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Karen C dos Santos,1 Maria Fatima GF da Silva,1 Edenir R Pereira-Filho,1 Joao B Fernandes,1 Igor Polikarpov,2 Moacir R Forim11Department of Chemistry, Federal University of Sao Carlos, Sao Carlos, 2Physics Institute of Sao Carlos, University of Sao Paulo, Sao Carlos, Sao Paulo, BrazilAbstract: This present investigation deals with the development and optimization of polymeric nanoparticle systems loaded with 3,5,3´-triiodothyroacetic acid (Triac). A 211–6 fractional factorial design and another 22 factorial design were used to study the contrasts on particle size distribution, morphology, surface charge, drug content, entrapment efficiency, and in vitro drug release profiles. The independent variables were the concentration of Triac, type and quantity of both polymer and oil, quantity of Span™ 60 and Tween® 80, volume of solvent and water, and velocity of both magnetic stirring and the transfer of the organic phase into the aqueous solution. The results of optimized formulations showed a narrow size distribution with a polydispersity index lower than 0.200. The particle sizes were on average 159.6 nm and 285.6 nm for nanospheres and nanocapsules, respectively. The zeta potential was higher than 20 mV (in module) and the entrapment efficiency was nearly 100%. A high-performance liquid chromatography method was developed, validated, and efficiently applied to Triac quantification in colloidal suspension. The main independent variables were the type and quantity of the polymer and oil. In vitro drug release profile depicted several features to sustain Triac release. Different formulations showed various release rates indicating an interaction between Triac and other formulation compounds such as polymer and/or oil quantity. Two different models were identified (biexponential and monoexponential) that allowed the control of both the release rate and Triac concentration. Thus, the prepared nanoparticles described here may be of clinical importance in delivering Triac for thyroid treatment.Keywords: Triac, nanoparticles, optimization, factorial design of experiments, HPLC analytical method

BACKGROUND: Tramadol is a well tolerated and effective analgesic used to treat moderate to severe pain. Several generic formulations of tramadol are available in Brazil; however, published information regarding their bioequivalence in the Brazilian population is not available. A study was designed for Brazilian regulatory authorities to allow marketing of a generic formulation. OBJECTIVE: The purpose of this study was to compare the bioequivalence of 2 commercial tablet preparations containing tramadol 100 mg marketed for use in Brazil. METHODS: A randomized, open-label, 2 x 2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a washout period of 12 days. Two tablet formulations of tramadol 100 mg (test and reference formulations) were administered as a single oral dose, and blood samples were collected over 24 hours. Tramadol plasma concentrations were quantified using a validated HPLC method. A plasma concentration-time profile was generated for each volunteer and then mean values were determined, from which C(max), T(max), AUC(0-infinity) k(e), and t(1/2) were calculated using a noncompartmental model. Bioequivalence between the products was determined by calculating 90% CIs for the ratios of C(max) AUC(0-t) and AUC(0-infinity), values for the test and reference products using log-transformed data. Tolerability was assessed by monitoring vital signs (temperature, blood pressure, heart rate), laboratory tests (hematology, blood biochemistry, hepatic function, urinalysis), and interviews with the volunteers before medication administration and every 2 hours during the study. RESULTS: Twenty-six healthy volunteers (13 men, 13 women) were enrolled in and completed the study. Mean (SD) age was 30 (6.8) years (range, 21-44 years), mean weight was 64 (8.3) kg (range, 53-79 kg), and mean height was 166 (6.4) cm (range, 155-178 cm). The 90% CIs for the ratios of Cmax (1.01-1.17), AUC(0-t) (1.00-1.13), and AUC(0-infinity). (1.00-1.14) values for the test and reference products fell within the interval of 0.80 to 1.25 proposed by most regulatory agencies, including the Brazilian regulatory body. No clinically important adverse effects were reported; only mild somnolence was reported by 4 volunteers and mild headaches by 5 volunteers, and there was no need to use medication to treat these symptoms. CONCLUSION: Pharmacokinetic analysis in these healthy Brazilian volunteers suggested that the test and reference formulations of tramadol 100-mg tablets met the regulatory requirements to assume bioequivalence based on the Brazilian regulatory definition. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has been the most significant health challenge of the last century. Multiple and successive waves of COVID-19 cases, driven particularly by the emergence of new SARS-CoV-2 variants, have kept the world in a constant state of alert., Methods: We present an observational, descriptive, cross-sectional study aimed at identifying SARS-CoV-2 variants circulating during two local waves of COVID-19 cases in southern Bahia, Brazil (late 2021 and late 2022), and analyzing the association between the detected variants and the epidemiological and clinical characteristics of the disease. For this purpose, data and nasopharyngeal samples from individuals in southern Bahia, Brazil, with suspected COVID-19 were included. Viral detection was performed by RT-qPCR, and SARS-CoV-2 variants were identified by next-generation viral sequencing., Results: A total of 368 nasopharyngeal samples were tested. Approximately 23% of the samples from late 2021 tested positive for SARS-CoV-2, while in 2022, the positivity rate was about 56%. All sequenced samples from 2021 were identified as the Delta variant, while in 2022, all samples were classified as the Omicron variant. Overall, individuals who tested positive for SARS-CoV-2 in 2022 were younger than those who tested positive in 2021. Moreover, we observed significant differences in the clinical spectrum of SARS-CoV-2 infection when comparing the two periods. Individuals who presented with anosmia/ageusia were more likely to test positive for SARS-CoV-2 infection in 2021 but not in 2022. Additionally, fever, dry cough, pharyngalgia, headache, and rhinorrhea were more frequent among individuals infected with the Omicron variant than among those infected with the Delta variant., Conclusions: The profile of COVID-19 in southern Bahia differed when analyzing two distinct waves of the pandemic in the region. These differences are likely related to the variants, which may differ in transmissibility and virulence, thereby altering the dynamics of the pandemic. This underscores the importance of genomic surveillance in better understanding the behavior of viral infections., (© 2024. The Author(s).)

