Enhanced Cytotoxicity against a Pancreatic Cancer Cell Line Combining Radiation and Gold Nanoparticles.

The present work consisted of an exploratory study aiming to evaluate in vitro the potential of AuNPs during Radiation Therapy (RT) in human pancreatic adenocarcinoma cells. AuNPs coated with hyaluronic and oleic acids (HAOA-AuNPs) or with bombesin peptides (BBN-AuNPs) were used. AuNPs were characterized by Atomic Force Microscopy (AFM) and Dynamic Light Scattering. BxPC-3 tumor cells were irradiated with a 6 MV X-rays beam, in the absence or presence of AuNPs. AFM showed that HAOA-AuNPs and BBN-AuNPs are spherical with a mean size of 83 ± 20 nm and 49 ± 12 nm, respectively. For RT alone, a reduction in cell viability of up to 33 ± 12% was obtained compared to the control (p ≤ 0.0001). HAOA-AuNPs alone at 200 and 400 µM showed a reduction in cell viability of 20 ± 4% and 35 ± 4%, respectively, while for BBN-AuNPs, at 50 and 200 µM, a reduction in cell viability of 25 ± 3% and 37 ± 3% was obtained, respectively, compared to the control (p < 0.0001). At 72 h post-irradiation, a decrease in cell viability of 26 ± 3% and 22 ± 2% between RT + HAOA-AuNPs at 400 µM and RT + BBN-AuNPs at 50 µM, compared to RT alone, was obtained (p < 0.004). The combination of RT with AuNPs led to a significant decrease in cell viability compared to the control, or RT alone, thus representing an improved effect.

A miniaturized flow batch chemical vapor generation system for Hg determination in fish by ICP-MS.

A new flow batch (FB) system for chemical vapor generation (CVG) is proposed for mercury (Hg) determination in fish. An inductively coupled plasma mass spectrometer was used as a detector. Low-cost peristaltic mini pumps were used to propel the solutions and different configurations of FB systems (reactor/gas/liquid separator) were studied. The proposed configuration of the FB-CVG system allows good sensitivity, low limit of detection (LOD) and low consumption of reagents and sample solutions. In summary, only 1 mL of reductant, 1 mL of acid and 0.16 mL of sample are needed. The proposed method has good linearity, precision (better than 5 %), LOD of 0.008 µg g-1 and LOQ of 0.012 µg g-1, and high sample throughput, allowing 90 measurements/h. The accuracy of the method was evaluated through the analysis of a certified reference material (DOLT-4 Dogfish Liver), whose result is in good agreement with certified value (t-test with 95 % confidence level) and the quantification limit meets current legislations, of 1.0 µg g-1 (Brazil) and 0.3 µg g-1 (EU). In addition, analyte recovery test was done, where Hg recovery was better than 95 %, demonstrating the good analytical performance of the method. To demonstrate the applicability of the method, five samples of fish tissue (muscle) were analyzed. The proposed FB-CVG system, in addition to being low cost, is robust and requires only the volume of reagents necessary for Hg vapor generation, producing a very low amount of waste. It can be concluded that the proposed system can be used for routine analysis for Hg determination in fish tissue. It is worth noting that with the appropriate adjustments, the system can be coupled to different Hg detectors.

Differential blood-based biomarkers of subcortical and deep brain small vessel disease.

Background: Cerebral small vessel disease is the most common cause of lacunar strokes (LS). Understanding LS pathogenesis is vital for predicting disease severity, prognosis, and developing therapies. Objectives: To research molecular profiles that differentiate LS in deep brain structures from those in subcortical white matter. Design: Prospective case-control study involving 120 patients with imaging-confirmed LS and a 120 control group. Methods: We examined the relationship between Alzheimer's disease biomarkers [amyloid beta (Aß1-40, Aß1-42)], serum inflammatory marker (interleukin-6, IL-6), and endothelial dysfunction markers [soluble tumor necrosis factor-like weak inducer of apoptosis, and pentraxin-3 (sTWEAK, PTX3)] with respect to LS occurring in deep brain structures and subcortical white matter. In addition, we investigated links between LS, leukoaraiosis presence (white matter hyperintensities, WMHs), and functional outcomes at 3 months. Poor outcome was defined as a modified Rankin scale >2 at 3 months. Results: Significant differences were observed in levels of IL-6, PTX3, and sTWEAK between patients with deep lacunar infarcts and those with recent small subcortical infarcts (20.8 versus 15.6 pg/mL, p < 0.001; 7221.3 versus 4624.4 pg/mL, p < 0.0001; 2528.5 versus 1660.5 pg/mL, p = 0.001). Patients with poor outcomes at 3 months displayed notably higher concentrations of these biomarkers compared to those with good outcomes. By contrast, Aß1-40 and Aß1-42 were significantly lower in patients with deep LS (p < 0.0001). Aß1-42 levels were significantly higher in patients with LS in subcortical white matter who had poor outcomes. WMH severity only showed a significant association with deep LS and correlated with sTWEAK (p < 0.0001). Conclusion: The pathophysiological mechanisms of lacunar infarcts in deep brain structures seem different from those in the subcortical white matter. As a result, specific therapeutic and preventive strategies should be explored.

