Unraveling the evolutionary origin of the complex Nuclear Receptor Element (cNRE), a cis-regulatory module required for preferential expression in the atrial chamber.

Cardiac function requires appropriate proteins in each chamber. Atria requires slow myosin to act as reservoirs, while ventricles demand fast myosin for swift pumping. Myosins are thus under chamber-biased cis-regulation, with myosin gene expression imbalances leading to congenital heart dysfunction. To identify regulatory inputs leading to cardiac chamber-biased expression, we computationally and molecularly dissected the quail Slow Myosin Heavy Chain III (SMyHC III) promoter that drives preferential expression to the atria. We show that SMyHC III gene states are orchestrated by a complex Nuclear Receptor Element (cNRE) of 32 base pairs. Using transgenesis in zebrafish and mice, we demonstrate that preferential atrial expression is achieved by a combinatorial regulatory input composed of atrial activation motifs and ventricular repression motifs. Using comparative genomics, we show that the cNRE might have emerged from an endogenous viral element through infection of an ancestral host germline, revealing an evolutionary pathway to cardiac chamber-specific expression.

Combination therapy of itraconazole and an acylhydrazone derivative (D13) for the treatment of sporotrichosis in cats.

Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis. IMPORTANCE: This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.

The Dietary Inflammatory Index is associated with diet quality and nutrient intake during the gestational period.

In pregnant women, the Energy-adjusted Dietary Inflammatory Index (E-DII) is adopted to measure the inflammatory potential of the diet, but it does not predict the quality of the diet. Our hypothesis is that a more pro-inflammatory diet during pregnancy is also a poorer quality diet. Thus, the objective of this study is to verify the association of the E-DII with the Diet Quality Index Adapted for Pregnancy (DQI-P) and the nutrient intake from the diet in terms of the second and third gestational trimesters. This is a cross-sectional study that took place in Brazil (2018-2019), with eligible adult women up to 72 hours' postpartum and in good health. Socioeconomic, gestational, anthropometric, and food consumption data were collected, enabling the calculation of E-DII, DQI-P, and nutrient intake. The sample (n = 260) had a median E-DII of 0.04 (-1.30 to 1.90) and DQI-P of 68.82 (18.82-98.22). There was no relevant difference between E-DII tertiles by sociodemographic, gestational, and anthropometric characteristics. The E-DII and the DQI-P showed agreement (55.7%) and inverse correlation (r = -0.53; P < .001). Each 1-unit increase in DQI-P, iron, iodine, magnesium, pyridoxine, and vitamin E decreased the E-DII score (P < .05). An increase of 1 unit in protein, saturated fatty acids, and vitamin C increased the E-DII score (P < .05). Thus, the results suggest that the E-DII can predict diet quality during pregnancy, with the added benefit of measuring the inflammatory potential of the diet.

Chemical characterization, antioxidant activity, and cytotoxicity of fatty acids methyl esters from Handroanthus impetiginosus (Mart. ex DC.) Mattos (Bignoniaceae) seeds.

Handroanthus impetiginosus, popularly known as "ipê-roxo", is used in folk medicine to treat skin inflammations, infections, stomach diseases, and cancer. Fatty acid methyl esters (FAMEs) obtained from the esterification reaction of fatty acids (FA) found in the hexane extract (HE) of seeds of H. impetiginosus were identified by gas chromatography-mass spectrometry (GC-MS). The antioxidant and cytotoxic activities of the HE and FAMEs were evaluated. Methyl palmitate, methyl linoleate, methyl oleate, and methyl stearate were the major FAMEs obtained from the HE. The samples, especially the HE, exhibited a significant antioxidant potential analyzed by ferric reducing ability power (FRAP) assay. In the A. salina larvae bioassay, the HE showed no cytotoxic effects, but the FAMEs exhibited a high toxicity. This study reported, for the first time, the antioxidant and cytotoxic activities of the HE and FAMEs obtained from H. impetiginosus seeds.

