The Absence of Caspase-8 in the Dopaminergic System Leads to Mild Autism-like Behavior.

In the last decade, new non-apoptotic roles have been ascribed to apoptotic caspases. This family of proteins plays an important role in the sculpting of the brain in the early stages of development by eliminating excessive and nonfunctional synapses and extra cells. Consequently, impairments in this process can underlie many neurological and mental illnesses. This view is particularly relevant to dopamine because it plays a pleiotropic role in motor control, motivation, and reward processing. In this study, we analyze the effects of the elimination of caspase-8 (CASP8) on the development of catecholaminergic neurons using neurochemical, ultrastructural, and behavioral tests. To do this, we selectively delete the CASP8 gene in cells that express tyrosine hydroxylase with the help of recombination through the Cre-loxP system. Our results show that the number of dopaminergic neurons increases in the substantia nigra. In the striatum, the basal extracellular level of dopamine and potassium-evoked dopamine release decreased significantly in mice lacking CASP8, clearly showing the low dopamine functioning in tissues innervated by this neurotransmitter. This view is supported by electron microscopy analysis of striatal synapses. Interestingly, behavioral analysis demonstrates that mice lacking CASP8 show changes reminiscent of autism spectrum disorders (ASD). Our research reactivates the possible role of dopamine transmission in the pathogenesis of ASD and provides a mild model of autism.

Intravaginal progesterone device (1. 9g) and estradiol benzoate for follicular control in the mare during spring and summer / [Implante intravaginal de progesterona (1, 9g) e benzoato de estradiol no controle folicular de éguas durante a primavera e o verão]

The objective of this study was to evaluate follicular growth and ovulatory rates in mares treated with an intravaginal progesterone device (P4) during the 10-day period, associated with the use of estradiol benzoate (EB). The results were compared during the transition period (ET) in the spring and the breeding season in the summer (ER). The variables were submitted to ANOVA (Tukey's test), considering P<0.05. No ovulation occurred during the permanence of the P4 implant in both experimental periods. The ovulatory rate in the ER was 100% (n = 8) and in the ET 62.5% (n = 5; P = 0.0547). Significant differences were observed (<0.001), in both periods, comparing follicular growth rates during the permanence of P4 device (ER: 1.33 ± 0.89mm/d; ET: 1.00 ± 0.81mm/d) to the period without P4 (ER: 3.63 ± 1.33 mm/d; ET: 3.31 ± 1.66 mm/d). The present study demonstrated applicability and efficiency of a hormonal protocol using P4 intravaginal device and EB for follicular control in mares, both during ET and ER.

O objetivo deste trabalho foi avaliar a taxa de crescimento folicular e a taxa ovulatória em éguas tratadas com dispositivo intravaginal de progesterona (P4) durante o período de 10 dias, associado à utilização de benzoato de estradiol (BE). Os resultados foram comparados durante o período de transição (ET) da primavera com a época de reprodução no verão (ER). As variáveis foram submetidas à ANOVA (teste de Tukey), considerando-se P<0,05. Nenhuma ovulação ocorreu durante a permanência do dispositivo de P4 em ambos os períodos experimentais. A taxa ovulatória na ER foi de 100% (n = 8) e na ET, de 62,5% (n=5; P=0,0547). Diferença significativas (<0,001) foram observadas, em ambos os períodos experimentais, comparando as taxas de crescimento folicular durante a permanência da P4 (ER: 1,33 ± 0,89mm/d; ET: 1,00 ± 0,81mm/d) com o período sem P4 (ER: 3,63 ± 1,33mm/d; ET: 3,31 ± 1,66mm/d). O presente estudo demonstrou aplicabilidade e eficiência do protocolo hormonal utilizando dispositivo intravaginal de P4 e BE para controle folicular de éguas, tanto na ET quanto na ER.

Double focus in the modelling of anti-influenza properties of 2-iminobenzimidazolines: pharmacology and toxicology.

