Cisplatin-Resistant Urothelial Bladder Cancer Cells Undergo Metabolic Reprogramming beyond the Warburg Effect.

Advanced urothelial bladder cancer (UBC) patients are tagged by a dismal prognosis and high mortality rates, mostly due to their poor response to standard-of-care platinum-based therapy. Mediators of chemoresistance are not fully elucidated. This work aimed to study the metabolic profile of advanced UBC, in the context of cisplatin resistance. Three isogenic pairs of parental cell lines (T24, HT1376 and KU1919) and the matching cisplatin-resistant (R) sublines were used. A set of functional assays was used to perform a metabolic screening on the cells. In comparison to the parental sublines, a tendency was observed towards an exacerbated glycolytic metabolism in the cisplatin-resistant T24 and HT1376 cells; this glycolytic phenotype was particularly evident for the HT1376/HT1376R pair, for which the cisplatin resistance ratio was higher. HT1376R cells showed decreased basal respiration and oxygen consumption associated with ATP production; in accordance, the extracellular acidification rate was also higher in the resistant subline. Glycolytic rate assay confirmed that these cells presented higher basal glycolysis, with an increase in proton efflux. While the results of real-time metabolomics seem to substantiate the manifestation of the Warburg phenotype in HT1376R cells, a shift towards distinct metabolic pathways involving lactate uptake, lipid biosynthesis and glutamate metabolism occurred with time. On the other hand, KU1919R cells seem to engage in a metabolic rewiring, recovering their preference for oxidative phosphorylation. In conclusion, cisplatin-resistant UBC cells seem to display deep metabolic alterations surpassing the Warburg effect, which likely depend on the molecular signature of each cell line.

State of the Art of Non-Invasive Technologies for Bladder Monitoring: A Scoping Review.

Bladder monitoring, including urinary incontinence management and bladder urinary volume monitoring, is a vital part of urological care. Urinary incontinence is a common medical condition affecting the quality of life of more than 420 million people worldwide, and bladder urinary volume is an important indicator to evaluate the function and health of the bladder. Previous studies on non-invasive techniques for urinary incontinence management technology, bladder activity and bladder urine volume monitoring have been conducted. This scoping review outlines the prevalence of bladder monitoring with a focus on recent developments in smart incontinence care wearable devices and the latest technologies for non-invasive bladder urine volume monitoring using ultrasound, optical and electrical bioimpedance techniques. The results found are promising and their application will improve the well-being of the population suffering from neurogenic dysfunction of the bladder and the management of urinary incontinence. The latest research advances in bladder urinary volume monitoring and urinary incontinence management have significantly improved existing market products and solutions and will enable the development of more effective future solutions.

Jogos de Realidade Virtual na Reabilitação de Pacientes Oncológicos: Revisão Sistemática da Literatura / Jogos de Realidade Virtual na Reabilitação de Pacientes Oncológicos: Revisão Sistemática da Literatura

Introdução: A fisioterapia mostra-se benéfica na reabilitação de pacientes oncológicos. Todavia, por se tratar de uma atividade monótona para muitos pacientes, vem perdendo seu espaço para novas técnicas como a gameterapia, que utiliza jogos eletrônicos de realidade virtual como instrumento reabilitador e preventivo. Objetivo: Investigar os efeitos da gameterapia em pacientes oncológicos. Método: Revisão sistemática da literatura seguindo o guia PRISMA. A busca dos artigos foi realizada nas bases PubMed, LILACS, MEDLINE e PEDro, utilizando os descritores neoplasm, cancer, virtual reality, rehabilitation e physiotherapy. Foram considerados elegíveis ensaios clínicos controlados e estudos prospectivos publicados nas línguas portuguesa, inglesa ou espanhola nos últimos 12 anos (julho de 2010 a julho de 2022). Resultados: Foram identificados 94 estudos, sendo nove considerados elegíveis para compor a amostra final. Dos ensaios clínicos selecionados, cinco utilizaram Nintendo Wii, dois utilizaram Xbox e um usou óculos de realidade virtual. Os estudos mostram que a gameterapia promoveu redução dos sintomas de ansiedade, fadiga e depressão, melhorou a coordenação motora fina e geral, e diminuiu o medo de se movimentar. Entretanto, não foi tão eficaz quanto a terapia tradicional para diminuir a dor crônica. Conclusão: A gameterapia exerce efeitos positivos sobre variáveis pertinentes à saúde em pacientes oncológicos, destacando-se a diminuição da fadiga relacionada ao câncer. Além disso, favorece a redução do tempo de internação de pacientes hospitalizados e aumenta a adesão dos pacientes ao tratamento.

