Effects of calcium supplementation on changes in the IL2, IL4, IL6, IL10 axes and oxidative stress in pregnant women at risk for pre-eclampsia.

BACKGROUND: Pregnant women with hypertensive disorders are at increased risk for inflammatory diseases and oxidative stress. The dilemma raised by the best dosage of calcium supplementation on these factors is evident. The aim of the current study was to examine the effects of calcium on biomarkers of the purinergic system, inflammation and oxidative stress, which are factors contributing to vascular damage in pregnant women at high risk of pre-eclampsia. METHODS: A prospective, double-blind and placebo-controlled study conducted with 101 women at risk of pre-eclampsia were randomized to take 500 mg calcium/day or 1,500 mg calcium/day or placebo for 6 weeks from the 20th gestational week until delivery. Fasting blood samples were collected at the beginning of the study and 6 weeks after the intervention. RESULTS: Taking calcium supplements (500 mg calcium/day) led to a significant increase in ATP hydrolysis (p < 0.05), NTPDase activity with increased hydrolysis of ADP and AMP nucleotides in platelets and lymphocytes. In the intragroup analysis IL-2, IL-6, IL-4 and interferon-É£ presented lower values in the calcium 1,500 mg/day group (p < 0.005). Oxidative stress was assessed by TBARS pro-oxidant marker, with an increase for the calcium groups when compared to the placebo group. The Vitamin C antioxidant marker presented a significant increase (p < 0.005) for the group that received high calcium doses. CONCLUSIONS: Calcium administration for 6 weeks had antioxidant action and positively modulated the purinergic system and inflammatory markers in pregnant women at risk of pre-eclampsia.

[Calculation of the alcohol per capita consumption in Brazil: using national dataCálculo del indicador del consumo de alcohol per cápita en Brasil: uso de datos nacionales]. / Cálculo do indicador de consumo de álcool per capita no Brasil: uso de dados nacionais.

Objective: To calculate the alcohol per capita consumption (APC) in Brazil (Brazil APC) using national data and to establish the Brazil APC as gold standard for the country, replacing the indicator previously calculated by the World Health Organization (WHO) based on international data. Method: The Brazilian public data sources necessary for calculating the recorded APC were selected, and the alcohol concentration was defined by beverage category. For the variables of tourist APC and unrecorded APC, which are unavailable in Brazil, estimates from the United Nations (UN) and the WHO were used. The Brazil APC indicator was calculated and compared to the indicator produced by the WHO through analysis of the medians obtained for the period from 2005 to 2020. Results: The national alcohol consumption indicator was 9.2 liters per capita in 2005, reaching 9.8 in 2020. The WHO indicator showed a consumption of 8.4 liters per capita in 2005, decreasing until 2016 and slightly increasing to 7.8 in 2020. Conclusion: The Brazil APC was calculated based on national sources and showed a distinct trend compared to the WHO indicator, which showed a decrease. The regular and transparent provision of this indicator through government channels will support the development of policies to address alcohol consumption in the country.

Objetivo: Calcular el indicador del consumo de alcohol per cápita en Brasil a partir de datos nacionales, con miras a establecerlo como patrón de referencia para el país en sustitución del indicador calculado anteriormente por la Organización Mundial de la Salud a partir de datos internacionales. Métodos: Se seleccionaron las fuentes públicas de datos de Brasil necesarias para estructurar el cálculo del consumo de alcohol per cápita registrado y se definió la concentración de alcohol por clase de bebida. Para las variables de consumo de alcohol per cápita por parte de turistas y consumo per cápita no registrado, que no están disponibles en Brasil, se utilizaron estimaciones de las Naciones Unidas y de la Organización Mundial de la Salud. Se calculó el indicador del consumo de alcohol per cápita en Brasil y se comparó con el indicador elaborado por la OMS mediante un análisis de las medianas correspondientes al período 2005-2020. Resultados: El indicador nacional del consumo de alcohol fue de 9,2 litros per cápita en el 2005, con un aumento a 9,8 en el 2020. El indicador de la Organización Mundial de la Salud mostró un consumo de 8,4 litros per cápita en el 2005, con una reducción hasta el 2016 y un leve aumento a 7,8 en el 2020. Conclusión: Se calculó el consumo de alcohol per cápita en Brasil a partir de fuentes nacionales, lo que mostró una tendencia distinta de la tendencia descendente del indicador de la Organización Mundial de la Salud. La disponibilidad transparente y regular de este indicador por medio de los canales gubernamentales permitirá su seguimiento, con lo cual se podrán formular políticas para enfrentar el consumo de alcohol en el país.