Influenza affects millions of people globally and the appearance of drug-resistant strains is an ongoing problem. Therefore, this work reports the development of quantitative structure-activity relationship (QSAR) models to predict some biological properties of new 2-iminobenzimidazoline candidates for the treatment of the flu. A series of 2-iminobenzimidazoline derivatives with experimentally available values for cytotoxicity (pCC50) and anti-influenza activity (pIC50) was used for multivariate image analysis applied to QSAR (MIA-QSAR). The models were vigorously validated according to the best practices in QSAR and the chemical features responsible for the response variables were analysed based on MIA-plots, which assess the PLS regression coefficients and variable importance in projection scores. MIA descriptors encoding atomic properties (van der Waals radius and electronegativity) were capable of properly modelling the pCC50 and pIC50 data. The internally and externally validated models were used to predict the selectivity indexes (SI = pCC50/pIC50) of unprecedented analogues, which were designed upon analysis of the MIA-plots that show the substituent groups most affecting the biological data and by the combination of substructures of selected molecules. At least three promising anti-influenza candidates could be proposed from the predictive MIA-QSAR models.

Zymosan enhances in vitro phagocyte function and the immune response of mice infected with Paracoccidioides brasiliensis.

Paracoccidioides brasiliensis is the major etiologic agent of Paracoccidioidomycosis (PCM), the most frequent human deep mycosis in Latin America. It is proposed that masking of ß-glucan in P. brasiliensis cell wall is a critical virulence factor that contributes to the development of a chronic disease characterized by a long period of treatment, which is usually toxic. In this context, the search for immunomodulatory agents for therapeutic purposes is highly desirable. One strategy is to use pattern recognition receptors (PRRs) ligands to stimulate the immune response mediated by phagocytes. Here, we sought to evaluate if Zymosan, a ß-glucan-containing ligand of the PRRs Dectin-1/TLR-2, would enhance phagocyte function and the immune response of mice challenged with P. brasiliensis. Dendritic cells (DCs) infected with P. brasiliensis and treated with Zymosan showed improved secretion of several proinflammatory cytokines and expression of maturation markers. In addition, when cocultured with splenic lymphocytes, these cells induced the production of a potential protective type 1 and 17 cytokine patterns. In macrophages, Zymosan ensued a significant fungicidal activity associated with nitric oxide production and phagolysosome acidification. Importantly, we observed a protective effect of Zymosan-primed DCs delivered intranasally in experimental pulmonary PCM. Overall, our findings support the potential use of ß-glucan-containing compounds such as Zymosan as an alternative or complementary antifungal therapy. LAY SUMMARY: We report for the first time that Paracoccidioides brasiliensis-infected phagocytes treated with Zymosan (cell wall extract from bakers' yeast) show enhanced cytokine production, maturation, and fungal killing. Also, Zymosan-primed phagocytes induce a protective immune response in infected mice.

Associations of feed efficiency with circulating IGF-1 and leptin, carcass traits and meat quality of lambs.

The aim of this study was to investigate the effects of feed efficiency classifications on live animal measurements, circulating IGF-1 and leptin concentrations, and carcass, non-carcass and meat quality traits of lambs. One-hundred and two lambs approximately 70 days-old with initial live weight of 24.6 ± 3.71 kg (mean ± SD) were individually fed for 56 days to determine residual feed intake (RFI) and residual feed intake and gain (RIG). Lambs were then classified as phenotypically Low-, Medium- or High-RFI and Low-, Medium- or High-RIG phenotypes. Circulating leptin and IGF-1 concentrations were higher in more efficient lambs (Low-RFI or High-RIG). Variation in RFI and RIG did not affect meat redness or tenderness, but High-RIG lambs had darker meat. These findings show that the phenotypically more efficient Low-RFI and High-RIG lambs produced carcasses with similar characteristics and meat quality as the less efficient High-RFI and Low-RIG lambs but have a strategic advantage of lower feed intake to achieve similar production outcomes.