Ordered mesoporous silicas for potential applications in solid vaccine formulations

In an effort to develop efficient vaccine formulations, the use of ordered mesoporous silica (SBA-15) as an antigen carrier has been investigated. SBA-15 has required properties such as high surface area and pore volume, including narrow pore size distribution to protect antigens inside its matrix. This study aimed to examine the impact of solvent removal methods, specifically freeze-drying and evaporation on the intrinsic properties of an immunogenic complex. The immunogenic complexes, synthesized and incorporated with BSA, were characterized by various physicochemical techniques. Small Angle X-ray Scattering measurements revealed the characteristic reflections associated to pure SBA-15, indicating the preservation of the silica mesostructured following BSA incorporation and the formation of BSA aggregates within the macropore region. Nitrogen Adsorption Isotherm measurements demonstrated a decrease in surface area and pore volume for all samples, indicating that the BSA was incorporated into the SBA-15 matrix. Fluorescence spectroscopy evidenced that the tryptophan residues in BSA inside SBA-15 or in solution displayed similar spectra, showing the preservation of the aromatic residues’ environment. The Circular Dichroism spectra of BSA in both conditions suggest the preservation of its native secondary structure after the encapsulation process. The immunogenic analysis with the detection of anti-BSA IgG did not give any significant difference between the non-dried, freeze-dried or evaporated groups. However, all groups containing BSA and SBA-15 showed results almost three times higher than the groups with pure BSA (control group). These facts indicate that none of the BSA incorporation methods interfered with the immunogenicity of the complex. In particular, the freeze-dried process is regularly used in the pharmaceutical industry, therefore its adequacy to produce immunogenic complexes was proved Furthermore, the results showed that SBA-15 increased the immunogenic activity of BSA.

Ordered mesoporous silicas for potential applications in solid vaccine formulations.

In an effort to develop efficient vaccine formulations, the use of ordered mesoporous silica (SBA-15) as an antigen carrier has been investigated. SBA-15 has required properties such as high surface area and pore volume, including narrow pore size distribution to protect antigens inside its matrix. This study aimed to examine the impact of solvent removal methods, specifically freeze-drying and evaporation on the intrinsic properties of an immunogenic complex. The immunogenic complexes, synthesized and incorporated with BSA, were characterized by various physicochemical techniques. Small Angle X-ray Scattering measurements revealed the characteristic reflections associated to pure SBA-15, indicating the preservation of the silica mesostructured following BSA incorporation and the formation of BSA aggregates within the macropore region. Nitrogen Adsorption Isotherm measurements demonstrated a decrease in surface area and pore volume for all samples, indicating that the BSA was incorporated into the SBA-15 matrix. Fluorescence spectroscopy evidenced that the tryptophan residues in BSA inside SBA-15 or in solution displayed similar spectra, showing the preservation of the aromatic residues' environment. The Circular Dichroism spectra of BSA in both conditions suggest the preservation of its native secondary structure after the encapsulation process. The immunogenic analysis with the detection of anti-BSA IgG did not give any significant difference between the non-dried, freeze-dried or evaporated groups. However, all groups containing BSA and SBA-15 showed results almost three times higher than the groups with pure BSA (control group). These facts indicate that none of the BSA incorporation methods interfered with the immunogenicity of the complex. In particular, the freeze-dried process is regularly used in the pharmaceutical industry, therefore its adequacy to produce immunogenic complexes was proved Furthermore, the results showed that SBA-15 increased the immunogenic activity of BSA.

High resting energy expenditure in women with episodic migraine: exploring the use of predictive formulas.