Precision Medicine for Blood Glutamate Grabbing in Ischemic Stroke.

Glutamate grabbers, such as glutamate oxaloacetate transaminase (GOT), have been proposed to prevent excitotoxicity secondary to high glutamate levels in stroke patients. However, the efficacy of blood glutamate grabbing by GOT could be dependent on the extent and severity of the disruption of the blood-brain barrier (BBB). Our purpose was to analyze the relationship between GOT and glutamate concentration with the patient's functional status differentially according to BBB serum markers (soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and leukoaraiosis based on neuroimaging). This retrospective observational study includes 906 ischemic stroke patients. We studied the presence of leukoaraiosis and the serum levels of glutamate, GOT, and sTWEAK in blood samples. Functional outcome was assessed using the modified Rankin Scale (mRS) at 3 months. A significant negative correlation between GOT and glutamate levels at admission was shown in those patients with sTWEAK levels > 2900 pg/mL (Pearson's correlation coefficient: -0.249; p < 0.0001). This correlation was also observed in patients with and without leukoaraiosis (Pearson's correlation coefficients: -0.299; p < 0.001 vs. -0.116; p = 0.024). The logistic regression model confirmed the association of higher levels of GOT with lower odds of poor outcome at 3 months when sTWEAK levels were >2900 pg/mL (OR: 0.41; CI 95%: 0.28-0.68; p < 0.0001) or with leukoaraiosis (OR: 0.75; CI 95%: 0.69-0.82; p < 0.0001). GOT levels are associated with glutamate levels and functional outcomes at 3 months, but only in those patients with leukoaraiosis and elevated sTWEAK levels. Consequently, therapies targeting glutamate grabbing might be more effective in patients with BBB dysfunction.

Exploring antioxidant and α-glucosidase inhibition in Eugenia L. extracts: a comprehensive phytochemical study.

This study analysed extracts obtained from the leaves of Eugenia uniflora, E. involucrata, and E. myrcianthes to determine their chemical composition, antioxidative properties, and α-glucosidase inhibitory capacity. By using liquid chromatography with a diode array detector, we identified chlorogenic acids, flavonoids, tannins, proanthocyanidins, saponins, and triterpenes in the extracts. The antioxidant activities of the extracts were found to be directly related to their total phenolic, flavonoid content and enzyme inhibition. The E. uniflora aqueous extract showed significant inhibition of α-glucosidase (IC50 0.98 µg mL-1), indicating its potential as a non-competitive inhibitor for managing Diabetes Mellitus. This study contributes to the existing knowledge on the chemical and biological aspects of Eugenia genus.

Surgical treatment outcomes in heavy eye syndrome - a case series.

Results: The study cohort comprised five patients, each presenting with unilateral high axial myopia and classic clinical features of HES, including large angle esotropia, hypotropia, and restricted abduction and supraduction. All patients displayed evident superotemporal globe prolapse on MRI imaging, corresponding to the downward displacement of the LR muscle and medial shift of the SR muscle.Following the surgical procedure, all patients demonstrated significant improvements in both vertical and horizontal deviations, effectively addressing the primary clinical manifestations of HES.Conclusions: In the management of HES, several surgical approaches have been explored, yielding mixed results. Our study, employing the technique of partial muscle splitting and scleral fixation, offers a promising avenue for effectively addressing this challenging condition. By adapting the full loop myopexy technique originally proposed by Yokoyama et al. we achieved satisfactory ocular alignment in all five patients. Notably, this approach mitigates the risk of anterior segment ischemia by preserving the unsecured portions of the SR and LR muscles along with MR retroequatorial myopexy.These findings support the consideration of this surgical technique as a safe and effective option for managing HES, providing both cosmetic and functional improvements to afflicted individuals.