Introduction: Physiotherapy is beneficial for the rehabilitation of cancer patients. However, as this is a monotonous activity for many patients, it has been losing its space to new techniques such as gametherapy, which uses virtual reality videogames as a rehabilitative and preventive instrument. Objective: To investigate the effects of gametherapy on cancer patients. Method: Systematic literature review following the PRISMA guide. The search for articles was performed in PubMed, LILACS, MEDLINE and PEDro databases, using the descriptors neoplasm, cancer, virtual reality rehabilitation and physiotherapy. Controlled clinical trials and prospective studies published in Portuguese, English or Spanish were eligible in the last 12 years (July 2010 to July 2022). Results: There were 94 studies identified, and nine were included in the final sample. Of the selected clinical trials, five used Nintendo Wii, two used Xbox and one used virtual reality glasses. The studies showed that gametherapy reduced symptoms of anxiety, fatigue and depression, improved fine and gross motor skills, and reduced fear of moving. However, it was not as effective as traditional therapy in decreasing chronic pain. Conclusion: Gametherapy has positive effects on health-related variables in cancer patients, standing out the decrease in cancer-related fatigue. In addition, it favors a reduction in the length of stay of hospitalized patients and increases patient adherence to treatment.

Introducción: La fisioterapia es beneficiosa en la rehabilitación de pacientes oncológicos. Sin embargo, por ser una actividad monótona para muchos pacientes, ha ido perdiendo su espacio para nuevas técnicas como la gameterapia, que utiliza videojuegos de realidad virtual como instrumento rehabilitador y preventivo. Objetivo: Investigar los efectos de la gameterapia en pacientes con cáncer. Método: Revisión sistemática de la literatura siguiendo la guía PRISMA. La búsqueda de artículos se realizó en PubMed, LILACS, MEDLINE y PEDro, utilizando los descriptores neoplasia, cáncer, realidad virtual, rehabilitación y fisioterapia. Se consideraron elegibles los ensayos clínicos controlados y los estudios prospectivos publicados en portugués, inglés o español en los últimos 12 años (julio de 2010 a julio de 2022). Resultados: Se identificaron 94 estudios, de los cuales nueve fueron considerados elegibles para componer la muestra final. De los ensayos clínicos seleccionados, cinco usaron Nintendo Wii, dos usaron Xbox y uno usó gafas de realidad virtual. Los estudios muestran que la terapia de juego redujo los síntomas de ansiedad, fatiga y depresión, mejoró la coordinación motora fina y general y disminuyó el miedo a moverse. Sin embargo, no fue tan eficaz como la terapia tradicional para disminuir el dolor crónico. Conclusión: La terapia de juego tiene efectos positivos en variables relacionadas con la salud en pacientes con cáncer, destacando la disminución de la fatiga relacionada con el cáncer. Además, favorece la reducción del tiempo de hospitalización de los pacientes hospitalizados y aumenta la adherencia del paciente al tratamiento.

Virtual reality and serious game therapy for post-stroke individuals: A preliminary study with humanized rehabilitation approach protocol.

