Blood levels of metallic chemical element exposure patterns and associated factors in a population living in an Industrial District in Brazil.

AIM: to estimate the level of metallic chemical elements in the population living in the Steel company vicinity in Santa Cruz, Rio de Janeiro, Brazil; and estimate the association between exposure to the Steel company and the blood metals concentrations patterns. METHOD: A cross-sectional study was carried out on 463 individuals aged 18+ years old residing 1+ years in the Steel company vicinity. Mg, Be, Co, Ba, Ni, Cd, Al, and Pb were assessed in blood by DRC-ICP-MS. Metallic chemical element concentration patterns were obtained by exploratory factor analysis in the studied population. Exposure was set as the distance (Km) from each participant's residence to the Steel company in Santa Cruz, georeferenced by GPS. The outcome was set as the positive factor loadings in the factor analysis, including Mg and Be (Factor-1), Co, Ba, and Ni (Factor-2), Cd, Al, and Pb (Factor-4). Crude and adjusted OR, and their respective 95 %CI, were estimated to explore associations between independent variables and the exposures to metallic elements positively associated with the factors using polychotomous logistic regression. RESULTS: A reduction of 19 % was found between each km distance from the residence and the Steel company and P50 concentration of Cd, Al, and Pb (ORP50=0.81; 95 %CI:0.67-0.97), after adjusting by age, sex, and smoking. No statistically significant associations were observed for the distance from residences and the Steel company, after adjusting for age, gender, having a domestic vegetable garden and chewing gum for Mg and Be concentrations (Factor-1) (ORP50=0.84; 95 %CI:0.70-1.01; ORP75=1.10; 95 %CI:0.91-1.34); nor for Co, Ba and Ni (Factor-2) blood concentrations(ORP50=1.10; 95 %CI:0.91-1.33; ORP75=1.03; 95 %CI:0.84-1.26), in the adjusted analysis. CONCLUSIONS: For each Km distance from residences to the Steel company, a 19 % reduction in the risk of Cd, Al, and Pb blood concentration was observed in the population living in Santa Cruz, Rio de Janeiro, Brazil.

Pon1 and Sult1a1 Polymorphisms and Breast Cancer Among Young Women in Brazil.

Purpose: To investigate the association of genetic polymorphisms Gln192Arg and Leu55Met of Paraoxonase 1 (PON1) gene, and Arg213His of Sulfotransferase 1A1 (SUT1A1) gene with occurrence of breast cancer among young women living in Rio de Janeiro city. Methods: This is a hospital-based case-control study including 265 women aged 18-35 years, diagnosed with breast cancer at National Cancer Institute; and 277 controls in the same age group selected among women patients and companions of three general hospitals from Rio de Janeiro public health network. Polymorphisms genotyping was performed using the PCR-RFLP technique. Results: For PON1 gene, breast cancer women had a greater chance of being homozygote for Leu55Met polymorphism (ORadjusted = 1.42, 95% CI= 0.67-3.00, recessive model) and a lower chance of having at least one allele of Gln192Arg polymorphism (ORadjusted = 0.75, 95% CI = 0.50-1.13, dominant model), but without statistical significance. Accordingly, frequency of the haplotype Met55/Arg192 was lower among breast cancer women, but no statistically significant association was observed (ORadjusted = 0.85; 95% CI = 0.48-1.51). SULT1A1 His/His genotype was significantly associated with a protective effect for breast cancer (OR adjusted = 0.51, 95% CI = 0.28-0.91, recessive model). Conclusion: Arg213His polymorphism of SUT1A1 gene showed a protective effect against breast cancer among Brazilian young women. More studies with different designs are needed to understand the role of PON1 and SULT1A1 polymorphisms in breast cancer development in young Brazilian women.

Ultrasonography of the superficial temporal and axillary arteries in giant cell arteritis diagnosis.

