Immunotherapy Combining Mimotopes Selected by Phage Display Plus Amphotericin B Is Effective for Treatment Against Visceral Leishmaniasis.

The treatment for visceral leishmaniasis (VL) causes toxicity in patients, entails high cost and/or leads to the emergence of resistant strains. No human vaccine exists, and diagnosis presents problems related to the sensitivity or specificity of the tests. Here, we tested two phage clones, B1 and D11, which were shown to be protective against Leishmania infantum infection in a murine model as immunotherapeutics to treat mice infected with this parasite species. The phages were used alone or with amphotericin B (AmpB), while other mice received saline, AmpB, a wild-type phage (WTP) or WTP/AmpB. Results showed that the B1/AmpB and D11/AmpB combinations induced polarised Th1-type cellular and humoral responses, which were primed by high levels of parasite-specific IFN-γ, IL-12, TNF-α, nitrite and IgG2a antibodies, which reflected in significant reductions in the parasite load in distinct organs of the animals when analyses were performed 1 and 30 days after the treatments. Reduced organic toxicity was also found in these animals, as compared with the controls. In conclusion, preliminary data suggest the potential of the B1/AmpB and D11/AmpB combinations as immunotherapeutics against L. infantum infection.

Determination of speed and assessment of conditioning in horses submitted to a lactate minimum test-alternative approaches.

The maximal lactate steady state (MLSS) is a well-known gold standard method for determining the aerobic capacity of athletic horses. Owing to its high cost and complex execution, there is a search for standardized exercise tests that can predict this value in a single session. One of the methods described for this purpose is the lactate minimum test (LMT), which could be more accurate despite being adequate to predict MLSS. This study aimed to examine the impact of training on the speed corresponding to lactate minimum speed (LMS) and to apply new mathematical methods to evaluate the fitness level of horses based on the curve obtained by the LMT. Ten Arabian horses underwent a 6-week training program based on LMS calculated by second-degree polynomial regression (LMSP). In addition, the LMS was also determined by visual inspection (LMSV), bi-segmented linear regression (LMSBI) and spline regression (LMSS). From the curve obtained during the LMT, it was possible to calculate angles α, ß and ω, as well as the total area under the curve (AUCTOTAL) before (AUCPRELMS) and after (AUCPOSLMS) the LMS. The methods for determining the LMS were evaluated by ANOVA, intraclass correlation coefficient (ICC) and effect size (ES) by Cohen's d test. The Pearson correlation coefficient (r) between the proposed LMS determination methods and other mathematical methods was also calculated. Despite showing a good correlation (ICC >0.7), the LMS determination methods differed from each other (p < 0.05), albeit without a significant difference resulting from conditioning. There were reductions in α:ß ratio, angle α, and AUCPOSTLMS, with the latter indicating lower lactate accumulation in the incremental phase of LMT after conditioning, in addition to an improvement in the animals' aerobic capacity. Considering that the most common methods for determining the LMS are applicable yet with low sensitivity for conditioning assessment, the approaches proposed herein can aid in analyzing the aerobic capacity of horses subjected to LMT. The mathematical models presented in this paper have the potential to be applied in human lactate-guided training program trials with a comparable study basis.

Effect of hormone therapy on blood pressure and hypertension in postmenopausal women: a systematic review and meta-analysis.

