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INTRODUCTION: The impacts of antidepressant pharmacotherapies on cardiovascular risk are unclear. We completed a systematic review with meta-analysis to assess the effect of paroxetine on heart rate variability (HRV) in patients with major depressive disorder (MDD). METHODS: The searches were accomplished via EMBASE, MEDLINE/PubMed (using the National Library of Medicine), Cochrane Library, CINAHL, Scopus, and Web of Science databases. We included non-blind, single, or double-blind randomized control trials in patients older than 18 diagnosed with MDD. Paroxetine needs to be enforced as a chronic therapeutic medication. We included individual studies that investigated resting HRV. RESULTS: We documented 402 studies, only following screening and eligibility phases; only six were included (five studies in the meta-analysis). No significant change was noticed for the SDNN index: subtotal = 8.23 [CI: -2.17, 18.63], p = 0.12, I2 = 54 % (very low quality of evidence). A significant change was distinguished for the LF index: subtotal = 0.74 [CI: 0.33, 1.15], p = 0.0004, I2 = 0 % (low quality of evidence). A significant alteration was perceived for the HF index: subtotal = 0.33 [CI: 0.06, 0.6], p = 0.02, I2 = 0 % (low quality of evidence). CONCLUSION: Meta-analysis demonstrated that paroxetine could advance HRV in MDD patients. Nevertheless, our supposition is founded only on statistical analysis and the very low quality of evidence breakdown reinforces the necessity for further studies to confirm or reject this theory.

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To evaluate the impact on the quality of filling with of low-fusion and conventional gutta-percha cones. Thirty-six maxillary canines were prepared and divided into three groups: I-conventional cone with Downpack at 200 °C at 4 mm from the WL; II-low-fusion cone with Downpack at 100 °C up to 4 mm from the WL; III-low-fusion cone with Downpack at 100 °C up to 7 mm from the WL. Temperature variations were measured in thirds on the external surface of the root. The bond strength was evaluated using the push-out test. The adhesive interface was analyzed by scanning electron microscopy. The bond strength and the temperature variation data were analyzed using analysis of variance and the failure type using the chi-square test. The low-fusion cone group with 7 mm Downpack showed higher bond strength (4.2 ± 2.7) compared with conventional cones (2.8 ± 1.6) and low-fusion cones with 4 mm Downpack (2.9 ± 1.6) (p < 0.05), with occurrence of a higher number of adhesive failures to the filling material and mixed failures. Relative to temperature variation, there was less temperature change in the apical third, in the low-fusion cone with Downpack 7 mm (1.0 ± 1.0) (p < 0.05). The use of low-fusion cones allowed the continuous wave condensation technique to be performed at a lower depth of Downpack at 100 °C at 7 mm, with less heating in the apical third, without compromising the quality of filling. Using gutta-percha cones with low fusion, which permits a lower condensation temperature and reduced Downpack depth, maintains the quality of filling, in order to minimize possible damage to the periapical tissues.

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AIM: To mensure the physicochemical properties of three ceramic cement endodontic sealers AH Plus Bioceramic, Bio-C Sealer and Bio-C Sealer Ion+ with an epoxy resin sealer, AH Plus. MATERIAL AND METHODS: These properties were measured: hardening time (HT), dimensional change (DC), solubility (SL), flow (FL) and radiopacity (RD). The distilled water obtained from the SL test was analyzed with atomic absorption spectrometry. A sample calculation was made considering n = 5 repetitions for each experimental sealer evaluated. Statistical analysis was performed using one-way ANOVA and post hoc Tukey tests (p < 0.05). RESULTS: For the HT, AH Plus (484 ± 2.76 min) and AH Plus Bioceramic (424 ± 1.23 min) set more slowly than of Bio-C Sealer (370 ± 4.50 min) and Bio-C Sealer Ion+ (380 ± 1.42 min) (p < 0.05). AH Plus Bioceramic (12.56 ± 2.71 %) was more soluble than Bio-C Sealer (6.69 ± 1.67 %), Bio-C Sealer Ion+ (5.67 ± 2.16 %) and AH Plus (0.15 ± 0.01 %) (p < 0.05). AH Plus (0.03 ± 0.01 %) had slight expansion while the cement-based sealers had shrinkage: AH Plus Bioceramic (-1.60 ± 0.63 %) and Bio-C Sealer (-1.38 ± 0.69 %), Bio-C Sealer Ion+ (-5.19 ± 1.23 %) (p < 0.05). Bio-C Sealer Ion+ (59.80 ± 0.86 mm) and Bio-C Sealer (58.60 ± 0.98 mm) had the highest flow compared with AH Plus (56.90 ± 0.56 mm) and AH Plus Bioceramic (49.50 ± 0.63 mm) (p < 0.05). AH Plus (9.17 ± 0.06 mmAl) and AH Plus Bioceramic (8.27 ± 0.84 mmAl) showed radiopacity values when compared with those of Bio-C Sealer (4.90 ± 0.08 mmAl) and Bio-C Sealer Ion+ (4.14 ± 0.05 mmAl) (p > 0.05). CONCLUSION: Ion release is inhered to these cement-based sealers and this result in calcium ion release.

