APOE4 impairs the microglial response in Alzheimer's disease by inducing TGFß-mediated checkpoints.

The APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). The contribution of microglial APOE4 to AD pathogenesis is unknown, although APOE has the most enriched gene expression in neurodegenerative microglia (MGnD). Here, we show in mice and humans a negative role of microglial APOE4 in the induction of the MGnD response to neurodegeneration. Deletion of microglial APOE4 restores the MGnD phenotype associated with neuroprotection in P301S tau transgenic mice and decreases pathology in APP/PS1 mice. MGnD-astrocyte cross-talk associated with ß-amyloid (Aß) plaque encapsulation and clearance are mediated via LGALS3 signaling following microglial APOE4 deletion. In the brains of AD donors carrying the APOE4 allele, we found a sex-dependent reciprocal induction of AD risk factors associated with suppression of MGnD genes in females, including LGALS3, compared to individuals homozygous for the APOE3 allele. Mechanistically, APOE4-mediated induction of ITGB8-transforming growth factor-ß (TGFß) signaling impairs the MGnD response via upregulation of microglial homeostatic checkpoints, including Inpp5d, in mice. Deletion of Inpp5d in microglia restores MGnD-astrocyte cross-talk and facilitates plaque clearance in APP/PS1 mice. We identify the microglial APOE4-ITGB8-TGFß pathway as a negative regulator of microglial response to AD pathology, and restoring the MGnD phenotype via blocking ITGB8-TGFß signaling provides a promising therapeutic intervention for AD.

Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer's disease.

Microglia play a critical role in brain homeostasis and disease progression. In neurodegenerative conditions, microglia acquire the neurodegenerative phenotype (MGnD), whose function is poorly understood. MicroRNA-155 (miR-155), enriched in immune cells, critically regulates MGnD. However, its role in Alzheimer's disease (AD) pathogenesis remains unclear. Here, we report that microglial deletion of miR-155 induces a pre-MGnD activation state via interferon-γ (IFN-γ) signaling, and blocking IFN-γ signaling attenuates MGnD induction and microglial phagocytosis. Single-cell RNA-sequencing analysis of microglia from an AD mouse model identifies Stat1 and Clec2d as pre-MGnD markers. This phenotypic transition enhances amyloid plaque compaction, reduces dystrophic neurites, attenuates plaque-associated synaptic degradation and improves cognition. Our study demonstrates a miR-155-mediated regulatory mechanism of MGnD and the beneficial role of IFN-γ-responsive pre-MGnD in restricting neurodegenerative pathology and preserving cognitive function in an AD mouse model, highlighting miR-155 and IFN-γ as potential therapeutic targets for AD.

Feeding preference and intraguild interactions between the parasitoid Trichogramma achaeae and the predator Macrolophus pygmaeus, two biological agents of Tuta absoluta.

BACKGROUND: Tuta absoluta is an exotic species and a major pest of tomato crops in Europe. Macrolophus pygmaeus and Trichogramma achaeae are two biocontrol agents widely used in integrated pest management programs of the South American tomato pinworm Tuta absoluta. In this study, we evaluated under laboratory conditions the (i) voracity of M. pygmaeus females fed on single diets of Tuta absoluta eggs parasitized or unparasitized by Trichogramma achaeae, (ii) voracity and feeding preference of M. pygmaeus females provided with mixed diets of Tuta absoluta eggs unparasitized and parasitized by Trichogramma achaeae and (iii) effect of competitive and intraguild interactions between M. pygmaeus and Trichogramma achaeae on the number of Tuta absoluta eggs consumed and/or parasitized. Lastly, we assessed under field conditions the effect of interspecific and intraspecific interactions between natural enemies on the number of Tuta absoluta eggs consumed and/or parasitized. RESULTS: Macrolophus pygmaeus consumed more unparasitized than parasitized eggs of Tuta absoluta. Under mixed diet regimes, Manly indices revealed a feeding preference for unparasitized eggs, and a decrease in the total number of eggs consumed, as the proportion of available parasitized eggs increased, whereas the unparasitized eggs were consumed in direct proportion to their availability. Conspecific interactions between M. pygmaeus, in contrast to Trichogramma achaeae, revealed the possible occurrence of intraspecific competition. For intraguild heterospecific interactions, the number of Tuta absoluta eggs consumed by M. pygmaeus and parasitized by Trichogramma achaeae was lower than that predicted for additive and non-interactive scenarios. Under field conditions, a significant difference between the conspecific treatment and heterospecific treatments revealed a slightly higher success rate in controlling Tuta absoluta when both M. pygmaeus and Trichogramma achaeae were used simultaneously. CONCLUSION: Macrolophus pygmaeus prefers unparasitized eggs of Tuta absoluta but inflicts intraguild predation on Trichogramma achaeae. In conspecific experiments, mutual interference between M. pygmaeus predators intensifies as the number of individuals increases, but for Trichogramma achaeae, it occurs in an unpredictable manner. Adding Trichogramma achaeae could significantly increase the level of control of Tuta absoluta compared to what could be achieved when only M. pygmaeus is present in glasshouse tomatoes. © 2023 Society of Chemical Industry.

