Assessment of Mannitol-Induced Chronic Blood-Brain Barrier Dysfunction In Vivo Using Magnetic Resonance.

The blood-brain barrier (BBB) is essential for protection and plays a crucial role in chronic neurological disorders like small-vessel disease and Alzheimer's disease. Its complexity poses significant challenges for effective diagnostics and treatments, highlighting the need for novel animal models and comprehensive BBB dysfunction studies. This study investigates chronic BBB dysfunction induction using osmotic disruption via mannitol in healthy adult male Sprague Dawley rats over 12 weeks. Group 1 received 1 bolus/week (2.0 g/kg), Group 2 received 3 boluses/week (1.5 g/kg), and Group 3 received 3 boluses/week (2.5 g/kg). BBB dysfunction was assessed using gadolinium (Gd) infusion and MRI to evaluate location, severity, evolution, and persistence. MR spectroscopy (MRS) examined the brain metabolism changes due to intravenous mannitol, with T2-weighted MRI assessing brain lesions. Biomarkers of neuroinflammation were analyzed in the highest mannitol dose group. Our data show chronic BBB dysfunction primarily in the cortex, hippocampus, and striatum, but not in the corpus callosum of rats under periodic mannitol dosing in groups 1 and 2. MRS identified a distinctive metabolite signature, including changes in alanine, choline, and N-acetyl aspartate in the striatum of Group 1. No significant differences were found in the serum levels of all pro- and anti-inflammatory cytokines analyzed in the high-dose Group 3. This study underscores the feasibility and implications of using osmotic disruption to model chronic BBB dysfunction, offering insights for future neuroprotection and therapeutic strategies research.

The insular cortex, autonomic asymmetry and cardiovascular control: looking at the right side of stroke.

PURPOSE: Evidence from animal and human studies demonstrates that cortical regions play a key role in autonomic modulation with a differential role for some brain regions located in the left and right brain hemispheres. Known as autonomic asymmetry, this phenomenon has been demonstrated by clinical observations, by experimental models, and currently by combined neuroimaging and direct recordings of sympathetic nerve activity. Previous studies report peculiar autonomic-mediated cardiovascular alterations following unilateral damage to the left or right insula, a multifunctional key cortical region involved in emotional processing linked to autonomic cardiovascular control and featuring asymmetric characteristics. METHODS: Based on clinical studies reporting specific damage to the insular cortex, this review aims to provide an overview of the prognostic significance of unilateral (left or right hemisphere) post-insular stroke cardiac alterations. In addition, we review experimental data aiming to unravel the central mechanisms involved in post-insular stroke cardiovascular complications. RESULTS AND CONCLUSION: Current clinical and experimental data suggest that stroke of the right insula  can present a worse cardiovascular prognosis.

Polynorepinephrine and polydopamine-bacterial laccase coatings for phenolic amperometric biosensors.

The successful fabrication of biosensors is greatly limited by the immobilization of their bioreceptor, thus we propose a facile and reproducible two-step method to modify graphite electrodes with a bacterial laccase, relying on a fast and controllable potentiostatic process to coat graphite surfaces with biomolecule-compatible thin films of polynorepinephrine (ePNE) and polydopamine (ePDA). Both polymers, synthesized with a similar thickness, were functionalized with bacterial laccase, displaying distinct electrochemical transducing behaviours at pH 5.0 and 7.0. ePNE layer enables adequate electron transfer of anionic and cationic species in acidic and neutral media, whereas transduction across ePDA strongly depends on pH and redox probe charge. ePNE stands out by improving the amperometric responses of the biosensing interface towards a phenolic acid (gallic acid) and a flavonoid (catechin), in respect to ePDA. The optimal graphite/ePNE/laccase interface outperforms biosensing interfaces based on fungal laccases at neutral pH, displaying detection sensitivities of 104 and 14.4 µA cm-2 mM-1for gallic acid and catechin, respectively. The fine synthetic control of the ePNE bio-inspired transduction layer and the use of an alkaliphilic bacterial laccase enabled the construction of an amperometric biosensing interface with extended pH range of polyphenols detection present in food products and agro-industrial waste.

XP-Endo Finisher behaviour and irrigant temperature in intracanal environment: Clinical measurements.

