Antioxidant Activity, Physicochemical and Sensory Properties of Stingless Bee Honey from Australia.

This study reports on the physicochemical and sensory attributes, total phenolic content, and antioxidant activity of 36 honey samples produced by two different stingless bee species (Tetragonula carbonaria and Tetragonula hockingsi) from Australia. The findings reveal moisture content across all samples ranges from 24.9% to 30.8% (w/w), electrical conductivity from 1.02 to 2.15 mS/cm, pH levels between 3.57 and 6.54, soluble solids from 69.2 to 75.1 °Brix, trehalulose concentrations from 6.20 to 38.2 g/100 g, fructose levels from 7.79 to 33.4 g/100 g, and glucose content from 3.36 to 26.8 g/100 g. Sucrose was undetectable in all investigated samples. In a sensory analysis involving 30 participants, Australian stingless bee honey was perceived as having a more pronounced sourness compared with New Zealand Manuka honey. The study reveals considerable variability in the composition of Australian stingless bee honey, influenced by factors such as floral availability, geographical origin, and time of harvest. It also demonstrates the presence of phenolic compounds and antioxidant activity in stingless bee honey, underlining their potential as a natural source of antioxidants. All investigated samples contain trehalulose, which supports the findings of other recent studies that propose this unusual disaccharide as a marker compound of stingless bee honey.

Metabolic priming by multiple enzyme systems supports glycolysis, HIF1α stabilisation, and human cancer cell survival in early hypoxia.

Adaptation to chronic hypoxia occurs through changes in protein expression, which are controlled by hypoxia-inducible factor 1α (HIF1α) and are necessary for cancer cell survival. However, the mechanisms that enable cancer cells to adapt in early hypoxia, before the HIF1α-mediated transcription programme is fully established, remain poorly understood. Here we show in human breast cancer cells, that within 3 h of hypoxia exposure, glycolytic flux increases in a HIF1α-independent manner but is limited by NAD+ availability. Glycolytic ATP maintenance and cell survival in early hypoxia rely on reserve lactate dehydrogenase A capacity as well as the activity of glutamate-oxoglutarate transaminase 1 (GOT1), an enzyme that fuels malate dehydrogenase 1 (MDH1)-derived NAD+. In addition, GOT1 maintains low α-ketoglutarate levels, thereby limiting prolyl hydroxylase activity to promote HIF1α stabilisation in early hypoxia and enable robust HIF1α target gene expression in later hypoxia. Our findings reveal that, in normoxia, multiple enzyme systems maintain cells in a primed state ready to support increased glycolysis and HIF1α stabilisation upon oxygen limitation, until other adaptive processes that require more time are fully established.

Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer.

Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy1-3. Consequently, spatially resolved omics-level analyses are gaining traction4-9. Despite considerable therapeutic interest, tumor metabolism has been lagging behind this development and there is a paucity of data regarding its spatial organization. To address this shortcoming, we set out to study the local metabolic effects of the oncogene c-MYC, a pleiotropic transcription factor that accumulates with tumor progression and influences metabolism10,11. Through correlative mass spectrometry imaging, we show that pantothenic acid (vitamin B5) associates with MYC-high areas within both human and murine mammary tumors, where its conversion to coenzyme A fuels Krebs cycle activity. Mechanistically, we show that this is accomplished by MYC-mediated upregulation of its multivitamin transporter SLC5A6. Notably, we show that SLC5A6 over-expression alone can induce increased cell growth and a shift toward biosynthesis, whereas conversely, dietary restriction of pantothenic acid leads to a reversal of many MYC-mediated metabolic changes and results in hampered tumor growth. Our work thus establishes the availability of vitamins and cofactors as a potential bottleneck in tumor progression, which can be exploited therapeutically. Overall, we show that a spatial understanding of local metabolism facilitates the identification of clinically relevant, tractable metabolic targets.

Mechanism of substrate hydrolysis by the human nucleotide pool sanitiser DNPH1.

