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Microplastics (MPs) raise concerns not only as pollutants themselves, but also due to their ability to act as vectors of pollutants adsorbed from seawater, transferring them to marine organisms. However, the relevance of MPs as carriers of pollutants compared to microalgae needs further exploration. This study compared the role of MPs (2-10 μm non-oxidized and 10-15 μm oxidized high-density polyethylene) and natural organic particles (Rhodomonas lens microalgae, MA) as carriers of mercury (Hg, 2.3 μg Hg/L) and chlorpyrifos (CPF, 1.0 μg CPF/L) to adult Acartia tonsa copepods, after 24-48 h exposure. Dose-response experiments were first performed with adult female copepods exposed to oxidized MPs (0.25-4.0 mg/L), waterborne Hg (0.01-10.0 μg/L) and Ox MPs + Hg (0.25-4.0 mg oxidized MPs/L + 0.50-8.0 μg Hg/L) for 48 h, to complement previous studies that focused on the pesticide CPF. Effects were evaluated with four replicates for physiological and reproductive responses (6 females/replicate), biochemical techniques (40 individuals/replicate) and Hg/CPF bioaccumulation measurements (1000 individuals/replicate). Copepods accumulated Hg/CPF similarly from dissolved pollutants (6204 ± 2265 ng Hg/g and 1251 ± 646 ng CPF/g) and loaded MPs (3125 ± 1389 ng Hg/g and 1156 ± 266 ng CPF/g), but significantly less from loaded MA (21 ± 8 ng Hg/g and 173 ± 80 ng CPF/g). After 24-48 h, copepods exposed to MPs + Hg/CPF showed generally greater biological effects than those exposed to dissolved Hg/CPF or to MA + Hg/CPF, although differences were not statistically significant. MA + CPF had significantly lower AChE inhibition (1073.4 nmol min -1  mg -1 ) and MA + Hg lower GRx induction (48.8 nmol min -1  mg -1 ) compared to MPs + Hg/CPF and dissolved Hg/CPF (182.8-236.4 nmol min -1  mg -1 of AChE and 74.1-101.7 nmol min -1  mg -1 of GRx). Principal component analysis suggested different modes of action for Hg and CPF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The clinical success of PARP1/2 inhibitors (PARPi) prompts the expansion of their applicability beyond homologous recombination deficiency. Here, we demonstrate that the loss of the accessory subunits of DNA polymerase epsilon, POLE3 and POLE4, sensitizes cells to PARPi. We show that the sensitivity of POLE4 knockouts is not due to compromised response to DNA damage or homologous recombination deficiency. Instead, POLE4 loss affects replication speed leading to the accumulation of single-stranded DNA gaps behind replication forks upon PARPi treatment, due to impaired post-replicative repair. POLE4 knockouts elicit elevated replication stress signaling involving ATR and DNA-PK. We find POLE4 to act parallel to BRCA1 in inducing sensitivity to PARPi and counteracts acquired resistance associated with restoration of homologous recombination. Altogether, our findings establish POLE4 as a promising target to improve PARPi driven therapies and hamper acquired PARPi resistance., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

This study investigated the role of ultraviolet (UV) radiation and oxidation in high-density polyethylene microplastics (2-15 μm) and nanoplastics (0.2-9.9 μm) (NMPs) on particle chemistry, morphology, and reactivity with cadmium (Cd). Additionally, toxicity of NMPs alone and with Cd was evaluated using RTgutGC cells, a model of the rainbow trout (Oncorhynchus mykiss) intestine. The role on NMPs on Cd bioaccumulation in RTgutGC cells was also evaluated. Dynamic light scattering indicated that after UV radiation NPs agglomerated size increased from 0.8 to 28 µm, and to 8 µm when Cd was added. Oxidized MPs agglomerated size increased from 11 and 7 to 46 and 27 µm in non-UV- and UV-aged oxidized MPs when adding Cd, respectively. Cd-coated particles exhibited generally significantly higher zeta potential than non-Cd-coated particles, while attenuated total reflectance-Fourier transform infrared spectroscopy showed that the functional chemistry of the particles was oxidized and modified after being exposed to UV radiation. Presence of NMPs resulted in a significant decrease in Cd bioaccumulation in RTgutGC cells (100.5-87.9 ng Cd/mg protein) compared to Cd alone (138.1 ng Cd/mg protein), although this was not quite significant for co-exposures with UV-aged NPs (105.7 ng Cd/mg protein). No toxicity was observed in RTgutGC cells exposed to NMPs alone for 24 h. Moreover, co-exposures with Cd indicated that NMPs reduce the toxicity of Cd. Altogether these results show that UV aging enhances NMP surface reactivity, increasing Cd absorption in solution, which resulted in a reduction in Cd bioavailability and toxicity., (© 2024. The Author(s).)

Background: Delivering difficult news to families is an essential but challenging skill. Pediatric trainees report limited confidence in this skill and perform poorly in simulation. We implemented the American Academy of Pediatrics (AAP) Resilience Curriculum and evaluated performance and self-efficacy in delivering difficult news., Methods: The AAP Resilience Curriculum, using the SPIKES (Set-up, Perception, Invitation, Knowledge, Empathy, and Summary) framework, was taught to pediatric fellows. Fellows' performance during simulations with standardized patients before and after curriculum implementation was scored with a SPIKES checklist. Pre- and post-test surveys assessed self-efficacy in delivering difficult news., Results: Fellows (n=19) significantly improved their performance in delivering difficult news, increasing the median SPIKES checklist scores from 78% to 90% completion (P<0.001). Pediatric fellows (n=35) reported improved confidence from 3.4/5 to 3.9 (P=0.01)., Conclusions: Pediatric fellows demonstrated significant improvement in their ability to deliver difficult news during a simulated patient encounter and reported increased self-efficacy in delivering difficult news.

We investigated the bioavailability of the calcium salt (HMB-Ca) and the free acid (HMB-FA) forms of β-hydroxy-β-methylbutyrate (HMB). Sixteen young individuals received the following treatments on three different occasions in a counterbalanced crossover fashion: (1) HMB-FA in clear capsules; (2) HMB-Ca in gelatine capsules; (3) HMB-Ca dissolved in water. All treatments provided 1 g of HMB. Blood samples were taken before and on multiple time points following ingestion. The following parameters were calculated: peak plasma (Cmax), time to peak (Tmax), slope of HMB appearance in blood, area under the curve (AUC), half-life time (t 1/2 ) and relative bioavailability (HMB-Ca in water set as reference). All treatments led to rapid and large increases in plasma HMB. HMB-Ca in capsules and in water showed similar plasma HMB values across time (p = 0.438). HMB-FA resulted in lower concentrations vs. the other treatments (both p < 0.001). AUC (HMB-Ca in capsules: 50,078 ± 10,507; HMB-Ca in water: 47,871 ± 10,783; HMB-FA: 29,130 ± 12,946 µmol L -1  × 720 min), Cmax (HMB-Ca in capsules: 229.2 ± 65.9; HMB-Ca in water: 249.7 ± 49.7; HMB-FA: 139.1 ± 67.2 µmol L -1 ) and relative bioavailability (HMB-Ca in capsules: 104.8 ± 14.9%; HMB-FA: 61.5 ± 17.0%) were lower in HMB-FA vs. HMB-Ca (all p < 0.001). HMB-Ca in water resulted in the fastest Tmax (43 ± 22 min) compared to HMB-Ca in capsules (79 ± 40 min) and HMB-FA (78 ± 21 min) (all p < 0.05), while t 1/2 was similar between treatments. To conclude, HMB-Ca exhibited superior bioavailability compared to HMB-FA, with HMB-Ca in water showing faster absorption. Elimination kinetics were similar across all forms, suggesting that the pharmaceutical form of HMB affects the absorption rates, but not its distribution or elimination., (© 2024. The Author(s).)

