Fast plasma sintering delivers functional graded materials components with macroporous structures and osseointegration properties.

We explored the osseointegration potential of two macroporous titanium surfaces obtained using fast plasma sintering (FPS): Ti macroporous structures with 400-600 µmØ pores (TiMac400) and 850-1000 µmØ pores (TiMac850). They were compared against two surfaces currently in clinical use: Ti-Growth® and air plasma spray (Ti-Y367). Each surface was tested, once placed over a Ti-alloy and once onto a CoCr bulk substrate. Implants were placed in medial femoral condyles in 24 sheep. Samples were explanted at four and eight weeks after surgery. Push-out loads were measured using a material-testing system. Bone contact and ingrowth were assessed by histomorphometry and SEM and EDX analyses. Histology showed early osseointegration for all the surfaces tested. At 8 weeks, TiMac400, TiMac850 and Ti-Growth® showed deep bone ingrowth and extended colonisation with newly formed bone. The mechanical push-out force was equal in all tested surfaces. Plasma spray surfaces showed greater bone-implant contact and higher level of pores colonisation with new bone than FPS produced surfaces. However, the void pore area in FPS specimens was significantly higher, yet the FPS porous surfaces allowed a deeper osseointegration of bone to implant. FPS manufactured specimens showed similar osseointegration potential to the plasma spray surfaces for orthopaedic implants. FPS is a useful technology for manufacturing macroporous titanium surfaces. Furthermore, its capability to combine two implantable materials, using bulk CoCr with macroporous titanium surfaces, could be of interest as it enables designers to conceive and manufacture innovative components. FPS delivers functional graded materials components with macroporous structures optimised for osseointegration.

Seasonal dynamics in community structure, abundance, body size and sex ratio in two species of Neotropical annual fishes.

Seven ephemeral pools on the coastal plain of southern Brazil were found to be inhabited by three annual and 22 non-annual fish species. Two common annual species (Austrolebias minuano and Cynopoecilus fulgens) exhibited clear seasonal dynamics, with the appearance of young fishes in the austral autumn (May to June) and a decline in abundance over the seasonal cycle. The third annual species, Austrolebias wolterstorffii, was rare. No seasonal dynamics were observed in non-annual fishes. The relative abundance of non-annual fishes compared with annual fishes increased over the seasonal cycle, but they coexisted widely. The size structure of annual fishes suggested the presence of a single age cohort in most pools though a second age cohort was registered in one pool in August, coinciding with a large flooding. Strong sexual dimorphism in body size was found in C. fulgens throughout the seasonal cycle, while no sexual dimorphism in body size was found in A. minuano. Female-biased sex ratios were recorded in both common annual fish species in the last three sampling dates (in spring), but not during the first two sampling dates (in winter). The natural lifespan of annual fishes was <8 months. Annual fishes disappeared before habitat desiccation in half of the pools, while non-annual fishes were still present.

Description of a New Phlebotomine Species of the Brazilian Cerrado from Sandstone Caves in Tocantins State, Brazil: Lutzomyia (Lutzomyia) elizabethrangelae sp. nov. (Diptera: Psychodidae).

The sand fly Lutzomyia (Lutzomyia) elizabethrangelae sp. nov. is described and illustrated based on the morphological characters of male and female specimens captured in sandstone caves in the municipality of Palmeirópolis, in the southern region of Tocantins state. The samples were collected as part of an entomological vector-monitoring project during the construction of the Peixe Angical Hydroelectric Plant. Based on the morphological characters of the new species, we believe this species can be included in the subgenus Lutzomyia. This species is closely related to two others, Lutzomyia forattinii Galati et al. 1985 and Lutzomyia almerioi Galati and Nunes 1999. The new species can be distinguished from Lutzomyia forattinii and Lutzomyia almerioi by the morphological characteristics of the male genitalia and the female cibarium.

Smokers and risk of hospital death by COVID calculated with SAVANA's natural language processing in the Castilla-La Mancha area.