Poly(ADP-ribose) polymerase (PARP) inhibitors are used in the clinic to treat BRCA-deficient breast, ovarian and prostate cancers. As their efficacy is potentiated by loss of the nucleotide salvage factor DNPH1 there is considerable interest in the development of highly specific small molecule DNPH1 inhibitors. Here, we present X-ray crystal structures of dimeric DNPH1 bound to its substrate hydroxymethyl deoxyuridine monophosphate (hmdUMP). Direct interaction with the hydroxymethyl group is important for substrate positioning, while conserved residues surrounding the base facilitate target discrimination. Glycosidic bond cleavage is driven by a conserved catalytic triad and proceeds via a two-step mechanism involving formation and subsequent disruption of a covalent glycosyl-enzyme intermediate. Mutation of a previously uncharacterised yet conserved glutamate traps the intermediate in the active site, demonstrating its role in the hydrolytic step. These observations define the enzyme's catalytic site and mechanism of hydrolysis, and provide important insights for inhibitor discovery.

Seasonal respiratory virus trends in pediatric patients during the COVID-19 pandemic in Brazil.

Acute respiratory infections are a constant public health problem causing childhood morbidity and mortality worldwide. Reported cases of major respiratory infections decreased in 2020 after restrictive measures were adopted to contain the COVID-19 pandemic, but there is little data on the impact after these measures were relaxed in the subsequent years. This study conducted molecular analysis to identify rhinovirus, respiratory syncytial virus, influenza A virus, and adenovirus in SARS-CoV-2-negative samples taken from symptomatic pediatric patients during 2021 and 2022 to ascertain the impact of pandemic response measures within the broader epidemiological scenario. The positivity rates found were 28.3% and 50.8%, in 2021 and 2022, respectively, representing a significant increase (1.8 times) in the circulation of non-SARS-CoV-2 viruses after the reduction of non-pharmacological measures to contain the COVID-19 pandemic. Within the positive samples, rhinovirus and respiratory syncytial virus were most frequent (44.4 and 18% in 2021; 44.5 and 22.5% in 2022), whereas influenza A and adenovirus were found in lower frequency (12.5 and 5.5% in 2021; 13.4 and 4.9% in 2022, respectively). Because these different respiratory virus diseases produce similar symptoms, diagnosis based on clinical condition alone can be inaccurate, and more reliable testing is required to select the best therapeutic approach for each case. The loosening of restrictive measures to contain the COVID-19 pandemic led to higher numbers of other respiratory infections in pediatric patients. Ongoing surveillance and differential diagnosis of respiratory viruses are required to better understand their seasonal patterns after the COVID-19 pandemic to guide prevention and control strategies.

Diet suppresses glioblastoma initiation in mice by maintaining quiescence of mutation-bearing neural stem cells.

Glioblastoma is thought to originate from neural stem cells (NSCs) of the subventricular zone that acquire genetic alterations. In the adult brain, NSCs are largely quiescent, suggesting that deregulation of quiescence maintenance may be a prerequisite for tumor initiation. Although inactivation of the tumor suppressor p53 is a frequent event in gliomagenesis, whether or how it affects quiescent NSCs (qNSCs) remains unclear. Here, we show that p53 maintains quiescence by inducing fatty-acid oxidation (FAO) and that acute p53 deletion in qNSCs results in their premature activation to a proliferative state. Mechanistically, this occurs through direct transcriptional induction of PPARGC1a, which in turn activates PPARα to upregulate FAO genes. Dietary supplementation with fish oil containing omega-3 fatty acids, natural PPARα ligands, fully restores quiescence of p53-deficient NSCs and delays tumor initiation in a glioblastoma mouse model. Thus, diet can silence glioblastoma driver mutations, with important implications for cancer prevention.

The aquatic macrophyte Salvinia molesta mitigates herbicides (glyphosate and aminomethylphosphonic acid) effects to aquatic invertebrates.