We conducted a comprehensive analysis of the surface microtexture of kefir biofilms grown on Theobroma grandiflorum Shum (cupuaçu) juice using atomic force microscopy. Our goal was to investigate the unique monofractal and multifractal spatial patterns of these biofilms to complement the existing limited literature. The biofilms were prepared dispersing four different concentrations of kefir grains in cupuaçu juice. Our morphological analysis showed that the surface of the obtained biofilms is essentially formed by the presence of cupuaçu fibers and microorganisms like lactobacilli and yeast. The topographic height-based parameter analysis reveals that there is a dependence between surface roughness and the concentration of kefir grains used. The strongly anisotropic well-centralized topographical height distribution of the biofilms also exhibited a quasi-symmetrical and platykurtic pattern. The biofilms exhibit comparable levels of spatial complexity, surface percolation and surface homogeneity, which can be attributed to their similar topographic uniformity. This aspect was further supported by the presence of similar multifractality in the biofilms, suggesting that despite their varying topographic roughness, their vertical growth dynamics follow a similar pattern. Our findings demonstrate that the surface roughness of kefir biofilms cultivated on cupuaçu juice is influenced by the concentration of kefir grains in the precursor solution. However, this dependence follows a consistent pattern across different concentrations. Graphical Abstract., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction  Laryngomalacia is the most common congenital laryngeal alteration, with spontaneous resolution in most cases. However, in the face of more severe presentations of the disease, it is necessary to perform supraglottoplasty surgery. Studies have been dedicated to researching changes in swallowing in children with laryngomalacia before and after surgical intervention. Objectives  To identify the prevalence of oropharyngeal dysphagia in children with pre and postsupraglottoplasty laryngomalacia. Data Synthesis  A search strategy was developed with terms and entreterms to designate a population pediatric with laryngomalacia , exposure supraglottoplasty , and outcome frequency of dysphagia , adapted to the requirements of the main databases in the health area. The analysis of the records found was performed by two independent examiners and, in the end, 6 articles were included in the study. The articles found enabled a sample of 330 children with laryngomalacia, 311 of whom underwent supraglottoplasty. Among the included studies, 5 were grouped and meta-analyzed. After supraglottoplasty surgery, a 59% reduction in the prevalence of oropharyngeal dysphagia was identified, with high heterogeneity I 2  = 93%. Conclusion  Despite the heterogeneity of the sample, the supraglottoplasty procedure significantly reduces the prevalence of dysphagia in children with laryngomalacia., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematologic disease caused by the transformation and uncontrolled proliferation of T-cell precursors. T-ALL is generally thought to originate in the thymus since lymphoblasts express phenotypic markers comparable to those described in thymocytes in distinct stages of development. Although around 50% of T-ALL patients present a thymic mass, T-ALL is characterized by peripheral blood and bone marrow involvement, and central nervous system (CNS) infiltration is one of the most severe complications of the disease., Summary: The CNS invasion is related to the expression of specific adhesion molecules and receptors commonly expressed in developing T cells, such as L-selectin, CD44, integrins, and chemokine receptors. Furthermore, T-ALL blasts also express neurotransmitters, neuropeptides, and cognate receptors that are usually present in the CNS and can affect both the brain and thymus, participating in the crosstalk between the organs., Key Messages: This review discusses how the thymus-brain connections, mediated by innervation and common molecules and receptors, can impact the development and migration of T-ALL blasts, including CNS infiltration., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The utilization of artificial intelligence (AI) applications has experienced tremendous growth in recent years, bringing forth numerous benefits and conveniences. However, this expansion has also provoked ethical concerns, such as privacy breaches, algorithmic discrimination, security and reliability issues, transparency, and other unintended consequences. To determine whether a global consensus exists regarding the ethical principles that should govern AI applications and to contribute to the formation of future regulations, this paper conducts a meta-analysis of 200 governance policies and ethical guidelines for AI usage published by public bodies, academic institutions, private companies, and civil society organizations worldwide. We identified at least 17 resonating principles prevalent in the policies and guidelines of our dataset, released as an open source database and tool. We present the limitations of performing a global-scale analysis study paired with a critical analysis of our findings, presenting areas of consensus that should be incorporated into future regulatory efforts., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Heart failure remains a condition with high morbidity and mortality affecting 23 million people globally with a cost burden equivalent to 5.4% of the total health care budget in the United States. These costs include repeated hospitalizations as the disease advances and care that may not align with individual wishes and values. The coincidence of comorbid conditions with advanced heart failure poses significant challenges in the geriatric population. Advance care planning, medication education, and minimizing polypharmacy are primary palliative opportunities leading to specialist palliative care such as symptom management at end of life and timing of referral to hospice., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Palliative care is no longer synonymous with end-of-life care, and because supply has been well outstripped by demand, much of the practice of palliative care early in a patient's illness journey will take place in the primary care clinic-referred to as primary palliative care. Referral to specialty palliative care for complex symptom management or clarification on decision-making is appropriate, and can facilitate hospice referral, if indicated and in line with patient/family goals., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Diverse drugs have been used for the management of inflammation disorders and pain. However, they present many side effects and stimulate the search for new pharmacotherapeutic alternatives. Plant-derived products such as copaiba essential oil (CO) offer beneficial pharmacological effects. On the other hand, essential oil's low water solubility and physical instability hinder its in vivo application. Thus, poly-ɛ-caprolactone (PCL)-based nanocarriers have been used to increase their stability and efficacy. This work aimed to encapsulate CO in PCL nanocapsules and evaluate their effect on inflammation models and pain. The polymeric nanocapsules loading CO (CO-NC) were prepared by nanoprecipitation technique, characterized, and analyzed for their anti-inflammatory effect in vitro and in vivo. The results showed that CO-NC presented a spherical shape, 229.3 ± 1.5 nm diameter, and a negative zeta potential (approximately -23 mV). CO and CO-NC presented anti-inflammatory and antioxidant effects by LPS-activated macrophages (J774 cells). In addition, CO-NC significantly reduced TNF-α secretion (3-fold) compared to CO. In vivo, pre-treatment with CO or CO-NC (50, 100, 200 mg/kg, intraperitoneal; i.p) reduced the mechanical allodynia, paw edema, and pro-inflammatory cytokines induced by intraplantar (i.pl) injection of carrageenan in mice. Specifically, CO-NC (200 mg/kg; i.p.) reduced the production of TNF-α similar to the control group. Our results support using polymeric nanocapsules for CO delivery in inflammatory conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction and Objective: Male detrusor underactivity (DUA) definition remains controversial and no effective treatment is consolidated. Transurethral resection of the prostate (TURP) is one of the cornerstones surgical treatments recommended in bladder outlet obstruction (BOO). However, the role of prostatic surgery in male DUA is not clear. The primary endpoint was the clinical and voiding improvement based on IPSS and the maximum flow rate in uroflowmetry (Qmax) within 12 months., Materials and Methods: We analyzed an ongoing prospective database that embraces benign prostata hyperplasia (BPH) male patients with lower urinary tract symptoms who have undergone to TURP. All patients were evaluated pre and postoperatively based on IPSS questionnaires, prostate volume measured by ultrasound, postvoid residual urine volume (PVR), Prostate Specific Antigen measurement and urodynamic study (UDS) before the procedure. After surgery, all patients were evaluated at 1-, 3-, 6- and 12-months. Patients were categorized in 3 groups: Group 1-Detrusor Underactive (Bladder Contractility Index (BCI) [BCI] < 100 and BOO index [BOOI] < 40); Group 2-Detrusor Underactive and BOO (BCI < 100 and BOOI ≥ 40); Group 3-BOO (BCI ≥ 100 and BOOI ≥ 0)., Results: It was included 158 patients underwent monopolar or bipolar TURP since November 2015 to March 2021. According to UDS, patients were categorized in: group 1 (n = 39 patients); group 2 (n = 41 patients); group 3 (n = 77 patients). Preoperative IPSS was similar between groups (group 1-24.9 ± 6.33; group 2-24.8 ± 7.33; group 3-24.5 ± 6.23). Qmax was statistically lower in the group 2 (group 1-5.43 ± 3.69; group 2-3.91 ± 2.08; group 3-6.3 ± 3.18) as well as greater PVR. The 3 groups presented similar outcomes regard to IPSS score during the follow-up. There was a significant increase in Qmax in the 3 groups. However, group 1 presented the lowest Qmax improvement., Conclusion: There were different objective outcomes depending on the degree of DUA at 12 months follow-up. Patients with DUA had similar IPSS improvement. However, DUA patients had worst Qmax improvement than men with normal bladder contraction., (© 2023 Wiley Periodicals LLC.)

