Action observation and motor imagery have no effect on balance and freezing of gait in Parkinson's disease: a randomized controlled trial.

BACKGROUND: Combining action observation (AO) and motor imagery (MI) training may induce greater brain activity in areas usually involved in Parkinson's disease (PD) and lead to greater behavioral and neurophysiological effects than when used separately. AIM: To determine the effects of combining AO, MI, and gait training on balance and freezing of gait in individuals with PD. DESIGN: This is a single-blinded, randomized controlled clinical trial. SETTING: Laboratory of Intervention and Analysis of Movement (LIAM) from the Department of Physical Therapy of a Brazilian University. POPULATION: Study sample consisted of individuals diagnosed with idiopathic PD by a neurologist specialized in movement disorders. METHODS: 39 individuals with PD were divided into experimental (EG=21) and control groups (CG=18). EG performed 12 sessions of AO, MI, and gait training, whereas CG watched PD-related educational videos and performed 12 sessions of gait training. Balance (measured using the Mini Balance Evaluation Systems Test [MiniBESTest]) and freezing of gait (measured using the Freezing of Gait Questionnaire) were reassessed one day after the end of the intervention. RESULTS: We did not observe significant intra- and intergroup differences in freezing of gait. For the EG, we observed a significant intragroup difference in the total score of MiniBESTest (F=5.2; P=0.02), and sensory orientation (F=4.5; P=0.04) and dynamic gait (F=3.6; P=0.03) domains. MiniBESTest domains were not different between groups. CONCLUSIONS: Combining AO, MI, and gait training was not more effective than isolated gait training for balance and freezing of gait in individuals with PD. CLINICAL REHABILITATION IMPACT: MI training can moderate AO effects and enhance motor learning when both therapies are combined. Therefore, this approach may still have the potential to be included in the treatment of PD. New studies should investigate whether the factors that influence these results are related to the protocol's sensitivity in changing the evaluated parameters or to the time and intensity of AO and MI training.

Direct Synthesis of α-Sulfenylated Ketones under Electrochemical Conditions.

We investigated the electrochemical sulfenylation reaction in both batch and continuous flow regimes, involving thiophenols/thiols and enol-acetates to yield α-sulfenylated ketones, without using additional oxidants or catalysts. Studies with different electrolytes were also performed, revealing that quaternary ammonium salts are the best mediators for this reaction. Notably, during the study of the reaction scope, a Boc-cysteine proved to be extremely tolerant to our protocol, thus increasing its relevance. The methodology also proved to be scalable in both batch and continuous flow conditions, opening up possibilities for further studies since these relevant functional groups are important moieties in organic synthesis.

Are biomechanical strategies to perform functional activities different between individuals with subacute and chronic stroke?

OBJECTIVE: To evaluate if the capacity to perform functional mobility activities change within the first year post-stroke using the Timed "Up and Go" Assessment of Biomechanical Strategies (TUG-ABS). METHODS: A cross-sectional study was conducted with thirty-eight stroke individuals. A motion analysis system was used during the Timed "Up and Go" (TUG) test to evaluate the following activities: sit-to-stand, gait, turn, and stand-to-sit. Kinematic variables related to each activity were obtained in addition to TUG-ABS scores. The ability to perform the activities was compared between subacute (up to 3 months post-stroke, n = 21) and chronic participants (4 to 12 months post-stroke, n = 17) using Mann-Whitney U tests (α= 5%). RESULTS: Results were expressed as median difference (MD) and 95% confidence intervals (95% CI). TUG-ABS scores: Sit-to-stand (MD = 0, 95% CI = 0.0 to 1), gait (MD = 0, 95% CI = 0.0 to 1), stand-to-sit (MD = 0, 95% CI = 0.0 to 1), and total score (MD = 2.0, 95% CI = 0.0 to 6) were not different between groups. Subacute participants presented significant better scores during turn activity (MD = 2.0, 95% CI 0.0 to 2.0). All kinematic variables were not different between participants. CONCLUSIONS: Capacity to perform functional activities was not different within the first year post-stroke, suggesting that biomechanical strategies are developed within the first three months following stroke.

Cytotoxicity of 4-substituted quinoline derivatives: Anticancer and antileishmanial potential.

Chemical modifications of quinoline moiety have been recognized as a useful strategy to development of new drugs. Here, the cytotoxicity of a set of twenty-four 4-substituted quinolines (named HTI) was screened for their antitumor and antileishmanial potential in vitro, and the underlying mechanisms investigated. HTI 21 and HTI 22 exhibited the highest cytotoxicity, being selected to the subsequent studies. Both derivatives induced caspase-dependent apoptosis associated to the dissipation of the mitochondrial transmembrane potential (ΔΨ) and ROS generation. HTI-induced cell death was calcium dependent, associated to thiol oxidation and cysteine proteases activation. In isolated mitochondria, HTI derivatives promoted mitochondrial permeabilization by different mechanisms. The inhibition of BCL-2 by venetoclax enhanced the HTI-induced cytotoxicity. Regarding the inhibition of cysteine proteases type B of Leishmania mexicana, HTI 15 exhibited the most potent inhibitory activity through a linear non-competitive mechanism. These data highlight the therapeutic potential of 4-substituted quinolines as antitumor and antileishmanial drugs.