We evaluated the individual and combined effects of different environmentally representative concentrations of glyphosate (0, 25, 50, 75, and 100 µg l-1) and aminomethylphosphonic acid (AMPA; 0, 12.5, 25, 37.5, and 50 µg l-1) on the physiology of Aedes aegypti larvae, as well as the capacity of the aquatic macrophyte Salvinia molesta to attenuate those compounds' toxicological effects. Larvae of Ae. aegypti (between the third and fourth larval stages) were exposed for 48 h to glyphosate and/or AMPA in the presence or absence of S. molesta. Glyphosate and AMPA induced sublethal responses in Ae. aegypti larvae during acute exposures. Plants removed up to 49% of the glyphosate and 25% of AMPA from the water, resulting in the exposure of larvae to lower concentration of those compounds in relation to media without plants. As a result, lesser effects of glyphosate and/or AMPA were observed on larval acetylcholinesterase, P450 reductase, superoxide dismutase, mitochondrial electron transport chain enzymes, respiration rates, and lipid peroxidation. In addition to evidence of deleterious effects by media contamination with glyphosate and AMPA on aquatic invertebrates, our results attest to the ability of S. molesta plants to mitigate the toxicological impacts of those contaminants.

Lysosomal damage drives mitochondrial proteome remodelling and reprograms macrophage immunometabolism.

Transient lysosomal damage after infection with cytosolic pathogens or silica crystals uptake results in protease leakage. Whether limited leakage of lysosomal contents into the cytosol affects the function of cytoplasmic organelles is unknown. Here, we show that sterile and non-sterile lysosomal damage triggers a cell death independent proteolytic remodelling of the mitochondrial proteome in macrophages. Mitochondrial metabolic reprogramming required leakage of lysosomal cathepsins and was independent of mitophagy, mitoproteases and proteasome degradation. In an in vivo mouse model of endomembrane damage, live lung macrophages that internalised crystals displayed impaired mitochondrial function. Single-cell RNA-sequencing revealed that lysosomal damage skewed metabolic and immune responses in alveolar macrophages subsets with increased lysosomal content. Functionally, drug modulation of macrophage metabolism impacted host responses to Mycobacterium tuberculosis infection in an endomembrane damage dependent way. This work uncovers an inter-organelle communication pathway, providing a general mechanism by which macrophages undergo mitochondrial metabolic reprograming after endomembrane damage.

MOG analogues to explore the MCT2 pharmacophore, α-ketoglutarate biology and cellular effects of N-oxalylglycine.

α-ketoglutarate (αKG) is a central metabolic node with a broad influence on cellular physiology. The αKG analogue N-oxalylglycine (NOG) and its membrane-permeable pro-drug derivative dimethyl-oxalylglycine (DMOG) have been extensively used as tools to study prolyl hydroxylases (PHDs) and other αKG-dependent processes. In cell culture media, DMOG is rapidly converted to MOG, which enters cells through monocarboxylate transporter MCT2, leading to intracellular NOG concentrations that are sufficiently high to inhibit glutaminolysis enzymes and cause cytotoxicity. Therefore, the degree of (D)MOG instability together with MCT2 expression levels determine the intracellular targets NOG engages with and, ultimately, its effects on cell viability. Here we designed and characterised a series of MOG analogues with the aims of improving compound stability and exploring the functional requirements for interaction with MCT2, a relatively understudied member of the SLC16 family. We report MOG analogues that maintain ability to enter cells via MCT2, and identify compounds that do not inhibit glutaminolysis or cause cytotoxicity but can still inhibit PHDs. We use these analogues to show that, under our experimental conditions, glutaminolysis-induced activation of mTORC1 can be uncoupled from PHD activity. Therefore, these new compounds can help deconvolute cellular effects that result from the polypharmacological action of NOG.

Telemonitoring of motor skills using the Alberta Infant Motor Scale for at-risk infants in the first year of life.