IMPORTANCE: Menopausal hormone therapy (HT) includes a wide variety of hormonal compounds, and its effect on blood pressure is still uncertain. OBJECTIVE: The aim of this study was to assess evidence regarding the effect of HT on blood pressure in postmenopausal women and its association with arterial hypertension. EVIDENCE REVIEW: This systematic review and meta-analysis included randomized clinical trials and prospective observational studies. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and the incidence of hypertension were assessed. All stages were independently performed by two reviewers. For blood pressure outcome, standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated as effect measures. Heterogeneity was assessed using the I2 statistic. The results are presented based on the HT type. The incidence of hypertension was compared using descriptive analyses. FINDINGS: Eleven studies were included with 81,041 women evaluated, of which 29,812 used HT. The meta-analysis, conducted with 8 studies and 1,718 women, showed an increase in SBP with the use of oral conjugated equine estrogens plus progestogen (SMD = 0.60 mm Hg, 95% CI = 0.19 to 1.01). However, oral or transdermal use of estradiol plus progestogen (SMD = -2.00 mm Hg, 95% CI = -7.26 to 3.27), estradiol alone, and tibolone did not show any significant effect. No significant effect on DBP was observed for any formulation. Women who used oral estrogen plus progestogen had a higher risk of incident hypertension than those who never used it. CONCLUSIONS AND RELEVANCE: The effect of HT on blood pressure is influenced by the formulation used, especially the type of estrogen. The combined formulations of conjugated equine estrogens plus progestogen increased SBP and the risk of hypertension, which was not observed among estradiol plus progestogen, estradiol alone, and tibolone users.

The scaffolding protein AKAP12 regulates mRNA localization and translation.

Regulation of subcellular messenger (m)RNA localization is a fundamental biological mechanism, which adds a spatial dimension to the diverse layers of post-transcriptional control of gene expression. The cellular compartment in which mRNAs are located may define distinct aspects of the encoded proteins, ranging from production rate and complex formation to localized activity. Despite the detailed roles of localized mRNAs that have emerged over the past decades, the identity of factors anchoring mRNAs to subcellular domains remains ill-defined. Here, we used an unbiased method to profile the RNA-bound proteome in migrating endothelial cells (ECs) and discovered that the plasma membrane (PM)-associated scaffolding protein A-kinase anchor protein (AKAP)12 interacts with various mRNAs, including transcripts encoding kinases with Actin remodeling activity. In particular, AKAP12 targets a transcript coding for the kinase Abelson Tyrosine-Protein Kinase 2 (ABL2), which we found to be necessary for adequate filopodia formation and angiogenic sprouting. Moreover, we demonstrate that AKAP12 is necessary for anchoring ABL2 mRNA to the PM and show that in the absence of AKAP12, the translation efficiency of ABL2 mRNA is reduced. Altogether, our work identified a unique post-transcriptional function for AKAP12 and sheds light into mechanisms of spatial control of gene expression.

Intracardiac echography-guided fluoroless ablation versus conventional fluoroscopy-guided ablation for cardiac arrhythmias: a systematic review and meta-analysis

BACKGROUND: Intracardiac echocardiography (ICE) has improved catheter ablation procedures, reducing reliance on fluoroscopy. Yet, the efficacy and safety of zero-fluoroscopy (ZF) procedures remain uncertain. METHODS: We conducted a systematic review and meta-analysis comparing ZF ablation procedures guided by ICE vs. conventional techniques regarding efficacy and safety outcomes. PubMed, Cochrane, and embase were searched. A random-effects model was used to calculate risk ratios (RRs), odds ratios (OR) and mean differences (MDs) with 95% confidence intervals (CI). RESULTS: We includedfourteen studies with 1,919 patients of whom 1,023 (58.72%) performed ZF ablation using ICE. We found a significant reduced ablation time (SMD -0.18; 95% CI -0.31;-0.04; p=0.009), procedure time (MD -7.54; 95% CI -14.68;-0.41; p=0.04), fluoroscopic time (MD -2.52; 95% CI -3.20;-1.84; p<0.001) in patients treated with ZF approach compared with NZF approach. However, there was no significant difference between the two groups in acute success rate (RR 1.00; 95% CI 0.99-1.01; p=0.85), long-term success rate (RR 0.99; 95% CI 0.93-1.05; p=0.77) and complications (RR 0.84, 95% CI: 0.48-1.46; p = 0.54). CONCLUSION: Our findings suggest that among patients undergoing arrhythmia ablation, fluoroscopy-free ICE-guided technique reduces procedure time and radiation exposure with comparable short and long-term success rates and complications.

Effects of superparamagnetic iron oxide nanoparticles (SPIONS) testicular injection on Leydig cell function and sperm production in a murine model.

