Prevention of chemotherapy-related bone loss with doxorubicin-loaded solid lipid nanoparticles.

Aim: Breast cancer and its metastases involve high mortality even with advances in chemotherapy. Solid lipid nanoparticles provide a platform for drug delivery, reducing side effects and treatment-induced bone loss. A solid nanoparticle containing doxorubicin was evaluated for its ability to prevent bone loss in a pre-clinical breast cancer model. Methods: We investigated the effects of SLNDox in an aggressive metastatic stage IV breast cancer model, which has some important features that are interesting for bone loss investigation. This study evaluates bone loss prevention potential from solid lipid nanoparticles containing doxorubicin breast cancer treatment, an evaluation of the attenuation of morphological changes in bone tissue caused by the treatment and the disease and an assessment of bone loss imaging using computed tomography and electron microscopy. Results: Chemotherapy-induced bone loss was also observed in tumor-free animals; a solid lipid nanoparticle containing doxorubicin prevented damage to the growth plate and to compact and cancellous bones in the femur of tumor-bearing and healthy animals. Conclusion: The association of solid lipid nanoparticles with chemotherapeutic drugs with proven efficacy promotes the prevention of serious consequences of chemotherapy, reducing tumor progression, increasing quality of life and improving prognosis and survival.

[Box: see text].

Integrating policy, data and technology in pursuing effective management of ecosystem services.

With the growing concerns about the protection of ecosystem functions and services, governments have developed public policies and organizations have produced an awesome volume of digital data freely available through their websites. On the other hand, advances in data acquisition through remote sensed sources and processing through geographic information systems (GIS) and statistical tools, allowed an unprecedent capacity to manage ecosystems efficiently. However, the real-world scenario in that regard remains paradoxically challenging. The reasons can be many and diverse, but a strong candidate relates with the limited engagement among the interest parties that hampers bringing all these assets into action. The aim of the study is to demonstrate that management of ecosystem services can be significantly improved by integrating existing environmental policies with environmental big data and low-cost GIS and data processing tools. Using the Upper Rio das Velhas hydrographic basin located in the state of Minas Gerais (Brazil) as example, the study demonstrated how Principal Components Analysis based on a diversity of environmental variables assembled sub-basins into urban, agriculture, mining and heterogeneous profiles, directing management of ecosystem services to the most appropriate officially established conservation plans. The use of GIS tools, on the other hand, allowed narrowing the implementation of each plan to specific sub-basins. This optimized allocation of preferential management plans to priority areas was discussed for a number of conservation plans. A paradigmatic example was the so-called Conservation Use Potential (CUP) devoted to the protection of aquifer recharge (provision service) and control of water erosion (regulation service), as well as to the allocation of uses as function of soil capability (support service). In all cases, the efficiency gains in readiness for plans' implementation and economy of resources were prognosed as noteworthy.

Corrigendum: Porcine circovirus 3: a new challenge to explore.

[This corrects the article DOI: 10.3389/fvets.2023.1266499.].

Myeloid­derived suppressor cells as targets of emerging therapies and nanotherapies (Review).

Breast cancer (BC) is the leading cause of cancer-related mortality among women worldwide. Immunotherapies are a promising approach in cancer treatment, particularly for aggressive forms of BC with high mortality rates. However, the current eligibility for immunotherapy remains limited to a limited fraction of patients with BC. Myeloid-derived suppressor cells (MDSCs), originating from myeloid cells, are known for their dual role in immunosuppression and tumor promotion, significantly affecting patient outcomes by fostering the formation of premetastatic niches. Consequently, targeting MDSCs has emerged as a promising avenue for further exploration in therapeutic interventions. Leveraging nanotechnology-based drug delivery systems, which excel in accumulating drugs within tumors via passive or active targeting mechanisms, are a promising strategy for the use of MDSCs in the treatment of BC. The present review discusses the immunosuppressive functions of MDSCs, their role in BC, and the diverse strategies for targeting them in cancer therapy. Additionally, the present review discusses future advancements in BC treatments focusing on MDSCs. Furthermore, it elucidates the mechanisms underlying MDSC activation, recruitment and differentiation in BC progression, highlighting the clinical characteristics that render MDSCs suitable candidates for the therapy and targeted nanotherapy of BC.

Three New Polyprenylated Benzophenone Derivatives Isolated from Clusia burle-marxii.