Introduction: Migraine is a common and disabling primary headache, and its pathophysiology is not fully understood. Previous studies have suggested that pain can increase humans' Resting Energy Expenditure (REE). However, no previous study has investigated whether the REE of individuals with migraine differs from the general population. Therefore, this study aims to assess whether the REE of women with migraine differs from that of women without headaches. We also tested the accuracy of REE predictive formulas in the migraine patients. Methods: This cross-sectional study involves 131 adult women aged between 18 and 65 years, 83 with migraine and 48 without (controls). We collected clinical, demographic, and anthropometric data. Migraine severity was measured using the Migraine Disability Test and Headache Impact Test, version 6. The REE was measured by indirect calorimetry, and it was compared with the predicted REE calculated by formulas. Results: Patients with migraine had higher REE when compared to controls (p < 0.01). There was a positive correlation between REE and the patient-reported number of migraine attacks per month (Rho = 0.226; p = 0.044). Mifflin-St Jeor and Henry and Rees were the predictive formulas that have more accuracy in predicting REE in women with migraine. Discussion: Considering the benefits of nutritional interventions on treating migraines, accurately measuring REE can positively impact migraine patient care. This study enhances our understanding of the relationship between pain and energy expenditure. Our results also provide valuable insights for healthcare professionals in selecting the most effective predictive formula to calculate energy expenditure in patients with migraine.

Miltefosine: A Repurposing Drug against Mucorales Pathogens.

Mucorales are a group of non-septated filamentous fungi widely distributed in nature, frequently associated with human infections, and are intrinsically resistant to many antifungal drugs. For these reasons, there is an urgent need to improve the clinical management of mucormycosis. Miltefosine, which is a phospholipid analogue of alkylphosphocholine, has been considered a promising repurposing drug to be used to treat fungal infections. In the present study, miltefosine displayed antifungal activity against a variety of Mucorales species, and it was also active against biofilms formed by these fungi. Treatment with miltefosine revealed modifications of cell wall components, neutral lipids, mitochondrial membrane potential, cell morphology, and the induction of oxidative stress. Treated Mucorales cells also presented an increased susceptibility to SDS. Purified ergosterol and glucosylceramide added to the culture medium increased miltefosine MIC, suggesting its interaction with fungal lipids. These data contribute to elucidating the effect of a promising drug repurposed to act against some relevant fungal pathogens that significantly impact public health.

Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains of Candida spp.

Candida species are one of the most concerning causative agents of fungal infections in humans. The treatment of invasive Candida infections is based on the use of fluconazole, but the emergence of resistant isolates has been an increasing concern which has led to the study of alternative drugs with antifungal activity. Sphingolipids have been considered a promising target due to their roles in fungal growth and virulence. Inhibitors of the sphingolipid biosynthetic pathway have been described to display antifungal properties, such as myriocin and aureobasidin A, which are active against resistant Candida isolates. In the present study, aureobasidin A did not display antibiofilm activity nor synergism with amphotericin B, but its combination with fluconazole was effective against Candida biofilms and protected the host in an in vivo infection model. Alterations in treated cells revealed increased oxidative stress, reduced mitochondrial membrane potential and chitin content, as well as altered morphology, enhanced DNA leakage and a greater susceptibility to sodium dodecyl sulphate (SDS). In addition, it seems to inhibit the efflux pump CaCdr2p. All these data contribute to elucidating the role of aureobasidin A on fungal cells, especially evidencing its promising use in clinical resistant isolates of Candida species.

Carbetocin Inhibits Behavioral Sensitization to Ethanol in Male and Female Mice, Independent of Corticosterone Levels.

