Quantifying gaps in the tuberculosis care cascade in Brazil: A mathematical model study using national program data.

BACKGROUND: In Brazil, many individuals with tuberculosis (TB) do not receive appropriate care due to delayed or missed diagnosis, ineffective treatment regimens, or loss-to-follow-up. This study aimed to estimate the health losses and TB program costs attributable to each gap in the care cascade for TB disease in Brazil. METHODS AND FINDINGS: We constructed a Markov model simulating the TB care cascade and lifetime health outcomes (e.g., death, cure, postinfectious sequelae) for individuals developing TB disease in Brazil. We stratified the model by age, human immunodeficiency virus (HIV) status, drug resistance, state of residence, and disease severity, and developed a parallel model for individuals without TB that receive a false-positive TB diagnosis. Models were fit to data (adult and pediatric) from Brazil's Notifiable Diseases Information System (SINAN) and Mortality Information System (SIM) for 2018. Using these models, we assessed current program performance and simulated hypothetical scenarios that eliminated specific gaps in the care cascade, in order to quantify incremental health losses and TB diagnosis and treatment costs along the care cascade. TB-attributable disability-adjusted life years (DALYs) were calculated by comparing changes in survival and nonfatal disability to a no-TB counterfactual scenario. We estimated that 90.0% (95% uncertainty interval [UI]: 85.2 to 93.4) of individuals with TB disease initiated treatment and 10.0% (95% UI: 7.6 to 12.5) died with TB. The average number of TB-attributable DALYs per incident TB case varied across Brazil, ranging from 2.9 (95% UI: 2.3 to 3.6) DALYs in Acre to 4.0 (95% UI: 3.3 to 4.7) DALYs in Rio Grande do Sul (national average 3.5 [95% UI: 2.8 to 4.1]). Delayed diagnosis contributed the largest health losses along the care cascade, followed by post-TB sequelae and loss to follow up from TB treatment, with TB DALYs reduced by 71% (95% UI: 65 to 76), 41% (95% UI: 36 to 49), and 10% (95% UI: 7 to 16), respectively, when these factors were eliminated. Total health system costs were largely unaffected by improvements in the care cascade, with elimination of treatment failure reducing attributable costs by 3.1% (95% UI: 1.5 to 5.4). TB diagnosis and treatment of false-positive individuals accounted for 10.2% (95% UI: 3.9 to 21.7) of total programmatic costs but contributed minimally to health losses. Several assumptions were required to interpret programmatic data for the analysis, and we were unable to estimate the contribution of social factors to care cascade outcomes. CONCLUSIONS: In this study, we observed that delays to diagnosis, post-disease sequelae and treatment loss to follow-up were primary contributors to the TB burden of disease in Brazil. Reducing delays to diagnosis, improving healthcare after TB cure, and reducing treatment loss to follow-up should be prioritized to improve the burden of TB disease in Brazil.

SAnDReS 2.0: Development of machine-learning models to explore the scoring function space.

Classical scoring functions may exhibit low accuracy in determining ligand binding affinity for proteins. The availability of both protein-ligand structures and affinity data make it possible to develop machine-learning models focused on specific protein systems with superior predictive performance. Here, we report a new methodology named SAnDReS that combines AutoDock Vina 1.2 with 54 regression methods available in Scikit-Learn to calculate binding affinity based on protein-ligand structures. This approach allows exploration of the scoring function space. SAnDReS generates machine-learning models based on crystal, docked, and AlphaFold-generated structures. As a proof of concept, we examine the performance of SAnDReS-generated models in three case studies. For all three cases, our models outperformed classical scoring functions. Also, SAnDReS-generated models showed predictive performance close to or better than other machine-learning models such as KDEEP, CSM-lig, and ΔVinaRF20. SAnDReS 2.0 is available to download at https://github.com/azevedolab/sandres.

The NADase CD38 is a central regulator in gouty inflammation and a novel druggable therapeutic target.

