Effects of trichlorfon on ecotoxicological biomarkers in farmed Colossoma macropomum (tambaqui).

Producers of fish have been looking for viable alternatives for the management of Colossoma macropomum (tambaqui) in confinement systems in order to avoid the harm and subsequent losses caused by parasitic diseases. One alternative used by farmers is pesticides, such as trichlorfon, which has a genotoxic effect. Thus, this study aimed to evaluate the changes in gene expression due to the side effects of trichlorfon in tambaqui. Two treatments were used based on LC50-96h of 0.870 mg/L using 30% and 50% trichlorfon with exposure periods of 48, 72 and 96 h. For differential expression of the genes in the liver, real-time PCR was performed for the AChE, GST, CYP2J6, CYP2C8, 18S and GAPDH genes. After 96 h of exposure to trichlorfon, an alteration in the gene expression profile of the antioxidant defense system (GST) of the tambaqui was observed. It was also observed that this organophosphate did not affect the expression of genes related to the isoenzymes that are responsible for the biotransformation of xenobiotics in phase I (2J6 and 2C8) and cholinesterase AChE. It was concluded that the reduction in gene expression of GST suggests a decrease in metabolization capacity in phase II.

Distribution of triglyceride-rich lipoproteins and their remnants and their contribution to cardiovascular risk in the Mexican population.

BACKGROUND AND AIMS: In recent years, scientific interest in triglyceride-rich lipoproteins (TRL) and remnant cholesterol has increased, focusing on the evidence that these lipoproteins are a causal factor for developing atherosclerotic cardiovascular disease (ASCVD). Furthermore, a high remnant concentration (>38 mg/dL) has been associated with several non-cardiovascular risks. We aimed in this study to describe the percentile distribution of remnant cholesterol. Additionally, we evaluated the association between remnant cholesterol plasma concentration and epidemiologically relevant cardio-metabolic outcomes such as hypertension, type 2 diabetes (T2D), and ASCVD. METHODS: We analyzed data from 9,591 adults from the National Survey of Health and Nutrition (ENSANUT) 2018 with fasting blood samples and complete medical history questionnaires. We built multivariate models to evaluate the association between chronic diseases and blood remnant concentration. To compare our 2018-sub-sample against a population reference, we used the NHANES (2005-2014) publicly available datasets by ethnicity. RESULTS: Remnants were independently associated with cardiovascular risk, diabetes, hypertension, obesity, and metabolic syndrome. For all outcomes, the blood remnant concentration was a stronger predictor than LDL. At all deciles, the blood remnant concentration was higher in ENSANUT-2018. CONCLUSIONS: A remnant blood concentration above 38 mg/dL was highly prevalent among Mexicans. Remnants were significantly associated with a higher risk of diabetes, hypertension, obesity, and cardiovascular risk. This association occurred independently of other lipid markers.

Prospective comparison of acute severe toxicities between smokers and non-smokers during radiotherapy for head and neck cancers.

BACKGROUND AND PURPOSE: The association between smoking and acute radiation toxicities of head and neck cancer (HNC) is currently unproven. The aim of the study was to compare the occurrence of acute severe toxicity between active and non-active smokers treated for HNC by radiotherapy. MATERIALS AND METHODS: A prospective monocentric cohort study included patients treated by (chemo)radiotherapy for HNC from January 2021 to January 2023. Smoking status was recorded. Patients underwent a medical exam weekly during the radiotherapy to report acute toxicities according to the Common Terminology Criteria for Adverse Effects system version 5.0. Primary endpoint was the occurrence of at least one grade ≥ 3 acute toxicity among mucositis, dysphagia and dermatitis. RESULTS: Among the 102 patients included, 27.4 % were active smokers, 58.8 % were former smokers and 13.7 % had never smoked. Regarding toxicity, 23.5 % (n = 24) patients experienced severe mucositis, 37.2 % (n = 38) severe dysphagia, 13.7 % (n = 14) severe dermatitis and 54.9 % (n = 56) experienced at least one of them. Occurrence of severe acute toxicity was not statistically associated with smoking during radiotherapy (64.3 % among active smokers versus 51.3 % among non-active smokers; p = 0.24). On multivariate analysis, concurrent chemotherapy (87.5 % vs 65.2 %; OR = 5.04 [1.64-15.52]; p = 0.004) and 2.12 Gy versus 2 Gy fractionation schedule (64.3 % vs 41.3 %; OR = 2.53 [1.09-5.90]; p = 0.03) were significantly associated with severe acute toxicity. CONCLUSION: This study did not find an association between smoking during radiotherapy for HNC and occurrence of severe acute toxicities.

