Autonomic modulation of heart rate during physical activity in pregnant women: A systematic review of literature.

BACKGROUND: There are important physiological changes in the heart rate autonomic modulation in pregnant women and these changes may affect the way their bodies respond to exercise stimulus. The objective of this review is to verify the physical exercise influence on autonomic modulation of heart rate in pregnant women. METHODS: This study is a Systematic Review. The electronic databases used to search for the studies were Cochrane Library, MEDLINE via PUBMED, Regional Health Portal and EMBASE. Experimental studies that evaluated heart-rate variability in pregnant women practicing physical exercises were included. And articles that addressed only fetal heart-rate variability, case reports, congress abstracts, clinical trial protocols without results, preprints, and gray literature were excluded. There were no language or publication year restrictions. The descriptors used in the Search were Cardiac Chronotropism, Sympathetic Nervous System, Pregnancy, and Physical Exercise. For statistical analysis, the fixed effect model was used. RESULTS: A total of 3106 articles were found, and 12 studies were included, which 5 were nonrandomized clinical trials, 4 were randomized clinical trials, and 3 were cross-sectional studies. Three hundred and four pregnant women were included in the studies. The application of physical exercise was varied, but in general they used aerobic exercises and with increased variability of the heart rate and reflex on the autonomic modulation of heart rate. CONCLUSION: Most studies demonstrate benefits heart rate in pregnant women, but limited research makes it hard to compare specific types of exercise and larger studies are needed to identify the best exercise.

Factors Associated with Symptoms of Posttraumatic Stress in Mothers During the COVID-19 Pandemic.

OBJECTIVES: The objective of the study was to evaluate the factors associated with symptoms of posttraumatic stress in mothers during the COVID-19 pandemic. METHODS: Cross-sectional study conducted with mothers of children and adolescents living in Brazil, who answered an online questionnaire containing sociodemographic variables and the Impact of Events Scale-Revised. The Poisson regression model with robust variance was used to identify the factors associated with posttraumatic stress. RESULTS: A percentage of 83.82% of mothers reported an overload in caring for their children during the pandemic. The prevalence of posttraumatic stress symptoms was 39.05%, and this condition was associated with younger age, living in the northern region of the country, using medications, presenting neuropsychiatric comorbidities and being little/more or less satisfied with life. CONCLUSIONS FOR PRACTICE: The mental health situation of mothers during and after the pandemic must be monitored, in order to guarantee public policies capable of optimizing the coping with the situation.

Symptoms of depression, anxiety and stress in Brazilian mothers during the COVID-19 pandemic.

The study aimed to identify the factors associated with symptoms of depression, anxiety and stress in Brazilian mothers of children and adolescents during the COVID-19 pandemic. This is a cross-sectional study carried in 2020 with the participation of 822 mothers who answered an online questionnaire containing sociodemographic variables and the Depression, Anxiety and Stress Scale (DASS-21). The adjusted model showed a higher depression score in women who became unemployed during the pandemic, who felt a greater burden in taking care of children, who took medication on a regular basis, and who self-assessed their health as regular or poor/very poor. Having a lower family income increased their anxiety scale score. In contrast, the variables associated with a reduced anxiety scale score included greater age, not feeling overwhelmed with demands to care for children, not using medications, not having gastrointestinal diseases, and good/very good self-assessed health. These variables, together with the benefits of living in the Northeast and Midwest regions of Brazil as well as sleeping more hours per night, were also associated with reduced stress. The present study is significant as it points out elements present in the daily lives of mothers that have an impact on their mental health. The study points to the need to (re)think mental health policies taking into account the needs of the public studied.

Spawning ecology of the Saint Paul's Gregory Stegastes sanctipauli, a damselfish endemic to the remote St Peter and St Paul's Archipelago.

