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This study evaluated the efficacy of the administration of different doses of equine chorionic gonadotropin (eCG; 0 IU, 200 IU, or 300 IU) at the time of the progesterone device removal in 2-year-old Nelore (Bos indicus) heifers synchronized for fixed-timed artificial insemination (FTAI). On day 0 (D0), a total of 398 heifers received 2 mg of oestradiol benzoate i.m., 0.53 mg of cloprostenol i.m., and an eight-day previously used (second use) intravaginal device containing 1 g of progesterone (P4). Eight days later (D8), simultaneous with the P4 device removal, 0.5 mg of oestradiol cypionate i.m. and 0.53 mg of cloprostenol i.m. were administered. At the same time, heifers were randomly assigned to receive one of the following treatments: G-0 IU (n = 141; no eCG treatment), G-200 IU (n = 132; treated with 200 IU of eCG), and G-300 IU (n = 125; treated with 300 IU of eCG). FTAI was performed 48 h after the P4 device removal (D10). Ultrasonographic evaluations were performed at D0, D10, and D17. Heifers were scanned to measure the size of the largest follicle (LF), the presence, number, and size of the corpus luteum (CL), and the ovulation rate. Subsequently, at D40, the heifers underwent scanning to determine the pregnancy rate and identify any twin pregnancies. Additionally, at D70, scans were performed to assess pregnancy loss (PG). Data were analysed by orthogonal contrasts [C1 (eCG effect): control x (200 IU + 300 IU) and C2 (eCG dose effect): 200 IU × 300 IU]. On D0, CL presence was similar between the groups [G-0 IU = 65.2% (92/141), G-200 IU = 55.3% (73/132), and G-300 IU = 63.2% (79/125); p = .16]. No interactions between the presence of CL on D0 and eCG treatment were found for any of the variables (p > .05). The diameter of the LF at FTAI (D10) was not influenced by eCG treatment (p = .22) or eCG dose (p = .18). However, treatment with eCG increased the diameter of the CL at D17 (G-0 IU = 15.7 ± 0.3 mmb , G-200 IU = 16.6 ± 0.2 mma , and G-300 IU = 16.6 ± 0.3 mma ; p = .001), regardless of the dose used (p = .94). The ovulation rate was higher in heifers treated with eCG [G-0 IU = 79.4%b (112/141), G-200 IU = 90.2%a (119/132), and G-300 IU = 93.6%a (117/125); p = .002], but there was no effect of eCG dose (p = .36). Pregnancy per AI (P/AI) on D40 [G-0 IU = 32.6%b (46/141), G-200 IU = 42.4%a (56/132), and G-300 IU = 42.4%a (53/125); P = 0.05] and D70 [G-0 IU = 29.1%b (41/141), G-200 IU = 40.9%a (54/132), and G-300 IU = 40.8%a (51/125); p = .02] were higher on heifers that received eCG; however, no dose effect was observed for P/AI on D40 (p = .89) nor D70 (p = .98). Pregnancy loss between D40 and D70 tended to reduce (p = .07) in eCG-treated heifers without dose effect (p = .91). Heifers with CL at D0 presented a greater follicle diameter (LF) on D10 (With CL = 11.2 ± 0.2 mm and Without CL = 10.2 ± 0.2 mm; p = .05), CL diameter on D17 (With CL = 15.8 ± 0.03 mm and Without CL = 11.8 ± 0.6 mm; p = .01), and ovulation rate [With CL = 95.5% (233/244) and Without CL = 74.7% (115/154); p = .01]. However, no difference in pregnancy rate at D40 (p = .52) and D70 (p = .84) was found. In conclusion, eCG treatment increases ovulation and pregnancy rates of heifers submitted to a FTAI protocol. Furthermore, eCG treatment increases the diameter of the CL after FTAI and reduces pregnancy losses. No dose effect was observed, suggesting Nelore (Bos indicus) heifers respond to 200 IU of eCG treatment for FTAI.

