Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents

Subthalamic nucleus (STN) high-frequency stimulation (HFS) is a routine treatment in Parkinson’s disease (PD), with confirmed long-term benefits. An alternative, but still experimental, treatment is cell replacement and restorative therapy based on transplanted dopaminergic neurons. The current experiment evaluated the potential synergy between neuromodulation and grafting by studying the effect of continuous STN-HFS on the survival, integration, and functional efficacy of ventral mesencephalic dopaminergic precursors transplanted into a unilateral 6-hydroxydopamine medial forebrain bundle lesioned rodent PD model. One group received continuous HFS of the ipsilateral STN starting a week prior to intrastriatal dopaminergic neuron transplantation, whereas the sham-stimulated group did not receive STN-HFS but only dopaminergic grafts. A control group was neither lesioned nor transplanted. Over the following 7 weeks, the animals were probed on a series of behavioral tasks to evaluate possible graft and/or stimulation-induced functional effects. Behavioral and histological data suggest that STN-HFS significantly increased graft cell survival, graft–host integration, and functional recovery. These findings might open an unexplored road toward combining neuromodulative and neuroregenerative strategies to treat severe neurologic conditions

Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat

Objective. Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (MFB) has provided rapid and dramatic reduction of depressive symptoms in a clinical trial. Early intracranial self-stimulation experiments of the MFB suggested detrimental side effects on the animals’ health; therefore, the current study looked at the viability of chronic and continuous MFB-DBS in rodents, with particular attention given to welfare issues and identification of stimulated pathways. Methods. Sprague-Dawley female rats were submitted to stereotactic microelectrode implantation into the MFB. Chronic continuous DBS was applied for 3–6 weeks. Welfare monitoring and behavior changes were assessed. Postmortem histological analysis of c-fos protein expression was carried out. Results. MFB-DBS resulted in mild and temporary weight loss in the animals, which was regained even with continuing stimulation. MFB-DBS led to increased and long-lasting c-fos expression in target regions of the mesolimbic/mesocortical system. Conclusions. Bilateral continuous chronic MFB-DBS is feasible, safe, and without impact on the rodent’s health. MFB-DBS results in temporary increase in exploration, which could explain the initial weight loss, and does not produce any apparent behavioral abnormalities. This platform represents a powerful tool for further preclinical investigation of the MFB stimulation in the treatment of depression

A EDUCAÇÃO DE ADULTOS E O PROGRAMA DE COMBATE AO ANALFABETISMO EM PRESIDENTE PRUDENTE

Neste artigo, após traçar breve quadro do histórico e da situação atual da Educação de Adultos no País, descrevemos o programa "Combate ao Analfabetismo" desenvolvido pela Prefeitura Municipal de Presidente Prudente, cuja direção pedagógica esta a cargo da FCT/UNESP - Campus de Presidente Prudente. Apontamos os principais problemas didático-pedagógicos e administrativos colocados ao programa e as soluções que foram encontradas

Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents

Subthalamic nucleus (STN) high-frequency stimulation (HFS) is a routine treatment in Parkinson’s disease (PD), with confirmed long-term benefits. An alternative, but still experimental, treatment is cell replacement and restorative therapy based on transplanted dopaminergic neurons. The current experiment evaluated the potential synergy between neuromodulation and grafting by studying the effect of continuous STN-HFS on the survival, integration, and functional efficacy of ventral mesencephalic dopaminergic precursors transplanted into a unilateral 6-hydroxydopamine medial forebrain bundle lesioned rodent PD model. One group received continuous HFS of the ipsilateral STN starting a week prior to intrastriatal dopaminergic neuron transplantation, whereas the sham-stimulated group did not receive STN-HFS but only dopaminergic grafts. A control group was neither lesioned nor transplanted. Over the following 7 weeks, the animals were probed on a series of behavioral tasks to evaluate possible graft and/or stimulation-induced functional effects. Behavioral and histological data suggest that STN-HFS significantly increased graft cell survival, graft–host integration, and functional recovery. These findings might open an unexplored road toward combining neuromodulative and neuroregenerative strategies to treat severe neurologic conditions

Perfis de distribuição volumétrica de pontas XR 11003 e TXVK-4 em diferentes condições de pulverização Spray distribution patterns of the XR 11003 and TXVK-4 hydraulic nozzles under different conditions

