Neuromodulation of deep brain structures (deep brain stimulation) is the current surgical procedure for treatment of Parkinson's disease (PD). Less studied is the stimulation of cortical motor areas ...to treat PD symptoms, although also known to alleviate motor disturbances in PD. We were able to show that optogenetic activation of secondary (M2) motor cortex improves motor functions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved in motor control, and makes synaptic contacts with dopaminergic neurons. Strikingly, optogenetic activation of M2 neurons or axons into the dorsomedial striatum increases striatal levels of dopamine and evokes locomotor activity. We found that dopamine neurotransmission sensitizes the locomotor behavior elicited by activation of M2 neurons. Furthermore, combination of intranigral infusion of glutamatergic antagonists and circuit specific optogenetic stimulation revealed that behavioral response depended on the activity of M2 neurons projecting to SNc. Interestingly, repeated M2 stimulation combined with l-DOPA treatment produced an unanticipated improvement in working memory performance, which was absent in control mice under l-DOPA treatment only. Therefore, the M2-basal ganglia circuit is critical for the assembly of the motor and cognitive function, and this study demonstrates a therapeutic mechanism for cortical stimulation in PD that involves recruitment of long-range glutamatergic projection neurons.
Some patients with Parkinson's disease are offered treatment through surgery, which consists of delivering electrical current to regions deep within the brain. This study shows that stimulation of an area located on the brain surface, known as the secondary motor cortex, can also reverse movement disorders in mice. Authors have used a brain stimulation technique called optogenetics, which allowed targeting a specific type of surface neuron that communicates with the deep part of the brain involved in movement control. The study also shows that a combination of this stimulation with drug treatment might be useful to treat memory impairment, a kind of cognitive problem in Parkinson's disease.
In situ conservation is an effective strategy to protect biodiversity, and Brazil has one of the largest protected area (PA) systems in the world. However, the distribution of Brazilian PAs is uneven ...and the Caatinga drylands are poorly protected. As financial resources are essential for effectively managing PAs, we analyzed the Brazilian Government’s budget allocated to 20 federal PAs in the Caatinga between 2008 and 2014, which ranged from 231,575 USD in 2008 to 13.5 Mi USD in 2011. Neither expenses, nor the availability of funds, were homogeneous among PAs or throughout the years. Land acquisition in a single PA consumed ~75% of the budget, and the two smallest PAs received proportionally the most money. Excluding land acquisition, the 20 PAs received 0.50 USD/ha/year. Funds were allocated not to biodiversity conservation per se but mainly to securing offices, cars, and equipment. From 2012 onwards, the PA budget was reduced. Even including salaries, the budget allocated for these PAs is ~13 times lower than what the Ministry of the Environment declared necessary for the basic operation of protected areas in Brazil, 1.5 times lower than values spent worldwide, up to 5 times lower than spent in Latin American and African parks, and up to 72 times lower than spent in the European Union, exposing one cause of the precarious situation of the Caatinga PAs.
La concepción de la autonomía y de la participación en la vida común de las personas afectadas por enfermedades, daños o discapacidades neuropsíquicas ha evolucionado y con ello lo han hecho las ...relaciones asistenciales, que son la piedra angular de la asistencia psiquiátrica.
El texto recoge (a) una breve historia de la evolución de la relación entre la enfermedad mental y la inclusión social y la autonomía, (b) la descripción de las dimensiones funcional, ejecutiva y narrativa de la autonomía, más allá de la autonomía decisoria que nos ha venido centrando estas décadas y que se enfoca en la información, la capacidad y su evaluación y el consentimiento informado, (c) las condiciones y procesos del desarrollo moral que implican a la autonomía relacional y a la ética del cuidado y finaliza (d) señalando valores que pueden entrar en conflicto como la confidencialidad, la información veraz, la libertad de elección, las buenas prácticas asistenciales, la calidad de vida y deberes necesarios como ser hospitalarias, tener un enfoque integral, favorecer la participación y la autodeterminación y alentar la esperanza.
To investigate the effect of different types of manual toothbrushes and brushing loads on the progression of erosive tooth wear (ETW) on enamel.
Bovine enamel specimens (n = 10) were submitted to a ...5-day erosive-abrasive cycling model (0.3 % citric acid for 5 min, artificial saliva for 60 min, 4x/day). Toothbrushing was carried out 2x/day for 15 s, according to the toothbrushes tested (ultra-soft (a): Curaprox 5460; ultra-soft (b): Sensodyne Repair & Protect; soft (a): Colgate Slim Soft; soft (b): Oral-B Indicator Plus; medium: Johnson’s Professional; hard: Tek) and brushing loads (1.5 N, 3 N). Surface loss (SL, in μm) was assessed by optical profilometry on conclusion of the cycling. Some of the toothbrush characteristics were evaluated. Data were statistically analyzed (α = 0.05).