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Hypothermic storage has been proposed as a method to reduce bacterial loads and promoting prudent use of antibiotics. Reducing temperature, however, can lead to cold shock damage and oxidative stress in boar semen. This study verified the effect of L-cysteine on the quality of semen stored at 5 °C for 120 h. Twenty-one normospermic ejaculates were diluted in Beltsville Thawing Solution into five treatments: Positive control (Pos_Cont, storage at 17 °C without L-cysteine) and groups with 0, 0.5, 1, and 2 mmol/L of L-cysteine supplementation stored at 5 °C. Variables were analyzed as repeated measures, considering treatment, storage time, and interaction as main factors. The effects of different L-cysteine concentrations were also evaluated using polynomial orthogonal contrasts. Sperm motility and pH were higher in the Pos_Cont compared to the groups stored at 5 °C (P < 0.05). In polynomial orthogonal contrast models, total motility was affected by the interaction between L-cysteine and storage time (P = 0.04), with a linear increase in motility when increasing the amount of L-cysteine at 72 and 120 h. Progressive motility increased quadratically as the L-cysteine reached 1 mmol/L (P < 0.01). In the thermoresistance test at 120 h, sperm motility increased quadratically up to an L-cysteine dose of 1 mmol/L (P < 0.05). Sulfhydryl content linearly increased with L-cysteine supplementation (P = 0.01), with no effect on intracellular ROS and sperm lipid peroxidation (P ≥ 0.06) in 5ºC-stored doses. In conclusion, L-cysteine supplementation has a positive effect on sperm motility up to 120 h of storage at 5 °C.

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AIM: To evaluate the bond strength (BS) and analysis of the adhesive interface in root canals filled with bioceramic gutta percha sealers and cones. MATERIAL AND METHODS: Ninety-six maxillary canines were divided into eight groups according to the endodontic sealer (AH Plus, AH Plus Bioceramic, Bio-C Sealer or Bio-C Sealer Ion+ and gutta percha cones (conventional or bioceramic) tested. They were analyzed using the BS test, failure pattern, analysis of the adhesive interface by scanning electron microscopy and confocal laser scanning microscopy. The BS data were compared between groups using the analysis of variance test with the Turkey post-test. The chi-square test was used to assess the type of failure and the non-parametric Mann-Whitney and Kruse-Wallis tests (P < 0.05). RESULTS: Analysis of variance showed higher BS values for the groups of bioceramic gutta percha cones in Bio-C Sealer Ion+ (8.38 ± 4.27), AH Plus Bioceramic (6.19 ± 3.28), Bio-C Sealer (5.70 ± 3.18), AH Plus (4.61 ± 2.11) and for conventional gutta percha cones in AH Plus sealers (4.26 ± 2.35), Bio-C Sealer Ion + (3.63 ± 2.29), Bio-C Sealer (2.94 ± 2.32) and AH Plus Bioceramic (1.19 ± 0.89) (P < 0.05). Relative to the type of failure and adaptation of the types of filling material, a higher percentage of mixed failures was observed (gaps between 1 µm-10 µm) for the group with bioceramic gutta percha cones (P < 0.001). CONCLUSION: The bond between sealers and bioceramic gutta percha cones showed higher bond strength values and greater penetration into the dentin tubules. CLINICAL RELEVANCE: The filling the root canal system with bioceramic sealers should be associated with bioceramic gutta percha cones.