A Step Forward for the Treatment of Localized Prostate Cancer Using Gold Nanoparticles Combined with Laser Irradiation.

Prostate cancer (PCA) is the second most common cancer diagnosis in men and the fifth leading cause of death worldwide. The conventional treatments available are beneficial to only a few patients and, in those, some present adverse side effects that eventually affect the quality of life of most patients. Thus, there is an urgent need for effective, less invasive and targeted specific treatments for PCA. Photothermal therapy (PTT) is a minimally invasive therapy that provides a localized effect for tumour cell ablation by activating photothermal agents (PTA) that mediate the conversion of the light beam's energy into heat at the site. As tumours are unable to easily dissipate heat, they become more susceptible to temperature increases. In the PTT field, gold nanoparticles (AuNPs) have been attracting interest as PTA. The aim of this study was to formulate AuNPs capable of remaining retained in the tumour and subsequently generating heat at the tumour site. AuNPs were synthesized and characterized in terms of size, polydispersity index (PdI), zeta potential (ZP), morphology and the surface plasmon resonance (SPR). The safety of AuNPs and their efficacy were assessed using in vitro models. A preliminary in vivo safety assessment of AuNPs with a mean size lower than 200 nm was confirmed. The morphology was spherical-like and the SPR band showed good absorbance at the laser wavelength. Without laser, AuNPs proved to be safe both in vitro (>70% viability) and in vivo. In addition, with laser irradiation, they proved to be relatively effective in PCA cells. Overall, the formulation appears to be promising for use in PTT.

Effect of Foraminal Enlargement on Periapical Healing in Necrotic Teeth: A Systematic Review.

Introduction: Foraminal Enlargement (FE) is a cleaning performed in the apical-most region of the tooth, in order to optimize root disinfection. This systematic review evaluated the influence of FE during root canal treatment on bacterial reduction and repair of the periapical lesion. Materials and Methods: Searches in PubMed/MEDLINE, Scopus, Cochrane Library, Web of Science, Embase, Scielo, Lilacs and OpenGrey were performed until January-2024. Ex vivo and in vivo studies evaluating the effects of FE in the bacterial reduction and repair of the periapical lesion were included, respectively, followed by risk of bias assessment (modified version of Joanna Briggs Institute's for ex vivo studies and Systematic Review Centre for Laboratory animal Experimentation's risk of bias tools for in vivo studies). The meta-analysis was not feasible and a qualitative summary for each outcome was provided. Results: Of 950 studies, 2 in vivo studies were eligible, using animal models with infected teeth. Of these two, periapical repair was evaluated with hematoxylin-eosin stain, and FE improved periapical healing. Regarding ex vivo studies, 3 were eligible, using extracted human teeth. The inoculations in ex vivo models were performed with Enterococcus (E.) faecalis, and FE reduced E. faecalis in the ex vivo models. Conclusions: Foraminal enlargement seems to increase bacterial reduction within the root canal, and provide major periapical tissue repair on the histological analysis in animal studies. However, caution is necessary when translating these results to the clinical environment.

Systemic biomarker associated with poor outcome after futile reperfusion.

BACKGROUND: Successful recanalization does not lead to complete tissue reperfusion in a considerable percentage of ischemic stroke patients. This study aimed to identify biomarkers associated with futile recanalization. Leukoaraiosis predicts poor outcomes of this phenomenon. Soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK), which is associated with leukoaraiosis degrees, could be a potential biomarker. METHODS: This study includes two cohorts of ischemic stroke patients in a multicentre retrospective observational study. Effective reperfusion, defined as a reduction of ≥8 points in the National Institutes of Health Stroke Scale (NIHSS) within the first 24 h, was used as a clinical marker of effective reperfusion. RESULTS: In the first cohort study, female sex, age, and high NIHSS at admission (44.7% vs. 81.1%, 71.3 ± 13.7 vs. 81.1 ± 6.7; 16 [13, 21] vs. 23 [17, 28] respectively; p < .0001) were confirmed as predictors of futile recanalization. ROC curve analysis showed that leukocyte levels (sensitivity of 99%, specificity of 55%) and sTWEAK level (sensitivity of 92%, specificity of 88%) can discriminate between poor and good outcomes. Both biomarkers simultaneously are higher associated with outcome after effective reperfusion (OR: 2.17; CI 95% 1.63-4.19; p < .0001) than individually (leukocytes OR: 1.38; CI 95% 1.00-1.64, p = .042; sTWEAK OR: 1.00; C I95% 1.00-1.01, p = .019). These results were validated using a second cohort, where leukocytes and sTWEAK showed a sensitivity of 100% and specificity of 66.7% and 75% respectively. CONCLUSIONS: Leukocyte and sTWEAK could be biomarkers of reperfusion failure and subsequent poor outcomes. Further studies will be necessary to explore its role in reperfusion processes.