OBJECTIVES: Cellular NAD+ declines in inflammatory states associated with increased activity of the leukocyte-expressed NADase CD38. In this study, we tested the potential role of therapeutically targeting CD38 and NAD+ in gout. METHODS: We studied cultured mouse wild type and CD38 knockout (KO) murine bone marrow derived macrophages (BMDMs) stimulated by monosodium urate (MSU) crystals and used the air pouch gouty inflammation model. RESULTS: MSU crystals induced CD38 in BMDMs in vitro, associated with NAD+ depletion, and IL-1ß and CXCL1 release, effects reversed by pharmacologic CD38 inhibitors (apigenin, 78c). Mouse air pouch inflammatory responses to MSU crystals were blunted by CD38 KO and apigenin. Pharmacologic CD38 inhibition suppressed MSU crystal-induced NLRP3 inflammasome activation and increased anti-inflammatory SIRT3-SOD2 activity in macrophages. BMDM RNA-seq analysis of differentially expressed genes (DEGs) revealed CD38 to control multiple MSU crystal-modulated inflammation pathways. Top DEGs included the circadian rhythm modulator GRP176, and the metalloreductase STEAP4 that mediates iron homeostasis, and promotes oxidative stress and NF-κB activation when it is overexpressed. CONCLUSIONS: CD38 and NAD+ depletion are druggable targets controlling the MSU crystal- induced inflammation program. Targeting CD38 and NAD+ are potentially novel selective molecular approaches to limit gouty arthritis.

Predictors of unsuccessful tuberculosis treatment outcomes in Brazil: an analysis of 259,484 patient records.

INTRODUCTION: Tuberculosis (TB) causes over 1 million deaths annually. Providing effective treatment is a key strategy for reducing TB deaths. In this study, we identified factors associated with unsuccessful treatment outcomes among individuals treated for TB in Brazil. METHODS: We obtained data on individuals treated for TB between 2015 and 2018 from Brazil's National Disease Notification System (SINAN). We excluded patients with a history of prior TB disease or with diagnosed TB drug resistance. We extracted information on patient-level factors potentially associated with unsuccessful treatment, including demographic and social factors, comorbid health conditions, health-related behaviors, health system level at which care was provided, use of directly observed therapy (DOT), and clinical examination results. We categorized treatment outcomes as successful (cure, completed) or unsuccessful (death, regimen failure, loss to follow-up). We fit multivariate logistic regression models to identify factors associated with unsuccessful treatment. RESULTS: Among 259,484 individuals treated for drug susceptible TB, 19.7% experienced an unsuccessful treatment outcome (death during treatment 7.8%, regimen failure 0.1%, loss to follow-up 11.9%). The odds of unsuccessful treatment were higher with older age (adjusted odds ratio (aOR) 2.90 [95% confidence interval: 2.62-3.21] for 85-100-year-olds vs. 25-34-year-olds), male sex (aOR 1.28 [1.25-1.32], vs. female sex), Black race (aOR 1.23 [1.19-1.28], vs. White race), no education (aOR 2.03 [1.91-2.17], vs. complete high school education), HIV infection (aOR 2.72 [2.63-2.81], vs. no HIV infection), illicit drug use (aOR 1.95 [1.88-2.01], vs. no illicit drug use), alcohol consumption (aOR 1.46 [1.41-1.50], vs. no alcohol consumption), smoking (aOR 1.20 [1.16-1.23], vs. non-smoking), homelessness (aOR 3.12 [2.95-3.31], vs. no homelessness), and immigrant status (aOR 1.27 [1.11-1.45], vs. non-immigrants). Treatment was more likely to be unsuccessful for individuals treated in tertiary care (aOR 2.20 [2.14-2.27], vs. primary care), and for patients not receiving DOT (aOR 2.35 [2.29-2.41], vs. receiving DOT). CONCLUSION: The risk of unsuccessful TB treatment varied systematically according to individual and service-related factors. Concentrating clinical attention on individuals with a high risk of poor treatment outcomes could improve the overall effectiveness of TB treatment in Brazil.