Plant organs harbour diverse components that connect their physiology to the whole organism. The turnover of metabolites may be higher in some organs than in others, triggering differential growth patterns throughout the organism. We revealed that Solanum lycopersicum exhibits more coordinated growth and physiology across the entire plant compared to wild tomato species. Specifically, young leaves of S. lycopersicum develop more slowly than mature leaves, whereas wild species do not exhibit this pattern. Wild tomato Solanum pennellii displays young leaves with higher photosynthetic rates than mature leaves. Consequently, sucrose metabolism in S. pennellii is quite similar between young and mature leaves, while expression patterns of circadian clock genes differ significantly between leaves of different ages. Additionally, we demonstrated that introducing alleles related to tomato domestication into the wild tomato Solanum pimpinellifolium promotes coordinated growth between young and mature leaves, resulting in similar patterns to those observed in S. lycopersicum. Collectively, S. lycopersicum appears to exhibit more coordinated regulation of growth and metabolism, and understanding this process is likely fundamental to explaining its elevated harvest index., (© 2024 John Wiley & Sons Ltd.)

The term cancer is used to describe a complex pathology characterized by the uncontrollable proliferation of cells, which displays a fast metastatic spread, being a disease with difficult treatment. In this context, Phosphatidylinositol 3-kinase (PI3K) represents a promising pathway to be inhibited, aiming to develop anticancer agents, since it performs a pivotal role in regulating essential cellular processes, including cell proliferation, growth, autophagy, and apoptosis. In parallel, natural compounds can effectively represent a therapeutic strategy to fight against malignant cells. Then, compounds derived from various plant sources, such as flavonoids, terpenoids, alkaloids, coumarins, and lignans, have exhibited remarkable in vitro and in vivo anticancer properties. This review focused in the exploration of natural products targeting the PI3K/AKT/m-TOR signaling pathway, demonstrating that these compounds could even further investigated to reveal novel and effective anticancer drugs in the future., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: There is interest in the public health impact of Long COVID, defined as symptoms that persist or begin after SARS-CoV-2 infection. We aimed to identify demographic and clinical risk factors associated with Long COVID over time in an Upper Middle-Income Country (UMIC) and potential biomarkers predictive of symptom trajectory., Methods: Prospective cohort study of adults with mild SARS-COV-2 during the Omicron period. We tracked symptom persistence and IgG antibody titers against the spike S1 subunit., Results: Of 383 participants, 276 had confirmed SARS-CoV-2 infection. Long COVID persisted for ≥ two months in 21 % and ≥ 12 months in 5 %. The most common symptoms were fatigue, upper respiratory symptoms, and myalgia/arthralgia: 15 % had fatigue for ≥ one month, 10 % for ≥ two months, and 5 % ≥ three months. Upper respiratory symptoms lasted ≥ one month in 17 %, ≥ two months in 7 %, and ≥ three months in 3 %. Fully 9 % reported myalgia/arthralgia lasting ≥ one month, 6 % ≥ two months, and 4 % ≥ three months. Risk factors for symptom persistence included female sex, not being fully vaccinated, and comorbidities. Participants experiencing persistent fatigue had lower anti-S1 IgG titers., Conclusions: In this population, symptom persistence declined after the acute phase, but 5 % of participants did not fully recover. Even in a population that was almost fully vaccinated, women, individuals with comorbidities, and the few remaining people who were unvaccinated were at greater risk for Long COVID. Immunoglobulins may have utility as a biomarker of Long COVID fatigue in this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Question: In people with shoulder pain, what is the effect of adding mobilisation with movement (MWM) to a standard exercise program on function and pain compared with sham MWM and the same exercise program?, Design: A randomised trial with concealed allocation, blinded outcome assessment and intention-to-treat analysis., Participants: Seventy people with chronic atraumatic rotator cuff related pain, with a mean age 48 years (SD 10)., Interventions: The experimental group received MWM plus exercise and the control group received sham MWM plus exercise. Treatments were delivered twice per week for 5 weeks., Outcome Measures: The primary outcome measures were function (0 to 100 Shoulder Pain and Disability Index) and pain (0 to 10 Numerical Pain Rating Scale). Secondary outcomes were self-efficacy, perceived improvement and active pain-free range of movement. Assessment time points were at baseline (week 0), the end of the treatment period (week 5) and a