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.

Effect of Different Circuit Training on Cardiovascular Responses in Cirrhotic Patients.

The purpose of this study was to analyze and compare heart rate (HR), heart rate variability (HRV), and blood pressure (BP) responses during and after circuit resistance training with 1 min. (CIR1) vs. 2 min. (CIR2) rest intervals between exercises in liver cirrhosis patients. 10 patients (7 women, 3 men) participated in 2 experimental sessions (CIR1 and CIR2) in random order. Each experimental session consisted of 6 exercises performed for 3 sets of 10 repetitions with 70% of the 10-RM load. The only difference between experimental sessions was taking either 1 min. (CIR1) or 2 min. (CIR2) of rest between exercises. Prior and during each session, BP, HR and HRV (beat-to-beat intervals) were assessed. Training efficiency were significant higher for CIR1 when compared to CIR2, since same total training volume was performed in less time. Both protocols elicited significant changes in HR, SBP, and SampEn. Based on the ∆HR and ∆IRR between protocols, higher cardiovascular stress was observed for CIR1 vs. CIR2. However, the patients presented a similar recovery pattern between experimental sessions, and did not present significant alterations in the HRV at 60 min post-workout. In summary, the fast adjustment of autonomic modulation in HRV and BP suggests that circuit resistance training with 1-min or 2-min rest intervals between exercises elicits typical cardiovascular responses in liver cirrhosis patients.

Serum levels of interleukin-33 and its soluble form receptor (sST2) are associated with cognitive performance in patients with schizophrenia.

OBJECTIVE: Changes in immune system have been reported in schizophrenia. This study aimed to evaluate the involvement of IL-33, a member of the IL-1 cytokine family, in schizophrenia and its association with cognitive performance in these patients. METHODS: Forty patients with chronic schizophrenia and 40 healthy subjects participated in the study. Serum levels of IL-33 and sST2 (soluble form of the IL-33 receptor) were measured using enzyme-linked immunosorbent assay (ELISA). Patients were evaluated with the Brief Assessment of Cognition in Schizophrenia (BACS) and the Schizophrenia Cognition Rating Scale (SCoRS). RESULTS: Patients with schizophrenia and controls presented similar serum levels of IL-33 and sST2. Levels of both markers were positively correlated with cognitive performance in patients with schizophrenia. CONCLUSION: We found a significant correlation between IL-33 and sST2 levels and cognition in schizophrenia. Our results might help in the understanding of how immune markers are associated with cognitive impairment in schizophrenia. It remains to be determined whether the association between IL-33/sST2 and cognition is restricted to patients with schizophrenia.

Short-Term Resistance Training Attenuates Cardiac Autonomic Dysfunction in Obese Adolescents.

PURPOSE: Cardiac autonomic dysfunction (CADysf) in children is often associated to obesity and may be attenuated by physical activity. In this study, we investigated the effects of resistance training (RT) upon CADysf assessed by heart rate variability (HRV) in obese adolescents. METHOD: Volunteers were assigned into groups according to standard deviation scores for body mass index (z-BMI) and percentile for age and sex: obese (OB; z-BMI from 2 to 3 and ≥ 95th percentile, n = 24) and normal weight controls (CG; z-BMI from -2-1 and < 85th percentile, n = 20). OB performed isolated RT during 12 weeks [3 sets of 6-10reps with 70-85% 10RM]. Waist circumference, systolic/diastolic blood pressures (SBP/DBP), lipids, and HRV were assessed at baseline. Only OB underwent postintervention assessments. RESULTS: At baseline, SBP (122.4 ± 9.1 vs. 109.7 ± 11.5 mmHg, p < .001) and DBP (76.1 ± 7.1 vs. 65.3 ± 5.9 mmHg, p < .001) were higher, while parasympathetic HRV indexes were lower (p < .05) in OB compared with CG. After RT, waist circumference (3%, p < .001) and SBP (10%, p < .001) reduced in OB. Parasympathetic indexes of HRV increased in OB (SDNN: 25%, p = .03; rMSSD: 48%, p = .0006; pNN50: 67%, p = .001; total power: 54%, p = .01; HF: 101%, p = .001) and baseline differences between groups for sympathetic and parasympathetic activities were no longer observed after RT. CONCLUSION: RT attenuated CAdyfs and BP in obese adolescents, by increasing parasympathetic activity and decreasing sympatho-vagal balance.

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.

Relationships between emerging cardiovascular risk factors, z-BMI, waist circumference and body adiposity index (BAI) on adolescents.

