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Wanessa da Silva Peres Bezerra,1 Everton Ferreira Lemos,2 Thiago Nascimento do Prado,3 Larissa Taemy Kayano,2 Stefany Zacarin de Souza,2 Cláudia Elizabeth Volpe Chaves,1,4 Anamaria Mello Miranda Paniago,1,2,4 Albert Schiaveto de Souza,5,6 Sandra Maria do Valle Leone de Oliveira2,4,6 1Postgraduate Program in Infectious and Parasitic Diseases, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil; 2School of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil; 3Nursing Department, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil; 4Maria Aparecida Pedrossian University Hospital, EBSERH, Campo Grande, Mato Grosso do Sul, Brazil; 5Biosciences Institute, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, Brazil; 6Postgraduate Program in Family Health, Biosciences Institute, Federal University of Mato Grosso do Sul, Campo Grande, Mato Grosso do Sul, BrazilCorrespondence: Sandra Maria do Valle Leone de OliveiraSchool of Medicine, Federal University of Mato Grosso do Sul, Cidade Universitária, Caixa Postal 549, Unidade 9, Campo Grande CEP 79070-900 Mato Grosso do Sul, BrazilTel +55 67 3345 7370Email sandra.leone@ufms.brPurpose: To study the factors associated with the risk of discontinuing active tuberculosis treatment among patients in an outpatient referral unit and to analyze the association between patients’ abandonment risk score and their odds of discontinuing the treatment.Patients and Methods: In this cohort study, tuberculosis patients were prospectively followed up from June 2012 through July 2019 at a secondary tuberculosis referral unit in Mato Grosso do Sul, Brazil. At initial consultation, patients were interviewed using a standardized questionnaire and were assigned a score for the risk of treatment abandonment by the nurse. Univariate and multivariate analyses were performed using logistic regression.Results: One hundred and forty-eight patients were included in the study, of which 65.0% (96/148) were male. Their mean age was 43.3 ± 14.8 years (range: 18– 89 years). Smoking, drug use, repeated admissions, and a high abandonment risk score were the variables associated with the highest risk of discontinuing the treatment. The rate of tuberculosis and human immunodeficiency virus coinfection was 37.2%. The overall rate of global treatment abandonment was 10.8% (95% confidence interval [CI]: 6.1– 16.2). Upon stratification of patients that abandoned by the risk score, 22.9% (8/35) of the ones that abandoned had a high risk, 10.9% (6/55) had an intermediate risk, and 3.5% (2/58) had a low risk of treatment abandonment. In multivariate analysis, the factors associated with abandoning the treatment were smoking [adjusted odds ratio (aOR) = 4.91 (95% CI: 1.08, 22.32)] and undergoing retreatment (aOR) = 3.66 (95% CI: 1.04, 12 88).Conclusion: Smoking and undergoing retreatment were independent risk factors for tuberculosis treatment abandonment in this center. Risk stratification can help prioritize the strengthening of treatment adherence among patients at higher risk of abandoning treatment in referral units.Keywords: tuberculosis, patient acceptance of health care, patient withdrawal, classification

ETHNOPHARMACOLOGICAL RELEVANCE: Geissospermum vellosii is a tree widely found throughout the Amazonic forest and frequently used by the native population for painful disorders. AIM OF THE STUDY: The present study examined the antinociceptive effects of Geissospermum vellosii in behavioral models of nociception. MATERIALS, METHODS AND RESULTS: Oral administration of crude extract of Geissospermum vellosii or its dichloromethane fraction (1-100 mg/kg) inhibited formalin-induced inflammatory nociception and acetic acid-induced visceral nociception. The antinociceptive effect of Geissospermum vellosii was unrelated with motor dysfunctions. Furthermore, the alkaloid 12-metoxy-1-methyl-aspidospermidine (0.001-1 mg/kg), isolated from the dichloromethane fraction, also produced antinociception. The antinociception caused by the dichloromethane fraction was significantly attenuated by pre-treatment of mice with p-chlorophenylalanine methyl ester (PCPA, an inhibitor of serotonin synthesis, 100 mg/kg once a day for 4 consecutive days) and WAY-100635 (a 5-HT(1A) receptor antagonist, 0.3 mg/kg). In contrast, dichloromethane fraction antinociception was not affected by pre-treatment of animals with ketanserin (a 5-HT(2) receptor antagonist, 0.3 mg/kg) or ondansetron (a 5-HT(3) receptor antagonist, 0.5 mg/kg). CONCLUSIONS: Together, these results indicate that Geissospermum vellosii produces antinociception through an interaction with 5-HT(1A) receptors. Furthermore, the alkaloid 12-metoxy-1-methyl-aspidospermidine contributes to the antinociceptive properties reported for Geissospermum vellosii. [ABSTRACT FROM AUTHOR]