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Snakebite envenomation (SBE)-induced immunity refers to individuals who have been previously bitten by a snake and developed a protective immune response against subsequent envenomations. The notion stems from observations of individuals, including in the indigenous population, who present only mild signs and symptoms after surviving multiple SBEs. Indeed, these observations have engendered scientific interest and prompted inquiries into the potential development of a protective immunity from exposure to snake toxins. This review explores the evidence of a protective immune response developing following SBE. Studies suggest that natural exposure to snake toxins can trigger protection from the severity of SBEs, mediated by specific antibodies. However, the evaluation of the immune memory response in SBE patients remains challenging. Further research is needed to elucidate the immune response dynamics and identify potential targets for therapeutic interventions. Furthermore, the estimation of the effect of previous exposures on SBE epidemiology in hyperendemic areas, such as in the indigenous villages of the Amazon region (e.g., the Yanomami population) is a matter of debate.

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Watermelon (Citrullus lanatus) is a fruit widely consumed by the Brazilian population; however, its rind is usually discarded, despite its nutritional value. This work aimed to develop a watermelon rind flour (WRF) and a fiber-rich bread. The WRF was submitted to microbiological analysis, proximate composition, antioxidant activity, and a profile of phenolic compounds. Six types of bread were developed: three using WRF (20%, 30%, and 40% of wheat flour replacement) and three control samples (only wheat flour), which were submitted to the same analysis, in addition to colorimetric properties, instrumental texture profile, and sensory evaluation (check-all-that-apply, purchase intent, and acceptance test). A high fiber content was observed in WRF (27.15%). The total concentration of phenolic compounds was 2.38 ± 0.20 mg of gallic acid equivalent per g and benzoic acid was the main compound found (73.50 mg/100 g WRF). The results of the antioxidant capacity through the DPPH method indicated a 30% reduction. The WRF 40% bread had 3.06 g of insoluble fiber, characterizing itself as a source of fiber. In the instrumental texture analysis, it was observed that bread hardness increased significantly as the WRF content increased. The formulation of the bread containing WRF is an alternative for the use of waste, favoring the development of a fiber-source product, with a functional food claim.

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INTRODUCTION: The aim of this study was to evaluate the influence on bond strength and interface quality of different canal drying protocols in roots filled with Bio-C Sealer (BCS; Angelus, Londrina, Paraná, Brazil). METHODS: Ninety-six roots of upper canines were prepared with an R50 file (Reciproc; VDW GmbH, Munich, Germany) and irrigated with 2.5% sodium hypochlorite and 17% EDTA under ultrasonic agitation. Roots were divided according to the drying protocol as follows: dry, the White Mac tip (Ultradent, Indaiatuba, SP, Brazil) for 5 seconds followed by aspiration with a capillary tip for 5 seconds and paper points; slightly moist, the White Mac tip followed by capillary aspiration without paper points; wet, the White Mac tip followed by a single paper point. The roots were filled with BCS or AH Plus (AHP; Dentsply Maillefer, Ballaigues, Switzerland) (n = 16) and sectioned for the push-out test after 3 months. Failure modes were assessed, and the interface morphology was analyzed under scanning electron microscopy. After 6 months, the other half of the roots were evaluated. Data were analyzed by analysis of variance/Tukey test at 5%. The chi-square test was used in the failure analysis and the Kruskal-Wallis/Dwass-Steel-Critchlow-Fligner for interface analysis. RESULTS: The AHP-filled roots had the highest bond strength when the canal was dried (P < .05). No difference was found for periods (P > .05). For BCS, the highest bond strength was found in the slightly moist canals (P < .05). A predominance of adhesive failures was observed. The dried canals filled with AHP had the highest percentage of good adaptation, whereas BCS had no difference. CONCLUSIONS: The best drying protocol for AHP is using the White Mac tip followed by capillary tip aspiration and paper points until complete dryness, and for BCS, it is using the White Mac tip followed by capillary aspiration without paper points.