OBJECTIVE: The body adiposity index (BAI) has been recently proposed as an alternative index to body mass index (BMI) and waist circumference (WC) to evaluate adiposity in adults, with special focus on its ability to discriminate gender specificities on adiposity. Endothelial dysfunction, circulating endothelial cells (CECs), endothelin-1 and adipocytokines are all related to atherosclerosis and nowadays considered as markers of emerging cardiovascular (CV) risk. This study aimed to determine in normal weight and obese adolescents which measures of body composition (BAI and z-BMI) or distribution (WC) correlate better with emerging CV risk markers. PATIENTS: Forty adolescents were selected according to BMI: normal weight (n = 20; 7 girls/13 boys, 14·7 ± 1·4 years, 53·4 ± 6·0 kg, z-BMI 0·6 ± 0·1) and obese ones (n = 20; 13 girls/7 boys, 14·1± 1·0 years, 86·7 ± 11·5 kg, z-BMI 2·7 ± 0·4). MEASUREMENTS: Body fat and fat mass were measured by dual-energy X-ray absorptiometry (DXA). Non-nutritive skin microvascular reactivity was evaluated by laser Doppler flowmetry with iontophoretic release of vasoactive drugs. Activated CECs were assessed by flow cytometric analysis. RESULTS: In adolescents, the measurement of % fat by DXA showed high correlation with BAI (ρ = 0·75, P < 0·0001), z-BMI (r = 0·84, P < 0·0001) and WC (r = 0·83, P < 0·0001). Endothelin-1 and activated CECs did not correlate with any anthropometric measures while adipocytokines expressed variable associations among them. Endothelium-dependent vasodilation showed higher correlation with BAI (r = -0·51, P < 0·0001) compared to z-BMI (r = -0·40, P < 0·001) or WC (r = -0·45, P < 0·001), specially on females. CONCLUSIONS: BAI was associated with emerging CV risk markers in adolescents but further research is needed to evaluate its potential in clinical and epidemiological sets.

Sleep and its association with depressive and anxiety symptoms during the last weeks of pregnancy: A population-based study.

OBJECTIVE: To evaluate the association between sleep characteristics and depressive and anxiety symptoms during the immediate postpartum period. METHODS: People who had hospital births during 2019 in the municipality of Rio Grande (southern Brazil) were assessed with a standardized questionnaire concerning sociodemographic (eg, age and self-reported skin color) and health-related variables (eg, parity and stillbirth) (n = 2314) 24-48 hours after birth. We used the Munich Chronotype Questionnaire to assess sleep latency, inertia, duration, and chronotype; the Edinburgh Postpartum Depression Scale for depressive symptoms; and the General Anxiety Disorder 7-Item Scale to evaluate anxiety symptoms. We used logistic regression models to calculate odds ratios. RESULTS: The prevalence of depressive symptoms was 13.7%, and of anxiety symptoms was 10.7%. Depressive symptoms were more likely in those with vespertine chronotype (odds ratios = 1.63; 95% CI: 1.14-2.35) and those with a sleep latency of more than 30 minutes (OR = 2.36; 95% CI: 1.68-3.32). The probability of depressive symptoms decreased by 16% for each additional hour of sleep (OR = 0.84; 95% CI: 0.77-0.92). Sleep inertia of 11-30 minutes increased the probability of anxiety on free days (OR = 1.73; 95% CI: 1.27-2.36) and increased the probability of depressive (OR = 2.68; 95% CI: 1.82-3.83) and anxiety symptoms (OR = 1.69; 95%CI: 1.16-2.44) on workdays. CONCLUSION: Participants with vespertine chronotype or shorter sleep duration were more likely to have depressive symptoms. Those who took more time to fall asleep or get out of bed were more likely to have both anxiety and depressive symptoms, but the association was stronger for depressive symptoms.

Effects of Resistance Training in Individuals with Lower Limb Amputation: A Systematic Review.

Individuals with lower-limb amputations may have a significant strength deficit. This deficit may be related to the stump length and can lead to changes in gait, reduced energy efficiency, walking resistance, altered joint load, and increased risk of osteoarthritis and chronic low back pain. This systematic review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines to examine the effects of resistance training in lower limb amputees. Interventions with resistance training and other training methods were sufficient to achieve muscle strength gain in muscles of the lower limbs, improved balance, and improvements in gait pattern and speed when walking. However, it was impossible to determine from the results whether resistance training was mainly responsible for these benefits or even whether the positive effects presented would be observed with only this training method. When combined with other exercises, interventions with resistance training made possible gains for this population. Accordingly, it is noteworthy that the main finding of this systematic review is that the effects may be different according to the level of amputation, with mainly transtibial and transfemoral amputations studied.

