Spheroid Model of Mammary Tumor Cells: Epithelial-Mesenchymal Transition and Doxorubicin Response.

Breast cancer is the most prevalent cancer among women worldwide. Therapeutic strategies to control tumors and metastasis are still challenging. Three-dimensional (3D) spheroid-type systems more accurately replicate the features of tumors in vivo, working as a better platform for performing therapeutic response analysis. This work aimed to characterize the epithelial-mesenchymal transition and doxorubicin (dox) response in a mammary tumor spheroid (MTS) model. We evaluated the doxorubicin treatment effect on MCF-7 spheroid diameter, cell viability, death, migration and proteins involved in the epithelial-mesenchymal transition (EMT) process. Spheroids were also produced from tumors formed from 4T1 and 67NR cell lines. MTSs mimicked avascular tumor characteristics, exhibited adherens junction proteins and independently produced their own extracellular matrix. Our spheroid model supports the 3D culturing of cells isolated from mice mammary tumors. Through the migration assay, we verified a reduction in E-cadherin expression and an increase in vimentin expression as the cells became more distant from spheroids. Dox promoted cytotoxicity in MTSs and inhibited cell migration and the EMT process. These results suggest, for the first time, that this model reproduces aspects of the EMT process and describes the potential of dox in inhibiting the metastatic process, which can be further explored.

Updates in inspiratory muscle training for older adults: A systematic review.

Systematic reviews support the benefits of inspiratory muscle training (IMT) for exercise performance. Recently, many health benefits from IMT have been reported in older adults. Therefore, this work reviewed the literature focusing on IMT effects beyond physical performance in older adults, such as cardiorespiratory, metabolic, and postural balance outcomes. Searches were conducted with the following terms: ("respiratory muscle training" OR "inspiratory muscle training") OR ("inspiratory muscle strength training") AND ("elderly" OR "older" OR "aging" OR "aging"), and using the databases: MEDLINE (PubMed), SCOPUS and EUROPE PMC. Of the 356 articles found, 13 matched the inclusion criteria after screening. Based on reviewed studies, four to eight weeks of IMT (Mostly from 50 % up to 75 % of MIP, 7 days/week) improve cardiac autonomic control at rest and post-exercise, cerebrovascular response to orthostatic stress, static and dynamic balance, blood pressure control, endothelial function, and oxidative stress in older adults. The benefits of IMT in cardiac autonomic and vascular functions are reversed after training cessation. It thus appears that IMT promotes broad physiological gains for the older population. It is necessary to carry out more randomized clinical trials on the subject to confirm the findings of this research.

Leishmania spp. in equids and their potential vectors in endemic areas of canine leishmaniasis.

Equids may be infected by zoonotic Leishmania spp., including Leishmania infantum, in regions where canine leishmaniasis (CanL) is endemic, and Leishmania martiniquensis, which has been reported in horses from Central Europe. This study was designed to evaluate the occurrence of both Leishmania spp. among equids living in CanL endemic areas of Italy, as well as to identify dipteran vectors from the same habitats. From March to October 2023, blood, serum and tissue samples from skin lesions were collected from equids (n = 98; n = 56 donkeys and n = 42 horses) living in Italy, as well as sand flies and biting midges. Blood samples (n = 98) and skin lesions (n = 56) were tested for Leishmania spp. by conventional and real time PCRs and sera were tested by immunofluorescence antibody tests (IFAT) for both L. infantum and L. martiniquensis. Insects were morphologically identified, and female specimens (n = 268 sand flies, n = 7 biting midges) analyzed for Leishmania DNA, as well as engorged sand flies (n = 16) for blood-meal detection. Two animals with skin lesions (i.e., one donkey and one horse) scored positive for Leishmania spp. DNA, and 19 animals (i.e., 19.4%; n = 13 donkeys and n = 6 horses) were seropositive for L. infantum, with five of them also for L. martiniquensis. Most seropositive animals had no dermatological lesions (i.e., 68.4%) while both animals molecularly positive for Leishmania spp. scored seronegative. Of the 356 sand flies collected, 12 females (i.e., n = 8 Sergentomyia minuta; n = 3 Phlebotomus perniciosus, n = 1 Phlebotomus perfiliewi) were positive for Leishmania spp. DNA, and one out of seven biting midges collected was DNA-positive for L. infantum. Moreover, engorged sand flies scored positive for human and equine DNA. Data suggest that equids living in CanL endemic areas are exposed to Leishmania spp., but their role in the circulation of the parasite needs further investigations.