OBJECTIVE: The current study proposed the development and preliminary validation of a humanized training approach for upper limb rehabilitation of chronic post-stroke individuals, using serious game (SG) and virtual reality (VR) technologies. MATERIALS AND METHODS: Ten individuals with chronic stroke participated in the study. Accompanied by a health professional, 15 sessions of the SG were performed in a laboratory, in a humanized way, lasting between 30 and 45 min each. The assessments were made pre- and post-intervention with the SG, and the following parameters were evaluated (considering the elbow joint): Modified Ashworth Scale (MAS), range of movement (ROM) and tonic stretch reflex threshold (TSRT). Global measures such as quality of life (QOL) were also assessed by the Stroke-Specific Quality of Life Scale (SSQL), Brunnstrom Recovery Scale (BRS) and General Health Questionnaire (GHQ-28). The following tests were applied to verify statistically significant differences: Shapiro-Wilk test, t-test, and Wilcoxon-Mann-Whitney test. RESULTS: The parameters ROM, TSRT, BRS, and SSQL showed statistically significant differences between pre- and post-intervention (p < 0.01). The ROM increase was about 8%. The objective evaluation of spasticity (provided by the TRST) showed an increase of 28% over the average pre- and post-intervention values. Three participants showed decreased resistance to passive stretching according to the results of the MAS, and seven participants moved to the next stage of the BRS. For QOL, the scores indicated around 20% of post-intervention improvement. CONCLUSION: The intervention had no adverse effects, showed a high degree of compliance, provided increased ROM, improved QOL, reduced spasticity and allowed these individuals the opportunity to test a promising technology for upper limb rehabilitation with emphasis in humanized aspects of therapy.

Wrist Rigidity Evaluation in Parkinson's Disease: A Scoping Review.

(1) Background: One of the main cardinal signs of Parkinson's disease (PD) is rigidity, whose assessment is important for monitoring the patient's recovery. The wrist is one of the joints most affected by this symptom, which has a great impact on activities of daily living and consequently on quality of life. The assessment of rigidity is traditionally made by clinical scales, which have limitations due to their subjectivity and low intra- and inter-examiner reliability. (2) Objectives: To compile the main methods used to assess wrist rigidity in PD and to study their validity and reliability, a scope review was conducted. (3) Methods: PubMed, IEEE/IET Electronic Library, Web of Science, Scopus, Cochrane, Bireme, Google Scholar and Science Direct databases were used. (4) Results: Twenty-eight studies were included. The studies presented several methods for quantitative assessment of rigidity using instruments such as force and inertial sensors. (5) Conclusions: Such methods present good correlation with clinical scales and are useful for detecting and monitoring rigidity. However, the development of a standard quantitative method for assessing rigidity in clinical practice remains a challenge.

Multidimensional Assessment of Individuals with Parkinson's Disease: Development and Structure Validation of a Self-Assessment Questionnaire.

(1) Background: Several instruments are used to assess individuals with Parkinson's disease (PD). However, most instruments necessitate the physical presence of a clinician for evaluation, were not designed for PD, nor validated for remote application. (2) Objectives: To develop and validate a self-assessment questionnaire that can be used remotely, and to assess the respondents' health condition. (3) Methods: A questionnaire, so-called Multidimensional Assessment Questionnaire for Individuals with PD (MAQPD), was developed, administered remotely, and completed by 302 people with PD. MAQPD was validated using factor analysis (FA). The participants' level of impairment was estimated using factor loadings. The scale's accuracy was assessed estimating floor and ceiling effects and Cronbach's alpha. (4) Results: FA suggested classifying the questions into daily activities, cognition, and pain. The respondents did not have extremely severe impairment (most scores ranged from 100 to 180 points), and the factors with the lowest scores were cognition and pain. The instrument had no significant floor or ceiling effects (rates less than 15%), and the Cronbach's alpha value was larger than 0.90. (5) Conclusion: MAQPD is the only remote self-administered tool found in the literature capable of providing a detailed assessment of the general health status of individuals with PD.