INTRODUCTION: Remote assessment creates opportunities for monitoring child development at home. Determining the possible barriers to and facilitators of the quality of telemonitoring motor skills allows for safe and effective practices. We aimed to: (1) determine the quality, barriers and facilitators of Alberta Infant Motor Scale (AIMS) home videos made by mothers; (2) verify interrater reliability; (3) determine the association between contextual factors and the quality of assessments. METHODS: Thirty infants at biological risk aged between three and ten months, of both sexes, and their mothers were included. Assessments were based on asynchronous home videos, where motor skills were evaluated by mothers at home according to AIMS guidelines. The following were analyzed: video quality; stimulus quality; camera position; and physical environment. The video characteristics were analyzed descriptively. The intraclass correlation coefficient was used to calculate interrater reliability and the regression model to determine the influence of contextual factors on the outcome variables. Significance was set at 5%. RESULTS: Remote assessment of AIMS exhibited high image and stimulus quality, and a suitable physical environment. Interrater reliability was high for all domains: prone (r = 0.976); supine (r = 0.965); sitting (r = 0.987); standing (r = 0.945) and total score (r = 0.980). The contextual factors had no relation with assessment quality. DISCUSSION: Assessments conducted remotely by the mothers showed high video quality and interrater reliability, and represent a promising assessment tool for telemedicine in at-risk infants in the first year of life.

Sleep and Professional Burnout in Nurses, Nursing Technicians, and Nursing Assistants During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic may trigger sleep disorders and burnout in nursing professionals. PURPOSE: This study was designed to describe the occurrence of sleep disorders and burnout in a nursing team during the COVID-19 pandemic and to identify the associated factors. METHODS: A cross-sectional approach was used. The questionnaire was administered via the Internet. All of the participants were nursing professionals who had provided care during the COVID-19 pandemic, and data were collected between June and August 2020. Sociodemographic and work characterization instruments, the Jenkins Sleep Scale, and the Maslach Burnout Inventory were used. RESULTS: Five hundred seventy-two nursing professionals (nurses, nursing technicians, and nursing assistants) responded. Slightly over one quarter (26.4%) presented a sleep disorder, and 17.3% presented burnout. Professional category was a factor found to be associated with having a sleep disorder. Moreover, a lower prevalence both of disorders and of starting to use sleep medication was found among nurses than nursing assistants. Moreover, an association was found between having a high level of emotional exhaustion burnout and being a nursing technician, having a higher number of patients needing care, and starting to use sleep medication. The level of burnout related to depersonalization was significantly higher for nursing assistants, those with a weekly workload of 50 hours or more, and those starting to use sleep medication. Furthermore, burnout related to personal accomplishment was significantly higher in those starting to use sleep medication. Among the participants with sleep disorders, according to Jenkins Sleep Scale results, all of the participants presented a high or moderate level of emotional exhaustion and a high level of burnout related to personal accomplishment. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The findings indicate that the incidence of sleep disorders and burnout were high among nursing professionals during the COVID-19 pandemic and mainly related with starting to use sleep medication. The results demonstrate the importance of detecting and assessing the frequency of sleep disorders and professional exhaustion. Interventions that aim to improve sleep quality and working conditions for these professionals should be developed.

Interrelationships of Touch and Proprioception with Motor Impairments in Individuals with Cerebral Palsy: A Systematic Review.

Considering that somatosensory impairments may impact motor performance in individuals with cerebral palsy (CP), a better understanding of these relations is relevant to planning interventions. To synthesize research evidence to date on the interrelationships between the somatosensory functions of touch and proprioception with motor functions in persons with CP, we systematically searched Embase, CINAHL, PsycINFO, and Medline databases for studies relating these variables that were published in English from the inception of these databases to November 2020. We targeted the following content categories in our literature search: (a) cerebral palsy; (b) sensory functions; (c) tactile functions; (d) proprioception functions; and (e) motor functions. The selection, data extraction, and methodological quality assessment of these studies were performed in duplicate. We retrieved and analyzed information regarding the studies' methodological approaches and synthesized results. The 11 studies that met our inclusion criteria showed that, in individuals with CP, impairments in tactile discrimination, proprioception, and stereognosis are related to motor functions in terms of overall manual ability, grip strength, postural control and locomotion. Thus, clinical practitioners should attend to somatosensory aspects of motor impairment in individuals with CP. More research is needed to clarify the direction of these associations.

Tele-care intervention performed by parents involving specific task- environment- participation (STEP protocol) for infants at risk for developmental delay: protocol of randomized controlled clinical trial.