Effect of organic compost and inorganic nitrogen fertigation on spinach growth, phytochemical accumulation and antioxidant activity.

The aim of this study was to evaluate the effect of the addition of organic compost in combination with the inorganic nitrogen fertigation on growth, phytochemical accumulation, and antioxidant activity of spinach (Spinacia oleracea L. cv. Manatee). Soil blocked spinach seedlings (six seedlings per block), three blocks per pot (316 plants m-2) were transplanted after 18 days after emergence into to 12 L pots. The treatments were: unfertilized soil, organic compost, organic compost +75 kg of N ha-1, applied as ammonium sulfate; and organic compost +75 kg N ha-1, applied as ammonium nitrate. The addition of organic compost to unfertilized soil increased the fresh yield. The application of inorganic N from the two sources in relation to organic compost treatment increased spinach fresh yield from 2.3 to 4.81 kg m-2 and shoot dry weight from 0.60 to 1,31 g plant-1. Levels of carotenoids also increased with inorganic N addition, producing higher values in plants grown with organic compost + ammonium nitrate (31.14 mg/100 g fresh weight). However, the addition of N led to a decrease in leaf-blade total phenols from 75 to 56 mg gallic acid equivalents/100mg fresh weight. The addition of inorganic N led to a dramatic decrease in leaf-blade ferric reducing antioxidant activity. This effect was higher with ammonium sulfate application. The application of organic compost and inorganic nitrogen had no influence on the petiole's phytochemical accumulation and antioxidant activity.

Encefalitis/encefalopatía leve con lesión reversible del esplenio del cuerpo calloso asociada a pielonefritis aguda; a propósito de un caso clínico / Mild encephalopathy/encephalitis with a reversible splenial lesion associated with acute pyelonephritis: A case report

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Photodynamic inactivation of the phytopathogenic bacterium Xanthomonas citri subsp. citri.

The present work intended to evaluate the applicability of photodynamic inactivation (PDI) of Xanthomonas citri subsp. citri with toluidine blue O (TBO), a commercial photosensitizer, as a strategy to control citrus canker. Assays were conducted with cell suspensions and biofilms, constructed either on polypropylene microtubes (in vitro assays) or on the surface of orange leaves (ex vivo assays), in the presence of TBO and under irradiation with artificial white light or natural sunlight. PDI assays using TBO alone caused a maximum 5·8 log10 reduction of X. citri viable cells in suspensions, and a much smaller inactivation (1·5 log10) in biofilms. However, concomitant use of KI potentiated the TBO photosensitization. Biofilms were inactivated down to the detection limit (>6 log10 reduction) with 5·0 µmol l-1 TBO + 10 mmol l-1 KI (in vitro) or 5·0 µmol l-1 TBO + 100 mmol l-1 KI (ex vivo) after artificial white light irradiation. Under natural sunlight, a reduction down to the detection limit of the Miles-Misra method was achieved with 50 µmol l-1 TBO and 100 mmol l-1 KI. PDI has potential to be applied in the control of citrus canker in field conditions although further studies are needed to show that there are no risks to plant physiology or fruit quality. SIGNIFICANCE AND IMPACT OF THE STUDY: Xanthomonas citri subsp. citri is a major cause of disease in citrus orchards. Because of the low efficacy and high environmental toxicity of copper-based treatments, there is growing interest on more sustainable phytosanitary approaches. Photodynamic inactivation (PDI) is being successfully used to control infectious agents and literature reports indicate that it is effective against some fungi and bacteria attacking fruit crops. The results of the present work open the perspective of using a low-cost photosensitizer and sunlight, as energy source, to control of the causative agent of citrus canker.

Feedlot performance and rumen morphometrics of Nellore cattle adapted to high-concentrate diets over periods of 6, 9, 14 and 21 days.