Three new polyprenylated benzophenone derivatives named burlemarxione G-I (1-3) were isolated from C. burle-marxii trunks (compound 1) and leaves (compounds 2 and 3), along with the known compound burlemarxione F. Burlemarxione G (1) was isolated after methylation with diazomethane and it is the keto-enol tautomeric pair of burlemarxione F. Burlemarxione H (2) derives from burlemarxiones F and G, but it has additional rings due to cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. Burlemarxione I (3) has two additional cyclizations: the first encompasses the cyclization of the former isopentenyl group into an 11,11-dimethyl-six-membered ring, whereas the second produces additional rings due to the cyclization of the prenyl group attached to C-5 that establishes new single bonds between C-1 and C-23, as well as, between C-24 and C-29. All three compounds showed moderate anti-glioma activity. These results show that C. burle-marxii is an important source of sophisticated polyprenylated benzophenone derivatives.

Long-term disability after cerebral ischemic stroke following a Bothrops atrox snakebite in the Brazilian Amazon.

Bothrops atrox envenomations in the Brazilian Amazon are responsible for a number of local and systemic effects. Among these, stroke presents the worst prognosis for the patient since it may evolve into disabilities and/or premature death. This complication is caused by coagulation disorders and generates hemorrhagic and thrombotic conditions. This study presents a case report of a 54-year-old female patient who presented extensive cerebral ischemia after a B. atrox envenomation that occurred in the state of Amazonas, Brazil. The patient was hospitalized for 102 days, which included a stay in the intensive care unit. Clinical and laboratory findings indicated a thrombogenic coagulopathy. On discharge, the patient had no verbal response, partial motor response, and right hemiplegia. The assessment carried out four years after discharge evidenced incapacitation, global aphasia and bilateral lower and upper limbs showed hypotrophy with a global decrease in strength. Ischemic stroke is a possible complication of B. atrox snakebites even after antivenom treatment, with the potential to cause debilitating long-term consequences.

Niobic acid as a support for microheterogeneous nanocatalysis of sodium borohydride hydrolysis under mild conditions.

This study explores the stabilization by niobic acid, of Pt, Ni, Pd, and Au nanoparticles (NPs) for the efficient microheterogeneous catalysis of NaBH4 hydrolysis for hydrogen production. Niobic acid is the most widely studied Nb2O5 polymorph, and it is employed here for the first time for this key reaction relevant to green energy. Structural insights from XRD, Raman, and FTIR spectroscopies, combined with hydrogen production data, reveal the role of niobic acid's Brønsted acidity in its catalytic activity. The supported NPs showed significantly higher efficiency than the non-supported counterparts regarding turnover frequency, average hydrogen production rate, and cost. Among the tested NPs, PtNPs and NiNPs demonstrate the most favorable results. The data imply mechanism changes during the reaction, and the kinetic isotope assay indicates a primary isotope effect. Reusability assays demonstrate consistent yields over five cycles for PtNPs, although catalytic efficiency decreases, likely due to the formation of reaction byproducts.

Thymol as adjuvant in oncology: molecular mechanisms, therapeutic potentials, and prospects for integration in cancer management.

Cancer remains a global health challenge, prompting a search for effective treatments with fewer side effects. Thymol, a natural monoterpenoid phenol derived primarily from thyme (Thymus vulgaris) and other plants in the Lamiaceae family, is known for its diverse biological activities. It emerges as a promising candidate in cancer prevention and therapy. This study aims to consolidate current research on thymol's anticancer effects, elucidating its mechanisms and potential to enhance standard chemotherapy, and to identify gaps for future research. A comprehensive review was conducted using databases like PubMed/MedLine, Google Scholar, and ScienceDirect, focusing on studies from the last 6 years. All cancer types were included, assessing thymol's impact in both cell-based (in vitro) and animal (in vivo) studies. Thymol has been shown to induce programmed cell death (apoptosis), halt the cell division cycle (cell cycle arrest), and inhibit cancer spread (metastasis) through modulation of critical signaling pathways, including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinase (ERK), mechanistic target of rapamycin (mTOR), and Wnt/ß-catenin. It also enhances the efficacy of 5-fluorouracil (5-FU) in colorectal cancer treatments. Thymol's broad-spectrum anticancer activities and non-toxic profile to normal cells underscore its potential as an adjunct in cancer therapy. Further clinical trials are essential to fully understand its therapeutic benefits and integration into existing treatment protocols.

Quality of life in children and adolescents with blood coagulation disorders and hemoglobinopathies.