N-Methyl-(2S,4R)-trans-4-hydroxy-L-proline isolated Sideroxylon obtusifolium attenuates TPA-induced irritant contact dermatitis in mice.

Dermatitis is defined as a set of inflammatory diseases that affect the skin, with varied causes. Among the different types of dermatitis, contact dermatitis is the most prevalent. Although the current therapy is often effective, it is associated with adverse effects and the possibility of drug tolerance. N-Methyl-(2S, 4R)-trans-4-hydroxy-L-proline is a L-proline amino acid derivative found in the leaves of Sideroxylon obtusifolium, a species traditionally used to treat inflammatory diseases. The aim of this study was to investigate the topical anti-inflammatory effect of N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline (NMP) in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced irritant contact dermatitis in mice. Topically administered NMP, at doses of 0.03 - 0.50 mg/ear, reduced TPA-induced ear edema and neutrophil migration, as evidenced by low tissue myeloperoxidase activity and verified by histological examination. In addition, NMP (0.06 mg/ear) reduced tissue levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß, INF-γ and MCP-1) and of the anti-inflammatory cytokine IL-10, and reduced gene expression of TNF-α, IL-6 and IL-1ß increased by TPA. The data suggest that N-methyl-(2S, 4R)-trans-4-hydroxy-L-proline acts as a topical anti-inflammatory agent that decreases the expression of inflammatory cytokines, making it useful for the treatment of skin inflammation. Further investigations are necessary for its development as a therapeutic agent.

Influence of sodium hypochlorite on cyclic fatigue resistance of nickel-titanium instruments: A systematic review and meta-analysis of in vitro studies.

OBJECTIVE: This systematic review/meta-analysis investigated the influence of NaOCl on cyclic fatigue resistance of endodontic NiTi instruments. MATERIALS AND METHODS: A systematic search until July 2022 in PubMed/MEDLINE, Embase, Scopus, Web of Science, SciELO, Cochrane Library, and grey literature was conducted. According to the PECOS strategy, only in vitro studies evaluating the effects of NaOCl on the cyclic fatigue resistance of NiTi instruments were eligible. Cyclic fatigue resistance was the primary outcome. A modified Joanna Briggs Institute's Checklist was used for risk of bias assessment. RESULTS: Of the 2,445 records screened, 37 studies were included. Most studies used simulated canals made of stainless-steel block with severe to moderate curvatures. NaOCl concentration varied from 1-6%, mainly at 37 °C. Regarding fatigue resistance, 23 studies using 1.2% to 6% NaOCl showed a reduction in the resistance compared to the control groups, especially when pre-heated. Four meta-analyses were performed according to the tested NiTi systems. The meta-analyses indicated that the PTU F2 files had higher reduction of fatigue resistance after exposure to 5.25% NaOCl; no differences between NaOCl and no immersion were observed for Reciproc R25, WaveOne 25.08, and WaveOne Gold Primary files. Included studies had low risk of bias. CONCLUSION: NaOCl appears to reduce cyclic fatigue resistance of certain NiTi files, especially when they are pre-heated, particularly in conventional NiTi files compared to some heat-treated instruments. It is possible that the temperature of the solution may have a greater influence on resistance than NaOCl itself. Important to note that an overall tendency toward no significant influence was observed among various systems. CLINICAL RELEVANCE: Precautions are necessary when a pre-heated high-concentration NaOCl is used to enhance its properties during root canal preparation, mainly using conventional wire.