Licuri Kernel (Syagrus coronata (Martius) Beccari): A Promising Matrix for the Development of Fermented Plant-Based Kefir Beverages.

New licuri-based kefir beverages were obtained using water kefir grains as fermentation inoculum (1, 2.5, and 5%) under different fermentation times (24 and 48 h). Metagenomic sequencing of the kefir grains adapted to the aqueous licuri extract revealed Lactobacillus hilgardii and Brettanomyces bruxellensis to be predominant in this inoculum. The excellent adaptation of the kefir grains to the licuri extract raised the possibility of prebiotic action of these almonds. The beverages showed acidity values between 0.33 ± 0.00 and 0.88 ± 0.00 mg lactic acid/100 mL and pH between 3.52 ± 0.01 and 4.29 ± 0.04. The viability of lactic acid bacteria in the fermented beverages was equal to or greater than 108 CFU/mL, while yeasts were between 104 and 105 CFU/mL. There were significant differences (p < 0.05) in the proximate composition of the formulations, especially in the protein (1.37 ± 0.33-2.16 ± 0.84) and carbohydrate (5.86 ± 0.19-11.51 ± 1.26) contents. In addition, all the samples showed good stability in terms of acidity, pH, and viability for LAB and yeasts during 28 days of storage (4 °C). Overall, the beverages showed a dominant yellow-green color, non-Newtonian pseudoplastic behavior, and high mean scores in the sensory evaluation. This study provided evidence of the emerging potential of licuri in the plant-based beverage industry.

Cytomegalovirus in Adenoma and Carcinoma Lesions: Detecting Mono-Infection and Co-Infection in Salivary Glands.

Salivary glands' neoplasms are hard to diagnose and present a complex etiology. However, several viruses have been detected in these neoplasms, such as HCMV, which can play a role in certain cancers through oncomodulation. The co-infections between HCMV with betaherpesviruses (HHV-6 and HHV-7) and polyomaviruses (JCV and BKV) has been investigated. The aim of the current study is to describe the frequency of HCMV and co-infections in patients presenting neoplastic and non-neoplastic lesions, including in the salivary gland. Multiplex quantitative polymerase chain reaction was used for betaherpesvirus and polyomavirus quantification purposes after DNA extraction. In total, 50.7% of the 67 analyzed samples were mucocele, 40.3% were adenoma pleomorphic, and 8.9% were mucoepidermoid carcinoma. Overall, 20.9% of samples presented triple-infections with HCMV/HHV-6/HHV-7, whereas 9.0% were co-infections with HCMV/HHV-6 and HCMV/HHV-7. The largest number of co-infections was detected in pleomorphic adenoma cases. All samples tested negative for polyomaviruses, such as BKV and JCV. It was possible to conclude that HCMV can be abundant in salivary gland lesions. A high viral load can be useful to help better understand the etiological role played by viruses in these lesions. A lack of JCV and BKV in the samples analyzed herein does not rule out the involvement of these viruses in one or more salivary gland lesion subtypes.

Development and validation of Mayaro virus with luciferase reporter genes as a tool for antiviral assays.

Arboviruses are etiological agents in an extensive group of emerging diseases with great clinical relevance in Brazil, due to the wide distribution of their vectors and the favorable environmental conditions. Among them, the Mayaro virus (MAYV) has drawn attention since its emergence as the etiologic agent of Mayaro fever, a highly debilitating disease. To study viral replication and identify new drug candidates, traditional antiviral assays based on viral antigens and/or plaque assays have been demonstrating low throughput, making it difficult to carry out larger-scale assays. Therefore, we developed and characterized two DNA-launched infectious clones reporter viruses based on the MAYV strain BeAr 20290 containing the reporter genes of firefly luciferase (FLuc) and nanoluciferase (NLuc), designated as MAYV-firefly and MAYV-nanoluc, respectively. The viruses replicated efficiently with similar properties to the parental wild-type MAYV, and luminescence expression levels reflected viral replication. Reporter genes were also preserved during passage in cell culture, remaining stably expressed for one round of passage for MAYV-firefly and three rounds for MAYV-nanoluc. Employing the infectious clone, we described the effect of Rimantadine, an FDA-approved Alzheimer's drug, as a repurposing agent for MAYV but with a broad-spectrum activity against Zika virus infection. Additionally, we validated MAYV-nanoluc as a tool for antiviral drug screening using the compound EIDD-2749 (4'-Fluorouridine), which acts as an inhibitor of alphavirus RNA-dependent RNA polymerase.