Oxytocin (OXT), a pro-social peptide, is increasingly recognized as a potential protective substance against drug addiction. In the context of ethanol, previous research has shown OXT's properties in reducing self-administration, alleviating motor impairment in rodents, and reducing craving in humans. However, its role in behavioral sensitization, a neuroadaptive response resulting from repeated drug exposure linked to an increased drug incentive, remains unexplored. OXT is recognized for its role in regulating the hypothalamic-pituitary-adrenal (HPA) axis, in which corticosterone is acknowledged as a significant factor in the development of behavioral sensitization. This study aimed to investigate the effects of carbetocin (CBT), an analogue of OXT, on the expression of behavioral sensitization to ethanol and the concurrent alterations in plasma corticosterone levels in male and female Swiss mice. We also aimed to confirm previous studies on OXT's impact on ethanol consumption in male mice, but with a focus on CBT, using the two-bottle choice model and the drinking in the dark (DID) methodology. For the sensitization study, the mice received either ethanol (1.8 g/kg, i.p.) or saline treatments daily for 15 consecutive days, followed by treatment with carbetocin (0.64 mg/kg, i.p.) or a vehicle for 6 days. Subsequently, on day 22, all the animals underwent an ethanol challenge to assess the expression of behavioral sensitization. The plasma corticosterone levels were measured on days 21 and 22. The CBT effectively prevented the expression of ethanol-induced behavioral sensitization in both male and female subjects, with no alterations having been detected in their corticosterone levels. In the ethanol consumption study, following an initial phase of ethanol acquisition, the male mice underwent a 6-day treatment with CBT i.p. or saline before being re-exposed to ethanol. We also found a reduction in their ethanol consumption due to the CBT treatment. In conclusion, carbetocin emerges as a promising and effective intervention for mitigating ethanol-induced behavioral sensitization and reducing ethanol intake, highlighting its potential significance in alcohol addiction treatment.

Superficial scald development in 'Granny Smith' and 'Nicoter' apples: The role of key volatile compounds when fruit are stored under dynamic controlled atmosphere.

A positive correlation of α-farnesene and its oxidation metabolites with superficial scald is commonly reported in apples stored in air or controlled atmosphere (CA) systems, where O2 levels are above the lower oxygen limit (LOL) tolerated by the fruit. Nevertheless, the LOL can be monitored by the dynamic controlled atmosphere (DCA) techniques and to provide different physiological responses. Therefore, this study aimed to evaluate key volatile metabolites from 'Granny Smith' and 'Nicoter' ('Kanzi®') apples stored under dynamic controlled atmosphere (DCA) monitored by respiratory quotient (RQ), i. e. at extremely low oxygen partial pressures (ELO) and correlate their emissions with the incidence of superficial scald (SS). The volatile compounds (VCs) were isolated by solid phase microextraction (HS-SPME) and analyzed by gas chromatography. For the first time, higher concentrations of α-farnesene and its oxidation metabolites (6-methyl-5-hepten-2-one, and 6-methyl-5-hepten-2-ol) were negatively correlated with SS in DCA-RQ. This is likely due to the higher levels of ethanol in fruit stored under this condition having an inhibitory effect on SS incidence even when α-farnesene, 6-methyl-5-hepten-2-one, and 6-methyl-5-hepten-2-ol accumulate. Additionally, SS is more correlated to internal ethylene concentration (IEC) than α-farnesene accumulation and their metabolites, even when fruit were stored under ELO, where ethylene action is reduced.

Microplastics and microfibers in the Guajará Bay, Amazon delta: Potential sources and variability.

The role of Amazon on the transport and as a source of microplastics (MPs) to the ocean is uncertain. This study is an assessment on the distribution of MPs and microfibers (MFs) in a portion of the Amazon delta. Guajará bay is a potential source for surrounding waters, since a metropolis is located at the right margin. Surface water samples were collected during the dry and rainy season of 2014/2015 at six stations. MP and MF abundance ranged from 218 to 5529.98 (1565.01 ± 196.94) particles·m-3. Transparent, white and blue particles were frequent. Higher values were detected on the right, urbanized margin of the bay (p = 0.0124). Most of the particles were anthropogenic cellulose fibers (68.8 %). Polyethylene terephthalate (52.9 %) and polyamide (34.4 %) were the dominant polymers. Our results indicate higher MP and MF abundances near to the potential source, the urban nucleus, and related to local hydrodynamic characteristics.

Miltefosine repositioning: A review of potential alternative antifungal therapy.