Gestão regional no enfrentamento à pandemia da Covid-19: estudo de casos em São Paulo / Regional management in the face of the COVID-19 pandemic: case study in São Paulo

RESUMO Ao final do ano de 2019 o mundo foi surpreendido pela Covid-19, que chegou ao Brasil no início de 2020, fazendo com que o Sistema Único de Saúde (SUS) adotasse estratégias imediatas para atender as necessidades de saúde da população, colocando em evidência todos os obstáculos que o sistema de saúde vinha enfrentando nos últimos anos. O estado de São Paulo não foi diferente do restante do País em relação ao enfrentamento. Este estudo objetivou identificar as principais estratégias adotadas em 5 regiões de saúde de São Paulo, com foco na gestão regional, analisando os processos e práticas adotados para o enfrentamento à pandemia da Covid-19. Tratou-se de um estudo qualitativo, realizado através de estudo de casos múltiplos, com abordagem exploratória, a partir de pesquisa de campo e realização de oficinas regionais. As regiões de saúde deste estudo puderam comprovar a importância da intersetorialidade nas ações de saúde como um todo. Notou-se o grande papel dos municípios nestas ações e a união destes, fortalecendo o papel da regionalização e ampliando a importância da governança em saúde. Ademais, as regiões de saúde saíram fortalecidas porque exerceram seu papel de liderança e organizaram ações junto aos municípios.

ABSTRACT At the end of 2019 the world was surprised by COVID-19, which arrived in Brazil at the beginning of 2020, causing the Unified Health System (SUS) to adopt immediate strategies to meet health needs, as well as putting in check all the obstacles that the health system has been facing in recent years. In the state of São Paulo it was not different from the rest of the country in relation to the confrontation. This study aimed to identify the main strategies adopted in 5 health regions of São Paulo, focusing on regional management, analyzing the processes and practices adopted to face the COVID-19 pandemic. It was a qualitative study, carried out through a multiple case study, with an exploratory approach, based on field research and regional workshops. In this study, the health regions were able to prove the importance of intersectoral actions in the health system. It was noted the great role of municipalities in these actions and their union, strengthening the role of regionalization and expanding the importance of governance in health. In addition, the health regions were strengthened because they exercised their leadership role and organized actions with the municipalities.

Índice de Dependência Regional e Macrorregional: uma contribuição ao processo de regionalização do SUS / Regional and Macro-regional Dependency Index: A contribution to the SUS regionalization process

RESUMO O estudo aborda a interdependência das regiões e macrorregiões de saúde no Brasil nas internações de média e alta complexidade, no ano de 2019. Foi realizada a análise dos fluxos estabelecidos, utilizando o Índice de Dependência Regional e Macrorregional, a partir de dados secundários do Sistema Único de Saúde (SUS) obtidos no Sistema de Informação Hospitalar. Os resultados demonstram que grande parte das regiões e macrorregiões de saúde absorvem em seus territórios as internações de média complexidade, com variações entre as especialidades. Nas internações de alta complexidade, a maioria das regiões de saúde apresenta grande dependência, sendo que a assistência está concentrada em 15% delas. Entre as macrorregiões de saúde, o cenário é significativamente heterogêneo, com dependência expressiva nas regiões Norte, Nordeste e Centro-Oeste, e alta resolutividade na região Sul. Em todas as análises, o porte populacional das regiões e macrorregiões de saúde apresenta relação inversa à dependência regional e macrorregional. O aprimoramento da regionalização pressupõe a organização de uma rede de atenção à saúde que considere as desigualdades e as diversidades territoriais, a interdependência e a autonomia entre os territórios e os atores implicados, e a coordenação entre as unidades federativas, de modo a garantir cuidado integral e equânime.

ABSTRACT The study addresses the interdependency between health regions and macro-regions in Brazil in 2019, concerning both medium and high complexity hospitalizations. The analysis of the flows established was carried out using the Regional and Macro-regional Dependency Index, based on secondary data provided by the Hospital Information System of the Unified Health System (SUS). The results show that a significant number of health regions and macro-regions absorb medium-complexity hospitalizations in their territories, varying according to specialties. In high-complexity hospitalizations, most health regions are highly dependent, assistance concentrated in 15% of these. Among health macro-regions, the scenario is significantly heterogeneous: highly dependent on the North, Northeast and Midwest Regions, and highly resolutive in the South Region. Analyses show that the population size of health regions and macro-regions is inversely related to the regional and macro-regional dependency. The improvement of regionalization requires an organized health care network, one that takes into account territorial inequalities and diversities, interdependency and autonomy among the territories and actors involved, and inter-federative coordination, so as to provide care that is both comprehensive and equitable.

Perfusion-weighted software written in Python for DSC-MRI analysis.

