Building momentum through networks: Bioimaging across the Americas.

In September 2023, the two largest bioimaging networks in the Americas, Latin America Bioimaging (LABI) and BioImaging North America (BINA), came together during a 1-week meeting in Mexico. This meeting provided opportunities for participants to interact closely with decision-makers from imaging core facilities across the Americas. The meeting was held in a hybrid format and attended in-person by imaging scientists from across the Americas, including Canada, the United States, Mexico, Colombia, Peru, Argentina, Chile, Brazil and Uruguay. The aims of the meeting were to discuss progress achieved over the past year, to foster networking and collaborative efforts among members of both communities, to bring together key members of the international imaging community to promote the exchange of experience and expertise, to engage with industry partners, and to establish future directions within each individual network, as well as common goals. This meeting report summarises the discussions exchanged, the achievements shared, and the goals set during the LABIxBINA2023: Bioimaging across the Americas meeting.

Cystatin C: immunoregulation role in macrophages infected with Porphyromonas gingivalis.

Background: Periodontitis is a chronic infectious disease, characterized by an exacerbated inflammatory response and a progressive loss of the supporting tissues of the teeth. Porphyromonas gingivalis is a key etiologic agent in periodontitis. Cystatin C is an antimicrobial salivary peptide that inhibits the growth of P. gingivalis. This study aimed to evaluate the antimicrobial activity of this peptide and its effect on cytokine production, nitric oxide (NO) release, reactive oxygen species (ROS) production, and programmed cell death in human macrophages infected with P. gingivalis. Methods: Monocyte-derived macrophages generated from peripheral blood were infected with P. gingivalis (MOI 1:10) and stimulated with cystatin C (2.75 µg/ml) for 24 h. The intracellular localization of P. gingivalis and cystatin C was determined by immunofluorescence and transmission electron microscopy (TEM). The intracellular antimicrobial activity of cystatin C in macrophages was assessed by counting Colony Forming Units (CFU). ELISA assay was performed to assess inflammatory (TNFα, IL-1ß) and anti-inflammatory (IL-10) cytokines. The production of nitrites and ROS was analyzed by Griess reaction and incubation with 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA), respectively. Programmed cell death was assessed with the TUNEL assay, Annexin-V, and caspase activity was also determined. Results: Our results showed that cystatin C inhibits the extracellular growth of P. gingivalis. In addition, this peptide is internalized in the infected macrophage, decreases the intracellular bacterial load, and reduces the production of inflammatory cytokines and NO. Interestingly, peptide treatment increased ROS production and substantially decreased bacterial-induced macrophage apoptosis. Conclusions: Cystatin C has antimicrobial and immuno-regulatory activity in macrophages infected with P. gingivalis. These findings highlight the importance of understanding the properties of cystatin C for its possible therapeutic use against oral infections such as periodontitis.

The ZIKV NS5 Protein Aberrantly Alters the Tubulin Cytoskeleton, Induces the Accumulation of Autophagic p62 and Affects IFN Production: HDAC6 Has Emerged as an Anti-NS5/ZIKV Factor.

Zika virus (ZIKV) infection and pathogenesis are linked to the disruption of neurogenesis, congenital Zika syndrome and microcephaly by affecting neural progenitor cells. Nonstructural protein 5 (NS5) is the largest product encoded by ZIKV-RNA and is important for replication and immune evasion. Here, we studied the potential effects of NS5 on microtubules (MTs) and autophagy flux, together with the interplay of NS5 with histone deacetylase 6 (HDAC6). Fluorescence microscopy, biochemical cell-fractionation combined with the use of HDAC6 mutants, chemical inhibitors and RNA interference indicated that NS5 accumulates in nuclear structures and strongly promotes the acetylation of MTs that aberrantly reorganize in nested structures. Similarly, NS5 accumulates the p62 protein, an autophagic-flux marker. Therefore, NS5 alters events that are under the control of the autophagic tubulin-deacetylase HDAC6. HDAC6 appears to degrade NS5 by autophagy in a deacetylase- and BUZ domain-dependent manner and to control the cytoplasmic expression of NS5. Moreover, NS5 inhibits RNA-mediated RIG-I interferon (IFN) production, resulting in greater activity when autophagy is inhibited (i.e., effect correlated with NS5 stability). Therefore, it is conceivable that NS5 contributes to cell toxicity and pathogenesis, evading the IFN-immune response by overcoming HDAC6 functions. HDAC6 has emerged as an anti-ZIKV factor by targeting NS5.