Toxicity of Trixis vauthieri DC essential oil on Lutzomyia longipalpis (Diptera, Psychodidae, Phlebotominae), a proven vector of visceral leishmaniasis in Brazil.

BACKGROUND OBJECTIVES: In Brazil, one of the visceral leishmaniasis control measures in urban environments is the elimination of Lutzomyia longipalpis, which occurs through the application of pyrethroid insecticides with residual action in homes and outbuildings. Due to the loss of sensitivity of this vector to these insecticides, the search for more efficient insecticide compounds against L. longipalpis has been intensified. The objective of this work was to evaluate the toxicity of Trixis vauthieri essential oil on adult sandflies of the species L. longipalpis, and identify the phytochemical composition of these essential oils. METHODS: Essential oils from leaves collected from T. vauthieri at different times were obtained at concentrations of 5, 10 and 20 mg/mL. Twenty sandflies were exposed to the essential oils and the mortality was evaluated after 1, 2, 4, 16, 24, 48 and 72 h. The chemical constituents of the essential oil were also identified. RESULTS: The essential oils of T. vauthieri at a concentration of 20 mg/mL were the most toxic to sandflies, reaching a mortality rate of 98.33% and 95%, respectively, after 72 h of exposure. The analysis of chemical constituents revealed the presence of triterpenes and/or steroids, tannins, flavonoids, alkaloids, saponins and coumarins. INTERPRETATION CONCLUSION: The results obtained suggest that T. vauthieri essential oil is fairly promising as an insecticidal potential against L. longipalpis. A more detailed analysis of the oil's phytochemical composition is necessary to identify active and pure compounds that can be used in vector control of visceral leishmaniasis.

Supercritical fluid technology as a sustainable alternative method for textile dyeing: An approach on waste, energy, and CO2 emission reduction.

The clothing industry is considered one of the most polluting industries on the planet due to the high consumption of water, energy, chemicals/dyes, and high generation of solid waste and effluents. Faced with environmental concerns, the textile ennoblement sector is the most critical of the textile production chain, especially the traditional dyeing processes. As an alternative to current problems, dyeing with supercritical CO2 (scCO2) has been presented as a clean and efficient process for a sustainable textile future. Supercritical fluid dyeing (SFD) has shown a growing interest due to its significant impact on environmental preservation and social, economic, and financial gains. The main SFD benefits include economy and reuse of non-adsorbed dyes; reduction of process time and energy expenditure; capture of atmospheric CO2 (greenhouse gas); use and recycling of CO2 in SFD; generation of carbon credits; water-free process; effluent-free process; reduction of CO2 emission and auxiliary chemicals. Despite being still a non-scalable and evolving technology, SFD is the future of dyeing. This review presented a comprehensive overview of the environmental impacts caused by traditional processes and confronted the advantages of SFD. The SFD technique was introduced, along with its latest advances and future perspectives. Financial and environmental gains were also discussed.

Yellow Fever Vaccine-Associated Viscerotropic Disease among Siblings, São Paulo State, Brazil.

We describe 5 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) in 2 familial clusters during the 2017-2018 yellow fever (YF) vaccination campaign in São Paulo state, Brazil. The first case was that of a 40-year-old white man who died of icterohemorrhagic syndrome, which was confirmed to be YEL-AVD by using real-time reverse transcription PCR to detect 17DD YF vaccine in the liver. Ten years previously, his brother died of a clinically similar disease without a confirmed diagnosis 9 days after YF vaccination. The second cluster included 3 of 9 siblings in whom hepatitis developed in the first week after receiving fractionated doses of YF vaccine. Two of them died of hemorrhagic diathesis and renal and respiratory failure, and 17DD-YF vaccine was detected in serum samples from all patients and in the liver in 1 case. Genetic factors might play a substantial role in the incidence of YEL-AVD.

Comparative analysis of photobiomodulation therapy and transcutaneous electrical nerve stimulation for burning mouth: a randomized clinical trial.