The Relationship between Inspiratory Muscle Strength and Cycling Performance: Insights from Hypoxia and Inspiratory Muscle Warm-Up.

Hypoxia increases inspiratory muscle work and consequently contributes to a reduction in exercise performance. We evaluate the effects of inspiratory muscle warm-up (IMW) on a 10 km cycling time trial in normoxia (NOR) and hypoxia (HYP). Eight cyclists performed four time trial sessions, two in HYP (FiO2: 0.145) and two in NOR (FiO2: 0.209), of which one was with IMW (set at 40% of maximal inspiratory pressure-MIP) and the other was with the placebo effect (PLA: set at 15% MIP). Time trials were unchanged by IMW (NORIMW: 893.8 ± 31.5 vs. NORPLA: 925.5 ± 51.0 s; HYPIMW: 976.8 ± 34.2 vs. HYPPLA: 1008.3 ± 56.0 s; p > 0.05), while ventilation was higher in HYPIMW (107.7 ± 18.3) than HYPPLA (100.1 ± 18.9 L.min-1; p ≤ 0.05), and SpO2 was lower (HYPIMW: 73 ± 6 vs. HYPPLA: 76 ± 6%; p ≤ 0.05). A post-exercise-induced reduction in inspiratory strength was correlated with exercise elapsed time during IMW sessions (HYPIMW: r = -0.79; p ≤ 0.05; NORIMW: r = -0.70; p ≤ 0.05). IMW did not improve the 10 km time trial performance under normoxia and hypoxia.

Heated environment increases blood pressure drop and postural sway during initial orthostasis in healthy subjects.

PURPOSE: We tested the hypothesis that heat stress influences the closed-loop cardio-postural control by an increased blood pressure (BP) drop and postural sway. METHODS: Fourteen healthy individuals (eight women) performed two orthostatic tests under thermal reference (TC; ~ 24 ºC) and HOT (~ 38 ºC) conditions. The center-of-pressure (COP) displacements and the electromyography (EMG) activity of the calf muscles (medial gastrocnemius and tibialis anterior) were recorded during the initial orthostasis (ORT onset) after the supine-to-stand challenge. At the same period, BP (beat-to-beat) was continuously monitored, and supine-to-stand variations (∆%) were calculated. Sublingual temperature (Tsl) was measured as a surrogate of internal temperature. RESULTS: Tsl increased in HOT compared to TC (TC 36.5 ± 0.3 vs. HOT 36.7 ± 0.3 ºC; p < 0.01). COP distance was greater in HOT compared to TC condition (TC 596.6 ± 242.4 vs. HOT 680.2 ± 249.1 mm; p < 0.01). EMG activity of the gastrocnemius decreased in HOT compared to TC condition (TC 95.5 ± 19.8 vs. HOT 78.4 ± 22.8%mV; p = 0.02). EMG of tibialis did not change between TC and HOT (TC 83.5 ± 42.9 vs. HOT 66.1 ± 31.9% mV; p = 0.29). BP showed a greater fall in HOT compared to TC condition (∆%TC - 24.5 ± 13.2 vs. ∆%HOT - 33.2 ± 20.2%; p = 0.01). CONCLUSION: Heat stress causes a greater fall in blood pressure and a reduction in musculoskeletal pump activity during orthostatic onset. These effects could be potential mechanisms that underlie augmented postural instability under a heated environment.

Biological Significance of Probiotic Microorganisms from Kefir and Kombucha: A Review.