In the domain of medical advancement, nanotechnology plays a pivotal role, especially in the synthesis of biocompatible materials for therapeutic use. Superparamagnetic Iron Oxide Nanoparticles (SPIONs), known for their magnetic properties and low toxicity, stand at the forefront of this innovation. This study explored the reproductive toxicological effects of Sodium Citrate-functionalized SPIONs (Cit_SPIONs) in adult male mice, an area of research that holds significant potential yet remains largely unknown. Our findings reveal that Cit_SPIONs induce notable morphological changes in interstitial cells and the seminiferous epithelium when introduced via intratesticular injection. This observation is critical in understanding the interactions of nanomaterials within reproductive biological systems. A striking feature of this study is the rapid localization of Cit_SPIONs in Leydig cells post-injection, a factor that appears to be closely linked with the observed decrease in steroidogenic activity and testosterone levels. This data suggests a possible application in developing nanostructured therapies targeting androgen-related processes. Over 56 days, these nanoparticles exhibited remarkable biological distribution in testis parenchyma, infiltrating various cells within the tubular and intertubular compartments. While the duration of spermatogenesis remained unchanged, there were many Tunel-positive germ cells, a notable reduction in daily sperm production, and reduced progressive sperm motility in the treated group. These insights not only shed light on the intricate mechanisms of Cit_SPIONs interaction with the male reproductive system but also highlight the potential of nanotechnology in developing advanced biomedical applications.

Multilevel analysis of social determinants of advanced stage colorectal cancer diagnosis.

The advanced stage at diagnosis of colorectal cancer (CRC) may be related to individual factors, socioeconomic conditions, and healthcare service availability. The objective of the study was to analyze the prevalence of advanced stage CRC at the time of diagnosis and its association with individual, contextual, socioeconomic, and healthcare service indicators. An observational, cross-sectional study was conducted, analyzing cases of malignant neoplasms of the colon and rectum in individuals of both sexes, aged between 18 and 99 years, diagnosed between 2010 and 2019 in Brazil (n = 69,047). Data were collected from the Hospital Cancer Registry (HCR), Atlas of Human Development in Brazil, and from the National Registry of Health Institutions (NRHI). A Multilevel Poisson Regression model with random intercept was used. The prevalence of advanced stage CRC at diagnosis was 65.6%. Advanced stage was associated with older age groups prevalence ratio (PR) 4.40 and younger age groups (PR 1.84), low Human Development Index (HDI) (PR 1.22), and low density of family health strategy teams (PR 1.10). The study highlights the unequal distribution of social determinants of health in the diagnosis CRC in Brazil, revealing the need to evaluate and redirect public policies aimed at improving early detection and prevention of CRC in the country.

Novel Fe3O4 Nanoparticles with Bioactive Glass-Naproxen Coating: Synthesis, Characterization, and In Vitro Evaluation of Bioactivity.

Immune response to biomaterials, which is intimately related to their surface properties, can produce chronic inflammation and fibrosis, leading to implant failure. This study investigated the development of magnetic nanoparticles coated with silica and incorporating the anti-inflammatory drug naproxen, aimed at multifunctional biomedical applications. The synthesized nanoparticles were characterized using various techniques that confirmed the presence of magnetite and the formation of a silica-rich bioactive glass (BG) layer. In vitro studies demonstrated that the nanoparticles exhibited bioactive properties, forming an apatite surface layer when immersed in simulated body fluid, and biocompatibility with bone cells, with good viability and alkaline phosphatase activity. Naproxen, either free or encapsulated, reduced nitric oxide production, an inflammatory marker, while the BG coating alone did not show anti-inflammatory effects in this study. Overall, the magnetic nanoparticles coated with BG and naproxen showed promise for biomedical applications, especially anti-inflammatory activity in macrophages and in the bone field, due to their biocompatibility, bioactivity, and osteogenic potential.

Congenital Zika virus infection impacts on male mouse offspring's reproductive biology.