OBJECTIVES: Giant cell arteritis (GCA) is the main systemic vasculitis in individuals aged ≥ 50 years. Color Doppler ultrasound (CDS) has an established role in GCA diagnosis and management. This study aims to assess the clinical characteristics associated with a positive CDS evaluation and the impact of additional axillary artery examination on diagnostic sensitivity. MATERIAL AND METHODS: We conducted a retrospective analysis of patients undergoing CDS of the superficial temporal arteries, with or without axillary artery assessment, at our hospital, between 2009 and 2023. Patients meeting the new 2022 diagnostic criteria for GCA were included and their characteristics were analyzed according to the presence of the halo sign on CDS. RESULTS: Of the 135 included patients (54 % female, mean age 75 ± 8 years), the halo sign was observed in 57 %, correlating with higher systemic symptom prevalence (61 % vs 42 %, p = 0.035), lower hemoglobin (p < 0.001), and higher erythrocyte sedimentation rate (p = 0.028). The halo sign inversely related to prior corticosteroid therapy (p = 0.033). Patients with axillary halo sign had fewer external carotid symptoms and a higher vertebral halo sign prevalence. Vertebral halo sign was associated with posterior circulation ischemic stroke (65 %, p < 0.001). Axillary artery studies improved diagnostic sensitivity by 9 %. CONCLUSION: In our study, the halo sign correlated with higher systemic symptoms and analytical abnormalities. Axillary artery examination enhanced CDS sensitivity, linked to severe outcomes like stroke. Prior corticosteroid therapy reduced CDS sensitivity. The correlation of clinical, laboratory, and ultrasound findings provides a more comprehensive understanding of GCA pathogenesis and evolution.

Emotional Eating and Uncontrolled Eating as Risk Predictors for Disordered Eating Attitudes in Candidates for Bariatric Surgery Treated at a Public Hospital in the Amazon.

This study analyzes the eating behavior and factors associated with the presence of disordered eating attitudes in patients undergoing bariatric surgery. It is a cross-sectional, descriptive, and analytical study conducted at a hospital in the Amazon region of Brazil. The Disordered Eating Attitude Scale reduced version (DEAS-s) was used to assess the risk of eating disorders and the Three-Factor Eating Questionnaire (TFEQ-R21) was used to characterize eating behavior. A total of 205 patients participated, with a mean age of 37.5 ± 8.6 years. The majority of participants were female (93.7%; p < 0.001), and the mean BMI was 45.3 ± 6.7 kg/m2. It was found that cognitive restraint had the highest mean (52.6 ± 19.9; p < 0.001). As for the DEAS-s, the question with the highest mean response was "spending one or more days without eating or consuming only liquids to lose weight" (2.80 ± 1.99). Female participants had a higher score for emotional eating (p = 0.016). Disordered eating attitudes showed a correlation with emotional eating and uncontrolled eating. These results suggest that candidates for bariatric surgery may have susceptibility to eating disorders. The importance of a multidisciplinary team conducting monitoring during the preoperative period is highlighted.

Association between Self-Perception of Chewing, Chewing Behavior, and the Presence of Gastrointestinal Symptoms in Candidates for Bariatric Surgery.

Given the changes in the digestive tract post-bariatric surgery, adapting to a new pattern of eating behavior becomes crucial, with special attention to the specifics of chewing mechanics. This study aimed to investigate the association between self-perception of chewing, chewing behavior, and the presence of gastrointestinal symptoms in preoperative patients undergoing bariatric surgery. Sixty adult candidates for bariatric surgery at a public hospital in Belém (Brazil) were analyzed. Participants predominantly exhibited unilateral chewing patterns (91.6%), a fast chewing rhythm (73.3%), a large food bolus (80%), liquid intake during meals (36.7%), and 41.7% reported that chewing could cause some issue. Significant associations were found between the perception of causing problems and chewing scarcity (p = 0.006), diarrhea (p = 0.004), absence of slow chewing (p = 0.048), and frequent cutting of food with front teeth (p = 0.034). These findings reveal a relationship between the perception of chewing problems and chewing scarcity, presence of diarrhea, and fast chewing.