The aim of this study was to evaluate the impact of oral conditions and health-related quality of life (HRQoL) on oral health-related quality of life (OHRQoL) in children and adolescents with blood coagulation disorders and hemoglobinopathies (BCDH). The study was cross-sectional and included 61 individuals aged 2 to 18 years with BCDH. Exams for dental caries (dmft/DMFT index), oral hygiene (simplified oral hygiene index - OHI-S), and gingival health (modified gingival index - MGI) were performed. The pediatric quality of life inventory™ (PedsQL™) generic core scale and oral health scale were used to measure HRQoL and OHRQoL. Spearman's correlation coefficient (ρ) and the Mann-Whitney test (α = 0.05) were conducted to assess the relationship between covariates and the PedsQL™ oral health scale. The mean PedsQL™ oral health scale score was 76.66 (SD = 21.36). Worse OHRQoL was correlated with poor oral hygiene (ρ = -0.383; p: 0.004), poor gingival health (ρ = -0.327; p = 0.014), and better HRQoL (ρ = 0.488; p < 0.001). Greater untreated dental caries experience was associated with worse OHRQoL (p = 0.009). Worse oral health status in children and adolescents with BCDH negatively impacts OHRQoL, and OHRQoL and quality of life analyzed from a generic perspective are positively correlated constructs in this population.

Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction.

Mood disorders and substance use disorder (SUD) are of immense medical and social concern. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, it is only relatively recently that the role of glia in these disorders has attracted attention. Detailed understanding of the glial functions in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, the specific contributions of neurotrophic factors, neuroinflammation, and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes, and synantocytes) on phenotypic manifestation of mood disorders or SUD are emphasized. In addition, use of this knowledge in the potential development of novel therapeutics is touched upon.

Iron toxicity, ferroptosis and microbiota in Parkinson's disease: Implications for novel targets.

Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized by loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Iron (Fe)-dependent programmed cell death known as ferroptosis, plays a crucial role in the etiology and progression of PD. Since SNpc is particularly vulnerable to Fe toxicity, a central role for ferroptosis in the etiology and progression of PD is envisioned. Ferroptosis, characterized by reactive oxygen species (ROS)-dependent accumulation of lipid peroxides, is tightly regulated by a variety of intracellular metabolic processes. Moreover, the recently characterized bi-directional interactions between ferroptosis and the gut microbiota, not only provides another window into the mechanistic underpinnings of PD but could also suggest novel interventions in this devastating disease. Here, following a brief discussion of PD, we focus on how our expanding knowledge of Fe-induced ferroptosis and its interaction with the gut microbiota may contribute to the pathophysiology of PD and how this knowledge may be exploited to provide novel interventions in PD.

Association Between Augmentation Index and Total Sleep Time in Night Shift Workers.

Augmentation index and pulse wave velocity are markers of vascular compromise and independent predictors of cardiovascular risk and mortality. While the link between shift work and heightened cardiovascular risk is established, the intricate genesis of early cardiovascular outcomes in shift workers remains incompletely understood. However, there is evidence that sleep duration plays a role in this regard. Here we evaluate the association of total sleep time with pulse wave velocity, augmentation index, and central blood pressure in night shift workers. This study cross-sectionally evaluated the association of total sleep time evaluated by 10-day monitoring actigraphy with augmentation index, pulse wave velocity, and brachial and central blood pressure evaluated by oscillometry in nursing professionals, 63 shift workers (89% women; age = 45.0 ± 10.5 years), and 17 (100% women; age = 41.8 ± 15.6) day workers. There were no differences in the studied variables between shift workers and day workers. Results of correlation analysis demonstrated that pulse wave velocity, central systolic blood pressure, central diastolic blood pressure, brachial systolic blood pressure, and brachial diastolic blood pressure tended to have significant correlation with each other, while these measures did not have a significant relationship with augmentation index in both groups. However, results of adjusted restricted cubic spline analysis showed a U-shaped-curve association between total sleep time and augmentation index (p < 0.001 for trend) with a nadir at 300-360 min of total sleep time in shift workers. The present study showed that total sleep time, assessed by actigraphy, had a U-shaped association with augmentation index in shift workers, which indicated better characteristics of vascular functionality when sleep time was 5-6 h in the workers studied.

Beyond land use planning and ecosystem services assessment with the conservation use potential framework: A study in the Upper Rio das Velhas basin, Brazil.