Cyclopalladated compounds containing 2,6-lutidine: Synthesis, spectral and biological studies.

Bridge splitting reactions between [Pd(C2,N-dmba)(µ-X)]2 (dmba = N,N-dimethylbenzylamine; X = Cl, I, N3, NCO) and 2,6-lutidine (lut) in the 1:2 molar ratio at room temperature afforded cyclopalladated compounds of general formulae [Pd(C2,N-dmba)(X)(lut)] {X = Cl- (1), I-(2), NNN-(3), NCO-(4)}, which were characterized by elemental analyses and infrared (IR), 1H NMR spectroscopy. The molecular structures of all synthesized palladacycles have been solved by single-crystal X-ray crystallography. The cytotoxicity of the cyclopalladated compounds has been evaluated against a panel of murine {mammary carcinoma (4T1) and melanoma (B16F10-Nex2)} and human {melanoma (A2058, SK-MEL-110 and SK-MEL-5) tumor cell lines. All complexes were about 10 to 100-fold more active than cisplatin, depending on the tested tumor cell line. For comparison purposes, the cytotoxic effects of 1-4 towards human lung fibroblasts (MRC-5) have also been tested. The late apoptosis-inducing properties of 1-4 compounds in SK-MEL-5 cells were verified 24 h incubation using annexin V-Fluorescein isothiocyanate (FITC)/propidium iodide (PI). The binding properties of the model compound 1 on human serum albumin (HSA) and calf thymus DNA (ct-DNA) have been studied using circular dichroism and fluorescence spectroscopy. Docking simulations have been carried out to gain more information about the interaction of the palladacycle and HSA. The ability of compounds 1-4 to inhibit the activity of cathepsin B and L has also been investigated in this work.

4'-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L.

A new flavone, 4'-hydroxy-6,7-methylenedioxy-3-methoxyflavone 1, and two other nucleosides, ribavirin 2 and adenosine 3, were isolated from the leaves of Dulacia egleri. The nucleosides were identified by spectroscopic techniques (1D, 2D-NMR) while the structure of the flavonoid was established by 1D, 2D-NMR analysis, including HRESIMS data. The results obtained in the biological assays showed that the compound 1 was able to inhibit cathepsins B and L with IC50 of 14.88 ±â€¯0.18 µM and 3.19 ±â€¯0.07 µM, respectively. The mechanism of inhibition for both enzymes were determined showing to be competitive at cathepsin B with Ki = 12.8 ±â€¯0.6 µM and non-linear non-competitive with positive cooperativity inhibition at cathepsin L with Ki = 322 ±â€¯33 µM, αKi = 133 ±â€¯15 µM, ßKi = 5.14 ±â€¯0.41 µM and γKi = 13.2 ±â€¯13 µM.

Porphyrins as Photoredox Catalysts in Csp2-H Arylations: Batch and Continuous Flow Approaches.

We have investigated both batch and continuous flow photoarylations of enol-acetates to yield different α-arylated aldehyde and ketone building blocks by using diazonium salts as the aryl-radical source. Different porphyrins were used as SET photocatalysts, and photophysical as well as electrochemical studies were performed to rationalize the photoredox properties and suggest mechanistic insights. Notably, the most electron-deficient porphyrin ( meso-tetra(pentafluorophenyl)porphyrin) shows the best photoactivity as an electron donor in the triplet excited state, which was rationalized by the redox potentials of excited states and the turnover of the porphyrins in the photocatalytic cycle. A two-step continuous protocol and multigram-scale reactions are also presented revealing a robust, cost-competitive, and easy methodology, highlighting the significant potential of porphyrins as SET photocatalysts.

Impact of continuous flow chemistry in the synthesis of natural products and active pharmaceutical ingredients.

We present a comprehensive review of the advent and impact of continuous flow chemistry with regard to the synthesis of natural products and drugs, important pharmaceutical products and definitely responsible for a revolution in modern healthcare. We detail the beginnings of modern drugs and the large scale batch mode of production, both chemical and microbiological. The introduction of modern continuous flow chemistry is then presented, both as a technological tool for enabling organic chemistry, and as a fundamental research endeavor. This part details the syntheses of bioactive natural products and commercial drugs.