Background and Purpose: Fibromyalgia is a complex clinical disorder with an unknown aetiology, characterized by generalized pain and co-morbid symptoms such as anxiety and depression. An imbalance of oxidants and antioxidants is proposed to play a pivotal role in the pathogenesis of fibromyalgia symptoms. However, the precise mechanisms by which oxidative stress contributes to fibromyalgia-induced pain remain unclear. The transient receptor potential ankyrin 1 (TRPA1) channel, known as both a pain sensor and an oxidative stress sensor, has been implicated in various painful conditions., Experimental Approach: The feed-forward mechanism that implicates reactive oxygen species (ROS) driven by TRPA1 was investigated in a reserpine-induced fibromyalgia model in C57BL/6J mice employing pharmacological interventions and genetic approaches., Key Results: Reserpine-treated mice developed pain-like behaviours (mechanical/cold hypersensitivity) and early anxiety-depressive-like disorders, accompanied by increased levels of oxidative stress markers in the sciatic nerve tissues. These effects were not observed upon pharmacological blockade or global genetic deletion of the TRPA1 channel and macrophage depletion. Furthermore, we demonstrated that selective silencing of TRPA1 in Schwann cells reduced reserpine-induced neuroinflammation (NADPH oxidase 1-dependent ROS generation and macrophage increase in the sciatic nerve) and attenuated fibromyalgia-like behaviours., Conclusion and Implications: Activated Schwann cells expressing TRPA1 promote an intracellular pathway culminating in the release of ROS and recruitment of macrophages in the mouse sciatic nerve. These cellular and molecular events sustain mechanical and cold hypersensitivity in the reserpine-evoked fibromyalgia model. Targeting TRPA1 channels on Schwann cells could offer a novel therapeutic approach for managing fibromyalgia-related behaviours., (© 2024 British Pharmacological Society.)

Objective: The aim of the study was to compare two labor induction regimens (4 and 6 h), to determine predictors of successful labor induction with intravaginal misoprostol 25 μg tablets, and to evaluate the association with adverse perinatal outcomes., Methods: This was a retrospective cohort study that included singleton pregnancies undergoing induction of labor with an intravaginal misoprostol 25 μg tablet between 37 and 42 weeks of gestation. The pregnant women were divided into two groups: Group 1-intravaginal misoprostol 25 μg every 4 h and Group 2-intravaginal misoprostol 25 μg every 6 h., Results: Pregnant women were divided into Group 1 (n=289) and Group 2 (n=278). Group 1 had a higher median number of intravaginal misoprostol 25 μg tablets (3.0 vs. 2.0 tablets, p<0.001), a lower prevalence of postpartum hemorrhage (7.6 vs. 32.7%, p<0.001), and a higher need for oxytocin (odds ratio [OR]: 2.1, 95%CI: 1.47-2.98, p<0.001) than Group 2. Models including intravaginal misoprostol 25 μg tablets every 4 and 6 h [x2(1)=23.7, OR: 4.35, p<0.0001], parity [x2(3)=39.4, OR: 0.59, p=0.031], and Bishop's score [x2(4)=10.8, OR: 0.77, p=0.019] were the best predictors of failure of labor induction. A statistically significant difference between groups was observed between the use of the first intravaginal misoprostol 25 μg tablet at the beginning (Breslow p<0.001) and the end of the active labor phase (Long Hank p=0.002)., Conclusion: Pregnant women who used intravaginal misoprostol 25 μg every 4 h had a longer time from the labor induction to the beginning of the active phase of labor and higher rates of adverse perinatal outcomes than women who used intravaginal misoprostol 25 μg every 6 h.