We studied the spawning ecology of Stegastes sanctipauli, a damselfish endemic to the small and remote St Peter and St Paul's Archipelago (Brazil), aiming to determine the main correlates of reproductive success, as inferred from rates of egg losses along a spawning season. New clutches appeared mostly in the last quarter moon, when egg predation intensified. Predation by heterospecifics, particularly Halichoeres radiatus (Linnaeus, 1758), accounted for most egg losses, while filial cannibalism showed negligible influence. Predation pressure was highest for larger nests with higher initial density of eggs. Hatching of eggs occurred close to the new moon (i.e., ~5 days after spawning). Most nests occur in shallow reefs (<16 m depth), where main food resources for adults (turf algae) are concentrated, but abundance of egg predators, particularly H. radiatus, is also highest. This latter result suggests that the spawning activity of S. sanctipauli is influenced by the trade-offs between food accessibility by adults and egg predation risk. The patterns recorded here are similar to those known for other tropical damselfish species and may reflect strategies for attenuating predation pressure over new fry and eggs.

Control of assembly of extra-axonemal structures: the paraflagellar rod of trypanosomes.

Eukaryotic flagella are complex microtubule-based organelles that, in many organisms, contain extra-axonemal structures, such as the outer dense fibres of mammalian sperm and the paraflagellar rod (PFR) of trypanosomes. Flagellum assembly is a complex process occurring across three main compartments, the cytoplasm, the transition zone and the flagellum itself. The process begins with the translation of protein components followed by their sorting and trafficking into the flagellum, transport to the assembly site and incorporation. Flagella are formed from over 500 proteins and the principles governing assembly of the axonemal components are relatively clear. However, the coordination and location of assembly of extra-axonemal structures are less clear. We have discovered two cytoplasmic proteins in Trypanosoma brucei that are required for PFR formation, PFR assembly factors 1 and 2 (PFR-AF1 and PFR-AF2, respectively). Deletion of either PFR-AF1 or PFR-AF2 dramatically disrupted PFR formation and caused a reduction in the amount of major PFR proteins. The existence of cytoplasmic factors required for PFR formation aligns with the concept that processes facilitating axoneme assembly occur across multiple compartments, and this is likely a common theme for extra-axonemal structure assembly.

Folic Acid-Doxorubicin-Double-Functionalized-Lipid-Core Nanocapsules: Synthesis, Chemical Structure Elucidation, and Cytotoxicity Evaluation on Ovarian (OVCAR-3) and Bladder (T24) Cancer Cell Lines.

PURPOSE: Folic acid-doxorubicin-double-functionalized-lipid-core nanocapsules (LNC-CS-L-Zn+2-DOX-FA) were prepared, characterized, and evaluated in vitro against ovarian and bladder cancer cell lines (OVCAR-3 and T24). METHODS: LNC-CS-L-Zn+2-DOX-FA was prepared by self-assembly and interfacial reactions, and characterized using liquid chromatography, particle sizing, transmission electron microscopy, and infrared spectroscopy. Cell viability and cellular uptake were studied using MTT assay and confocal microscopy. RESULTS: The presence of lecithin allows the formation of nanocapsules with a lower tendency of agglomeration, narrower size distributions, and smaller diameters due to an increase in hydrogen bonds at the surface. LNC-L-CS-Zn+2-DOX-FA, containing 98.00 ± 2.34 µg mL-1 of DOX and 105.00 ± 2.05 µg mL-1 of FA, had a mean diameter of 123 ± 4 nm and zeta potential of +12.0 ± 1.3 mV. After treatment with LNC-L-CS-Zn+2-DOX-FA (15 µmol L-1 of DOX), T24 cells had inhibition rates above 80% (24 h) and 90% (48 h), whereas OVCAR-3 cells showed inhibition rates of 68% (24 h) and 93% (48 h), showing higher cytotoxicity than DOX.HCl. The fluorescent-labeled formulation showed a higher capacity of internalization in OVCAR-3 compared to T24 cancer cells. CONCLUSION: Lecithin favored the increase of hydrogen bonds at the surface, leading to a lower tendency of agglomeration for nanocapsules. LNC-CS-L-Zn+2-DOX-FA is a promising therapeutic agent against tumor-overexpressing folate receptors.

Effectiveness of Pilates and circuit-based exercise in reducing arthralgia in women during hormone therapy for breast cancer: a randomized, controlled trial.