Accuracy of chest radiography for positioning of the umbilical venous catheter / Acurácia da radiografia de tórax para o posicionamento do cateter venoso umbilical

Abstract Objectives: To evaluate the accuracy of the simultaneous analysis of three radiographic anatomical landmarks - diaphragm, cardiac silhouette, and vertebral bodies - in determining the position of the umbilical venous catheter distal end using echocardiography as a reference standard. Methods: This was a cross-sectional, observational study, with the prospective inclusion of data from all neonates born in a public reference hospital, between April 2012 and September 2013, submitted to umbilical venous catheter insertion as part of their medical care. The position of the catheter distal end, determined by the simultaneous analysis of three radiographic anatomical landmarks, was compared with the anatomical position obtained by echocardiography; sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. Results: Of the 162 newborns assessed by echocardiography, only 44 (27.16%) had the catheter in optimal position, in the thoracic portion of the inferior vena cava or at the junction of the inferior vena cava with the right atrium. The catheters were located in the left atrium and interatrial septum in 54 (33.33%) newborns, in the right atrium in 26 (16.05%), intra-hepatic in 37 (22.84%), and intra-aortic in-one newborn (0.62%). The sensitivity, specificity and accuracy of the radiography to detect the catheter in the target area were 56%, 71%, and 67.28%, respectively. Conclusion: Anteroposterior radiography of the chest alone is not able to safely define the umbilical venous catheter position. Echocardiography allows direct visualization of the catheter tip in relation to vascular structures and, whenever possible, should be considered to identify the location of the umbilical venous catheter.

Resumo Objetivos: Avaliar a acurácia da análise simultânea dos três marcos anatômicos radiográficos - diafragma, silhueta cardíaca e corpos vertebrais - na determinação da posição da extremidade distal do cateter venoso umbilical com a ecocardiografia como padrão de referência. Métodos: Estudo transversal, observacional, com inclusão prospectiva de dados de todos os neonatos nascidos em uma maternidade pública de referência, entre abril de 2012 e setembro de 2013, submetidos à inserção de cateter venoso umbilical como parte do atendimento clínico. A posição da extremidade distal do cateter, determinada pela análise simultânea dos três marcos anatômicos radiográficos, foi comparada com a posição anatômica obtida pela ecocardiografia. Sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e acurácia foram calculados. Resultados: Dos 162 recém-nascidos avaliados por ecocardiografia, somente 44 (27,16%) estavam com o cateter em posição ótima, na porção torácica da veia cava inferior ou na junção da veia cava inferior com o átrio direito. Os cateteres foram localizados no átrio esquerdo e no septo interatrial em 54 (33,33%), no átrio direito em 26 (16,05%), no intra-hepático em 37 (22,84%) e na aorta em um recém-nascido (0,62%). A sensibilidade, especificidade e acurácia da radiografia para detectar cateter na zona-alvo foram de 56%, 71% e 67,28%, respectivamente. Conclusão: A radiografia anteroposterior de tórax isolada não é capaz de definir com segurança a posição do cateter venoso umbilical. A ecocardiografia permite a visibilização direta da ponta do cateter em relação às estruturas vasculares e, sempre que possível, deve ser considerada para localização do cateter venoso umbilical.

Accuracy of chest radiography for positioning of the umbilical venous catheter.

OBJECTIVES: To evaluate the accuracy of the simultaneous analysis of three radiographic anatomical landmarks - diaphragm, cardiac silhouette, and vertebral bodies - in determining the position of the umbilical venous catheter distal end using echocardiography as a reference standard. METHODS: This was a cross-sectional, observational study, with the prospective inclusion of data from all neonates born in a public reference hospital, between April 2012 and September 2013, submitted to umbilical venous catheter insertion as part of their medical care. The position of the catheter distal end, determined by the simultaneous analysis of three radiographic anatomical landmarks, was compared with the anatomical position obtained by echocardiography; sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. RESULTS: Of the 162 newborns assessed by echocardiography, only 44 (27.16%) had the catheter in optimal position, in the thoracic portion of the inferior vena cava or at the junction of the inferior vena cava with the right atrium. The catheters were located in the left atrium and interatrial septum in 54 (33.33%) newborns, in the right atrium in 26 (16.05%), intra-hepatic in 37 (22.84%), and intra-aortic in-one newborn (0.62%). The sensitivity, specificity and accuracy of the radiography to detect the catheter in the target area were 56%, 71%, and 67.28%, respectively. CONCLUSION: Anteroposterior radiography of the chest alone is not able to safely define the umbilical venous catheter position. Echocardiography allows direct visualization of the catheter tip in relation to vascular structures and, whenever possible, should be considered to identify the location of the umbilical venous catheter.

Early treatment with metformin induces resistance against tumor growth in adult rats.

It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer.