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Although a growing body of evidence demonstrates that altered mtDNA content (mtDNAc) has clinical implications in several types of solid tumours, its prognostic relevance in acute promyelocytic leukaemia (APL) patients remains largely unknown. Here, we show that patients with higher-than-normal mtDNAc had better outcomes regardless of tumour burden. These results were more evident in patients with low-risk of relapse. The multivariate Cox proportional hazard model demonstrated that high mtDNAc was independently associated with a decreased cumulative incidence of relapse. Altogether, our data highlights the possible role of mitochondrial metabolism in APL patients treated with ATRA., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Heart failure (HF) is the most prevalent disease among chronic diseases and has been associated with a high prevalence of erectile dysfunction (ED)., Objective: this study aims to analyze research that has as its object of study the sexual activity of patients with HF., Methods: A high-sensitivity search was performed in databases (PUBMED via MEDLINE, Cochrane, EMBASE, Web of Science, SCOPUS AND CINAHL) using descriptors linked to sexuality and heart failure., Results: Fifteen studies from 7 countries with a total sample of 6244 participants were included., Conclusion: It was identified that patients with HF have alterations in their sexual activities, which are more common in males. Among men, it was noticed that the most reported sexual disorder was erectile dysfunction., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Stathmin 1 (STMN1) is a microtubule-destabilizing protein highly expressed in hematological malignancies and involved in proliferation and differentiation. Although a previous study found that the PML-RARα fusion protein, which contributes to the pathophysiology of acute promyelocytic leukemia (APL), positively regulates STMN1 at the transcription and protein activity levels, little is known about the role of STMN1 in APL. In this study, we aimed to investigate the STMN1 expression levels and their associations with laboratory, clinical, and genomic data in APL patients. We also assessed the dynamics of STMN1 expression during myeloid cell differentiation and cell cycle progression, and the cellular effects of STMN1 silencing and pharmacological effects of microtubule-stabilizing drugs on APL cells. We found that STMN1 transcripts were significantly increased in samples from APL patients compared with those of healthy donors (all p < 0.05). However, this had no effect on clinical outcomes. STMN1 expression was associated with proliferation- and metabolism-related gene signatures in APL. Our data confirmed that STMN1 was highly expressed in early hematopoietic progenitors and reduced during cell differentiation, including the ATRA-induced granulocytic differentiation model. STMN1 phosphorylation was predominant in a pool of mitosis-enriched APL cells. In NB4 and NB4-R2 cells, STMN1 knockdown decreased autonomous cell growth (all p < 0.05) but did not impact ATRA-induced apoptosis and differentiation. Finally, treatment with paclitaxel (as a single agent or combined with ATRA) induced microtubule stabilization, resulting in mitotic catastrophe with repercussions for cell viability, even in ATRA-resistant APL cells. This study provides new insights into the STMN1 functions and microtubule dynamics in APL., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim was to describe the criteria for construction, validation of content, and appearance of a questionnaire for the identification of violence in affective relationships in adolescence. Transverse methodological study, with a quantitative approach, conducted in the period between June and November 2017, with the construction of a questionnaire and validation of the content and appearance, by means of a Delphi survey with 20 experts on the area of violence and adolescence. To evaluate the clarity and pertinence of the items of the questionnaire, a pilot test was conducted with 76 adolescents, and analysis of the validity of content and reliability of the items by means of Content Validity Index (CVI), the Interrater Agreement (IRA), and the Cronbach alpha. The data were analyzed and processed by means of the Excel and Stata , version 14.0, programs. The indexes calculated in the first round of Delphi provided the following results: CVI = 0.93 and IRA = 0.93, showing evidence of the validity and reliability of the construct content, and in the second round, the questionnaire yielded a percentage of 100% agreement among the professionals and researchers. Verification of the internal consistency presented a mean value of 0.803, calculated by means of the Cronbach alpha. The questionnaire has validity of content and appearance in accordance with the proposed objective, bearing in mind that the indexes of faithfulness and agreement and the Cronbach alpha attained values above those of the established pattern of 80%.

The retinal tissue of warm-blooded vertebrates performs surprisingly complex and accurate transduction of visual information. To achieve precision, a multilayered neuroglia structure is established throughout the embryonic development, and the presence of radial Müller (glial) cells ensure differentiation, growth and survival for the neuronal elements within retinal environment. It is assumed that Müller cells serve as a dynamic reservoir of progenitors, capable of expressing transcription factors, differentiating and proliferating as either neuronal or glial cells depending on extrinsic cues. In the postnatal period, Müller glia may re-enter cell cycle and produce new retinal neurons in response to acute damage. In this context, glutathione (GSH), a virtually ubiquitous tripeptide antioxidant, which is found at milimolar concentrations in central glial cells, plays a vital role as a reducing agent, buffering radical oxygen species (ROS) and preventing cell death in severely injured retinal tissues. Despite its antioxidant role, data also point to GSH as a signaling agent, suggesting that GABA release and P2X 7 R-mediated calcium inwards occur in Müller cells in a GSH-enriched environment. These phenomena indicate a novel mechanistic response to damage in the vertebrate retinal tissue, particularly in neuron-glia networks.