Abnormal neurovascular control during central and peripheral chemoreceptors stimulation in heart failure patients with preserved ejection fraction.

PURPOSE: Central and peripheral chemoreceptors are hypersensitized in patients with heart failure with reduced ejection fraction. Whether this autonomic alteration occurs in patients with heart failure with preserved ejection fraction (HFpEF) remains little known. We test the hypothesis that the central and peripheral chemoreflex control of muscle sympathetic nerve activity (MSNA) is altered in HFpEF. METHODS: Patients aged 55-80 years with symptoms of heart failure, body mass index ≤ 35 kg/m2, left ventricular ejection fraction > 50%, left atrial volume index > 34 mL/m2, left ventricular early diastolic filling velocity and early diastolic tissue velocity of mitral annulus ratio (E/e' index) ≥ 13, and BNP levels > 35 pg/mL were included in the study (HFpEF, n = 9). Patients without heart failure with preserved ejection fraction (non-HFpEF, n = 9), aged-paired, were also included in the study. Peripheral chemoreceptors stimulation (10% O2 and 90% N2, with CO2 titrated) and central chemoreceptors stimulation (7% CO2 and 93% O2) were conducted for 3 min. MSNA was evaluated by microneurography technique, and forearm blood flow (FBF) by venous occlusion plethysmography. RESULTS: During hypoxia, MSNA responses were greater (p < 0.001) and FBF responses were lower in patients with HFpEF (p = 0.006). Likewise, MSNA responses during hypercapnia were higher (p < 0.001) and forearm vascular conductance (FVC) levels were lower (p = 0.030) in patients with HFpEF. CONCLUSIONS: Peripheral and central chemoreflex controls of MSNA are hypersensitized in patients with HFpEF, which seems to contribute to the increase in MSNA in these patients. In addition, peripheral and central chemoreceptors stimulation in patients with HFpEF causes muscle vasoconstriction.

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.

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.

Loss of S-nitrosoglutathione reductase disturbs phytohormone homeostasis and regulates shoot side branching and fruit growth in tomato.

S-Nitrosoglutathione plays a central role in nitric oxide (NO) homeostasis, and S-nitrosoglutathione reductase (GSNOR) regulates the cellular levels of S-nitrosoglutathione across kingdoms. Here, we investigated the role of endogenous NO in shaping shoot architecture and controlling fruit set and growth in tomato (Solanum lycopersicum). SlGSNOR silencing promoted shoot side branching and led to reduced fruit size, negatively impacting fruit yield. Greatly intensified in slgsnor knockout plants, these phenotypical changes were virtually unaffected by SlGSNOR overexpression. Silencing or knocking out of SlGSNOR intensified protein tyrosine nitration and S-nitrosation and led to aberrant auxin production and signaling in leaf primordia and fruit-setting ovaries, besides restricting the shoot basipetal polar auxin transport stream. SlGSNOR deficiency triggered extensive transcriptional reprogramming at early fruit development, reducing pericarp cell proliferation due to restrictions on auxin, gibberellin, and cytokinin production and signaling. Abnormal chloroplast development and carbon metabolism were also detected in early-developing NO-overaccumulating fruits, possibly limiting energy supply and building blocks for fruit growth. These findings provide new insights into the mechanisms by which endogenous NO fine-tunes the delicate hormonal network controlling shoot architecture, fruit set, and post-anthesis fruit development, emphasizing the relevance of NO-auxin interaction for plant development and productivity.

Hospitalizations of children and adolescents with complex chronic conditions in Brazil: a temporal analysis from 2009 to 2020.