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.

Effects of Six-week Periodized Versus Non-Periodized Kettlebell Swing Training on Strength, Power and Muscular Endurance.

The purpose of this study was to compare a periodized versus a non-periodized protocol of kettlebell (KTB) swings over six weeks on strength, power, and muscular endurance. Twenty-eight high intensity functional training (HIFT) practitioners were assigned to non-periodized (NPG = 11), periodized (PG = 11), or control groups (CG = 6). NPG used the same load (20 kg) throughout the training period while the PG used a step loading progression (with an added four kilograms every two weeks). Measures of strength and muscular endurance in the deadlift exercise, and power in the countermovement jump were assessed before and after six weeks. A two-way ANOVA was used to verify pre- to post-test differences in strength, power, and muscular endurance. An analysis of the effect size was also incorporated. For strength and power, statistical differences from pre- to post-test were found for both the NPG (p < 0.001; 1-RM improvement = 8.7%; jump height improvement = 8.7%) and PG (p < 0.001; 1-RM improvement = 7.8%; jump height improvement = 10.1%), with no difference between groups. For muscular endurance, only the PG showed significant differences from pre- to post-test (p = 0.013; muscular endurance improvement = 23.8%). In conclusion, when the goal is to increase strength and power performances in HIFT practitioners, periodized and non-periodized KTB models appear to be equally effective, and this can simplify the strength coach's practice in programming KTB swing training periods. For muscular endurance, the addition of KTB swing on a periodized basis seems to be a more effective strategy.

Effects of aerobic, strength, and combined training during pregnancy in the blood pressure: A systematic review and meta-analysis.

Gestational hypertension can lead to fetal complications, and, if untreated, high blood pressure during pregnancy may cause eclampsia and even death in the mother and fetus. Exercise is a strategy for preventing blood pressure disorders. There is little knowledge about the physiological impacts of different physical types of training on blood pressure during pregnancy. For that, this meta-analysis aimed to compare the effects of different physical exercise modalities (i.e., aerobic training-AT, strength training-ST, and combined training-AT + ST) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) of pregnant women. A search was performed on PUBMED, LILACS, CINAHL, Sport discus, EMBASE, SCOPUS, and Cochrane Central Register of Controlled Trials to identify researchers. From 3,450 studies, 20 and 19 were included in the qualitative and quantitative analyses. AT studies presented a medium effect size (ES) on SBP [-0.29 (-2.95 to 2.36) p = 0.83], with substantial heterogeneity (I2 = 64%), and had a large impact on DBP [-1.34 (-2.98 to 0.30) p = 0.11], with moderate heterogeneity (I2 = 30%). ST researchers showed a large ES on SBP [-1.09 (-3.66 to 1.49) p = 0.41], with a reduced heterogeneity (I2 = 0%), and a medium ES on DBP [-0.26 (-2.77 to 2.19) p = 0.83] with moderate heterogeneity (I2 = 38%). AT + ST studies had a large ES on SBP [-1.69 (-3.88 to 0.49) p = 0.13] and DBP [-01.29 (-2.26 to 0.31) p = 0.01] with considerable (I2 = 83%) and moderate heterogeneity (I2 = 47%), respectively. These findings are essential for developing new research protocols to avoid gestational hypertension and preeclampsia. AT + ST had a large impact on the SBP and DBP reduction; however, there is a need for more similar procedures to reduce heterogeneity between studies, promoting consensual results. Systematic Review Registration: [PROSPERO], identifier [CRD42021256509].

Adiponectin and Stnfr2 peripheral levels are associated with cardiovascular risk in patients with schizophrenia.

OBJECTIVES: To investigate the association between cytokine peripheral levels and the risk of cardiovascular disease in patients with schizophrenia and controls. METHODS: A sample of 40 patients and 40 control subjects participated in the study. Psychiatric diagnosis was established following structured clinical assessment. The Framingham Score was used to assess cardiovascular risk (CVR). Serum levels of the cytokines IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were determined by cytometric bead array (CBA) technique, and the serum levels of IL-33, sST2, sTNFR1, sTNFR2, Leptin and Adiponectin by Enzyme-Linked Immunosorbent assay (ELISA). RESULTS: Patients with schizophrenia showed greater frequency of moderate CVR when compared with controls (p = 0.14). In addition, patients showed higher levels of sTNFR2 and Adiponectin compared to controls (p = 0.007 and p < 0.001, respectively). Adiponectin and sTNFR2 were associated with CVR only in patients (p = 0.0002 and p = 0.033, respectively). In multivariate analysis controlling for socio-demographic and clinical confounders, illness duration (r = 0.492; p < 0.002) and sTNFR2 (r = 0.665; p < 0.004) were independent predictors of CVR. CONCLUSION: Our results reinforce the concept that patients with schizophrenia are at greater risk to develop cardiovascular diseases, and suggest that the associated chronic low-grade inflammation might play a role in this process.