OBJECTIVE: To compare the effect of photobiomodulation (PBM) and transcutaneous electrical nerve stimulation (TENS) in the treatment of burning mouth. MATERIALS AND METHODS: Randomized clinical trial of 25 patients with burning mouth treated by TENS (n=12) and PBM (n=13). The patients were treated weekly for 8 weeks. Two-factor ANOVA was used to determine whether the two interventions promoted significant differences in symptoms (measured with a visual analogue scale), unstimulated salivary flow, xerostomia, and dysgeusia between T0 (baseline), T1 (after the 4th treatment session), T2 (after the 8th treatment session), and T3 (30 days after the end of treatment). RESULTS: Intragroup comparison of VAS scores for pain showed a significant difference between T0xT1, T0xT2, and T0xT3 in the TENS group and between T0xT2 and T0xT3 in the PBM group (p˂0.001). Intergroup comparison of VAS scores for pain between T2xT3 showed a better response to PBM than to TENS (p=0.003). Patients of the TENS group showed an increase in salivary flow between T1 and T2 (p=0.052). There were no expressive variations in xerostomia or dysgeusia in the two groups analyzed. CONCLUSION: TENS and PBM were effective in reducing the symptoms of burning mouth during and after treatment. The PBM group showed a better response during follow-up. TRIAL REGISTRATION: This clinical trial was registered at http://clinicaltrials.gov (Number: NCT05816200). CLINICAL RELEVANCE: TENS was found to be a safe and effective therapy for burning mouth. Trial registration number (TRN) and date of registration: This clinical trial was registered at http://clinicaltrials.gov (Number: NCT05816200; date: May 08, 2023).

High-intensity interval training is not superior to continuous aerobic training in reducing body fat: A systematic review and meta-analysis of randomized clinical trials.

Background/Objective: Guidelines on obesity management reinforce regular exercise to reduce body fat. Exercise modalities, including high-intensity interval training (HIIT), appear to produce a similar effect to continuous aerobic training (CAT) on body fat. However, they have not addressed the chronic effect of HIIT vs. CAT on body fat assessed by dual energy X-ray absorptiometry (DEXA). Thus, we compared the effectiveness of CAT vs. HIIT protocols on body fat (absolute or relative) (%BF) and abdominal visceral fat reduction, assessed by DEXA, in adults with overweight and obesity. Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) including both female or male adults with excess body weight. We performed searches in the databases MEDLINE (PubMed), EMBASE, Scopus, LILACS, Web of Science and Cochrane. Results: In our analysis (11 RCTs), we found no greater benefit on %BF of HIIT vs. CAT (MD -0.55%, 95% CI -1.42 to 0.31; p = 0.209). As for abdominal visceral fat, no training modality was superior (SMD: -0.05, 95% CI -0.29 to 0.19; p = 0.997). Regarding secondary outcomes (body weight, BMI, VO2 max, glycemic and lipid profiles), HIIT shows greater benefit than CAT in increasing VO2 max and fasting blood glucose and reducing total cholesterol. Conclusion: HIIT is not superior to CAT in reducing %BF or abdominal visceral fat in individuals characterized by excess weight. However, HIIT showed beneficial effects on cardiorespiratory fitness, total cholesterol and fasting blood glucose when compared to CAT.

Effectiveness of CPP-ACP and fluoride products in tooth remineralization.

OBJECTIVES: To compare the effectiveness of the casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP) in the in situ remineralization of enamel exposed with two different degrees of preformed enamel lesions. METHODS: One hundred and sixty 3 × 3 × 2 mm human enamel slabs were demineralized and divided into two subgroups according to the baseline surface hardness (SH = B1≤150 and B2 >150). During each of four 10-day experimental periods, 10 participants wore intra-oral removable acrylic palatal expanders with four human enamel slabs with preformed lesions (B1 and B2): CO1 and CO2-Control: silica dentifrice without fluoride; MP1 and MP2: MI Paste; MPP1 and MPP2: MI Paste Plus; and FD1 and FD2: Fluoride dentifrice. The Knoop hardness test (50/15s Micromet 2001, Buehler) was performed after demineralization (B1 and B2) and after treatment (T1 and T2). RESULTS: SH was higher in all treatment groups, when compared with the controls, except for CO2 (Mann-Whitney Wilcoxon Test; p < 0.05). The %SH was similar between MPP2 and FD2 and between MPP2 and MP2; however, FD2 and MPP2 products were more effective in microhardness recovery. In B1, all treatment groups were similar. CONCLUSION: MPP and FD are more effective in preventing demineralization in enamel subsurface lesions.

