Miguel Patrício

Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes.

Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [(14)C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased (P= 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant (P< 0.001) decrease in the isoproterenol-stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation-related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment.

Genetic gains and losses in oral squamous cell carcinoma: impact on clinical management

PurposeThe identification of genetic markers associated with oral cancer is considered essential to improve the diagnosis, prognosis, early tumor and relapse detection and, ultimately, to delineate individualized therapeutic approaches. Here, we aimed at identifying such markers.MethodsMultiplex Ligation-dependent Probe Amplification (MLPA) analyses encompassing 133 cancer-related genes were performed on a panel of primary oral tumor samples and its corresponding resection margins (macroscopically tumor-free tissue) allowing, in both types of tissue, the detection of a wide arrange of copy number imbalances on various human chromosomes.ResultsWe found that in tumor tissue, from the 133 cancer-related genes included in this study, those that most frequently exhibited copy number gains were located on chromosomal arms 3q, 6p, 8q, 11q, 16p, 16q, 17p, 17q and 19q, whereas those most frequently exhibiting copy number losses were located on chromosomal arms 2q, 3p, 4q, 5q, 8p, 9p, 11q and 18q. Several imbalances were highlighted, i.e., losses of ERBB4, CTNNB1, NFKB1, IL2, IL12B, TUSC3, CDKN2A, CASP1, and gains of MME, BCL6, VEGF, PTK2, PTP4A3, RNF139, CCND1, FGF3, CTTN, MVP, CDH1, BRCA1, CDKN2D, BAX, as well as exon 4 of TP53. Comparisons between tumor and matched macroscopically tumor-free tissues allowed us to build a logistic regression model to predict the tissue type (benign versus malignant). In this model, the TUSC3 gene showed statistical significance, indicating that loss of this gene may serve as a good indicator of malignancy.ConclusionsOur results point towards relevance of the above mentioned cancer-related genes as putative genetic markers for oral cancer. For practical clinical purposes, these genetic markers should be validated in additional studies.

GABA deficiency in NF1 A multimodal [11C]-flumazenil and spectroscopy study

Objective: To provide a comprehensive investigation of the γ-aminobutyric acid (GABA) system in patients with neurofibromatosis type 1 (NF1) that allows understanding the nature of the GABA imbalance in humans at pre- and postsynaptic levels. Methods: In this cross-sectional study, we employed multimodal imaging and spectroscopy measures to investigate GABA type A (GABAA) receptor binding, using [11C]-flumazenil PET, and GABA concentration, using magnetic resonance spectroscopy (MRS). Fourteen adult patients with NF1 and 13 matched controls were included in the study. MRS was performed in the occipital cortex and in a frontal region centered in the functionally localized frontal eye fields. PET and MRS acquisitions were performed in the same day. Results: Patients with NF1 have reduced concentration of GABA+ in the occipital cortex (p = 0.004) and frontal eye fields (p = 0.026). PET results showed decreased binding of GABAA receptors in patients in the parieto-occipital cortex, midbrain, and thalamus, which are not explained by decreased gray matter levels. Conclusions: Abnormalities in the GABA system in NF1 involve both GABA concentration and GABAA receptor density suggestive of neurodevelopmental synaptopathy with both pre- and postsynaptic involvement.

Distinct functional properties of the vertical and horizontal saccadic network in Health and Parkinson's disease: An eye-tracking and fMRI study.