Com o objetivo de avaliar a uniformidade da distribuição volumétrica e o efeito da angulação dos bicos na barra em pulverizações, foi conduzido experimento em laboratório, com dez unidades de cada uma das pontas de jato plano XR 11003 e de jato cônico vazio TXVK-4, fabricadas pela Spraying Systems Co. As pontas XR 11003 foram avaliadas, isoladamente, em mesa de prova para bicos construída conforme a Norma ISO 5682-1:1996, a 0,30; 0,40 e 0,50 m de altura, submetidas à pressão de 200 e 300 kPa e posicionadas com ângulos de 30º e 45º no sentido horário e anti-horário e na vertical; as pontas TXVK-4 foram avaliadas nas mesmas alturas, porém a 300 e 400 kPa, e somente na vertical. A distribuição média do volume coletado em cada configuração, das dez unidades de cada ponta, foi inserida num programa computacional, desenvolvido para o estudo, que permitiu a simulação do padrão de deposição de uma barra pulverizadora, com 24 bicos, com sobreposições variáveis, obtendo-se, ao final, o coeficiente de variação da sobreposição, o desvio- padrão e a média do volume aplicado. Os resultados sugerem a necessidade de ajustes no espaçamento entre bicos para a obtenção de melhor uniformidade na distribuição, principalmente quando se utiliza ângulo na barra; há menor influência da variação da altura da barra sobre a uniformidade da distribuição quando o espaçamento entre bicos é reduzido.<br>The objective of this study was to evaluate the uniformity of spray distribution as well as the angle effect of hydraulic nozzles in a spray boom. Ten units of flat fan nozzle XR 11003 and hollow cone TXVK-4 (Spraying Systems Co) were tested in a patternator table built in accordance to the standard ISO 5682-1:1996. Each one of the units was tested separately, at the height of 0.30, 0.40 and 0.50 m, at 200 and 300 kPa and angles of 30º and 45º , clockwise and counterclockwise and in the vertical position. TXVK-4 nozzles were tested at same heights but at 300 and 400 kPa and only in the vertical position. The mean of the collected spray volume distribution of each nozzle type tip was entered in a computer program developed. This program simulated the distribution pattern of 24 nozzles boom at different overlapping and calculated the coefficient of variation corresponding to each configuration. The results pointed out to the necessity of the adaptation in nozzles spacing especially if any angle is in use and that the distribution uniformity is less vulnerable to boom height variation at reduced nozzle spacing

Everything old is new again. revisiting hypophysectomy for the treatment of refractory cancer-related pain: a systematic review

Cancer-related pain is a common and debilitating condition that can significantly affect the quality of life of patients. Opioids, NSAIDs, and antidepressants are among the first-line therapies, but their efficacy is limited or their use can be restricted due to serious side effects. Neuromodulation and lesioning techniques have also proven to be a valuable instrument for managing refractory pain. For patients who have exhausted all standard treatment options, hypophysectomy may be an effective alternative treatment. We conducted a comprehensive systematic review of the available literature on PubMed and Scielo databases on using hypophysectomy to treat refractory cancer-related pain. Data extraction from included studies included study design, treatment model, number of treated patients, sex, age, Karnofsky Performance Status (KPS) score, primary cancer site, lead time from diagnosis to treatment, alcohol injection volume, treatment data, and clinical outcomes. Statistical analysis was reported using counts (N, %) and means (range). The study included data from 735 patients from 24 papers treated with hypophysectomy for refractory cancer-related pain. 329 cancer-related pain patients were treated with NALP, 216 with TSS, 66 with RF, 55 with Y90 brachytherapy, 51 with Gamma Knife radiosurgery (GK), and 18 with cryoablation. The median age was 58.5 years. The average follow-up time was 8.97 months. Good pain relief was observed in 557 out of 735 patients, with complete pain relief in 108 out of 268 patients. Pain improvement onset was observed 24 h after TSS, a few days after NALP or cryoablation, and a few days to 4 weeks after GK. Complications varied among treatment modalities, with diabetes insipidus (DI) being the most common complication. Although mostly forgotten in modern neurosurgical practice, hypophysectomy is an attractive option for treating refractory cancer-related pain after failure of traditional therapies. Radiosurgery is a promising treatment modality due to its high success rate and reduced risk of complications