Bortezomib suppresses acute myelogenous leukaemia stem-like KG-1a cells via NF-κB inhibition and the induction of oxidative stress.

Acute myelogenous leukaemia (AML) originates and is maintained by leukaemic stem cells (LSCs) that are inherently resistant to antiproliferative therapies, indicating that a critical strategy for overcoming chemoresistance in AML therapy is to eradicate LSCs. In this work, we investigated the anti-AML activity of bortezomib (BTZ), emphasizing its anti-LSC potential, using KG-1a cells, an AML cell line with stem-like properties. BTZ presented potent cytotoxicity to both solid and haematological malignancy cells and reduced the stem-like features of KG-1a cells, as observed by the reduction in CD34- and CD123-positive cells. A reduction in NF-κB p65 nuclear staining was observed in BTZ-treated KG-1a cells, in addition to upregulation of the NF-κB inhibitor gene NFΚBIB. BTZ-induced DNA fragmentation, nuclear condensation, cell shrinkage and loss of transmembrane mitochondrial potential along with an increase in active caspase-3 and cleaved PARP-(Asp 214) level in KG-1a cells. Furthermore, BTZ-induced cell death was partially prevented by pretreatment with the pancaspase inhibitor Z-VAD-(OMe)-FMK, indicating that BTZ induces caspase-mediated apoptosis. BTZ also increased mitochondrial superoxide levels in KG-1a cells, and BTZ-induced apoptosis was partially prevented by pretreatment with the antioxidant N-acetylcysteine, indicating that BTZ induces oxidative stress-mediated apoptosis in KG-1a cells. At a dosage of 0.1 mg/kg every other day for 2 weeks, BTZ significantly reduced the percentage of hCD45-positive cells in the bone marrow and peripheral blood of NSG mice engrafted with KG-1a cells with tolerable toxicity. Taken together, these data indicate that the anti-LSC potential of BTZ appears to be an important strategy for AML treatment.

Association between extrapolated time in range and large for gestational age infants in pregnant women with type 1 diabetes.

AIMS: To evaluate the association between extrapolated time in range (eTIR), measured by self-monitoring of blood glucose (SMBG), and large-for-gestational-age (LGA) infants in pregnancies with type 1 diabetes (T1D). METHODS: Retrospective cohort analysis including singleton pregnancies with T1D who started antenatal care before 20 gestational weeks and delivered live newborns at a Brazilian hospital between 2010 and 2019, with LGA fetuses as the main outcome. Glycemic records acquired using SMBG were categorized as eTIR, extrapolated time below range (eTBR), and extrapolated time above range (eTAR). Women were divided into two groups (LGA and adequate for gestational age [AGA]) and compared regarding clinical characteristics, obstetric outcomes, and frequencies of eTIR, eTBR, and eTAR. Logistic regression analysis verified the independent predictive variables for LGA infants. RESULTS: Data from 125 pregnancies were analyzed. For the first, second and third trimesters, each 1 % increase in eTIR was associated with a decreased risk of LGA by 2.9 % (OR: 0.971; 95%CI: 0.945-0.998), 2.5 % (OR: 0.975; 95%CI: 0.951-0.999) and 2.3 % (OR: 0.977; 95%CI: 0.955-0.998) and each 1 % increase in eTAR was associated with an increased risk of LGA by 2.7 % (OR: 1.027; 95%CI: 1.005-1.050), 3.9 % (OR: 1.039; 95%CI: 1.014-1.063) and 4.6 % (OR: 1.046; 95%CI: 1.018-1.075), respectively. CONCLUSION: The concept of TIR can be extrapolated to patients undergoing SMBG to assess the risk of LGA infants in pregnant women with T1D.

Emetine induces oxidative stress, cell differentiation and NF-κB inhibition, suppressing AML stem/progenitor cells.