INTRODUCTION: During the COVID pandemic, it was speculated that patients with the virus who were smoking-related might have a lower likelihood of disease exacerbation or death. To assess whether there is an association between smoking and risk of in-hospital mortality, SAVANA's big data and Natural Language Processing (NLP) technology is used. METHOD: A retrospective, observational, non-interventional cohort study was conducted based on real-life data extracted from medical records throughout Castilla La Mancha using Natural Language Processing and Artificial Intelligence techniques developed by SAVANA. The study covered the entire population of this region with Electronic Medical Records in SESCAM presenting with a diagnosis of COVID from March 1, 2020 to February 28, 2021. RESULTS: Smokers had a significantly higher percentage of cardiovascular risk factors (hypertension, dyslipidemia and diabetes), COPD, asthma, IDP, IC, CVD, PTE, cancer in general and lung cancer in particular, bronchiectasis, heart failure and a history of pneumonia (p < 0.0001).Former smokers, current smokers and non-smokers have a significant age difference. As for in-hospital deaths, they were more frequent in the case of ex-smokers, followed by smokers and then non-smokers (p < 0.0001). CONCLUSION: There is an increased risk of dying in hospital in SARS-COV2-infected patients who are active smokers or have smoked in the past.

Successful factorial design for the optimization of methylprednisolone encapsulation in biodegradable nanoparticles.

Due to their crystalline nature, the encapsulation of hydrophobic corticosteroids within polymeric nanoparticles by o/w solvent evaporation method is often difficult to achieve. The aim of this study was to evaluate the effect of both process and formulation parameters on the encapsulation of a model corticosteroid: methylprednisolone (MP). For this purpose, a 3(2)factorial design was performed evaluating the effects of the concentration of emulsifiers and sonication time on the manufactured nanoparticles, followed by a multiresponse optimization. The study also included the evaluation of other parameters such as the type of organic solvent used, polymer characteristics and the initial mass of drug. The optimal nanoparticle formulation using 0.25% (w/v) of emulsifying agent (Polyvinyl-alcohol, PVA) and 5 min of sonication was then characterized. The highest encapsulation was obtained with an organic phase consisting of acetone: dichloromethane (1:1), polyD,L-lactide-co-glycolide (PLGA) 50:50 as polymer and an initial mass of 6.6 mg of methylprednisolone. Nanoparticles size and ζ potential of optimized formulation were respectively around 230 nm and -14 mV. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) demonstrated that the drug was molecularly dispersed within the nanoparticles. Release study showed that MP-loaded nanoparticles sustained drug release for up to 120 h. This study reflects the importance of factorial design to optimize the manufacture of nanoparticles encapsulating hydrophobic drugs.

A preliminary approach to embryonic development of Austrolebias wolterstorffi, an endangered neotropical annual fish species.

Annual fish live exclusively in temporary wetlands and are among the shortest-lived vertebrates in the world. These fish persist in these habitats due to drought-resistant eggs, that which, through diapauses are able to detect stimuli from the environment to start the development processes. They are also able to direct their embryonic development in different trajectories with different development times. Our objective in this paper was to describe the different stages of embryonic development of Austrolebias wolterstorffi, a critically endangered annual fish. A total of 27 stages of embryonic development were identified for the two observed developmental pathways (direct and diapause 2). Of these 27 developmental stages observed, 24 were identical between the two types of trajectories and three different. A total of 90% of the embryos that completed their development proceeded normally, without pauses. One embryo had a different development from the others, entering diapause 2, with a pause in development for 48 h. Although the embryonic development of A. wolterstorffi is similar to that of other Neotropical annual fish species, the diapause 2 occurs when the embryo has a large body size and a well-developed brain, indicating that the lack of embryonic information of the genus Austrolebias may hide characteristics still undescribed or even different survival strategies than what has been observed for other annual fish.

Effects of ortho-eugenol on anxiety, working memory and oxidative stress in mice.