AIM: To evaluate the behaviour of the XP-Endo Finisher and the variation in the intracanal temperature of the irrigant at rest and when activated over time. METHODOLOGY: Differential scanning calorimetry (DSC) determined the transformation temperatures of XP-Endo Finisher instruments. A digital thermocouple was used to measure the temperature of the irrigant inside the pulp chamber. Two measurements were performed for each tooth (n = 12): with the irrigant at rest and during XP-Endo agitation for 60 s to observe the temperature evolution. The data were statistically analysed using a t-test with a confidence level of 95%. RESULTS: DSC results suggested that the XP-Endo Finisher had a mixed R-phase and austenitic structure at room temperature. The temperature values at predetermined time points (0, 10, 40, 70, 120 and 240 s) were measured, and no statistical difference was observed between the values of the resting and activated solutions at any of the selected points (p > .05). For the protocol performed with the XP-Endo file, the mean irrigant temperature observed at instrument insertion inside the root canal was 28.65°C. After 60 s of agitation, the temperature was 34.02°C. The solution temperature stabilized inside the canal only after 211 s at 35.5°C. The mean maximum irrigation solution temperature recorded inside the canal was 35.5°C without agitation and after XP-endo agitation (p > .05). CONCLUSIONS: Although the XP-Endo Finisher system does not promote heating of the irrigation solution, file expansion responsible for improved instrument cleaning starts at a temperature below the expected value.

Reducing the Wallacean and the Haeckelian Deficits in Apobaetis Day, 1955 (Ephemeroptera: Baetidae).

During an ongoing project aiming to understand the dynamics of Ephemeroptera biodiversity in the Doce River Basin after the disaster, an unusual large number of Apobaetis Day, 1955 were analyzed. The occurrence of Apobaetis is quite relevant, since the combination of factors such as its small body size and its habitat preferences makes their collection difficult and its presence often neglected. For the first time in science, adults of Apobaetis irai De Lima, Massariol, Cruz & Hamada, 2022 and Apobaetis fiuzai Salles & Lugo-Ortiz, 2002 are described and diagnosed. Apobaetis irai can be easily distinguished, among other characteristics by turbinate portion of compound eyes touching each other along midline; abdominal terga II-III and V-VII with well-marked lines on lateral and posterior margins; posterior margin of subgenital plate with projection broadly rounded to slightly truncate. Apobaetis fiuzai are diagnosed by turbinate portion of compound eyes touching each other posteriorly; mesothorax brown, except for broad cream marks on anterior margin of PSp and SLS, SSLi tinged with white, posterior corner of SMS with a red spot; abdominal terga II-VI translucent orangish-brown, terga VII-X brown, terga II-III and VI with conspicuous red medial mark; posterior margin of subgenital plate with subtriangular projection, apex narrowly truncate; forceps base wider at base, inner irregular edges. The new records of A. irai and A. fiuzai extend the distribution of Apobaetis within Minas Gerais and Espírito Santo States, Brazil. Furthermore, it is reported for the first time cases of gynandromorphs for Apobaetis.

Intranasal Multiepitope PD-L1-siRNA-Based Nanovaccine: The Next-Gen COVID-19 Immunotherapy.

The first approved vaccines for human use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are nanotechnology-based. Although they are modular, rapidly produced, and can reduce disease severity, the currently available vaccines are restricted in preventing infection, stressing the global demand for novel preventive vaccine technologies. Bearing this in mind, we set out to develop a flexible nanovaccine platform for nasal administration to induce mucosal immunity, which is fundamental for optimal protection against respiratory virus infection. The next-generation multiepitope nanovaccines co-deliver immunogenic peptides, selected by an immunoinformatic workflow, along with adjuvants and regulators of the PD-L1 expression. As a case study, we focused on SARS-CoV-2 peptides as relevant antigens to validate the approach. This platform can evoke both local and systemic cellular- and humoral-specific responses against SARS-CoV-2. This led to the secretion of immunoglobulin A (IgA), capable of neutralizing SARS-CoV-2, including variants of concern, following a heterologous immunization strategy. Considering the limitations of the required cold chain distribution for current nanotechnology-based vaccines, it is shown that the lyophilized nanovaccine is stable for long-term at room temperature and retains its in vivo efficacy upon reconstitution. This makes it particularly relevant for developing countries and offers a modular system adaptable to future viral threats.

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.

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.

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.

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.