Acute myeloid leukemia (AML) is a fatal malignancy of the blood and bone marrow. Leukemic stem cells (LSCs) are a rare subset of leukemic cells that promote the development and progression of AML, and eradication of LSCs is critical for effective control of this disease. Emetine is an FDA-approved antiparasitic drug with antitumor properties; however, little is known about its potential against LSCs. Herein, we explored the antileukemic potential of emetine, focusing on its effects on AML stem/progenitor cells. Emetine exhibited potent cytotoxic activity both in hematologic and solid cancer cells and induced AML cell differentiation. Emetine also inhibited AML stem/progenitor cells, as evidenced by decreased expression of CD34, CD97, CD99, and CD123 in KG-1a cells, indicating anti-AML stem/progenitor cell activities. The administration of emetine at a dosage of 10 mg/kg for two weeks showed no significant toxicity and significantly reduced xenograft leukemic growth in vivo. NF-κB activation was reduced in emetine-treated KG-1a cells, as shown by reduced phospho-NF-κB p65 (S529) and nuclear NF-κB p65. DNA fragmentation, YO-PRO-1 staining, mitochondrial depolarization and increased levels of active caspase-3 and cleaved PARP (Asp214) were detected in emetine-treated KG-1a cells. Moreover, treatment with the pancaspase inhibitor Z-VAD(OMe)-FMK partially prevented the apoptotic cell death induced by emetine. Emetine treatment also increased cellular and mitochondrial reactive oxygen species, and emetine-induced apoptosis in KG-1a cells was partially prevented by the antioxidant N-acetylcysteine, indicating that emetine induces apoptosis, at least in part, by inducing oxidative stress. Overall, these studies indicate that emetine is a novel potential anti-AML agent with promising activity against stem/progenitor cells, encouraging the development of further studies aimed at its clinical application.

Piplartine eliminates CD34 + AML stem/progenitor cells by inducing oxidative stress and suppressing NF-κB signalling.

Acute myeloid leukaemia (AML) is a haematological malignancy characterised by the accumulation of transformed myeloid progenitors in the bone marrow. Piplartine (PL), also known as piperlongumine, is a pro-oxidant small molecule extracted from peppers that has demonstrated antineoplastic potential in solid tumours and other haematological malignancies. In this work, we explored the potential of PL to treat AML through the use of a combination of cellular and molecular analyses of primary and cultured leukaemia cells in vitro and in vivo. We showed that PL exhibits in vitro cytotoxicity against AML cells, including CD34+ leukaemia-propagating cells, but not healthy haematopoietic progenitors, suggesting anti-leukaemia selectivity. Mechanistically, PL treatment increased reactive oxygen species (ROS) levels and induced ROS-mediated apoptosis in AML cells, which could be prevented by treatment with the antioxidant scavenger N-acetyl-cysteine and the pancaspase inhibitor Z-VAD(OMe)-FMK. PL treatment reduced NFKB1 gene transcription and the level of NF-κB p65 (pS536), which was depleted from the nucleus of AML cells, indicating suppression of NF-κB p65 signalling. Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies.

Low back pain, pelvic pain, and associated factors in type 1 diabetic pregnant women.