Ortho-eugenol is a synthetic derivative from eugenol, the major compound of clove essential oil, which has demonstrated antidepressant and antinociceptive effects in pioneering studies. Additionally, its effects appear to be dependent on the noradrenergic and dopaminergic systems. Depression and anxiety disorders are known to share a great overlap in their pathophysiology, and many drugs are effective in the treatment of both diseases. Furthermore, high levels of anxiety are related to working memory deficits and increased oxidative stress. Thus, in this study we investigated the effects of acute treatment of ortho-eugenol, at 50, 75 and 100 mg/kg, on anxiety, working memory and oxidative stress in male Swiss mice. Our results show that the 100 mg/kg dose increased the number of head-dips and reduced the latency in the hole-board test. The 50 mg/kg dose reduced malondialdehyde levels in the prefrontal cortex and the number of Y-maze entries compared to the MK-801-induced hyperlocomotion group. All doses reduced nitrite levels in the hippocampus. It was also possible to assess a statistical correlation between the reduction of oxidative stress and hyperlocomotion after the administration of ortho-eugenol. However, acute treatment was not able to prevent working memory deficits. Therefore, the present study shows that ortho-eugenol has an anxiolytic and antioxidant effect, and was able to prevent substance-induced hyperlocomotion. Our results contribute to the elucidation of the pharmacological profile of ortho-eugenol, as well as to direct further studies that seek to investigate its possible clinical applications.

Increased STAT3 Activation in Periodontitis Drives Inflammatory Bone Loss.

Periodontitis is one of the most prevalent human inflammatory diseases. It is characterized by periodontal tissue destruction, progressively driven by the host response. In this regard, cytokines associated with tissue destruction, such as interleukin (IL)-6 and IL-23, use a common signaling pathway mediated by STAT3. This transcription factor is also needed for IL-17A production, a key mediator in periodontitis pathogenesis. Although several studies have reported increased activation of STAT3 in experimental periodontitis, a detailed characterization of STAT3 activation in human gingival tissues and its involvement in alveolar bone loss has yet to be explored. Using a cross-sectional study design, we detected increased proportions of pSTAT3-positive cells during periodontitis compared with health, particularly in epithelial cells and T cells. Other cell types of hematopoietic and nonhematopoietic origin also display STAT3 activation in gingival tissues. We detected increased STAT3 phosphorylation and expression of STAT3-related genes during experimental periodontitis. Next, we evaluated the role of STAT3 in alveolar bone destruction using a mouse model of STAT3 loss of function (mut-Stat3 mice). Compared with controls, mut-Stat3 mice had reduced alveolar bone loss following ligature-induced periodontitis. We also evaluated pharmacologic inhibition of STAT3 in ligature-induced periodontitis. Like mut-Stat3 mice, mice treated with STAT3 small-molecule inhibitor had reduced bone loss compared with controls. Our results demonstrate that STAT3 activation is increased in epithelial and T cells during periodontitis and indicate a pathogenic role of STAT3 in inflammatory alveolar bone loss.

The impact of maternal post-partum depression on the language development of children at 12 months.

BACKGROUND: Language is one of the most important acquisitions made during childhood. Before verbal language, a child develops a range of skills and behaviours that allow the child to acquire all communication skills. Factors such as environmental factors, socio-economic status and interaction with parents can affect the acquisition of vocabulary in children. Post-partum depression can negatively affect the first interactions with the child and, consequently, the emotional, social and cognitive development of the child. OBJECTIVE: To analyse the effect of the duration of the mother's depression on the language development of children at 12 months old. METHODS: This was a longitudinal study. The participants of this study were mothers who had received prenatal care from the Brazilian National System of Public Health in Pelotas city, State of Rio Grande do Sul, Brazil. The mothers were interviewed at two different time points: from 30 to 90 days after delivery and at 12 months after delivery; the children were also evaluated at this later time point. To diagnose maternal depression, we used the Mini International Neuropsychiatric Interview, and to assess child development, we used the language scale of the Bayley Scales of Infant Development III. RESULTS: We followed 296 dyads. Maternal depression at both time points (post partum and at 12 months) was significantly associated with the language development of infants at 12 months of age. This impact was accentuated when related to the duration of the disorder. Older women and women with more than two children were more likely to have children with poorer language development, while women who were the primary caregiver had children with higher scores on the language test. CONCLUSION: The findings indicate that maternal age, parity, primary caregiver status and duration of post-partum depression are associated with the language development of the child.