Investigation of the anti-inflammatory effects of stigmasterol in mice: insight into its mechanism of action.

Stigmasterol is a phytosterol that presents pharmacologic properties. However, its anti-inflammatory mechanism and antinociceptive effect are not yet elucidated. Thus, the present study aimed to investigate the anti-inflammatory and antinociceptive activities of stigmasterol and its mechanism of action in mice. The antinociceptive activity was assessed by the acetic acid-induced writhing test, formalin test, and hot plate test. The anti-inflammatory activity was investigated by carrageenan-induced peritonitis and paw edema induced by arachidonic acid. The involvement of glucocorticoid receptors in the mechanism of stigmasterol anti-inflammatory action was investigated by molecular docking, also by pretreating mice with RU-486 (glucocorticoid receptor antagonist) in the acetic acid-induced writhing test. Mice motor coordination was evaluated by the rota-rod test and the locomotor activity by the open field test. The lowest effective dose of stigmasterol was standardized at 10 mg/kg (p.o.). It prevented abdominal writhes and paw licking, but it did not increase the latency time in the hot plate test, suggesting that stigmasterol does not show an antinociceptive effect in response to a thermal stimulus. Stigmasterol decreased leukocyte infiltration in peritonitis assay and reduced paw edema elicited by arachidonic acid. Molecular docking suggested that stigmasterol interacts with the glucocorticoid receptor. Also, RU-486 prevented the effect of stigmasterol in the acetic-acid abdominal writhing test, which might indicate the contribution of glucocorticoid receptors in the mechanism of stigmasterol action. Stigmasterol reduced the number of crossings but did not impair mice's motor coordination. Our results show that stigmasterol presents anti-inflammatory effects probably mediated by glucocorticoid receptors.

Mango and carrot mixed juice: a new matrix for the vehicle of probiotic lactobacilli.

This study evaluated the pH, acidity, soluble solids, color, dietary fiber, sensory acceptance and the viability of Lactobacillus rhamnosus, Lactobacillus plantarum and Lactobacillus acidophilus in mango and carrot mixed juices. In addition, this study verified the resistance of L. plantarum that presented greater viability to the gastrointestinal tract simulated in vitro. Three formulations were elaborated (varying the pulps concentration) and the products were stored at 8 °C for 35 days. No difference was found in the total soluble solids and color of the products during storage time at 8 °C. A reduction in pH and an increase in acidity were observed in all samples during storage, probably due to the fermentative action of probiotics, which negatively influenced acceptance after 35 days of storage. On the other hand, juices with a higher concentration of mango pulp were more accepted and may be a strategy to improve the acceptance of fermented juices. Microorganisms showed greater viability in juices that had higher amount of carrot pulp, probably due to the higher fiber content in these samples. During the 35-day shelf life, all juices with L. plantarum maintained counts above 7 log CFU mL-1 after gastrointestinal conditions simulation. Therefore, mango and carrot mixed juice showed to be as a good vehicle for probiotic bacteria and meets the needs of consumers looking for functional, healthy, non-dairy and low-sugar foods.

Insights Into the Controversial Aspects of Adiponectin in Cardiometabolic Disorders.

In 2016, the World Health Organization estimated that more than 1.9 billion adults were overweight or obese. This impressive number shows that weight excess is pandemic. Overweight and obesity are closely associated with a high risk of comorbidities, such as insulin resistance and its most important outcomes, including metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Adiponectin has emerged as a salutary adipocytokine, with insulin-sensitizing, anti-inflammatory, and cardiovascular protective properties. However, under metabolically unfavorable conditions, visceral adipose tissue-derived inflammatory cytokines might reduce the transcription of the adiponectin gene and consequently its circulating levels. Low circulating levels of adiponectin are negatively associated with various conditions, such as insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. In contrast, several recent clinical trials and meta-analyses have reported high circulating adiponectin levels positively associated with cardiovascular mortality and all-cause mortality. These results are biologically intriguing and counterintuitive, and came to be termed "the adiponectin paradox". Adiponectin paradox is frequently associated with adiponectin resistance, a concept related with the downregulation of adiponectin receptors in insulin-resistant states. We review this contradiction between the apparent role of adiponectin as a health promoter and the recent evidence from Mendelian randomization studies indicating that circulating adiponectin levels are an unexpected predictor of increased morbidity and mortality rates in several clinical conditions. We also critically review the therapeutic perspective of synthetic peptide adiponectin receptors agonist that has been postulated as a promising alternative for the treatment of metabolic syndrome and type 2 diabetes mellitus.

