Successful treatment with alectinib after crizotinib-induced hepatitis in ALK-rearranged advanced lung cancer patient: a case report.

BACKGROUND: Besides the clinical benefit of crizotinib in ALK-rearranged metastatic non-small cell lung cancer (NSCLC), concerns about its hepatotoxicity have arisen. It is not clear whether this is a drug class side effect or if the use of other selective ALKs inhibitors is safe after this serious adverse event. While evidence from clinical trials is scarce, reports of treatment after crizotinib-induces hepatitis may add to clinical decision. CASE PRESENTATION: Herein, we report a case of acute hepatitis induced by crizotinib in a 32-years-old female diagnosed with metastatic NSCLC, harboring the ALK-rearrangement. After 60 days of crizotinib therapy, the patient presented with acute hepatitis, diagnosed after investigation of non-specific symptoms, such as nausea and fatigue. Serum aspartate aminotransferase and alanine aminotransferase levels had increased from baseline to 3010 IU/L and 9145 IU/L, respectively. Total bilirubin increased up to 7.91 mg/dL, but she did not develop liver failure. After crizotinib discontinuation, a gradual hepatic function recovery occurred. Unfortunately, during the period without specific oncology treatment, her disease showed an unequivocal progression. Therefore, she started on alectinib with great response, and no liver function alteration recurred. CONCLUSIONS: This case suggests that alectinib, even belonging to the same drug class, could be used as an alternative agent when crizotinib is the etiology of liver damage, but more robust evidence has awaited.

Effects of Aerobic Exercise on Anxiety Symptoms and Cortical Activity in Patients with Panic Disorder: A Pilot Study.

BACKGROUND: The effects of the aerobic exercise on anxiety symptoms in patients with Panic Disorder (PD) remain unclear. Thus, the investigation of possible changes in EEG frontal asymmetry could contribute to understand the relationship among exercise, brain and anxiety. OBJECTIVE: To investigate the acute effects of aerobic exercise on the symptoms of anxiety and the chronic effects of aerobic exercise on severity and symptoms related to PD, besides the changes in EEG frontal asymmetry. METHODS: Ten PD patients were divided into two groups, Exercise Group (EG; n=5) and Control Group (CG; n=5), in a randomized allocation. At baseline and post-intervention, they submitted the psychological evaluation through Panic Disorder Severity Scale (PDSS), Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II), EEG frontal asymmetry, and maximal oxygen consumption (VO2max). On the second visit, the patients of EG being submitted to the aerobic exercise (treadmill, 25 minutes, and 50-55% of heart rate reserve) and the CG remained seated for the same period of time. Both groups submitted a psychological evaluation with Subjective Units of Distress Scale (SUDS) at baseline, immediately after (Post-0), and after 10 minutes of the rest pause (Post-10). The patients performed 12 sessions of aerobic exercise with 48-72 hours of interval between sessions. RESULTS: In EG, SUDS increased immediately after exercise practice and showed chronic decrease in BAI and BDI-II as well as increased in VO2max (Post-intervention). CONCLUSION: Aerobic exercise can promote increase in anxiety acutely and regular aerobic exercise promotes reduction in anxiety levels.

Panic disorder and cardiovascular diseases: an overview.

The association between panic disorder (PD) and cardiovascular diseases (CVD) has been extensively studied in recent years and, although some studies have shown anxiety disorders co-existing or increasing the risk of heart disease, no causal hypothesis has been well established. Thus, a critical review was performed of the studies that evaluated the association between PD and cardiovascular diseases; synthesizing the evidence on the mechanisms mediators that theoretically would be the responsible for the causal pathway between PD and CVD, specifically. This overview shows epidemiological studies, and discusses biological mechanisms that could link PD to CVD, such as pleiotropy, heart rate variability, unhealthy lifestyle, atherosclerosis, mental stress, and myocardial perfusion defects. This study tried to provide a comprehensive narrative synthesis of previously published information regarding PD and CVD and open new possibilities of clinical management and pathophysiological understanding. Some epidemiological studies have indicated that PD could be a risk factor for CVD, raising morbidity and mortality in PD, suggesting an association between them. These studies argue that PD pathophysiology could cause or potentiate CVD. However, there is no evidence in favour of a causal relationship between PD and CVD. Therefore, PD patients with suspicions of cardiovascular symptoms need redoubled attention.