follow-up 1 month after the end of treatment (week 9)., Results: At week 5, the experimental group improved more than the control group in function (MD -15 points, 95% CI -24 to -7), pain at night (MD -2.1, 95% CI -3.1 to -1.1), pain on movement (MD -1.5, 95% CI -2.5 to -0.6) and active range of movement in flexion (MD 16 deg, 95% CI 1 to 30), abduction (MD 23 deg, 95% CI 6 to 40), external rotation (MD 11 deg, 95% CI 4 to 17) and hand behind back (MD 20 deg, 95% CI 8 to 32). At week 9, benefits were seen in the Shoulder Pain and Disability Index (MD -9 points, 95% CI -17 to -1), pain at night (MD -1.9, 95% CI -2.9 to -0.8) and on movement (MD -1.3, 95% CI-2.3 to -0.3). The effects of the experimental intervention on other outcomes were mostly unclear due to wide confidence intervals. Blinding was successful., Conclusions: Adding MWM to exercise improved function, pain and active range of movement in people with shoulder pain. These benefits were not placebo effects., Registration: NCT04175184., (Copyright © 2024 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.)

Red pitaya fruit has become a source of natural colorant, because it is rich in betalains, a pigment that imparts a red-purple color that interests the food and cosmetics industries. This fruit also possesses high nutritional value, with a range of bioactive compounds known to confer potential health benefits and prevent chronic diseases, such as diabetes, which makes it useful for use as pharmaceutical agents and dietary supplements. In order to improve its technological and biological effects, a concentration will be required. Thus, the microfiltration, followed by vacuum concentration, can be an interesting strategy for this purpose. This study aimed to explore tangential microfiltration to produce microfiltered material, which is an important step to obtain the microfiltered red-purple pitaya concentrate. Therefore, physicochemical and chemical characterization (including 1 H NMR analysis) and biological properties (toxicity and diabetes) of this concentrate were assessed, using adult zebrafish as a model. The results show that microfiltration was carried out efficiently, with an average consumption of 95.75 ± 3.13 and 74.12 ± 3.58 kW h m -3 , varying according to the material used ("unpeeled pitaya pulp" or "pitaya pulp with peel," respectively). The in vivo tests indicated non-toxicity and hypoglycemic effect of the concentrate, since the blood glucose levels were significantly lower in the zebrafish groups treated with this concentrate in comparison with that of control group. Thus, this study suggests the potential of microfiltered red-purple pitaya concentrate as a promising multifunctional food-derived colorant, exhibiting beneficial biological effects far beyond its attractive color. PRACTICAL APPLICATION: Hylocereus polyrhizus (F.A.C. Weber) Britton & Rose has attracted attention as a potential source of natural colorants because of its red-purple skin and flesh color. In addition, this fruit has a range of bioactive compounds, which make it a valuable resource for providing potential health benefits and preventing chronic diseases such as diabetes. In this paper, the microfiltered red-purple pitaya concentrate showed beneficial biological effects far beyond its attractive color. Thus, this product can be considered a promising multifunctional food-derived colorant to use in the food, pharmaceutical, or cosmetics industries., (© 2024 Institute of Food Technologists.)

Black women living with HIV (BWLWH) face barriers that impact health outcomes. However, positive psychosocial indicators may influence HIV care outcomes. Among this cross-sectional study of 119 BWLWH, a network analysis was utilized to examine relationships between positive psychosocial factors and HIV-related health outcomes. A preliminary polychoric analysis was conducted to examine correlations between the variables, and the network analyzed connections between resilience, self-efficacy, self-esteem, perceived social support, religious coping, post-traumatic growth, and an indicator variable for suboptimal HIV care outcomes (low medication adherence, detectable viral load, and missed HIV-related health visits) and determined the centrality measures within the network. Seven significant associations were found among the factors: self-efficacy and self-esteem, post-traumatic growth and resilience, post-traumatic growth and self-efficacy, post-traumatic growth and religious coping, perceived social support and resilience, self-esteem and resilience, self-esteem and perceived social support (bootstrapped 95% CI did not contain zero). Self-efficacy was the strongest indicator associated with the other factors. Although not statistically significant, the indicator for suboptimal HIV care outcomes was negatively associated with perceived social support and religious coping. Future interventions incorporating self-efficacy may be beneficial to the overall well-being of Black women.