INTRODUCTION: Pregnancy and diabetes mellitus promote several musculoskeletal changes predisposing this population to complaints of Lower Back (LB) and Pelvic Pain (PP). OBJECTIVE: To assess the frequency of LB and PP and associated factors in type 1 Diabetic (DM1) pregnant women. METHOD: An observational analytical cross-sectional study. Thirty-six pregnant women with DM1 were evaluated through a postural assessment with a focus on pelvic positioning and what patients reported. The associated factors were assessed using the State-Trait Anxiety Inventory (STAI), the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Female Sexual Function Index (FSFI). RESULTS: The frequency of LB and PP was 55.6 % and 30.6 %, respectively. The presence of anxiety was not associated with a higher prevalence of pain. The incidence of sexual dysfunctions was higher in the GD. DM1 duration had a mean of 14.9 years (± 8.2 SD) in the GD and 9.0 years (± 6.9 SD) in the GSD, which was statistically significant (p ≤ 0.050). In the multiple binary regression analysis for the occurrence of pain, the independent factor was DM1 duration ≥ 17 years (OR = 11.2; 95 % CI = 1.02‒124.75). The association between DM1 duration ≥ 17 years and being overweight showed a probability of 95 % for the studied population in the analysis of the probabilities of occurrence of the pain event. CONCLUSION: There was a high frequency of LB and PP related to pregnancy in DM1 pregnant women in the second trimester of pregnancy. The incidence of sexual dysfunction and DM1 duration ≥ 17 years increases the chance that DM1 pregnant women will experience pain. There was no association between anxiety. urinary incontinence and pain in DM1 pregnant women.

Low back pain, pelvic pain, and associated factors in type 1 diabetic pregnant women

Abstract Introduction Pregnancy and diabetes mellitus promote several musculoskeletal changes predisposing this population to complaints of Lower Back (LB) and Pelvic Pain (PP). Objective To assess the frequency of LB and PP and associated factors in type 1 Diabetic (DM1) pregnant women. Method: An observational analytical cross-sectional study. Thirty-six pregnant women with DM1 were evaluated through a postural assessment with a focus on pelvic positioning and what patients reported. The associated factors were assessed using the State-Trait Anxiety Inventory (STAI), the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Female Sexual Function Index (FSFI). Results The frequency of LB and PP was 55.6 % and 30.6 %, respectively. The presence of anxiety was not associated with a higher prevalence of pain. The incidence of sexual dysfunctions was higher in the GD. DM1 duration had a mean of 14.9 years (± 8.2 SD) in the GD and 9.0 years (± 6.9 SD) in the GSD, which was statistically significant (p ≤ 0.050). In the multiple binary regression analysis for the occurrence of pain, the independent factor was DM1 duration ≥ 17 years (OR = 11.2; 95 % CI = 1.02‒124.75). The association between DM1 duration ≥ 17 years and being overweight showed a probability of 95 % for the studied population in the analysis of the probabilities of occurrence of the pain event. Conclusion There was a high frequency of LB and PP related to pregnancy in DM1 pregnant women in the second trimester of pregnancy. The incidence of sexual dysfunction and DM1 duration ≥ 17 years increases the chance that DM1 pregnant women will experience pain. There was no association between anxiety. urinary incontinence and pain in DM1 pregnant women.

Polychaete (Alitta virens) meal inclusion as a dietary strategy for modulating gut microbiota of European seabass (Dicentrarchus labrax).

Recent research has revealed the significant impact of novel feed ingredients on fish gut microbiota, affecting both the immune status and digestive performance. As a result, analyzing the microbiota modulatory capabilities may be a useful method for assessing the potential functionality of novel ingredients. Therefore, this study aimed to evaluate the effects of dietary polychaete meal (PM) from Alitta virens on the autochthonous and allochthonous gut microbiota of European seabass (Dicentrarchus labrax). Two diets were compared: a control diet with 25% fishmeal (FM) and a diet replacing 40% of fishmeal with PM, in a 13-week feeding trial with juvenile fish (initial weight of 14.5 ± 1.0 g). The feed, digesta, and mucosa-associated microbial communities in fish intestines were analyzed using high-throughput sequencing of the 16S rRNA gene on the Illumina MiSeq platform. The results of feed microbiota analyses showed that the PM10 feed exhibited a higher microbial diversity than the FM diet. However, these feed-associated microbiota differences were not mirrored in the composition of digesta and mucosal communities. Regardless of the diet, the digesta samples consistently exhibited higher species richness and diversity than the mucosa samples. Overall, digesta samples were characterized by a higher abundance of Firmicutes in PM-fed fish. In contrast, at the gut mucosa level, the relative abundances of Mycobacterium, Taeseokella and Clostridium genera were lower in the group fed the PM10 diet. Significant differences in metabolic pathways were also observed between the FM and PM10 groups in both mucosa and digesta samples. In particular, the mucosal pathways of caffeine metabolism, phenylalanine metabolism, and sulfur relay system were significantly altered by PM inclusion. The same trend was observed in the digesta valine, leucine, and isoleucine degradation and secretion pathways. These findings highlight the potential of PM as an alternative functional ingredient in aquafeeds with microbiota modulatory properties that should be further explored in the future.