Leishmaniasis is a tropical infectious disease caused by Leishmania parasites. The disease can be spread by the bite of an infected sand fly. Currently, five chemotherapeutic drugs are available in leishmaniasis treatment. However, these drugs exhibit toxicity and serious adverse effects on infected individuals, necessitating alternative treatment strategies. One such strategy involves using combinations of existing antileishmanial drugs. In this study, we evaluated the interaction between artesunate (AS) and three antileishmanial drugs-amphotericin B (AmB), miltefosine (MF), and paromomycin (PM) against Leishmania infantum . This evaluation marks the first time such an assessment has been conducted. The Chou-Talalay combination index method was employed to analyze the drug interaction. The findings revealed that the interaction between AS and AmB ranged from antagonistic to synergistic, while the interaction between AS and MF showed moderate to strong synergism. In contrast, the interaction between AS and PM resulted in an antagonistic interaction, which differs from the combinations with AmB or MF. This study provides valuable insights for developing novel drug regimens for leishmaniasis treatment, emphasizing the potential of AS and its combination with existing antileishmanial drugs. Further research is necessary to optimize drug combinations and minimize adverse effects, leading to more effective therapeutic outcomes.

Burns are a global health problem and can be caused by several factors, including ultraviolet (UV) radiation. Exposure to UVB radiation can cause sunburn and a consequent inflammatory response characterised by pain, oedema, inflammatory cell infiltration, and erythema. Pharmacological treatments available to treat burns and the pain caused by them include nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antimicrobials and glucocorticoids, which are associated with adverse effects. Therefore, the search for new therapeutic alternatives is needed. Diosmetin, an aglycone of the flavonoid diosmin, has antinociceptive, antioxidant and anti-inflammatory properties. Thus, we evaluated the antinociceptive and anti-inflammatory effects of topical diosmetin (0.01, 0.1 and 1%) in a UVB radiation-induced sunburn model in mice. The right hind paw of the anaesthetised mice was exposed only once to UVB radiation (0.75 J/cm 2 ) and immediately treated with diosmetin once a day for 5 days. The diosmetin antinociceptive effect was evaluated by mechanical allodynia and pain affective-motivational behaviour, while its anti-inflammatory activity was assessed by measuring paw oedema and polymorphonuclear cell infiltration. Mice exposed to UVB radiation presented mechanical allodynia, increased pain affective-motivational behaviour, paw oedema and polymorphonuclear cell infiltration into the paw tissue. Topical Pemulen® TR2 1% diosmetin reduced the mechanical allodynia, the pain affective-motivational behaviour, the paw oedema and the number of polymorphonuclear cells in the mice's paw tissue similar to that presented by Pemulen® TR2 0.1% dexamethasone. These findings indicate that diosmetin has therapeutic potential and may be a promising strategy for treating patients experiencing inflammatory pain, especially those associated with sunburn., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a phenol commonly found in grapes and wine, has been associated as protective in experimental models involving alterations in different neurotransmitter systems. However, studies are reporting that resveratrol could have adverse effects. This study evaluated if the association of a low dose of ketamine and resveratrol could induce behavioral manifestations associated with biochemical alterations. Moreover, the effects of treatment with resveratrol and/or ketamine on monoamine oxidase (MAO) activity, oxidative stress markers, and IL-6 levels in the brain were also investigated. Male Swiss mice received a low dose of ketamine (20 mg/kg) for 14 consecutive days, and resveratrol (10, 30, or 100 mg/kg) from day 8 up to day 14 of the experimental period, intraperitoneally. Locomotor, stereotyped behavior, Y-maze, novel recognition object test (NORT), and social interaction were quantified as well as ex vivo analysis of MAO activity, IL-6 levels, and oxidative stress markers (TBARS and total thiol levels) in brain tissues. Ketamine per se reduced the number of bouts of stereotyped behavior on day 8 of the experimental period. Resveratrol per se reduced the locomotor and exploratory activity in the open field, the time of exploration of new objects in the NORT, MAO-A activity in the striatum and increased the IL-6 levels in the cortex. These effects were attenuated when the mice were co-treated with ketamine and resveratrol. There was a decrease in MAO-A activity in the cortex of mice treated with ketamine + resveratrol 100 mg/kg. No significant alterations were found in oxidative stress markers. Resveratrol does not appear to cause summative effects with ketamine on behavioral alterations. However, the effect of resveratrol per se, mainly on locomotor and