Using Graphene-Based Materials for Stiff and Strong Poly(ethylene glycol) Hydrogels.

Blood-contacting devices are increasingly important for the management of cardiovascular diseases. Poly(ethylene glycol) (PEG) hydrogels represent one of the most explored hydrogels to date. However, they are mechanically weak, which prevents their use in load-bearing biomedical applications (e.g., vascular grafts, cardiac valves). Graphene and its derivatives, which have outstanding mechanical properties, a very high specific surface area, and good compatibility with many polymer matrices, are promising candidates to solve this challenge. In this work, we propose the use of graphene-based materials as nanofillers for mechanical reinforcement of PEG hydrogels, and we obtain composites that are stiffer and stronger than, and as anti-adhesive as, neat PEG hydrogels. Results show that single-layer and few-layer graphene oxide can strengthen PEG hydrogels, increasing their stiffness up to 6-fold and their strength 14-fold upon incorporation of 4% w/v (40 mg/mL) graphene oxide. The composites are cytocompatible and remain anti-adhesive towards endothelial cells, human platelets and Staphylococcus aureus, similar to neat hydrogels. To the best of our knowledge, this is the first work to report such an increase of the tensile properties of PEG hydrogels using graphene-based materials as fillers. This work paves the way for the exploitation of PEG hydrogels as a backbone material for load-bearing applications.

NBCAL violation of products that compete with breastfeeding on the social network Instagram. / Violação à NBCAL de produtos que competem com a amamentação na rede social Instagram.

The article aims to identify NBCAL violations and analyze the content of messages posted on the Instagram social network. This qualitative-quantitative study consisted of a convenience sample of profiles identified through specific terms preceded by the hashtag symbol (#). Data were collected for two months by trained researchers using a structured questionnaire. We calculated the product promotion frequency that characterized violation of the NBCAL per category and manufacturer. The messages were analyzed using the content analysis technique. We identified 64 personal accounts of mothers with violations in 89 products, mainly food (n = 72), dairy compounds (54.2%), and infant formulas (45.8%) were the most publicized. Two thematic categories emerged from the posted texts, one related to the quality of the products and the other about breastfeeding difficulty, especially low milk production. The study identified NBCAL violations on the Instagram social network, alerting the need to recognize digital marketing to include it in the rules imposed by the Norm in the virtual context, considering the capillarity of social networks in disseminating information to the public in question.

O artigo objetiva identificar infrações à NBCAL e analisar o conteúdo das mensagens postadas na rede social Instagram. Estudo de abordagem quali-quantitativa, com amostra de conveniência composta por perfis identificados por meio de termos específicos, precedidos do símbolo hashtag (#). A coleta de dados foi realizada durante dois meses por pesquisadores treinados, por meio de questionário estruturado. Calculou-se a frequência de promoção de produtos que caracterizava violação à NBCAL, segundo categoria e fabricante. As mensagens foram analisadas por meio da técnica de análise de conteúdo. Foram identificadas 64 contas pessoais de mulheres mães com infrações em 89 produtos, a maioria alimentos (n = 72), sendo os compostos lácteos (54,2%) e as fórmulas infantis para lactentes (45,8%) os mais divulgados. Duas categorias temáticas emergiram dos textos postados, uma relativa à qualidade dos produtos e a outra sobre a dificuldade com a amamentação, especialmente a baixa produção de leite. O estudo identificou violações à NBCAL na rede social Instagram, alertando para a necessidade do reconhecimento do marketing digital para incluí-lo nas regras impostas pela norma no contexto virtual, considerando a capilaridade das redes sociais na divulgação de informações para o público em questão.

Nasal-PAMPA: A novel non-cell-based high throughput screening assay for prediction of nasal drug permeability.

In nasal drug product development, screening studies are vital to select promising compounds or formulations. The Parallel Artificial Membrane Permeability Assay (PAMPA), a high throughput screening tool, has been applied to evaluate drug permeability across several barriers such as the skin or blood-brain barrier. Herein, a new nasal-PAMPA model was optimized to predict nasal permeability, using a biorelevant donor medium containing mucin. The apparent permeability (Papp) of 15 reference compounds was assessed in six different experimental conditions, and the most discriminating and predictive model was applied to a test drug (piroxicam) and mucoadhesive powder formulations loading the same drug. The model with 0.5% (w/v) mucin in the donor compartment and 2% (w/v) phosphatidylcholine in the lipid membrane accurately distinguished high and low permeable compounds. Additionally, it exhibited the highest correlation with permeation across human nasal epithelial cells, RPMI 2650 (R2 = 0.93). When applied to powder formulations, this model was sensitive to the presence of mucoadhesive excipients and the drug solid state. Overall, the nasal-PAMPA model was more rapid than cell-based assays, without requiring specialized training or equipment, showing to be a promising in vitro tool that can be applied in drug and formulation screening for nasal delivery.