BACKGROUND: With the implementation of social distancing due to the Covid-19 pandemic, many at-risk infants are without therapy. An alternative mode of therapy in this situation is tele-care, a therapy in which assessments and interventions are carried out online, in the home environment. We describe a tele-care protocol involving parent delivered task and context specific movement training, participation and environmental adaptation for infants at risk for developmental delay. METHODS: Randomized controlled trial. Infants at risk, with 3 to 9 months corrected age, will be included, and randomized into two groups: control group (conventional guidelines) and experimental group (task, environment and participation in context-specific home program). Infants will be assessed for motor capacity (Infant Motor Profile and Alberta Infant Motor Scale); participation (Young Children's Participation and Environment Measure) and environment factors (Parent-Child Early Relational Assessment; Affordances in the Home Environment for Motor Development). The intervention period will be 10 weeks, and evaluations will be carried out before and after that period. All the assessment and intervention procedures will be carried out online, with instructions to parents for home therapy. The statistical analysis will be guided according to the distribution of the data, and a significance level of 5% will be adopted. All ethical approvals were obtained by the Ethics Committee of the University of São Carlos (Case number 31256620.5.0000.5504). The protocol will follow the SPIRIT statement. Findings will be disseminated in peer-reviewed publications and presented at national and international conferences. DISCUSSION: The results of this study will describe the effectiveness of a home intervention, focusing on specific activities, participation and environmental changes. These results will support the implementation of a remote protocol, with lower financial costs and focused on the particularities of the family. This type of care model can possibly help public policies to ensure equal access to evidence-based quality healthcare. TRIAL REGISTRATION: Brazilian Clinical Trials Registry: RBR8xrzjs , registered September 1, 2020.

Pet dogs as reservoir of oxacillin and vancomycin-resistant Staphylococcus spp.

The aim of this study was to verify the bacterial resistance profile and detect the presence of mecA gene in Staphylococcus spp. isolated from the nasal microbiota of domiciled dogs. For this purpose 100 nasal swabs from 100 domiciled dogs were collected from the central area of the city of Umuarama (PR), along with a questionnaire answered by their owners. After the isolation all Staphylococcus spp. isolates were submitted to the diffusion disc test by the Kirby-Bauer method, and only oxacillin-resistant samples were submitted to the PCR technique to search for the mecA gene and the results were then submitted to statistical analysis to verify possible risk variables. The 100 Staphylococcus spp. and coagulase negative, among which 41 isolates were resistant to oxacillin, no samples were positive for the mecA gene presence, however, 12 resistant to vancomycin were found. It can be concluded that the domiciled dogs are carriers of Staphylococcus spp. multiresistant, being these a possible source of human contamination.

Do they really support "your freedom of choice"? FoPNL and the food industry in Brazil.

Introduction: In 2020, Brazil approved the introduction of a new front-of-package nutrition labeling (FoPNL) in the format of a magnifying glass (MG) after years of discussion. There is currently a lack of understanding of the role of the food industry in that process. This study aimed to describe the corporate political activity (CPA) of the food industry and conflicts of interest situations, as they happened during the development and approval of a new FoPNL system in Brazil. Materials and methods: We undertook bibliographical and documentary searches using material from food companies, trade associations and front groups involved in the regulatory process. We (1) collected information about the case study context, (2) collected data from documentary sources, and (3) prepared a synthesis of the results and a timeline of key events. Results/Discussion: During the FoPNL regulatory process in Brazil, the food industry opposed the introduction of warning labels, a model supported by health authorities and implemented with success in other countries in Latin America. The food industry rather promoted a traffic-light labeling system, known to be less effective at guiding individuals to make healthier food choices. Later in the process, when it was evident that its preferred model would not be used, and a MG would rather be introduced, the food industry argued for the use of a different version of this FoPNL model. We found that the food industry, all along the process, was directly involved in and influenced the development of the FoPNL, by providing technical support, advising and lobbying policymakers. The food industry also established relationships with a consumer non-governmental organization and nutrition professional societies. The food industry also produced and disseminated information supporting its position in order to influence public opinion and high-level decision makers, and used the legal system to delay the process. Conclusion: The FoPNL in Brazil is neither aligned with the recommendations of international health organizations nor with existing independent scientific evidence. The new FoPNL, as adopted in Brazil, reflects some of the preferences of the industry; it is likely that the influence of that sector during the legislative process was pivotal, even if its initial proposal was not adopted.