Development of a mixed jussara and mango juice with added Lactobacillus rhamnosus GG submitted to sub-lethal acid and baric stresses.

This study evaluated the interference of sub-lethal acid (SLA) stress and high isostatic pressure (HIP) stress on the survival of Lactobacillus rhamnosus GG (LGG) in mixed jussara and mango juice with the pH adjusted to 3.0 and 3.5, during 90 days of storage at 6 °C. The SLA stress at pH 4.0 previously applied to the LGG cells had no effect on the survival of this bacterium in mixed jussara and mango juices. On the other hand, the application of 200 MPa/5 min/25 °C treatment to LGG cells was shown to be efficient in the cross protection of this bacterium in an acid medium. Pressures above 400 MPa/5 min/25 °C caused a reduction in the viability in an acid medium and lower pressures (< 100 MPa) showed similar results compared to control treatment in the LGG survival. No changes in pH, acidity and soluble solids were observed in mixed juices. In addition, these products showed elevated levels of anthocyanins, phenolic compounds and antioxidant capacity. This highlights the capacity of the HIP process to promote the cross protection of LGG in an acid medium.

Computational MitoTarget Scanning Based on Topological Vacancies of Single-Walled Carbon Nanotubes with the Human Mitochondrial Voltage-Dependent Anion Channel (hVDAC1).

We present an in silico approach for modeling the noncovalent interactions between the human mitochondrial voltage-dependent anion channel (hVDAC1) and a family of single-walled carbon nanotubes (SWCNTs) with a defined pattern of topological vacancies ( v = 1-16), obtained by removing atoms from the SWCNT surface. The general results showed more stable docking interaction complexes (SWCNT-hVDAC1), with more negative Gibbs free energy of binding affinity values, and a strong dependence on the vacancy number ( R2 = 0.93) and vacancy formation energy ( R2 = 0.96). In addition, for most of the SWCNT vacancies that were analyzed, the interatomic distances for the interactions of the SWCNT-hVDAC1 complex with the functional catalytic residues (i.e., Pro7, Gln199, Gln182, Phe181, Val20, Asp19, Lys15, Gly14, Asp12, Ala11, and Arg18) that form the hVDAC1 active site (i.e., the voltage-sensing N-terminal α-helix segment) were very similar to or shorter than the interatomic distances of these residues for ATP-hVDAC1 interactions. In particular, the hVDAC1 residues that can be phosphorylated like Tyr10, Tyr198, and Se16 were significantly perturbed by the interactions with SWCNT with at least nine vacancies. In addition, the SWCNT vacancy family members can affect the flexibility properties of the hVDAC1 N-terminal α-helix segment inducing different patterns of local perturbations in inter-residue communication. Finally, vacancy quantitative structure-binding relationships (V-QSBRs) were unveiled for setting up a robust model that can predict the strength of docking interactions between SWCNTs with a specific topological vacancy and hVDAC1. The developed V-QSBR model classified properly all of the SWCNTs with a different number of SWCNT vacancies with exceptional sensitivity and specificity (both equal to 100%), indicating a strong potential to unequivocally predict the influence of SWCNT vacancies on the mitochondrial channel interactions.

Spilanthol, the Principal Alkylamide from Acmella oleracea, Attenuates 5-Fluorouracil-Induced Intestinal Mucositis in Mice.

Mucositis is one of the commonest side effects in cancer patients undergoing treatment with radiotherapy and/or chemotherapy, and it currently lacks appropriate and effective treatment. Acmella oleracea, a species of flowering herb from South America, contains spilanthol, an alkylamide that has several pharmacological properties, including anesthetic, analgesic, and anti-inflammatory activities. Therefore, the purpose of this work was to evaluate the effect of spilanthol in intestinal mucositis in Swiss mice induced by 5-fluorouracil (5-FU), an antineoplastic agent administered systemically for the treatment of many different cancers. The repeated administration of 5-FU resulted in intestinal mucositis and consequent decreased food intake, together with weight loss, in all the animals. Daily administration of spilanthol significantly lowered the severity of intestinal mucositis, reducing histopathological changes and increasing the villus height in the animals treated with spilanthol at a dosage of 30 mg/kg (p < 0.0044) compared to a group exposed only to 5-FU. A decrease of myeloperoxidase activity was also observed in the animals treated with 30 mg/kg of spilanthol (p < 0.05), although several pro-inflammatory cytokines were not quantifiable in any group. In conclusion, the data demonstrated that spilanthol effectively reduced inflammation in a mouse model of intestinal mucositis induced by 5-FU, and that the compound might be a promising therapeutic candidate for the prevention and treatment of this condition.

