SCFA) did not change by age group and were higher for dogs fed the FF and SM diets compared with dogs fed the NFF diet ( < 0.05). An age and diet interaction was observed for lactate and was increased in the feces of old dogs compared with adult dogs fed the FF diet ( < 0.05). Fecal putrescine, cadaverine, and spermine were increased for old dogs compared with adult dogs ( < 0.05), and the spermidine fecal concentration was increased for dogs fed the SM diet regardless of age ( < 0.05). Old dogs had reduced peripheral T and B lymphocytes ( < 0.05). An age and diet interaction was observed for fecal IgA ( < 0.001). Adult dogs fed the SM diet had increased IgA in feces compared with animals fed the NFF and FF diets ( < 0.05). However, for old dogs, both the FF and SM diets induced increased IgA compared with the NFF diet ( < 0.05). In conclusion, beet pulp may reduce digestibility and induce increased lactate in the feces of old dogs. The protein and oligosaccharides of soybean meal are digestible by dogs, induce the production of SCFA and spermidine, and increase fecal IgA. Old dogs had increased putrecine, cadaverine, and spermine fecal concentrations.

Immature Stages of Six Species of Adelpha Hübner (Lepidoptera: Nymphalidae: Limenitidinae) from Southern Brazil Coastal Forests.

Six species of Adelpha Hübner from Balneário Barra do Sul (Santa Catarina) and Morretes (Paraná) were collected as eggs or larvae and reared in captivity, aiming to provide descriptions and photography of the immature stages and imagoes. The species studied were Adelpha radiata radiata Fruhstorfer; Adelpha serpa serpa (Boisduval); Adelpha plesaure plesaure Hübner; Adelpha thesprotia (C. Felder & R. Felder); Adelpha lycorias lycorias (Godart); and Adelpha capucinus velia (C. Felder & R. Felder). Two new records of host plants were provided, Tapirira guianensis Aubl. for A. radiata radiata and Heteropterys for A. capucinus velia. This study provides a summary of host plants and the seasonality of occurrence of immature stages of these species. Data were organized in photographic plates that could be useful for the identification process.

BRAF and RAS mutations as prognostic factors in metastatic colorectal cancer patients undergoing liver resection.

BACKGROUND: Despite major advances in the management of metastatic colorectal cancer (mCRC) with liver-only involvement, relapse rates are high and reliable prognostic markers are needed. METHODS: To assess the prognostic impact of BRAF and RAS mutations in a large series of liver-resected patients, medical records of 3024 mCRC patients were reviewed. Eligible cases undergoing potentially curative liver resection were selected. BRAF and RAS mutational status was tested on primary and/or metastases by means of pyrosequencing and mass spectrometry genotyping assay. Primary endpoint was relapse-free survival (RFS). RESULTS: In the final study population (N=309) BRAF mutant, RAS mutant and all wild-type (wt) patients were 12(4%), 160(52%) and 137(44%), respectively. Median RFS was 5.7, 11.0 and 14.4 months respectively and differed significantly (Log-rank, P=0.043). At multivariate analyses, BRAF mutant had a higher risk of relapse in comparison to all wt (multivariate hazard ratio (HR)=2.31; 95% CI, 1.09-4.87; P=0.029) and to RAS mutant (multivariate HR=2.06; 95% CI, 1.02-4.14; P=0.044). Similar results were obtained in terms of overall survival. Compared with all wt patients, RAS mutant showed a higher risk of death (HR=1.47; 95% CI, 1.05-2.07; P=0.025), but such effect was lost at multivariate analyses. CONCLUSIONS: BRAF mutation is associated with an extremely poor median RFS after liver resection and with higher probability of relapse and death. Knowledge of BRAF mutational status may optimise clinical decision making in mCRC patients potentially candidate to hepatic surgery. RAS status as useful marker in this setting might require further studies.

The Neotropical genus Ginungagapus gen. nov. (Hesperiidae, Hesperiinae, Moncini): phylogenetic position and taxonomic review.

A taxonomic and phylogenetic study based on morphological characters revealed the type species of the genus Lucida Evans, 1955, Lucida lucia (Capronnier, 1874) to be paraphyletic to other species of the genus. As a result, a new genus, Ginungagapus gen. nov., is erected including four species previously placed in Lucida: Ginungagapus schmithi (Bell, 1930) comb. nov., Ginungagapus bocus (Bell, 1947) comb. nov., Ginungagapus ranesus (Schaus, 1902) comb. nov., and Ginungagapus rogan (Evans, 1955) comb. nov.; and four new species are added: Ginungagapus awarreni, sp. nov., Ginungagapus tangerinii, sp. nov., Ginungagapus fiedleri, sp. nov. and Ginungagapus brasilia, sp. nov. The new genus is taxonomically revised, genitalia are illustrated, except of the female of G. rogan (Evans, 1955) and of the male of G. brasilia, sp. nov., which are still unknown. An identification key is provided.