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.
(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.
(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.
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.
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.
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.
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.
•The metodology proposed may have contributed to the high adherence of volunteers and the improvement of clinical parameters.•Results showed the success of the methodology for rehabilitation of the upper limbs of post-stroke individuals.•The application of an instrument dedicated to objectively evaluate spasticity, provided assertive results of this parameter.•The applied methodology obtained positive results beyond the motor aspects, it also influenced the quality of life.
Bradykinesia is the main motor symptom of Parkinson's disease (PD). The clinical assessment of bradykinesia is mainly based on clinical scales, however, this type of assessment is subjective and ...inaccurate. This study aimed to evaluate bradykinesia objectively using a developed serious game, called RehaBEElitation. Fifteen individuals with PD (experimental group - EG) and 15 healthy individuals (control group - CG) participated in this study. Data collection was performed in the ON and OFF states of medication. Bradykinesia was evaluated using the gold standard clinical assessment scale, and calculating the response time (RT) and the participants' angular velocity (AV) of movement when playing RehaBEElitation. The t-test and the Wilcoxon-Mann-Whitney test were used for each variable, RT and AV, to confirm the differences between CG and EG, EG in the two medication states, CG and EG in the ON state, and CG and EG in the OFF state. Significant differences between groups were found in all comparisons (p<0.001). CG participants had the smallest RT, followed by EG participants in the ON state and EG participants in the OFF state. CG exhibited the largest AV, followed by EG in the ON state and EG in the OFF state. In short, the RehaBEElitation serious game is an alternative tool to objectively assess bradykinesia of individuals with PD.
TRV027 is a biased agonist for the Angiotensin (Ang)-II type 1 receptor (AT
R), able to recruit β-arrestin 2 independently of G-proteins activation. β-arrestin activation in the central nervous ...system (CNS) was suggested to oppose the effects of Ang-II. The present study evaluates the effect of central infusion of TRV027 on arterial pressure (AP), autonomic function, baroreflex sensitivity (BRS), and peripheral vascular reactivity. Spontaneously hypertensive (SH) and Wistar Kyoto (WKY) rats were treated with TRV027 for 14 days (20 ng/h) delivered to the lateral ventricle via osmotic minipumps. Mechanistic studies were performed in HEK293T cells co-transfected with AT
R and Ang converting enzyme type 2 (ACE2) treated with TRV027 (100 nM) or Ang-II (100 nM). TRV027 infusion in SH rats (SHR) reduced AP (~20 mmHg,
<0.05), sympathetic vasomotor activity (ΔMAP = -47.2 ± 2.8 compared with -64 ± 5.1 mmHg,
<0.05) and low-frequency (LF) oscillations of AP (1.7 ± 0.2 compared with 5.8 ± 0.4 mmHg,
<0.05) compared with the SHR control group. TRV027 also increased vagal tone, improved BRS, reduced the reactivity of mesenteric arteries to Ang-II and increased vascular sensitivity to phenylephrine (Phe), acetylcholine, (ACh), and sodium nitroprusside (SNP).
, TRV027 prevented the Ang-II-induced up-regulation of ADAM17 and in contrast with Ang-II, had no effects on ACE2 activity and expression levels. Furthermore, TRV027 induced lesser interactions between AT
R and ACE2 compared with Ang-II. Together, these data suggest that due to its biased activity for the β-arrestin pathway, TRV027 has beneficial effects within the CNS on hypertension, autonomic and vascular function, possibly through preserving ACE2 compensatory activity in neurones.
A adesão ao tratamento em ambulatórios psiquiátricos é um elemento vital do cuidado em saúde mental. Embora sejam enfrentados desafios significativos, é possível melhorar a adesão por meio de ...estratégias educacionais, de suporte e de colaboração entre pacientes e profissionais de saúde. Ao reconhecer a importância desse aspecto e trabalhar para superar os obstáculos, pode-se melhorar os resultados para os pacientes e promover uma saúde mental mais robusta e resiliente em nossas comunidades. Este estudo teve como objetivo investigar os principais fatores que influenciam a adesão ao tratamento nos ambulatórios psiquiátricos. Para isso, foi conduzida uma revisão sistemática da literatura, selecionando artigos científicos publicados entre 2019 e 2024, disponíveis nas bases de dados Scielo, Medline e Lilacs. Após uma análise aprofundada e discussão dos resultados, chegou-se à conclusão de que a adesão ao tratamento nos ambulatórios psiquiátricos é influenciada por uma variedade de fatores, incluindo a continuidade no acompanhamento terapêutico, a capacidade de mentalização dos pacientes, o modelo de atendimento e as influências sociodemográficas e clínicas, destacando a necessidade de abordagens personalizadas e integradas para melhorar o cuidado nesses ambientes.
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