(1) Background: The human microbiota is essential for maintaining a healthy body. The gut microbiota plays a protective role against pathogenic bacteria. Probiotics are live microorganisms capable of preventing and controlling gastrointestinal and balancing the immune system. They also aid in better nutrients and vitamins absorption. Examples of natural probiotic cultures are kefir and kombucha. (2) Methods: Therefore, the aim of this review was to address the beneficial properties of probiotic kefir and kombucha using a Boxplot analysis to search for scientific data in the online literature up to January 2024: (Latin American and Caribbean Health Sciences (LILACS), PubMed, Medical Literature Analysis (MED-LINE), Science Direct, Google Scholar/Google Academic, Bioline Inter-national and Springer Link). Boxplots showed the summary of a set of data "Index Terms-Keywords" on kefir and kombucha in three languages (English, Portuguese and Spanish). (3) Results: Google Scholar was the database with the highest number of articles found, when the search for the keywords used in the study (containing ~4 × 106-~4 million articles available). This was Followed by the Science Direct database, containing ~3 × 106-~3 million articles available, and the BVS databases-Biblioteca Virtual de Saúde (Virtual Health Library) e Lilacs, both containing a value of ~2 × 106-~2 million articles available. The databases containing the smallest number of articles found were Nutrients and Medline, both containing a value of ≤0.1 × 106-≤100 thousand articles. (4) Conclusions: Scientific studies indicate that kefir and kombucha certainly contain various functional properties, such as antimicrobial, antitumor, anticarcinogenic and immunomodulatory activity, in addition to having a microbiological composition of probiotic bacteria and yeasts. Kefir and kombucha represent key opportunities in the food and clinic/medical fields.

The latency to awake from induced-obstructive sleep apnea is reduced in rats with chronic epilepsy.

OSA is known to increase the risk for SUDEP in persons with epilepsy, but the relationship between these two factors is not clear. Also, there is no study showing the acute responses to obstructive apnea in a chronic epilepsy model. Therefore, this study aimed to characterize cardiorespiratory responses to obstructive apnea and chemoreceptor stimulation in rats. In addition, we analyzed respiratory centers in the brain stem by immunohistochemistry. Epilepsy was induced with pilocarpine. About 30-60 days after the first spontaneous seizure, tracheal and thoracic balloons, and electrodes for recording the electroencephalogram, electromyogram, and electrocardiogram were implanted. Intermittent apneas were made by inflation of the tracheal balloon during wakefulness, NREM sleep, and REM sleep. During apnea, respiratory effort increased, and heart rate fell, especially with apneas made during wakefulness, both in control rats and rats with epilepsy. Latency to awake from apnea was longer with apneas made during REM than NREM, but rats with epilepsy awoke more rapidly than controls with apneas made during REM sleep. Rats with epilepsy also had less REM sleep. Cardiorespiratory responses to stimulation of carotid chemoreceptors with cyanide were similar in rats with epilepsy and controls. Immunohistochemical analysis of Phox2b, tryptophan hydroxylase, and NK1 in brain stem nuclei involved in breathing and sleep (retrotrapezoid nucleus, pre-Bötzinger complex, Bötzinger complex, and caudal raphe nuclei) revealed no differences between control rats and rats with epilepsy. In conclusion, our study showed that rats with epilepsy had a decrease in the latency to awaken from apneas during REM sleep, which may be related to neuroplasticity in some other brain regions related to respiratory control, awakening mechanisms, and autonomic modulation.

Comparison of Radiographic Outcomes Assessed via the Radiographic Union Scale for Tibial Fractures and Alkaline Phosphatase Levels during the Tibial Healing Process: A Series of Case Reports.

BACKGROUND/OBJECTIVES: Tibial diaphysis fractures are common injuries resulting from high-to-low-energy traumas in patients of all age groups, but few reports currently provide complementary parameters for the assessment of bone healing processes in the postoperative period. Serum alkaline phosphatase (ALP) and the scores from the Radiographic Union Scale for Tibial Fractures (RUST) can promote new horizons in this context. Therefore, the aim of this study was to assess the behavior of ALP and RUST through within-subject comparisons from immediately post-surgery to 49 days after tibial diaphysis fracture repair. METHODS: This article included four case studies where patients underwent the same procedures. Adults of both sexes aged 18 to 60 years with tibial fractures requiring surgery were included. After surgical intervention (T1), the patients were followed for 49 days after surgery, returning for follow-up appointments on the 21st (T2) and 49th (T3) days. At the follow-up appointments, new X-ray images were obtained, and blood samples were collected for ALP measurement. RESULTS: Serum ALP levels increased by T2 following tibial reamed intramedullary nailing surgery. While this increase persisted into T3 for two patients, a decline was observed during the same period for the other two patients. Both events are indicative of the bone consolidation process, and RUST scores at the T3 corroborate this perspective for all patients included in this study. Considering that delta ALP (T3-T1 value) was lower in patients who exhibited the highest RUST score, we suggest that a synchronized analysis between ALP and RUST allows medics to diagnose bone consolidation. CONCLUSIONS: Therefore, it can be concluded that the analysis of ALP alongside RUST may be complementary for evaluating bone consolidation following tibial reamed intramedullary nailing surgery, but future studies are needed to confirm this assertion.