Green Process for Xylooligosaccharides Production using an Eucalyptus Kraft Pulp.

Xylooligosaccharides (XOS) are oligomers with recognized and important prebiotic properties, whose consumption is associated with several health benefits, including a positive impact on the immune system. In this work, XOS were produced through a green process of enzymatic hydrolysis performed directly on an intermediate product from a pulp and paper industry, Eucalyptus bleached kraft pulp. Focusing on an industrial, sustainable and more economical application, two goals were defined and validated: (i) no pretreatment of the substrate and (ii) the replacement of the commonly used buffer solution as reaction medium for only water. The influence of the most relevant operating conditions on the production of XOS as well as the respective yields obtained were very similar when using either buffer or water as the reaction medium. For the use of water, although the solution pH decreases during the enzymatic reaction, this change did not affect the production of XOS. For the optimized conditions, 80 °C and 100 U/g pulp, a maximum yield of 31.4 ± 2.6% per total xylan in the pulp was obtained, resulting in more than 50 kg of XOS per ton of pulp. The correspondent hydrolysate was mainly composed by xylobiose (66%) and xylotriose (29%), oligomers with the highest prebiotic effect.

Kisspeptin treatment reverses high prolactin levels and improves gonadal function in hypothyroid male rats.

We evaluated whether the administration of kisspeptin-10 (Kp10) is capable of restoring gonadal function in hypothyroid male rats. Hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals were treated with Kp10. Hypothyroidism reduced testicular and sex gland mass, decreased the proliferation of the seminiferous epithelium, and compromised sperm morphology, motility, and vigor. A decrease in plasma LH and testosterone levels and an increase in prolactin secretion were observed in the hypothyroid rats. Hypothyroidism reduced Kiss1 and Kiss1r protein and gene expression and Star and Cyp11a1 mRNA levels in the testis. Furthermore, it reduced Lhb, Prl, and Drd2 and increased Tshb and Gnrhr expression in the pituitary. In the hypothalamus, hypothyroidism increased Pdyn and Kiss1r while reducing Gnrh1. Kp10 treatment in hypothyroid rats restored testicular and seminal vesicle morphology, improved sperm morphology and motility, reversed high prolactin levels, and increased LH and testosterone levels. In addition, Kp10 increased testicular expression of Kiss1, Kiss1r, Fshr, and Nr5a1 and pituitary Kiss1 expression. Our findings describe the inhibitory effects of hypothyroidism on the male gonadal axis and sperm quality and demonstrate that Kp10 treatment reverses high prolactin levels and improves gonadal function and sperm quality in hypothyroid rats.

Spray dried powders for nasal delivery: Process and formulation considerations.

Powders for nasal delivery have been recognized as advantageous dosage forms over liquids due to increased stability and residence time on nasal mucosa, with improved bioavailability. They can be manufactured by spray-drying, allowing the optimization of the particle properties that are critical to guarantee nasal deposition, as size and shape. It is also a scalable and flexible method already explored extensively in the pharmaceutical industry. However, it is important to understand how process parameters, particle physical properties and formulation considerations affect the product performance. Hence, this review aims to provide an overview of nasal powder formulation and processing through spray drying, with an emphasis on the variables that impact on performance. To this purpose, we describe the physical, biological and pharmacological phenomena prior to drug absorption as well as the most relevant powder properties. Formulation considerations including qualitative and quantitative composition are then reviewed, as well as manufacturing considerations including spray drying relevant parameters.

[Conceptions in dispute in the use of micronutrient supplementation and/or fortification in school programs for prevention of anemia]. / Concepções em disputa no uso da suplementação e/ou fortificação de micronutrientes na alimentação escolar para prevenção da anemia.

Iron deficiency anemia affects different populations worldwide, and in Brazil it is one of the principal childhood nutritional deficiencies. Different strategies have been proposed by international agencies and the Brazilian Ministry of Health for its prevention. The study aimed to analyze the ideas in dispute, expressed in official documents and narratives by health and education workers concerning the use of nutritional supplementation and/or fortification as a measure in schools to prevent anemia. The study was based on government documents and semi-structured interviews with workers in municipalities that implemented the school food fortification strategy (NutriSUS) in the state of Rio de Janeiro. The ideas expressed in the government documents highlight the efficiency of home supplementation and fortification for prevention of anemia, based on scientific studies and adjusted to the objectives of the public policies set out in them. Some ideas in the workers' narratives are critical of the need for this type of intervention, others they favor them, indicating controversies in the process of local operationalization of federal policies. Tensions were observed in the concepts of promotion, prevention, and treatment through NutriSUS, dosage, and form of administration. Criticisms of supplementation highlight healthy eating practices as the best strategy. Medicalization rather than health promotion measures can strain the pedagogical perspective in schools and produce contradictory ideas on the best strategies for the promotion of healthy eating.