Psychedelics and Mental Health: An Alternative Strategy to Treat Mental Impairments Triggered or Aggravated by COVID-19.

Despite the discovery of vaccines for COVID-19, one of the best security measures to contain the spread of the virus is social distancing and isolation. However, isolation might trigger negative mental outcomes, such as onset of a depressive and anxious condition, increased consumption of alcohol and drugs, relapse to substances of abuse, and even induce post-traumatic stress disorder. Interestingly, recent research with psychedelics suggests that when these substances are used in combination with psychotherapy, they may reduce these mental impairments. Nevertheless, scientists are still working to elucidate the possible mechanisms behind these phenomena.

Postnatal ontogeny of the femur in fossorial and semiaquatic water voles in the 3D-shape space.

Water voles of the genus Arvicola constitute an excellent subject to investigate to which extent function affects postnatal developmental growth of limb structures in phylogenetically close species. We performed a comparative analysis of postweaning femur form changes between Arvicola sapidus (semiaquatic) and Arvicola scherman (fossorial) using three-dimensional landmark-based geometric morphometrics. In both species, we observed greater femur robustness in juvenile individuals than in adult ones, probably due to the accommodation of high loads on the bone during initial locomotor efforts. Significant interspecific differences were also found in the femur size and shape of adult specimens, as well as in the postnatal allometric and phenotypic trajectories. In terms of phenotypic variation, fossorial water voles show relatively wider third and lesser trochanters, and greater femur robustness than A. sapidus, characters associated to the digging activity. In contrast, A. sapidus displays a slight increase of the greater trochanter in comparison with A. scherman, which is seemingly an adaptive response for enhancing propulsion through the water. Results evidence that certain morphological traits and differences between A. sapidus and A. scherman in the allometric and phenotypic trajectories of the femur are associated with their different locomotor mode.

Evaluation of Masseter Muscle Dimensions Through Ultrasonography

ABSTRACT: The objective this study was to determine mean values of masseter muscle thickness in male and female, at rest and contraction, in healthy individuals. At first, 102 questionnaires were distributed between students. Thirty patients were selected, 15 male and 15 female, according to the inclusion criteria, excluding all individuals with symptoms of temporo-mandibular dysfunction or syndromes with craniofacial disorders. Masseter muscle thickness was determined bilaterally, at rest and contraction. As a reference point for the measurement of thickness (axial plane), the posterior prolon gation of the labial commissure was used. Normality values of the masseter muscle in females were 11.75 ± 1,14 mm in contraction and 10.19 ± 1.04 mm in relaxation; and in the male were 13.95 ± 1.62 mm in contraction and 11.64 mm ± 1.68 mm in relaxation. The results obtained are in agreement with those described in the literature. Demonstrating the accuracy and reproductibility of the ultrasound if a protocol is applied, mainly aimed at controlling the pressure applied by the transducer.

RESUMEN: El objetivo de este estudio fue determinar los valores medios del grosor del músculo masetero, en reposo y contracción, en hombres y mujeres sanos. Inicialmente se distribuyeron 102 cuestionarios entre los estudiantes. Se seleccionaron 30 pacientes, 15 hombres y 15 mujeres, según los criterios de inclusión, excluyendo a todos los individuos con síntomas de disfunción temporo-mandibular o síndromes con alteraciones craneofaciales. El grosor del músculo masetero se determinó de forma bilateral, en reposo y contracción. Como punto de referencia para la medición del espesor (plano axial), la prolongación posterior de la comisura labial. Los valores de normalidad del músculo masetero en las mujeres fue de 11,75 ± 1,14 mm en contracción y 10,19 ± 1,04 mm en relajación; y en los varones 13,95 ± 1,62 mm en contracción y 11,64 mm ± 1,68 mm en relajación. Los resultados obtenidos coinciden con los descritos en la literatura, señalando la precisión y reproducibilidad del ultrasonido si se aplica un protocolo, principalmente dirigido a controlar la presión aplicada por el transductor.