Effects of Intravenous Lidocaine on Quality of Recovery After Laparoscopic Bariatric Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis aimed to assess the effects of pre and intraoperative lidocaine infusion on short-term recovery quality after laparoscopic bariatric surgeries. In the search across MEDLINE, Embase, and Cochrane databases, we considered randomized controlled trials comparing intravenous lidocaine vs placebo (saline) for patients with obesity undergoing laparoscopic bariatric surgery. Seven studies (640 patients) were included. The lidocaine group had a significantly higher recovery quality score, a lower morphine consumption, and a notably reduced rate of nausea and vomiting compared with the placebo group. Additionally, Lidocaine infusion was associated with a shorter hospital stay, while no significant difference was observed in the time to bowel function recovery between both groups. In conclusion, lidocaine infusion before and during laparoscopic bariatric surgery contributes to an enhanced quality of recovery.

Fusarium keratitis in a Brazilian tropical semi-arid area: Clinical-epidemiological features, molecular identification and antifungal susceptibility.

BACKGROUND: Fungal keratitis is a severe eye infection that can result in blindness and visual impairment, particularly in developing countries. Fusarium spp. are the primary causative agents of this condition. Diagnosis of Fusarium keratitis (FK) is challenging, and delayed treatment can lead to serious complications. However, there is limited epidemiological data on FK, especially in tropical areas. OBJECTIVES: This study aimed to describe the clinical, laboratorial and epidemiological characteristics of FK in a tropical semi-arid region of Brazil. PATIENTS/METHODS: Adult patients with laboratory-confirmed FK diagnosed between October 2019 and March 2022 were evaluated. Fusarium isolates were characterized at molecular level and evaluated regarding antifungal susceptibility. RESULTS: A total of 226 clinical samples from patients suspected of keratitis were evaluated; fungal growth was detected in 50 samples (22.12%); out of which 42 were suggestive of Fusarium spp. (84%). Molecular analysis of a randomly selected set of 27 isolates identified F. solani species complex (n = 14); F. fujikuroi sensu lato (n = 6) and F. dimerum sensu lato (n = 7); a total of 10 haplotypes were identified among the strains. All but one Fusarium strains were inhibited by amphotericin B, natamycin and fluconazole. Most patients were male (71.42%; 30 out of 42), aged from 27 to 73 years old. Trauma was the most important risk factor for FK (40.47%; 17 out of 42). Patients were treated with antifungals, corticoids and antibiotics; keratoplasty and eye enucleation were also performed. CONCLUSIONS: The study provided insights into the characteristics of FK in tropical regions and emphasized the importance of enhanced surveillance and management strategies.

International Trauma Questionnaire and Posttraumatic Cognitions Inventory-9: validity evidence and measurement invariance of their Brazilian versions.

BACKGROUND: The International Trauma Questionnaire (ITQ) is used to measure posttraumatic stress disorder (PTSD) and complex posttraumatic stress disorder (CPTSD) symptoms, and the Posttraumatic Cognitions Inventory-9 (PTCI-9) is used to measure posttraumatic cognitions. Both tools have been translated for use in Brazil. However, the psychometric properties of the Brazilian versions were not investigated, and no study has verified the invariance of these tools for many traumatic event types. OBJECTIVE: This study examined the validity, reliability, and measurement invariance of the Brazilian versions of the ITQ and the PTCI-9 for trauma type, gender, race, age group, education level, and geographical region. METHODS: A total of 2,111 people (67.74% women) participated in an online survey. The scale models were tested via confirmatory factor analyses and measurement invariance through multigroup analyses. Pearson's correlation analyses were used to examine the relationships between PTSD, CPTSD, posttraumatic cognitions, and depressive symptoms. RESULTS: Except for the affective dysregulation factor, the reliabilities of the ITQ and PTCI-9 dimensions were adequate. Models with six correlated dimensions for the ITQ and three correlated dimensions for the PTCI-9 showed adequate fit to the data. The ITQ and PTCI-9 exhibited scalar invariance for gender, race, age group, education level, and geographical region. The ITQ also demonstrated full invariance for trauma type. The factors of both instruments were related to each other and to depressive symptoms, with higher effect sizes for posttraumatic cognitions and complex posttraumatic stress disorder symptoms. CONCLUSION: We recommend using the Brazilian versions of the ITQ and PTCI-9, which are crucial tools for assessing and treating trauma-related disorders.