PARP1, an established anti-cancer target that regulates many cellular pathways, including DNA repair signaling, has been intensely studied for decades as a poly(ADP-ribosyl)transferase. Although recent studies have revealed the prevalence of mono-ADP-ribosylation upon DNA damage, it was unknown whether this signal plays an active role in the cell or is just a byproduct of poly-ADP-ribosylation. By engineering SpyTag-based modular antibodies for sensitive and flexible detection of mono-ADP-ribosylation, including fluorescence-based sensors for live-cell imaging, we demonstrate that serine mono-ADP-ribosylation constitutes a second wave of PARP1 signaling shaped by the cellular HPF1/PARP1 ratio. Multilevel chromatin proteomics reveals histone mono-ADP-ribosylation readers, including RNF114, a ubiquitin ligase recruited to DNA lesions through a zinc-finger domain, modulating the DNA damage response and telomere maintenance. Our work provides a technological framework for illuminating ADP-ribosylation in a wide range of applications and biological contexts and establishes mono-ADP-ribosylation by HPF1/PARP1 as an important information carrier for cell signaling., Competing Interests: Declaration of interests E.J.L., H.D., J.J.B., T.C., and I.M. declare the following competing financial interests: Max-Planck-Innovation, the technology transfer center of the Max Planck Society, has licensed the antibodies AbD33204, AbD33205, AbD33644, AbD34251, AbD33641, and AbD43647 to Bio-Rad Laboratories., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Infections have emerged as a novel target in managing skin and mucosa diseases. Bacterial resistance to antimicrobials and biofilm elimination from surfaces remains a challenge. Because polymeric nanocapsules (NC) can increase antimicrobial activity, this study aimed to produce and characterize NC into chitosan films (CSF). Copaiba essential oil (CO) presents antimicrobial activity and was chosen to load NC. In addition, the antibacterial activity was evaluated to obtain a new biodegradable polymeric platform system with the potential to treat topical diseases associated with bacterial infections. The CO-NC produced by nanoprecipitation presented particle size lower than 250 nm, negative charge, and encapsulation efficiency higher than 70 %. Direct incorporation of CO into CSF (CO-CSF) by casting method worsened the film's characteristics. However, incorporating CO-NC into CSF (CO-NC-CSF) avoided these drawbacks demonstrating improved physical, mechanical, morphological, and topographical properties. FTIR results demonstrated possible intermolecular interactions among the polymers and CO. The CO-NC-CSF and CO-CSF presented antibacterial properties against Staphylococcus aureus, and Pseudomonas aeruginosa, especially the formulation containing 1 % of CO. These results indicated that CO-NC-CSF is a promising candidate for treating skin disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The growing use of plastics, including microplastics (MPs), has enhanced their potential release into aquatic environments, where microalgae represent the basis of food webs. Due to their physicochemical properties, MPs may act as carriers of organic and inorganic pollutants. The present study aimed to determine the toxicity of polyethylene MPs (plain and oxidized) and the model pollutants chlorpyrifos (CPF) and mercury (Hg) on the red microalgae Rhodomonas lens, to contribute to the understanding of the effects of MPs and associated pollutants on marine ecosystems, including the role of MPs as vectors of potentially harmful pollutants to marine food webs. R. lens cultures were exposed to MPs (1-1000 μg/L; 25-24,750 particles/mL), CPF (1-4900 μg/L), Hg (1-500 μg/L), and to CPF- and Hg-loaded MPs, for 96 h. Average specific growth rate (ASGR, day -1 ), cellular viability and pigment concentration (chlorophyll a, c2 and carotenoids) were measured at 48 and 96 h. No significant effects were observed on the growth pattern of the microalgae after 96-h exposure to plain and oxidized MPs. However, a significant increase in cell concentration was detected after 48-h exposure to plain MPs. A decrease of the ASGR was noticed after exposure to CPF, Hg and to CPF/Hg-loaded MPs, whereas viability was affected by exposure to MPs, CPF and Hg, alone and in combination. Chlorophyll a and c2 significantly decreased when microalgae were exposed to plain MPs and CPF, while both pigments significantly increased when exposed to CPF-loaded MPs. Similarly, chlorophyll and carotenoids content significantly decreased after exposure to Hg, whereas a significant increase in chlorophyll a was observed after 48-h exposure to Hg-loaded MPs, at the higher tested concentration. Overall, the presence of MPs modulates the toxicity of Hg and CPF to these microalgae, decreasing the toxic effects on R. lens, probably due to a lower bioavailability of the contaminants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Health care services express social and structural inequalities, especially for Dalits and women, due to the indignity and discrimination experienced in health care facilities. Jagrutha Mahila Sanghatane (JMS), a grass-roots organization led by neo-literate Dalit women in rural Karnataka in India, adopted a human rights-based social accountability (SA) approach to address discrimination and dignity in accessing maternal health services. This approach integrated community-based evidence with multi-pronged and multi-level accountability processes with their goal of socio-political empowerment., Methods: The methodological approach is qualitative and uses document analysis, including thematic and content analysis, in-depth group discussions with the campaign leaders, participant observation and interviews with the community health workers., Results: JMS embedded the practice and processes of SA in the politics of empowerment which was central to addressing the structural issues of discrimination and social exclusion faced by Dalit women. The human rights perspective and the pathway of conscientize-organize-struggle provided by the Dalit liberation leader, Dr B. R. Ambedkar, facilitated the organization to conceptualize SA as a process of claiming dignity and justice for Dalit women. Integrating the evidence generation and its deployment into the community campaign cycles, Dalit women could use the accountability process for intensifying mobilization and empowerment. The cumulative impact of the community enquiry relentlessly pursued through the framework of a campaign brought changes in several aspects of primary health care and specific dimensions of maternal health care. Community ownership of the SA process, participation and empowerment were integral to the generation, synthesis and deploying of evidence. Deploying evidence in multiple forms, both horizontally with the communities and vertically with the authorities deepened communities' mobilization and intensified Dalit women's negotiating power with the authorities. The iterative and persistent process of SA provides insights into re-articulating SA beyond the usual recognition of outputs such as report cards into the politics of meaning-making by the mobilized community of the marginalized. The community-based organization posited the SA itself as the process of resistance to structural injustice and as an avenue or their empowerment., Conclusions: For marginalized communities, the SA process has the potential to be a tool for their empowerment in addressing structural power inequities. For such a repositioning of SA, it is critical to focus not only on the technicality of generating evidence but also on the framework driving such a process, the mode of evidence generation and deployment, and integration into the organizational strategy. Such a process can be equally empowering, efficient in addressing the systemic challenges of increasing marginalized community's access to health care services, and valuable in sustaining those changes. The analysis of the strategies of JMS offers significant insights for researchers and practitioners working on SA and maternal health to re-articulate SA from the point of politics of empowerment of the marginalized communities., (© 2022. The Author(s).)