Evidence of micro-evolution in Crocidura russula from two abandoned heavy metal mines: potential use of Cytb, CYP1A1, and p53 as gene biomarkers.

Heavy metals accumulated in the environment due to the mining industry may impact on the health of exposed wild animals with consequences at the population level via survival and selection of the most resistant individuals. The detection and quantification of shifts in gene frequencies or in the genetic structure in populations inhabiting polluted sites may be used as early indicators of environmental stress and reveal potential 'candidate gene biomarkers' for environmental health assessment. We had previously observed that specimens of the Greater white-toothed shrew (Crocidura russula) from two heavy metal mines in Southern Portugal (the Aljustrel and the Preguiça mines) carried physiological alterations compared to shrews from an unpolluted site. Here, we further investigated whether these populations showed genetic differences in genes relevant for physiological homeostasis and/or that are associated with pathways altered in animals living under chronic exposure to pollution, and which could be used as biomarkers. We analysed the mitochondrial cytochrome b (Cytb) gene and intronic and/or exonic regions of four nuclear genes: CYP1A1, LCAT, PRPF31, and p53. We observed (1) population differences in allele frequencies, types of variation, and diversity parameters in the Cytb, CYP1A1, and p53 genes; (2) purifying selection of Cytb in the mine populations; (3) genetic differentiation of the two mine populations from the reference by the p53 gene. Adding to our previous observations with Mus spretus, we provide unequivocal evidence of a population effect exerted by the contaminated environment of the mines on the local species of small mammals.

Narrow versus broad: sexual dimorphism in the wing form of western European species of the subgenus Avaritia (Culicoides, Ceratopogonidae).

While wing form is known to differ between males and females of the genus Culicoides, detailed studies of sexual dimorphism are lacking. In this study, we analyze sex-specific differences in the wing form of 5 species of the subgenus Avaritia, using geometric morphometrics and comparative phylogenetic methods. Our results confirm the existence of marked sexual dimorphism in the wing form of the studied species and reveal for the first time that while there is a shared general pattern of sexual shape dimorphism within the subgenus, sexual size dimorphism, and particular features of sexual shape dimorphism differ among species. Sexual shape dimorphism was found to be poorly associated to size and the evolutionary history of the species. The tight association of sexual shape dimorphism with aspect ratio suggests that the shape of the wing is optimized for the type of flight of each sex, that is, dispersal flight in females versus aerobatic flight in males. Moreover, the fact that interspecific shape differences are greater and more strongly associated to aspect ratio in males than in females might be indicating that in males the selective pressures affecting flight performance characteristics are more heterogeneous and/or stronger than in females among the studied species.

In Utero Exposure to Environmental Tobacco Smoke Increases Neuroinflammation in Offspring.

The embryonic stage is the most vulnerable period for congenital abnormalities. Due to its prolonged developmental course, the central nervous system (CNS) is susceptible to numerous genetic, epigenetic, and environmental influences. During embryo implantation, the CNS is more vulnerable to external influences such as environmental tobacco smoke (ETS), increasing the risk for delayed fetal growth, sudden infant death syndrome, and immune system abnormalities. This study aimed to evaluate the effects of in utero exposure to ETS on neuroinflammation in the offspring of pregnant mice challenged or not with lipopolysaccharide (LPS). After the confirmation of mating by the presence of the vaginal plug until offspring birth, pregnant C57BL/6 mice were exposed to either 3R4F cigarettes smoke (Kentucky University) or compressed air, twice a day (1h each), for 21 days. Enhanced glial cell and mixed cell cultures were prepared from 3-day-old mouse pups. After cell maturation, both cells were stimulated with LPS or saline. To inhibit microglia activation, minocycline was added to the mixed cell culture media 24 h before LPS challenge. To verify the influence of in utero exposure to ETS on the development of neuroinflammatory events in adulthood, a different set of 8-week-old animals was submitted to the Autoimmune Experimental Encephalomyelitis (EAE) model. The results indicate that cells from LPS-challenged pups exposed to ETS in utero presented high levels of proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNFα) and decreased cell viability. Such a proinflammatory environment could modulate fetal programming by an increase in microglia and astrocytes miRNA155. This scenario may lead to the more severe EAE observed in pups exposed to ETS in utero.

Environmental Tobacco Smoke During the Early Postnatal Period of Mice Interferes With Brain 18 F-FDG Uptake From Infancy to Early Adulthood - A Longitudinal Study.