Access to advanced and sophisticated health technologies made it possible to increase the survival of children with complex chronic conditions. Thus, the profile of pediatric patients admitted to hospitals has changed in recent decades. In Brazil, there are few epidemiological studies on this subject. This study aims to evaluate the main characteristics and temporal trend of hospital admissions of children and adolescents with complex chronic conditions in Brazil, 2009-2020. This is a cross-sectional study with data on hospitalizations of children and adolescents with complex chronic conditions, extracted from the Hospital Information System of the Unified Health System, 2009-2020, in the 26 Brazilian states and the Federal District. The analysis included descriptive statistics and a generalized linear model. From 2009 to 2020, there were 1,337,120 hospitalizations of children and adolescents with complex chronic conditions, and of these, 735,820 (55.0%) were male. The percentage of hospital deaths during the analyzed period was 4.0%. The most recurrent diagnostic category was malignancy (41.0%), with an annual incidence increase of 2.61 (95% CI: 1.16-4.05). Between 2009 and 2019, the increase in hospitalizations for complex chronic conditions was 27.4% for boys and 25.2% for girls, and the reductions in the number of hospitalizations for other causes were 15.4% and 11.9% for boys and girls, respectively.  Conclusions: Hospitalizations for complex chronic conditions in pediatrics are increasing in Brazil. This increase is a new challenge for the Brazilian public health system. What is Known: • The profile of pediatric patients admitted to hospitals has changed in recent decades, with a reduction in the total number of hospitalizations, but with an increase in the complexity and costs of these hospitalizations. • The world's scientific production on CCC is concentrated in the United States health care system. Epidemiological studies on the topic in universal health care systems are scarce. What is New: • This is the first study that evaluated the temporal trend of hospitalizations of children and adolescents with CCC in Brazil. • Hospitalizations for CCC in pediatrics are increasing in Brazil, with emphasis on the condition of malignancy, higher incidence in males and in children under one year of age. Furthermore, our study found a decrease in hospitalizations for other pediatric causes.

Validity and Reliability of Pain and Behavioral Scales for Preterm Infants: A Systematic Review.

OBJECTIVE: To systematically review the instruments used to assess behavior, stress, and/or pain in preterm newborns in the neonatal intensive care unit (NICU) and verify the validity and reliability of these instruments. DATA SOURCES: Electronic searches were conducted in PubMed/MEDLINE, Cochrane Library, Web of Science, Scientific Electronic Library Online (SciELO), Latin American and Caribbean Literature on Health Sciences (LILACS), and EBSCOhost Research Platform. 12,295 records were found. REVIEW/ANALYSIS METHODS: 37 studies met the inclusion and exclusion criteria.  The COnsensus-based Standards for selecting health Measurement INstruments (COSMIN) checklist was used to assess the quality assessment and measurement properties. RESULTS: We identified 25 scales that assessed behavior, pain, and/or stress in preterm newborns. The Behavioral Indicators of Infant Pain (BIPP), Crying, Requires Oxygen, Increased Vital Signs, Expression, Sleeplessness (CRIES), Premature Infant Pain Profile (PIPP), and Premature Infant Pain Profile-Revised (PIPP-R) had scored "very good" in quality data. The PIPP and PIPP-R scales received the "very good" classification in validity assessment. The Evaluation Enfant Douleur (EVENDOL), Children's and Infants Postoperative Pain Scale (CHIPPS), PIPP-R, Neonatal Pain Agitation and Sedation Scale (N-PASS), Bernese Pain Scale for Neonates (BPSN), Faceless Acute Neonatal Pain Scale (FANS), BIIP, and Pain Assessment Scale for Preterm Infants (PASPI) obtained an assessment classified as excellent on reliability, both for inter-rater reliability and internal consistency, and the BPSN demonstrated a very strong value to intra-rater reliability. CONCLUSIONS: Considering the assessments of inter-rater reliability, internal consistency, and quality of scales by COSMIN, the BIPP, and PIPP-R, were the scales considered appropriate.

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).

Trends in tuberculosis incidence and mortality coefficients in Brazil, 2011-2019: analysis by inflection points.