In brief: Congenital ZIKV infection promotes alarming effects on male offspring's reproductive biology. This study showed the presence of the ZIKV antigen in the testis parenchyma, decreased testosterone levels, and sperm abnormalities in male offspring born to infected mothers. Abstract: Infection with ZIKV during pregnancy is associated with fetal developmental problems. Although neurological issues are being explored more in experimental studies, limited research has focused on the reproductive health consequences for offspring born to infected mothers. In this context, this study aimed to assess the impact of ZIKV infection during pregnancy on the testes and sperm of adult male offspring. Female mice were intraperitoneally inoculated with a Brazil strain of ZIKV during the 5.5th day of embryonic gestation. The offspring were evaluated 12 weeks after birth to analyze cellular and molecular changes in the testes and sperm. A novel approach combining variable-angle spectroscopic ellipsometry and machine learning modeling was also introduced for sperm sample analysis. The study revealed the presence of ZIKV protein in the testis parenchyma of adult male offspring born to infected mothers. It was shown that the testes exhibited altered steroidogenesis and inflammatory mediators, in addition to significant issues with spermiogenesis that resulted in sperm with DNA fragmentation, head defects, and protamination failure. Additionally, sperm dielectric properties and artificial intelligence showed potential for rapid identification and classification of sperm samples from infected mice. These findings provide crucial insights into the reproductive risks for men born from ZIKV-infected pregnant women.

Preventive effects of hesperidin in an experimental model ofs acute lung inflammation.

In this study, we hypothesized that long-term administration of hesperidin can modulate the inflammatory response and oxidative stress in animals submitted to mechanical ventilation (MV). Twenty-five C57BL/6 male mice were divided into 5 groups: control, MV, animals receiving hesperidin in three doses 10, 25 and 50 mg/kg. The animals received the doses of hesperidin for 30 days via orogastric gavage, and at the end of the period the animals were submitted to MV. In animals submitted to MV, increased lymphocyte, neutrophil and monocyte/macrophage cell counts were observed in the blood and airways. Associated to this, MV promoted an increase in inflammatory cytokine levels such as CCL2, IL-12 and TNFα. The daily administration of hesperidin in the three doses prevented the effects caused by MV, which was observed by a lower influx of inflammatory cells into the airways, a reduction in inflammatory markers and less oxidative damage.

Avian iPSC Derivation to Recover Threatened Wild Species: A Comprehensive Review in Light of Well-Established Protocols.

Induced pluripotent stem cells (iPSCs) were first generated by Yamanaka in 2006, revolutionizing research by overcoming limitations imposed by the use of embryonic stem cells. In terms of the conservation of endangered species, iPSC technology presents itself as a viable alternative for the manipulation of target genetics without compromising specimens. Although iPSCs have been successfully generated for various species, their application in nonmammalian species, particularly avian species, requires further in-depth investigation to cover the diversity of wild species at risk and their different protocol requirements. This study aims to provide an overview of the workflow for iPSC induction, comparing well-established protocols in humans and mice with the limited information available for avian species. Here, we discuss the somatic cell sources to be reprogrammed, genetic factors, delivery methods, enhancers, a brief history of achievements in avian iPSC derivation, the main approaches for iPSC characterization, and the future perspectives and challenges for the field. By examining the current protocols and state-of-the-art techniques employed in iPSC generation, we seek to contribute to the development of efficient and species-specific iPSC methodologies for at-risk avian species. The advancement of iPSC technology holds great promise for achieving in vitro germline competency and, consequently, addressing reproductive challenges in endangered species, providing valuable tools for basic research, bird genetic preservation and rescue, and the establishment of cryobanks for future conservation efforts.

Bovine serum albumin nanoparticles containing Poly (I:C) can enhance the neutralizing antibody response induced by envelope protein of Orthoflavivirus zikaense.