Objectives: The primary objective was to study the totality of inferior vena cava filter placements and their temporal and geographic distribution in the Brazilian Public Health System, which insures more than 160 million Brazilians. The secondary objective was to analyze in-hospital mortality after filter placement and deaths due to pulmonary embolism., Methods: Public and open data on in-hospital mortality due to pulmonary embolism and on rates of inferior vena cava filters placement, its associated diagnosis, and in-hospital mortality in Brazilian public hospitals between January 2008 and December 2019 were extracted from Ministry of Health databases., Results: A total of 9108 inferior vena cava filters were placed, 98.18% of which was therapeutic. We observed a significant increase in the use of these devices over the years, from 508 inferior vena cava filters placed in 2008 to 965 in 2019. In-hospital mortality rate in patients who received inferior vena cava filters was 6.21%, stable over time, and 96.64% of causes of these causes were attributed to venous thromboembolism. The in-hospital mortality rate due to pulmonary embolism, regardless of the placement of vena cava filters, has increased significantly., Conclusion: We observed a low but increasing rate of inferior vena cava filter placements in Brazil between 2008 and 2019, most indications were therapeutic. Our findings were heterogeneous across Brazilian regions and contrasted to those observed in the USA, which is likely due to cultural and socioeconomic factors., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The hydrothermal pretreatment process stands out as a pivotal step in breaking down the hemicellulosic fraction of lignocellulosic biomasses, such as sugarcane bagasse and eucalyptus sawdust. This pretreatment step is crucial for preparing these materials for subsequent processes, particularly in food applications. This technique aims to disintegrate plant wall components like cellulose, hemicellulose, and lignin, and facilitating access in later phases such as enzymatic hydrolysis, and ultimately making fermentable sugars available. In this study, sugarcane bagasse and eucalyptus sawdust biomass underwent hydrothermal pretreatment at specific conditions, yielding two key components: dry biomass and hemicellulose liquor. The primary focus was to assess the impact of hydrothermal pretreatment followed by enzymatic hydrolysis, using the Celic Ctec III enzyme cocktail, to obtain fermentable sugars. These sugars were then transformed into membranes via strain Gluconacetobacter xylinus bacterial biosynthesis. Notably, the addition of a nitrogen source significantly boosted production to 14.76 g/ in hydrolyzed sugarcane bagasse, underscoring its vital role in bacterial metabolism. Conversely, in hydrolyzed eucalyptus, nitrogen source inclusion unexpectedly decreased yield, highlighting the intricate interactions in fermentation media and the pivotal influence of nitrogen supplementation. Characterization of membranes obtained in synthetic and hydrolyzed media through techniques such as FEG-SEM, FTIR, and TGA, followed by mass balance assessment, gauged their viability on an industrial scale. This comprehensive study aimed not only to understand the effects of pretreatment and enzymatic hydrolysis but to also evaluate the applicability and sustainability of the process on a large scale, providing crucial insights into its feasibility and efficiency in practical food-related scenarios, utilizing nanocellulose bacterial (BNC) as a key component., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Three novel coordination polymers (CPs), namely [Cu(μ-1κO,2κN-L) 2 ] n (1), [Zn (μ-1κO,2κN-L) 2 (H 2 O) 2 ] n (2) and [Cd (μ-1κOO',2κN-L) 2 ] n (3) [where HL = 4-(pyrimidin-5-ylcarbamoyl)benzoic acid], were synthesized and characterized by elemental analysis, ATR-IR, TGA, XPS and single-crystal X-ray diffraction. Despite having the same organic ligand, the various metal cations had an impact in the subsequent frameworks. Hirshfeld surface analysis was performed to investigate the intermolecular interactions and to examine the stability of the crystal structures of the three polymers. Their catalytic performances were screened for the peroxidative oxidation of Volatile Organic Compounds (VOCs), with toluene and p-xylene selected as model substrates. Tert-butyl hydroperoxide (t-BuOOH or TBHP) (aq. 70 %) was employed as the oxidant. The catalytic oxidation of toluene yielded benzyl alcohol, benzaldehyde and benzoic acid. The copper CP 1 exhibited the highest total yield for toluene oxidation, reaching approximately 36% in an aqueous medium. For p-xylene oxidation, tolualdehyde, methylbenzyl alcohol, and toluic acid were produced as the primary products, accompanied by minor ones. The experiments were conducted under diverse conditions, manipulating key parameters such as the choice of solvent (water or acetonitrile), type of oxidant (t-BuOOH or H 2 O 2 ), the concentration of the oxidant and reaction temperature. In the presence of catalyst 1, a maximum total yield of ca. 80% was achieved for p-xylene oxidation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)