OBJECTIVE: To investigate the effect of Pilates compared with circuit-based exercise in reducing arthralgia in women during hormone therapy for breast cancer. DESIGN: Single-blind randomized controlled trial, parallel. SETTING: University hospital of Brasilia and Brazilian Association for Assistance to People with Cancer. PARTICIPANTS: Sixty women with arthralgia were recruited. Eligibility criteria included women complaining of arthralgia during hormone therapy for breast cancer. The exclusion criteria were women with active cancer, lymphedema, limitations to physical exercise, or limitation to answer some questionnaires. MAIN OUTCOME MEASURES: Primary: Pain. Secondary: Function, flexibility, and sleep quality. Outcomes were assessed at baseline and the end of the intervention (8 weeks) by the same blinded evaluator. INTERVENTION: Sixty participants were randomly assigned 20 to each of the three groups: Pilates, circuit-based exercise, and control groups. Exercise was performed twice per week for 75 min, over a period of 8 weeks. Participants in the control group were instructed to continue their usual activities. The Kolmogorov-Smirnov test was used to verify the normality of the outcomes. Intergroup differences were calculated using Kruskal-Wallis test with post hoc Mann Whitney U testing and the parametric data between the three groups with ANOVA of repeated measures with Bonferroni post hoc. RESULTS: The Pilates group demonstrated a significant difference in pain reduction compared to the circuit group (mean difference: -1.95 points, p = 0.020). CONCLUSION: Pilates was more effective than circuit-based exercise in reducing arthralgia in women during hormone therapy for breast cancer. TRIAL REGISTRATION: http://www.ensaiosclinicos.gov.br/rg/RBR-3wsdhs/ Registered on Octob 16th 2017.

Organic Nanocarriers for Bevacizumab Delivery: An Overview of Development, Characterization and Applications.

Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.

A TIE Approach to Identify Substances Causing Sediment Pore Water Toxicity After a Major Fire at Fuel Storage Tanks in the Port of Santos (SE, Brazil).

The major fire at the fuel storage tanks of a Chemical Terminal in April 2015 at the Port of Santos (SP), SE Brazil, potentially caused significant environmental impacts to the Santos Estuarine System (SES). The aim of the study was to identify the classes of substances causing pore water toxicity in the SES sediments in the vicinity of the port terminal before and after the incident using the TIE approach. Our results suggest that nonpolar compounds (e.g. PAHs, BTX, oil and grease) from the storage tanks that burned, and surfactants present in the formulation of foam fire extinguishing agents were the responsible for the sediment toxicity observed in the vicinity of the incident site. The contribution of metals to the toxicity related to the incident was ruled out. A long-term monitoring of the environmental effects of the incident is recommended since substances for which evidence of toxicity was found are toxic, persistent and can accumulate in the biota.

Chitosan-Coated Lipid-Core Nanocapsules Functionalized with Gold-III and Bevacizumab Induced In Vitro Cytotoxicity against C6 Cell Line and In Vivo Potent Antiangiogenic Activity.

PURPOSE: Bevacizumab (BCZ) is a recombinant monoclonal antibody that inhibits the biological activity of the vascular endothelial growth factor, which has an important role in angiogenesis for tumoral growth and progression. In this way, our objective was to develop chitosan-coated lipid-core nanocapsules functionalized with BCZ by an organometallic complex using gold-III. METHODS: The formulation was produced and characterized in relation to physicochemical characteristics. Furthermore, the antitumoral and antiangiogenic activities were evaluated against C6 glioma cell line and chicken embryo chorioallantoic membrane (CAM), respectively. RESULTS: Final formulation showed nanometric size, narrow polydispersity, positive zeta potential and gold clusters size lower than 2 nm. BCZ in aqueous solution (0.01-0.10 µmol L-1) did not show cytotoxic activity in vitro against C6 glioma cell line; although, MLNC-Au-BCZ showed cytotoxicity with a median inhibition concentration of 30 nmol L-1 of BCZ. Moreover, MLNC-Au-BCZ demonstrated cellular internalization dependent on incubation time and BCZ concentration. BCZ solution did not induce significant apoptosis as compared to MLNC-Au-BCZ within 24 h of treatment. CAM assay evidenced potent antiangiogenic activity for MLNC-Au-BCZ, representing a decrease of 5.6 times in BCZ dose comparing to BCZ solution. CONCLUSION: MLNC-Au-BCZ is a promising product for the treatment of solid tumors.