Limited cardiopulmonary capacity in patients with liver cirrhosis when compared to healthy subjects.

OBJECTIVES: The present study compared cardiorespiratory capacity between cirrhotic patients and healthy subjects. METHODS: Nineteen cirrhotic patients and 19 healthy subjects, paired by age and gender, participated in the study. Volunteers performed an incremental cardiopulmonary test with a ramp protocol, a ventilatory and metabolic variables were obtained and analyzed. The recovery was analyzed by calculating the time needed for 50% of oxygen consumption (VO2) recovery to occur as the median between the peak of the exercise and the end of recovery on the VO2 curve (T1/2). The VE/VCO2 slope were performed by the linear regression of ventilation (VE) and carbon dioxide production (VCO2) data. RESULTS: During resting condition, cirrhotic patients presented significantly higher levels of VO2 compared to healthy subjects. The VE/ VO2 and VE/ VCO2 values were significantly higher in the control group at the anaerobic threshold and at the peak of the test compared to cirrhotic patients. Time under effort was significantly higher for healthy subjects. CONCLUSIONS: Based on these findings, it is possible to conclude that liver cirrhosis can compromise the patients' quality of life, mainly by inducing metabolic alterations which can impair functional capacity and lead to a sedentary lifestyle.

Interaction effects of different orders of resistance exercises and rest intervals on performances by young athletes.

OBJECTIVE: The purpose of this study was to verify the acute effects of different exercise orders and rest intervals between sets on young athletes performance. METHOD: Sixteen young male football players (73.2 ± 4.8 kg, 177.5 ± 5.1 cm, BMI 23.2 ± 1.1, 19.8 ± 0.9 years) completed six experimental strength training (ST) sessions with different exercise order sequences (A and B) and rest interval lengths (1 min, 3 min, and self-selected).In Sequence A the exercises were: bench press (BP), back squat (BS), biceps curl (BC) and plantar flexion (PF); while Sequence B was performed in the opposite order (i.e. PF, BC, BS and BP).The total work volume (TWV) per exercise (sets x repetitions x load) and per training session (sum of the TWV of all exercises) were evaluated for all ST sessions. RESULTS: BC and PF exercises presented higher TWV in sequence B (p ≤ 0.05). Already, the exercises BP, BS and PF presented higher TWV with 3 min and self-selected rest intervals (p ≤ 0.05). The 3-min and self-selected rest intervals presented higher values of TWV per training session compared to the 1-min rest interval (p ≤ 0.05). CONCLUSION: The exercise order influenced certain exercises (BC and PF), which presented higher TWV when positioned at the beginning of a sequence. While the longer rest intervals (3 min and self-selected) resulted in higher TWV per exercise (BP, BS and PF) and per training session. These results suggest that self-selected rest interval can be implemented to increase training efficiency in young athletes.

Effects of 12 Months of Vitamin D Supplementation on Physical Fitness Levels in Postmenopausal Women with Type 2 Diabetes.

INTRODUCTION: It is common for postmenopausal women to receive a vitamin D supplementation prescription to assist in preventing future falls and to maintain bone health. However, the association between vitamin D supplementation and physical fitness components has not been studied in older women with diabetes. OBJECTIVE: We examined the influence of 12 months of vitamin D supplementation on the components of physical fitness in postmenopausal women with type 2 diabetes mellitus (T2DM). METHODS: Thirty-five postmenopausal women (62.48 ± 7.67 years; 154.6 ± 5.11 cm; 73.93 ± 15.43 kg; 31.13 ± 5.82 BMI) with a diagnosis of T2DM participated in this longitudinal study where participants were supplemented with 1000 IU/day of vitamin D over 12 months. Subjects performed fasting blood samples, anthropometric assessments, body composition, clinical exams, and physical tests at 6-month intervals (P0, P6, and P12). RESULTS AND CONCLUSION: Vitamin D supplementation alone was effective in postmenopausal women in increasing serum vitamin D levels, altering muscle strength levels, promoting improvements in muscle function, as well as preventing and controlling fragility caused by T2DM and aging.