A anemia por deficiência de ferro afeta, mundialmente, diferentes populações e, no Brasil, é uma das principais carências nutricionais na infância. Diferentes estratégias são propostas por organismos internacionais e pelo Ministério da Saúde para sua prevenção. O objetivo do estudo foi analisar as ideias em disputa, presentes em documentos oficiais e narrativas dos profissionais da saúde e educação acerca do uso da suplementação e/ou fortificação nutricional como medida de prevenção da anemia no âmbito escolar. Baseou-se na análise de documentos governamentais e entrevistas semiestruturadas com profissionais atuantes em municípios que implementaram a estratégia de fortificação da alimentação escolar (NutriSUS) no Estado do Rio de Janeiro. As ideias disseminadas nos documentos governamentais ressaltam a eficiência da suplementação e da fortificação caseira para prevenção de anemia, com base em pesquisas científicas e se adequa aos objetivos das políticas públicas neles formalizados. As ideias presentes nas narrativas dos profissionais são, por vezes, críticas à necessidade desse tipo de intervenção e, por outras, favoráveis, indicando as controvérsias presentes no próprio processo de operacionalização local das políticas federais. Observaram-se tensões em torno dos conceitos de promoção, prevenção e tratamento por meio do NutriSUS, da dosagem e da forma de administração. As críticas à suplementação ressaltam as práticas alimentares saudáveis como estratégia preferencial. A medicalização em detrimento de ações de promoção da saúde pode tencionar a perspectiva pedagógica no contexto escolar e produzir ideias contraditórias sobre as melhores estratégias de promoção de alimentação saudável.

La anemia por deficiencia de hierro afecta mundialmente a diferentes poblaciones y, en Brasil, es una de las principales carencias nutricionales durante la infancia. Se proponen diferentes estrategias por parte de organismos internacionales y el Ministerio de Salud para su prevención. El objetivo del estudio fue analizar las ideas en disputa, presentes en documentos oficiales y narraciones de los profesionales de salud y educación, acerca del uso de los suplementos y/o enriquecimientos nutricionales, como medida de prevención de la anemia en el ámbito escolar. Se basó en el análisis de documentos gubernamentales y entrevistas semiestructuradas con profesionales que actuaban en municipios que implementaron la estrategia de fortificación de la alimentación escolar (NutriSUS) en el estado de Río de Janeiro. Las ideas difundidas en los documentos gubernamentales resaltan la eficiencia de la suplementación y del enriquecimiento alimenticio casero para la prevención de anemia, basadas investigaciones científicas, y se adecua a los objetivos de las políticas públicas en ellos formalizados. Las ideas presentes en las narraciones de los profesionales son, a veces, críticas con la necesidad de este tipo de intervención y, otras veces, favorables, indicando las controversias presentes en el propio proceso de operacionalización local de las políticas federales. Se observaron tensiones en torno a los conceptos de promoción, prevención y tratamiento mediante NutriSUS, así como sobre la dosificación y la forma de administración. Las críticas a los suplementos resaltan las prácticas alimentarias saludables como estrategia preferente. La medicalización en detrimento de acciones de promoción de la salud puede tensionar la perspectiva pedagógica en el contexto escolar y producir ideas contradictorias sobre las mejores estrategias de promoción de alimentación saludable.

Hypothalamic Expression of Estrogen Receptor Isoforms Underlies Estradiol Control of Luteinizing Hormone in Female Rats.

Luteinizing hormone (LH) secretion during the ovarian cycle is governed by fluctuations in circulating estradiol (E2) that oppositely regulate kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) of the hypothalamus. However, how these effects are orchestrated to achieve fertility is unknown. Here, we have tested the hypothesis that AVPV and ARC neurons have different sensitivities to E2 to coordinate changes in LH secretion. Cycling and ovariectomized rats with low and high E2 levels were used. As an index of E2 responsiveness, progesterone receptor (PR) was expressed only in the AVPV of rats with high E2, showing the preovulatory LH surge. On the other hand, kisspeptin neurons in the ARC responded to low E2 levels sufficient to suppress LH release. Notably, the Esr1/Esr2 ratio of gene expression was higher in the ARC than AVPV, regardless of E2 levels. Accordingly, the selective pharmacological activation of estrogen receptor α (ERα) required lower doses to induce PR in the ARC. The activation of ERß, in turn, amplified E2-induced PR expression in the AVPV and the LH surge. Thus, ARC and AVPV neurons are differently responsive to E2. Lower E2 levels activate ERα in the ARC, whereas ERß potentiates the E2 positive feedback in the AVPV, which appears related to the differential Esr1/Esr2 ratio in these 2 brain areas. Our findings provide evidence that the distinct expression of ER isoforms in the AVPV and ARC plays a key role in the control of periodic secretion of LH required for fertility in females.