Effects of Microplastics Associated with Triclosan on the Oyster Crassostrea brasiliana: An Integrated Biomarker Approach.

Urban waste is a complex mixture of different substances, including microplastics and pharmaceuticals and personal care products. Microplastics have a high affinity for hydrophobic substances. One of these substances is triclosan, a bactericide used in a variety of hygiene products. Therefore, microplastics (MPs) may serve as a vector between triclosan and aquatic organisms. The current study sought to evaluate the effects of the interaction between microplastics and triclosan based on a mechanistic approach in which the oyster Crassostrea brasiliana was used as a model. The organisms were exposed to three conditions: the control, microplastic (MP), and microplastic contaminated with triclosan (MPT). The organisms were exposed for 3 or 7 days. After the exposure time, hemolymph was sampled for performing the neutral red retention time assay and, subsequently, the gills, digestive glands, and adductor muscles were dissected for measuring biomarkers responses (EROD, DBF, GST, GPx, GSH, lipid peroxidation, DNA strand breaks, and AChE). Our results demonstrate combined effects of MPs associated with triclosan on oyster physiology and biochemistry, as well as on lysosomal membrane stability. These results contribute to understanding the effects of contaminants of emerging concern and microplastics on aquatic organisms.

Erlotinib-Loaded Poly(ε-Caprolactone) Nanocapsules Improve In Vitro Cytotoxicity and Anticlonogenic Effects on Human A549 Lung Cancer Cells.

Lung cancer is the most frequent type of cancer and the leading cause of cancer-related mortality worldwide. This study aimed to develop erlotinib (ELB)-loaded poly(ε-caprolactone) nanocapsules (NCELB) and evaluated their in vitro cytotoxicity in A549 cells. The formulation was characterized in relation to hydrodynamic diameter (171 nm), polydispersity index (0.076), zeta potential (- 8 mV), drug content (0.5 mg.mL-1), encapsulation efficiency (99%), and pH (6.0). NCELB presented higher cytotoxicity than ELB in solution against A549 cells in the MTT and LIVE/DEAD cell viability assays after 24 h of treatment. The main mechanism of cytotoxicity of NCELB was the induction of apoptosis in A549 cells. Further, a significant decrease in A549 colony formation was verified after NCELB treatment in comparison with the unencapsulated drug treatment. The reduction in clonogenic capacity is very relevant as it can reduce the risk of tumor recurrence and metastasis. In conclusion, erlotinib-loaded PCL nanocapsules are promising nanoparticles carriers to increase the efficacy of ELB in lung cancer treatment.

Long-term Quality of Life in Adult Patients Surviving Purpura Fulminans: An Exposed-Unexposed Multicenter Cohort Study.

BACKGROUND: Long-term health-related quality of life (HR-QOL) of patients surviving the acute phase of purpura fulminans (PF) has not been evaluated. METHODS: This was a French multicenter exposed-unexposed cohort study enrolling patients admitted in 55 intensive care units (ICUs) for PF from 2010 to 2016. Adult patients surviving the acute phase of PF (exposed group) were matched 1:1 for age, sex, and Simplified Acute Physiology Score II with septic shock survivors (unexposed group). HR-QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36) questionnaire, the Hospital Anxiety and Depression (HAD) scale, the Impact of Event Scale-Revised (IES-R), and the activity of daily living (ADL) and instrumental ADL (IADL) scales. The primary outcome measure was the physical component summary (PCS) of the SF-36 questionnaire. RESULTS: Thirty-seven survivors of PF and 37 of septic shock were phone-interviewed at 55 (interquartile range [IQR], 35-83) months and 44 (IQR, 35-72) months, respectively, of ICU discharge (P = .23). The PCS of the SF-36 was not significantly different between exposed and unexposed patients (median, 47 [IQR, 36-53] vs 54 [IQR, 36-57]; P = .18). There was also no significant difference between groups regarding the mental component summary of the SF-36, and the HAD, IES-R, ADL and IADL scales. Among the 37 exposed patients, those who required limb amputation (n = 12/37 [32%]) exhibited lower PCS (34 [IQR, 24-38] vs 52 [IQR, 42-56]; P = .001) and IADL scores (7 [IQR, 4-8] vs 8 [IQR, 7-8]; P = .021) compared with nonamputated patients. CONCLUSIONS: Long-term HR-QOL does not differ between patients surviving PF and those surviving septic shock unrelated to PF. Amputated patients have an impaired physical HR-QOL but a preserved mental health. CLINICAL TRIALS REGISTRATION: NCT03216577.