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Guavira (Campomanesia adamantium, Myrtaceae) is a native fruit from the Brazilian Cerrado savanna and is socio-economically important for the indigenous and traditional people living in the Central-West. This is a bibliographic review of the biological properties of guavira and its derivatives, and, after discussing experimental studies, an interdisciplinary approach is conducted highlighting the im-portance of Agroforestry Systems as an ecological restoration tool to leverage the production chain of guavira while providing ecosystem services. Many research groups studied effects of polyphenols and other bioactive compounds and biological properties of this fruit and other plant parts such as antibiotic, antioxidant, anti-inflammatory, anti-hyperlipidemic, anti-diarrheic and antitumoral activities, cardiovascular and hepatic protection and action against neuropathic pain. Besides, guavira by-products benefit poultry intestinal health, similarly to antibiotics added to their feed. Furthermore, several biotechnological products were found, like pulp flour, seasoning from the peel, sunscreen, and seed oil similar to olive oil with pharmaceutical and industrial potential. We conclude by emphasizing the importance of guavira for restoration and preservation of the threatened Brazilian Cerrado, and for the socio-environmental development of family agriculture. The same approach and study are welcome and necessary in other regions and domains worldwide having their native flora as means for a restorative end.

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6-Nitrodopamine is a novel catecholamine released by vascular tissues, heart, and vas deferens. The aim of this study was to investigate whether 6-nitrodopamine is released from the thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) and to evaluate the relaxing and anti-contractile actions of this catecholamine. Release of 6-nitrodopamine, dopamine, noradrenaline, and adrenaline was assessed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The relaxations induced by 6-nitrodopamine and by the selective dopamine D2 receptor antagonist L-741,626 were evaluated on U-46619 (3 nM)-pre-contracted vessels. The effects of 6-nitrodopamine and L-741,626 on the contractions induced by electric-field stimulation (EFS), dopamine, noradrenaline, and adrenaline were also investigated. Both aorta and pulmonary artery rings exhibited endothelium-dependent release of 6-nitrodopamine, which was significantly reduced by the NO synthesis inhibitor L-NAME. Addition of 6-nitrodopamine or L-741,626 caused concentration-dependent relaxations of both vascular tissues, which were almost abolished by endothelium removal, whereas L-NAME and the soluble guanylate cyclase inhibitor ODQ had no effect on 6-nitrodopamine-induced relaxations. Additionally, pre-incubation with 6-nitrodopamine antagonized the dopamine-induced contractions, without affecting the noradrenaline- and adrenaline-induced contractions. Pre-incubation with L-741,626 antagonized the contractions induced by all catecholamines. The EFS-induced contractions were significantly increased by L-NAME, but unaffected by ODQ. Immunohistochemical assays showed no immunostaining of the neural tissue markers S-100 and calretinin in either vascular tissue. The results indicated that 6-nitrodopamine is the major catecholamine released by marmoset vascular tissues, and it acts as a potent and selective antagonist of dopamine D2-like receptors. 6-nitrodopamine release may be the major mechanism by which NO causes vasodilatation.

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6-Nitrodopamine is a novel catecholamine released by vascular tissues, heart, and vas deferens. The aim of this study was to investigate whether 6-nitrodopamine is released from the thoracic aorta and pulmonary artery rings of marmosets (Callithrix spp.) and to evaluate the relaxing and anti-contractile actions of this catecholamine. Release of 6-nitrodopamine, dopamine, noradrenaline, and adrenaline was assessed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The relaxations induced by 6-nitrodopamine and by the selective dopamine D2 receptor antagonist L-741,626 were evaluated on U-46619 (3 nM)-pre-contracted vessels. The effects of 6-nitrodopamine and L-741,626 on the contractions induced by electric-field stimulation (EFS), dopamine, noradrenaline, and adrenaline were also investigated. Both aorta and pulmonary artery rings exhibited endothelium-dependent release of 6-nitrodopamine, which was significantly reduced by the NO synthesis inhibitor L-NAME. Addition of 6-nitrodopamine or L-741,626 caused concentration-dependent relaxations of both vascular tissues, which were almost abolished by endothelium removal, whereas L-NAME and the soluble guanylate cyclase inhibitor ODQ had no effect on 6-nitrodopamine-induced relaxations. Additionally, pre-incubation with 6-nitrodopamine antagonized the dopamine-induced contractions, without affecting the noradrenaline- and adrenaline-induced contractions. Pre-incubation with L-741,626 antagonized the contractions induced by all catecholamines. The EFS-induced contractions were significantly increased by L-NAME, but unaffected by ODQ. Immunohistochemical assays showed no immunostaining of the neural tissue markers S-100 and calretinin in either vascular tissue. The results indicated that 6-nitrodopamine is the major catecholamine released by marmoset vascular tissues, and it acts as a potent and selective antagonist of dopamine D2-like receptors. 6-nitrodopamine release may be the major mechanism by which NO causes vasodilatation.