Since the Orthoflavivirus zikaense (ZIKV) has been considered a risk for Zika congenital syndrome development, developing a safe and effective vaccine has become a high priority. Numerous research groups have developed strategies to prevent ZIKV infection and have identified the domain III of the ZIKV envelope protein (zEDIII) as a promising target. Subunit antigens are often poorly immunogenic, necessitating the use of adjuvants and/or delivery systems to induce optimal immune responses. The subject of nanotechnology has substantial expansion in recent years in terms of research and applications. Nanoparticles could be used as drug delivery systems and to increase the immunogenicity and stability of a given antigen. This work aims to characterize and validate the potential of a vaccine formulation composed of domain zEDIII and bovine serum albumin nanoparticles containing polyinosinic-polycytidylic acid (NPPI). NPPI were uptake in vitro by immature bone marrow dendritic cells and histological analysis of the skin of mice treated with NPPI showed an increase in cellularity. Immunization assay showed that mice immunized with zEDIII in the presence of NPPI produced neutralizing antibodies. Through the passive transfer of sera from immunized mice to ZIKV-infected neonatal mice, it was demonstrated that these antibodies provide protection, mitigating weight loss, clinical or neurological signs induced by infection, and significantly increased survival rates. Protection was further substantiated by the reduction in the number of viable infectious ZIKV, as well as a decrease in inflammatory cytokines and tissue alterations in the brains of infected mice. Taken together, data presented in this study shows that NPPI + zEDIII is a promising vaccine candidate for ZIKV.

The bladder microbiota is not significantly altered by intravesical BCG therapy.

INTRODUCTION: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls. We also longitudinally analyzed the impact of BCG therapy on the bladder microbiota of NMIBC patients and addressed whether bladder microbiota is associated with BCG efficacy. METHODS: We collected catheterized urine samples from males with intermediate/high-risk NMIBC (cancer group, n = 32) or benign prostatic hyperplasia (control group, n = 41). The cancer group also provided urine samples during and after BCG induction. We used 16S rRNA gene sequencing to characterize the bladder microbiota. Bladder microbiota parameters, such as diversity and taxonomic composition, were compared between groups and associated with clinicopathological data and BCG efficacy. RESULTS: We observed no significant differences between the bladder microbiota of NMIBC patients and controls. BCG intravesical instillations did not significantly alter the bladder microbiota of NMIBC patients, and BCG was rarely detected in the bladder during and after BCG therapy. Microbiota diversity and overall composition before BCG induction did not influence disease persistence at 3 months. However, higher abundance of Lactobacillus, Streptococcus, and Cutibacterium in the pre-BCG bladder microbiota was associated with BCG effectiveness. CONCLUSION: We were unable to identify markers of bladder microbiota dysbiosis among male NMIBC patients. Moreover, we demonstrated for the first time using longitudinally collected samples that BCG cannot persist in the bladder microbiota nor significantly alter its diversity and composition. The associations found between bladder microbes and BCG efficacy highlight the potential of microbial-based therapeutic and risk-stratification strategies in the intermediate/high-risk NMIBC setting.

Risk factors for death and illness severity in vaccinated versus unvaccinated COVID-2019 inpatients: a retrospective cohort study.

OBJECTIVE: To determine the clinical profile of COVID-19 inpatients who were vaccinated prior to hospitalization and to compare the risk factors for death and the 28-day survival rate of between those inpatients vaccinated with one, two, or three doses and unvaccinated COVID-19 inpatients. METHODS: This was a retrospective observational cohort study involving COVID-19 patients admitted to a referral hospital in the city of Recife, Brazil, between July of 2020 and June of 2022. RESULTS: The sample comprised 1,921 inpatients, 996 of whom (50.8%) were vaccinated prior to hospitalization. After adjusting the mortality risk for vaccinated patients, those undergoing invasive mechanical ventilation (IMV) had the highest mortality risk (adjusted OR [aOR] = 7.4; 95% CI, 3.8-14.1; p < 0.001), followed by patients > 80 years of age (aOR = 7.3; 95% CI, 3.4-15.4; p < 0.001), and those needing vasopressors (aOR = 5.6; 95% CI, 2.9-10.9; p < 0.001). After adjusting the mortality risk for all patients, having received three vaccine doses (aOR = 0.06; 95% CI, 0.03-0.11; p < 0.001) was the most important protective factor against death. There were progressive benefits of vaccination, reducing the frequency of ICU admissions, use for IMV, and death (respectively, from 44.9%, 39.0% and 39.9% after the first dose to 16.7%, 6.2% and 4.4% after the third dose), as well as significant improvements in survival after each subsequent dose (p < 0.001). CONCLUSIONS: Vaccines were effective in reducing illness severity and death in this cohort of COVID-19 inpatients, and the administration of additional doses conferred them with accumulative vaccine protection.