exploratory activity, should be better investigated., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Fibromyalgia is a potentially disabling idiopathic disease characterized by widespread chronic pain associated with comorbidities such as fatigue, anxiety, and depression. Current therapeutic approaches present adverse effects that limit adherence to therapy. Diosmetin, an aglycone of the flavonoid glycoside diosmin found in citrus fruits and the leaves of Olea europaea L., has antinociceptive, anti-inflammatory, and antioxidant properties. Here, we investigated the effect of diosmetin on nociceptive behaviors and comorbidities in an experimental fibromyalgia model induced by reserpine in mice. To induce the experimental fibromyalgia model, a protocol of subcutaneous injections of reserpine (1 mg/kg) was used once a day for three consecutive days in adult male Swiss mice. Mice received oral diosmetin on the fourth day after the first reserpine injection. Nociceptive (mechanical allodynia, muscle strength, and thermal hyperalgesia) and comorbid (depressive-like and anxiety behavior) parameters were evaluated. Potential adverse effects associated with diosmetin plus reserpine (locomotor alteration, cataleptic behavior, and body weight and temperature changes) were also evaluated. Oral diosmetin (0.015-1.5 mg/kg) reduced the mechanical allodynia, thermal hyperalgesia, and loss of muscle strength induced by reserpine. Diosmetin (0.15 mg/kg) also attenuated depressive-like and anxiety behaviors without causing locomotor alteration, cataleptic behavior, and alteration in weight and body temperature of mice. Overall, diosmetin can be an effective and safe therapeutic alternative to treat fibromyalgia symptoms, such as pain, depression and anxiety., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Colorectal cancer (CRC) responses to KRAS-targeted inhibition have been limited due to low response rates, the mechanisms of which remain unknown. Herein, we explored the cancer-associated fibroblasts (CAFs) secretome as a mediator of resistance to KRAS silencing. CRC cell lines HCT15, HCT116, and SW480 were cultured either in recommended media or in conditioned media from a normal colon fibroblast cell line (CCD-18Co) activated with rhTGF-β1 to induce a CAF-like phenotype. The expression of membrane stem cell markers was analyzed by flow cytometry. Stem cell potential was evaluated by a sphere formation assay. RNAseq was performed in KRAS-silenced HCT116 colonospheres treated with either control media or conditioned media from CAFs. Our results demonstrated that KRAS-silencing up-regulated CD24 and down-regulated CD49f and CD104 in the three cell lines, leading to a reduction in sphere-forming efficiency. However, CAF-secreted factors restored stem cell marker expression and increased stemness. RNA sequencing showed that CAF-secreted factors up-regulated genes associated with pro-tumorigenic pathways in KRAS-silenced cells, including KRAS, TGFβ, NOTCH, WNT, MYC, cell cycle progression and exit from quiescence, epithelial-mesenchymal transition, and immune regulation. Overall, our results suggest that resistance to KRAS-targeted inhibition might derive not only from cell-intrinsic causes but also from external elements, such as fibroblast-secreted factors.

Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system (CNS) generating neuropathic pain and anxiety. Primary progressive MS (PPMS) is the most disabling clinical form, and the patients present an intense neurodegenerative process. In this context, the advanced oxidation protein products (AOPPs) are oxidized compounds and their accumulation in plasma has been related to clinical disability in MS patients. However, the involvement of AOPPs in neuropathic pain- and anxiety-like symptoms was not previously evaluated. To assess this, female mice C57BL/6J were used to induce progressive experimental autoimmune encephalomyelitis (PMS-EAE). Clinical score, weight, strength of plantar pressure, rotarod test, mechanical allodynia, and cold hypersensitivity were evaluated before induction (baseline) and on days 7 th , 10 th , and 14 th post-immunization. We assessed nest building, open field, and elevated plus-maze tests 13 days post-immunization. Animals were killed at 14 days post-immunization; then, AOPPs levels, NADPH oxidase, and myeloperoxidase (MPO) activity were measured in the prefrontal cortex, hippocampus, and spinal cord samples. The clinical score increased 14 th post-immunization without changes in weight and mobility. Reduced paw strength, mechanical allodynia, and cold allodynia increased in the PMS-EAE animals. PMS-EAE mice showed spontaneous nociception and anxiety-like behavior. AOPPs concentration, NADPH oxidase, and MPO activity increase in CNS structures. Multivariate analyses indicated that the rise of AOPPs levels, NADPH oxidase, and MPO activity influenced the clinical score and cold allodynia. Thus, we indicated the association between non-stimuli painful perception, anxiety-like, and CNS oxidative damage in the PMS-EAE model., (© 2024 International Society for Neurochemistry.)