Aspergillus awamori was cultivated in a modified Breccia medium, and the extracellular fraction was obtained, which presented 260 ± 15 µg of protein/mg and specific protease activity of 3.87 ± 0.52 mM.min -1 .mg of protein -1 using N α -p-tosyl-L-arginine methyl ester hydrochloride ( L -TAME) as substrate. This fraction showed major proteins about 104 and 44 kDa and maximal protease activity at pH 5.5, 6.5, and 9.0, suggesting that A. awamori secretes acidic, neutral, and alkaline proteases with expressive thermal stability, however, aspartic protease was the most important activity. When yeast extract was supplemented to a modified Breccia medium, A. awamori protein secretion and protease activity were maximal and the affinity chromatography on pepstatin-agarose was employed to isolate the aspartic protease activity, which was called ASPA, with approximately 75 kDa. ASPA maximal activity was obtained at pH 4.5 and 6.5, and 50 °C. Pepstatin inhibited about 80% of ASPA activity, with IC 50 and Ki values of 0.154 and 0.072 μM, respectively. ASPA cleaved protein and peptides substrates with the highest activity against gelatin (95 U/mg) and good peptidase activity with K M 0.0589 mM and V max 1.909 mM.min -1 .mg protein -1 , using L -TAME as substrate. A. awamori extracellular fraction is a source of proteases with important activity, and the supplementation of modified Breccia medium increased the aspartic protease production. This enzyme presented different biochemical characteristics from the previously reported A. awamori aspartic proteases. Therefore, ASPA is an excellent candidate for biotechnological application due to its important activity and thermostability., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Objective: to investigate the use of the iChirp stimulus in the infant's audiological diagnosis compared to stimuli typically used in the ABR in infants, in addition to suggesting reference values for the assessment of this population., Methods: 62 infants participated in the study, 29 females and 33 males. The subjects underwent the recording of the Auditory Brainstem Response in the Smart Ep equipment, with the stimuli click, iChirp-broadband, tone burst and iChirp-narrowband, which were presented at three levels of intensity (20 dB, 40 dB and 60 dB) and, for tone burst and iChirp-narrowband stimuli, at different frequencies (0.5, 1 k, 2 k and 4 KHz). The data were later analyzed using Student's t-test., Results: In general, the iChirp-broadband and iChirp-narrowband stimuli showed higher latency values and greater amplitudes when compared to click and tone burst stimuli. Furthermore, better signal-to-noise ratios were observed when contrasting iChirp-narrowband with tone burst. Additionally, reference values were established for the assessment of ABR in infants with the iChirp-broadband and iChirp-narrowband in the Smart-Ep equipment., Conclusion: The iChirp stimulus appears to be promising in the infant's audiological diagnosis, as its use promoted greater amplitudes and better wave morphology, which facilitates to mark the waveforms and provides greater efficiency in the investigation of the auditory thresholds. The indication of normative data also enables the clinical use of these stimuli in the infant's audiological diagnosis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Abstract: Gomes-Santos, JAF, Lambertucci, RH, Vardaris, CV, Passos, MEP, Silva-Junior, EP, Hatanaka, E, Gorjão, R, McAnulty, SR, Souza-Junior, TP, and Barros, MP. Early signs of inflammation with mild oxidative stress in Mixed Martial Arts athletes after simulated combat. J Strength Cond Res 36(1): 180-186, 2022-Combat sports involve a combination of strenuous physical activity, usually at the anaerobic threshold, followed by intermittent low-intensity recovery periods for energy re-establishment. Oxidative stress and inflammation are inevitable exercise-related processes that could drastically affect athletic performance and practitioners' health, unless efficiently controlled during and after physical activities. This study aims to measure oxidative stress and inflammation biomarkers in the plasma of 12 top ranked professional Mixed Martial Arts (MMAs) athletes before and after simulated combats under official rules (pre-post study). Our results show that the athletes exhibited mild oxidative imbalances in plasma, evidenced by significant (p < 0.01) higher contents of both reduced (+7.3%) and oxidized glutathione (+28%), uric acid (+21%), and "free" iron (+21%) after combat, whereas variation tendencies (0.05 < p < 0.01) were observed in the antioxidant capacity in plasma (-40%), and SOD (-27%) or GPX (+20%) antioxidant activities in erythrocytes. However, a clear pro-inflammatory state was detected by increases in circulating cytokines IL-6 (+6,020%), IL-1β (+4,357%), and tumor necrosis factor alpha (+63%), and by an abrupt drop of the anti-inflammatory cytokine IL-10 (-98%). A significant correlation was observed between pre-post variations of IL-6 and GSH/GSSG ratio in plasma (p < 0.0001), which reinforces the integration between oxidative stress and inflammation during MMA combats. Considering metabolic and mechanical stresses (imposed by combat techniques, e.g., punches and joint locks), this study indicates pre-existing inflammation, although minor oxidative stress, in MMA professionals after combat., (Copyright © 2019 National Strength and Conditioning Association.)

Background: Burnout is high in primary care physicians and negatively impacts the quality of patient care. While many studies have evaluated burnout, there have been few which investigate those physicians who are satisfied with their careers and life-a phenomenon we term "thriving.", Objective: To identify factors contributing to both career and life satisfaction through qualitative interviews., Participants: The subjects were primary care physicians., Approach: Qualitative interviews were performed between July 2018 and March 2020. Physicians were identified by snowball sampling and were asked to complete validated instruments to identify job/life satisfaction and lack of burnout. Semi-structured interviews were conducted, focused on aspects of participants' career and life which contributed to their thriving, including work environment, social networks, family life, institutional support, coping strategies, and extracurricular activities. Transcripts were analyzed using thematic content analysis using a grounded theory approach., Main Measures: Personal, professional, and life factors that contributed to achieving career and life satisfaction in primary care physicians and potential solutions for burnout., Results: Thirty-two physicians were interviewed (9.4% family physicians, 9.4% combined internists-pediatricians, 40.6% internists, and 40.6% pediatricians) with a mean age 54.7 years and 23.8 years in practice. No physicians included met the criteria for burnout. All met the criteria for career and life satisfaction. Five themes were identified as critical to thriving: an intrinsic love for the work, a rich social network, a fulfilling doctor-patient relationship, a value-oriented belief system, and agency in the work environment., Conclusions: Several factors contribute to professional fulfillment and life satisfaction among primary care physicians, which we propose as a model for physicians thriving. Some factors were intrinsic, such as having value-oriented beliefs and inherent love for medicine, while others were extrinsic, such as having a fulfilling social network. Barriers and opportunities to apply these lessons for the wider physician community are discussed., (© 2021. Society of General Internal Medicine.)

This paper distils the key insights from thematic and inter-thematic deliberations of the Global Symposium on Citizenship, Governance and Accountability in Health. It describes the evolution of the symposium theme on linking accountability to citizenship and governance in health while providing an overview of the symposium. The paper further synthesises the key discussions of the core-themes, then lays out analytical reflections that have emerged from the deliberations that touch upon the issues of power and politics surrounding accountability, viz civil society, democracy, power, civic space and the role of private non-state actors that affect health rights of the marginalised.

In this paper, we introduced an advanced discussion of the 3D morphology of TiO 2 coatings deposited on ITO substrate by electrodeposition under different deposition times. Atomic force microscopy was applied for obtaining topographic images of the samples. The images were processed using the MountainsMap 8.0 commercial software according to ISO 25178-2:2012. Moreover, fractal theory was applied to study the surface microtexture of coatings. The morphology was affected by the deposition time, where the grain size decreased with the increase of the time, making film's surfaces smoother. In addition, the surface roughness exhibited a random behaviour, but does not presented significant difference between samples. The fractal dimension showed similar values for all coatings. In contrast, surface texture isotropy also exhibited random behaviour. However, advanced fractal parameters revealed that when the deposition time increased, the coatings microtexture has become uniform and less porous. Furthermore, all coatings presented high topographic uniformity, regardless of deposition time. These results revealed that the morphology and microtexture of TiO 2 -based coatings can be controlled by the deposition time. LAY DESCRIPTION: An advanced characterization on the micromorphology of 3D morphology, using AFM images, of Titanium dioxide (TiO 2 ) coatings deposited on ITO substrate by electrodeposition under different deposition times. TiO 2 is one of the most studied semiconductors to make photovoltaic devices. The versatility of this semiconductor is associated with low toxicity, high photochemical stability, abundance, and the facility to obtain by conventional synthesis routes. The obtention of a homogeneous and stable layer in the semiconductor TiO 2 film deposition is a crucial stage in the assembly of sensitized photovoltaic devices. Atomic Force Microscopy (AFM) is a technique which can magnify up to a billion times and it uses a tip or probe which touches the sample surface point by point. The tip deflection is interpreted as the surface topography by the software, producing 2D or 3D images that generate several tribological parameters such as roughness in respect to a scanned area, has been a technique widely reported in the morphological characterization, determination of thickness, roughness, and particle size in thin films. Therefore, in this paper, the morphology was studied by atomic force microscopy using MountainsMap commercial software. The main goal was to study the influence of the deposition time on the morphology and microtexture of the material. New parameters such as surface entropy, fractal succolarity and fractal lacunarity were obtained for studying coatings microtexture's complexity., (© 2020 Royal Microscopical Society.)