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Previous studies have shown that 17ß-estradiol plays a cardioprotective role in the central nervous system (CNS) of male rats. The aim of the present study was to determine the influence of 17ß-estradiol on sympathetic vasomotor activity and blood pressure in a renovascular hypertensive Goldblatt two-kidney one-clip (2K-1C) male rat model. We also determined the influence of angiotensin II AT1 receptor on the expression of estrogen receptors (ERα, ERß, and G protein-coupled ER (GPER)) in the rostral ventrolateral medulla (RVLM) of Goldblatt rats. Experiments were performed in Goldblatt and age-matched control rats six weeks after clipping of renal artery to induce hypertension. Microinjection of 17ß-estradiol into the RVLM led to a greater reduction in mean arterial pressure and renal sympathetic nerve activity in controls than in 2K-1C rats. Microinjection of the GPER agonist G-1 into the RVLM led to a significantly greater increase in mean arterial pressure and renal sympathetic nerve activity in 2K-1C rats. Expression levels of estrogen receptors GPER and ERα, but not ERß, were significantly higher in the RVLM of 2K-1C rats than in that of the control rats. Chronic treatment with losartan significantly reduced the expression levels of estrogen receptors in the RVLM of 2K-1C rats. Taken altogether, the data suggest that the imbalance of actions between ERα and GPER, particularly with the predominance of GPER in the RVLM, contributes to sympathetic overactivation in male rats with Goldblatt hypertension. AT1-Angiotensin II receptor in the RVLM upregulated estrogen receptor expression in male Goldblatt rats.

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OBJECTIVE: In this study, we investigated the occurrence of papillomavirus (PV) infection in non-human primates (NHPs) in northeastern Argentina. We also explored their evolutionary history and evaluated the co-speciation hypothesis in the context of primate evolution. METHODS: We obtained DNA samples from 57 individuals belonging to wild and captive populations of Alouatta caraya, Sapajus nigritus, and Sapajus cay. We assessed PV infection by PCR amplification with the CUT primer system and sequencing of 337 bp (112 amino acids) of the L1 gene. The viral sequences were analyzed by phylogenetic and Bayesian coalescence methods to estimate the time to the most common recent ancestor (tMRCA) using BEAST, v1.4.8 software. We evaluated viral/host tree congruence with TreeMap v3.0. RESULTS: We identified two novel putative PV sequences of the genus Gammapapillomavirus in Sapajus spp. and Alouatta caraya (SPV1 and AcPV1, respectively). The tMRCA of SPV1 was estimated to be 11,941,682 years before present (ybp), and that of AcPV1 was 46,638,071 ybp, both before the coalescence times of their hosts (6.4 million years ago [MYA] and 6.8 MYA, respectively). Based on the comparison of primate and viral phylogenies, we found that the PV tree was no more congruent with the host tree than a random tree would be (P > 0.05), thus allowing us to reject the model of virus-host coevolution. CONCLUSION: This study presents the first evidence of PV infection in platyrrhine species from Argentina, expands the range of described hosts for these viruses, and suggests new scenarios for their origin and dispersal.

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In order to evaluate the environmental performance generated by a "semi-technified" pig farm, as well as the comparison of different pig production scenarios, pig feed and animal production subsystems were evaluated considering both: (a) origin of feed ingredients and (b) variations in pig weight. Life cycle assessment methodology was used to evaluate the environmental performance, establishing 1 market pig as the functional unit (FU). Three ingredient origin distances (400, 950, and 1800 km) and three slaughter weights (110, 100, and 90 kg) were considered for the simulation analysis and comparison. The feed production subsystem was the main generator of environmental impacts, mainly caused by the cultivation of sorghum and the production of fat. The origin of the inputs represented the main increase in environmental impact for the feed production subsystem, mainly in the Fossil Depletion category, with a fivefold increase by acquiring inputs from 900 km and a ninefold increase at a distance of 1800 km. Producing lighter pigs resulted in the best environmental alternative, given the resultant 11% reduction in environmental impact.

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Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.