Mycobacterium tuberculosis and Paracoccidioides brasiliensis Formation and Treatment of Mixed Biofilm In Vitro.

Co-infection of Mycobacterium tuberculosis and Paracoccidioides brasiliensis, present in 20% in Latin America, is a public health problem due to a lack of adequate diagnosis. These microorganisms are capable of forming biofilms, mainly in immunocompromised patients, which can lead to death due to the lack of effective treatment for both diseases. The present research aims to show for the first time the formation of mixed biofilms of M. tuberculosis and P. brasiliensis (Pb18) in vitro, as well as to evaluate the action of 3'hydroxychalcone (3'chalc) -loaded nanoemulsion (NE) (NE3'chalc) against monospecies and mixed biofilms, the formation of mixed biofilms of M. tuberculosis H37Rv (ATCC 27294), 40Rv (clinical strains) and P. brasiliensis (Pb18) (ATCC 32069), and the first condition of formation (H37Rv +Pb18) and (40Rv + Pb18) and second condition of formation (Pb18 + H37Rv) with 45 days of total formation time under both conditions. The results of mixed biofilms (H37Rv + Pb18) and (40Rv + Pb18), showed an organized network of M. tuberculosis bacilli in which P. brasiliensis yeasts are connected with a highly extracellular polysaccharide matrix. The (Pb18 + H37Rv) showed a dense biofilm with an apparent predominance of P. brasiliensis and fragments of M. tuberculosis. PCR assays confirmed the presence of the microorganisms involved in this formation. The characterization of NE and NE3'chalc displayed sizes from 145.00 ± 1.05 and 151.25 ± 0.60, a polydispersity index (PDI) from 0.20± 0.01 to 0.16± 0.01, and zeta potential -58.20 ± 0.92 mV and -56.10 ± 0.71 mV, respectively. The atomic force microscopy (AFM) results showed lamellar structures characteristic of NE. The minimum inhibitory concentration (MIC) values of 3'hidroxychalcone (3'chalc) range from 0.97- 7.8 µg/mL and NE3'chalc from 0.24 - 3.9 µg/mL improved the antibacterial activity when compared with 3'chalc-free, no cytotoxicity. Antibiofilm assays proved the efficacy of 3'chalc-free incorporation in NE. These findings contribute to a greater understanding of the formation of M. tuberculosis and P. brasiliensis in the mixed biofilm. In addition, the findings present a new possible NE3'chalc treatment alternative for the mixed biofilms of these microorganisms, with a high degree of relevance due to the lack of other treatments for these comorbidities.

Metabolic turnover and dynamics of modified ribonucleosides by 13C labeling.

Tandem mass spectrometry (MS/MS) is an accurate tool to assess modified ribonucleosides and their dynamics in mammalian cells. However, MS/MS quantification of lowly abundant modifications in non-ribosomal RNAs is unreliable, and the dynamic features of various modifications are poorly understood. Here, we developed a 13C labeling approach, called 13C-dynamods, to quantify the turnover of base modifications in newly transcribed RNA. This turnover-based approach helped to resolve mRNA from ncRNA modifications in purified RNA or free ribonucleoside samples and showed the distinct kinetics of the N6-methyladenosine (m6A) versus 7-methylguanosine (m7G) modification in polyA+-purified RNA. We uncovered that N6,N6-dimethyladenosine (m62A) exhibits distinct turnover in small RNAs and free ribonucleosides when compared to known m62A-modified large rRNAs. Finally, combined measurements of turnover and abundance of these modifications informed on the transcriptional versus posttranscriptional sensitivity of modified ncRNAs and mRNAs, respectively, to stress conditions. Thus, 13C-dynamods enables studies of the origin of modified RNAs at steady-state and subsequent dynamics under nonstationary conditions. These results open new directions to probe the presence and biological regulation of modifications in particular RNAs.