Introduction: The onset of the COVID-19 pandemic brought about global uncertainties and fears, escalating the dissemination of fake news. This study aims to analyze the impact of fake news on COVID-19 vaccine adherence among pregnant women, providing crucial insights for effective communication strategies during the pandemic., Methods: A cross-sectional, exploratory study was conducted with 113 pregnant women under care at a Women's Health Reference Center. Data analysis included relative frequency and odds ratio to assess the relationship between sociodemographic and behavioral variables regarding vaccination., Results: In the behavioral context of vaccination, internet access shows a significant association with decision-making, influencing vaccine refusal due to online information. Nuances in the odds ratios results highlight the complexity of vaccine hesitancy, emphasizing the importance of information quality. Pre-vaccination sentiments include stress (87.61%), fear (50.44%), and anxiety (40.7%), indicating the need for sensitive communication strategies., Discussion: Results revealed that pregnant women with higher education tend to adhere more to vaccination. Exposure to news about vaccine inefficacy had a subtle association with hesitancy, while finding secure sources was negatively associated with hesitancy. The behavioral complexity in the relationship between online information access and vaccination decision underscores the need for effective communication strategies., Conclusions: In the face of this challenging scenario, proactive strategies, such as developing specific campaigns for pregnant women, are essential. These should provide clear information, debunk myths, and address doubts. A user-centered approach, understanding their needs, is crucial. Furthermore, ensuring information quality and promoting secure sources are fundamental measures to strengthen trust in vaccination and enhance long-term public health.

Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to understand its pathogenesis to manage it better. Thus, we explored the involvement of peripheral mast cells in an experimental model of fibromyalgia induced by reserpine. Reserpine (1 mg/kg) was subcutaneously (s.c.) injected once daily in the back of male Swiss mice for three consecutive days. We analysed mechanical and cold allodynia, muscle fatigue and number of mast cell in plantar tissue. The fibromyalgia induction produced mast cell infiltration (i.e., mastocytosis) in the mice's plantar tissue. The depletion of mast cell mediators with the compound 48/80 (0.5-4 mg/kg, intraperitoneal (i.p.)) or the mast cell membrane stabilizer ketotifen fumarate (10 mg/kg, oral route (p.o.) widely (80-90 %) and extensively (from 1 up to 10 days) prevented reserpine-induced mechanical and cold allodynia and muscle fatigue. Compound 48/80 also prevented the reserpine-induced mastocytosis. Finally, we demonstrated that PAR-2, 5-HT 2A , 5-HT 3 , H 1 , NK1 and MrgprB2 receptors, expressed in neuronal or mast cells, seem crucial to mediate fibromyalgia-related cardinal symptoms since antagonists or inhibitors of these receptors (gabexate (10 mg/kg, s.c.), ENMD-1068 (10 mg/kg, i.p.), ketanserin (1 mg/kg, i.p.), ondansetron (1 mg/kg, p.o.), promethazine (1 mg/kg, i.p.), and L733,060 (5 mg/kg, s.c.), respectively) transiently reversed the reserpine-induced allodynia and fatigue. The results indicate that mast cells mediate painful and fatigue behaviours in this fibromyalgia model, representing potential therapy targets to treat fibromyalgia syndrome., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Anastrozole, an aromatase inhibitor, induces painful musculoskeletal symptoms, which affect patients' quality of life and lead to therapy discontinuation. Efforts have been made to understand the mechanisms involved in these painful symptoms to manage them better. In this context, we explored the role of the Transient Receptor Potential Vanilloid 4 (TRPV4), a potential transducer of several nociceptive mechanisms, in anastrozole-induced musculoskeletal pain in mice. Besides, we evaluated the possible sensibilization of TRPV4 by signalling pathways downstream, PLC, PKC and PKCε from kinin B 2 (B 2 R) and B 1 (B 1 R) receptors activation in anastrozole-induced pain. Anastrozole