Introduction: Dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion studies in magnetic resonance imaging (MRI) provide valuable data for studying vascular cerebral pathophysiology in different rodent models of brain diseases (stroke, tumor grading, and neurodegenerative models). The extraction of these hemodynamic parameters via DSC-MRI is based on tracer kinetic modeling, which can be solved using deconvolution-based methods, among others. Most of the post-processing software used in preclinical studies is home-built and custom-designed. Its use being, in most cases, limited to the institution responsible for the development. In this study, we designed a tool that performs the hemodynamic quantification process quickly and in a reliable way for research purposes. Methods: The DSC-MRI quantification tool, developed as a Python project, performs the basic mathematical steps to generate the parametric maps: cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), signal recovery (SR), and percentage signal recovery (PSR). For the validation process, a data set composed of MRI rat brain scans was evaluated: i) healthy animals, ii) temporal blood-brain barrier (BBB) dysfunction, iii) cerebral chronic hypoperfusion (CCH), iv) ischemic stroke, and v) glioblastoma multiforme (GBM) models. The resulting perfusion parameters were then compared with data retrieved from the literature. Results: A total of 30 animals were evaluated with our DSC-MRI quantification tool. In all the models, the hemodynamic parameters reported from the literature are reproduced and they are in the same range as our results. The Bland-Altman plot used to describe the agreement between our perfusion quantitative analyses and literature data regarding healthy rats, stroke, and GBM models, determined that the agreement for CBV and MTT is higher than for CBF. Conclusion: An open-source, Python-based DSC post-processing software package that performs key quantitative perfusion parameters has been developed. Regarding the different animal models used, the results obtained are consistent and in good agreement with the physiological patterns and values reported in the literature. Our development has been built in a modular framework to allow code customization or the addition of alternative algorithms not yet implemented.

Neuropsychological Characterization of Autosomal Recessive Intellectual Developmental Disorder 59 Associated with IMPA1 (MRT59).

Biallelic loss of function of IMPA1 causes autosomal recessive intellectual developmental disorder 59 (MRT59, OMIM #617323). MRT59 has been reported to present with significant intellectual disability and disruptive behavior, but little is known about the neurocognitive pattern of those patients. Thus, the aims of this study were: (1) to assess the cognitive profile of these patients, and (2) to evaluate their functional dependence levels. Eighteen adults, aged 37 to 89 years, participated in this study: nine MRT59 patients, five heterozygous carriers and four non-carrier family members. All of them were from a consanguineous family living in Northeast Brazil. All IMPA1 patients had the (c.489_493dupGGGCT) pathogenic variant in homozygosis. For cognitive assessment, the WASI battery was applied in nine MRT59 patients and compared to heterozygous carriers and non-carrier family members. Functional dependence was evaluated using the functional independence measure (FIM). Patients showed moderate to severe intellectual disability and severe functional disabilities. Heterozygous carriers did not differ from non-carriers. MRT59 patients should be followed up by health professionals in an interdisciplinary way to understand their cognitive disabilities and functional needs properly.

Choroidal Metastasis as the Initial Presentation of Lung Cancer: A Case Report.

This case report presents an 82-year-old woman with decreased visual acuity. Clinical and multimodal evaluation revealed an elevated macular lesion with choroidal thickening. Fluorescein angiography and optical coherence tomography (OCT) showed characteristic patterns of choroidal metastasis. Thoracic CT scan confirmed a nodular mass in the right hilus, suggesting bronchogenic neoplastic process. A pleural biopsy demonstrated malignant neoplasia with characteristics of adenocarcinoma, and immunohistochemistry was positive for thyroid transcription factor 1 (TTF-1). These findings emphasize the critical role of ophthalmological examinations in early detection and intervention, as choroidal tissue is highly susceptible to metastasis, particularly from breast and lung cancers. Additionally, the poor prognosis associated with metastatic lung cancer underscores the urgency for prompt action.

Polyoxazoline-Based Nanovaccine Synergizes with Tumor-Associated Macrophage Targeting and Anti-PD-1 Immunotherapy against Solid Tumors.

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)-ß 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.

Trabeculectomy Vs Non-penetrating Deep Sclerectomy for the Surgical Treatment of Open-Angle Glaucoma: A Long-Term Report of 201 Eyes.