Objective: To evaluate the indications for performing magnetic resonance imaging of the female pelvis at a referral center for cancer., Materials and Methods: This was a retrospective, single-center study, conducted by reviewing medical records and imaging reports. We included 1060 female patients who underwent magnetic resonance imaging of the pelvis at a cancer center between January 2013 and June 2014. The indications for performing the examination were classified according to the American College of Radiology (ACR) criteria., Results: The mean age of the patients was 52.6 ± 14.8 years, and 49.8% were perimenopausal or postmenopausal. The majority (63.9%) had a history of cancer, which was gynecologic in 29.5% and nongynecologic in 34.4%. Of the patients evaluated, 44.0% had clinical complaints, the most common being pelvic pain (in 11.5%) and bleeding (in 9.8%), and 34.7% of patients had previously had abnormal findings on ultrasound. Most (76.7%) of the patients met the criteria for undergoing magnetic resonance imaging, according to the ACR guidelines. The main indications were evaluation of tumor recurrence after surgical resection (in 25.9%); detection and staging of gynecologic neoplasms (in 23.3%); and evaluation of pelvic pain or of a mass (in 17.1%)., Conclusion: In the majority of the cases evaluated, magnetic resonance imaging was clearly indicated according to the ACR criteria. The main indication was local recurrence after surgical treatment of pelvic malignancies, which is consistent with the routine protocols at cancer centers.

Neuroglia interactions are essential for the nervous system and in the retina Müller cells interact with most of the neurons in a symbiotic manner. Glutathione (GSH) is a low-molecular weight compound that undertakes major antioxidant roles in neurons and glia, however, whether this compound could act as a signaling molecule in neurons and/or glia is currently unknown. Here we used embryonic avian retina to obtain mixed retinal cells or purified Müller glia cells in culture to evaluate calcium shifts induced by GSH. A dose response curve (0.1-10 mM) showed that 5-10 mM GSH, induced calcium shifts exclusively in glial cells (later labeled and identified as 2M6 positive cells), while neurons responded to 50 mM KCl (labeled as βIII tubulin positive cells). BBG 100 nM, a P2X7 blocker, inhibited the effects of GSH on Müller glia. However, addition of DNQX 70 μM and MK-801 20 μM, non-NMDA and NMDA blockers, had no effect on GSH calcium induced shift. Oxidized glutathione (GSSG) at 5 mM failed to induce calcium mobilization in glia cells, indicating that the antioxidant and/or structural features of GSH are essential to promote elevations in cytoplasmic calcium levels. Indeed, a short GSH pulse (60s) protects Müller glia from oxidative damage after 30 min of incubation with 0.1% H2O2. Finally, GSH induced GABA release from chick embryonic retina, mixed neuron-glia or from Müller cell cultures, which were inhibited by BBG or in the absence of sodium. GSH also induced propidium iodide uptake in Müller cells in culture in a P2X7 receptor dependent manner. Our data suggest that GSH, in addition to antioxidant effects, could act signaling calcium shifts at the millimolar range particularly in Müller glia, and could regulate the release of GABA, with additional protective effects on retinal neuron-glial circuit.

Introduction: Obesity is a disease in which inflammation is directly involved and can lead to impaired renal function., Objective: To evaluate the influence of short term exposure to cafeteria diet on kidney tissue inflammation and advanced glycation end products (AGEs) in the rat plasma., Methods: Male Wistar rats (10 weeks of age, weighing 350 g) were assigned to receive commercial chow diet (C; n = 8 animals/group, 5% of energy from fat) or cafeteria diet (CAF-D, n = 8 animals/group: 29% energy fat) and sucrose in drinking water (300 g/L) for 6 weeks., Results: adiposity index at six weeks was higher in CAF-D group compared to C. The same behavior was observed for plasma levels of glucose, triglycerides, leptin, insulin and AGEs. The gene expression of IL-6 and TNF-α in renal tissue was higher in CAF-D group and no significant difference in adipose tissue. There was no increase of these cytokines in plasma and kidney or histologically. There was a significant decrease of adiponectin in the CAF-D group., Conclusion: The short exposure CAF-D reflects changes in metabolism, increased plasma levels of AGEs, which may reflect the increased expression of inflammatory cytokines in the kidney.

