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A low response rate, acquired resistance and severe side effects have limited the clinical outcomes of immune checkpoint therapy. Here, we show that combining cancer nanovaccines with an anti-PD-1 antibody (αPD-1) for immunosuppression blockade and an anti-OX40 antibody (αOX40) for effector T-cell stimulation, expansion and survival can potentiate the efficacy of melanoma therapy. Prophylactic and therapeutic combination regimens of dendritic cell-targeted mannosylated nanovaccines with αPD-1/αOX40 demonstrate a synergism that stimulates T-cell infiltration into tumours at early treatment stages. However, this treatment at the therapeutic regimen does not result in an enhanced inhibition of tumour growth compared to αPD-1/αOX40 alone and is accompanied by an increased infiltration of myeloid-derived suppressor cells in tumours. Combining the double therapy with ibrutinib, a myeloid-derived suppressor cell inhibitor, leads to a remarkable tumour remission and prolonged survival in melanoma-bearing mice. The synergy between the mannosylated nanovaccines, ibrutinib and αPD-1/αOX40 provides essential insights to devise alternative regimens to improve the efficacy of immune checkpoint modulators in solid tumours by regulating the endogenous immune response.

Advances in reducing poverty and inequalities in the 2000s had a paradoxical effect in Brazil. This article examines how socioeconomic transformations, and the complexity of health services, are expressed in the regions established for planning purposes and the inter-governmental management of the Brazilian Unified Health System. An effort was made to identify and explain differences in the compositions of the 438 existing health regions and their spatial distribution by comparing situations observed in 2016 with those in 2000. Factor analysis and grouping techniques were used to construct a typology in the two years of the series, which was based on a diverse set of secondary data sources. It was found that there was an evolution in terms of income levels and service provision within the health regions, with a significant improvement in the socioeconomic conditions of the population. These results suggest that there was a positive impact from the combination of strategies related to social, economic and regional policies for the promotion of development, which generated more widespread well-being within the affected areas. However, limitations remain regarding the policies implemented for the universalization of the health system.

The aim of this article was to reflect on the challenges faced in building the Health Regions and Networks in Brazil. These reflections result from studies conducted in several health regions. The central challenges for the constitution of the Health Regions and Networks are as follows: the Care Model, Primary Health Care, Care for Users with Chronic Diseases, and Hospital Care. In order to consolidate the regions and networks the organization needs to incorporate an ethical sense: focusing on social, public and individual needs, derived from comprehensive care, human and social rights, in broad, multi-scale and inter-sectorial interactions, with the constitution of a systemic, regionalized innovation. Of prime importance is the capacity to devise which general principles are responsible for maintaining the unity(mode of care), seeking to outline the coherence of the different provision models that the system might develop according to the social needs in regional settings. Without that, users will continue to seek and create ways of accessing health services that challenge the rationale of those very services. Hospital reform is also required to integrate and reorient the hospital networks. These reflections are important for the SUS to uphold its solidarity project, expressed in the trinity of universality-comprehensiveness-equality.

In recent years, gold nanoparticles (AuNPs) have aroused the interest of many researchers due to their unique physicochemical and optical properties. AuNPs are being explored in a variety of biomedical fields, either in diagnostics or therapy, particularly for localized thermal ablation of cancer cells after light irradiation. Besides the promising therapeutic potential of AuNPs, their safety constitutes a highly important issue for any medicine or medical device. For this reason, in the present work, the production and characterization of physicochemical properties and morphology of AuNPs coated with two different materials (hyaluronic and oleic acids (HAOA) and bovine serum albumin (BSA)) were firstly performed. Based on the above importantly referred issue, the in vitro safety of developed AuNPs was evaluated in healthy keratinocytes, human melanoma, breast, pancreatic and glioblastoma cancer cells, as well as in a three-dimensional human skin model. Ex vivo and in vivo biosafety assays using, respectively, human red blood cells and Artemia salina were also carried out. HAOA-AuNPs were selected for in vivo acute toxicity and biodistribution studies in healthy Balb/c mice. Histopathological analysis showed no significant signs of toxicity for the tested formulations. Overall, several techniques were developed in order to characterize the AuNPs and evaluate their safety. All these results support their use for biomedical applications.