Differential Effect of 4H-Benzo[d] [1, 3]oxazines on the Proliferation of Breast Cancer Cell Lines.

BACKGROUND: A family of 4H-benzo[d][1,3]oxazines were obtained from a group of N-(2-alkynyl)aryl benzamides precursors via gold(I) catalysed chemoselective 6-exo-dig C-O cyclization. METHOD: The precursors and oxazines obtained were studied in breast cancer cell lines MCF-7, CAMA-1, HCC1954 and SKBR-3 with differential biological activity showing various degrees of inhibition with a notable effect for those that had an aryl substituted at C-2 of the molecules. 4H-benzo[d][1,3]oxazines showed an IC50 rating from 0.30 to 157.4 µM in MCF-7, 0.16 to 139 in CAMA-1, 0.09 to 93.08 in SKBR-3, and 0.51 to 157.2 in HCC1954 cells. RESULTS: We observed that etoposide is similar to benzoxazines while taxol effect is more potent. Four cell lines responded to benzoxazines while SKBR-3 cell line responded to precursors and benzoxazines. Compounds 16, 24, 25 and 26 have the potent effect in cell proliferation inhibition in the 4 cell lines tested and correlated with oxidant activity suggesting a possible mechanism by ROS generation. CONCLUSION: These compounds represent possible drug candidates for the treatment of breast cancer. However, further trials are needed to elucidate its full effect on cellular and molecular features of cancer.

Imaging findings of children with PTEN-related hamartoma tumor syndrome: a 20-year multicentric pediatric cohort.

BACKGROUND: PTEN-related hamartoma tumor syndrome results from a mutation in the PTEN gene located at 10q23.31. This syndrome represents a spectrum of different phenotypes of variable expressions, now recognized as part of the same condition. Patients with this mutation have an increased risk of developing a wide range of findings, including malignancies. Although widely described in adults, there are no large series describing the imaging findings in patients before adulthood. Knowledge of the findings seen in children and adolescents with PTEN-related hamartoma tumor syndrome can help guide further management and improve surveillance recommendations. OBJECTIVE: To describe the spectrum of imaging abnormalities in pediatric patients with PTEN-related hamartoma tumor syndrome. MATERIALS AND METHODS: We performed a retrospective, cross-sectional, multicenter study conducted between January 2000 and October 2021 in three tertiary pediatric institutions evaluating the imaging findings in children and adolescents (≤ 18 years) with confirmed diagnoses of a PTEN mutation. For each patient, the imaging findings, histopathology reports, and at least a 2-year follow-up of clinical outcomes for non-operative cases were documented. RESULTS: The cohort included 78 children (37 girls), with a mean age at diagnosis of 7.5 years (range 0 days to 18 years). Benign brain findings included enlarged Virchow-Robin perivascular spaces, white matter changes, developmental venous anomalies, and cerebellar hamartomas. Benign thyroid findings were common, but 5/45 (11.1%) with thyroid abnormalities had a malignant nodule. Soft tissue adipocytic tumors, GI/GU polyps, other soft tissue abnormalities, along with vascular anomalies in various anatomic locations were common. CONCLUSION: Brain abnormalities, benign non-vascular soft tissue abnormalities, and vascular anomalies are commonly seen in children and adolescents with PTEN-related hamartoma tumor syndrome. However, malignancies involving the thyroid gland are not uncommon. Familiarity with the phenotype of PTEN-related hamartoma tumor syndrome in the pediatric population can improve diagnosis and prompt appropriate clinical surveillance of abnormal findings that warrant further management.