Exposure of Domestic Cats to Distinct Ehrlichia canis TRP Genotypes.

Cats naturally exposed to Ehrlichia canis have been described in different regions of the world, but little is known about the genotypes associated with infection in these animals. To detect E. canis-specific antibodies and investigate the E. canis TRP genotypes in cats, serum samples from 76 domestic cats reactive to crude E. canis antigens by the indirect fluorescence antibody test (IFAT) were analyzed by ELISA, using E. canis-specific peptides (i.e., TRP19 and TRP36 /BR/US/CR). Of these, 25 (32.9%) cats reacted to at least one TRP peptide, confirming their specific exposure to E. canis. Eighteen (23.7%) cats reacted to TRP19, 15 (19.8%) to BRTRP36, and 11 (14.5%) to USTRP36, but none of them reacted to CRTRP36. Eight (10.5%) cats reacted to TRP19 but not to any TRP36 genotype, demonstrating the possible existence of a new E. canis genotype infecting felines. Nevertheless, this study provides the first report of anti-E. canis-specific antibodies in domestic cats.

Cell signaling pathways as molecular targets to eliminate AML stem cells.

Acute myeloid leukemia (AML) remains the most lethal of leukemias and a small population of cells called leukemic stem cells (LSCs) has been associated with disease relapses. Some cell signaling pathways play an important role in AML survival, proliferation and self-renewal properties and are abnormally activated or suppressed in LSCs. This includes the NF-κB, Wnt/ß-catenin, Hedgehog, Notch, EGFR, JAK/STAT, PI3K/AKT/mTOR, TGF/SMAD and PPAR pathways. This review aimed to discuss these pathways as molecular targets for eliminating AML LSCs. Herein, inhibitors/activators of these pathways were summarized as a potential new anti-AML therapy capable of eliminating LSCs to guide future researches. The clinical use of cell signaling pathways data can be useful to enhance the anti-AML therapy.

Maternal mental health before and during the COVID-19 pandemic in the 2019 Rio Grande birth cohort.

OBJECTIVE: To describe and compare measures of maternal depression, anxiety, and posttraumatic stress symptoms before and during the coronavirus disease 2019 (COVID-19) pandemic in a Brazilian birth cohort. METHODS: All hospital births occurring in the municipality of Rio Grande (southern Brazil) during 2019 were identified. Mothers were invited to complete a standardized questionnaire on sociodemographic and health-related characteristics. Between May and July 2020, we tried to contact all cohort mothers of singletons, living in urban areas, to answer a standardized web-based questionnaire. They completed the Edinburgh Postnatal Depression Scale (EPDS) and Generalized Anxiety Disorder 7-item (GAD-7) in both follow-ups, and the Impact of Event Scale (IES) in the online follow-up. RESULTS: We located 1,136 eligible mothers (n=2,051). Of those, 40.5% had moderate to severe stress due to the current pandemic, 29.3% had depression, and 25.9% had GAD. Mothers reporting loss of income during the pandemic (57.2%) had the highest proportions of mental health problems. Compared to baseline, the prevalence of depression increased 5.7 fold and that of anxiety increased 2.4-fold during the pandemic (both p < 0.001). CONCLUSION: We found a high prevalence of personal distress due to the ongoing COVID-19 pandemic, and a clear rise in both maternal depression and anxiety.

Influence of moderately intense strength training on flexibility in sedentary young women.

The present study is the first to examine whether moderately intense resistance training improves flexibility in an exclusively young, sedentary women population. Twenty-four, young, sedentary women were divided into 3 groups as follows: agonist/antagonist (AA) training group, alternated strength training (AST) group, or a control group (CG). Training occurred every other day for 8 weeks for a total of 24 sessions. Training groups performed 3 sets of 10 to 12 repetitions per set except for abdominal training where 3 sets of 15 to 20 reps were performed. Strength (1 repetition maximum bench press) and flexibility were assessed before and after the training period. Flexibility was assessed on 6 articular movements: shoulder flexion and extension, horizontal shoulder adduction and abduction, and trunk flexion and extension. Both groups increased strength and flexibility significantly from baseline and significantly when compared with the CG (p ≤ 0.05). The AST group increased strength and flexibility significantly more than the AA group (p ≤ 0.05) in all but one measurement. This study shows that resistance training can improve flexibility in young sedentary women in 8 weeks.