Saccadic behaviour ranges from reflexive (e.g., prosaccade) to goal oriented voluntary movements (e.g., antisaccade). Behavioural asymmetries between vertical and horizontal saccades have been described both in normal individuals (greater delay of vertical prosaccades) and in disease states such as Parkinsons disease (PD) (prosaccades are short and antisaccades are delayed, especially in the vertical plane, possibly due to a frontostriatal deficit). Importantly, the cortical mechanisms for the generation of vertical saccades are largely unknown, both in health and disease, when compared with their horizontal counterpart. Moreover, studies exploring saccadic neural correlates and putative compensatory mechanisms at a functional level in PD are scarce. We investigated horizontal and vertical prosaccades and antisaccades in an eye tracking paradigm in 19 PD patients off medication and 22 healthy controls, followed by a block-design functional Magnetic Resonance Imaging (fMRI) study, consisting of two runs (prosaccade, antisaccade) of 6 blocks each (3 vertical, 3 horizontal). While saccade metrics were not significantly different between groups, PD showed left frontal underactivation during horizontal prosaccades and right parietal overactivation during horizontal and vertical prosaccades and horizontal antisaccades. Moreover, controls showed greater deactivation of the default-mode network (DMN) during antisaccades. Vertical prosaccades were associated with greater right frontal and cerebellar activity in controls, and cuneus hypoactivity in PD. Vertical antisaccades were associated with greater DMN deactivation in both groups and left frontal hypoactivity in PD. Putative functional compensatory changes in the right parietal cortex in PD patients may help to keep saccadic behaviour at the same level as the healthy controls. We provide first time evidence showing that functional cortical asymmetries between vertical and horizontal saccades occur distinctively in PD patients and healthy controls.

Voxel-based morphometry analyses in Alzheimer's disease

Alzheimers disease (AD) is a neurodegenerative disease recognized as one of the most important medical problems affecting the elderly. It is characterized by an irreversible loss of neurons which is mostly pronounced in the grey matter and specifically in the hippocampus. The aim of this paper is to identify alterations in grey matter in MRI images of AD patients, when compared to those of healthy volunteers, using Voxel-Based Morphometry (VBM). The latter is a widely used statistical-based technique that allows the detection of alterations in brain tissue. In our study, we used VBM to detect significant grey matter alterations of the hippocampal region in AD patients, which is consistent with previous findings reported in the literature. We also examined how the Mini Mental State Examination (MMSE) scores relates to the volume differences detected by VBM1.

Physical Fitness and Frailty Syndrome in Institutionalized Older Women

Associations between frailty and physical-functional fitness (PFF) indicators in frail women over 65 years of age remain largely unexplored. This study analyzed the relationship between frailty syndrome (FS) and PFF indicators and assessed how the latter might predict the former. Participants were 119 elderly women (81.96 ± 7.89 years) recruited from four social and healthcare centers. PFF was assessed through muscle strength tests of upper and lower limbs, endurance, agility-dynamic balance, flexibility, and body composition. The following FS indicators were assessed: weight loss, exhaustion, weakness, slowness, and low physical activity level. Significant correlations were found between FS and endurance, agility-dynamic balance, upper and lower limbs muscle strength tests. Comparitive analyses also revealed that, among FS groups, the frail subgroup performed significantly poorer on all PFF measures except body composition. Additionally, a receiving operating characteristics curve analysis revealed good diagnostic accuracy for predicting FS using the agility-dynamic balance test (Area Under Curve [AUC] = .82, 95% CI [0.74, 0.90]; sensitivity and specificity were 70.4% and 84.8% for the cutoff = 16.22 seconds). Accurately, the risk of frail condition (not pre-frail) increases about 2.12% per second spent in this test. Thus, the agility-dynamic balance test is a promising tool for screening institutionalized older people for risk of FS.

Tremor modulations across periods with and without voluntary motion and limb load task demands using movement quantification

Understanding the neurobiological mechanisms underlying different types of tremor and the altered functional connectivity of the involved areas is a timely goal in clinical neuroscience. If successful, this quest may open new perspectives on how to achieve tremor modulation, which is notably relevant, in Parkinsons disease (PD). Tremor can be characterized by simple parameters such as frequency and amplitude. It is therefore prone to be objectively targeted by neuromodulation and quantitatively investigated using multimodal techniques, such as, accelerometry, EMG and functional Magnetic Resonance Imaging (fMRI). Embarking on the latter challenge requires an a priori knowledge of how effective functional connectivity is altered in PD tremor. This works aims to ascertain which postural and voluntary movement tasks with distinct types of physical load are suitable for designing efficient fMRI protocols, by performing an accelerometry analysis to measure spontaneous and imposed tremor modulation on cohorts of PD patients, essential tremor patients and a group of voluntary healthy controls.