Exposure to environmental tobacco smoke (ETS) is associated with high morbidity and mortality, mainly in childhood. Our aim was to evaluate the effects of postnatal ETS exposure in the brain 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) uptake of mice by positron emission tomography (PET) neuroimaging in a longitudinal study. C57BL/6J mice were exposed to ETS that was generated from 3R4F cigarettes from postnatal day 3 (P3) to P14. PET analyses were performed in male and female mice during infancy (P15), adolescence (P35), and adulthood (P65). We observed that ETS exposure decreased 18F-FDG uptake in the whole brain, both left and right hemispheres, and frontal cortex in both male and female infant mice, while female infant mice exposed to ETS showed decreased 18F-FDG uptake in the cerebellum. In addition, all mice showed reduced 18F-FDG uptake in infancy, compared to adulthood in all analyzed VOIs. In adulthood, ETS exposure during the early postnatal period decreased brain 18F-FDG uptake in adult male mice in the cortex, striatum, hippocampus, cingulate cortex, and thalamus when compared to control group. ETS induced an increase in 18F-FDG uptake in adult female mice when compared to control group in the brainstem and cingulate cortex. Moreover, male ETS-exposed animals showed decreased 18F-FDG uptake when compared to female ETS-exposed in the whole brain, brainstem, cortex, left amygdala, striatum, hippocampus, cingulate cortex, basal forebrain and septum, thalamus, hypothalamus, and midbrain. The present study shows that several brain regions are vulnerable to ETS exposure during the early postnatal period and these effects on 18F-FDG uptake are observed even a long time after the last exposure. This study corroborates our previous findings, strengthening the idea that exposure to tobacco smoke in a critical period interferes with brain development of mice from late infancy to early adulthood.

Analysis of the Buccal Bone Plate, Root Inclination and Alveolar Bone Dimensions in the Jawbone. A Descriptive Study Using Cone-Beam Computed Tomography.

OBJECTIVES: This study aims to determine if there are enough buccal alveolar bone thickness to perform an immediate dental implant placement in anterior and posterior maxillary teeth. MATERIAL AND METHODS: A total of 1463 teeth were examined, from 202 cone-beam computed tomography scans with voxel sizes of 0.15 mm. On each tooth, the following measures were determined: the alveolar bone thickness in two locations; the vertical distance between the buccal alveolar crest and cementoenamel junction; the angle between the tooth's long axis and the alveolar bone axial inclination in the sagittal plane. RESULTS: In the most coronal location of maxillary teeth, the thickness of alveolar bone was lower than 0.6 (SD 0.6) mm in 50% of the teeth, and in the middle of the root the bone thickness was, on average, 0.96 (SD 0.6) mm. For the same maxillary teeth, the vertical distance between the buccal alveolar crest and cementoenamel junction and the angulation measured were, on average, 3.6 (SD 1.2) mm and 12.1º (SD 1.4º), respectively. CONCLUSIONS: The present study revealed that in most cases the thickness of buccal alveolar bone was less than 1 mm. Consequently, in such cases, immediate dental implant placement operation is not recommended, or should be combined with bone regeneration techniques.

Mast cells: A key component in the pathogenesis of Neuromyelitis Optica Spectrum Disorder?

Neuromyelitis Optica Spectrum Disorder (NMOSD) is characterized as an autoimmune, inflammatory and demyelinating disease of the Central Nervous System (CNS). Its pathogenesis is due to the presence of anti-aquaporin 4 immunoglobulin G1 antibodies (anti-AQP4IgG), with presence of lymphocytes T Helper 1 and 17 (TH1 and TH17), in addition to previous neuroinflammation. The Mast cell (MC) is a granular cell present in all vascularized tissues, close to vessels, nerves, and meninges. In CNS, MCs are in the area postrema, choroid plexus, thalamus and hypothalamus. MC has ability to transmigrate between the nervous tissue and the lymphoid organs, interacting with the cells of both systems. These cells reach the CNS during development through vessel migration. Most MCs reside on the abluminal side of the vessels, where it can communicate with neurons, glial cells, endothelial cells and the extracellular matrix. Considering the role of MCs in neurodegenerative diseases has been extensively discussed, we hypothesized MCs participate in the pathogenesis of NMOSD. This cell represents an innate and adaptive immune response regulator, capable of faster responses than microglial cells. The study of MCs in NMOSD can help to elucidate the pathogenesis of this disease and guide new research for the treatment of patients in the future. We believe this cell is an important component in the cascade of NMOSD neuroinflammation.

Population effects of heavy metal pollution in wild Algerian mice (Mus spretus).