Studying the first order hyperpolarizability spectra in chalcone-based derivatives and the relation with one- and two-photon absorption transitions.

The first-order molecular hyperpolarizability (ß) dispersion was measured in seven chalcone-based molecules utilizing the tunable femtosecond hyper-Rayleigh scattering (tHRS) technique. Additionally, a theoretical model based on photophysical parameters was employed to better understand ß dispersion. Due to the distinct substitution patterns of the aryl/heteroaryl rings within the chalcone structure, varying profiles of one- and two-photon absorption spectra and ß dispersion were observed. The applied model highlighted two important factors contributing to achieving high ß values: (i) the presence of red-shifted one-photon and two-photon absorption bands; and (ii) the number of discernible absorption bands. To contextualize these results with other molecular structures, we employed the HRS figure of merit (FOM). Remarkably, it was revealed that chemically engineered small chalcone molecules exhibit a FOM comparable to larger quadrupolar and octupolar ones. This underscores the significance of tHRS scattering measurements and their correlation with absorptive parameters in the design and characterization of nonlinear optical materials.

Exercise of professional autonomy of intensive care nurses in the pandemic scenario.

OBJECTIVE: To analyze the exercise of professional autonomy of intensive care nurses during times of the new coronavirus pandemic. METHOD: A descriptive, qualitative study, conducted with 19 nurses from Intensive Care Units of two public hospitals and one private hospital. The information was produced from October 2020 to January 2021, through semi-structured interviews, using content analysis in thematic modality, guided by Eliot Freidson's Sociology of Professions. RESULTS: Nursesargued that it was difficult, amidst the pandemic, to act with all the prerogatives assigned to them by their social mandate, for various reasons, such as limited knowledge about the disease, fragile teamwork communication, and scarcity of material and human resources. CONCLUSION: The exercise of professional autonomy is shaped by the confrontation of multiple factors that impact the performance of intensive care nurses, especially in a context of pandemic crisis.

Variant rs17619600 in the gene encoding serotonin receptor 2B (HTR2B) increases the risk of gestational diabetes mellitus: a case-control study.

BACKGROUND: During pregnancy, the increase in maternal insulin resistance is compensated by hyperplasia and increased function of maternal pancreatic beta cells; the failure of this compensatory mechanism is associated with gestational diabetes mellitus (GDM). Serotonin participates in beta cell adaptation, acting downstream of the prolactin pathway; the blocking of serotonin receptor B (HTR2B) signaling in pregnant mice impaired beta cell expansion and caused glucose intolerance. Thus, given the importance of the serotoninergic system for the adaptation of beta cells to the increased insulin demand during pregnancy, we hypothesized that genetic variants (single nucleotide polymorphisms [SNPs]) in the gene encoding HTR2B could influence the risk of developing GDM. METHODS: This was a case-control study. Five SNPs (rs4973377, rs765458, rs10187149, rs10194776, and s17619600) in HTR2B were genotyped by real-time polymerase chain reaction in 453 women with GDM and in 443 pregnant women without GDM. RESULTS: Only the minor allele C of SNP rs17619600 conferred an increased risk for GDM in the codominant model (odds ratio [OR] 2.15; 95% confidence interval [CI] 1.53-3.09; P < 0.0001) and in the rare dominant model (OR 2.32; CI 1.61-3.37; P < 0.0001). No associations were found between the SNPs and insulin use, maternal weight gain, newborn weight, or the result of postpartum oral glucose tolerance test (OGTT). In the overall population, carriers of the XC genotype (rare dominant model) presented a higher area under the curve (AUC) of plasma glucose during the OGTT, performed for diagnostic purposes, compared with carriers of the TT genotype of rs17619600. CONCLUSIONS: SNP rs17619600 in the HTR2B gene influences glucose homeostasis, probably affecting insulin release, and the presence of the minor allele C was associated with a higher risk of GDM.