Grafting MSI-78A onto chitosan microspheres enhances its antimicrobial activity.

MSI-78A (Pexiganan A) is one of the few antimicrobial peptides (AMPs) able to kill Helicobacter pylori, a pathogenic bacterium that colonizes the gastric mucosa of half of the world's population. Antibiotics fail in 20-40% of H. pylori-infected patients, reinforcing the need for alternative treatments. Herein, a bioengineered approach was developed. MSI-78A with a C-terminal cysteine was grafted onto chitosan microspheres (AMP-ChMic) by thiol-maleimide (Michael-addition) chemistry using a long heterobifunctional spacer (NHS-PEG113-MAL). Microspheres with ∼4 µm diameter (near H. pylori length) and stable at low pH were produced by spray drying using a chitosan solution with an incomplete genipin crosslinking. A 3 × 10-5 µg AMP/microsphere grafting was estimated/confirmed by UV/Vis and FTIR spectroscopies. AMP-ChMic were bactericidal against H. pylori J99 (highly pathogenic human strain) at lower concentrations than the free peptide (∼277 µg grafted MSI-78A-SH/mL vs 512 µg free MSI-78A-SH/mL), even after pre-incubation in simulated gastric conditions with pepsin. AMP-ChMic killed H. pylori by membrane destabilization and cytoplasm release in a ratio of ∼10 bacteria/microsphere. This can be attributed to H. pylori attraction to chitosan, facilitating the interaction of grafted AMP with bacterium membrane. Overall, it was demonstrated that the peptide-microsphere conjugation chemistry did not compromise the MSI-78A antimicrobial activity, instead it boosted its bactericidal performance against H. pylori. STATEMENT OF SIGNIFICANCE: Half of the world's population is infected with Helicobacter pylori, a gastric bacterium that is responsible for 90% of non-cardia gastric cancers. Therefore, H. pylori eradication is now advocated in all infected individuals. However, available antibiotic therapies fail in up to 40% patients. Antimicrobial peptides (AMPs) are appealing alternatives to antibiotics, but their high susceptibility in vivo limits their clinical translation. AMP immobilization onto biomaterials surface will overcome this problem. Herein, we demonstrate that immobilization of MSI-78A (one of the few AMPs with activity against H. pylori) onto chitosan microspheres (AMP-ChMic) enhances its anti-H. pylori activity even at acidic pH (gastric settings). These results highlight the strong potential of AMP-ChMic as an antibiotic alternative for H. pylori eradication.

Kisspeptin Treatment Restores Ovarian Function in Rats with Hypothyroidism.

Background: Hypothyroidism causes ovarian dysfunction and infertility in women, in addition to being associated with hyperprolactinemia and reduced hypothalamic expression of kisspeptin (Kp). However, it remains unknown whether and how Kp is able to reverse the ovarian dysfunction caused by hypothyroidism. Methods: Hypothyroidism was induced in adult female Wistar rats using 6-propyl-2-thiouracil for 3 months. In the last month, half of the animals received Kp10. Blood samples were collected for dosage of free thyroxine, thyrotropin (TSH), luteinizing hormone (LH), prolactin (PRL), progesterone (P4), and estradiol (E2), and uteruses and ovaries were collected for histomorphometry. Body and ovarian weight and the number of corpora lutea were also evaluated. Half of the brains were evaluated by immunohistochemistry to Kp, and the other half had the arcuate nucleus of hypothalamus (ARC) and preoptic area microdissected for gene evaluation of Kiss1, Nkb, Pdyn, and Gnrh1. The pituitary gland and corpora lutea were also dissected for gene evaluation. Results: Hypothyroidism kept the animals predominantly acyclic and promoted a reduction in ovarian weight, number of corpora lutea, endometrial thickness, number of endometrial glands, and plasma LH, in addition to increasing the luteal messenger RNA (mRNA) expression of Star and Cyp11a1 and reducing 20αHsd. An increase in plasma PRL and P4 levels was also caused by hypothyroidism. Kp immunoreactivity and Kiss1 and Nkb mRNA levels in the ARC and Kiss1 in the anteroventral periventricular nucleus of hypothalamus were reduced in hypothyroid rats. Hypothyroid animals had lower pituitary gene expression of Gnrhr, Lhb, Prl, and Drd2, and an increase in Tshb. The treatment with Kp10 restored estrous cyclicality, plasma LH, ovarian and uterine morphology, and Cyp11a1, 3ßHsd, and 20αHsd mRNA levels in the corpora lutea. Kp10 treatment did not alter gene expression for Kiss1 or Nkb in the ARC of hypothyroid rats. Nevertheless, Kp10 increased Lhb mRNA levels and reduced Tshb in the pituitary compared with the hypothyroid group. Conclusions: The present findings characterize the inhibitory effects of hypothyroidism on the hypothalamic-pituitary-gonadal axis in female rats and demonstrate that Kp10 is able to reverse the ovarian dysfunction caused by hypothyroidism, regardless of hyperprolactinemia.