A grape-supplemented diet prevented ultraviolet (UV) radiation-induced cataract by regulating Nrf2 and XIAP pathways.

The purpose of this study is to investigate if grape consumption, in the form of grape powder (GP), could protect against ultraviolet (UV)-induced cataract. Mice were fed with the regular diet, sugar placebo diet, or a grape diet (regular diet supplemented with 5%, 10%, and 15% GP) for 3 months. The mice were then exposed to UV radiation to induce cataract. The results showed that the GP diet dose-dependently inhibited UV-induced cataract and preserved glutathione pools. Interestingly, UV-induced Nrf2 activation was abolished in the groups on the GP diet, suggesting GP consumption may improve redox homeostasis in the lens, making Nrf2 activation unnecessary. For molecular target prediction, a total of 471 proteins regulated by GP were identified using Agilent Literature Search (ALS) software. Among these targets, the X-linked inhibitor of apoptosis (XIAP) was correlated with all of the main active ingredients of GP, including resveratrol, catechin, quercetin, and anthocyanins. Our data confirmed that GP prevented UV-induced suppression of XIAP, indicating that XIAP might be one of the critical molecular targets of GP. In conclusion, this study demonstrated that GP protected the lens from UV-induced cataract development in mice. The protective effects of GP may be attributed to its ability to improve redox homeostasis and activate the XIAP-mediated antiapoptotic pathway.

Helper T cell immunity in humans with inherited CD4 deficiency.

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαß+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αß T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.

Dynamic microglia alterations associate with hippocampal network impairments: A turning point in amyloid pathology progression.

Alzheimer's disease is a progressive neurological disorder causing memory loss and cognitive decline. The underlying causes of cognitive deterioration and neurodegeneration remain unclear, leading to a lack of effective strategies to prevent dementia. Recent evidence highlights the role of neuroinflammation, particularly involving microglia, in Alzheimer's disease onset and progression. Characterizing the initial phase of Alzheimer's disease can lead to the discovery of new biomarkers and therapeutic targets, facilitating timely interventions for effective treatments. We used the AppNL-G-F knock-in mouse model, which resembles the amyloid pathology and neuroinflammatory characteristics of Alzheimer's disease, to investigate the transition from a pre-plaque to an early plaque stage with a combined functional and molecular approach. Our experiments show a progressive decrease in the power of cognition-relevant hippocampal gamma oscillations during the early stage of amyloid pathology, together with a modification of fast-spiking interneuron intrinsic properties and postsynaptic input. Consistently, transcriptomic analyses revealed that these effects are accompanied by changes in synaptic function-associated pathways. Concurrently, homeostasis- and inflammatory-related microglia signature genes were downregulated. Moreover, we found a decrease in Iba1-positive microglia in the hippocampus that correlates with plaque aggregation and neuronal dysfunction. Collectively, these findings support the hypothesis that microglia play a protective role during the early stages of amyloid pathology by preventing plaque aggregation, supporting neuronal homeostasis, and overall preserving the oscillatory network's functionality. These results suggest that the early alteration of microglia dynamics could be a pivotal event in the progression of Alzheimer's disease, potentially triggering plaque deposition, impairment of fast-spiking interneurons, and the breakdown of the oscillatory circuitry in the hippocampus.

Recommendations for quantitative cerebral perfusion MRI using multi-timepoint arterial spin labeling: Acquisition, quantification, and clinical applications.

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.