Valuation of consumption and sale of forest goods from a Central American rain forest

Researchers recognize that society needs accurate and comprehensive estimates of the economic value of rain forests to assess conservation and management options. Valuation of forests can help us to decide whether to implement policies that reconcile the value different groups attach to forests. Here we have measured the value of the rain forest to local populations by monitoring the foods, construction and craft materials, and medicines consumed or sold from the forest by 32 Indian households in two villages in Honduras over 2.5 years. We have directly measured the detailed, comprehensive consumption patterns of rain forest products by an indigenous population and the value of that consumption in local markets. The combined value of consumption and sale of forest goods ranged from US$17.79 to US$23.72 per hectare per year, at the lower end of previous estimates (between US$49 and US$1,089 (mean US$347) per hectare per year). Although outsiders value the rain forest for its high-use and non-use values, local people receive a small share of the total value. Unless rural people are paid for the non-local values of rain forests, they may be easily persuaded to deforest.

Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients.

Several cellular and molecular alterations have been described in skeletal and respiratory muscles of patients with chronic obstructive pulmonary disease (COPD), but information on potential abnormalities of mitochondrial function is scarce. The aim of the present study was to investigate mitochondrial function in the vastus lateralis (VL) and external intercostalis (EI) of COPD patients. Biopsies from VL and EI were obtained during surgery for lung cancer in 13 patients with mild to moderate COPD (age 68+/-6 yrs, forced expiratory volume in one second (FEV(1)) 66+/-15% predicted) and 19 control subjects (age 67+/-9 yrs, FEV(1) 95+/-18% pred). State 3 and 4 mitochondrial oxygen consumption (V'(O(2),m)), ATP synthesis, citrate synthase, cytochrome oxidase (COX) and complex I-III activities, as well as reactive oxygen species (ROS) production, were determined. In COPD patients, in both muscles, COX activity (VL: COPD 3.0+/-0.8 versus control 2.0+/-0.8; EI: 3.7+/-1.6 versus 2.4+/-0.9 micromol min(-1) mg(-1)) and ROS production (VL: 1,643+/-290 versus 1,285+/-468; EI: 1,033+/-210 versus 848+/-288 arbitrary units) were increased, whereas state 3 V'(O(2),m) was reduced (VL: 2.9+/-0.3 versus 3.6+/-0.4; EI: 3.6+/-0.3 versus 4.1+/-0.4 mmol min(-1) kg(-1)). Skeletal muscle mitochondria of patients with chronic obstructive pulmonary disease show electron transport chain blockade and excessive production of reactive oxygen species. The concurrent involvement of both vastus lateralis and external intercostalis suggests a systemic (rather than a local) mechanism(s) already occurring in relatively early stages (Global Initiative for Chronic Obstructive Lung Disease stage II) of the disease.

Influence of helminth infections on childhood nutritional status in lowland Bolivia.

Infectious disease, such as diarrheal disease, respiratory infections, and parasitic infections, are an important source of nutritional and energetic stress in many populations. Inspired by the research and methodological innovations of A. Roberto Frisancho, this work considers the impact of childhood environment and local disease ecology on child health and nutritional patterns among an indigenous group in lowland Bolivia. Specifically, we examine the association between soil-transmitted helminth infection, especially hookworm species, and anthropometric markers of short- and long-term nutritional status. Fecal samples, anthropometric dimensions, and health interviews were collected for 92 children ranging in age from 2.0 to 10.9 years. Microscopic examination revealed high levels of parasitic infection, with 76% of children positive for hookworm species infections (77% of girls and 74% of boys). Less common infections included Ascaris lumbricoides, Trichurius trichiura, and Strongyloides stercoralis with only 15% of children positive for multiple-species infections. After adjusting for sex and age, no statistically significant associations were observed between helminth infections and the frequency of reported illness or anthropometric measures of nutritional status. These data demonstrate the difficulty of assessing nutritional impacts of endemic infections.

Pressure and force on the canine neck when exercised using a collar and leash.