Background Physician shortage is a global issue that concerns Brazil’s authorities. The organizational structure and the environment of a medical institution can hide a low-quality life of a physician. This study examines the relationship between the hospital work environment and physicians’ job satisfaction and motivation when working in a large public academic hospital. Methods The study was restricted to one large, multispecialty Brazil’s hospital. Six hundred hospital physicians were invited to participate by e-mail. A short version of the Physician Worklife Survey (PWS) was used to measure working satisfaction. Physicians were also asked for socio-demographic information, medical specialty, and the intention to continue working in the hospital. Results Data from 141 questionnaires were included in the analyses. Forty-five physicians graduated from the hospital’s university, and they did not intend to leave the hospital under any circumstance (affective bond). The motivating factor for beginning the career at the hospital and to continue working there were the connection to the medical school and the hospital status as a “prestigious academic hospital”; the physicians were more satisfied with the career than the specialty. Only 30% completely agreed with the statement “If I had to start my career over again, I would choose my current specialty,” while 45% completely agreed with the statement “I am not well compensated given my training and experience.” The greater point of satisfaction was the relationship with physician colleagues. They are annoyed about the amount of calls they are requested to take and about how work encroaches on their personal time. No significant differences between medical specialties were found in the analysis. Conclusions The participants were satisfied with their profession. The fact that they remained at the hospital was related to the academic environment, the relationship with colleagues, and the high prestige in which society holds the institution. The points of dissatisfaction were inadequate remuneration and the fact that work invaded personal time. Routinely, there is a need for organizations to examine the impact of their structures, policies, and procedures on the stress and quality of life of physicians.

We report a straightforward and reproducible electrochemical approach to develop polydopamine-ethanolamine (ePDA-ETA) films to be used as immunosensing interfaces. ETA is strongly attached to polydopamine films during the potentiodynamic electropolymerization of dopamine. The great advantage of the electrochemical methods is to generate the oxidized species (quinones), which can readily react with ETA amine groups present in solution, with the subsequent incorporation of this molecule in the polymer. The presence of ETA and its effect on the electrosynthesis of polydopamine was accessed by cyclic voltammetry, ellipsometry, atomic force microscopy, FTIR and X-ray photoelectron spectroscopy. The adhesive and biocompatible films enable a facile protein linkage, are resilient to flow assays, and display intrinsic anti-fouling properties to block non-specific protein interactions, as monitored by real-time surface plasmon resonance, and confirmed by ellipsometry. Immunoglobulin G (IgG) and Anti-IgG were used in this work as model proteins for the affinity sensor. By using the one-step methodology (ePDA-ETA), the lower amount of immobilized biorecognition element, IgG, compared to that deposited on ePDA or on ETA post-modified film (ePDA/ETA), allied to the presence of ETA, improved the antibody-antigen affinity interaction. The great potential of the developed platform is its versatility to be used with any target biorecognition molecules, allowing both optical and electrochemical detection.

There is inherent tension between the idea of health as a social right and of health as a private good. From the latter perspective, healthcare provision is brought closer to the logic of ownership, where access depends on ability to pay. The prioritization of markets (over governments), economic incentives (over social or cultural norms), and entrepreneurship (over collective or community action), one of the hallmarks of neoliberalism, constitutes a project to dismantle the welfare state, defined as a set of policy mechanisms designed to meet collective needs. This article examines the above process and its consequences for social protection and health by reflecting upon two phenomena that threaten the principle of health as a social right: neoliberal ideas and policies; and financial capitalism. We argue that the common good must be defended or insulated from the negative effects of financial capitalism and from the erosion and fragmentation of public institutions and social protection systems caused by neoliberalism.