Relationship Among Physical Activity Level, Mood and Anxiety States and Quality of Life in Physical Education Students.

BACKGROUND: Physical activity level (PAL) is known to play an important role in reducing risk factors associated with sedentarism, in addition to improving the mental health and health-related quality of life (HRQL). OBJECTIVE: Investigate the relationship of PAL and their domains with HRQL, mood state (MS) and anxiety. Method: 140 Physical Education students (23.6 ± 3.7 years) were evaluated. The Baecke Habitual Physical Activity and Quality of Life (QOL-36) questionnaires, State-Trait Anxiety Inventories (STAI-S and STAI-T) and Profile of Mood States (POMS) scale were used to investigate PAL, HRQL and mental health indicators. Pearson's correlation coefficient examined the association between PAL and both mental health and HRQL parameters. RESULTS: There was a correlation between state anxiety and both the domain leisure-time physical activity (LTPA) (p = 0.013) and total PAL score (p = 0.010). In relation to MS, a negative correlation was found between LTPA and total mood disorder (TMD) (p = 0.004). However, there were positive correlations between the vigor subscale and both LTPA (p=0.001) and total PAL (p=0.019). With respect to HRQL, analysis of the relationship between LTPA and total PAL demonstrated positive coefficients with the physical component summary (PCS) (p=0.000; p = 0.005), mental component summary (MCS) (p = 0.000; p = 0.006) and total HRQL (p = 0.000; p = 0.003). CONCLUSION: The findings suggest that the rise in LTPA was related to an increase in HRQL and MS. However, PAL was positively related to anxiety.

The Role of Physical Activity on Mood State and Functional Skills of Elderly Women.

INTRODUCTION: Ageing is associated with several physical, psychological and behavioral changes. These changes are closely related with global health and functional capacity in the elderly. Mood disturbances are common among the elderly and may significantly increase apathy, resulting in decreased habitual physical activity levels. MATERIALS AND METHODS: The purpose of this cross-sectional study was to evaluate the mood state and functional motor capacities of elderly women engaged in a public physical activity program in Brazil and compare them with physically inactive elderly. Thirty elderly women were included in the study and categorized into two groups: physically active group, composed of participants enrolled on a public physical activity program (n = 16, 69±5 years) and physically inactive group (n = 14, 68±4 years). Total mood disturbance was assessed using the Profile of Mood States, whereas functional motor capacity was evaluated with the Sitting and Rising test. Independent t test and Mann-Whitney U] were used to compare groups. RESULTS: The physically active group had lower total mood disturbance (p=0.02), confusion (p<0.01), tension (p<0.01), hostility (p=0.05) and fatigue (p=0.01) compared to the physically inactive group. There were no group differences regarding vigor, depression and sitting and rising performance (p>0.05). CONCLUSION: Lack of difference in functional motor capacity between the physically active and inactive elderly may be explained by the absence of exercise systematization in these programs.

Relationship Between Brain-Derived Neurotrofic Factor (Bdnf) and Sleep on Depression: A Critical Review.

The Brain-Derived Neurotrofic Factor (BDNF) is one of the most important neurotrophins in the brain and it is suggested influences the activity of the serotonergic, noradrenergic and dopaminergic pathways. In the last few years, it has been hypothesized that BDNF level is related with depression and sleep. Several studies show that depressive subjects present low levels of BDNF in the brain. Poor sleep quality is also related with alterations in the BDNF concentration. Some authors argue that most of the cases show that impaired sleep quality increases the stress and, consequently, the vulnerability to depressive disorders, suggesting that there is a relationship between sleep, depression and BDNF levels.

Mental Practice Combined with Motor Rehabilitation to Treat Upper Limb Hemiparesis of Post-Stroke Patients: Clinical and Experimental Evidence.