For the 1.5 N load, the hard brush showed the highest SL value, with statistical significance. The other toothbrushes did not differ significantly, except that ultra-soft (a) caused significantly higher SL than ultra-soft (b). For the 3 N load, hard and soft (a) exhibited the highest SL. Soft (b) and medium had the lowest SL value, with statistical significance. Only soft (a) and ultra-soft (b) showed significant difference between loads, with lower SL for the load of 1.5 N. None of the toothbrush characteristics were significantly correlated with SL.
Although different degrees of enamel surface loss were observed with use of the different toothbrushes, no association was found between the toothbrush characteristics and SL. Depending on the toothbrush, the force of brushing was capable of modulating the ETW of enamel. Based on the brushing loads usually applied by healthy individuals, hard brushes are not recommended for use by patients with ETW.
The use of hard bristle brushes is not recommended for use by individuals who exert healthy forces when brushing their teeth. The toothbrush characteristics are of secondary importance in terms of causing enamel loss in ETW.
Introduction Pancreatic adenocarcinoma is an extremely aggressive neoplasm, with many challenges to be overcome in order to achieve a truly effective treatment. It is characterized by a mostly ...immunosuppressed environment, with dysfunctional immune cells and active immunoinhibitory pathways that favor tumor evasion and progression. Thus, the study and understanding of the tumor microenvironment and the various cells subtypes and their functional capacities are essential to achieve more effective treatments, especially with the use of new immunotherapeutics. Methods Seventy cases of pancreatic adenocarcinoma divided into two groups 43 with resectable disease and 27 with unresectable disease were analyzed using immunohistochemical methods regarding the expression of programmed cell death ligand 1 (PD-L1), programmed cell death ligand 2 (PD-L2), and human leukocyte antigen G (HLA-G) molecules as well as the populations of CD4+ and CD8+ T lymphocytes, regulatory T cells (Tregs), and M2 macrophages (MM2). Several statistical tests, including multivariate analyses, were performed to examine how those immune cells and immunoinhibitory molecules impact the evolution and prognosis of pancreatic adenocarcinoma. Results CD8+ T lymphocytes and M2 macrophages predominated in the group operated on, and PD-L2 expression predominated in the unresectable group. PD-L2 was associated with T stage, lymph node metastasis, and clinical staging, while in survival analysis, PD-L2 and HLA-G were associated with a shorter survival. In the inoperable cases, Tregs cells, MM2, PD-L1, PD-L2, and HLA-G were positively correlated. Conclusions PD-L2 and HLA-G expression correlated with worse survival in the cases studied. Tumor microenvironment was characterized by a tolerant and immunosuppressed pattern, mainly in unresectable lesions, where a broad positive influence was observed between immunoinhibitory cells and immune checkpoint proteins expressed by tumor cells.
Errorful learning suggests that, when perfect learning has not yet been attained, errors can enhance future learning if followed by corrective feedback. Research on memory updating has shown that ...after retrieval, memory becomes more malleable and prone to change. Thus, retrieval of a wrong answer might provide a good context for the incorporation of feedback. Here, we tested this hypothesis using sentences including pragmatic sentence implications, commonly used for the study of false memories. Across two experiments with young adults, we hypothesized that corrective feedback would be more efficient at reducing false memories if provided immediately after retrieval, when memory is more malleable than after being exposed to the material. Participants’ memory was assessed as a function of the type of learning task (Experiment 1: retrieval vs. restudy; and Experiment 2: active vs. passive recognition); and whether participants received corrective feedback or not. In both experiments, we observed that retrieval not only improved correct recall (replicating the testing effect) but also promoted the correction of false memories. Notably, corrective feedback was more effective when given after errors that were committed during retrieval rather than after restudy (Experiment 1) or after passive recognition (Experiment 2). Our results suggest that the benefits of retrieval go beyond the testing effect since it also facilitates false memories correction. Retrieval seems to enhance memory malleability, thus improving the incorporation of feedback, compared to the mere presentation of the information. Our results support the use of learning strategies that engage in active and explicit retrieval because, even if the retrieved information is wrong—when immediate feedback is provided—memory updating is promoted and errors are more likely to be corrected.