Background/Objectives: β-Caryophyllene is a plant-derived sesquiterpene with recognized therapeutic potential; however, high lipophilicity and low aqueous solubility limit its parenteral application. Nanoemulsion-based systems represent a rational strategy to address these challenges. This study aimed to develop and physicochemically characterize an injectable β-caryophyllene nanoemulsion and to evaluate its preclinical safety following intramuscular administration. Methods: Five nanoemulsions (NBCP1–NBCP5) were prepared by low-energy emulsification using different hydrophilic–lipophilic balance (HLB) values and characterized in terms of particle size, polydispersity index, zeta potential, and encapsulation efficiency. The optimized formulation (NBCP1) was evaluated in a 14-day subacute intramuscular toxicity study in male Wistar rats (n = 5 per group) at doses of 5 and 15 mg/kg. Clinical observations, food and water intake, body weight, hematological and biochemical parameters, and histopathological analyses of muscle, liver, and kidney tissues were assessed. Results: NBCP1 exhibited favorable physicochemical properties, including a mean particle size of 102.39 nm, PDI of 0.27, zeta potential of −27.5 mV, and encapsulation efficiency of 97.16%, and remained stable under stress conditions. Repeated intramuscular administration did not induce behavioral alterations, changes in consumption patterns, or differences in body weight between the control and treated groups. Hematological and biochemical parameters remained within physiological ranges, and histopathological analysis revealed preserved tissue architecture without inflammatory or degenerative changes. Conclusions: The results support the suitability of NBCP1 as a stable nanoemulsion platform for the parenteral delivery of β-caryophyllene under the evaluated conditions. These findings address the limited information available on injectable formulations of this sesquiterpene and provide a foundation for future pharmacokinetic, longer-term safety, and efficacy studies.

ObjectivesThis study aims to evaluate the effects of cyclic loading on the bending moments and the developed stress state of austenitic and R-phase endodontic files through finite element analysis.Materials and methodsThe mechanical properties of two groups of NiTi wires, austenite and R-phase, were measured in samples at two different conditions: uncycled and cycled. The cycled condition was achieved by subjecting samples of the two groups to 80% of the corresponding fatigue life under rotating bending efforts. The measured mechanical properties were then used in the finite element analysis, where the boundary and loading conditions were set to replicate a standard bending test.ResultsThe results showed that mechanical cycling leads to decreasing stress levels and bending moments in the simulated files, especially in the austenitic ones. In comparison with austenite, R-phase presented a more stable mechanical behavior during cycling.ConclusionsThe results show that the moment and stress calculated for an instrument under bending can be considerably decreased after some cyclic work.Clinical relevanceThe fatigue related to the clinical use of an endodontic file decreases the moment (as well as the forces) imposed by the instrument during the shaping of a curved root canal. This decrease is directly related to the type of atomic array present in the alloy.

Immune checkpoint blockade reaches remarkable clinical responses. However, even in the most favorable cases, half of these patients do not benefit from these therapies in the long term. It is hypothesized that the activation of host immunity by co‐delivering peptide antigens, adjuvants, and regulators of the transforming growth factor (TGF)‐β expression using a polyoxazoline (POx)‐poly(lactic‐co‐glycolic) acid (PLGA) nanovaccine, while modulating the tumor‐associated macrophages (TAM) function within the tumor microenvironment (TME) and blocking the anti‐programmed cell death protein 1 (PD‐1) can constitute an alternative approach for cancer immunotherapy. POx‐Mannose (Man) nanovaccines generate antigen‐specific T‐cell responses that control tumor growth to a higher extent than poly(ethylene glycol) (PEG)‐Man nanovaccines. This anti‐tumor effect induced by the POx‐Man nanovaccines is mediated by a CD8+‐T cell‐dependent mechanism, in contrast to the PEG‐Man nanovaccines. POx‐Man nanovaccine combines with pexidartinib, a modulator of the TAM function, restricts the MC38 tumor growth, and synergizes with PD‐1 blockade, controlling MC38 and CT26 tumor growth and survival. This data is further validated in the highly aggressive and poorly immunogenic B16F10 melanoma mouse model. Therefore, the synergistic anti‐tumor effect induced by the combination of nanovaccines with the inhibition of both TAM‐ and PD‐1‐inducing immunosuppression, holds great potential for improving immunotherapy outcomes in solid cancer patients. Remodeling of a tumor immunosuppressive microenvironment via a polyoxazoline‐poly(lactic‐co‐glycolic) acid nanovaccine combined with modulators of αCSF‐1R and αPD‐1 controls tumor growth and prolongs survival of three murine solid tumor models (CT26, MC38, and B16F10), thus constituting a promising approach to improve cancer immunotherapy.