Nasal Drug Delivery of Anticancer Drugs for the Treatment of Glioblastoma: Preclinical and Clinical Trials.

Glioblastoma (GBM) is the most lethal form of brain tumor, being characterized by the rapid growth and invasion of the surrounding tissue. The current standard treatment for glioblastoma is surgery, followed by radiotherapy and concurrent chemotherapy, typically with temozolomide. Although extensive research has been carried out over the past years to develop a more effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in terms of the overall survival of patients. Consequently, new therapeutic approaches are urgently needed. Overcoming the blood-brain barrier (BBB) is a major challenge in the development of therapies for central nervous system (CNS) disorders. In this context, the intranasal route of drug administration has been proposed as a non-invasive alternative route for directly targeting the CNS. This route of drug administration bypasses the BBB and reduces the systemic side effects. Recently, several formulations have been developed for further enhancing nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review is to provide an overview of the strategies that have been developed for delivering anticancer compounds for the treatment of GBM while using nasal administration. In particular, the specific properties of nanomedicines proposed for nose-to-brain delivery will be critically evaluated. The preclinical and clinical data considered supporting the idea that nasal delivery of anticancer drugs may represent a breakthrough advancement in the fight against GBM.

The importance of a gatekeeper residue on the aggregation of transthyretin: implications for transthyretin-related amyloidoses.

Protein aggregation into ß-sheet-enriched amyloid fibrils is associated with an increasing number of human disorders. The adoption of such amyloid conformations seems to constitute a generic property of polypeptide chains. Therefore, during evolution, proteins have adopted negative design strategies to diminish their intrinsic propensity to aggregate, including enrichment of gatekeeper charged residues at the flanks of hydrophobic aggregation-prone segments. Wild type transthyretin (TTR) is responsible for senile systemic amyloidosis, and more than 100 mutations in the TTR gene are involved in familial amyloid polyneuropathy. The TTR 26-57 segment bears many of these aggressive amyloidogenic mutations as well as the binding site for heparin. We demonstrate here that Lys-35 acts as a gatekeeper residue in TTR, strongly decreasing its amyloidogenic potential. This protective effect is sequence-specific because Lys-48 does not affect TTR aggregation. Lys-35 is part of the TTR basic heparin-binding motif. This glycosaminoglycan blocks the protective effect of Lys-35, probably by neutralization of its side chain positive charge. A K35L mutation emulates this effect and results in the rapid self-assembly of the TTR 26-57 region into amyloid fibrils. This mutation does not affect the tetrameric protein stability, but it strongly increases its aggregation propensity. Overall, we illustrate how TTR is yet another amyloidogenic protein exploiting negative design to prevent its massive aggregation, and we show how blockage of conserved protective features by endogenous factors or mutations might result in increased disease susceptibility.

Bovine Serum Albumin Nanoparticles Containing Amphotericin B: Characterization, Cytotoxicity and In Vitro Antifungal Evaluation.

In this study, nanoparticles based on bovine serum albumin (BSA) containing amphotericin B (AmB) were obtained by the desolvation method and characterized with respect to size, size distribution, AmB encapsulation efficiency, AmB state of aggregation, and AmB in vitro release profile. After, the effect of nanoparticles on the cytotoxicity of human erythrocytes in vitro and efficacy over strains of Candida spp. were evaluated. The mean particle size was 156 nm and the AmB encapsulation efficiency was over 82%. The in vitro release profile revealed a sustained release of approximately 48% of AmB over 5 days. AmB is present in BSA nanoparticles as monomer. AmB-loaded nanoparticles showed very low index of hemolysis (less than 8%) in 72 h of assay compared to free AmB, which presented 100% of hemolysis in 2 h of incubation. The AmB-loaded BSA nanoparticles were as effective as free AmB against Candida albicans and Candida tropicalis, considering their sustained release profile. Thus, BSA nanoparticles are potential carriers for AmB, reducing its molecular aggregation and prolonging its release, resulting in lower cytotoxicity while maintaining its antifungal activity.