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Sepsis causes long-term disability, such as immune dysfunction, neuropsychological disorders, persistent inflammation, catabolism, and immunosuppression, leading to a high risk of death in survivors, although the contributing factors of mortality are unknown. The purpose of this experimental study in rats was to examine renal (rSNA) and splanchnic (sSNA) sympathetic nerve activity, as well as baroreflex sensitivity, in acute and chronic post-sepsis periods. The rats were divided into two groups: control group with naïve Wistar rats and sepsis group with 2-mL intravenous inoculation of Escherichia coli at 108 CFU/mL. Basal mean arterial pressure, heart rate, rSNA, sSNA, and baroreflex sensitivity were evaluated in all groups at the acute (6 h) and chronic periods (1 and 3 months). Basal rSNA and sSNA were significantly reduced in the surviving rats, as was their baroreflex sensitivity, for both pressor and hypotensive responses, and this effect lasted for up to 3 months. A single episode of sepsis in rats was enough to induce long-term alterations in renal and splanchnic sympathetic vasomotor nerve activity, representing a possible systemic event that needs to be elucidated. These findings showed that post-sepsis impairment of sympathetic vasomotor response may be one of the critical components in the inability of sepsis survivors to respond effectively to new etiological illness factors, thereby increasing their risk of post-sepsis morbidity.

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Candida spp. is considered to be the third or fourth most common cause of bloodstream infections associated with healthcare services in the world. Currently, several strains exhibit resistance to the traditional treatments, making the development of new therapeutic molecules necessary. Drug repositioning is an alternative that can be used to work around problems such as toxicity, cost and time in the development of new drugs. This study aims to evaluate the in vitro antifungal effect of tropicamide, molecule of anticholinergic action, against planktonic cells of Candida spp. and biofilm of C. albicans. Six strains of different Candida species were used to determine the minimum inhibitory concentration (MIC) of tropicamide and fluconazole according to CLSI document M27-A3 and one strain of C. albicans was used to evaluate the activity of tropicamide against biofilms. In concentrations of 64µg/mL, the tropicamide exhibited 50% of inhibitory activity in planktonic cell and in concentrations of 128µg/mL is able to inhibit the formation of C. albicans biofilm. Despite the inhibitory activity shown at the present study, the use of a larger number of strains, as well as in vivo cytotoxicity assays, is necessary to confirm the hypothesis that tropicamide can be used as an adjuvant agent in the treatment of infections by the Candida genus.

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This study aimed to evaluate the effects of egg dormancy times on susceptibility of larvae of the floodwater mosquito Aedes albifasciatus (Diptera: Culicidae) to parasitism by their natural enemy Strelkovimermis spiculatus (Nematoda: Mermithidae) and on their life history traits. Aedes albifasciatus eggs stored for 2, 4, 6, 8 and 10 months were hatched, and the larvae either exposed to S. spiculatus (treatment group) or not exposed (control group). Egg dormancy time had a negative effect on the retention of parasites, but no effect on the prevalence and intensity of parasitism or the melanization of nematodes. The survival to adulthood of control individuals decreased as dormancy time increased, whereas that of exposed individuals that remained uninfected was constant and low. A trend towards increasing development times with longer dormancy times was detected in the control group, but not in the exposed noninfected group. The results suggest nonconsumptive effects of parasites in exposed but not infected larvae from eggs with short dormancy times. In contrast, the relatively low fitness of larvae from eggs with long dormancy times regardless of their contact with the nematodes may be the result of the nutritional deprivation during the egg stage.

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Mesenchymal stromal cells (MSCs) are promising candidates for cell-based therapies, mainly due to their unique biological properties such as multipotency, self-renewal and trophic/immunomodulatory effects. However, clinical use has proven complex due to limitations such as high variability of MSCs preparations and high number of cells required for therapies. These challenges could be circumvented with cell immortalization through genetic manipulation, and although many studies show that such approaches are safe, little is known about changes in other biological properties and functions of MSCs. In this study, we evaluated the impact of MSCs immortalization with the TERT gene on the purinergic system, which has emerged as a key modulator in a wide variety of pathophysiological conditions. After cell immortalization, MSCs-TERT displayed similar immunophenotypic profile and differentiation potential to primary MSCs. However, analysis of gene and protein expression exposed important alterations in the purinergic signaling of in vitro cultured MSCs-TERT. Immortalized cells upregulated the CD39/NTPDase1 enzyme and downregulated CD73/NT5E and adenosine deaminase (ADA), which had a direct impact on their nucleotide/nucleoside metabolism profile. Despite these alterations, adenosine did not accumulate in the extracellular space, due to increased uptake. MSCs-TERT cells presented an impaired in vitro immunosuppressive potential, as observed in an assay of co-culture with lymphocytes. Therefore, our data suggest that MSCs-TERT have altered expression of key enzymes of the extracellular nucleotides/nucleoside control, which altered key characteristics of these cells and can potentially change their therapeutic effects in tissue engineering in regenerative medicine.