Introduction: Glaucoma is the second leading cause of vision loss worldwide. The reduction of intraocular pressure remains the backbone of its therapy. Among surgical techniques for its treatment, deep non-penetrating sclerotomy is the most widely practiced non-penetrating surgery. The purpose of this study was to evaluate the long-term efficacy and safety of deep non-penetrating sclerotomy compared to standard trabeculectomy in patients with open-angle glaucoma. Patients and methods: Retrospective study including 201 eyes with open-angle glaucoma. Closed-angle and neovascular cases were excluded. Absolute success was considered when intraocular pressure under 18 mmHg, or a reduction of at least 20% in patients with a baseline intraocular pressure below 22 mmHg, was obtained after 24 months, without the use of medication. Qualified success was considered when those targets were met with or without the use of hypotensive medication. Results: Deep non-penetrating sclerectomy showed a slightly lower long-term hypotensive effect compared to standard trabeculectomy, with significant differences at 12 months, but not at 24 months of follow-up. The absolute and qualified success rates were 51.85% and 65.43% for the trabeculectomy group and 50.83% and 60.83% for the deep non-penetrating sclerectomy, without significant differences. Regarding postoperative complications, mainly due to postoperative hypotonia, or related to the filtration bleb, they were significantly different between groups, with 10.8% and 24.7%, in deep-nonpenetrating sclerectomy and trabeculectomy groups, respectively. Conclusion: Deep non-penetrating sclerectomy seems to be an effective and safe surgical option for patients with open-angle glaucoma unable to be controlled by non-invasive strategies. Data suggests that the intraocular pressure-lowering effect of this technique may be marginally lower than that of trabeculectomy, but the achieved efficacy outcomes were similar, with a significantly lower risk of complications.

Guided Tissue Regeneration in Class IV External Cervical Resorption: A Case Report.

External cervical resorption (ECR) is a type of dental resorption that originates from the loss of the cementum's protective layer. The direct exposure of dentin to the periodontal ligament may lead to the invasion of clastic cells through an entry point on the external root surface into the dentinal tissue, causing resorption. Depending on the extension of ECR, different treatments are proposed. Although the literature presents distinct materials and methods for restoring ECR areas, an existing gap is related to care in the treatment of the supporting periodontal tissue. Guided tissue regeneration (GTR)/guided bone regeneration includes the stimulation of bone formation in bone defects using different types of membranes (resorbable and nonresorbable), regardless of its association with bone substitutes or grafts. Despite the benefits of guided bone regeneration, the application of this method in cases of ECR is still under-explored in the literature. Thus, the present case report uses GTR with xenogenic material and polydioxanone membrane in a case of class IV ECR. The success of the present case is related to the correct diagnosis and treatment plan. Complete debridement of resorption areas and restoration with biodentine were effective in tooth repair. GTR contributed to the stabilization of supporting periodontal tissues. The association of the xenogeneic bone graft with the polydioxanone membrane proved to be a viable option for restoring the health of the periodontium.

Neurogenic Background for Emotional Stress-Associated Hypertension.

PURPOSE OF REVIEW: The response to natural stressors involves both cardiac stimulation and vascular changes, primarily triggered by increases in sympathetic activity. These effects lead to immediate flow redistribution that provides metabolic support to priority target organs combined with other key physiological responses and cognitive strategies, against stressor challenges. This extremely well-orchestrated response that was developed over millions of years of evolution is presently being challenged, over a short period of time. In this short review, we discuss the neurogenic background for the origin of emotional stress-induced hypertension, focusing on sympathetic pathways from related findings in humans and animals. RECENT FINDINGS: The urban environment offers a variety of psychological stressors. Real or anticipatory, emotional stressors may increase baseline sympathetic activity. From routine day-to-day traffic stress to job-related anxiety, chronic or abnormal increases in sympathetic activity caused by emotional stressors can lead to cardiovascular events, including cardiac arrhythmias, increases in blood pressure and even sudden death. Among the various alterations proposed, chronic stress could modify neuroglial circuits or compromise antioxidant systems that may alter the responsiveness of neurons to stressful stimuli. These phenomena lead to increases in sympathetic activity, hypertension and consequent cardiovascular diseases. The link between anxiety, emotional stress, and hypertension may result from an altered neuronal firing rate in central pathways controlling sympathetic activity. The participation of neuroglial and oxidative mechanisms in altered neuronal function is primarily involved in enhanced sympathetic outflow. The significance of the insular cortex-dorsomedial hypothalamic pathway in the evolution of enhanced overall sympathetic outflow is discussed.