Is it in their eyes? Correlation between microorganisms isolated from bronchial aspirates and conjunctival swabs in a Pediatric Intensive Care Unit / ¿Está en sus ojos? Correlación entre microorganismos aislados de aspirados bronquiales e hisopos conjuntivales en una Unidad de Cuidados Intensivos Pediátricos

Objectives. Our observational, retrospective study aimed to determine the correlation between bacteria isolated from bronchial aspirates of pediatric ICU patients (PICU) with respiratory infections and those obtained from conjunctival swabs of the same patients exhibiting clinical conjunctivitis. Material and methods. Throughout the period from 2015 to 2022, we reviewed all clinically significant bronchial aspirates (≥105 CFU/mL) and positive conjunctival swabs obtained from PICU patients. These records were retrieved from the microbiology database, cross-referencing the data to identify patients who tested positive for both during the same clinical episode. Results. The median age of the patients was 5 months (interquartile range: 1-7). Among the cohort, twenty-one patients exhibited positivity in both bronchial aspirate and conjunctival swab samples, showcasing a microbial match in 85.71% of cases (18 out of 21). The most frequently isolated microorganisms were Haemophilus influenzae (55.6%), followed by Pseudomonas aeruginosa (14.3%), Klebsiella aerogenes (9.5%), and Escherichia coli, Stenotrophomonas maltophilia, and Enterobacter cloacae, each accounting for 4.8% of the isolates. Conclusions. Our study demonstrates a strong concordance between the isolated microorganisms from both samples in patients presenting clear symptoms of clinical conjunctivitis. These findings provide a basis for future prospective studies that may leverage conjunctival swabs as a predictive tool for identifying microorganisms involved in respiratory infections. (AU)

Objetivos. Nuestro estudio observacional y retrospectivo tuvo como objetivo determinar la correlación entre las bacterias aisladas de aspirados bronquiales de pacientes de UCI pediátrica (UCIP) con infecciones respiratorias y las obtenidas de hisopos conjuntivales de los mismos pacientes que presentaban conjuntivitis clínica. Material y métodos. A lo largo del periodo comprendido entre 2015 y 2022, se revisaron todos los aspirados bronquiales clínicamente significativos (≥105 UFC/mL) y los hisopos conjuntivalespositivos obtenidos de pacientes de UCIP. Estos registros se recuperaron de la base de datos de microbiología, cruzando los datos para identificar a los pacientes que dieron positivo en ambos durante el mismo episodio clínico. Resultados. La mediana de edad de los pacientes fue de 5 meses (rango intercuartílico: 1-7). Entre la cohorte, veintiún pacientes presentaron positividad tanto en las muestras de aspirado bronquial como en las de hisopo conjuntival, mostrando una coincidencia microbiana en el 85,71% de los casos (18 de 21). Los microorganismos más frecuentemente aislados fueron Haemophilus influenzae (55,6%), seguido de Pseudomonas aeruginosa (14,3%), Klebsiella aerogenes (9,5%) y Escherichia coli, Stenotrophomonas maltophiliay Enterobacter cloacae, cada uno de los cuales representó el 4,8% de los aislamientos. Conclusiones. Nuestro estudio demuestra una fuerte concordancia entre los microorganismos aislados de ambas muestras en pacientes que presentan síntomas claros de conjuntivitis clínica. Estos hallazgos proporcionan una base para futuros estudios prospectivos que podrían aprovechar los hisopos conjuntivales como herramienta predictiva para identificar microorganismos implicados en infecciones respiratorias. (AU)

High-Performance, Low-Cost, Additively Manufactured Electrospray Ion Sources for Mass Spectrometry.

We report novel 3D-printed electrospray sources for mass spectrometry (MS) that produce twice the signal strength of their mainstream counterparts. Leveraging 3D printing to fabricate in bulk nano- and microscale-featured electrospray emitters, this work shows a path for scalable integration in clinically relevant diagnostics. This solution improves the device performance by simultaneously tuning the surface hydrophilicity, solvent evaporation, and geometry. The emitters are made of stainless-steel (SS) 316L via binder jetting and coated in a conformal, hydrothermally grown zinc oxide nanowire (ZnONW) forest. The printed emitters are designed as surface mount devices that can be directly soldered to printed circuit boards with built-in digital microfluidics as part of an automated device assembly. The electrospray sources use a novel extractor electrode design that enables operation at ∼24% larger bias voltages compared with conventional MS cylindrical inlets. The 3D-printed electrospray emitters were characterized against their state-of-the-art counterparts (coated blades and paper spray). MS data from the 3D-printed electrospray emitters show detection of therapeutically relevant targets at 1 µg/ml concentrations with a variety of solvents; for nicardipine, such emitters attain 116% higher signal-to-noise ratios and far greater stability than their counterparts.