A case of self-improving collodion ichthyosis associated with a rare variant of the ALOX12B gene.

Collodion baby is usually a manifestation of autosomal recessive congenital ichthyosis, a heterogeneous group of congenital hyperkeratotic genodermatoses with highly variable severity and genetic background. Herein, we report a case of self-improving collodion ichthyosis, a rare subtype of autosomal recessive congenital ichthyosis, characterized by an almost-complete spontaneous resolution of symptoms.

Time-to-treatment initiation for cutaneous melanoma reflects disparities in healthcare access in Brazil: a retrospective study.

OBJECTIVES: This study aimed at identifying the sociodemographic and first treatment characteristics affecting time-to-treatment initiation (TTI) of patients with cutaneous melanoma assisted by the Brazilian Unified Health System (SUS). STUDY DESIGN: Retrospective observational study using cutaneous melanoma cases recorded in the Brazilian Hospital-Based Cancer Registries (HBCR). METHODS: A total of 12,783 cutaneous melanoma cases were included in the analysis. Based on the legislation, TTI in Brazil is 60 days; therefore, the cohort was dichotomized into TTI within 60 days and over. The association among variables was evaluated through the Chi-squared test. Kaplan-Meier method and log-rank hypothesis test were used to determine the probability of initiating treatment within 60 days. Cox proportional hazards regression model was used for multivariate analysis. RESULTS: Median TTI was 28 days (95% CI, 25-29). First treatment in SUS provided more than 60 days after diagnosis (34.8%) was associated with females; low level of formal education; living or getting treatment in northern Brazil; being diagnosed in SUS and treated at different healthcare facilities, in addition to starting treatment with radiotherapy or systemic therapy. There were no significant differences in access to health care before and after the enactment of the 60-day law. CONCLUSION: Increased TTI for cutaneous melanoma is associated with sociodemographic and first treatment characteristics in Brazil; approximately one-third of cases did not have access to first treatment within the period established by law. Receiving the diagnosis and treatment at different healthcare facilities (transitions in care) is the main independent factor associated with TTI longer than 60 days.

Dupilumab for atopic dermatitis: a real-world Portuguese multicenter retrospective study.

INTRODUCTION: Atopic dermatitis (AD) is a difficult-to-treat inflammatory skin disease with a high impact on patients' quality of life. Dupilumab, an IL-4 and IL-13 inhibitor, was the first monoclonal antibody approved for the treatment of moderate-to-severe AD and is currently approved in patients aged 6 or older. METHODS: This is a nationwide, multicenter, retrospective, 48-week study designed by the Portuguese Group of AD to assess real-world efficacy and safety of dupilumab for the treatment of AD. RESULTS: A total of 169 patients were enrolled, with a mean disease duration of 22.75 (±11.98) years. The percentage of patients achieving an improvement of at least 75% in Eczema Area and Severity Index (EASI) compared to baseline (EASI75 response) at weeks 12 and 48 was 67.6% and 74.1%, respectively. In the same timepoints, 25.0% and 44.1% achieved an EASI90 response. Patient-reported outcome measures also improved throughout the study period. Regarding safety, 32.0% of the patients developed adverse events, with conjunctivitis (26.6%), persistent facial erythema (4.7%), and arthritis/arthralgia (3.6%) as the more frequently reported. CONCLUSION: Data from real-world populations are crucial to guide clinicians in their daily decisions. This study provides data demonstrating that dupilumab is an effective and safe therapeutic option for AD.

Street-level implementers of population-based oral health policies: the case of water fluoridation supply in Brazil's small towns.