Genetic testing has become increasingly used in medical practice to enable genetic cancer risk assessment. In Hereditary Breast and Ovarian Cancer syndrome (HBOC), it can be used to screen pathogenic ...germline variants. The access to early diagnosis, from the request until the proper interpretation of genetic tests depends on medical knowledge. The aim of this study was to evaluate the knowledge of family physicians, oncologists, geneticists and gynecologists regarding genetic testing for patients with suspected HBOC in Brazil. A cross-sectional survey of physicians was performed using a self-administered questionnaire. One hundred and ninety-two physicians answered the questionnaire (23 were geneticists, 38 gynecologists, 39 family physicians, and 92 oncologists). Only 15.4% of family physicians and 26% of gynecologists feel prepared to order genetic testing for patients with personal and/or family history of breast and/or ovarian cancer. Even though 87% of the oncologists have genetic testing available in their clinical practice, only 51.1% consider they have sufficient knowledge to manage patients after detecting a pathogenic germline variant and 17.4% do not feel comfortable interpreting them. Most oncologists and geneticists are very knowledgeable about recommendations for genetic testing order and management of HBOC patients. On the other hand, gynecologists and family physicians order genetic testing less frequently (28.9% and 7.7%, respectively) and have difficulties interpreting (26.3% and 2.3%, respectively) and managing these patients. These observations raise important issues regarding the implementation of genetic testing in Brazil, including the development of training programs for physicians from different specialties.
to evaluate the effectiveness of the 50 IU/mL heparin solution compared to the 0.9% isotonic saline solution in preventing occlusion of the double lumen Hickman® catheter, 7 and 9 French, in patients ...undergoing hematopoietic stem cell transplantation.
a triple-blind randomized clinical trial. 17 double-lumen catheters (heparin group: n=7 and 0.9% isotonic saline group: n=10) were analyzed in which the two catheter routes were evaluated separately, totaling 34 lumens. The outcome variables were occlusion without reflux and complete occlusion. Descriptive analyses were performed using the Chi-square test and, of survival, according to the Kaplan-Meier test.
the mean number of days until the occlusion outcome was 52 in the heparin group and 13.46 in the 0.9% isotonic saline group in the white catheter route (p<0.001). In the red route, the mean follow-up days in the heparin group were 35.29, with no occlusion and 22.30 in the 0.9% isotonic saline group until the first occlusion (p=0.030).
blocking with 50 IU/mL heparin solution is more effective than 0.9% isotonic saline in preventing occlusion of the Hickman® catheter. Brazilian Registry of Clinical Trials: RBR-3ht499.
Introduction Real-world data on COVID-19 vaccine effectiveness are needed to validate evidence from randomized clinical trials. Accordingly, this study aims to evaluate, in a real-world setting in ...Brazil, the effectiveness of Pfizer-BioNTech BNT162b2 against symptomatic COVID-19 and COVID-19-related complications across diverse populations. Materials and methods A test-negative case-control study with follow-up of cases is currently being conducted in Toledo, a city in southern Brazil, following a mass COVID-19 vaccination campaign with BNT162b2. The study is being conducted among patients aged 12 years or older seeking care in the public health system with acute respiratory symptoms and tested for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). Cases are RT-PCR positive and controls RT-PCR negative. Test-positive cases are prospectively followed through structured telephone interviews performed at 15 days post-enrollment, and at 1, 3, 6, 9 and 12 months. Baseline demographic, clinical, and vaccination data are being collected by means of structured interviews and medical registry records reviews at the time of enrollment. All RT-PCR-positive samples are screened for mutations to identify SARS-CoV-2 variants. Ethics and dissemination The study protocol has been approved by the research ethics committee of all participant sites. Study findings will be disseminated through peer-reviewed publications and conference presentations. Trail registration Clinicatrials.gov: NCT05052307.
Pediatric tumors remain the highest cause of death in developed countries. Research on novel therapeutic strategies with lesser side effects is of utmost importance. In this scenario, the role of ...Renin-Angiotensin System (RAS) axes, the classical one formed by angiotensinconverting enzyme (ACE), Angiotensin II and AT1 receptor and the alternative axis composed by ACE2, Angiotensin-(1-7) and Mas receptor, have been investigated in cancer.
This review aimed to summarize the pathophysiological role of RAS in cancer, evidence for anti-tumor effects of ACE2/Angiotensin-(1-7)/Mas receptor axis and future therapeutic perspectives for pediatric cancer.
Pubmed, Scopus and Scielo were searched in regard to RAS molecules in human cancer and pediatric patients. The search terms were "RAS", "ACE", "Angiotensin-(1-7)", "ACE2", "Angiotensin II", "AT1 receptor", "Mas receptor", "Pediatric", "Cancer".
Experimental studies have shown that Angiotensin-(1-7) inhibits the growth of tumor cells and reduces local inflammation and angiogenesis in several types of cancer. Clinical trials with Angiotensin-( 1-7) or TXA127, a pharmaceutical grade formulation of the naturally occurring peptide, have reported promising findings, but not enough to recommend medical use in human cancer. In regard to pediatric cancer, only three articles that marginally investigated RAS components were found and none of them evaluated molecules of the alternative RAS axis.
Despite the potential applicability of Angiotensin-(1-7) in pediatric tumors, the role of this molecule was never tested. Further clinical trials are necessary, also including pediatric patients, to confirm safety and efficiency and to define therapeutic targets.
PDF