The energy content of finishing diets offered to feedlot cattle may vary across countries. We assumed that the lower is the energy content of the finishing diet, the shorter can be the adaptation period to high-concentrate diets without negatively impacting rumen health while still improving feedlot performance. This study was designed to determine the effects of adaptation periods of 6, 9, 14 and 21 days on feedlot performance, feeding behaviour, blood gas profile, carcass characteristics and rumen morphometrics of Nellore cattle. The experiment was designed as a completely randomised block, replicated 6 times, in which 96 20-month-old yearling Nellore bulls (391.1 ± 30.9 kg) were fed in 24 pens (4 animals/pen) according to the adaptation period adopted: 6, 9, 14 or 21 days. The adaptation diets contained 70%, 75% and 80.5% concentrate, and the finishing diet contained 86% concentrate. After adaptation, one animal per pen was slaughtered (n = 24) for rumen morphometric evaluations and the remaining 72 animals were harvested after 88 days on feed. Orthogonal contrasts were used to assess linear, quadratic and cubic relationships between days of adaptation and the dependent variable. Overall, as days of adaptation increased, final BW (P = 0.06), average daily gain (ADG) (P = 0.07), hot carcass weight (P = 0.04) and gain to feed ratio (G : F) (P = 0.07) were affected quadratically, in which yearling bulls adapted by 14 days presented greater final BW, ADG, hot carcass weight and improved G : F. No significant (P > 0.10) days of adaptation effect was observed for any of feeding behaviour variables. As days of adaptation increased, the absorptive surface area of the rumen was affected cubically, where yearling bulls adapted by 14 days presented greater absorptive surface area (P = 0.03). Thus, Nellore yearling bulls should be adapted by 14 days because it led to improved feedlot performance and greater development of rumen epithelium without increasing rumenitis scores.

Sensory neuronopathy is a specific and disabling neurological manifestation of autoimmune hepatitis.

BACKGROUND AND PURPOSE: Neurological manifestations have been identified in the context of autoimmune hepatitis (AIH). Previous case reports highlighted the association between AIH and sensory neuronopathy (SN). Despite that, little is known about the frequency of AIH-related SN and its clinical/neurophysiological profile. Moreover, it is not clear whether SN is an AIH-specific manifestation or related to chronic liver damage. METHODS: Seventy consecutive AIH patients were enrolled and their characteristics were compared with 52 consecutive patients with chronic active hepatitis B. All subjects underwent clinical and neurophysiological evaluation. Further comparisons were performed between AIH SN and AIH non-SN patients. RESULTS: Mean ages and male:female proportions in the AIH and chronic active hepatitis B groups were 42.2 ± 16.3/51.7 ± 13.6 years and 14:56/29:23, respectively. The frequencies of carpal tunnel syndrome, radiculopathy and polyneuropathy were similar between groups. In contrast, SN was identified only in AIH patients (5/70 vs. 0/52, P = 0.04); the overall prevalence of AIH-related SN was 7% with an average profile of a woman in her 40s with asymmetric onset of sensory deficits that chronically evolved to disabling proprioceptive ataxia associated with marked dysautonomia. Neurological disability and hepatocellular damage did not follow in parallel. Anti-fibroblast growth factor receptor type 3 antibodies were found in 3/5 (60%) of the patients with AIH-related SN. Clinical or demographic predictors of SN in the context of AIH could not be identified. CONCLUSION: Sensory neuronopathy, but not other peripheral nervous system diseases, is a specific AIH neurological manifestation. It is often disabling and, in contrast to hepatocellular injury, does not respond to immunosuppression.

Post-exposure prophylaxis following consented sexual exposure: impact of national recommendations on user profile, drug regimens and estimates of averted HIV infections.