Human actions can damage the ecosystems and affect the services depending on them, with ample detrimental consequences. In earlier studies, the Conservation Use Potential (PCU) framework proved useful in assessing the capacity for aquifer recharge, suitable land uses and resistance to erosion at the river basin scale. On the other hand, the joint analysis of PCU and land uses allowed identifying the adequacy of current uses in relation to suitability (natural uses) in various basins. This was especially useful from the management perspective in basins with environmental conflicts, where current uses differed from suitability, because the PCU indicated how and where the conflicts should be mitigated. Besides the use as management tool, the PCU has potential to shed light over environmental issues such as ecosystem services, but that was not tempted so far. The aim of this work was therefore to bridge that knowledge gap and frame the PCU's application from the standpoint of Ecosystem Services (ES) assessment. We demonstrated how the PCU could be used to improve provision (recharge), support (sustainable agriculture) and regulation (resistance to erosion) services in a specific basin with land use conflicts (the Upper Rio das Velhas basin, located in Minas Gerais, Brazil), through the planning of suitable uses. It was noted that the studied basin is mostly composed of Very Low, Low and Medium potentials. These classes occur because steep slopes, fragile soils and lithologies with high denudation potential and low nutrient supply dominate in the basin. On the other hand, urban sprawl has a negative impact on all ES, while maintaining agricultural areas with appropriate management can effectively regulate erosion. As per the current results, the premise of using the PCU as joint management-environmental tool was fully accomplished, and is recommended a basis for public policy design and implementation in Brazil and elsewhere.

Nicotinic Acetylcholine Receptors in Glial Cells as Molecular Target for Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by resting tremor, bradykinesia, rigidity, and postural instability that also includes non-motor symptoms such as mood dysregulation. Dopamine (DA) is the primary neurotransmitter involved in this disease, but cholinergic imbalance has also been implicated. Current intervention in PD is focused on replenishing central DA, which provides remarkable temporary symptomatic relief but does not address neuronal loss and the progression of the disease. It has been well established that neuronal nicotinic cholinergic receptors (nAChRs) can regulate DA release and that nicotine itself may have neuroprotective effects. Recent studies identified nAChRs in nonneuronal cell types, including glial cells, where they may regulate inflammatory responses. Given the crucial role of neuroinflammation in dopaminergic degeneration and the involvement of microglia and astrocytes in this response, glial nAChRs may provide a novel therapeutic target in the prevention and/or treatment of PD. In this review, following a brief discussion of PD, we focus on the role of glial cells and, specifically, their nAChRs in PD pathology and/or treatment.

Immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) using two-dose primary protocol in children and adolescents (Immunita-002, Brazil): A phase IV six-month follow up.

Introduction: Vaccines are essential for the prevention and control of several diseases, indeed, monitoring the immune response generated by vaccines is crucial. The immune response generated by vaccination against SARS-CoV-2 in children and adolescents is not well defined regarding to the intensity and medium to long-term duration of a protective immune response, which may point out the need of booster doses and might support the decisions in public health. Objective: The study aims to evaluate the immunogenicity and safety of inactivated SARS-CoV-2 vaccine (CoronaVac) in a two-dose primary protocol in children and adolescent aging from 3 to 17 years old in Brazil. Methods: Participants were invited to participate in the research at two public healthcare centers located in Serrana (São Paulo) and Belo Horizonte (Minas Gerais), Brazil. Participants underwent medical interviews to gather their medical history, including COVID-19 history and medical records. Physical exams were conducted, including weight, blood pressure, temperature, and pulse rate measurements. Blood samples were obtained from the participants before vaccination, 1 month after the first dose, and 1, 3, and 6 months after the second dose and were followed by a virtual platform for monitoring post-vaccination reactions and symptoms of COVID-19. SARS-CoV-2 genome from Swab samples of COVID-19 positive individuals were sequenced by NGS. Total antibodies were measured by ELISA and neutralizing antibodies to B.1 lineage and Omicron variant (BA.1) quantified by PRNT and VNT. The cellular immune response was evaluated by flow cytometry by the quantification of systemic soluble immune mediators. Results: The follow-up of 640 participants showed that the CoronaVac vaccine (Sinovac/Butantan Institute) was able to significantly induce the production of total IgG antibodies to SARS-CoV-2 and the production of neutralizing antibodies to B.1 lineage and Omicron variant. In addition, a robust cellular immune response was observed with wide release of pro-inflammatory and regulatory mediators in the early post-immunization moments. Adverse events recorded so far have been mild and transient except for seven serious adverse events reported on VigiMed. Conclusions: The results indicate a robust and sustained immune response induced by the CoronaVac vaccine in children and adolescents up to six months, providing evidences to support the safety and immunogenicity of this effective immunizer.