We performed qualitative and quantitative analysis of surfaces of kefir biofilms loaded with Amazon rainforest fruit extract. Scanning electron microscopy and atomic force microscopy were used to evaluate the micromorphology of the biofilms. The films surface displayed a lower density of microorganisms (∼ 0.061 microorganisms/μm 2 ) for the lowest concentration of fruit extract, however, a greater density (∼0.220 microorganisms/μm 2 ) was observed for the higher concentration. Height stereometric parameters revealed that the biofilms with the highest concentration presented the highest roughness. However, almost all the stereometric parameters related to texture showed no significant difference. Furthermore, the Hurst coefficients of the average power spectrum density were similar for all biofilms. Fractal parameters confirmed that higher concentrations of fruit extract induced a superior topographic irregularity. However, fractal lacunarity does not show any significant difference confirming the similarity of the microtextures. Moreover, fractal succolarity and surface entropy exhibited values that suggested ideal percolation and strong topographic uniformity, respectively, indicating that these films can uniformly adhere to other surfaces. Our results confirm that the stereometric and fractal parameters can be relevant for the surface characterization of microbial films, which can be of great importance to the biomedical field., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Main Conclusion: AFM, profilometry and SEM measurements on both sides of the Anacardium occidentale L. leaf reveal that ultrastructure presented some singularities due to their different morphologies and roughness. The advanced stereometry and power spectrum density of both sides of the Anacardium occidentale L. leaf were carefully studied. We use three different microscopy techniques such as scanning electron microscopy, profilometry, and atomic force microscopy for a complete description of the leaf surface morphology. The morphology of the adaxial and abaxial sides revealed a surface composed of striated cuticles and stomata cells, respectively. The height parameters obtained by profilometry revealed that the abaxial side was rougher. However, both sides presented similar Gaussian height distribution and asymmetry. The advanced stereometric parameters obtained by the topographic maps of AFM revealed that the two sides have some singularities due to their different morphologies and roughness, but with similar microtextures. However, average PSD spectra showed that adaxial and abaxial sides are dominated by relatively low and high spatial frequencies, showing that the microtextures, unlike what was shown in stereometric parameters, are different. These results revealed that leaves surface morphology under different aspects and scales and the quantitative parameters confirmed the different spatial patterns displayed, which can be of great interest for the study of the biological behavior of plants from their leaves.

Objective: to characterize the latency, amplitude and area variables of the Mismatch Negativity (MMN) elicited with verbal stimuli in children with PD, in addition to assessing whether this potential can be a useful tool in capturing auditory perception and discrimination deficits related to this disorder., Methods: MMN was recorded using a combination of speech contrast consisting of acoustic syllables [da vs ta], as the standard and deviant stimuli, in 34 children aged between 5 and 8 years. 14 children of the sample were already diagnosed with Phonological Disorder (PD) while 19 were characterized with typical development., Results: No statistically significant differences were observed for the MMN responses recorded between children with PD and their typically developed peers., Conclusion: The results suggest that the MMN may not be the most suitable procedure to assess auditory perception and discrimination deficits that could potentially be related to PD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of this study was to report the first discussion of statistical parameters and possible applications related to the surface of kefir biofilms prepared with Maytenus rigida Mart. extract through micromorphology, using atomic force microscopy (AFM). Four different samples were produced. The reference contained demerara sugar with a concentration of 40 g/L and the others had added extract whose concentrations were 0.25, 0.50, and 0.75 g/L, respectively. AFM was used to image the surface in tapping mode, on square areas of 30 μm × 30 μm. Images were studied by the MountainsMap premium commercial software. The main parameter of the surface, roughness, grew with the increase of the extract concentration up to 0.50 g/L. In addition, asymmetry and kurtosis showed that the biofilm with the best peak distribution was the one with 0.25 g/L of plant extract. The other parameters followed the main results for the surface and were observed for the depth and volume parameters. The power spectrum density spectrum confirmed the reliability of the results for the sample with 0.25 g/L. Therefore, the sample with 0.25 g/L of plant extract produced the best balance in relation to the surface properties. These results showed that the biofilm morphology and microtexture were affected by the incorporation of the plant extract and can be useful to define possible applications., (© 2020 Wiley Periodicals LLC.)

The present study evaluated the effects of low doses of atrazine administered during gestation and breastfeeding on sperm characteristics of the wild rodent Calomys laucha. Adult females were divided into groups of 10 and administered different doses of atrazine through gavage, during gestational or breastfeeding period. At 3 months of age, the F1 adult male progeny of these females was evaluated. We observed a drastic reduction in the total and progressive motility of male sperm cells at all doses and during both the exposure periods. Moreover, the plasma membrane integrity of adult male sperm cells decreased at all doses of atrazine administered during the breastfeeding, whereas the membrane fluidity of these cells increased at all tested doses. Atrazine led to a decrease in the sperm mitochondrial functionality at all doses and during both exposure periods. The damage to the sperm DNA was higher in males exposed to the highest dose (1.0 mg/kg) during the gestation period, and in animals exposed to the lowest dose of atrazine (0.1 mg/kg) during breastfeeding period. Furthermore, the highest dose (1.0 mg/kg) of atrazine reduced the sperm concentration. Furthermore, the reduced levels of reactive oxygen species (ROS) were observed at all evaluated doses in males exposed during the gestation period. These results suggest that the administration of low doses of atrazine at critical periods of development may permanently reduce the sperm quality in C. laucha.

The presence in EU waters of invasive tetrodotoxin (TTX) -harbouring puffer fishes has been receiving increasingly attention due to potential new threats posed by this potent neurotoxin. The present study investigates the occurrence of tetrodotoxin, saxitoxin (STX), and their analogues in two native puffer fish species from the NE Atlantic. High TTX content was detected by LC-MS/MS in several tissues of the Guinean puffer Sphoeroides marmoratus from Madeira Island (Portugal), reaching concentrations as high as 15 mg TTX kg -1 in the digestive tract of a male specimen and 7.4 mg TTX kg -1 in gonads of a female specimen. Several TTX analogues were also detected, including the 4-epi-TTX, 4,9-Anhydro-TTX, 5- 11- deoxyTTX and 6,11-dideoxyTTX. Although at low levels, STX was detected in liver of the Oceanic puffer Lagocephalus lagocephalus. Trace levels of decarbamoylsaxitoxin (dcSTX) were also observed in L. lagocephalus. This study reports the presence of TTX and STX in native fish from EU waters, highlighting the need for a proper understating of the origin, distribution and fate of these toxins in NE Atlantic., (Copyright © 2019. Published by Elsevier Ltd.)

Objective  To describe the profile of patients with developmental dysplasia of the hip (DDH) diagnosed by physical and ultrasound examination, with the implementation of a protocol for the treatment and follow-up of DDH. Methods  A cross-sectional study with DDH patients born between January 2014 and December 2016, in the city of Pelotas, Southern Brazil. Ethnicity, gender, birth weight, fetal presentation, affected side of the hip, gestational age, maternal age and family history were considered. The data on the medical records were compared with the characteristics of the general population described on the Brazilian National Information System on Live Births (Sistema de Informação sobre Nascidos Vivos [SINASC]). Results  A total of 33 DDH patients were identified, mostly female, with a four-fold higher probability of having the condition ( p  < 0.001); the left was the most affected side. No statistically significant association was found regarding the following factors: birth weight, gestational age, ethnicity, and maternal age. The newborns in breech presentation had a 15-fold higher probability of presenting DDH ( p  < 0.001). A total of 21 newborns required immediate treatment of the hips, since the ultrasound showed a Graf classification of IIb or higher, or the radiography showed dislocation in DDH patients older than 6 months of age. Conclusion  Screening for DDH is essential in all newborns; physical examinations revealing alterations must be complemented with ultrasound imaging to avoid the delayed diagnosis of the condition., Competing Interests: Conflitos de Interesse Os autores declaram não haver conflitos de interesse.