OBJECTIVES: The aim of the study was to describe the characteristics, impact and outreach of post-exposure prophylaxis (PEP) for sexual exposure in Brazil. METHODS: We used secondary data from the Brazilian Ministry of Health to describe the impact of national guidelines on the frequency of prescription, user profile and antiretroviral regimens. We also estimated the number of potentially averted HIV infections attributable to PEP for consented sexual exposure between 2009 and 2017. RESULTS: A total of 260 457 PEP regimens were prescribed to individuals ≥ 14 years old; 104 613 (40.2%) were prescribed for consented sexual exposure, with an increasing frequency since 2011. Drugs used in PEP regimens underwent significant modifications during the period, reflecting national recommendations. We estimated that there were up to 3138 potentially averted HIV infections attributable to PEP for consented sexual exposure between 2009 and 2017. CONCLUSIONS: In the context of a combined HIV prevention strategy, PEP is still an essential tool for individuals for whom other methods are contraindicated or fail to be applied.

[Glycerol kinase deficiency: a metabolic cause of global developmental delay]. / Deficiencia de glicerolcinasa: una causa metabolica de retraso global del desarrollo.

TITLE: Deficiencia de glicerolcinasa: una causa metabolica de retraso global del desarrollo.

[Acute parainfectious transverse myelitis with radiculitis in a child with closed spinal dysraphism]. / Mielitis transversa parainfecciosa aguda con radiculitis en una niña con disrafismo espinal cerrado.

TITLE: Mielitis transversa parainfecciosa aguda con radiculitis en una niña con disrafismo espinal cerrado.

Osteoradionecrosis prevalence and associated factors: A ten years retrospective study.

BACKGROUND: Osteoradionecrosis (ORN) is one of the most serious complications of head and neck radiotherapy and is considered a public health problem worldwide. This study aims to determine the prevalence and associated factors of ORN in patients undergoing radiotherapy for head and neck malignancy. MATERIAL AND METHODS: A cross-sectional retrospective study was conducted, in which all medical records of patients undergoing head and neck radiation in the period between 2006 to 2015 (10 years) were examined. Clinical and demographic data were extracted. Multivariate Poisson regression analysis with robust variance was employed to access the relationship between ORN and independent variables (p < 0.05; 95% CI). RESULTS: The sample comprised 413 medical records of patients undergoing radiotherapy. The prevalence of ORN was 9.7 %. Most participants were males (78.2%). The mean age of subjects was 55 years (± 14 years). The mandible was the main site of occurrence of ORN (85.0%). The following variables were associated with ORN : presence of oral mucositis (PR = 3.03; 95% CI: 1.30-7.03), history of smoking (PR = 0.23; 95% CI: 0.07-0.74), number of teeth removed before radiotherapy (PR = 1.06; 95% CI: 1.01-1.11) and visit to the dentist before radiation (PR = 0.08; 95% CI: 1.02-1.11). CONCLUSIONS: The prevalence of ORN was low and was associated with the presence of oral mucositis and the number of removed teeth before radiation. Visiting the dentist before radiotherapy and stop-ping smoking were protective factors for ORN.

Plant growth, phytochemical accumulation and antioxidant activity of substrate-grown spinach.

Spinach production in soilless cultivation systems, mainly in substrate, transplanted with soil blocks and drip-irrigation is increasing worldwide. However, spinach establishment with soil blocks, with several seedlings per block compared with traditional planting methods, may affect light interception by plant canopy, wetting and salt patterns in root medium and therefore the plant growth and functional value of spinach. The effects of soil block number (plant density) and emitters spacing on plant growth, nitrate, proline and total phenols content and antioxidant activity were evaluated in spinach (Spinacia oleracea L). Five seedlings per soil block were transplanted to Styrofoam boxes filled with the substrate and grown during winter in an unheated greenhouse. Four treatments were carried out with two soil block numbers [8 (160 plants/m2) and 14 (280 plants/m2) soil blocks per Styrofoam box] and two emitter spacing [emitters spaced every 25 and 12.5 cm, respectively, with 4 and 8 emitters per Styrofoam box]. Neither plant density nor emitter spacing had any effect on shoot dry weight. Fresh yield increased as planting density and the number of emitters per Styrofoam box increased. The yield in Styrofoam boxes with 160 plants/m2 and 8 emitters (3.85 kg m-2) was ≈31 % lower than that obtained in treatment with 280 plants/m2 and 8 emitters (5.09 kg m-2). However, the leaf blade of the latter treatment presented a higher content of phenols and proline and greater antioxidant activity (FRAP and DPPH) as well as lower content of nitrate and lesser PDH activity. Decrease of space between emitters reduced the leaf blade nitrate concentration of spinach grown in a greenhouse during the winter. Leaf blade antioxidant activity (FRAP) decreased as planting density increased.