The Phytochemical Agathisflavone Modulates miR146a and miR155 in Activated Microglia Involving STAT3 Signaling.

MicroRNAs (miRs) act as important post-transcriptional regulators of gene expression in glial cells and have been shown to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Here, we investigated the effects of agathisflavone, a biflavonoid purified from the leaves of Cenostigma pyramidale (Tul.), on modulating the expression of miRs and inflammatory mediators in activated microglia. C20 human microglia were exposed to oligomers of the ß-amyloid peptide (Aß, 500 nM) for 4 h or to lipopolysaccharide (LPS, 1 µg/mL) for 24 h and then treated or not with agathisflavone (1 µM) for 24 h. We observed that ß-amyloid and LPS activated microglia to an inflammatory state, with increased expression of miR-146a, miR-155, IL1-ß, IL-6, and NOS2. Treatment with agathisflavone resulted in a significant reduction in miR146a and miR-155 induced by LPS or Aß, as well as inflammatory cytokines IL1-ß, IL-6, and NOS2. In cells stimulated with Aß, there was an increase in p-STAT3 expression that was reduced by agathisflavone treatment. These data identify a role for miRs in the anti-inflammatory effect of agathisflavone on microglia in models of neuroinflammation and AD.

Restabelecimento da dimensão vertical de oclusão em paciente com erosão ácida devido à refluxo gastroesofágico

Objetivo: relatar o caso clínico de um paciente com perda de dimensão vertical de oclusão (DVO) associada à erosão dentária causada por refluxo gastroesofágico, discorrendo aspectos inerentes ao diagnóstico, planejamento, execução e tratamento reabilitador com restaurações indiretas cerâmicas. Descrição do caso clínico: Paciente de 37 anos queixou-se de desgaste dentário, que provocava dor e incômodo estético com o seu sorriso. O paciente relatou ser portador da doença do refluxo gastroesofágico e possuir dores de cabeça frequentes, e o exame clínico denotou perda da DVO. Após os protocolos fotográficos, molde e análise do exame radiográfico, determinou-se clinicamente o restabelecimento da DVO, sendo que por meio dos mock-ups, verificou-se a adaptação do paciente com relação a nova DVO. Preparos para facetas e tabletops foram realizados, seguidos de selamento imediato da dentina. A reabilitação foi iniciada pelo arco superior, sendo que para este arco, optou-se pelo fluxo analógico. Peças em dissilicato de lítio fresado e maquiado foram confeccionadas, e cimentadas com cimento resinoso dual. Para o arco inferior, foi utilizado o fluxo digital, e as peças foram obtidas por fresagem. Após a finalização da reabilitação, o paciente mostrou-se satisfeito com o tratamento, com melhora no aspecto estético-facial-dental, além das dores de cabeça. Considerações finais: O restabelecimento da DVO por meio de restaurações indiretas em pacientes com erosão dental é um procedimento previsível, desde que seja precedido de uma anamnese completa, diagnóstico da DVO por meio de restaurações provisórias e estratégias de adesão e cimentação adequadas.

Risk factors for postoperative urinary retention after deep brain stimulation surgery: the role of the subthalamic nucleus.