Stroke is one of the major causes of disability in the world. Due to the extended lifetime of the world's population, the number of people affected by stroke has increased substantially over the last years. Stroke may lead to sensorimotor deficits, usually causing hemiplegia or hemiparesia. In order to reduce motor deficits and accelerate functional recovery, MP combined with motor rehabilitation was introduced to the rehabilitation process of post-stroke patients. Evidence has shown that MP combining with motor rehabilitation based on activities of daily living was more effective than conventional motor rehabilitation used per se. This combination proved very useful and effective, with significant results in improvement of motor deficits in post-stroke patients. However, further studies must be conducted to determine specific parameters, such as type of imagery, frequency or duration.

Relationship Among Body Image, Anthropometric Parameters and Mental Health in Physical Education Students.

BACKGROUND: The prevalence of body image dissatisfaction (BID) is currently high. Given that psychological well-being is associated with the body measurements imposed by esthetic standards, BID is an important risk factor for mental disorders. OBJECTIVE: Identify the prevalence of BID, and compare anthropometric and mental health parameters between individuals satisfied and dissatisfied with their body image. METHOD: A total of 140 university students completed the silhouette scale to screen for BID. Anthropometric measures, body mass index (BMI), waist circumference (WC) and body fat percentage (BFP) were used. To investigate mental health, The State-Trait Anxiety Inventories (STAI-S and STAI-T), Profile of Mood States (POMS) scale and Quality of Life (QOL-36) questionnaire were used to investigate mental health. The Student's t-test was applied to compare anthropometric and mental health parameters. RESULTS: 67.1% of university students exhibited BID. There was a significant difference (p = 0.041) in BF and WC (p = 0.048) between dissatisfied and satisfied individuals. With respect to mood states, significant differences were observed for anger (p = 0.014), depression (p = 0.011), hostility (p = 0.006), fatigue (p = 0.013), mental confusion (p = 0.021) and total mood disturbance (TMD) (p = 0.001). The mental aspect of QOL was significantly higher (p = 0.001) in satisfied university students compared to their dissatisfied counterparts. CONCLUSION: BID was high and it seems to be influenced by anthropometric measures related to the amount and distribution of body fat. This dissatisfaction may have a negative effect on the quality of life and mood state of young adults.

Treatment of Cognitive Deficits in Alzheimer's disease: A psychopharmacological review.

The growing and aging population has contributed to the increased prevalence of Alzheimer's disease (AD) and other types of dementia in the world. AD is a progressive and degenerative brain disease with an onset characterized by episodic memory impairments, although progressive deficits can be observed in several domains including language, executive functions, attention and working memory. The relationship between cognitive impairments and the topography and progression of brain neuropathology is well established. The pathophysiologic mechanisms and processes that underline the course of cognitive and clinical decline have been the theoretical support for the development of pharmacological treatments for AD. Cholinesterase inhibitors (ChEIs) and N-methyl-D-aspartate (NMDA) antagonists are the main drugs used in the management of global cognitive impairment and several studies also explore the effects of both in specific cognitive measures. Recent research trends also examine the effects of combination therapy using both compounds. This review aims to update practical recommendations for the treatment of global cognitive functioning and specific neurocognitive deficits in AD using ChEIs, NMDA antagonists and combination therapy with both drugs.

Comparative study of subcortical atrophy in patients with frontotemporal dementia and dementia with extrapyramidal signs.

OBJECTIVES: To investigate the severity of subcortical atrophy in frontotemporal dementia (FTD) without extrapyramidal symptoms (EPS) and dementia with EPS. In addition, we aim to verify if there is correlation between demographic and clinical characteristics and subcortical atrophy in the groups. Methodology : The sample was composed of 21 patients with dementia and EPS as well as 19 patients with FTD without EPS. A linear assessment was conducted in order to identify the degree of subcortical atrophy (i.e., bifrontal index - BFI) using MRI. Moreover, the Mini-Mental State Examination (MMSE), Pfeffer Functional Activities Questionnaire (FAQ) and the Clinical Dementia Rating (CDR) were used to investigate clinical aspects. Results : It was verified that patients with dementia and EPS was older than the patients with FTD (p=0.01). The severity of cognitive deficits was associated with BFI, as well as the dementia severity in the EPS group. Conclusion : FTD group presented mean BFI scores above the cutoff for normal elderly population, indicating the presence of subcortical atrophy in this group. Mean BFI was higher (although not statistically significant) in FTD group than in dementia with EPS, which can suggest at least that subcortical pathology in FTD may be as important as in the dementia with EPS group. Subcortical atrophy is a good biological marker for cognitive deterioration in FTD and in dementia with EPS.