Staphylococcus spp. isolated from wild birds apprehended in the local illegal trade in Rio de Janeiro, Brazil, and relevance in public health.

This work aimed to investigate the prevalence of Staphylococcus in wild birds seized in illegal trade and their antimicrobial resistance patterns. Cloacal samples were obtained from 109 wild birds apprehended in the street markets in Rio de Janeiro, Brazil. Staphylococcus spp. were phenotypically and genotypically identified, and resistance profile was evaluated according to Clinical and Laboratory Standards Institute guidelines and by polymerase chain reaction of mecA and blaZ genes. Staphylococcus was detected in 45·9% (50/109) of the cloacal swab samples, and 39 (78·0%) isolates were resistant to one or more of the nine antimicrobials tested and were also positive to mecA (12/39) or blaZ genes (14/39). High percentage of resistance was detected to ampicillin, oxacillin, cefoxitin, clindamycin and tetracycline, with the absence of resistance to vancomycin. Wild birds captured and submitted to captive stress conditions of illegal trade market of Brazil may have an important role as reservoirs of Staphylococcus spp. and its antimicrobial resistance mechanisms. The significance of this study is revealed by the zoonotic and pathogenic potential of staphylococci and that impact to public health and requires monitoring polices of wild birds health in tropical areas. SIGNIFICANCE AND IMPACT OF THE STUDY: The isolation of Staphylococcus species that are not commonly isolated from wild bird faeces, the relatively high proportion of strains showing degrees of resistance to ß-lactamics, lincosamides and tetracycline, and also the presence of mecA and blaZ genes that has been associated with multidrug phenotype reveal its public health relevance and zoonotic potential. Consequently, this represents an important route to transmission of this pathogen and its antimicrobial resistance mechanisms throughout national and international frontiers fostered by the illegal trade of wild animals and close contact with humans.

Individual variation is the key to the development of a vaccine against Staphylococcus aureus: a comparative study between mice lineages.

Bacterial infections occur worldwide and are a major public health problem. Among pathogens, Staphylococcus aureus is the main causative agent of bacterial diseases in the world. This study aimed to evaluate which components of the immune system could act protectively against a S. aureus infection in intradermally immunized mice. C57BL/6 and A/j mice were immunized intradermally with S. aureus inactivated by heat and then challenged with viable strains in an air pouch model. At 6, 12, and 24 h after the challenge, euthanasia was performed, and the cellular profile of the inflammatory infiltrate, cytokines, and the bacterial load were evaluated in the air pouch lavages. Immunized mice demonstrated that the intradermal immunization with S. aureus promoted protection in C57BL/6 mice by reducing the bacterial, which was correlated with increased serum concentration of IgG antibodies (IgG1 and IgG2a) against S. aureus. The increase in IgG2a antibody levels was correlated with a decrease of bacterial load in intradermally immunized C57BL/6 mice, along with production of IL-17A at the inflammation site, as well as IgG1consumption. Similar results were not found in the A/j lineage. In conclusion, a vaccine against S. aureus should focus more on the individual characteristics of the host because it is a determinant factor for the success of the immunization.