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OBJECTIVES: To evaluate the prevalence and morphological characteristics of DI using CBCT. METHODS: A literature search was performed in PubMed, Embase, Scopus, and Web of Science. Inclusion criteria were randomized clinical trials, cross-sectional studies, and prospective and retrospective cohort studies evaluating the morphological characteristics of DI in anterior teeth using CBCT. Three reviewer authors independently screened the studies, applied the eligibility criteria, assessed the risk of bias, and extracted until September (2022). The risk of bias was evaluated using the Joanna Briggs Institute criteria. Meta-analyses of proportions were used for estimate the prevalence DI according to factors at participant and tooth levels. RESULTS: Six studies were included in the meta-analysis. Among 7373 individuals, a prevalence of 7.45 % of DI was observed (n = 258; τ2 = 0.0096; CI of 4.51-11.3; p < 0.05), with no significant influence of sex. Regarding laterality, unilateral DI showed higher mean prevalence (4.30 %; CI of 2.03-7.33). Among the 382 anterior teeth with DI (0.72 %), the most affected tooth was the upper lateral incisor (5.12 %; n = 329; CI of 2.35-8.86; p < 0.001), type I was the most prevalent (0.59 %; CI of 0.24-1.08) and the presence of open apex and periradicular pathology ranged from 4.3 % to 22.72 % and 3.5-77.92 %, respectively. CONCLUSIONS: The prevalence of individuals with dens invaginatus was 7.45 %, the most affect tooth was the upper lateral incisor with a prevalence of 5.12 % unilaterally and type I was the most prevalent morphology.

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Transport of extended boar semen doses is a common practice in the swine industry. This study aimed to verify the effect of agitation time on sperm parameters during storage in two semen extenders. One normospermic ejaculate from each boar (n = 20) was diluted in a split sample design with long-term (LONG, Androstar® Plus) and short-term (SHORT, Beltsville Thawing Solution) extenders. Extended semen doses were filled with a total volume of 45 mL and 1.5 billion sperm cells and submitted to 0, 3, 6, and 12 h of agitation in an orbital shaker at 70 rpm. The samples were stored at 17 °C for 120 h. Sperm parameters were evaluated for sperm motility, plasma membrane integrity, pH, thermo-resistance test (TRT), oxidative stress status, and mitochondrial membrane potential. Total and progressive motility were affected by the interaction between the agitation time and the extender, with a linear reduction in sperm motility as the agitation time increased for LONG extender (P ≤ 0.05). Semen doses diluted with SHORT showed a higher pH (P < 0.01), and agitation time had a positive quadratic effect with the highest pH observed after 6 h of agitation, regardless of the extender used (P < 0.01). Sperm motility after TRT and plasma membrane integrity potential were not affected by agitation time (P > 0.05). Mitochondrial membrane potential and oxidative stress status quadratically decreased as agitation time increased (P ≤ 0.05). Based on the results, long transport durations of AI doses under mild vibration emissions affect boar semen quality.