caused mechanical allodynia and muscle strength loss in mice. HC067047, TRPV4 antagonist, reduced the anastrozole-induced mechanical allodynia and muscle strength loss. In animals previously treated with anastrozole, the local administration of sub-nociceptive doses of the TRPV4 (4α-PDD or hypotonic solution), B 2 R (Bradykinin) or B 1 R (DABk) agonists enhanced the anastrozole-induced pain behaviours. The sensitizing effects induced by local injection of the TRPV4, B 2 R and B 1 R agonists in animals previously treated with anastrozole were reduced by pre-treatment with TRPV4 antagonist. Furthermore, inhibition of PLC, PKC or PKCε attenuated the mechanical allodynia and muscle strength loss induced by TRPV4, B 2 R and B 1 R agonists. The generation of painful conditions caused by anastrozole depends on direct TRPV4 activation or indirect, e.g., PLC, PKC and PKCε pathways downstream from B 2 R and B 1 R activation. Thus, the TRPV4 channels act as sensors of extracellular and intracellular changes, making them potential therapeutic targets for alleviating pain related to aromatase inhibitors use, such as anastrozole., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cisplatin is a platinum-based chemotherapy drug widely used to treat various solid tumours. Although it is effective in anti-cancer therapy, many patients develop peripheral neuropathy during and after cisplatin treatment. Peripheral neuropathy results from lesions or diseases in the peripheral somatosensory nervous system and is a significant cause of debilitation and suffering in patients. In recent years, preclinical studies have been conducted to elucidate the mechanisms involved in chemotherapy-induced peripheral neuropathic pain, as well as to promote new therapeutic targets since current treatments are ineffective and are associated with adverse effects. G-protein coupled receptors and ion channels play a significant role in pain processing and may represent promising targets for improving the management of cisplatin-induced neuropathic pain. This review describes the role of G protein-coupled receptors and ion channels in cisplatin-induced pain, analysing preclinical experimental studies that investigated the role of each receptor subtype in the modulation of cisplatin-induced pain.

Dexamethasone has a high anti-inflammatory efficacy in treating skin inflammation. However, its use is related to the rebound effect, rosacea, purple, and increased blood glucose levels. Nanotechnology approaches have emerged as strategies for drug delivery due to their advantages in improving therapeutic effects. To reduce dexamethasone-related adverse effects and improve the anti-inflammatory efficacy of treatments, we developed nanocarriers containing this corticosteroid and oleic acid. Nanocapsules and nanoemulsion presented dexamethasone content close to the theoretical value and controlled dexamethasone release in an in vitro assay. Gellan gum-based hydrogels were successfully prepared to employ the nanostructured systems. A permeation study employing porcine skin showed that hydrogels containing non-nanoencapsulated dexamethasone (0.025%) plus oleic acid (3%) or oleic acid (3%) plus dexamethasone (0.025%)-loaded nanocapsules provided a higher amount of dexamethasone in the epidermis compared to non-nanoencapsulated dexamethasone (0.5%). Hydrogels containing oleic acid plus dexamethasone-loaded nanocapsules effectively inhibited mice ear edema (with inhibitions of 89.26 ± 3.77% and 85.11 ± 2.88%, respectively) and inflammatory cell infiltration (with inhibitions of 49.58 ± 4.29% and 27.60 ± 11.70%, respectively). Importantly, the dexamethasone dose employed in hydrogels containing the nanocapsules that effectively inhibited ear edema and cell infiltration was 20-fold lower (0.025%) than that of non-nanoencapsulated dexamethasone (0.5%). Additionally, no adverse effects were observed in preliminary toxicity tests. Our study suggests that nanostructured hydrogel containing a reduced effective dose of dexamethasone could be a promising therapeutic alternative to treat inflammatory disorders with reduced or absent adverse effects. Additionally, testing our formulation in a clinical study on patients with skin inflammatory diseases would be very important to validate our study.