Inverted Layering Technique as a Biomimetic Procedure in a Multidisciplinary Resolution of Discolored Teeth: A Case Report.

The objective of this work is to report a restorative approach with composite resin applied in reverse in the aesthetic resolution of darkened anterior teeth. A 27-year-old female patient presented with the main complaint of dissatisfaction with the aesthetics of her smile due to dental darkening, a result of childhood trauma, without painful symptoms, pathological clinical signs or change in care. In the intraoral examination, a darkening of teeth 11 and 21 was observed, which radiographically showed thickening of the periodontal ligament, with disharmonious configuration of the marginal gingiva. From the clinical and radiographic characteristics, we opted for periodontal intervention for recovery and gingival levelling, followed by endodontic intervention and aesthetic restorative restoration. The restorative step was carried out sequentially by internal tooth bleaching, removal of dentin still pigmented after bleaching and enamel preservation. Soon after, it was restored in an alternative way and layered using a technique called reverse, using strips of polyethylene fiber over the dentin resin. The technique preserved the remaining enamel with the maintenance of the original remaining guides, proving to be a viable conservative alternative since of the diagnosis to the restorative conclusion in view of the longitudinal confirmation of the restorative efficacy after 1 year.

Energy metabolism and respirometry of lambs fed sun or shade dried hays of banana crop residues.

We aimed to evaluate the effects of different drying methods for banana residues on the energy metabolism and respirometry of growing lambs. Twenty Santa Inês x Dorper lambs were fed five experimental diets: Tifton 85 grass hay (Control), shade-dried banana leaf hay (LH Shade), shade-dried pseudostem banana hay (PH Shade), sun-dried banana leaf hay (LH Sun), and sun-dried banana pseudostem hay (PH Sun). Nutrient intake and digestibility were assessed in metabolic cages, whereas O2 consumption and CO2, methane, and heat production were measured in a respirometry chamber with animals fed at maintenance and ad libitum levels. Nutrient and energy intake was not influenced by diet. Pseudostem hay had higher apparent digestibility of dry matter (71.5%), organic matter (72.4%), and neutral detergent fiber (58.0%). However, this led to greater energy loss in the form of methane (12.1%). The banana residue hays and drying methods did not alter oxygen consumption, CO2 production, or heat production of animals fed ad libitum or during maintenance. On the other hand, the use of leaf hay resulted in a reduction of 24.7% in enteric methane production of animals fed ad libitum. The inclusion of pseudostem hay is recommended in sheep feedlot diet. This residue provided greater use of DM, however promoted a greater loss of energy in the form of methane, resulting in similar energy consumption. The drying methods did not reduce the availability of nutrients and the sun drying method is recommended, since it is a faster drying method.

The effect of low dose intra-articular S(+) ketamine on osteoarthritis in rats: an experimental study.

BACKGROUND: This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model. METHODS: Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg-1). Behavioral and histopathological assessments were conducted up to day 28. RESULTS: S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation. CONCLUSION: Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes. IRB APPROVAL NUMBER: 23115 012030/2009-05.

Aerobic exercise on the treadmill combined with transcranial direct current stimulation on the gait of people with Parkinson's disease: A protocol for a randomized clinical trial.