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Chemical composition of temporary cements interferes in the bond strength and quality of the bond interface of glass fiber posts to root dentin. The aim of the present study was to evaluate the influence of different temporary cements on the bond strength of fiberglass posts and resin cement. Thirty-two maxillary central incisor roots were standardized at 15 mm length. The root canals were prepared with Reciproc R50 and filled with a R50 single cone and AH Plus. Ten mm of filling material was removed with a heated Schilder condenser, leaving 5 mm of apical filling material. The roots were randomly distributed into 4 groups (n = 8). In the control group, the root canal was prepared with a standard drill according to the post diameter (DC #1, FGM, Joinville, Brazil), irrigated with 5 mL of distilled water and immediately received the fiberglass post cemented with self-adhesive resin cement. For the other groups, cores were made with temporary intraradicular retainers cemented with different temporary cements: methacrylate-based resin (Bifix Temp - Voco), calcium hydroxide-based (Provicol - Voco) and zinc oxide-based - eugenol-free (Relyx Temp NE - 3M). After 7 days, mechanical removal of the temporary retainers, preparation, irrigation of the root canal and cementation of the fiberglass post were performed, following the same protocol that had been performed in the control group. The roots were sectioned to obtain 3 slices per root third. The most cervical section of each third was used for the push-out test and failure pattern analysis, while the most apical section was subjected to analysis of the adhesive interface by scanning electron microscopy (SEM). The BS data were compared between groups using the two-way ANOVA and Tukey post-test. The failure pattern results were expressed in percentage and compared between groups using the chi-square test and the material adaptation data at the bond interface were evaluated using the Kruskal-Wallis and Dwass-Steel-Critchlow-Fligner tests. The results showed higher BS in the cervical third, with a higher value in the control group (10.8 ± 0.94) and Bifix Temp group (9.78 ± 0.71), with no statistically significant difference between these groups (P > .05). The middle and apical thirds showed no statistically significant difference (P > .05). As regards the type of failure, a higher percentage of mixed adhesive failures was observed for all groups. Analysis of the adhesive interface by SEM showed that the temporary cement Bifix Temp showed greater adaptation at the bond interface. It was concluded that the methacrylate-based resin temporary cement showed the highest bond strength values and best adaptation to root dentin than the zinc oxide-based and calcium hydroxide-based temporary cements.

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AIM: To evaluate the influence of root canal filling quality on periapical lesion status using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: The bibliographic search was conducted in electronic databases of PubMed, Embase, Scopus, and Web of Science without restrictions related to the year of publication and language. Inclusion criteria were prospective or retrospective cohort studies that followed periapical pathosis for, at least, 1 year. Three reviewers independently evaluated the eligibility for inclusion, extracted data, and assessed the risk of bias. The quality of the studies was based on the Newcastle-Ottawa Scale. This meta-analysis was performed to evaluate the quality of treatment by the homogeneity and apical extension of the filling. RESULTS: Of the 1179 studies initially recovered, six cohort studies were included, out of which four were considered with a low risk of bias. The results showed that the absence of gaps in the filling reduced the chance of unhealed periapical lesions by 2.39 times (RR = 2.39; 95% CI: 1.62-3.53; p < 0.00001; I2 = 55%). An apical filling extension of 0-2 mm below the apex also contributed significantly to the absence of unhealed periapical lesions (RR = 1.49; 95% CI: 1.15-1.94; p = 0.003; I2 = 2%). CONCLUSION: The homogeneity and apical extension of the filling influenced the presence of unhealed periapical lesions in endodontically treated teeth evaluated using CBCT. CLINICAL RELEVANCE: Apical extension of the filling ranging between 0 and 2 mm short of the apical foramen and the homogeneity of the filling without gaps are directly related to the success rate of root canal treatment.

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BACKGROUND: Most cystic echinococcosis cases in Southern Brazil are caused by Echinococcus granulosus and Echinococcus ortleppi. Proteomic studies of helminths have increased our knowledge about the molecular survival strategies that are used by parasites. Here, we surveyed the protein content of the hydatid fluid compartment in E. granulosus and E. ortleppi pulmonary bovine cysts to better describe and compare their molecular arsenal at the host-parasite interface. METHODS: Hydatid fluid samples from three isolates of each species were analyzed using mass spectrometry-based proteomics (LC-MS/MS). In silico functional analyses of the identified proteins were performed to examine parasite survival strategies. RESULTS: The identified hydatid fluid protein profiles showed a predominance of parasite proteins compared to host proteins that infiltrate the cysts. We identified 280 parasitic proteins from E. granulosus and 251 from E. ortleppi, including 52 parasitic proteins that were common to all hydatid fluid samples. The in silico functional analysis revealed important molecular functions and processes that are active in pulmonary cystic echinococcosis, such as adhesion, extracellular structures organization, development regulation, signaling transduction, and enzyme activity. CONCLUSIONS: The protein profiles described here provide evidence of important mechanisms related to basic cellular processes and functions that act at the host-parasite interface in cystic echinococcosis. The molecular tools used by E. granulosus and E. ortleppi for survival within the host are potential targets for new therapeutic approaches to treat cystic echinococcosis and other larval cestodiases.