Heavy metal mining is one of the largest sources of environmental pollution. The analysis of different types of biomarkers in sentinel species living in contaminated areas provides a measure of the degree of the ecological impact of pollution and is thus a valuable tool for human and environmental risk assessments. In previous studies we found that specimens from two populations of the Algerian mice (Mus spretus) living in two abandoned heavy metal mines (Aljustrel and Preguiça, Portugal) had higher body burdens of heavy metals, which led to alterations in enzymatic activities and in haematological, histological and genotoxic parameters, than mice from a nearby reference population. We have now analysed individuals from the same sites at the biometric and genetic levels to get a broader portrayal of the impact of heavy metal pollution on biodiversity, from molecules to populations. Size and shape variations of the mouse mandible were searched by implementing the geometric morphometric method. Population genetic differentiation and diversity parameters (φST estimates; nucleotide and haplotype diversities) were studied using the mitochondrial cytochrome b gene (Cytb) and the control region (CR). The morphometric analyses revealed that animals from the three sites differed significantly in the shape of the mandible, but mandibular shape varied in a more resembling way within individuals of both mine sites, which is highly suggestive for an effect of environmental quality on normal development pathways in Algerian mice. Also, antisymmetry in mandible size and shape was detected in all populations, making these traits not reliable indicators of developmental instability. Overall little genetic differentiation was found among the three populations, although pairwise φST comparisons revealed that the Aljustrel and the Preguiça populations were each differentiated from the other two populations in Cytb and in CR, respectively. Genetic diversity parameters revealed higher genetic diversity for Cytb in the population from Aljustrel, while in the population from Preguiça diversity of the two markers changed in opposite directions, higher genetic diversity in CR and lower in Cytb, compared to the reference population. Demographic changes and increased mutation rates may explain these findings. We show that developmental patterns and genetic composition of wild populations of a small mammal can be affected by chronic heavy metal exposure within a relatively short time. Anthropogenic stress may thus influence the evolutionary path of natural populations, with largely unpredictable ecological costs.

Efeitos da exposição à fumaça do cigarro e suas implicações na neuroinflamação / Effects of exposure to cigarette smoke and its implications on neuroinflammation

O Sistema Nervoso Central (SNC) humano é formado por cerca de 86,1 bilhões de neurônios entre o encéfalo e a medula espinhal. O desenvolvimento pré-natal humano (tempo da concepção ao nascimento) possui cerca de 38 semanas, e é dividido na fase embrionária que corresponde ao período das 8 semanas iniciais da gestação, seguido pela fase fetal. A fase embrionária é o período mais vulnerável à ocorrência de anormalidades congênitas. Por ser um órgão com grande período de desenvolvimento, o SNC está sujeito às alterações genéticas, epigenéticas e ambientais. Durante a fase de implantação do embrião, o DNA é mais vulnerável às influências externas, como à fumaça do cigarro, aumentando o risco de retardo do desenvolvimento fetal, o risco de morte súbita pós-natal e de anormalidades do sistema imune. Neste contexto, o objetivo deste trabalho é avaliar os efeitos da exposição à fumaça do cigarro sobre o processo de neuroinflamação da prole de camundongos C57BL/6 expostos à fumaça do cigarro durante a gestação e desafiados ou não com LPS. Para tanto, camundongos C57BL/6 fêmeas prenhes foram expostas à fumaça do cigarro desde o plug vaginal até o nascimento da prole. No 3º dia de vida, os filhotes foram separados para três linhas de trabalho: 1) in vivo: os animais foram desafiados com LPS pelo período de 4h, seguidos de eutanasia e análises de PCR Array do SNC. 2) in vitro: os encéfalos dissecados foram utilizados para a preparação de cultura mista de glia e da cultura enriquecida com neurônio. Após a maturação celular, as células foram estimuladas com LPS 100 ng/mL e, após 24h, foram realizados ensaios de CBA, citometria de fluxo, PCR, dosagem de NO, avaliação de morte celular e metilação global. 3) Encefalomielite Autoimune Experimental (EAE): após o desmame, os animais foram mantidos em suas caixas moradia por 8 semanas sem nenhum estímulo externo, e então foram imunizados com MOG35-55 para o desenvolvimento da EAE. Nos experimentos in vivo observamos o aumento da transcrição de genes relacionados ao processo inflamatório, como interleucinas e quimiocinas. Em relação aos experimentos in vitro observamos maior crescimento de células astrocitárias (astrogliose), e células da microglia com aumento de moléculas co-estimuladoras (CD80 e CD86) bem como da transcrição e concentração de citocinas pró-inflamatórias e produção de NO. Em cultura enriquecida de neurônio, foi observado aumento na porcentagem de células em apoptose no grupo exposto à fumaça do cigarro desafiados ou não com LPS. O bloqueio da atividade da microglia pela minociclina reverteu a apoptose e diminuiu a produção de NO minimizando a morte celular. Em relação aos experimentos de EAE, os animais expostos à fumaça do cigarro no período gestacional, quando imunizados na vida adulta apresentam aumento no grau da doença bem como maior persistência da mesma quando observado escore clínico, além de acompanhados de um grau maior de infiltrado celular e desmielinização. Desta forma podemos concluir que a exposição à fumaça do cigarro durante o período gestacional leva a uma programação fetal com aumento da resposta neuroinflamatória frente a um estimulo sistêmico, trazendo consequências na vida adulta