Triphenyltin (TPT) is an organotin compound (OT), primarily used in agriculture and in the composition of antifouling paints for ships worldwide. Studies have showed its effects as an endocrine disrupter in several organisms by preventing enzymatic expression and causing reproductive toxicity. This study aimed to evaluate the effects of exposure to TPT, via breastfeeding, on reproductive physiology in the Calomys laucha species. The experimental design was compound of five groups, two controls and three with different doses of TPT. Moreover, females were exposed by gavage to the TPT for 20 days, from the 1st day postpartum to the 21st postnatal day (PND). Then, the pups were euthanized and the kinetics, organelles, and biochemistry of the sperm were evaluated. The results presented a reduction in total motility in the groups exposed to TPT. Regarding cellular organelles analysis, a loss in membrane integrity was evidenced; the functionality of mitochondria showed diminution followed by increased acrosome reaction. In conclusion, the TPT causes alteration of the reproductive parameters, decreasing the activity and sperm quality in individuals exposed in the breastfeeding phase.

The present study aims to evaluate the influence of triphenyltin (TPT) exposure on reproductive physiology on Calomys laucha species, since this species inhabits regions susceptible to exposure to this contaminant. Animals exposed to the highest dose (10.0 mg/kg) presented signs of severe intoxication in only 7 days of exposure, demonstrating a higher sensitivity of this species to triphenyltin. The 10.0 mg TPT/kg dose was analyzed separately for short-term exposure and results suggest that exposure to this dose was severely detrimental to sperm activity. Among the main results obtained in the evaluation of sperm kinetics, a reduction in total motility was observed from the 0.5 mg TPT/kg group, accentuated according to the increase in the doses of TPT. In progressive motility, there was a decrease from the dose of 0.5 mg TPT/kg and maintained the plateau until the dose of 5.0 mg TPT/kg. It was also observed an increase in the distances and velocities average path, rectilinear and curvilinear in doses of 2.5 and 5.0 mg/kg. From the flow cytometry, evaluation a decrease in mitochondrial functionality was observed as the dose increased. Increased membrane fluidity was also observed from the 5.0 mg TPT/kg dose and the acrosome reaction presented higher values at doses of 0.5 and 5.0 mg TPT/kg. We can conclude that TPT causes impairment of the sperm activity, reducing it in individuals exposed in the adult phase., (Copyright © 2018. Published by Elsevier Ltd.)

Objectives: Due to the uncontrolled increase of the mobile health applications and their scarce use by elderly for reason of absence credibility of measurements by lack scientific support, the aim of this study was to evaluate the differences between the biophysical measurements based on standard instrument against a mobile application using controlled experiments with elderly to propose an effective validation model of the developed apps., Methods: The subjects of the study (50 people) were elderly people who wanted to check their weight and cardiac status. For this purpose, two mobile applications were used to measure energy expenditure based on physical activity (Activ) and heart rate (SMCa) during controlled walking at specific speeds. Minute-by-minute measurements were recorded to evaluate the average error and the accuracy of the data acquired through confidence intervals by means of statistical analysis of the data., Results: The experimental results obtained by the Activ/SMCa apps showed a consistent statistical similarity with those obtained by specialized equipment with confidence intervals of 95%. All the subjects were advised and trained on the use of the applications, and the initial registration of data to characterize them served to significantly affect the perceived ease of use., Conclusions: This is the first model to validate a health-app with elderly people allowed to demonstrate the anthropometric and body movement differences of subjects with equal body mass index (BMI) but younger. Future studies should consider not only BMI data but also other variables, such as age and usability perception factors., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Background: Functional characterization of non-coding elements in the human genome is a major genomic challenge and the maturation of genome-editing technologies is revolutionizing our ability to achieve this task. Oncogene-induced senescence, a cellular state of irreversible proliferation arrest that is enforced following excessive oncogenic activity, is a major barrier against cancer transformation; therefore, bypassing oncogene-induced senescence is a critical step in tumorigenesis. Here, we aim at further identification of enhancer elements that are required for the establishment of this state., Results: We first apply genome-wide profiling of enhancer-RNAs (eRNAs) to systematically identify enhancers that are activated upon oncogenic stress. DNA motif analysis of these enhancers indicates AP-1 as a major regulator of the transcriptional program induced by oncogene-induced senescence. We thus constructed a CRISPR-Cas9 sgRNA library designed to target senescence-induced enhancers that are putatively regulated by AP-1 and used it in a functional screen. We identify a critical enhancer that we name Enh AP1-OIS1 and validate that mutating the AP-1 binding site within this element results in oncogene-induced senescence bypass. Furthermore, we identify FOXF1 as the gene regulated by this enhancer and demonstrate that FOXF1 mediates Enh AP1-OIS1 effect on the senescence phenotype., Conclusions: Our study elucidates a novel cascade mediated by AP-1 and FOXF1 that regulates oncogene-induced senescence and further demonstrates the power of CRISPR-based functional genomic screens in deciphering the function of non-coding regulatory elements in the genome.

Reproductive effects caused by the exposure to environmentally relevant dosages of atrazine on wild animals are poorly understood. This study evaluated the effects of three dosages of atrazine on sperm parameters of adult Calomys laucha males. Adult mice were orally exposed to dosages of 0 (water and vehicle control), 0.1, 1, and 10 mg/kg of animal weight for a 21-day period. Following exposure, analyses were performed to determine sperm motility parameters, plasma membrane integrity and fluidity, mitochondrial functionality, acrosome integrity, DNA damage, lipid peroxidation, and production of reactive oxygen species (ROS) in the sperm samples. Total and progressive motility were reduced in all dosages in comparison to control groups. Membrane integrity and mitochondrial functionality of sperm were reduced in all dosages, and the sperm membrane fluidity increased in the higher dosages of atrazine (1 and 10 mg/kg), in comparison with the vehicle control. A decrease in the acrosome integrity was noted at 10 mg/kg of atrazine, compared to the control groups. The integrity of DNA, ROS generation, and lipid peroxidation of sperm showed no significant differences when compared with the control groups. These results suggest that exposure to low dosages of atrazine can affect sperm parameters of Calomys laucha and therefore reduce the reproductive capacity of wild rodent species.

This paper, which is part of a primary interdisciplinary doctoral research work with a qualitative research design, seeks to understand the ethical principles that intersect healthcare jurisprudence in litigations where citizens, who have encountered death or violations in the provision of critical care, have had to take recourse to the courts to get justice.