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Schistosomiasis has been controlled for more than 40 years with a single drug, praziquantel, and only one molluscicide, niclosamide, raising concern of the possibility of the emergence of resistant strains. However, the molecular targets for both agents are thus far unknown. Consequently, the search for lead compounds from natural sources has been encouraged due to their diverse structure and function. Our search for natural compounds with potential use in schistosomiasis control led to the identification of an algal species, Laurencia dendroidea, whose extracts demonstrated significant activity toward both Schistosoma mansoni parasites and their intermediate host snails Biomphalaria glabrata. In the present study, three seaweed-derived halogenated sesquiterpenes, (-)-elatol, rogiolol, and obtusol are proposed as potential lead compounds for the development of anthelminthic drugs for the treatment of and pesticides for the environmental control of schistosomiasis. The three compounds were screened for their antischistosomal and molluscicidal activities. The screening revealed that rogiolol exhibits significant activity toward the survival of adult worms, and that all three compounds showed activity against S. mansoni cercariae and B. glabrata embryos. Biomonitored fractioning of L. dendroidea extracts indicated elatol as the most active compound toward cercariae larvae and snail embryos.

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The need to estimate the orientation between frames of reference is crucial in spacecraft navigation. Robust algorithms for this type of problem have been built by following algebraic approaches, but data-driven solutions are becoming more appealing due to their stochastic nature. Hence, an approach based on convolutional neural networks in order to deal with measurement uncertainty in static attitude determination problems is proposed in this paper. PointNet models were trained with different datasets containing different numbers of observation vectors that were used to build attitude profile matrices, which were the inputs of the system. The uncertainty of measurements in the test scenarios was taken into consideration when choosing the best model. The proposed model, which used convolutional neural networks, proved to be less sensitive to higher noise than traditional algorithms, such as singular value decomposition (SVD), the q-method, the quaternion estimator (QUEST), and the second estimator of the optimal quaternion (ESOQ2).

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Trypanosoma cruzi, the etiological agent of Chagas disease in humans, infects a wide variety of vertebrates. Trypomastigotes, the parasite infective forms, invade mammalian cells by a still poorly understood mechanism. Adhesion of tissue culture- derived trypomastigotes to the extracellular matrix (ECM) prior to cell invasion has been shown to be a relevant part of the process. Changes in phosphorylation, S-nitrosylation, and nitration levels of proteins, in the late phase of the interaction (2 h), leading to the reprogramming of both trypomastigotes metabolism and the DNA binding profile of modified histones, were described by our group. Here, the involvement of calcium signaling at a very early phase of parasite interaction with ECM is described. Increments in the intracellular calcium concentrations during trypomastigotes-ECM interaction depends on the Ca2+ uptake from the extracellular medium, since it is inhibited by EGTA or Nifedipine, an inhibitor of the L-type voltage gated Ca2+ channels and sphingosine-dependent plasma membrane Ca2+ channel, but not by Vanadate, an inhibitor of the plasma membrane Ca2+-ATPase. Furthermore, Nifedipine inhibits the invasion of host cells by tissue culture- derived trypomastigotes in a dose-dependent manner, reaching 95% inhibition at 100 µM Nifedipine. These data indicate the importance of both Ca2+ uptake from the medium and parasite-ECM interaction for host-cell invasion. Previous treatment of ECM with protease abolishes the Ca2+ uptake, further reinforcing the possibility that these events may be connected. The mitochondrion plays a relevant role in Ca2+ homeostasis in trypomastigotes during their interaction with ECM, as shown by the increment of the intracellular Ca2+ concentration in the presence of Antimycin A, in contrast to other calcium homeostasis disruptors, such as Cyclopiazonic acid for endoplasmic reticulum and Bafilomycin A for acidocalcisome. Total phosphatase activity in the parasite decreases in the presence of Nifedipine, EGTA, and Okadaic acid, implying a role of calcium in the phosphorylation level of proteins that are interacting with the ECM in tissue culture- derived trypomastigotes. In summary, we describe here the increment of Ca2+ at an early phase of the trypomastigotes interaction with ECM, implicating both nifedipine-sensitive Ca2+ channels in the influx of Ca2+ and the mitochondrion as the relevant organelle in Ca2+ homeostasis. The data unravel a complex sequence of events prior to host cell invasion itself.