The human central nervous system (CNS) is made up of about 86.1 billion neurons between the brain and the spinal cord. The human prenatal development (time from conception to birth) is about 38 weeks, and is divided into the embryonic phase that corresponds to the period of the initial 8 weeks of gestation, followed by the fetal phase. The embryonic stage is the period most vulnerable to the occurrence of congenital abnormalities. Because it is an organ with a long period of development, the CNS is subject to genetic, epigenetic and environmental changes. During the embryo implantation phase, DNA is more vulnerable to external influences such as cigarette smoke, increasing the risk of delay on fetal development, risk of sudden postnatal death, and abnormalities of the immune system. In this context, the aim of this work is to evaluate the effects of exposure to cigarette smoke on the neuroinflammation process of offspring of C57BL/6 mice exposed to cigarette smoke during gestation and challenged or not with LPS. For this, pregnant female C57BL/6 mice were exposed to cigarette smoke from vaginal plug to offspring birth. On the 3rd day of life the offspring were separated into three lines of work: 1) in vivo: the animals were challenged with 1mg/Kg LPS and after 4h they followed to euthanasia; PCR analysis of the CNS was made in this period. 2) in vitro: dissected encephalons were used for the preparation of mixed culture of glia and the culture enriched with neuron. After cell maturation, the cells were stimulated with 100 ng/mL LPS and, after 24 hours, CBA, flow cytometry, PCR, NO assay, cell death and global methylation assays were performed. 3) Experimental Autoimmune Encephalomyelitis (EAE): After weaning, the animals were kept in their housing for 8 weeks without any external stimulus, and then were immunized with MOG35-55 for the development of EAE. In the in vivo experiments we observed increased transcription of genes related to the inflammatory process, such as interleukins and chemokines. In vitro experiments showed higher growth of astrocytes (astrogliosis) and microglia cells with increased stimulatory molecules (CD80 and CD86) as well as the transcription and concentration of proinflammatory cytokines and NO production. In the enriched neuron culture, an increase in the percentage of cells in apoptosis was observed in the group exposed to cigarette smoke challenged or not with LPS. Blocking microglial activity by minocycline reversed apoptosis and decreased NO production by minimizing cell death. The EAE experiments shows that the animals exposed to cigarette smoke in the gestational period, when immunized in adulthood, present an increase in the degree of the disease as well as a greater persistence of the disease; The higher as the clinical score higher is the degree of cellular infiltration and demyelination. In this way we can conclude that the exposure to cigarette smoke during the gestational period leads to a fetal programming with increased neuroinflammatory response to a systemic stimulus and that this is able to last until the adult stage

Potential of Trichogramma achaeae (Hymenoptera: Trichogrammatidae) in Biological Control of Tuta absoluta (Lepidoptera: Gelechiidae) in Azorean Greenhouse Tomato Crops.

Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) is an important pest of tomato crops. It is native to South America and has rapidly extended its range into Mediterranean countries. The parasitoid Trichogramma achaeae Nagaraja and Nagarkatti (Hymenoptera: Trichogrammatidae) has been recommended as a possible biological control agent of this invasive pest. The pest and parasitoid were accidentally introduced into the Azores Islands and became well-established owing to the climate conditions of the region. During an undertaken survey to determine the presence of natural parasitism, 2.5% of the T. absoluta eggs were found to be parasitized by Tr. achaeae, and no other egg parasitoid was observed. Other Trichogramma species, Trichogramma cordubensis Vargas & Cabello, was also selected to test, along with Tr. achaeae, against T. absoluta on caged tomato plants (microhabitats), and the effectiveness of these parasitoids in limiting the T. absoluta populations was assessed. The results revealed that Tr. achaeae had a high parasitism and emergence rate (29.6% and 65.9%, respectively), relative to those rates observed for T. cordubensis (6.1% and 39.3%, respectively). Greenhouse assays were also carried out between May and July in 2013 and 2014 on commercially produced tomatoes with the aim of evaluating the potential of Tr. achaeae mass releases for the control of T. absoluta under these conditions. In the second year, we observed a reduction in the mean number of leaf mines and of eggs, larvae, and pupae of T. absoluta per leaflet, and an increase in the Tr. achaeae parasitism rate.