OBJECTIVE: Deep brain stimulation (DBS) is a common procedure in neurosurgery used for the treatment of Parkinson's disease (PD) and essential tremor (ET) among other disorders. Lower urinary tract dysfunction is a common complication in PD, and this study aimed to evaluate the risk factors of postoperative urinary retention (POUR) after DBS surgery in patients with PD compared with patients with ET. Understanding the risk factors associated with this complication may help in the development of strategies to minimize its occurrence and improve patient outcomes. METHODS: The study was a retrospective analysis of patients who underwent DBS surgery for PD and ET at the University of Florida between 2010 and 2021. The surgical technique used has been described in previous articles and included a two-stage procedure, with stage 1 involving burr hole placement, microelectrode recording, and electrode implantation and stage 2 involving the placement of an implantable pulse generator (IPG). Data were collected on patient characteristics and surgical details and analyzed using univariate and mixed-linear models. Post hoc propensity score matching was used to confirm the association between subthalamic nucleus (STN)-DBS and POUR. RESULTS: The study included 350 patients (153 with PD and 197 with ET) who underwent 1086 DBS surgeries (lead implantations, IPG placement, and IPG replacements). The POUR rates were 16.6% (79/477), 5.2% (19/363), and 0.4% (1/246) for stage 1, stage 2, and IPG replacement procedures, respectively. Optimal mixed-effects logistic modeling revealed history of urinary retention (OR 9.3, p = 0.004), male sex (OR 2.7, p = 0.011), having an electrode placed or connected for the first time (OR 2.2, p = 0.014), anesthesia time (OR 1.5 for each 30-minute increase, p < 0.0001), preoperative opioid use (OR 1.4 for each additional 10 morphine milligram equivalents, p = 0.032), and Charlson Comorbidity Index (OR 1.4 per comorbidity, p = 0.017) to be significant risk factors for POUR. Having an electrode in the STN was found to be protective of POUR (propensity score-matched analysis: OR 0.2, p = 0.010). CONCLUSIONS: Most risk factors found to increase the risk of POUR in DBS are not modifiable but are still important to consider in preoperative planning. Opioid use reduction and shorter anesthesia time may be modifiable risk factors to weigh against their alternative. Targeting the STN during DBS may result in decreased rates of POUR. This highlights the potential for STN-targeted DBS in reducing POUR risk in PD and ET patients.

Effect of the Flavonoid Rutin on the Modulation of the Myenteric Plexuses in an Experimental Model of Parkinson's Disease.

Recent discoveries have shown that enteric glial cells play an important role in different neurodegenerative disorders, such as Parkinson's disease (PD), which is characterized by motor dysfunctions caused by the progressive loss of dopaminergic neurons in the substance nigra pars compacta and non-motor symptoms including gastrointestinal dysfunction. In this study, we investigated the modulatory effects of the flavonoid rutin on the behavior and myenteric plexuses in a PD animal model and the response of enteric glia. Adult male Wistar rats were submitted to stereotaxic injection with 6-hydroxydopamine or saline, and they were untreated or treated with rutin (10 mg/kg) for 14 days. The ileum was collected to analyze tissue reactivity and immunohistochemistry for neurons (HuC/HuD) and enteric glial cells (S100ß) in the myenteric plexuses. Behavioral tests demonstrated that treatment with rutin improved the motor capacity of parkinsonian animals and improved intestinal transit without interfering with the cell population; rutin treatment modulated the reactivity of the ileal musculature through muscarinic activation, reducing relaxation through the signaling pathway of nitric oxide donors, and increased the longitudinal contractility of the colon musculature in parkinsonian animals. Rutin revealed modulatory activities on the myenteric plexus, bringing relevant answers regarding the effect of the flavonoid in this system and the potential application of PD adjuvant treatment.

Caffeine Mouth Rinse Plus Ingestion Improves the 10-Km Time Trial Compared to Caffeine Mouth Rinse Alone.

Background: The benefits of caffeine to physical performance have been extensively demonstrated, however, it has recently been speculated that there is an effect of the administration route on its effectiveness. Purpose: The current study investigated the effect of caffeine mouth rinse in isolation or combined with ingestion on performance in a 30-minute constant-load exercise followed by a 10-km cycling time trial. Methods: Ten physically active men performed a 30-minute constant-load exercise at 50% of the graded test Wmax, followed by a 10-km cycling time trial. Before and at the middle points of the constant-load exercise and 10-km cycling time trial, the following conditions were administered: PLA (cellulose ingestion plus mouth rinsing with magnesium sulfate), ING (5 mg.kg-1 of caffeine ingestion plus mouth rinsing with magnesium sulfate), MR (cellulose ingestion plus mouth rinsing with 1.2% caffeine), and COMB (5 mg.kg-1 of caffeine ingestion plus mouth rinsing with 1.2% caffeine). Results: During the 30-minute constant-load exercise, COMB presented a lower rating of perceived exertion (RPE) than MR (p = .04). For the 10-km time trial, the COMB was faster than MR (MR = 1363 ± 345 vs. COMB = 1291 ± 308s, Δ% = 5.57, p = .05). Mean power output was higher in COMB than PLA, ING, and MR (234 ± 15 vs. 169 ± 29, 148 ± 11, and 145 ± 12 W, respectively). There were no differences between conditions for heart rate and RPE during the 10-km time trial. Conclusion: In summary, caffeine mouth rinsing potentiated the effects of caffeine ingestion during the 10-km time trial compared to caffeine mouth rinsing alone.