Gait impairments negatively affect the quality of life of people with Parkinson's disease (PwPD). Aerobic exercise (AE) is an alternative to alleviate these impairments and its combination with transcranial direct current stimulation (tDCS) has demonstrated synergistic effects. However, the effect of multitarget tDCS application (i.e., motor, and prefrontal cortices simultaneously) combined with physical exercise on gait impairments is still little known. Thus, the proposed randomized clinical trial will verify the acute effects of AE combined with tDCS applied on motor and prefrontal cortices separately and simultaneously on gait (spatial-temporal and cortical activity parameters) in PwPD. Twenty-four PwPD in Hoehn & Yahr stages I-III will be recruited for this crossover study. PwPD will practice AE on treadmill simultaneously with the application of anodal tDCS during four intervention sessions on different days (∼ one week of interval). Active tDCS will be applied to the primary motor cortex, prefrontal cortex, and both areas simultaneously (multitarget), with an intensity of 2 mA for 20 min. For sham, the stimulation will remain at 2 mA for 10 s. The AE will last a total of 30 min, consisting of warm-up, main part (20 min with application of tDCS), and recovery. Exercise intensity will be controlled by heart rate. Spatial-temporal and cortical activity parameters will be acquired before and after each session during overground walking, walking with obstacle avoidance, and walking with a cognitive dual task at self-preferred velocity. An accelerometer will be positioned on the fifth lumbar vertebra to obtain the spatial-temporal parameters (i.e., step length, duration, velocity, and swing phase duration). Prefrontal cortex activity will be recorded from a portable functional near-infrared spectroscopy system and oxygenated and deoxygenated hemoglobin concentrations will be analyzed. Two-way ANOVAs with repeated measures for stimulation and moment will be performed. The findings of the study may contribute to improving gait in PwPD. Trial registration: Brazilian Clinical Trials Registry (RBR-738zkp7).

Artisanal mining of monazite and cassiterite in the Amazon: Potential risks of rare earth elements for the environment and human health.

Artisanal mining is intensely carried out in developing countries, including Brazil and especially in the Amazon. This method of mineral exploration generally does not employ mitigation techniques for potential damages and can lead to various environmental problems and risks to human health. The objectives of this study were to quantify the concentrations of rare earth elements (REEs) and estimate the environmental and human health risks in cassiterite and monazite artisanal mining areas in the southeastern Amazon, as well as to understand the dynamics of this risk over time after exploitation. A total of 35 samples of wastes classified as overburden and tailings in active areas, as well as in areas deactivated for one and ten years were collected. Samples were also collected in a forest area considered as a reference site. The concentrations of REEs were quantified using alkaline fusion and ICP-MS. The results were used to calculate pollution indices and environmental and human health risks. REEs showed higher concentrations in anthropized areas. Pollution and environmental risk levels were higher in areas deactivated for one year, with considerable contamination factors for Gd and Sm and significant to extreme enrichment factors for Sc. Human health risks were low (< 1) in all studied areas. The results indicate that artisanal mining of cassiterite and monazite has the potential to promote contamination and enrichment by REEs.

Relationship between tumor thickness and GATA3 immunoexpression in lip and tongue squamous cell carcinomas.

PURPOSE: Lower lip squamous cell carcinomas (LLSCCs) exhibit lower levels of aggressiveness, low relations with metastases and better prognosis when compared with intraoral squamous cell carcinomas. Differently from the oral tongue squamous cell carcinomas (OTSCCs) have a high tendency towards local invasion and lymph nodal dissemination. Our aim was to evaluate tumor thickness in cases of oral squamous cell carcinoma and correlate it with histological grade of malignancy and GATA3 immunoreactivity. METHODS: Sixty specimens (30 LLSCCs and 30 OTSCCs) were scanned and digitized for the subsequent measurement of tumor thickness, histopathological examination, and quantitative analysis of GATA3 in the parenchyma and stroma of the tumors. RESULTS: Tumor thickness was lower in LLSCC compared to OTSCCs. Immunohistochemical analysis of GATA3 in parenchyma, stroma and both compartments showed higher immunoreactivity in LLSCCs compared to OTSCCs. We observed a negative correlation between tumor thickness and GATA3 expression in parenchyma, stroma, and both compartments. Our results revealed the presence of GATA3 in all cases both in the parenchyma and in the stroma. Higher expression was more related to LLSCCs, which are known to be less aggressive tumors than OTSCCs. CONCLUSIONS: A greater tumor thickness was found in OTSCCs, which was correlated with lower expression of GATA3, suggesting that this protein is involved in the inhibition of proliferative, migratory, and invasive capacity.