Real-World Evidence of Ribociclib Plus Aromatase Inhibitors as First-Line Treatment in Advanced Breast Cancer: The BrasiLEEira Study.

PURPOSE: Cyclin inhibitors plus endocrine therapy represent the reference standard for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer (ABC). Efficacy results on hard end points such as overall survival come from well-designed randomized clinical trials (RCTs). However, a limitation of RCTs is the low external results validity, and their extrapolation to a broader population may not be appropriate. Real-world studies can overcome these limitations, also increasing the reliability of RCTs. MATERIALS AND METHODS: The BrasiLEEira was an observational, longitudinal, retrospective, multicenter study to evaluate the effectiveness and safety of ribociclib plus nonsteroidal aromatase inhibitors in Brazilian women age 18 years or older with HR+/HER2- ABC. The study was approved by the institutional review boards of all 11 hospitals. Data were collected anonymously from medical records using an electronic case report form designed by an independent academic research organization, which conducted the study considering all recommendations of international guidelines. The primary end point was 1-year progression-free survival (PFS) rate. Secondary end points included mortality, dose reduction, and safety. RESULTS: The mean age of 76 patients was 57 years, and 28.9% were Black/Brown. The most prevalent comorbidity was arterial hypertension (34.7%). About 26.0% had endocrine-resistant disease, and 54.1% had more than three metastatic sites. The PFS rate was 77.6%. Three patients died (3.9%). Dose reductions occurred in 37.7% of patients. The most common adverse event was neutropenia (68.4%). CONCLUSION: The high-quality evidence from the BrasiLEEira study corroborates the RCTs' findings, expanding its validity to a broader spectrum and underrepresented population who may benefit from ribociclib treatment.

Comorbidity of depression and anxiety: association with poor quality of life in type 1 and 2 diabetic patients.

BACKGROUND: Diabetes is associates with depression and impairment in Quality of Life (QoL). OBJECTIVE: The objective is to define the frequencies of depressive and anxiety symptoms in a sample of patients diagnosed with type 1 and 2 diabetes, the amount of impairment of QoL and the weight of depression and anxiety in determining the QoL in such of patients. METHODS: A total of 210 patients were divided into two groups (type 1 and type 2). Patients completed the HADS and WHOQoL-bref. RESULTS: Groups showed a high prevalence of anxiety (type 1 = 60%, type 2 = 43.8%) and depression (type 1 = 52.4%, type 2 = 38.1%), both measures were significantly higher (p < 0.05) in diabetes type 1 patients. Type 1 patients also showed a QoL in the overall assessment and the physical, psychological and social relations domains. In both Type 1 and 2 diabetes poor QoL was found associated by anxiety and depression comorbidity. CONCLUSION: In overall diabetes patients depression and anxiety seems to be a determinant of poor QoL.

The role of positive emotion and contributions of positive psychology in depression treatment: systematic review.

The present study aims to conduct a systematic review of the literature by checking the impact of positive emotion in the treatment of depression and on the use of strategies of positive psychology which involves positive emotion to treat and reduce symptoms of depression. For this purpose, we conducted searches in databases ISI Web of Knowledge, PsycINFO and PubMed and found a total of 3400 studies. After inclusion application and exclusion criteria, 28 articles remained, presented and discussed in this study. The studies have important relations between humor and positive emotion as well as a significant improvement in signs and symptoms of depression using differents strategies of positive psychology. Another relevant aspect is the preventative character of the proposed interventions by positive psychology by the fact that increase well-being and produce elements such as resilience and coping resources that reduce the recurrent relapses in the treatment of depression. The strategies of positive psychology, such as increasing positive emotions, develop personal strengths: seeking direction, meaning and engagement for the day-to-day life of the patients, appear as potentially tools for the prophylaxis and treatment of depression, helping to reduce signs and symptoms as well as for prevention of relapses.

Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat Social Anxiety Disorder: Case Reports and a Review of the Literature.

OBJECTIVES: Social anxiety disorder (SAD) is a common and debilitating anxiety disorders. However, few studies had been dedicated to the neurobiology underlying SAD until the last decade. Rates of non-responders to standard methods of treatment remain unsatisfactorily high of approximately 25%, including SAD. Advances in our understanding of SAD could lead to new treatment strategies. A potential non invasive therapeutic option is repetitive transcranial magnetic stimulation (rTMS). Thus, we reported two cases of SAD treated with rTMS Methods: The bibliographical search used Pubmed/Medline, ISI Web of Knowledge and Scielo databases. The terms chosen for the search were: anxiety disorders, neuroimaging, repetitive transcranial magnetic stimulation. RESULTS: In most of the studies conducted on anxiety disorders, except SAD, the right prefrontal cortex (PFC), more specifically dorsolateral PFC was stimulated, with marked results when applying high-rTMS compared with studies stimulating the opposite side. However, according to the "valence hypothesis", anxiety disorders might be characterized by an interhemispheric imbalance associated with increased right-hemispheric activity. With regard to the two cases treated with rTMS, we found a decrease in BDI, BAI and LSAS scores from baseline to follow-up. CONCLUSION: We hypothesize that the application of low-rTMS over the right medial PFC (mPFC; the main structure involved in SAD circuitry) combined with high-rTMS over the left mPFC, for at least 4 weeks on consecutive weekdays, may induce a balance in brain activity, opening an attractive therapeutic option for the treatment of SAD.

Changes in Cortical Activity During Real and Imagined Movements: an ERP Study.

This study aims to compare the topographic distribution of cortical activation between real and imagined movement through event-related potential (ERP). We are specifically interested in identifying, the topographic distribution of activated areas, the intensity of activated areas, and the temporal occurrence of these activations on preparation and motor response phases. Twelve healthy and right handed subjects were instructed to perform a task under real and imagery conditions. The task was performed simultaneously to electroencephalographic (EEG) recording. When compared the conditions, we found a statistically significant difference in favor of real condition revealed by performing an unpaired t-test with multiple corrections of Bonferroni, demonstrating negative activity on electrode C3 and positive activity on the electrode C4 only in motor response phase. These findings revealed similar functional connections established during real and imagery conditions, suggesting that there are common neural substrate and similar properties of functional integration shared by conditions.

A randomized, naturalistic, parallel-group study for the long-term treatment of panic disorder with clonazepam or paroxetine.

This long-term extension of an 8-week randomized, naturalistic study in patients with panic disorder with or without agoraphobia compared the efficacy and safety of clonazepam (n = 47) and paroxetine (n = 37) over a 3-year total treatment duration. Target doses for all patients were 2 mg/d clonazepam and 40 mg/d paroxetine (both taken at bedtime). This study reports data from the long-term period (34 months), following the initial 8-week treatment phase. Thus, total treatment duration was 36 months. Patients with a good primary outcome during acute treatment continued monotherapy with clonazepam or paroxetine, but patients with partial primary treatment success were switched to the combination therapy. At initiation of the long-term study, the mean doses of clonazepam and paroxetine were 1.9 (SD, 0.30) and 38.4 (SD, 3.74) mg/d, respectively. These doses were maintained until month 36 (clonazepam 1.9 [SD, 0.29] mg/d and paroxetine 38.2 [SD, 3.87] mg/d). Long-term treatment with clonazepam led to a small but significantly better Clinical Global Impression (CGI)-Improvement rating than treatment with paroxetine (mean difference: CGI-Severity scale -3.48 vs -3.24, respectively, P = 0.02; CGI-Improvement scale 1.06 vs 1.11, respectively, P = 0.04). Both treatments similarly reduced the number of panic attacks and severity of anxiety. Patients treated with clonazepam had significantly fewer adverse events than those treated with paroxetine (28.9% vs 70.6%, P < 0.001). The efficacy of clonazepam and paroxetine for the treatment of panic disorder was maintained over the long-term course. There was a significant advantage with clonazepam over paroxetine with respect to the frequency and nature of adverse events.