BACKGROUND: Knowledge of conditions influencing the performance of street-level operators when implementing population-based policies could increase the understanding of local implementation dynamics. OBJECTIVE: We analyzed how street-level operators claim to act to implement fluoridation policy in the water treatment units of small Brazilian municipalities and identified conditions shaping behavior against adherence to policy. METHODS: A case study using narratives obtained through in-depth interviews with key informants in two pairs of municipalities with contrasting levels of implementation. Analysis identified themes in the data and in the street-level bureaucracy literature. RESULTS: Institutional characteristics such as administrative fragility of local entities, low priority given locally to policy, poor physical structure of the water treatment plants, isolated working relations, low effectiveness of monitoring devices, and local actors' uncertainties about the policy favored the expansion of the discretionary power of street-level operators configuring important barriers for water fluoridation. CONCLUSION: These data highlight the complexity of policy implementation and inform policymakers about the importance of inter-federal and inter-sectoral coordination when implementing population-based health policies in small towns.

Familial hypercholesterolemia: Is there a role for PCSK9 and thrombin generation?

INTRODUCTION: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease. The prevalence of FH has previously been reported as 1 in 500 in the general population. This study aimed to evaluate the proprotein convertase subtilisin/kexin 9 (PCSK9) levels, lipid profile and thrombin generation in FH patients undergoing treatment or not. METHODS: Eighty individuals with FH were selected and distributed in 2 groups: individuals treated with statins alone or conjugate therapy (statin + ezetimibe) (T = 53) and those non treated (NT = 27). PCSK9 levels were determined by ELISA, the lipid profile by colorimetric enzyme method and thrombin generation assay (TGA) by CAT method. RESULTS: Individuals treated with conjugate therapy (statin + ezetimibe) showed a significant reduction in the levels of total cholesterol (TC) low density lipoprotein cholesterol (LDLc) and in the potential for thrombin generation (ETP with low and high concentration of tissue factor), compared to the treated individuals with monotherapy (statins). PCSK9 was positively correlated with increased levels of TC, LDLc and triglycerides, while TGA parameters were positively correlated with PCSK9 and lipid profile. CONCLUSION: PCSK9 levels appear to be associated with components of the lipid and hemostatic profiles, in addition to being influenced by age. In general, our findings suggest that combined therapy for the treatment of FH is associated with a significant improvement in both lipid and hemostatic profiles assessed by TGA, suggesting a reduction in atherogenic and thrombogenic risks and, therefore, more promising compared to the use of statin monotherapy.

Impact of total variation minimization in volume rendering visualization of breast tomosynthesis data.

BACKGROUND AND OBJECTIVE: Total Variation (TV) minimization algorithms have achieved great attention due to the virtue of decreasing noise while preserving edges. The purpose of this work is to implement and evaluate two TV minimization methods in 3D. Their performance is analyzed through 3D visualization of digital breast tomosynthesis (DBT) data with volume rendering. METHODS: Both filters were studied with real phantom and one clinical DBT data. One algorithm was applied sequentially to all slices and the other was applied to the entire volume at once. The suitable Lagrange multiplier used in each filter equation was studied to reach the minimum 3D TV and the maximum contrast-to-noise ratio (CNR). Imaging blur was measured at 0° and 90° using two disks with different diameters (0.5 mm and 5.0 mm) and equal thickness. The quality of unfiltered and filtered data was analyzed with volume rendering at 0° and 90°. RESULTS: For phantom data, with the sequential filter, a decrease of 25% in 3D TV value and an increase of 19% and 30% in CNR at 0° and 90°, respectively, were observed. When the filter is applied directly in 3D, TV value was reduced by 35% and an increase of 36% was achieved both for CNR at 0° and 90°. For the smaller disk, variations of 0% in width at half maximum (FWHM) at 0° and a decrease of about 2.5% for FWHM at 90° were observed for both filters. For the larger disk, there was a 2.5% increase in FWHM at 0° for both filters and a decrease of 6.28% and 1.69% in FWHM at 90° with the sequential filter and the 3D filter, respectively. When applied to clinical data, the performance of each filter was consistent with that obtained with the phantom. CONCLUSIONS: Data analysis confirmed the relevance of these methods in improving quality of DBT images. Additionally, this type of 3D visualization showed that it may play an important complementary role in DBT imaging. It allows to visualize all DBT data at once and to analyze properly filters applied to all the three dimensions. Concise Abstract Total Variation (TV) minimization algorithms are one compressed sensing technique that has achieved great attention due to the virtue of decrease noise while preserve edges transitions. The purpose of this work is to solve the same TV minimization problem in DBT data, by studying two 3D filters. The obtained results were analyzed at 0° and 90° with a 3D visualization through volume rendering. The filters differ in their application. One considers a slice-by-slice optimization, sequentially traversing all slices of the data. The other considers the intensity values of adjacent slices to make this optimization on each voxel. The performance of each filter was also tested with a clinical case. The results obtained were very encouraging with a significantly increased contrast to noise ratio at 0° and 90° and a small reduction in blur at 90° (slight reduction of the out-of-plane artifact).