Background and Objectives: This project is a continuation of a larger project entitled "Treatment with intragastric balloon (IGB) in patients with overweight and obesity in Recife" developed by Professor Dr. Gustavo Lopes de Carvalho. It is a project studying the effectiveness of treatment with IGB evaluating the loss of weight and body mass index and its impact on blood pressure, blood glucose, triglycerides, total cholesterol and fractions. It also assesses the lifestyle of patients studying whether treatment with IGB interferes in smoking, alcohol consumption, eating habits and physical exercises performed by patients. The present study added a larger project, the separate evaluation of the different types of abdominal fat-visceral fat and subcutaneous cell tissue fat - and was conducted to discover which of the 2 types of fat undergoes the greater reduction after IGB treatment. To measure these 2 types of fat, we used the ultrasonography technique, because it has been shown to be accurate and noninvasive., Methods: Twenty-five patients were evaluated before and after 6 months of IGB treatment., Results: The patients' ages ranged from 20 to 61 years, with 60% being 40 years of age or older. The majority (72%) were women. All variables (weight, body mass index [BMI], VF, and SCTF) showed a significant reduction (P < .05) in mean values after treatment. The difference was highest in the SCTF (17.5%) and ranged from an 11.4% to an 11.6% reduction in all other variables. The average loss of SCTF was highest among the patients who had lost up to 10.0% of their initial weight (19.2% for the ≤10.0% group vs 15.9% for the >10.0% group); however, the difference was not significant (P = .66). The average loss of VF was higher in the subgroup of patients who had lost >10.0% of their initial weight (16.2% vs 6.3%; P = .003). The Pearson correlation between the reductions in SCTF vs VF was negative, low, and nonsignificant (-0.17; P = .41)., Conclusions: After 6 months of IGB treatment, there was no significant difference between the reduction in abdominal SCTF and VF, but the results signify a possible correlation between the percentage of body weight loss and the type of abdominal fat reduced, as the impact on the VF was higher when the patients lost >10.0% of their initial weight.

The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration.

Several mechanisms underlying ethanol action in GABAergic synapses have been proposed, one of these mechanisms is on GABA release. Here, we report that in ovo exposure to ethanol induces an increase on GABA release in the embryonic chick retina. Eleven-day-old chick embryos (E11) received an injection of either phosphate buffer saline (PBS) or ethanol (10%, v/v, diluted in PBS), and were allowed to develop until E16. A single glutamate stimulus (2 mM) showed approximately a 40% increase on GABA release in E16 retinas when compared to controls. The effect was dependent on NMDA receptors and GAD65 mRNA levels, which were increased following the ethanol treatment. However, the numbers of GABA-, GAD-, and NR1-immunoreactive cells, and the expression levels of these proteins, were not affected. We conclude that ethanol treatment at a time point when synapses are being formed during development selectively increases GABA release in the retina via a NMDA receptor-dependent process., (Copyright 2009 ISDN. Published by Elsevier Ltd. All rights reserved.)

Glia represents the most numerous group of nervous system cells and CNS development and function depend on glial cells. We developed a purified Muller glia culture to investigate the expression of several neurotransmitter markers on these cells, such as dopaminergic, cholinergic, GABAergic and peptidergic receptors or enzymes, based on functional assays measuring second messenger levels or Western blot for specific proteins. Purified Muller cell culture was obtained from 8-day-old (E8) embryonic chick. Glial cells cultured for 15 days (E8C15) expressed D1A and D1B receptors mRNAs, but not D1D, as detected by RT-PCR. The binding of [3H]-SCH 23390 revealed an amount of expressed receptors around 40 fmol/mg protein. Dopamine (100 microM), PACAP (50 nM) and forskolin (10 microM) induced a 50-, 30- and 40-fold cAMP accumulation on glial cells, respectively, but not ip3 production. The dopamine-promoted cAMP accumulation was blocked by 2 microM SCH 23390. Carbachol stimulated a 3-fold ip3 accumulation. Western blot analysis also revealed the expression of tyrosine hydroxylase, L-dopa decarboxylase, PAC1 receptor, GAD67 and beta2-nicotinic receptor subunit by these cells. These results indicate that several components of neurotransmitter signaling and metabolism are found in cultured Muller cells.

1. Previous studies have shown that phorbol esters induce protein kinase C (PKC) mediated phosphorylation of the vesicular acetylcholine transporter (VAChT) and change its interaction with vesamicol. However, it is not clear whether physiological activation of receptors coupled to PKC activation can alter VAChT behavior. 2. Here we tested whether activation of kaianate (KA) receptors alters VAChT. Several studies suggest that the cholinergic amacrine cells display KA/AMPA receptors that mediate excitatory input to these neurons. In addition, KA in the chicken retina can generate intracellular messengers with the potential to regulate cellular functions. 3. In cultured chicken retina (E8C11) KA reduced vesamicol binding to VAChT by 53%. This effect was potentiated by okadaic acid, a protein phosphatase inhibitor, and was totally prevented by BIM, a PKC inhibitor. 4. Phorbol myristate acetate (PMA), but not alpha-PMA, reduced in more than 85% the number of L-[3H]-vesamicol-specific binding sites in chicken retina, confirming that activation of PKC can influence vesamicol binding to chicken VAChT. 5. The data show that activation of glutamatergic receptors reduces [3H]-vesamicol binding sites (VAChT) likely by activating PKC and increasing the phosphorylation of the ACh carrier.

A previously healthy girl, without heart disease, who ingested 2400 mg of verapamil developed hypotension, trifasicular block pattern, mental confusion, mild metabolic acidosis, and hyperglycemia. She recovered with symptomatic and supportive therapy. A discussion is presented about the action mechanism of the drug.