Fungal infections are a global health problem with high mortality and morbidity rates. Available antifungal agents have high toxicity and pharmacodynamic and pharmacokinetic limitations. Moreover, the increased incidence of antifungal-resistant isolates and the emergence of intrinsically resistant species raise concerns about seeking alternatives for efficient antifungal therapy. In this context, we review literature data addressing the potential action of miltefosine (MFS), an anti-Leishmania and anticancer agent, as a repositioning drug for antifungal treatment. Here, we highlight the in vitro and in vivo data, MFS possible mechanisms of action, case reports, and nanocarrier-mediated MFS delivery, focusing on fungal infection therapy. Finally, many studies have demonstrated the promising antifungal action of MFS in vitro, but there is little or no data on antifungal activity in vertebrate animal models and clinical trials, so have a need to develop more research for the repositioning of MFS as an antifungal therapy.

Association between contextual factors and coverage of the Acwy meningococcal vaccine, after three years of its overdue, in the vaccination calendar of adolescents in the state of Minas Gerais, Brazil: global space regressions.

The objective of the study was to analyze the spatial distribution of vaccination coverage of bacterial meningitis vaccine: A, C, W and Y (menacwy) and identify the association between socioeconomic and social environment factors with menacwy vaccine coverage among adolescents in the state of Minas Gerais (MG), Brazil. This is an ecological, mixed study, conducted with secondary data from the 853 municipalities of the State of MG, Brazil, from 2020 to 2022, provided by the information system of the National Immunization Program. For spatial statistical analysis, spatial dependence and the presence of spatial clusters formed by municipalities with high and low vaccination coverage of Menacwy were evaluated. In the year 2021, MG presented the largest vaccination coverage (60.58%) since the introduction of the Menacwy vaccine by the PNI. Regarding the analysis of global regressions, it is observed that for the year 2020, as the MG Index of Social Responsibility-Health increased and MG Index of Social Responsibility-Public Security increased, increased the vaccination coverage of the municipalities of the Menacwy vaccine. Finally, compared to 2021, similar association was observed in relation to the proportion of the population served by the Family Health Strategy of the municipalities of the state of MG and per capita spending on education activities: as this indicator increased, with increased coverage of the Vaccine of the Menacwy vaccine of the state municipalities. They reinforce the importance of assessing the quality-of-care management and health surveillance system, professional training, and damage reduction to populations, especially adolescents.

The influence of neighborhood safety and built environment on childhood obesity: isolated and combined effect of contextual factors.

This study aims to analyze the isolated and combined effect of objective measures concerning neighborhood safety, food, and physical activity environments on students' obesity. This is a cross-sectional study conducted with 9- and 10-year-old children enrolled in the municipal education network of a Brazilian metropolis. Environment objective measures comprised neighborhood unsafety (annual criminality and road traffic accident rates), availability of public parks and spaces for physical activity practicing, and index of establishments that predominantly sell ultra-processed food. Euclidean buffers of 1,000m around the children's house were used as eligible geographic units. This study adopted the Principal Component Analysis and Generalized Estimation Equation models. Stratified analyses were conducted based on neighborhood unsafety and on child's family income. In total, 717 students were assessed, 12.2% of them were children with obesity. The latent variable of the obesogenic environment (deduced by environment unsafety rates and the index of establishments that predominantly sell ultra-processed food) was a risk factor for obesity in children with lower socioeconomic levels (OR = 2.37; 95%CI: 1.06-5.19). Public parks and spaces for physical activity practicing were protective factors against childhood obesity only in locations recording the lowest environment unsafety rates (OR = 0.30; 95%CI: 0.09-0.94). Based on our findings, social conditions change the effect of the environment on childhood obesity, reinforcing the relevance of inter-sectoral policies and strategies against this condition.

A Review of Software and Mobile Apps to Support the Clinical Diagnosis of Hansen Disease.

This scoping review indicates a lack of scientific articles that specifically explore software and mobile applications designed to assist in the clinical diagnosis of leprosy, and our findings have provided insights into the available tools, their usage methods, and the benefits offered by health technologies.