Stroke in systemic lupus erythematosus: epidemiology, mechanism, and long-term outcome.

OBJECTIVE: To determine stroke prevalence, mechanisms, and long-term outcome in a cohort of Hispanic patients with systemic lupus erythematosus (SLE). METHODS: We analyzed demographical data, the timing between SLE diagnosis and stroke onset, stroke type, recurrence, and outcomes from an institutional database of 4451 patients with SLE followed from 1993 to 2018. RESULTS: We observed 139 strokes (3.1%), for an incidence rate of 1.25 per 1000 person-years: 81 (58.3%) acute ischemic stroke (AIS), 19 (13.7%) subarachnoid hemorrhage (SAH), 17 (12.2%) cerebral venous thrombosis, 13 (9.4%) intracerebral hemorrhage (ICH), and 9 (6.5%) transient ischemic attack. Median time from SLE diagnosis to acute stroke was 60 months (interquartile range 12-132 months). AIS had a bimodal presentation with 26% occurring within the first year and 30% >10 years after SLE diagnosis. In contrast, 75% of ICH cases occurred >3 years (and 34% >10 years) after SLE diagnosis. The most important cause of AIS was secondary antiphospholipid syndrome (48%). Hypertension was associated with 69% of ICH cases, while aneurysmal rupture was observed in 78% of SAH cases. Excellent recovery at hospital discharge was observed in 65%. Stroke recurrence was observed in 7%. The long-term all-cause fatality rate was 8%. CONCLUSIONS: The prevalence of stroke in this cohort was 3.1%. Ischemic strokes had a bimodal presentation, occurring either early after SLE diagnosis or after a several-year delay. Half of the hemorrhagic strokes occurred >10 years after the diagnosis of SLE. Clinical outcome was usually good with a relatively low recurrence rate.

¿Existe respuesta diferente a los distintos inhibidores de PCSK9? / Are there different responses to different PCSK9 inhibitors?

Planteamos un paciente de 62 años que precisa tratamiento hipolipemiante con inhibidor de la proproteína convertasa subtilisina/kexina tipo9 (PCSK9) en el que empíricamente decidimos cambiar un fármaco a otro de los dos disponibles en la actualidad, obteniendo diferente respuesta. Nuestro objetivo es transmitir nuestra experiencia y reflexionar sobre una posible opción terapéutica en los pacientes en los que excepcionalmente esto pudiera ocurrir

The case is presented of a 62-year-old patient who required lipid-lowering therapy with proprotein convertase subtilisin/kexin type9 (PCSK9). It was empirically decided to change one drug to another of the two currently available, obtaining a different response. Our objective is to present our experience and to consider a possible therapeutic option in patients in whom, exceptionally, this could happen

[Are there different responses to different PCSK9 inhibitors?] / ¿Existe respuesta diferente a los distintos inhibidores de PCSK9?

The case is presented of a 62-year-old patient who required lipid-lowering therapy with proprotein convertase subtilisin/kexin type9 (PCSK9). It was empirically decided to change one drug to another of the two currently available, obtaining a different response. Our objective is to present our experience and to consider a possible therapeutic option in patients in whom, exceptionally, this could happen.

Degradation of the diuretic hydrochlorothiazide by UV/Solar radiation assisted oxidation processes.