Norepinephrine modulation of heat dissipation in female rats lacking estrogen.

Postmenopausal hot flushes are caused by lack of estradiol (E2) but their neuroendocrine basis is still poorly understood. Here, we investigated the interrelationship between norepinephrine and hypothalamic neurons, with emphasis on kisspeptin neurons in the arcuate nucleus (ARC), as a regulatory pathway in the vasomotor effects of E2. Ovariectomized (OVX) rats displayed increased tail skin temperature (TST), and this increase was prevented in OVX rats treated with E2 (OVX + E2). Expression of Fos in the hypothalamus and the number of ARC kisspeptin neurons coexpressing Fos were increased in OVX rats. Likewise, brainstem norepinephrine neurons of OVX rats displayed higher Fos immunoreactivity associated with the increase in TST. In the ARC, the density of dopamine-ß-hydroxylase (DBH)-immunoreactive (ir) fibers was not altered by E2 but, importantly, DBH-ir terminals were found in close apposition to kisspeptin cells, revealing norepinephrine inputs to ARC kisspeptin neurons. Intracerebroventricular injection of the α2-adrenergic agonist clonidine (CLO) was used to reduce central norepinephrine release, confirmed by the decreased 3-methoxy-4-hydroxyphenylglycol/norepinephrine ratio in the preoptic area and ARC. Accordingly, CLO treatment in OVX rats reduced ARC Kiss1 mRNA levels and TST to the values of OVX + E2 rats. Conversely, CLO stimulated Kiss1 expression in the anteroventral periventricular nucleus (AVPV) and increased luteinizing hormone secretion. These findings provide evidence that augmented heat dissipation in OVX rats involves the increase in central norepinephrine that modulates hypothalamic areas related to thermoregulation, including ARC kisspeptin neurons. This neuronal network is suppressed by E2 and its imbalance may be implicated in the vasomotor symptoms of postmenopausal hot flushes.

Prior aerobic physical training modulates neuropeptide expression and central thermoregulation after ovariectomy in the rat.

This study compared the effects of aerobic physical training and estradiol (E2) replacement on central pathways involved with thermoregulation in ovariectomized rats. Rats were assigned to untrained ovariectomized treated with placebo (UN-OVX), untrained ovariectomized treated with E2 (E2-OVX), and trained ovariectomized (TR-OVX) groups. Tail skin temperature (TST), internal temperature (Tint), and basal oxygen consumption (VO2) were recorded. Neuronal activity, brain expression of Kiss1, NKB and Prodyn, and central norepinephrine (NE) levels were measured. UN-OVX had the highest TST. Compared to UN-OVX rats, TR-OVX and E2-OVX had lower Fos expression in the paraventricular and arcuate (ARC) nuclei, and lower double labeling for Tyrosine Hydroxylase and Fos in the brainstem. Compared to UN-OVX, only TR-OVX group exhibited lower kisspeptin (Kiss1), neurokinin B (NKB), and prodynorphin expression in the ARC and higher central NE levels. Aerobic physical training before menopause may prevent the heat dissipation imbalance induced by reduction of E2, through central NE release, modulation of Kiss1, NKB and prodynorphin expression in neurons from ARC nucleus.

Food environment surrounding public and private schools: an opportunity or challenge for healthy eating? / Ambiente alimentar do entorno de escolas públicas e privadas: oportunidade ou desafio para alimentação saudável?

The study analyzed and compared the types of food sold in the surroundings of 30 private and 26 public elementary schools in the city of Niterói, Rio de Janeiro. Data were collected by audit using a checklist instrument to characterize establishments (formal or informal) and identify the types of food and beverages sold, which were classified by processing level (fresh, processed, and ultraprocessed). Mann-Whitney statistical tests were used to verify the difference in the type of trade outlets d the categories of food sold between schools. The Kruskal-Wallis test was used to verify the difference in the amount of food traded between the categories. The amount of ultraprocessed food in the surroundings of public and private schools was statistically higher (p=0.0001) than the other categories. Some culinary preparations had a high rate of energy contribution from ultraprocessed foods (above 15%). There was no statistically significant difference (p = 0.478) in the categories of food sold between public and private schools. The sale of ultraprocessed products predominates around public and private schools, favoring the exposure of children to an environment that encourages the consumption of these products.