Objective: To analyze the temporal trend of tuberculosis incidence and mortality rates in Brazil between 2011 and 2019. Methods: This was an ecological time series study of tuberculosis incidence and mortality rates in Brazil between 2011 and 2019. Data were extracted from the Notifiable Disease Information System and the Mortality Information System, and population estimates were from the Brazilian Institute of Geography and Statistics. Trends were analyzed by Joinpoint regression, which recognizes inflection points for temporal analysis. Results: The average incidence rate of tuberculosis in Brazil in the period was 35.8 cases per 100 000 population. From 2011 to 2015, this coefficient had an annual percentage change of -1.9% (95% CI [-3.4, -0.5]) followed by an increase of 2.4% (95% CI [0.9, 3.9]) until 2019. The average mortality rate between 2011 and 2019 was 2.2 deaths per 100 000 population, with an average annual percentage change of -0.4% (95% CI [-1.0, 0.2]). Amazonas was the only state with an increase in the annual average percentage variation for the incidence rate (3.2%; 95% CI [1.3, 5.1]) and mortality rate (2.7%; 95% CI [1.0, 4.4]) over the years, while Rio de Janeiro state had an increasing inflection for incidence from 2014 to 2019 (2.4%; 95% CI [1.4, 3.5]) and annual average of decreasing percentage variation (-3.5%; 95% CI [-5.0, -1.9]). Conclusions: During the period analyzed, a decreasing trend in incidence was observed between 2011 and 2015, and an increasing trend for the period from 2015 to 2019. On the other hand, no change in the trend for mortality was found in Brazil.

Immunomodulatory Effects of Cinnamaldehyde in Staphylococcus aureus-Infected Wounds.

Cinnamaldehyde (CNM) is an essential-oil component with reported anti-infective, anti-inflammatory, and healing effects, making it an interesting compound for the treatment of wound infection. Herein, we evaluated the effects of topical administration of CNM in experimental wounds infected by Staphylococcus aureus. Swiss mice (n = 12/group) were randomly allocated into three groups (CON: animals with uninfected lesions; Sa: animals with untreated infected lesions; Sa + CNM: animals with infected wounds and treated with CNM). Excisional lesions (64 mm2) were induced at the dorsal area followed by the addition of S. aureus (80 µL of a 1.5 × 108 CFU/mL bacterial suspension). The wounds were treated with CNM (200 µg/wound/day) or vehicle (2% DMSO) for 10 days. Skin samples were taken on the 3rd or 10th treatment day for quantification of inflammatory mediators, bacterial load, immunophenotyping, and histological analysis. The treatment with CNM improved the healing process and attenuated the severity of skin lesions infected by S. aureus. These effects were associated with significant decreases in bacterial loads in CNM-treated wounds. The levels of neutrophils, TNF-α, IL-6, NO, and VEGF were decreased in the lesions treated with CNM. Taken together, these data provide further evidence of the effectiveness of CNM for the treatment of skin infections.

Microalgae as Raw Materials for Aquafeeds: Growth Kinetics and Improvement Strategies of Polyunsaturated Fatty Acids Production.

Studies have shown that ancient cultures used microalgae as food for centuries. Currently, scientific reports highlight the value of nutritional composition of microalgae and their ability to accumulate polyunsaturated fatty acids at certain operational conditions. These characteristics are gaining increasing interest for the aquaculture industry which is searching for cost-effective replacements for fish meal and oil because these commodities are one of the most significant operational expenses and their dependency has become a bottleneck for their sustainable development of the aquaculture industry. This review is aimed at highlighting the use of microalgae as polyunsaturated fatty acid source in aquaculture feed formulations, despite their scarce production at industrial scale. Moreover, this document includes several approaches to improve microalgae production and to increase the content of polyunsaturated fatty acids with emphasis in the accumulation of DHA, EPA, and ARA. Furthermore, the document compiles several studies which prove microalgae-based aquafeeds for marine and freshwater species. Finally, the study explores the aspects that intervene in production kinetics and improvement strategies with possibilities for upscaling and facing main challenges of using microalgae in the commercial production of aquafeeds.