Masseter muscle measurement performed by ultrasound: a systematic review.

The aim of this study was to systematically review the existing scientific literature and evidence about (a) the validation of masseter muscle ultrasonography for accurate assessment of muscle thickness and (b) the reproducibility of masseter muscle thickness measures. An electronic literature search was conducted using determined keywords on specific databases. Preliminary search revealed 298 articles listed in Medline, Scopus and Web of Science. 60 duplicates were rejected, leaving 238 articles for review. After reading titles and abstracts, 31 articles remained. 23 articles were assessed for eligibility. These articles were categorized as follows: thickness, cross-section, volume and the length of the masseter muscle measured by ultrasonography. It is possible to verify the thickness of the masseter muscle in males and females in relaxation (10-15 and 9-13 mm, respectively) and contraction (14-19 and 12-15 mm, respectively). A similar tendency can also be evidenced in other measurements. Many studies evaluate masseter muscle dimensions to relate it to cephalometric analysis as such to evaluate morphological variations. It can be concluded that ultrasound is a reliable clinical tool for masseter muscle measurements, yet there is a need for standardization of methods and parameters to be recorded.

Sella landmark variability and its effect on the Angles SNA and SNB: a comparative study / Variabilidade do ponto Sela e seu efeito em ângulos SNA e SNB: um estudo comparativo

ABSTRACT Objective: To determine intra- and inter-observer precision in Sella (S), Nasion (N), point A and B identification. Additionally, to determine how it can interfere with angular measurements of SNA and SNB by orthodontists and dentomaxillofacial radiologists. Methods: Twenty digital lateral cephalometric radiographs were evaluated by five orthodontists and five dentomaxillofacial radiologists. Results: Differences in linear and angular measuremts were assessed. Intra- and inter-observer agreement was evaluated. Intra- and inter-observer reproducibility of the horizontal and vertical components of the S landmark identification (ICC: 0.75/0.90). Orthodontists tended to produce larger SNA (-0.18º), while SNB angle had a tendency to be smaller (0.55º). In general, SNA angle was smaller (DMFRs: -0.308º and orthodontists: -0.092º), and SNB presented with larger values (DMFR: 0.078º and orthodontists: -0.074º). Conclusion: Identification of the Sella landmark revealed a better agreement amongst dentomaxillofacial radiologists. Orthodontists, however, showed a larger variability in S identification and, consequently, the SNA and SNB angles drifted significantly.

RESUMO Objetivo: Determinar a precisão intra e inter-observador na identificação dos pontos Sella (S), Násio (N), A e B. Também, verificar como a identificação dos pontos pode interferir nas medições angulares de SNA e SNB por ortodontistas e radiologistas odontológicos. Métodos: Vinte telerradiografias laterais digitais foram avaliadas por cinco ortodontistas e cinco radiologistas odontológicos. Diferenças de medidas lineares e angulares foram avaliadas. Resultados: Concordância intra e inter-observador foi avaliada e a reprodutibilidade intra e inter-observador dos componentes horizontais e verticais da identificação S marco (ICC: 0,75 / 0,90). Ortodontistas tenderam a produzir maior valor para SNA (-0.18º), enquanto que para o ângulo SNB houve tendência a dimininuição do valor (0.55º). Em geral, os valores obtidos para o ângulo SNA foram menores (radiologistas: -0.308º e ortodontistas: -0.092º) e SNB apresentados com valores maiores (radiologistas: -0.074º: 0.078º e ortodontistas). Concordância intra e inter-observador foi avaliada e a reprodutibilidade intra e inter-observador dos componentes horizontais e verticais da identificação S marco (ICC: 0,75 / 0,90). Ortodontistas tenderam a produzir maior valor para SNA (-0.18º), enquanto que para o ângulo SNB houve tendência a dimininuição do valor (0.55º). Em geral, os valores obtidos para o ângulo SNA foram menores (radiologistas: -0.308º e ortodontistas: -0.092º) e SNB apresentados com valores maiores (radiologistas: -0.074º: 0.078º e ortodontistas). Conclusão: A identificação do ponto Sella revelou uma melhor concordância entre os radiologistas odontológicos. Ortodontistas, no entanto, mostraram uma maior variabilidade na identificação do ponto S e, consequentemente, os ângulos SNA e SNB variaram significativamente. A identificação do ponto Sella revelou uma melhor concordância entre os radiologistas odontológicos. Ortodontistas, no entanto, mostraram uma maior variabilidade na identificação do ponto S e, consequentemente, os ângulos SNA e SNB variaram significativamente.