Prefrontal activity during IOWA Gambling Task in young adult women.

This study aims to investigate the relationships between personality traits of impulsivity, using the UPPS-P Impulsive Behaviour Scales shortened version, and prefrontal cortex (PFC) activity during the IOWA Gambling Task (IGT) in young adult women. The study included a sample of 83 young, healthy females (19.8 ± 1.4 years), who voluntarily took part in the study. Repeated measures analysis during the IGT revealed a significant increase in HbO (all p <.001; ηp2 >.31) and a decrease in Hbr (all p <.003; ηp2 >.08) in all prefrontal quadrants. This increase in oxygenation occurs primarily during the choice period under ambiguity (r =.23; p =.039). Additionally, there was a significant linear decrease in selecting the decks associated with a high frequency of losses (p <.001), while the favorable deck with low losses showed a linear increase (F = 12.96; p <.001). Notably, discrepancies were found between UPPS-P and IGT impulsivity ratings. The Lack of Perseverance and Lack of Premeditation scales from the UPPS-P were identified as significant predictors of HbO levels, mainly in the two quadrants of the left hemisphere's, lateral (adjusted R2 =.23; p <.001; f2 =.34) and rostral (adjusted R2 =.13; p <.002; f2 =.17). These findings suggest that young adult women predominantly adopt a punishment-avoidance strategy during IGT, exhibiting increased activation in the left hemisphere, especially during the task's initial phase characterized by ambiguity.

Intravenous administration of ultrasound contrast to critically ill pediatric patients.

BACKGROUND: The off-label use of contrast-enhanced ultrasound has been increasingly used for pediatric patients. OBJECTIVE: The purpose of this retrospective study is to report any observed clinical changes associated with the intravenous (IV) administration of ultrasound contrast to critically ill neonates, infants, children, and adolescents. MATERIALS AND METHODS: All critically ill patients who had 1 or more contrast-enhanced ultrasound scans while being closely monitored in the neonatal, pediatric, or pediatric cardiac intensive care units were identified. Subjective and objective data concerning cardiopulmonary, neurological, and hemodynamic monitoring were extracted from the patient's electronic medical records. Vital signs and laboratory values before, during, and after administration of ultrasound contrast were obtained. Statistical analyses were performed using JMP Pro, version 15. Results were accepted as statistically significant for P-value<0.05. RESULTS: Forty-seven contrast-enhanced ultrasound scans were performed on 38 critically ill patients, 2 days to 17 years old, 19 of which were female (50%), and 19 had history of prematurity (50%). At the time of the contrast-enhanced ultrasound scans, 15 patients had cardiac shunts or a patent ductus arteriosus, 25 had respiratory failure requiring invasive mechanical oxygenation and ventilation, 19 were hemodynamically unstable requiring continual vasoactive infusions, and 8 were receiving inhaled nitric oxide. In all cases, no significant respiratory, neurologic, cardiac, perfusion, or vital sign changes associated with IV ultrasound contrast were identified. CONCLUSION: This study did not retrospectively identify any adverse clinical effects associated with the IV administration of ultrasound contrast to critically ill neonates, infants, children, and adolescents.

Ewing sarcoma of the cervix: an unusual site of presentation.