O estudo analisou e comparou os tipos de alimentos comercializados no entorno de 30 escolas privadas e 26 públicas de Ensino Fundamental do município de Niterói, Rio de Janeiro. A coleta de dados foi realizada por auditoria utilizando um instrumento tipo checklist para caracterização dos estabelecimentos (formal ou informal) e identificação dos tipos de alimentos e bebidas comercializados. Estes foram classificados segundo o grau de processamento (in natura, processados e ultraprocessados). Para análise dos dados foram utilizados os testes estatísticos de Mann-Whitney para verificar diferença do tipo de comércio e das categorias de alimentos comercializados entre as escolas e o de Kruskal-Wallis para verificar diferença na quantidade de alimentos comercializada entre as categorias. A quantidade de ultraprocessados no entorno das escolas foi estatisticamente maior (p=0,0001) do que as outras categorias. Algumas preparações culinárias apresentaram alto percentual de contribuição energética de ultraprocessados. Não houve diferença estatisticamente significativa (p=0,478) nas categorias de alimentos comercializados entre escolas públicas e privadas. No entorno das escolas predomina a comercialização de ultraprocessados, favorecendo a exposição de crianças a um ambiente que estimula o consumo destes produtos.

Graphene Oxide Coating Improves the Mechanical and Biological Properties of Decellularized Umbilical Cord Arteries.

The lack of small-diameter vascular grafts (inner diameter <5 mm) to substitute autologous grafts in arterial bypass surgeries has a massive impact on the prognosis and progression of cardiovascular diseases, the leading cause of death globally. Decellularized arteries from different sources have been proposed as an alternative, but their poor mechanical performance and high collagen exposure, which promotes platelet and bacteria adhesion, limit their successful application. In this study, these limitations were surpassed for decellularized umbilical cord arteries through the coating of their lumen with graphene oxide (GO). Placental and umbilical cord arteries were decellularized and perfused with a suspension of GO (C/O ratio 2:1) with ∼1.5 µm lateral size. A homogeneous GO coating that completely covered the collagen fibers was obtained for both arteries, with improvement of mechanical properties being achieved for umbilical cord decellularized arteries. GO coating increased the maximum force in 27%, the burst pressure in 29%, the strain in 25%, and the compliance in 10%, compared to umbilical cord decellularized arteries. The achieved theoretical burst pressure (1960 mmHg) and compliance (13.9%/100 mmHg) are similar to the human saphenous vein and mammary artery, respectively, which are used nowadays as the gold standard in coronary and peripheral artery bypass surgeries. Furthermore, and very importantly, coatings with GO did not compromise the endothelial cell adhesion but decreased platelet and bacteria adhesion to decellularized arteries, which will impact on the prevention of thrombosis and infection, until full re-endothetialization is achieved. Overall, our results reveal that GO coating has an effective role in the improvement of decellularized umbilical cord artery performance, which is a huge step toward their application as a small-diameter vascular graft.

Graphene-based materials: the key for the successful application of pHEMA as a blood-contacting device.

Thrombosis and infection are the leading causes of blood-contacting device (BCD) failure, mainly due to the poor performance of existing biomaterials. Poly(2-hydroxyethyl methacrylate) (pHEMA) has excellent hemocompatibility but the weak mechanical properties impair its use as a bulk material for BCD. As such, pHEMA has been explored as a coating, despite the instability and difficulty of attachment to the underlying polymer compromise its success. This work describes the hydrogel composites made of pHEMA and graphene-based materials (GBM) that meet the biological and mechanical requirements for a stand-alone BCD. Five GBM differing in thickness, oxidation degree, and lateral size were incorporated in pHEMA, revealing that only oxidized-GBM can reinforce pHEMA. pHEMA/oxidized-GBM composites are cytocompatible and prevent the adhesion of endothelial cells, blood platelets, and bacteria (S. aureus), thus maintaining pHEMA's anti-adhesive properties. As a proof of concept, the thrombogenicity of the tubular prototypes of the best formulation (pHEMA/Graphene oxide (GO)) was evaluated in vivo, using a porcine arteriovenous-shunt model. pHEMA/GO conduits withstand the blood pressure and exhibit negligible adhesion of blood components, revealing better hemocompatibility than ePTFE, a commercial material for vascular access. Our findings reveal pHEMA/GO, a synthetic and off-the-shelf hydrogel, as a preeminent material for the design of blood-contacting devices that prevent thrombosis and bacterial adhesion.

[Competing ideas on the State's roles in the prevention and control of childhood obesity in Brazil]. / Ideias em disputa sobre as atribuições do Estado na prevenção e controle da obesidade infantil no Brasil.