Exposure of Neonatal Mice to Tobacco Smoke Disturbs Synaptic Proteins and Spatial Learning and Memory from Late Infancy to Early Adulthood.

Exposure to environmental tobacco smoke (ETS) in the early postnatal period has been associated with several diseases; however, little is known about the brain effects of ETS exposure during this critical developmental period or the long-term consequences of this exposure. This study investigated the effects of the early postnatal ETS exposure on both reference and working memory, synaptic proteins and BDNF from late infancy to early adulthood (P3-P73). BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes (0.73 mg of nicotine/cigarette) from P3 to P14. Spatial reference and working memory were evaluated in the Morris water maze during infancy (P20-P29), adolescence (P37-P42) and adulthood (P67-P72). Synapsin, synaptophysin, PSD95 and brain-derived neurotrophic factor (BDNF) were assessed at P15, P35 and P65 by immunohistochemistry and immunoblotting. Mice that were exposed to ETS during the early postnatal period showed poorer performance in the spatial reference memory task. Specifically, the ETS-exposed mice exhibited a significantly reduced time and distance traveled in the target quadrant and in the platform location area than the controls at all ages evaluated. In the spatial working memory task, ETS disrupted the maintenance but not the acquisition of the critical spatial information in both infancy and adolescence. ETS also induced changes in synaptic components, including decreases in synapsin, synaptophysin, PSD95 and BDNF levels in the hippocampus. Exposure to ETS in the early postnatal period disrupts both spatial reference and working memory; these results may be related to changes in synaptogenesis in the hippocampus. Importantly, most of these effects were not reversed even after a long exposure-free period.

Influence of lateral cephalometric radiography in orthodontic diagnosis and treatment planning.

OBJECTIVE: To evaluate the impact of additional lateral cephalometric radiography in orthodontic diagnosis and treatment planning. MATERIALS AND METHODS: Forty-three patients seeking orthodontic treatment, and for whom pretreatment diagnostic records were available, were randomly selected. Ten qualified orthodontists were involved in this study. The patients' records included three photographs of the angle trimmed dental casts, digital lateral cephalometric and panoramic radiographs, and standard clinical photographs comprising seven intra- and four extraoral pictures. Records were evaluated in two sessions. At the first session, orthodontists evaluated records without lateral cephalometric radiography (LCR). In the second session, the same information was presented, but with LCR. Between the two sessions the order in which the cases were presented was altered to avoid bias. RESULTS: The percentage of agreement between sessions was lower for diagnosis than for treatment planning. Concerning skeletal classification, the least experienced orthodontist was the least consistent (28%), while the more experienced orthodontist was the more reliable (67%). In terms of treatment modalities, in general there was an agreement of 64%. The most frequent modifications in treatment modalities were seen in Class II malocclusion patients. CONCLUSIONS: The results of our study suggest that the majority of Portuguese orthodontists judge that LCR is important to producing a treatment plan. Despite that, it does not seem to have an influence on orthodontic treatment planning.

Cephalometric landmark variability among orthodontists and dentomaxillofacial radiologists: a comparative study.

PURPOSE: The aim this study was to compare the accuracy of orthodontists and dentomaxillofacial radiologists in identifying 17 commonly used cephalometric landmarks, and to determine the extent of variability associated with each of those landmarks. MATERIALS AND METHODS: Twenty digital lateral cephalometric radiographs were evaluated by two groups of dental specialists, and 17 cephalometric landmarks were identified. The x and y coordinates of each landmark were recorded. The mean value for each landmark was considered the best estimate and used as the standard. Variation in measurements of the distance between landmarks and measurements of the angles associated with certain landmarks was also assessed by a subset of two observers, and intraobserver and interobserver agreement were evaluated. RESULTS: Intraclass correlation coefficients were excellent for intraobserver agreement, but only good for interobserver agreement. The least reliable landmark for orthodontists was the gnathion (Gn) point (standard deviation [SD], 5.92 mm), while the orbitale (Or) was the least reliable landmark (SD, 4.41 mm) for dentomaxillofacial radiologists. Furthermore, the condylion (Co)-Gn plane was the least consistent (SD, 4.43 mm). CONCLUSION: We established that some landmarks were not as reproducible as others, both horizontally and vertically. The most consistently identified landmark in both groups was the lower incisor border, while the least reliable points were Co, Gn, Or, and the anterior nasal spine. Overall, a lower level of reproducibility in the identification of cephalometric landmarks was observed among orthodontists.