Development, Characterization and Cell Viability Inhibition of PVA Spheres Loaded with Doxorubicin and 4'-Amino-1-Naphthyl-Chalcone (D14) for Osteosarcoma.

Chalcones (1,3-diaryl-2-propen-1-ones) are naturally occurring polyphenols with known anticancer activity against a variety of tumor cell lines, including osteosarcoma (OS). In this paper, we present the preparation and characterization of spheres (~2 mm) from polyvinyl alcohol (PVA) containing a combination of 4'-Amino-1-Naphthyl-Chalcone (D14) and doxorubicin, to act as a new polymeric dual-drug anticancer delivery. D14 is a potent inhibitor of osteosarcoma progression and, when combined with doxorubicin, presents a synergetic effect; hence, physically crosslinked PVA spheres loaded with D14 and doxorubicin were prepared using liquid nitrogen and six freeze-thawing cycles. Physical-chemical characterization using a scanning electron microscope (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) presented that the drugs were incorporated into the spheres via weak interactions between the drugs and the polymeric chains, resulting in overall good drug stability. The cytotoxicity activity of the PVA spheres co-encapsulating both drugs was tested against the U2OS human osteosarcoma cell line by 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay, and compared to the spheres carrying either D14 or doxorubicin alone. The co-delivery showed a cytotoxic effect 2.6-fold greater than doxorubicin alone, revealing a significant synergistic effect with a coefficient of drug interaction (CDI) of 0.49. The obtained results suggest this developed PVA sphere as a potential dual-drug delivery system that could be used for the prominent synergistic anticancer activity of co-delivering D14 and doxorubicin, providing a new potential strategy for improved osteosarcoma treatment.

Percepção de discentes do curso de Fisioterapia sobre as normas de biossegurança no ambiente hospitalar / Students' perception of Physical therapy course on biosafety standards in hospital environment

Introdução: As normas de biossegurança consistem em um conjunto de políticas, regras e procedimentos necessários aos profissionais que interagem com agentes microbiológicos. Apesar de essencial, essa ainda é uma temática pouco abordada durante a graduação em fisioterapia, na qual observa-se uma maior valorização das disciplinas de caráter técnico-profissionalizante. Objetivo: Avaliar o conhecimento de estudantes de Fisioterapia sobre as normas de biossegurança no ambiente hospitalar e propor alternativas para a ampliação da discussão acerca desta temática durante o período de graduação destes discentes. Métodos: Foi realizado um estudo quali-quantitativo do tipo descritivo exploratório de caráter transversal através da aplicação de um questionário a respeito do tema abordado. A amostra foi definida por conveniência, totalizando 105 discentes. Resultados: 96% dos estudantes declararam que é necessário adotar as medidas de precaução padrão independentemente do diagnóstico do paciente e 98% afirmaram que se deve implantar a normatização dos conceitos de biossegurança. Conclusão: Com base no estudo, conclui-se que a capacitação continuada é condição indispensável para a segurança dos trabalhadores em qualquer que seja a área de atuação. (AU)

Introduction: Biosafety standards consist of a set of policies, rules, and procedures necessary for professionals who interact with microbiological agents. Although essential, this is still a topic that is rarely addressed during the graduation course in Physical therapy, in which there is a greater appreciation of disciplines of technical-professional character. Objective: To assess the knowledge of Physical therapy students on biosafety standards in hospital environment and propose alternatives to expand the discussion on this topic during the graduation period of these students. Methods: A qualitative quantitative study, descriptive and exploratory type, of transversal approach, was carried out through the application of a questionnaire. The sample was defined by convenience, totalizing 105 students. Results: 96% of the students declared that is necessary to adopt the standard precautionary measures independent of the diagnosis and 98% stated that the standardization of the concepts of biosafety should be implemented. Conclusion: Based on the study, we concluded that continued training is an indispensable condition for the safety of workers in any area of activity. (AU)