Cigarette filters were utilized as carbon source for the production of solid carbon acid catalysts. In this study, the process of carbonization and simultaneous sulfonation via hydrothermal treatment was employed. The catalysts were prepared by mixing cigarette filters and sulfuric acid at temperatures of 100, 150, and 190 °C for durations ranging from 2 to 8 h. It was observed that the highest conversion of oleic acid occurred when the catalyst was synthesized at 190 °C for 4 h. The optimized conditions for the esterification reaction using this catalyst included an oleic acid to methanol molar ratio of 1:12, a catalyst loading of 5 wt%, and a temperature of 100 °C for 1 h. Additionally, the catalyst was successfully reused four times without significantly impacting the reaction yield. These findings highlight a promising approach for the utilization of waste materials, with immediate implications for waste management practices and positive environmental impacts., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The phytochemical study of Cattleya intermedia (Orchidaceae) led to the isolation of two new stilbenoids and one new 9,10-dihydrophenanthrene, 4',5-dihydroxy-2',3-dimethoxy-dihydrostilbene ( 1 ), 3,6'-dihydroxy-4'-methoxy-dihydrostilbene ( 2 ) and 1,2,6-trihydroxy-3,8-dimethoxy-9,10-dihydrophenanthrene ( 3 ), named cattleymediol, cattleyol and phenanmediol, respectively, in addition to other five known compounds ( 4-8 ). The structural elucidations of the isolated compounds were carried out through the analyses of the one-dimensional 1 H, 1 ³C and NOE NMR spectra, and the 2D HSQC, HMBC, COSY and NOESY spectra, besides high-resolution mass spectrometry. In addition to this, the crude extract and its main fractions were analysed by ultra-high performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-QTOF-MS/MS), leading to the putative identification of several other compounds, including flavonoids and organic acids derivatives. Finally, the main fractions of the crude extract, and the pure compounds cattleymediol ( 1 ) and lusiantridine ( 7 ), had their antiproliferative activities evaluated against human cancerous HeLa and non-cancerous VERO cells.

Musculoskeletal pain is a widely experienced public healthcare issue, especially after traumatic muscle injury. Besides, it is a common cause of disability, but this pain remains poorly managed. However, the pathophysiology of traumatic muscle injury-associated pain and inflammation has not been fully elucidated. In this regard, the transient receptor potential ankyrin 1 (TRPA1) has been studied in inflammatory and painful conditions. Thus, this study aimed to evaluate the antinociceptive and anti-inflammatory effect of the topical application of a TRPA1 antagonist in a model of traumatic muscle injury in rats. The mechanical trauma model was developed by a single blunt trauma impact on the right gastrocnemius muscle of Wistar male rats (250-350 g). The animals were divided into four groups (Sham/Vehicle; Sham/HC-030031 0.05%; Injury/Vehicle, and Injury/HC-030031 0.05%) and topically treated with a Lanette® N cream base containing a TRPA1 antagonist (HC-030031, 0.05%; 200 mg/muscle) or vehicle (Lanette® N cream base; 200 mg/muscle), which was applied at 2, 6, 12, 24, and 46 h after muscle injury. Furthermore, we evaluated the contribution of the TRPA1 channel on nociceptive, inflammatory, and oxidative parameters. The topical application of TRPA1 antagonist reduced biomarkers of muscle injury (lactate/glucose ratio), spontaneous nociception (rat grimace scale), inflammatory (inflammatory cell infiltration, cytokine levels, myeloperoxidase, and N-acetyl-β-D-glucosaminidase activities) and oxidative (nitrite levels and dichlorofluorescein fluorescence) parameters, and mRNA Trpa1 levels in the muscle tissue. Thus, these results demonstrate that TRPA1 may be a promising anti-inflammatory and antinociceptive target in treating muscle pain after traumatic muscle injury., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To determine risk factors for the development of long coronavirus disease 2019 (COVID-19) in healthcare personnel (HCP)., Methods: We conducted a case-control study among HCP who had confirmed symptomatic COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Cases were defined as those having long COVID according to the Centers for Disease Control and Prevention definition. Controls were defined as HCP who had documented COVID-19 but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up., Results: Of 7,051 HCP diagnosed with COVID-19, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with the development of long COVID were female sex (OR, 1.21; 95% CI, 1.05-1.39), age (OR, 1.01; 95% CI, 1.00-1.02), and 2 or more SARS-CoV-2 infections (OR, 1.27; 95% CI, 1.07-1.50). Those infected with the SARS-CoV-2 δ (delta) variant (OR, 0.30; 95% CI, 0.17-0.50) or the SARS-CoV-2 o (omicron) variant (OR, 0.49; 95% CI, 0.30-0.78), and those receiving 4 COVID-19 vaccine doses prior to infection (OR, 0.05; 95% CI, 0.01-0.19) were significantly less likely to develop long COVID., Conclusions: Long COVID can be prevalent among HCP. Acquiring >1 SARS-CoV-2 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.