Fludroxycortide cream as an alternative therapy for actinic cheilitis.

OBJECTIVES: The objective of the study is to assess, by clinical follow-up, the efficacy of the dermatological cream Fludroxycortide 0.125 mg/g (Drenison®) in the treatment of actinic cheilitis (AC). MATERIAL AND METHODS: Twenty-three patients diagnosed with AC participated in the study. Fifteen were submitted to corticotherapy with Fludroxycortide, applied three times a day for up to 6 weeks, associated with lip sunscreen (LS) before sun exposure. In the control group of eight patients, only the use of LS was established. At each weekly return, a photographic record was made of the lesion. After treatment, images were evaluated and scores were assigned to verify clinical evolution. Also, patients treated with Fludroxycortide responded to a questionnaire, to assess drug tolerability and treatment satisfaction. RESULTS: In the group treated with Fludroxycortide (n = 15), five patients showed total improvement, seven presented partial improvement, and three showed no clinical change. Concerning the patients treated with LS (n = 8), one presented total remission of the clinical lesion characteristics, four exhibited partial improvement, and three exhibited no clinical lip alteration. No case presented symptom worsening. Of the 15 patients undergoing corticotherapy, 12 were satisfied and reported that the product was not irritating and contributed to lesion improvement. CONCLUSIONS: Conventional treatment with LS was effective in the remission of some AC lesions, but treatment responses were improved when associated with Fludroxycortide, especially in the more severe cases. CLINICAL RELEVANCE: As it is a non-invasive therapy leading, in most cases, to adequate clinical results, safety, and tolerability, Fludroxycortide can be considered an effective alternative treatment for AC.

Factors associated with common mental disorders and use of psychiatric drugs in cancer outpatients.

BACKGROUND: Considering the high incidence of cancer in Brazil and worldwide, the high prevalence and relevance of Common Mental Disorders (CMD) in the treatment of cancer patients, and the use of psychiatric drugs without reliably proven effectiveness, studies that contemplate this topic are needed to understand and provide rationale for the treatment of CMD in these individuals. OBJECTIVES: This study identified prevalence and factors associated with Common Mental Disorders (CMD) and psychotropic use in cancer outpatients. METHOD: This is a cross-sectional study with descriptive correlational design. It was developed in the chemotherapy sector of a hospital specialized in cancer. The tools used were: Self Reporting Questionnaire (SRQ-20) and structured questionnaires. FINDINGS: Among 403 respondents, CMD prevalence was 31.5% and psychotropic use was 25.8%. CMD were associated with gender, education, family income, psychotropic use and cancer surgery. Psychotropic use was associated with gender, employment status, cancer surgery, treatment period and other physical health conditions. Logistic regressions showed CMD were associated with gender and other physical health conditions; psychotropic use was associated with gender, employment status and other conditions.

Suppression of a single BAHD gene in Setaria viridis causes large, stable decreases in cell wall feruloylation and increases biomass digestibility.

Feruloylation of arabinoxylan (AX) in grass cell walls is a key determinant of recalcitrance to enzyme attack, making it a target for improvement of grass crops, and of interest in grass evolution. Definitive evidence on the genes responsible is lacking so we studied a candidate gene that we identified within the BAHD acyl-CoA transferase family. We used RNA interference (RNAi) silencing of orthologs in the model grasses Setaria viridis (SvBAHD01) and Brachypodium distachyon (BdBAHD01) and determined effects on AX feruloylation. Silencing of SvBAHD01 in Setaria resulted in a c. 60% decrease in AX feruloylation in stems consistently across four generations. Silencing of BdBAHD01 in Brachypodium stems decreased feruloylation much less, possibly due to higher expression of functionally redundant genes. Setaria SvBAHD01 RNAi plants showed: no decrease in total lignin, approximately doubled arabinose acylated by p-coumarate, changes in two-dimensional NMR spectra of unfractionated cell walls consistent with biochemical estimates, no effect on total biomass production and an increase in biomass saccharification efficiency of 40-60%. We provide the first strong evidence for a key role of the BAHD01 gene in AX feruloylation and demonstrate that it is a promising target for improvement of grass crops for biofuel, biorefining and animal nutrition applications.