SpES: A new portable device for objective assessment of hypertonia in clinical practice.

Spasticity is a motor disorder that affects millions around the world. It is a particular type of hypertonia characterized by the speed-dependent increase of the muscle stretch reflex, where its correct evaluation is essential for rehabilitation. The preferred method for this assessment is the Modified Ashworth Scale (MAS), a rank derived from clinical observations. Currently, few methods can quantify this disorder objectively. Tonic Stretch Reflex Threshold (TSRT) is a parameter speed-dependent obtained from electromyographic (EMG) measurements and angular signals. Therefore, the objective was to develop portable equipment for quantitative assessments of hypertonia based on TSRT. To this end, we designed an instrument composed of single-channel EMG, flexible optical goniometer, and software for the online computing of TSRT from acquired signals. The new equipment named SpES (Spasticity Evaluation System) was applied to measuring hypertonia of the biceps brachii in twenty-two participants. The experiment was performed during manual passive stretching of the affected limb at predefined speeds. The results provided by SpES presented a satisfactory coefficient of determination (0.70) and a strong correlation with MAS (0.79). In summary, while MAS depends on precise clinical observations, SpES has the TSRT quantitative method embedded for reaching an objective assessment of hypertonia in clinical practice.

Antispasmodic effects of the essential oil of Croton zehnteneri, anethole, and estragole, on tracheal smooth muscle.

Croton zehntneri is a plant well adapted to the semi-arid climate of northeastern region of Brazil. The essential oil of C. zehntneri (EOCz) has been described to have several pharmacologic properties, including effect on airflow resistance of in vivo respiratory system. For this reason, we investigated the hypothesis that EOCz and its major constituents, anethole and estragole, have antispasmodic activity on tracheal muscle. In tracheal rings of Wistar rats, maintained in Krebs-Henseleit's solution, EOCz, anethole and estragole inhibited contractions induced by 60mM [K+], ACh (10µM), Ba2+ and Phorbol dibutirate (1 µM). For EOCz, anethole and estragole, the IC50 for inhibition of KCl-induced contractions were 145.8 ± 14.8, 89.9 ± 7.4 and 181.0 ± 23.3 µg/mL, respectively, and for ACh-induced contraction, they were 606.1 ± 122.0, 160.5 ± 33.0 and 358.6 ± 49.2 µg/mL. Pharmacodynamic efficacy was maximal in all cases. These data in Ba2+-induced contraction and the differential IC50 suggested that blockade of Voltage Dependent Calcium Channels (VDCC) is a component of the mechanism of action of the three agents. Evaluation of the direct effect of anethole, on VDCC, showed inhibition of the Ca2+ current through this type of channel. These results show that EOCz and the constituents have antispasmodic activity and the mechanism includes blockade of VDCC channels.

Polymer Optical Fiber Goniometer: A New Portable, Low Cost and Reliable Sensor for Joint Analysis.

The quantitative measurement of an articular motion is an important indicator of its functional state and for clinical and pathology diagnoses. Joint angle evaluation techniques can be applied to improve sports performance and provide feedback information for prostheses control. Polymer optical fiber (POF) sensors are presented as a novel method to evaluate joint angles, because they are compact, lightweight, flexible and immune to electromagnetic interference. This study aimed to characterize and implement a new portable and wearable system to measure angles based on a POF curvature sensor. This study also aimed to present the system performance in bench tests and in the measurement of the elbow joint in ten participants, comparing the results with a consolidated resistive goniometer. Results showed high repeatability of sensors between cycles and high similarity of behavior with the potentiometer, with the advantage of being more ergonomic. The proposed sensor presented errors comparable to the literature and showed some advantages over other goniometers, such as the inertial measurement unit (IMU) sensor and over other types of POF sensors. This demonstrates its applicability for joint angle evaluation.

1,8-Cineole blocks voltage-gated L-type calcium channels in tracheal smooth muscle.