In this study, sacha inchi oil (SIO) was microencapsulated by emulsion-based systems using ovalbumin (Ova), pectin (Pec), and xanthan gum (XG), followed by freeze-drying. The microencapsulation was confirmed using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The stability of omega-3 in SIO alone as well as in microencapsulated SIO was assessed by nuclear magnetic resonance ( 1 H NMR) spectroscopy after human gastric simulation (HGS). The SEM results revealed distinct structures for the two types of microcapsules. The thermograms showed that the thermal resistance was increased in the microencapsulated SIO, indicating that the emulsion-based system may be a way to protect the omega-3 in the SIO. In addition, the microencapsulation conferred an increased crystallinity degree, indicating a higher structural organization. Moreover, this method did not affect the stability of SIO, as confirmed by 1 H NMR. The release of omega-3 acyl units from the SIO was correlated with the decrease of the methynic proton (sn, 2 position) of triacylglycerol (TAG). In contrast, the increase of 1,3-diglycerides was negatively correlated with the decrease of glyceryl groups (sn, 1,3 positions). The HGS conditions did not significantly alter the stability of the omega-3 of SIO over 180min. The SIO-Ova microcapsules had a similar behavior to the SIO, and the presence of Ova was not enough to prevent the decrease of omega-3 content over 180min. The SIO-Ova-Pec and SIO-Ova-XG microcapsules were shown to protect the omega-3 content effectively. In conclusion, the microcapsules developed in this study can be used to transport nutraceutical compounds because they are resistant to the human gastric conditions tested in vitro., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Adaptive responses of antioxidant defense systems (ADS) to changes in increased levels of activity are critical, especially in Antarctic fishes. The benthopelagic marbled notothen (Notothenia rossii) shows higher spontaneous activity than the benthonic and sluggish rockcod (N. coriiceps). Therefore, we hypothesize that species-related responses of ADS would occur to counteract different rates of reactive oxygen species formation in these two Antarctic fish. Here we evaluated ADS and oxidative damage in tissues (brain, gills, liver and white muscle) of the two Antarctic fish. Despite no significant differences in lipid and protein oxidative damage were observed, we actually found species- and tissue-specific differences in ADS. Gill metallothionein-like proteins (MTLP) and liver reduced glutathione (GSH) concentrations were higher in N. coriiceps than in N. rossii. Brain and gill antioxidant capacity against peroxyl radicals (ACAP); gill enzyme [glutamate-cysteine ligase (GSL), superoxide dismutase (SOD) and catalase (CAT)] activity; liver GCL and SOD activity; and white muscle CAT activity were higher in N. rossii than in N. coriiceps. Therefore, the more active fish (N. rossii) maintains higher activities of enzymes involved in superoxide ions (O 2 .- ) detoxification and GSH production in peripheral tissues (gills, liver and white muscle). This allows the more active fish (N. rossii) to keep levels of lipid and protein oxidative damage similar to those observed in the sluggish fish (N. coriiceps). It is worth noting that the more active fish also shows a higher brain antioxidant capacity, which could involve other non-enzymatic antioxidants like vitamins C and E. In contrast, N. coriiceps shows lower consumption of non-enzymatic antioxidants in peripheral tissues than N. coriiceps. As hypothesized, our results indicate that differences in ADS profiles between fish species are likely related to their habits and metabolic rates. This would imply in different fish abilities to deal with oxidative stress associated with increasing seawater temperature., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Antioxidant defense system (ADS) and oxidative stress parameters were evaluated in the Antarctic fish Notothenia rossii and N. coriiceps exposed to increasing temperature. Acclimated fish were kept at 0°C or exposed to 4°C for 1day (N. rossii) or to 2 and 4°C for 1 and 6 days (N. coriiceps). Measurements were assessed in brain, gills, liver, white muscle and erythrocytes. Parameters analyzed included antioxidant capacity against peroxyl radicals (ACAP); reduced glutathione (GSH) and metallothionein-like proteins (MTLP) concentration; superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutamate-cysteine ligase (GCL) activity; lipid peroxidation (LPO) level and protein carbonyl (PC) concentration. Increased liver GST activity was observed in N. rossii exposed to 4°C for 1day. Increased muscle GPx activity was observed in N. coriiceps after exposure to 2°C for 1day. Reduced gill GPx activity and increased liver SOD activity were observed after exposure to 4°C for 1day. In N. coriiceps, increased gill GCL activity and reduced gill GPx activity, as well as reduced liver MTLP were observed after exposure to 2°C for 6 days. Reduced brain SOD activity and increased brain LPO; reduced gill ACAP, GSH concentration and GPx activity, as well as increased gill GCL activity; reduced liver ACAP, MTLP, SOD activity, GST activity and increased liver and erythrocytes LPO were observed after exposure to 4°C for 6 days. These findings indicate that ADS is more responsive to short-term increasing temperature in the sluggish N. coriiceps than in the active N. rossii. However, responses of N. coriiceps to long-term increasing temperature were transient and did not prevent tissue oxidative damage. Considering the predicted increase in temperature in the Southern Ocean over the next decades, our findings suggest that Antarctic fishes are sensitive to ocean warming, displaying tissue oxidative damage associated with the thermal stress., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Integral grape juice is extracted from the grape through processes that allow the retention of their natural composition. However, due to the severity of some processes, fruit juices can undergo changes in their quality. The present study evaluated the cytotoxic and mutagenic effects of integral grape juice by a cytokinesis-blocked micronucleus assay in Rattus norvegicus hepatoma cells (HTC) in vitro. Vitis labrusca L. (variety Concord) were produced organically and by a conventional system, and their juice was extracted by a hot extraction process. The organic grapes were subjected to ultraviolet-type C radiation (UV-C). Experiments were performed after production and after 6 months in storage. Physicochemical analyses revealed that UV-C irradiation of organic grapes, the juice production process, and storage resulted in nutraceutical alterations. However, none of the juice concentrations were cytotoxic to HTC cells by the cytokinesis-blocked proliferation index results or were mutagenic, because the formation of micronucleated cells was not induced. In general, juice induced cell proliferation, possibly due to the presence of vitamins and sugar content (total soluble solid). The data increased the understanding of food technology and confirmed the quality and safety consumption of these juices.

Objective: to analyze time trends and describe the causes of hospitalizations for Ambulatory Care Sensitive Conditions (ACSC) in children under five years old in Ceará, Brazil, 2000-2012., Methods: this is an ecological time series study using data from the National Hospital Information System; trends were analyzed using Prais-Winsten regression., Results: from 2000 and 2016 ACSC hospitalization rates fell from 32.5 to 11.2/1,000 inhabitants under five years old (annual variation of -16.8%; 95%CI -20.6;-10.9); the cause groups with the largest reductions were nutritional deficiencies (-94.7%), infectious gastroenteritis (-52.6%), asthma (-59.0%) and bacterial pneumonias (-8.9%); the greatest reduction was found in the post-neonatal component (-22.4%); the hospitalization rate for prenatal and childbirth-related diseases increased 15 times among children under one year old., Conclusion: despite reduced ACSC hospitalization rates, preventable conditions were found that may reflect gaps in Primary Health Care.

Background: During glioma surgery "maximal safe resection" must be the main goal. Intraoperative magnetic resonance imaging (iMRI) associated with awake craniotomy (AC) is a valuable tool to achieve this objective. In this article, AC with a "next-door" iMRI concept is described in a stepwise protocol., Methods: This is a retrospective analysis of 18 patients submitted to AC using iMRI; a stepwise protocol is also discussed., Results: The mean age was 41.7 years. Hemiparesis, aphasia, and seizures were the main initial symptoms of the patients. Sixty-six percent of the tumors were located in the left hemisphere. All tumors were near or within eloquent areas. Fifty-three percent of the cases were glioblastomas multiforme and 47% of the patients had low grade gliomas. The mean surgical time and iMRI time were 4 h 4 min and 30 min, respectively. New resection was performed in 33% after iMRI. Extent of resection (EOR) higher than 95% was possible in 66.7% of the patients. The main reason of EOR lower than 95% was positive mapping of eloquent areas (6 patients). Eighty percent of the patients experienced improvement of their deficits immediately after the surgery or had a stable clinical status whereas 20% had neurological deterioration, however, all of them improved after 30 days., Conclusion: AC associated with "next-door" iMRI is a complex procedure, but if performed using a meticulous technique, it may improve the overall tumor resection and safety of the patients., Competing Interests: There are no conflicts of interest.

Exposure to high levels of cortisol and self-reported stress, as well as cognitive reserve, have been linked to Alzheimer's disease pathology. However, there are no studies on the interaction of these variables. The present study aims to assess the associations of measures of cortisol, self-reported stress, and cognitive reserve with neuropsychological performance in healthy elderly people; besides, to test the interactions between these variables. Cross-sectional analyzes were conducted using data on stress, cognitive reserve and clinical conditions in 145 healthy elderly adults. A neuropsychological battery was used to assess executive functions, verbal memory and processing speed. Measurement of salivary cortisol at the circadian nadir was taken. A negative association between different stress measures and performance on tasks of memory, executive functions and processing speed was observed. Elderly people with higher cognitive reserve showed superior performance on all neuropsychological measures. No significant interaction between stress and cognitive reserve to neuropsychological performance was observed. These results indicate that older adults with high levels of stress and reduced cognitive reserve may be more susceptible to cognitive impairment.