Predicting insulin use among women with gestational diabetes diagnosed in oral glucose tolerance test.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the most common complications affecting pregnant women. While most women will achieve adequate glycemic levels with diet and exercise, some will require pharmacological treatment to reach and maintain glucose levels between the desired thresholds. Identifying these patients early in pregnancy could help direct resources and interventions. METHODS: This retrospective cohort of women with GDM diagnosed with an abnormal 75g-OGTT presents data from 869 patients (724 in the diet group and 145 in the insulin group). Univariate logistic regression was used to compare the groups, and multivariable logistic regression was used to identify independent factors associated with the need for insulin. A log-linear function was used to estimate the probability of requiring pharmacological treatment. RESULTS: Women in the insulin group had higher pre-pregnancy BMI index (29.8 vs 27.8 kg/m2, odds ratio [OR] 1.06, 95% confidence interval [CI] 1.03-1.09), more frequent history of previous GDM (19.4% vs. 7.8%, OR 2.84, 95% CI 1.59-5.05), were more likely to have chronic hypertension (31.7% vs. 23.2%, OR 1.54, 95% CI 1.04-2.27), and had higher glucose levels at all three OGTT points. Multivariable logistic regression final model included age, BMI, previous GDM status, and the three OGTT values as predictors of insulin requirement. CONCLUSIONS: We can use regularly collected data from patients (age, BMI, previous GDM status, and the three OGTT values) to calculate the risk of a woman with GDM diagnosed in OGTT needing insulin. Identifying patients with a greater risk of requiring pharmacological treatment could help healthcare services to better allocate resources and offer closer follow-up to high-risk patients.

Iron Limitation Restores Autophagy and Increases Lifespan in the Yeast Model of Niemann-Pick Type C1.

Niemann-Pick type C1 (NPC1) is an endolysosomal transmembrane protein involved in the export of cholesterol and sphingolipids to other cellular compartments such as the endoplasmic reticulum and plasma membrane. NPC1 loss of function is the major cause of NPC disease, a rare lysosomal storage disorder characterized by an abnormal accumulation of lipids in the late endosomal/lysosomal network, mitochondrial dysfunction, and impaired autophagy. NPC phenotypes are conserved in yeast lacking Ncr1, an orthologue of human NPC1, leading to premature aging. Herein, we performed a phosphoproteomic analysis to investigate the effect of Ncr1 loss on cellular functions mediated by the yeast lysosome-like vacuoles. Our results revealed changes in vacuolar membrane proteins that are associated mostly with vesicle biology (fusion, transport, organization), autophagy, and ion homeostasis, including iron, manganese, and calcium. Consistently, the cytoplasm to vacuole targeting (Cvt) pathway was increased in ncr1∆ cells and autophagy was compromised despite TORC1 inhibition. Moreover, ncr1∆ cells exhibited iron overload mediated by the low-iron sensing transcription factor Aft1. Iron deprivation restored the autophagic flux of ncr1∆ cells and increased its chronological lifespan and oxidative stress resistance. These results implicate iron overload on autophagy impairment, oxidative stress sensitivity, and cell death in the yeast model of NPC1.

Emerging drugs targeting cellular redox homeostasis to eliminate acute myeloid leukemia stem cells.