1,8-Cineole is a cyclic monoterpenoid used in folk medicine for treatment of numerous respiratory diseases and other infections. 1,8-Cineole has anti-inflammatory, antioxidant, and myorelaxant effects, as well as low toxicity. In the present study, the effects of 1,8-cineole on contractility and voltage-gated calcium channels (VGCC) in tracheal smooth muscle were investigated. Intact and dissociated tracheal smooth muscle were used for muscle contraction and patch-clamp recordings, respectively. In experiments involving muscle contraction, 1,8-cineole potentiated contractions at low concentrations and relaxed contractions induced by isotonic K+ at high concentrations. AMTB (a TRPM8 channel blocker) reduced the potentiation induced by 1,8-cineole while indomethacin (a COX inhibitor) did not block this effect. In dissociated myocytes, 1,8-cineole partially blocked Ba2+ currents through VGCC in a concentration-dependent manner. 1,8-Cineole shifted the steady-state activation and inactivation curves to the left and also reduced the current decay time constant. In conclusion, 1,8-cineole has a dual effect on tracheal smooth muscle contraction resulting in a biphasic effect. Our data suggest that the potentiation effect is mediated by activation of TRPM8 channels and the relaxation effect is mediated by the blockage of L-type VGCC.

Avaliação clínica da eficácia do óleo de andiroba na queimadura pós-depilação com luz intensa pulsada: estudo prospectivo, comparativo e duplo-cego / Clinical evaluation of the effectiveness of andiroba oil in burns caused by hair removal with intense pulsed light: a prospective, comparative and double-blind study

Introdução: A depilação com luz intensa pulsada é método de uso corrente, utlizando-se geralmente corticosteroides de baixa ou média potência para o alívio da dor e a reação inflamatória que se seguem ao procedimento. Compostos botânicos, como a emulsão de óleo de andiroba, têm demonstrado efeitos hidratantes e anti-inflamatórios. Objetivo: Como opção aos corticosteroides tópicos, os autores testam a eficácia da emulsão do óleo de andiroba comparando-a à da desonida. Métodos: Foi desenhado estudo prospectivo, comparativo e duplo-cego com nove pacientes do sexo feminino, submetidas à depilação com luz intensa pulsada na região inguinal e tratadas imediatamente após o procedimento com desonida num lado e emulsão de óleo de andiroba no outro lado, aleatoriamente. As pacientes avaliaram a sensação de dor segundo a escala visual analógica de dor, e uma médica dermatologista observadora avaliou a reação inflamatória gerada pelo procedimento, comparando-se os dois lados de forma cega. Resultados: Não houve diferenças significativas no alívio da dor e da reação inflamatória, na comparação dos dois produtos. O potencial analgésico e anti-inflamatório da emulsão do óleo de andiroba praticamente equivaleu ao da desonida. Conclusões: Os resultados deste estudo-piloto indicam que a emulsão do óleo de andiroba pode ser opção no tratamento após a fotoepilação.

Introduction: Intense pulsed light is commonly used for hair removal. Corticosteroids of low or medium potency are generally employed for pain and inflammatory reaction relief following such procedures. Botanical compounds, such as andiroba oil emulsion, have been proven to have moisturizing and anti-inflammatory effects. Objective: To compare the effectiveness of andiroba oil emulsion to desonide as an option to topical corticosteroids. Methods: A prospective, comparative, double-blind study evaluated nine female patients who underwent air removal with intense pulsed light in the inguinal region. The patients were treated immediately after the procedure with desonide on one side and andiroba oil emulsion on the other. The patients rated the pain sensation using a visual analog pain scale, and an observer dermatologist physician evaluated the inflammatory reaction caused by the procedure, comparing the two sides blindly. Results: There were no significant differences in pain relief or inflammation between the two products. The analgesic and anti-inflammatory potential of andiroba oil emulsion practically equaled that of desonide. Conclusions: This pilot study's results indicate that andiroba oil emulsion can be a treatment option following photoepilation.