The study analyzed competing ideas on the State's roles in the prevention and control of childhood obesity in Brazil, with cognitive analysis of public policies as the frame of reference. The study included document analysis and semi-structured interviews with 20 individuals from government, organized civil society, and the commercial private sector. The State was viewed as the main party responsible for dealing with childhood obesity, but the definitions of its roles varied according to the narratives on the factors that condition obesity and the proposed solutions. Members of the commercial private sector criticized the regulatory State in the name of parents' freedom of choice. Civil society representatives and part of the government defended regulatory measures, which they considered essential. They contended that agreements between government and the food industry to reduce unhealthy ingredients are ineffective. However, some government representatives defended such agreements. These tensions and contradictions were also expressed in the policy documents acknowledging that practices by the commercial private sector favor obesity, even while considering the private sector a partner in this process. The arguments against the regulatory State were based on individual factors conditioning obesity, but the object of regulation is institutional practices by the commercial private sector, not individual behaviors. However, this kind of argument is part of corporate policy activity, since it overlooks the conflicts of interests that have contributed to delaying the reduction in obesity prevalence.

O estudo analisou as ideias em disputa em torno das atribuições do Estado na prevenção e controle da obesidade infantil no Brasil com base no referencial de análise cognitiva de políticas públicas. Realizou-se análise documental e entrevista semiestruturada com 20 depoentes referenciados às esferas do Estado/Governo, sociedade civil organizada e do setor privado comercial. O Estado foi considerado o principal responsável pelo enfrentamento da obesidade infantil, mas as concepções sobre suas atribuições variaram de acordo com as narrativas sobre os condicionantes da obesidade e as soluções apresentadas. O setor privado comercial critica o Estado regulador em nome da liberdade de decisão dos pais. Representantes da sociedade civil e de parte do governo valorizam ações regulatórias e reconhecem que são fundamentais. Consideram que os acordos para a redução de ingredientes, realizados entre o governo e a indústria alimentícia, não são efetivos. Porém, alguns representantes do governo os defendem. Essas tensões e contradições também se expressam nos documentos de políticas que reconhecem que as práticas do setor privado comercial favorecem a obesidade, mas o consideram parceiro. Os argumentos contrários ao Estado regulador são pautados nos condicionantes individuais da obesidade, contudo, as práticas institucionais do setor privado comercial é que são objeto de regulação e não o comportamento dos indivíduos. No entanto, esse tipo de argumento é parte da ação política corporativa, pois omite os conflitos de interesses que vêm contribuindo para retardar a redução da prevalência da obesidade.

El estudio analizó las ideas en disputa en torno a las atribuciones del Estado en cuanto a la prevención y control de la obesidad infantil en Brasil, basándose en el marco referencial del análisis cognitivo de políticas públicas. Se realizó un análisis documental, al igual que una entrevista semiestructurada con 20 participantes, relacionados con diferentes esferas del Estado/Gobierno, sociedad civil organizada, así como del sector privado comercial. El Estado fue considerado el principal responsable del combate a la obesidad infantil, pero las concepciones sobre sus atribuciones variaron de acuerdo con las narraciones sobre los condicionantes de la obesidad y las soluciones presentadas. El sector privado comercial critica al Estado regulador, en nombre de la libertad de decisión de los padres. Los representantes de la sociedad civil y del gobierno valoran las acciones regulatorias y reconocen que son fundamentales. Consideran que los acuerdos para la reducción de ingredientes, realizados entre el gobierno y la industria alimentaria, no son efectivos. Sin embargo, algunos representantes del gobierno los defienden. Estas tensiones y contradicciones también se expresan en los documentos de políticas que reconocen que las prácticas del sector privado comercial favorecen la obesidad, pero lo consideran como un aliado. Los argumentos contrarios al Estado regulador se encuentran pautados en los condicionantes individuales de la obesidad, no obstante, las prácticas institucionales del sector privado comercial son las que son objeto de regulación, y no el comportamiento de los individuos. Sin embargo, este tipo de argumento forma parte de la acción política corporativa, puesto que omite los conflictos de intereses que han contribuido a retrasar la reducción de la prevalencia de la obesidad.

Erratum: Borges, I., et al. Exposure of Smaller and Oxidized Graphene on Polyurethane Surface Improves its Antimicrobial Performance. Nanomaterials 2020, 10, 349.

The authors wish to make the following corrections to this paper [...].

Exposure of Smaller and Oxidized Graphene on Polyurethane Surface Improves its Antimicrobial Performance.