The aim of this study was to assess the pressure and force applied to the canine neck at walk when using collars of different material. Three different collars of equal size but different construction were used. A double-layer polyester and nylon weave (DN), a single layer nylon weave (SN), and a single layer canvas (SC). Eight dogs wore all three types of collar and were led in a randomized order through a course containing straight, clockwise and counterclockwise sections. Force and pressure were measured and recorded using a TekscanⓇ F-Scan In-shoe system and analyzed using SPSS statistical software. Peak force and contact pressure were significantly higher under DN collar when compared with the others (p < 0.0005 and p = 0.001, respectively). Whilst differences in mean force were not observed between collars, there were significant differences depending on the direction of travel of the dog (p < 0.0005), being highest in a counter-clockwise direction, and lowest in a straight line. Peak contact pressure was not significantly different in any condition. Results suggest that collar construction material will alter contact pressures and peak force exerted on the neck, and that a double layer nylon weave collar with ethylene-vinyl acetate cushioning has a higher contact pressure than either a single layer nylon or canvas construction, which may be contrary to an owners expectations when purchasing a collar. Furthermore, forces will vary depending on the direction of travel in relation to the handler.

Antennal Morphology and Localization of a Pheromone-Binding Protein of Lobesia botrana (Denis & Schiffermüller) (Lepidoptera: Tortricidae).

In the sensory system of insects, olfactory sensilla constitute important functional elements for discriminating odors. Therefore, we used light microscopy and scanning electron microscopy to investigate the morphology and distribution of sensilla in the antennae of Lobesia botrana (Denis & Schiffermüller). In addition, we studied the expression of the gene encoding for pheromone-binding protein 1 (LbotPBP1) by in situ hybridization. Lobesia botrana antennae are filiform and are subdivided into three segments: scape, pedicel, and flagellum. The number of flagellum and their overall length were significantly higher and longer in males than in females. Six morphological types of sensilla (trichodea, chaetica, coeloconica, auricillica, basiconica, and styloconica) were identified on the antennae of both sexes. Trichodea sensilla were the most abundant on the antennae of L. botrana, and three subtypes, discerned by their lengths, were observed. However, sensilla trichodea subtype III was only present in male antennae. Moreover, LbotPBP1 expression was restricted to this type of sensilla, thus confirming its olfactory role, specifically under the context of sexual pheromone perception.

Steroid binding sites in liver membranes: interplay between glucocorticoids, sex steroids, and pituitary hormones.

Steroid hormones activate target cells through specific receptors that discriminate among ligands based upon recognition of distinct structural features. For most known steroids, membrane and nuclear receptors co-exist in many target cells. However, while the structure of the nuclear receptors and their function as transcriptional activators of specific target genes is generally well understood, the identity of the membrane receptors remains elusive. Using pharmacological and biochemical approaches, we are beginning to characterize receptors for glucocorticoids and anabolic-androgenic steroids in male rat liver membranes. Male rat liver endoplasmic reticulum contains two steroid binding sites which are functionally related and associated with a 90-134 kDa oligomeric protein: (1) the low-affinity glucocorticoid binding site (LAGS), composed at least in part of two peptides (37 and 53 kDa) that bind glucocorticoids and (2) the stanozolol binding protein (STBP), composed at least in part of three peptides (22, 31, and 55 kDa) that bind the synthetic androgen stanozolol. These steroid binding proteins have many properties different from those of classical nuclear receptors, with the salient differences being a failure to recognize "classical" ligands for nuclear receptors together with marked differences in biochemical properties and physiological regulation. The mechanism of interaction of glucocorticoids with the LAGS can be clearly distinguished from that with STBP. Moreover, STBP shows an extremely narrow pharmacological profile, being selective for ST and its analog, danazol, among more than 100 steroids and non-steroidal compounds that were assayed, including those that are able to displace glucocorticoids from the LAGS. The level of LAGS activity undergoes dramatic variations following changes from the physiological serum levels of thyroid hormones, glucocorticoids, GH, vitamin A, and E2. However, neither thyroid hormones nor GH have a critical role on STBP activity. The STBP is functionally related to LAGS. We have suggested a novel mechanism for STBP whereby membrane-associated glucocorticoid binding activity is targeted by stanozolol (and 16beta-hydroxylated stanozolol): stanozolol modulates glucocorticoid activity in the liver through negative allosteric modulation of the LAGS resulting in an effective increase in classical GR-signaling by increasing glucocorticoid availability to the cytosolic GR.