Health-service performance of TB treatment for indigenous and non-indigenous populations in Brazil: a cross-sectional study.

BACKGROUND: Health-service evaluation studies are fundamental for proposing interventions and ensuring improvements in healthcare quality. The present study assesses the performance of health services for indigenous and non-indigenous populations with regard to tuberculosis (TB) control. METHODS: Interviews with TB patients who underwent treatment between 2009 and 2011 were conducted using the Primary Care Assessment Tool adapted for TB care in Brazil. RESULTS: Primary healthcare (PHC) was the first treatment for most patients at symptom onset, and the diagnoses were typically performed by specialized services. Many patients experienced delayed TB diagnoses that required more than three medical appointments (51% and 47% for indigenous and non-indigenous populations, respectively). Indigenous people received social support, such as basic-needs grocery packages (2.19 ± 1.63 vs. 1.13 ± 0.49 for non-indigenous people, p < 0.01) and home visits from health professionals, with an emphasis on the performance of directly observed treatment strategies (DOT; 4.57 ± 0.89 vs. 1.68 ± 1.04 for non-indigenous people, p < 0.01). CONCLUSIONS: Regardless of the differences between indigenous and non-indigenous populations, the time needed to receive a TB diagnosis was unsatisfactory for both groups. Furthermore, DOT must be performed with better coverage among non-indigenous patients.

Luminescent solid phase for sialic acid determination: a promising sensor for milk-adulterated samples.

This article presents the synthesis, characterization and spectroscopic study of silica modified with thenoyltrifluoroacetonate (SilTTA) and coordinated to an europium (III) ion, for the determination of sialic acid (NANA). Elemental analysis and infrared spectroscopy suggest silica functionalization, as well as coordination of beta-diketone to the lanthanide ion. The emission spectra of compound-free and coordinated Eu-SilTTA to NANA showed significant changes with respect to the maximum emission and spectral profile, suggesting that the NANA ion is coordinated to the Eu(III). The values of the phenomenological intensity parameters show an increase in polarizability around the Eu(III) in the case of Eu-SilTTA coordinated to NANA, as expected, since water molecules are less polarizable than sialic acid. The results of the batch assay showed that luminescent silica can be used for sialic acid determination in milk-adulterated samples, with a correlation coefficient of 0.9992; and a detection limit of 0.4 mg/L; relative standard deviation (RSD%) = 0.0028.

LRRC56 is an IFT cargo required for assembly of the distal dynein docking complex in Trypanosoma brucei.

Outer dynein arms (ODAs) are responsible for ciliary beating in eukaryotes. They are assembled in the cytoplasm and shipped by intraflagellar transport (IFT) before attachment to microtubule doublets via the docking complex. The LRRC56 protein has been proposed to contribute to ODAs maturation. Mutations or deletion of the LRRC56 gene lead to reduced ciliary motility in all species investigated so far, but with variable impact on dynein arm presence. Here, we investigated the role of LRRC56 in the protist Trypanosoma brucei, where its absence results in distal loss of ODAs, mostly in growing flagella. We show that LRRC56 is a transient cargo of IFT trains during flagellum construction and surprisingly, is required for efficient attachment of a subset of docking complex proteins present in the distal portion of the organelle. This relation is interdependent since the knockdown of the distal docking complex prevents LRRC56's association with the flagellum. Intriguingly, lrrc56-/- cells display shorter flagella whose maturation is delayed. Inhibition of cell division compensates for the distal ODAs absence thanks to the redistribution of the proximal docking complex, restoring ODAs attachment but not the flagellum length phenotype. This work reveals an unexpected connection between LRRC56 and the docking complex.