Acute myeloid leukemia (AML) is a very heterogeneous group of disorders with large differences in the percentage of immature blasts that presently are classified according to the specific mutations that trigger malignant proliferation among thousands of mutations reported thus far. It is an aggressive disease for which few targeted therapies are available and still has a high recurrence rate and low overall survival. The main reason for AML relapse is believed to be due to leukemic stem cells (LSCs) that have unlimited self-renewal capacity and long residence in a quiescent state, which promote greater resistance to traditional therapies for this cancer. AML LSCs have low oxidative stress levels, which appear to be caused by a combination of low mitochondrial activity and high activity of ROS-removing pathways. In this sense, oxidative stress has been thought to be an important new potential target for the treatment of AML patients, targeting the eradication of AML LSCs. The aim of this review is to discuss some drugs that induce oxidative stress to direct new goals for future research focusing on redox imbalance as an effective strategy to eliminate AML LSCs.

Validation of the Brazilian version of the Hip Sports Activity Scale (HSAS) for patients with femoroacetabular impingement: a cross-sectional study

ABSTRACT BACKGROUND: The Hip Sports Activity Scale (HSAS) is a hip-specific instrument for assessing the present levels of physical activity among patients with femoroacetabular impingement (FAI) syndrome. When evaluating treatment outcomes in patients with FAI syndrome, it is necessary to use joint-specific instruments and ones that can evaluate the levels of physical activity in these patients, such as the HSAS-Brazil. OBJECTIVE: To validate the HSAS-Brazil among a group of physically active patients after arthroscopic treatment of FAI syndrome. DESIGN AND SETTING: Cross-sectional research of quantitative and qualitative types using data obtained from July 2018 to October 2019. METHODS: A total of 58 patients of both genders diagnosed with FAI syndrome and who had undergone hip arthroscopy participated in this research. To establish reliability and validity, patients first answered the Brazilian versions of the 12-Item Short-Form Health Survey (SF-12), Nonarthritic Hip Score (NAHS), and HSAS; after a 48-hour interval, they answered the HSAS-Brazil again. RESULTS: For test-retest reliability, the interclass correlation was 0.908 (P < 0.001). The HSAS-Brazil correlated to the NAHS-Brazil (r = 0.63, P < 0.001), as well as the SF-12 (Physical Health) (r = 0.42, P = 0.001). CONCLUSION: The HSAS-Brazil was validated and proved to be a reliable and valid scale to assess sports activity levels in physically active patients with FAI syndrome after arthroscopic treatment.

Pregnancy in women living with perinatally acquired HIV: Perinatal outcomes and drug resistance profile.

OBJECTIVES: To analyze the perinatal outcomes of Perinatally acquired HIV Infection (PHIV) in pregnant women. METHOD: This retrospective cohort study included singleton pregnancies in Women Living with HIV (WLH) between 2006 and 2019. Patient charts were revised, and maternal characteristics, type of HIV infection (perinatal vs. behavioral), Antiretroviral Therapy (ART) exposure, and obstetric and neonatal outcomes were assessed. The HIV-related aspects considered were: Viral Load (VL), CD4+ cell count, opportunistic infections, and genotype testing. Laboratory analyses were performed at baseline (first appointment) and 34 weeks of gestation. RESULTS: There were 186 WLH pregnancies, and 54 (29%) patients had PHIV. Patients with PHIV were younger (p < 0.001), had less frequently stable partnerships (p < 0.001), had more commonly serodiscordant partners (p < 0.001), had a longer time on ART (p < 0.001), and had lower rates of undetectable VL at baseline (p = 0.046) and at 34 weeks of gestation (p < 0.001). No association was observed between PHIV and adverse perinatal outcomes. Among patients with PHIV, third trimester anemia was associated with preterm birth (p = 0.039). Genotype testing was available only for 11 patients with PHIV, who presented multiple mutations related to ART resistance. CONCLUSIONS: PHIV did not seem to increase the risk of adverse perinatal outcomes. However, PHIV pregnancies have a higher risk of viral suppression failure and exposure to complex ARTs.