Premise: The Amazonian hyperdominant genus Eperua (Fabaceae) currently holds 20 described species and has two strongly different inflorescence and flower types, with corresponding different pollination syndrome. The evolution of these vastly different inflorescence types within this genus was unknown and the main topic in this study., Methods: We constructed a molecular phylogeny, based on the full nuclear ribosomal DNA and partial plastome, using Bayesian inference and maximum likelihood methods, to test whether the genus is monophyletic, whether all species are monophyletic and if the shift from bat to bee pollination (or vice versa) occurred once in this genus., Results: All but two species are well supported by the nuclear ribosomal phylogeny. The plastome phylogeny, however, shows a strong geographic signal suggesting strong local hybridization or chloroplast capture, rendering chloroplast barcodes meaningless in this genus., Conclusions: With our data, we cannot fully resolve the backbone of the tree to clarify sister genera relationships and confirm monophyly of the genus Eperua. Within the genus, the shift from bat to bee and bee to bat pollination has occurred several times but, with the bee to bat not always leading to a pendant inflorescence., (© 2023 The Authors. American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

This study evaluated the effects of previous exposure to Transcranial Direct Current Stimulation (tDCS) on nociceptive, neuroinflammatory, and neurochemical parameters, in rats subjected to an incisional pain model. Forty adult male Wistar rats (60 days old; weighing ∼ 250 g) were divided into five groups: 1. control (C); 2. drugs (D); 3. surgery (S); 4. surgery + sham-tDCS (SsT) and 5. surgery + tDCS (ST). Bimodal tDCS (0.5 mA) was applied for 20 min/day/8 days before the incisional model. Mechanical allodynia (von Frey) was evaluated at different time points after surgery. Cytokines and BDNF levels were evaluated in the cerebral cortex, hippocampus, brainstem, and spinal cord. Histology and activity of myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) were evaluated in the surgical lesion sites in the right hind paw. The results demonstrate that the surgery procedure increased BDNF and IL-6 levels in the spinal cord levels in the hippocampus, and decreased IL-1β and IL-6 levels in the cerebral cortex, IL-6 levels in the hippocampus, and IL-10 levels in the brainstem and hippocampus. In addition, preemptive tDCS was effective in controlling postoperative pain, increasing BDNF, IL-6, and IL-10 levels in the spinal cord and brainstem, increasing IL-1β in the spinal cord, and decreasing IL-6 levels in the cerebral cortex and hippocampus, IL-1β and IL-10 levels in the hippocampus. Preemptive tDCS also contributes to tissue repair, preventing chronic inflammation, and consequent fibrosis. Thus, these findings imply that preemptive methods for postoperative pain management should be considered an interesting pain management strategy, and may contribute to the development of clinical applications for tDCS in surgical situations., 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 © 2023 Elsevier B.V. All rights reserved.)

Background: A new classification for periodontitis has been adopted in clinical practice. However, there are still discussions regarding this new classification and difficulties in its adoption, both by professionals and researchers. Thus, this study aimed to evaluate which salivary biomarkers are present in periodontitis, following the new classification of periodontal diseases through meta-analysis., Material and Methods: A literature search was carried out in the scientific databases: PubMed, Scielo and Google scholar to select studies. The selection of studies was followed by two authors upon reading of the title, abstract and full text. The necessary data were collected and statistical analyses were performed using the Review Manager statistical software version 5.4, with calculation of Mean Difference, heterogeneity (I²) and funnel plot with P < 0.05., Results: After following the selection criteria, 9 articles were selected for comparison. The studies address the presence of biomarkers in the saliva of patients with periodontitis and their possible use in the monitoring and diagnosis of the disease. For the meta-analytic comparison, a sample size of 1,983 individuals was used. Statistical analyses showed that nitric oxide, IL-6, IL-1B and osteoprotegerin are substances that are significantly present in patients with periodontitis (P < 0.05)., Conclusions: IL-6, nitric oxide, IL-1B, TNF-α and osteoprotegerin are among the most present biomarkers in patients with periodontitis, and may be used in the future as a monitoring of periodontal disease. The present study also revealed that there was no statistically significant difference in the concentration of these biomarkers for clinical distinction from periodontitis.