Are visual assessments of the single-leg squat valid to be used in clinical practice? A systematic review of measurement properties based on the COSMIN guideline.

OBJECTIVE: Evaluate the discriminative and convergent validity of visual scales for the assessment of movement quality in the single-leg squat. METHODS: Searches performed in CINAHL, Cochrane, Embase, PubMed, SPORTDiscus and Web of Science databases. Studies evaluating discriminative and convergent validity of movement quality visual assessments in single-leg squats were included. The COSMIN risk of bias checklist was used to assess the risk of bias, and certainty of evidence was assessed by the GRADE modified version. RESULTS: Ten studies evaluating three different methods of visual assessment of the single-leg squat (Crossley scale; Whatman score and Medial knee displacement) were included. Very low certainty evidence suggests that the Crossley scale had sufficient discriminative validity for patient-centred outcomes. Very low to moderate certainty evidence suggests that the three visual methods of assessment of the single-leg squat had insufficient discriminative validity for surrogate outcomes and groups. None of the three methods had the convergent validity assessed. CONCLUSION: The Crossley scale exhibited sufficient discriminative validity for patient-centred outcomes, although the evidence supporting this conclusion is of very low certainty. Visual scales for the assessment of the single-leg squat movement quality should be used with caution in clinical practice as most methods had insufficient discriminative validity and no reports of convergent validity.

The emergence of hybrid cellulose nanomaterials as promising biomaterials.

Cellulose nanomaterials (CNs) are promising green materials due to their unique properties as well as their environmental benefits. Among these materials, cellulose nanofibrils (CNFs) and nanocrystals (CNCs) are the most extensively researched types of CNs. While they share some fundamental properties like low density, biodegradability, biocompatibility, and low toxicity, they also possess unique differentiating characteristics such as morphology, rheology, aspect ratio, crystallinity, mechanical and optical properties. Therefore, numerous comparative studies have been conducted, and recently, various studies have reported the synergetic advantages resulting from combining CNF and CNC. In this review, we initiate by addressing the terminology used to describe combinations of these and other types of CNs, proposing "hybrid cellulose nanomaterials" (HCNs) as the standardized classifictation for these materials. Subsequently, we briefly cover aspects of properties-driven applications and the performance of CNs, from both an individual and comparative perspective. Next, we comprehensively examine the potential of HCN-based materials, highlighting their performance for various applications. In conclusion, HCNs have demonstraded remarkable success in diverse areas, such as food packaging, electronic devices, 3D printing, biomedical and other fields, resulting in materials with superior performance when compared to neat CNF or CNC. Therefore, HCNs exhibit great potential for the development of environmentally friendly materials with enhanced properties.

Monocyte-to-lymphocyte ratio as predictor of cancer therapy-related cardiotoxicity in patients with breast cancer: a pilot cohort study.