Worldwide, about 22 million children under five years old are overweight. Environmental factors are the main trigger for this epidemic. The purpose of this study was to evaluate the eating and physical activity habits in a cohort of eight-year-old children in Pelotas, Brazil. Eating habits were assessed based on the Ten Steps to Healthy Eating proposed by the Ministry of Health. To assess the level of physical activity, the physical activity questionnaire for children and adolescents (PAQ-C) was used. Of the 616 interviewed children at 8 years, it was observed that 50.3% were male; 70.3% were white and just over half belonged to economic class C. None of the children were classified as very active and none acceded to a daily consumption of six servings of the cereals, tubers, and roots. The steps that had higher adhesion were 8 (do not add salt to ready foods); 4 (consumption of beans, at least 5 times per week) and 1 (have 3 meals and 2 snacks per day), respectively. The high prevalence of physical inactivity and low level of healthy eating habits confirm the importance of strategies to support and encourage the practice of physical activity and healthy eating among youth.

Sperm quality tests on fish are classically used for evaluating cryopreservation procedures, and they are also promising to assess aquatic toxicity and biomarkers of xenobiotic effects on reproduction. Osmotic shock from the storage medium is one of the main factors affecting sperm quality during evaluation. Thus, the objective of this study was to evaluate the effects of different osmolalities (240-460 mOsm/kg) for at least 4 days on the sperm quality parameters of the viviparous fish Jenynsia multidentata. The level of significance was (P < 0.05). The plasma osmolality of J. multidentata is 326 ± 3.9 mOsm/kg. The motility of fresh semen was higher in osmolalities of 280 and 300 mOsm/kg but did not differ between osmolalities from 240 to 320 mOsm/kg. Above 380 mOsm/kg, the motility observed was 0%. Over the time period studied motility increased with increasing osmolality, and the most constant and long-lasting rates were between 300 and 320 mOsm/kg. On the 4th day of evaluation, higher membrane integrity rates were observed between 280 and 360 mOsm/kg, higher mitochondrial membrane potential was observed between 300 and 460 mOsm/kg, and higher DNA integrity rates were observed between 260 and 380 mOsm/kg. Moreover, osmolalities ≥460 and ≤240 resulted in the lowest motility and DNA integrity levels. Over 4 days, the plasma membrane integrity was significantly lower at ≤260 and ≥400 mOsm/kg, and the mitochondrial membrane potential was significantly lower only in osmolalities ≤240 mOsm/kg. Therefore, we conclude that for sperm quality preservation in J. multidentata, an osmolality of 300-320 mOsm/kg of the most suitable diluent is necessary. Furthermore, we conclude that the storage of sperm in a hyposmotic (<260 mOsm/kg) or hyperosmotic (>400 mOsm/kg) solution affects not only motility but also other sperm quality parameters.

Strenuous exercise is detrimental to athletes because of the overproduction of reactive oxygen species. Melatonin, a classic antioxidant, has been shown to exhibit beneficial effects regarding intense exercise and tissue repair. In this study, we evaluated the onset and resolution of inflammation in melatonin-treated and nontreated rats subjected to a strenuous exercise session. We also analyzed the formation of thiobarbituric acid reactive substances (TBARS) and the activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Control and treated rats were subjected to exhaustive exercise after a period of 10 days of melatonin treatment (20 mg/dL). Plasma and muscle levels of tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), cytokine-induced neutrophil chemoattractant-2-alpha/beta (CINC-2α/β), l-selectin, macrophage inflammatory protein-3-alpha (MIP-3α), and vascular endothelial growth factor (VEGF) were measured prior to, immediately after, and 2 hr after exercise. Our data revealed decreases in the muscle concentrations of IL-1β (35%), TNF-α (13%), IL-6 (48%), and TBARS (40%) in the melatonin-treated group compared with the control group. We also observed decreases in the plasma concentrations of IL-1β (17%) in the melatonin-treated group. VEGF-α concentrations and SOD activity increased by 179% and 22%, respectively, in the melatonin-treated group compared with the control group. We concluded that muscle inflammation and oxidative stress resulting from exhaustive exercise were less severe in the muscles of melatonin-treated animals than in the muscles of control animals. Thus, melatonin treatment may reverse exercise-induced skeletal muscle inflammation and stimulate growth factor synthesis., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chlorophyte microalgae have a cell wall containing a large quantity of cellulose Iα with a triclinic unit cell hydrogen-bonding pattern that is more susceptible to hydrolysis than that of the cellulose Iβ polymorphic form that is predominant in higher plants. This study addressed the enzymatic hydrolysis of untreated Chlorella homosphaera biomass using selected enzyme preparations, aiming to identify the relevant activity profile for the microalgae cellulose hydrolysis. Enzymes from Acremonium cellulolyticus, which secretes a complete pool of cellulases plus β-glucosidase; Trichoderma reesei, which secretes a complete pool of cellulases with low β-glucosidase; Aspergillus awamori, which secretes endoglucanases and β-glucosidase; blends of T. reesei-A. awamori or A. awamori-A. cellulolyticus enzymes; and a purified A. awamori β-glucosidase were evaluated., Results: The highest initial glucan hydrolysis rate of 140.3 mg/g/h was observed for A. awamori enzymes with high β-glucosidase, low endoglucanase, and negligible cellobiohydrolase activities. The initial hydrolysis rates when using A. cellulolyticus or T. reesei enzymes were significantly lower, whereas the results for the T. reesei-A. awamori and A. awamori-A. cellulolyticus blends were similar to that for the A. awamori enzymes. Thus, the hydrolysis of C. homosphaera cellulose was performed exclusively by the endoglucanase and β-glucosidase activities. X-ray diffraction data showing negligible cellulose crystallinity for untreated C. homosphaera biomass corroborate these findings. The A. awamori-A. cellulolyticus blend showed the highest initial polysaccharide hydrolysis rate of 185.6 mg/g/h, as measured by glucose equivalent, in addition to the highest predicted maximum glucan hydrolysis yield of 47% of total glucose (w/w). T. reesei enzymes showed the lowest predicted maximum glucan hydrolysis yield of 25% (w/w), whereas the maximum yields of approximately 31% were observed for the other enzyme preparations. The hydrolysis yields were proportional to the enzyme β-glucosidase load, indicating that the endoglucanase load was not rate-limiting., Conclusions: High rates of enzymatic hydrolysis were achieved for untreated C. homosphaera biomass with enzymes containing endoglucanase and β-glucosidase activities and devoid of cellobiohydrolase activity. These findings simplify the complexity of the enzyme pools required for the enzymatic hydrolysis of microalgal biomass decreasing the enzyme cost for the production of microalgae-derived glucose syrups.

In indigenous populations, age can be estimated based on family structure and physical examination. However, the accuracy of such methods is questionable. The aim of this cross-sectional study was to evaluate occlusal tooth wear related to estimated age in the remote indigenous populations of the Xingu River, Amazon. Two hundred and twenty three semi-isolated indigenous subjects with permanent dentition from the Arara (n = 117), Xicrin-Kayapó (n = 60) and Assurini (n = 46) villages were examined. The control group consisted of 40 non-indigenous individuals living in an urban area in the Amazon basin (Belem). A modified tooth wear index was applied and then associated with chronological age by linear regression analysis. A strong association was found between tooth wear and chronological age in the indigenous populations (p <0.001). Tooth wear measurements were able to explain 86% of the variation in the ages of the Arara sample, 70% of the Xicrin-Kaiapó sample and 65% of the Assurini sample. In the urban control sample, only 12% of ages could be determined by tooth wear. These findings suggest that tooth wear is a poor estimator of chronological age in the urban population; however, it has a strong association with age for the more remote indigenous populations. Consequently, these findings suggest that a simple tooth wear evaluation method, as described and applied in this study, can be used to provide a straightforward and efficient means to assist in age determination of newly contacted indigenous groups.