EEG-based brain-computer interfaces: an overview of basic concepts and clinical applications in neurorehabilitation.

Some patients are no longer able to communicate effectively or even interact with the outside world in ways that most of us take for granted. In the most severe cases, tetraplegic or post-stroke patients are literally 'locked in' their bodies, unable to exert any motor control after, for example, a spinal cord injury or a brainstem stroke, requiring alternative methods of communication and control. But we suggest that, in the near future, their brains may offer them a way out. Non-invasive electroencephalogram (EEG)-based brain-computer interfaces (BCI) can be characterized by the technique used to measure brain activity and by the way that different brain signals are translated into commands that control an effector (e.g., controlling a computer cursor for word processing and accessing the internet). This review focuses on the basic concepts of EEG-based BCI, the main advances in communication, motor control restoration and the downregulation of cortical activity, and the mirror neuron system (MNS) in the context of BCI. The latter appears to be relevant for clinical applications in the coming years, particularly for severely limited patients. Hypothetically, MNS could provide a robust way to map neural activity to behavior, representing the high-level information about goals and intentions of these patients. Non-invasive EEG-based BCIs allow brain-derived communication in patients with amyotrophic lateral sclerosis and motor control restoration in patients after spinal cord injury and stroke. Epilepsy and attention deficit and hyperactive disorder patients were able to downregulate their cortical activity. Given the rapid progression of EEG-based BCI research over the last few years and the swift ascent of computer processing speeds and signal analysis techniques, we suggest that emerging ideas (e.g., MNS in the context of BCI) related to clinical neurorehabilitation of severely limited patients will generate viable clinical applications in the near future.

Mental Rotation Test Performance in Brazilian and German Adolescents: The Role of Sex, Processing Speed, and Physical Activity in Two Different Cultures.

It was the main goal of this study to investigate performance on the mental rotation test (MRT) in Brazilian and German adolescents. Mental rotation is the ability to mentally transform a three-dimensional stimulus in mind and relates to science education. 60 German and 60 Brazilian adolescents (76 males and 44 females, 11-17 years) completed the Mental Rotation Test, a physical activity and media use questionnaire and a Number Connection Test. The result showed no difference between Brazilian and German adolescents in the cognitive processing speed measurement. German adolescents are more active and show a less media use compared to the Brazilian adolescents. Furthermore, German adolescents demonstrate a better MRT performance than Brazilian ones, as well as boys show a better performance than girls do. A multiple regression analysis indicated that the MRT performance could be predicted by nationality, sex, and cognitive processing speed. Since cognitive processing speed did not differ between Brazilian and German adolescents, the worse MRT performance of the Brazilian adolescents could be explained by different educational systems. Further studies have to follow which investigate the reasons for the different nations in more detail.

Exercise-induced neuroprotective effects on neurodegenerative diseases: the key role of trophic factors.

Age-related neurodegenerative disorders, like Alzheimer's or Parkinson's disease, are becoming a major issue to public health care. Currently, there is no effective pharmacological treatment to address cognitive impairment in these patients. Here, we aim to explore the role of exercise-induced trophic factor enhancement in the prevention or delay of cognitive decline in patients with neurodegenerative diseases. There is a significant amount of evidence from animal and human studies that links neurodegenerative related cognitive deficits with changes on brain and peripheral trophic factor levels. Several trials with elderly individuals and patients with neurodegenerative diseases report exercise induced cognitive improvements and changes on trophic factor levels including BDNF, IGF-I, among others. Further studies with healthy aging and clinical populations are needed to understand how diverse exercise interventions produce different variations in trophic factor signaling. Genetic profiles and potential confounders regarding trophic factors should also be addressed in future trials.