BACKGROUND: Elevated pre-treatment baseline inflammation has been associated with cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer. Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and systemic immune-inflammation index (NLR × platelets) have emerged in clinical context as markers of disease-related inflammation. OBJECTIVES: To evaluate development of CTRCD according to pre-treatment blood inflammatory biomarkers in patients with breast cancer. METHODS: Pilot cohort study including consecutive female patients ≥ 18 years with HER2-positive early breast cancer who consulted at the institution's breast oncology outpatient clinic between march/2019 and march/2022. CTRCD: absolute reduction in LVEF > 10% to below 53% (2D-echocardiogram). Survival analysis was performed using Kaplan-Meier curves, compared by the log-rank test, and discrimination ability was evaluated through AUC-ROC. RESULTS: Forty-nine patients (53.3 ± 13.3 y) were included and followed-up for a median of 13.2 months. CTRCD was observed in 6 (12.2%) patients. Patients with high blood inflammatory biomarkers had lower CTRCD-free survival (P < 0.050 for all). MLR showed statistically significant AUC (0.802; P = 0.017). CTRCD was observed in 27.8% of patients with high MLR versus 3.2% with low MLR (P = 0.020); negative predictive value was 96.8% (95%CI 83.3-99.4%). CONCLUSION: In patients with breast cancer, elevated pre-treatment inflammatory markers were associated with increased risk of cardiotoxicity. Among these markers, MLR had good discriminatory performance and high negative predictive value. The incorporation of MLR might improve risk evaluation and selection of patients for follow-up during cancer therapy.

Epidemiology of laryngeal cancer in Brazil: Historical data from 2000 to 2019.

INTRODUCTION: To determine the incidence, morbidity, and mortality rate of laryngeal cancer in two decades and its epidemiological, clinical, and histological characteristics by sex in Brazil. METHODS: This ecological study used three reliable sources of secondary data: population- and hospital-based cancer registries and the national mortality database. All data available from 2000 to 2019 were considered. RESULTS: The incidence of male laryngeal cancer decreased from 9.20 to 4.95 per 100,000 from 2000 to 2018, while mortality slightly decreased from 3.37 to 3.30 per 100,000 from 2000 to 2019. In the same period, the female incidence decreased from 1.26 to 0.48 per 100,000; however, mortality slightly increased from 0.34 to 0.36 per 100,000. Of 221,566 individuals with head and neck cancer, 27 % presented laryngeal cancer. The median age was 61 years (54-69), and most individuals were male (86.6 %), smokers (66.2 %), diagnosed with locally advanced cancer (66.7 %), and squamous cell carcinoma as the main histological type (93.2 %). Male tended to be older (p < 0.001), white (p < 0.001), smokers (p < 0.001), and present late treatment initiation (p < 0.001) and early death (p < 0.001) compared with female. CONCLUSION: The male laryngeal cancer affected mainly at productive age but with a decreased incidence, probably due to a reduction in smoking habit. However, mortality did not change, which may be explained by the late diagnosis and lack of access to radiotherapy.

Molecular BCR::ABL1 Quantification and ABL1 Mutation Detection as Essential Tools for the Clinical Management of Chronic Myeloid Leukemia Patients: Results from a Brazilian Single-Center Study.

Chronic myeloid leukemia (CML) is a well-characterized oncological disease in which virtually all patients possess a translocation (9;22) that generates the tyrosine kinase BCR::ABL1 protein. This translocation represents one of the milestones in molecular oncology in terms of both diagnostic and prognostic evaluations. The molecular detection of the BCR::ABL1 transcription is a required factor for CML diagnosis, and its molecular quantification is essential for assessing treatment options and clinical approaches. In the CML molecular context, point mutations on the ABL1 gene are also a challenge for clinical guidelines because several mutations are responsible for tyrosine kinase inhibitor resistance, indicating that a change may be necessary in the treatment protocol. So far, the European LeukemiaNet and the National Comprehensive Cancer Network (NCCN) have presented international guidelines on CML molecular approaches, especially those related to BCR::ABL1 expression. In this study, we show almost three years' worth of data regarding the clinical treatment of CML patients at the Erasto Gaertner Hospital, Curitiba, Brazil. These data primarily comprise 155 patients and 532 clinical samples. BCR::ABL1 quantification by a duplex-one-step RT-qPCR and ABL1 mutations detection were conducted. Furthermore, digital PCR for both BCR::ABL1 expression and ABL1 mutations were conducted in a sub-cohort. This manuscript describes and discusses the clinical importance and relevance of molecular biology testing in Brazilian CML patients, demonstrating its cost-effectiveness.