Catheter-related infections are a common worldwide health problem, highlighting the need for antimicrobial catheters. Here, antibacterial potential of graphene nanoplatelets (GNP) incorporated in the commonly used polymer for catheter manufacture-polyurethane (PU)-is investigated. Two strategies are explored: melt-blending, producing a composite, and dip coating, where a composite layer is deposited on top of PU. GNP with different lateral sizes and oxidation degrees-GNP-M5, GNP-M15, GNP-M5ox, GNP-M15ox-are applied in both strategies, and the antimicrobial potential towards Staphylococcus epidermidis of GNP dispersions and GNP-containing PU evaluated. As dispersions, oxidized and smaller GNP powders (GNP-M5ox) inhibit 74% bacteria growth at 128 µg/mL. As surfaces, GNP exposure strongly impacts their antimicrobial profile: GNP absence at the surface of composites yields no significant effects on bacteria, while by varying GNP: PU ratio and GNP concentration, coatings enhance GNP exposure, depicting an antimicrobial profile. Oxidized GNP-containing coatings induce higher antibacterial effect than non-oxidized forms, particularly with smaller GNPox, where a homogeneous layer of fused platelets is formed on PU, leading to 70% reduction in bacterial adhesion and 70% bacterial death. This pioneering work unravels how to turn a polymer clinically used to produce catheters into an antimicrobial surface, crucial to reducing risk of infection associated with catheterization.

Graphene Surfaces Interaction with Proteins, Bacteria, Mammalian Cells, and Blood Constituents: The Impact of Graphene Platelet Oxidation and Thickness.

Graphene-based materials (GBMs) have been increasingly explored for biomedical applications. However, interaction between GBMs-integrating surfaces and bacteria, mammalian cells, and blood components, that is, the major biological systems in our body, is still poorly understood. In this study, we systematically explore the features of GBMs that most strongly impact the interactions of GBMs films with plasma proteins and biological systems. Films produced by vacuum filtration of GBMs with different oxidation degree and thickness depict different surface features: graphene oxide (GO) and few-layer GO (FLGO) films are more oxidized, smoother, and hydrophilic, while reduced GO (rGO) and few-layer graphene (FLG) are less or nonoxidized, rougher, and more hydrophobic. All films promote glutathione oxidation, although in a lower extent by rGO, indicating their potential to induce oxidative stress in biological systems. Human plasma proteins, which mediate most of the biological interactions, adsorb less to oxidized films than to rGO and FLG. Similarly, clinically relevant bacteria, Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, adhere less to GO and FLGO films, while rGO and FLG favor bacterial adhesion and viability. Surface features caused by the oxidation degree and thickness of the GBMs powders within the films have less influence toward human foreskin fibroblasts; all materials allow cell adhesion, proliferation and viability up to 14 days, despite less on rGO surfaces. Blood cells adhere to all films, with higher numbers in less or nonoxidized surfaces, despite none having caused hemolysis (<5%). Unlike thickness, oxidation degree of GBMs platelets strongly impact surface morphology/topography/chemistry of the films, consequently affecting protein adsorption and thus bacteria, fibroblasts and blood cells response. Overall, this study provides useful guidelines regarding the choice of the GBMs to use in the development of surfaces for an envisioned application. Oxidized materials appear as the most promising for biomedical applications that require low bacterial adhesion without being cytotoxic to mammalian cells.

Reduced dopaminergic tone during lactation is permissive to the hypothalamic stimulus for suckling-induced prolactin release.

Dopamine from tuberoinfundibular dopaminergic (TIDA) neurones tonically inhibits prolactin (PRL) secretion. Lactational hyperprolactinaemia is associated with a reduced activity of TIDA neurones. However, it remains controversial whether the suckling-induced PRL surge is driven by an additional decrease in dopamine release or by stimulation from a PRL-releasing factor. In the present study, we further investigated the role of dopamine in the PRL response to suckling. Non-lactating (N-Lac), lactating 4 hour apart from pups (Lac), Lac with pups return and suckling (Lac+S), and post-lactating (P-Lac) rats were evaluated. PRL levels were elevated in Lac rats and increased linearly within 30 minutes of suckling in Lac+S rats. During the rise in PRL levels, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the median eminence (ME) and neurointermediate lobe of the pituitary did not differ between Lac+S and Lac rats. However, dopamine and DOPAC were equally decreased in Lac and Lac+S compared to N-Lac and P-Lac rats. Suckling, in turn, reduced phosphorylation of tyrosine hydroxylase in the ME of Lac+S. Domperidone and bromocriptine were used to block and activate pituitary dopamine D2 receptors, respectively. Domperidone increased PRL secretion in both N-Lac and Lac rats, and suckling elicited a robust surge of PRL over the high basal levels in domperidone-treated Lac+S rats. Conversely, bromocriptine blocked the PRL response to suckling. The findings obtained in the present study provide evidence that dopamine synthesis and release are tonically reduced during lactation, whereas dopamine is still functional with respect to inhibiting PRL secretion. However, there appears to be no further reduction in dopamine release associated with the suckling-induced rise in PRL. Instead, the lower dopaminergic tone during lactation appears to be required to sensitise the pituitary to a suckling-induced PRL-releasing factor.