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INTRODUCTION: Obesity may lead to hyperandrogenia and affect female sexual function. The study aims to evaluate female sexual function and androgenic profile in obese women after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Forty obese women with a mean age of 34 years were prospectively studied. Diabetes and psychiatric and pelvic disorders were the exclusion criteria. All patients underwent LRYGB. Total (TT) and free (FT) testosterone, androstenedione (AD), dehydroepiandrosterone (DHEA) and the Sexual Quotient - Female Version were evaluated, preoperatively, 6 and 12 months after the operation. RESULTS: Preoperative incidence of sexual dysfunction was 10% and hyperandrogenia was 40%. At 6 months, sexual function was not different; and FT (0.49-0.33 ng/dl) and AD (2.0-1.3 ng/dl) decreased significantly. At 12 months, there was an improvement in female sexual function (77-84 points), related to desire and interest (22-25 points) and comfort (15.9-17.3 points) without case of sexual dysfunction at 12 months. Hyperandrogenia (40-8%), FT levels (0.5-0.3 ng/dl), and AD (2.0-1.4 ng/dl) decreased, while DHEA levels (3.4-4.2 ng/dl) increased. The percentage of weight loss was 22% and 31% at 6 and 12 months, respectively. Sexual function did not correlate with BMI, weight, or androgen levels in any period. CONCLUSION: Female sexual function in obese women with no diabetes and psychiatric and pelvic disorders improved in patients undergoing LRYGB, especially in desire, interest, and sexual comfort, and this occured after 6 months of the operation and unrelated to BMI, percentage of weight loss, or androgen levels. KEY POINTS: • In obese women with no diabetes and psychiatric and pelvic disorders the FSD improvement after LRYGB. • FSD no correlation with weight loss and BMI. • FSD no correlation with androgens levels.

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Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1) is a mitochondrial inner membrane protein involved in Ca2+ and K+ homeostasis in mammalian cells. Here, we demonstrate that the Letm1 orthologue of Trypanosoma cruzi, the etiologic agent of Chagas disease, is important for mitochondrial Ca2+ uptake and release. The results show that both mitochondrial Ca2+ influx and efflux are reduced in TcLetm1 knockdown (TcLetm1-KD) cells and increased in TcLetm1 overexpressing cells, without alterations in the mitochondrial membrane potential. Remarkably, TcLetm1 knockdown or overexpression increases or does not affect mitochondrial Ca2+ levels in epimastigotes, respectively. TcLetm1-KD epimastigotes have reduced growth, and both overexpression and knockdown of TcLetm1 cause a defect in metacyclogenesis. TcLetm1-KD also affected mitochondrial bioenergetics. Invasion of host cells by TcLetm1-KD trypomastigotes and their intracellular replication is greatly impaired. Taken together, our findings indicate that TcLetm1 is important for Ca2+ homeostasis and cell viability in T cruzi.

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Non-T cell activation linker (NTAL) membrane protein depletion from lipid rafts by alkylphospholipids or downregulation by shRNA knockdown decreases cell viability through regulation of the Akt/PI3K pathway in mantle cell lymphoma and acute promyelocytic leukemia cells. Here, we confirmed that the knockdown of NTAL in acute myeloid leukemia (AML) cell lines was associated with decreased cell proliferation and survival. Similarly, a xenograft model using AML cells transduced with NTAL-shRNA and transplanted into immunodeficient mice led to a 1.8-fold decrease in tumor burden. Using immunoprecipitation, LC-MS/MS analysis, and label-free protein quantification, we identified interactors of NTAL in two AML cell lines. By evaluating the gene expression signatures of the NTAL protein interactors using the PREdiction of Clinical Outcomes from Genomic Profiles database, we found that 12 NTAL interactors could predict overall survival in AML, in at least two independent cohorts. In addition, patients with AML exhibiting a high expression of NTAL and its interactors were associated with a leukemic granulocyte-macrophage progenitor-like state. Taken together, our data provide evidence that NTAL and its protein interactors are relevant to AML cell proliferation and survival and represent potential therapeutic targets for granulocyte-macrophage progenitor-like leukemias.

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