Diclofenac sodium gel therapy as an alternative to actinic cheilitis.

OBJECTIVE: Actinic cheilitis (AC) is a potentially malignant lesion caused by prolonged exposure to ultraviolet light. The aim of this research was to analyze the efficacy of diclofenac sodium 3% gel in the treatment of this condition, through clinical follow-up. METHODS: Thirty-one patients diagnosed with AC were instructed to perform a topical application of the gel three times a day for a period of 90 days. In each visit, a digital photography was obtained for verified progress and response to treatment. Two researchers evaluated all images after treatment was completed and assigned the following scores regarding clinical aspect of the lip: 1, complete improvement; 2, partial improvement; 3, no changes; 4, worsening of the clinical condition. In addition, the patients' tolerability to the drug and their satisfaction after treatment were evaluated. RESULTS: Twelve cases abandoned the treatment for reasons unrelated to the study. Ten participants showed total remission of all clinical features of the lesion and three had partial improvement of the characteristics. One participant presented worsening of clinical condition, and in five cases, treatment was discontinued due to development of mild adverse effects at the site of gel application. Regarding satisfaction analyses and tolerability to the drug, from 14 patients who completed treatment without adverse effects or complications, most agreed fully that they were satisfied with the therapy (n = 11) and that the drug was not irritating to the mouth (n = 9). Patients are being monitored without clinical signs of recurrence and/or progression of the lesions. CONCLUSION: Topical application of the drug has provided a convenient and well tolerated in most cases. CLINICAL RELEVANCE: Diclofenac sodium gel (3%) may be a promising alternative for treatment of actinic cheilitis.

Nortriptyline inhibits aggregation and neurotoxicity of alpha-synuclein by enhancing reconfiguration of the monomeric form.

The pathology of Parkinson's disease and other synucleinopathies is characterized by the formation of intracellular inclusions comprised primarily of misfolded, fibrillar α-synuclein (α-syn). One strategy to slow disease progression is to prevent the misfolding and aggregation of its native monomeric form. Here we present findings that support the contention that the tricyclic antidepressant compound nortriptyline (NOR) has disease-modifying potential for synucleinopathies. Findings from in vitro aggregation and kinetics assays support the view that NOR inhibits aggregation of α-syn by directly binding to the soluble, monomeric form, and by enhancing reconfiguration of the monomer, inhibits formation of toxic conformations of the protein. We go on to demonstrate that NOR inhibits the accumulation, aggregation and neurotoxicity of α-syn in multiple cell and animal models. These findings suggest that NOR, a compound with established safety and efficacy for treatment of depression, may slow progression of α-syn pathology by directly binding to soluble, native, α-syn, thereby inhibiting pathological aggregation and preserving its normal functions.

Real-time in vivo monitoring of magnetic nanoparticles in the bloodstream by AC biosusceptometry.

BACKGROUND: We introduce and demonstrate that the AC biosusceptometry (ACB) technique enables real-time monitoring of magnetic nanoparticles (MNPs) in the bloodstream. We present an ACB system as a simple, portable, versatile, non-invasive, and accessible tool to study pharmacokinetic parameters of MNPs, such as circulation time, in real time. We synthesized and monitored manganese doped iron oxide nanoparticles in the bloodstream of Wistar rats using two different injection protocols. Aiming towards a translational approach, we also simultaneously evaluated cardiovascular parameters, including mean arterial pressure, heart rate, and episodes of arrhythmia in order to secure the well-being of all animals. RESULTS: We found that serial injections increased the circulation time compared with single injections. Immediately after each injection, we observed a transitory drop in arterial pressure, a small drop in heart rate, and no episodes of arrhythmia. Although some cardiovascular effects were observed, they were transitory and easily recovered in both protocols. CONCLUSIONS: These results indicate that the ACB system may be a valuable tool for in vivo, real-time MNP monitoring that allows associations with other techniques, such as pulsatile arterial pressure and electrocardiogram recordings, helping ensuring the protocol safety, which is a fundamental step towards clinical applications.