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OBJECTIVE: To evaluate the efficacy of a levonorgestrel 52-mg intrauterine system (LNG 52-mg IUS) in controlling abnormal uterine bleeding and improving quality of life in women with inherited bleeding disorders. STUDY DESIGN: We assessed 20 participants laboratory diagnosed with inherited bleeding disorders, who presented with abnormal uterine bleeding and were registered in a Central Blood Center. The primary outcomes were menstrual bleeding volume and quality of life before and after LNG 52-mg IUS placement. We used the Pictorial Blood Loss Assessment Chart (PBAC) score for measuring menstrual bleeding and the Short Form-36 Health Survey to assess quality of life before and after LNG 52-mg IUS placement. We also conducted blood tests to evaluate the hematimetric level. Follow-up visits were conducted at 1, 3, 6, and 12 months after LNG 52-mg IUS placement. Statistical analyses were performed using the Friedman non-parametric test. RESULTS: The use of LNG 52-mg IUS reduced uterine bleeding in women with inherited bleeding disorders. The median PBAC score was higher before LNG 52-mg IUS placement than at 3, 6, and 12 months after placement (p < 0.001). The amenorrhea rate was 70% after 12 months. There was an improvement in all eight parameters of quality of life (p < 0.001). The mean hemoglobin, ferritin, and serum iron levels were also higher at 12 months than before LNG 52-mg IUS placement. CONCLUSION: LNG 52-mg IUS placement can effectively control abnormal uterine bleeding in women with inherited bleeding disorders and consequently improve their quality of life. IMPLICATIONS: The results from our study suggest that women with inherited bleeding disorders who present with heavy menstrual bleeding can benefit from the use of a levonorgestrel-releasing intrauterine system similar to women without bleeding disorders.

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This study highlights the species diversity of Ceratopogonidae from the Paranaense forest and adjacent grassland in a protected natural area of Argentina, and emphasizes the importance of conserving the last remaining marginal forest area surrounded by a strong urbanization. A total 46 species belonging to 10 genera were recorded from these two habitats. Species diversity was higher in the grassland, while dominance was greater in the forest. Twelve species were abundant, while the rest were scarce or rare. The composition of the ceratopogonid community differs between habitats: 15 species were exclusive to the forest, 4 to the grasslands, and 27 used both habitats indistinctly. Differences between habitats were observed in the abundances of Alluaudomyia schnacki Spinelli, Atrichopogon albinensis Ingram and Macfie, and Forcipomyia rioplatensis Marino and Spinelli. The sex ratio of the most abundant species did not show a definite pattern in relation to the habitats, except for Culicoides caridei (Brèthes), in which females were dominant. Atrichopogon balseiroi Spinelli and Forcipomyia williamsi Marino & Spinelli have only been recorded in Buenos Aires Province and were found exclusively in the forest during this study.

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OBJECTIVE: The aim of this study was to determine whether remission and low disease activity state protect systemic lupus erythematosus patients from being hospitalized. MATERIALS AND METHODS: Patients from the Almenara Lupus Cohort were included. Visits were performed every 6 months. Variables were measured at each visit. Hospitalizations were evaluated in the interval between two visits. Remission was defined as: a SLEDAI-2 K of 0, prednisone ≤5 mg/day and immunosuppressants on maintenance dose; low disease activity state as: a SLEDAI-2 K of ≤4, prednisone ≤7.5 mg/day and immunosuppressants on maintenance dose. Univariable and multivariable interval-censored survival regression models were used. In multivariable analysis, possible confounders were gender, age at diagnosis, socioeconomic status, educational level, disease duration, antimalarial use, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI) and Charlson comorbidity index. Confounders were determined in the same visit as disease activity state. RESULTS: Of the 308 patients, 92.5% of them (n = 285) were women, had a mean age at diagnosis of 34.8 (13.4) years and a disease duration of 7.7 (6.5) years. At baseline the mean SDI was 1.13 (1.34). A total of 163 of the patients were hospitalized. In the multivariable analysis remission (hazard ratio 0.445 (0.274-0.725), P = 0.001) and low disease activity state (relative risk 0.504 (0.336-0.757), P = 0.001) at baseline were found to decrease the risk of hospitalization in systemic lupus erythematosus patients. A total of 158 hospitalizations presented a discernible cause. Disease activity was the most common cause of hospitalization, with 84 admissions (53.16%), the majority, 38, was due to active kidney disease (45.23%). CONCLUSION: Remission and low disease activity state decreased the risk of hospitalizations in these systemic lupus erythematosus patients. Disease activity, particularly renal, was the most frequent cause of hospitalization.

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