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.

Violacein negatively modulates the colorectal cancer survival and epithelial-mesenchymal transition.

Violacein is a secondary metabolite produced by several microorganisms including Chromobacterium violaceum, and it is already used in food and cosmetics. However, due to its potent anticancer and low side effects, its molecular action needs to be deeply scrutinized. Therefore, the main objective of this study was to evaluate the violacein's ability to interfere with three cancer hallmarks: growth factors receptor-dependent signaling, proliferation, and epithelial-mesenchymal transition (EMT). Violacein has been associated with the induction of apoptosis in colorectal cancer (CRC) cells. Here, we demonstrate that this molecule is also active in CRC spheroids and inhibits cell migration. Violacein treatment reduced the amount of EGFR and AXL receptors in the HT29 cell line. Accordingly, the inhibition of the AKT, ERK, and PKCδ kinases, which are downstream mediators of the signaling pathways triggered by EGFR and AXL, is detected. Another interesting finding was that even when the cells were stimulated with transforming growth factor-ß, the EMT marker (N-cadherin) decreased. Therefore, this study provides further evidence that reinforces the potential of violacein as an antitumor agent, once this biomolecule can "switch off" properties associated with cancer plasticity.

Comparison of Sample Preparation Techniques for the (-)ESI-FT-ICR-MS Analysis of Humic and Fulvic Acids.

Soil organic matter (SOM) plays a key role in the global carbon and nitrogen cycles. Soil biogeochemistry is regularly studied by extracting the base-soluble fractions of SOM: acid-insoluble humic acid (HA) and acid-soluble fulvic acid (FA). Electrospray ionization-Fourier transform-ion cyclotron resonance-mass spectrometry (ESI-FT-ICR-MS) is commonly utilized for molecularly characterizing these fractions. Different sample preparation techniques exist for the analysis of HA and FA though questions remain regarding data comparability following different preparations. Comparisons of different sample preparation techniques here revealed that the negative-mode ESI-FT-ICR-MS analytical window can be skewed to detect different groups of molecules, with primary differences in oxygenation, aromaticity, and molecular weight. It was also observed that HA and FA from soils versus an aquatic matrix behaved very differently. Thus, we conclude that sample preparation techniques determined to be "most optimal" in our study are in no way universal. We recommend that future studies of HA and FA involve similar comparative studies for determining the most suitable sample preparation technique for their particular type of HA or FA matrices. This will enhance data comparability among different studies and environmental systems and ultimately allow us to better understand the complex composition of environmental matrices.

Violacein switches off low molecular weight tyrosine phosphatase and rewires mitochondria in colorectal cancer cells.

In the last decade, emerging evidence has shown that low molecular weight protein tyrosine phosphatase (LMWPTP) not only contributes to the progression of cancer but is associated with prostate low survival rate and colorectal cancer metastasis. We report that LMWPTP favors the glycolytic profile in some tumors. Therefore, the focus of the present study was to identify metabolic enzymes that correlate with LMWPTP expression in patient samples. Exploratory data analysis from RNA-seq, proteomics, and histology staining, confirmed the higher expression of LMWPTP in CRC. Our descriptive statistical analyses indicate a positive expression correlation between LMWPTP and energy metabolism enzymes such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN). In addition, we examine the potential of violacein to reprogram energetic metabolism and LMWPTP activity. Violacein treatment induced a shift of glycolytic to oxidative metabolism associated with alteration in mitochondrial efficiency, as indicated by higher oxygen consumption rate. Particularly, violacein treated cells displayed higher proton leak and ATP-linked oxygen consumption rate (OCR) as an indicator of the OXPHOS preference. Notably, violacein is able to bind and inhibit LMWPTP. Since the LMWPTP acts as a hub of signaling pathways that offer tumor cells invasive advantages, such as survival and the ability to migrate, our findings highlight an unexplored potential of violacein in circumventing the metabolic plasticity of tumor cells.