The objective of this study was to analyse the effectiveness of advanced oxidation processes (AOPs) with Solar and UV radiation (UV/H2O2, UV/K2S2O8) for the degradation of hydrochlorothiazide (HCTZ), a widely used diuretic drug, in aqueous solution focusing on the influence of four experimental parameters: initial concentration of HCTZ, solution pH, nature of the water matrix, and initial concentration of radicals. The obtained results showed that using both kinds of direct photolysis (UV and Solar), the percentage of degraded HCTZ was low, but there was a decrease in the degradation rate favored by the increase of the initial concentration of this pollutant. In addition, the degradation rates were higher at acid pHs. With regard to the nature of water, the degradation rate varied in the order: ultrapure > superficial > tap water. This is due to the presence of organic and inorganic matter (bicarbonates, nitrates, and chlorides) in surface and tap water, that react with the radicals generated, which reduces the availability of radical species, generating competitive kinetics. The presence of radical-promoter species increased the degradation rate of the pollutant, reaching a degradation of 100% of HCTZ after 20 min of treatment. The results obtained point out that the degradation rate was higher in the presence of HO radicals. This behavior was attributed to the higher oxidation power of HO versus radicals. The determination of the degradation by-products led to structures very similar to the parent compound. For example, the corresponding hydroxylated dechlorinated derivative of HCTZ was found in all the systems used. The cytotoxicity test showed that these byproducts have a lower toxicity than the original product. Finally, the economic viability study confirmed that the UV/K2S2O8 system has the lowest cost.

Position statement: topical calcineurin inhibitors in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease in both adults and children. Whilst topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, have proven efficacy for the treatment of AD, it is important to involve experts to obtain their opinion on its optimal treatment. OBJECTIVE: Using a modified Delphi approach, this project aimed to generate consensus amongst experts on the use of TCIs in the treatment of AD, with a focus on the differentiation between tacrolimus and pimecrolimus. METHODS: Six expert dermatologists from different European countries participated in this project based on their experience with AD and its treatment, which was evaluated by literature analysis and expert opinion. Consensus amongst the experts was generated using a modified Delphi approach, consisting of three distinct phases, during which a web meeting (June 2017), two online rounds of blinded Delphi voting (July-September 2017) and a face-to-face meeting (November 2017) were conducted. The consensus statements concerned two main topics: (i) Background of AD; and (ii) TCIs in AD. Hot topics in the treatment of AD not supported by meta-analysis, clinical trials or large observational studies were also discussed based on clinical experience. RESULTS: In total, 25 consensus statements were defined and validated: eight statements on the general background of AD and 17 statements on the use of TCIs in AD, including their mechanism of action and therapeutic indications in AD, efficacy in adult and paediatric AD patients, pharmacokinetics, incidence of adverse events and safety concerns. Hot topics on the use of TCIs for the treatment of AD included cream vs. ointment, dosages, TCIs contact allergy, burning sensation management, superinfection and vaccination concerns. CONCLUSION: Topical calcineurin inhibitors are a suitable therapy for AD, and selection of the specific TCI should be based on factors which differentiate tacrolimus from pimecrolimus.

Geometry-dependent DNA-TiO2 immobilization mechanism: A spectroscopic approach.

DNA nucleotides are used as a molecular recognition system on electrodes modified to be applied in the detection of various diseases, but immobilization mechanisms, as well as, charge transfers are not satisfactorily described in the literature. An electrochemical and spectroscopic study was carried out to characterize the molecular groups involved in the direct immobilization of DNA structures on the surface of nanostructured TiO2 with the aim of evaluating the influence of the geometrical aspects. X-ray photoelectron spectroscopy at O1s and P2p core levels indicate that immobilization of DNA samples occurs through covalent (POTi) bonds. X-ray absorption spectra at the Ti2p edge reinforce this conclusion. A new species at 138.5eV was reported from P2p XPS spectra analysis which plays an important role in DNA-TiO2 immobilization. The POTi/OTi ratio showed that quantitatively the DNA immobilization mechanism is dependent on their geometry, becoming more efficient for plasmid ds-DNA structures than for PCR ds-DNA structures. The analysis of photoabsorption spectra at C1s edge revealed that the molecular groups that participate in the C1s→LUMO electronic transitions have different pathways in the charge transfer processes at the DNA-TiO2 interface. Our results may contribute to additional studies of immobilization mechanisms understanding the influence of the geometry of different DNA molecules on nanostructured semiconductor and possible impact to the charge transfer processes with application in biosensors or aptamers.