Ewing sarcoma is an exceedingly rare form of cancer that affects the cervix. It falls within the spectrum of neoplastic diseases known as Ewing's family of tumours, typically observed in osseous tissues. A woman in her 40s, experiencing symptoms of leucorrhoea and transvaginal bleeding that commenced 3 months before her consultation, was referred to our gynaecological oncology clinic with a preliminary diagnosis of ovarian teratoma. A colposcopy procedure was conducted unveiling a complete loss of cervical anatomy with friable and malodorous tissue. Pelvic ultrasound identified a lesion of uncertain origin in the cervix, suggestive of malignancy. Histopathological assessment of cervical biopsy specimens confirmed the presence of a small, round, blue cell neoplasm consistent with Ewing sarcoma. She underwent chemotherapy and pelvic radiotherapy, achieving complete remission 9 months after diagnosis, without experiencing any systemic adverse effects or sequelae.

Microvascular imaging findings in infants with bacterial meningitis: a case series.

Bacterial meningitis is a severe and life-threatening disease that rapidly progresses in neonates and infants; prompt diagnosis and appropriate treatment are lifesaving. Magnetic resonance imaging remains the primary imaging technique for diagnosing meningitis; however, due to its limited availability and cost, ultrasound is often used for initial screening. Microvascular imaging ultrasound (MVI) is an emerging technique that offers insight into the brain microvasculature beyond conventional ultrasound. Here we present three patients with confirmed bacterial meningitis and associated cerebral microvascular findings on brain MVI to instigate further validation of cerebral microvascular imaging markers of bacterial meningitis for early detection and intervention.

Collateral Damage in the Placenta during Viral Infection in Pregnancy: A Possible Mechanism for Vertical Transmission and an Adverse Pregnancy Outcome.

In mammals, the placenta is a connection between a mother and a new developing organism. This tissue has a protective function against some microorganisms, transports nutrients, and exchanges gases and excretory substances between the mother and the fetus. Placental tissue is mainly composed of chorionic villi functional units called trophoblasts (cytotrophoblasts, the syncytiotrophoblast, and extravillous trophoblasts). However, some viruses have developed mechanisms that help them invade the placenta, causing various conditions such as necrosis, poor perfusion, and membrane rupture which, in turn, can impact the development of the fetus and put the mother's health at risk. In this study, we collected the most relevant information about viral infection during pregnancy which can affect both the mother and the fetus, leading to an increase in the probability of vertical transmission. Knowing these mechanisms could be relevant for new research in the maternal-fetal context and may provide options for new therapeutic targets and biomarkers in fetal prognosis.

Surgical waiting lists and queue management in a Brazilian tertiary public hospital.

BACKGROUND: Centralized management of queues helps to reduce the surgical waiting time in the publicly funded healthcare system, but this is not a reality in the Brazilian Unified Healthcare System (BUHS). We describe the implementation of the "Patients with Surgical Indication" (PSI) in a Brazilian public tertiary hospital, the impact on waiting time, and its use in rationing oncological surgeries during the COVID-19 Pandemic. METHODS: Retrospective observational study of elective surgical requests (2016-2022) in a Brazilian general, public, tertiary university hospital. We recovered information regarding the inflows (indications), outflows and their reasons, the number of patients, and waiting time in queue. RESULTS: We enrolled 82,844 indications in the PSI (2016-2022). The waiting time (median and interquartile range) in days decreased from 98(48;168) in 2016 to 14(3;152) in 2022 (p < 0.01). The same occurred with the backlog that ranged from 6,884 in 2016 to 844 in 2022 (p < 001). During the Pandemic, there was a reduction in the number of non-oncological surgeries per month (95% confidence interval) of -10.9(-18.0;-3.8) during Phase I (January 2019-March 2020), maintenance in Phase II (April 2020-August 2021) 0.1(-10.0;10.4) and increment in Phase III (September 2021-December 2022) of 23.0(15.3;30.8). In the oncological conditions, these numbers were 0.6(-2.1;3.3) for Phase I, an increase of 3.2(0.7;5.6) in Phase II and 3.9(1,4;6,4) in Phase III. CONCLUSION: Implementing a centralized list of surgical indications and developing queue management principles proved feasible, with effective rationing. It unprecedentedly demonstrated the decrease in the median waiting time in Brazil.