Cortical control of vertical and horizontal saccades in progressive supranuclear palsy: An exploratory fMRI study

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder showing predominant brainstem involvement, characterized by marked slowing of rapid eye movements (saccades), particularly along the vertical plane. While the contribution of the brainstem damage for the saccadic disturbance in PSP has been extensively studied, much less is known about its cortical and subcortical pathomechanisms. We measured reflexive (prosaccades) and voluntary (antisaccades) saccades in the vertical and horizontal plane in PSP patients (n=8) and controls (n=10) in an eye tracking study, followed by the measurement of blood oxygenation-level dependent (BOLD) activation (PSP, n=6; controls, n=10) during similar saccade paradigms. Behaviorally, PSP patients evidenced slower and lower amplitude prosaccades (horizontal and vertical) and lower amplitude antisaccades (vertical) than controls. Functionally, patients showed decreased frontostriatal BOLD activation during prosaccades (horizontal and vertical) and antisaccades (vertical), relative to controls. Additionally, PSP patients showed less default mode network (DMN) deactivation than controls for all types of saccades. Within groups, controls showed no BOLD differences between horizontal and vertical prosaccades while PSP patients demonstrated greater DMN deactivation during vertical prosaccades. Both groups evidenced greater DMN deactivation during vertical antisaccades when compared to their horizontal counterpart and patients further showed relative frontostriatal BOLD hypoactivity during vertical antisaccades. We found fMRI evidence of frontostriatal hypoactivity in PSP patients relative to controls, especially during vertical saccades. These new findings highlight the impact of cortical impairment in saccadic disturbance of PSP.

Burnout in radiation therapists: Systematic review with meta-analysis

The main aim of this review is to evaluate the burnout levels experienced by radiation therapists. PubMed, Lilacs and Google Scholar were searched for articles reporting burnout levels in radiation therapists. Only studies explicitly assessing burnout and using a validated instrument were retrieved. Meta-analyses were undertaken, based on articles that used the Maslach Burnout Inventory to assess burnout, to determine 95% confidence intervals for the overall prevalence of radiation therapists with high burnout risk in three dimensions: emotional exhaustion, depersonalisation or low personal accomplishment. Additionally, meta-analyses were also performed to determine the overall mean reported for each of the three dimensions. A total of eleven studies were found to be eligible for inclusion in this systematic review, nine of which used the Maslach Burnout Inventory questionnaire. The 95% confidence intervals for radiation therapists with high emotional exhaustion scores, high depersonalisation scores and low personal accomplishment scores were [24.8; 54.6], [10.1; 40.2] and [17.4; 41.6] respectively. The 95% confidence intervals for the corresponding means were found to be [20.0; 26.2], [5.1; 8.8] and [35.9, 39.6] respectively. The meta-analysis revealed an arguably high prevalence of burnout in radiation therapists in spite of it varying substantially between studies.

Transcranial Magnetic Stimulation as an Intervention Tool to Recover from Language, Swallowing and Attentional Deficits after Stroke: A Systematic Review

Background: Following a stroke event, patients often are severely affected by disabilities that hinder their quality-of-life. There are currently several rehabilitative options and strategies, and it is crucial to find the most effective interventions. The applicability of transcranial magnetic stimulation (TMS) to the recovery of nonmotor functions such as communication skills, swallowing ability and spatial attention after stroke remains important clinical questions. Summary: We searched PubMed and ISI Web of Science for articles that used repetitive TMS protocols to rehabilitate post-stroke deficits. We analysed qualitatively 38 articles that met the eligibility criteria; of these, 21 dealt with aphasia, 8 with dysphagia, 8 with neglect and 1 with visual extinction. The efficacy of TMS as an intervention for post-stroke rehabilitation of these nonmotor deficits was studied as well as the current limitations were assessed. Key Messages: Most part of the included studies reported statistically significant functional improvements, supporting the use of TMS for the rehabilitation of aphasia, dysphagia and neglect. Future research, with larger sample sizes, is mandatory to confirm its efficacy, determine the optimal stimulation parameters and investigate inter-subject variability.