Detection of adulteration in Eragrostis tef (Zucc.) Trotter flour using EDXRF and ComDim-MLR data fusion.

The teff cereal gained worldwide attention because it is gluten-free and rich in iron; thus, its flour is subject to fraud. This study evaluated the ability of Energy Dispersive X-Ray Fluorescence Spectroscopy (EDXRF) to identify teff flours adulterated with rice, whole wheat, oat, and rye flours. The adulteration followed a {5,4} simplex-lattice design. After smoothing and pretreatments, 15 kV and 50 kV spectra were fused by Common Dimension Analysis (ComDim). Multiple Linear Regression (MLR) models using EDXRF-ComDim scores and percentage of teff were adjusted. The best model presented four common dimensions (CD), r2prediction = 0.8534, low RMSEP (0.0564), and absence of overfitting. The obtained model was robust to quantify adulteration in teff flour even with the differences in the intensity of EDXRF spectra of different crops. Therefore, EDXRF, in tandem with ComDim data fusion, was an efficient tool for the adulteration control of teff flours.

Inclusion complex of O-allyl-lawsone with 2-hydroxypropyl-ß-cyclodextrin: Preparation, physical characterization, antiparasitic and antifungal activity.

The subclass naphthoquinone represents a substance group containing several compounds with important activities against various pathogenic microorganisms. Accordingly, we evaluated O-allyl-lawsone (OAL) antiparasitic and antifungal activity free and encapsulated in 2-hydroxypropyl-ß-cyclodextrin (OAL MKN) against Trypanosoma cruzi and Sporothrix spp. OAL and OAL MKN were synthesized and characterized by physicochemical methods. The IC50 values of OAL against T. cruzi were 2.4 µM and 96.8 µM, considering epimastigotes and trypomastigotes, respectively. At the same time, OAL MKN exhibited a lower IC50 value (0.5 µM) for both trypanosome forms and low toxicity for mammalian cells. Additionally, the encapsulation showed a selectivity index approximately 240 times higher than that of benznidazole. Regarding antifungal activity, OAL and OAL MKN inhibited Sporothrix brasiliensis growth at 16 µM, while Sporothrix schenckii was inhibited at 32 µM. OAL MKN also exhibited higher selectivity toward fungus than mammalian cells. In conclusion, we described the encapsulation of O-allyl-lawsone in 2-hydroxypropyl-ß-cyclodextrin, increasing the antiparasitic activity compared with the free form and reducing the cytotoxicity and increasing the selectivity towardSporothrix yeasts and the T. cruzi trypomastigote form. This study highlights the potential development of this inclusion complex as an antiparasitic and antifungal agent to treat neglected diseases.

Evaluation of Nutrient Consumption for the Prevention of Chronic Diseases in Health Promotion Services: A Controlled and Randomized Community Trial to Promote Fruits and Vegetables.

To evaluate the effectiveness of a collective intervention to encourage the consumption of fruits and vegetables on the nutrients intake for the prevention of chronic non-communicable diseases (NCDs), a randomized controlled community trial was conducted with a representative sample from the Health Academy Program. While the individuals in the control group (CG) participated in regular physical exercise, those in the intervention group (IG) also participated in a collective intervention. After 12 months, IG and CG showed a reduction in energy, omega 3 and sodium intake and an increase in the consumption of carbohydrates, fiber, vitamins, and minerals. Individuals from the CG showed an increase in phosphorus consumption and, in the IG, a reduction in the consumption of total, saturated, and polyunsaturated fats as well as an increase in the consumption of monounsaturated fats was seen. In both groups, there was an increase in the prevalence of adequate nutrients. Participation in the nutritional intervention was associated with lower consumption of energy and protein in the diet. The results pointed to the importance of individuals' participation in the program, which, associated with nutritional intervention, promoted an improvement in the nutrient profile of the diet and the prevention and control of NCDs.