Evaluating average bioequivalence using methods for high variability drugs: a case study.

The purpose of this study was to determine if different methods for average bioequivalence in high variability drugs coincide or not in their conclusions when applied to the same dataset, and to discuss the method validity and reliability of the conclusions. Different approaches for the evaluation of average bioequivalence were applied to the results of a bioavailability trial on the diuretic drug Furosemide. These methods included widening the bioequivalence limits according to regulatory recommendations, scaling the limits and scaling the bioequivalence statistic, jointly with evaluating alternative bioavailability measures. The methods to establish the bioequivalence limits were also combined with some alternative methods to construct confidence intervals. The decision on bioequivalence depends much more on the bioavailability measures than on the statistical approach. The reliability of the final decision lies mainly in the interpretation of these measures and on the special characteristics of each drug.

Rain, temperature, and child-adolescent height among Native Amazonians in Bolivia.

BACKGROUND: Global climate change and recent studies on early-life origins of well-being suggest that climate events early in life might affect health later in life. AIM: The study tested hypotheses about the association between the level and variability of rain and temperature early in life on the height of children and adolescents in a foraging-farming society of native Amazonians in Bolivia (Tsimane'). SUBJECT AND METHODS: Measurements were taken for 525 children aged 2-12 and 218 adolescents aged 13-23 in 13 villages in 2005. Log of standing height was regressed on mean annual level and mean intra-annual monthly coefficient of variation (CV) of rain and mean annual level of temperature during gestation, birth year, and ages 2-4. Controls include age, quinquennium and season of birth, parent's attributes, and dummy variables for surveyors and villages. RESULTS: Climate variables were only related with the height of boys age 2-12. The level and CV of rain during birth year and the CV of rain and level of temperature during ages 2-4 were associated with taller stature. There were no secular changes in temperature (1973-2005) or rain (1943-2005). CONCLUSION: The height of young females and males is well protected from climate events, but protection works less well for boys ages 2-12.

Comparison of aquatic macrophyte community structure between natural wetlands and rice fields with different cultivation ages.

Recent studies indicate that rice fields contribute to the conservation of aquatic plants, however, repeated cultivation can reduce the species diversity harbored by rice fields. Repeated tillage, agrochemical application and environmental homogeneity can reduce plant diversity and select for species more tolerant to disturbance. Our hypotheses were: 1) macrophyte richness and biomass decrease with increased rice crop age; and 2) macrophyte species of rice fields are a subsample of natural wetlands and species loss will increase with crop age. We investigated three rice fields of each different ages (old, intermediate and new ones) and three natural intermittent wetlands for this study. Each area was sampled four times throughout the rice cultivation cycle (off-season, initial growth, final growth and post-harvest). Our results showed that the mean macrophyte richness and biomass were similar between rice fields of different ages and lower than that of natural wetlands. Although species composition in the different-aged rice fields was not markedly different, there was nestedness in the rice fields as age increased. In this study, we verified that macrophyte richness and biomass in rice fields was lower than natural wetlands and the species composition was different among wetland types (rice fields and natural wetlands), however our hypothesis that species richness and biomass will decrease with crop age was not confirmed. All rice crops had similar macrophyte assemblage structure (richness, biomass and species composition). However, the another hypothesis tested was confirmed, macrophyte assemblage of rice fields is a subset of natural wetlands and as, the age of a rice field increases, the species that occur in older rice field are subsets of species that occur in younger ones.

Description of Evandromyia piperiformis sp. nov. (Diptera: Psychodidae).

Brazil presents great sand fly species diversity, with new species constantly being described, as new areas are surveyed to monitor sand flies. In captures undertaken in Porto Velho, Rondônia state-Brazil, a new species, Evandromyia (Aldamyia) piperiformissp. nov. (Godoy, Cunha & Galati 2017), was found and is here described. Both sexes of this new species may be distinguished from those of the Aldamyia subgenus through morphometric and morphological characters. Further, we present an identification key for the subgenus Aldamyia.