Emerging pharmacotherapy for cancer patients with cognitive dysfunction

Advances in the diagnosis and multi-modality treatment of cancer have increased survival rates for many cancer types leading to an increasing load of long-term sequelae of therapy, including that of cognitive dysfunction. The cytotoxic nature of chemotherapeutic agents may also reduce neurogenesis, a key component of the physiology of memory and cognition, with ramifications for the patient's mood and other cognition disorders. Similarly radiotherapy employed as a therapeutic or prophylactic tool in the treatment of primary or metastatic disease may significantly affect cognition. A number of emerging pharmacotherapies are under investigation for the treatment of cognitive dysfunction experienced by cancer patients. Recent data from clinical trials is reviewed involving the stimulants modafinil and methylphenidate, mood stabiliser lithium, anti-Alzheimer's drugs memantine and donepezil, as well as other agents which are currently being explored within dementia, animal, and cell culture models to evaluate their use in treating cognitive dysfunction

Enfermagem e saúde ambiental na escola Enfermeria y salud ambiental en la escuela Nursing and environmental health in schools

OBJETIVO: Descrever e analisar os significados atribuídos por um grupo de adolescente à saúde ambiental. MÉTODOS: Estudo de abordagem qualitativa, descritivo, exploratório, que utilizou a pesquisa-ação em uma escola pública do interior do Ceará, que se encontra nas proximidades da construção de uma usina termoelétrica a carvão mineral. Foram utilizados a observação livre, o diário de campo e a abordagem grupal, esta por meio da técnica do desenho história com tema, tendo como eixo norteador a questão: O que você entende como saúde ambiental? RESULTADOS: Emergiram discussões a respeito da interferência do homem na natureza, malefícios das fábricas, desenvolvimento sustentável e risco da poluição na comunidade. CONCLUSÃO: Constatou-se que o enfermeiro pode ser um educador ambiental e atuar nesse espaço, favorecendo momentos de reflexão sobre ações comprometidas com o lócus socioambiental.<br>OBJETIVO: Describir y analizar los significados atribuídos por un grupo de adolescentes a la salud ambiental. MÉTODOS: Estudio con abordaje cualitativo, descriptivo, exploratorio, en el que se usó la investigación acción en una Escuela pública del interior de Ceará, ubicada en las proximidades de la construcción de una usina termoeléctrica a carbón mineral. Fueron utilizados la observación libre, el diario de campo y el abordaje grupal, esta última por medio de la técnica del dibujo de una historia con tema, teniendo como eje norteador la pregunta: ¿Qué entiende ud.como salud ambiental? RESULTADOS: Emergieron discusiones respecto a la interferencia del hombre en la naturaleza, daño de las fábricas, desarrollo sustentable y riesgo de contaminación en la comunidad. CONCLUSIÓN: Se constató que el enfermero puede ser un educador ambiental y actuar en ese espacio, favoreciendo momentos de reflexión sobre acciones comprometidas con el locus socioambiental.<br>OBJECTIVE: To describe and analyze the meanings attributed by a group of adolescents to environmental health. METHODS: A qualitative, descriptive, exploratory study, that utilized action research in a public school in the interior of Ceará, that was located in proximity to the construction of a thermoelectric coal power plant. We used free observation, field notes and a group approach, by means of the technique of historical design of the theme, and were guided by the question: What do you understand about environmental health? RESULTS: Discussions emerged with respect to the interference of man on nature, harming the plants, sustainable development and pollution risk in the community. CONCLUSION: We found that nurses can be environmental educators and work in this space, encouraging moments of reflection about actions committed to the socioenvironmental locus

The outcome of Morton’s neurectomy in the treatment of metatarsalgia

Morton’s neuroma is a common cause of metatarsalgia caused by intermetarsal digital nerve thickening. This study reviews the pathology, presentation, symptoms and signs, and patient satisfaction with surgical treatment. Seventy-eight patients (82 feet) were treated for Morton’s metatarsalgia by excision of the interdigital nerve. The patients were followed-up for a mean of 4.6 years (range 0.8–8.1 years) and scored using the Foot Functional Index and the American Orthopedic Foot Ankle Society scoring system. In 74 patients the Foot Functional Index was more than 85 (maximum score 100). Seventy-one patients scored more than 90 on the American Orthopedic Foot Ankle Society scoring system with two patients scoring 100 (maximum score). Postoperatively, 82% reported excellent or good results, 10% had a fair result with restriction of activities or pain and 8% had no improvement at all after surgery while 71% had restrictions with footwear

Activation of the GABAergic Parafacial Zone Maintains Sleep and Counteracts the Wake-Promoting Action of the Psychostimulants Armodafinil and Caffeine

We previously reported that acute and selective activation of GABA-releasing parafacial zone (PZVgat) neurons in behaving mice produces slow-wave-sleep (SWS), even in the absence of sleep deficit, suggesting that these neurons may represent, at least in part, a key cellular substrate underlying sleep drive. It remains, however, to be determined if PZVgat neurons actively maintain, as oppose to simply gate, SWS. To begin to experimentally address this knowledge gap, we asked whether activation of PZVgat neurons could attenuate or block the wake-promoting effects of two widely used wake-promoting psychostimulants, armodafinil or caffeine. We found that activation of PZVgat neurons completely blocked the behavioral and electrocortical wake-promoting action of armodafinil. In some contrast, activation of PZVgat neurons inhibited the behavioral, but not electrocortical, arousal response to caffeine. These results suggest that: (1) PZVgat neurons actively maintain, as oppose to simply gate, SWS and cortical slow-wave-activity; (2) armodafinil cannot exert its wake-promoting effects when PZVgat neurons are activated, intimating a possible shared circuit/molecular basis for mechanism of action; (3) caffeine can continue to exert potent cortical desynchronizing, but not behavioral, effects when PZVgat neurons are activated, inferring a shared and divergent circuit/molecular basis for mechanism of action; and 4) PZVgat neurons represent a key cell population for SWS induction and maintenance

Inter-hemispheric oscillations in human sleep

Sleep is generally categorized into discrete stages based on characteristic electroencephalogram (EEG) patterns. This traditional approach represents sleep architecture in a static way, but it cannot reflect variations in sleep across time and across the cortex. To investigate these dynamic aspects of sleep, we analyzed sleep recordings in 14 healthy volunteers with a novel, frequency-based EEG analysis. This approach enabled comparison of sleep patterns with low inter-individual variability. We then implemented a new probability dependent, automatic classification of sleep states that agreed closely with conventional manual scoring during consolidated sleep. Furthermore, this analysis revealed a previously unrecognized, interhemispheric oscillation during rapid eye movement (REM) sleep. This quantitative approach provides a new way of examining the dynamic aspects of sleep, shedding new light on the physiology of human slee

Common Childhood Epilepsy Mimics

Unusual movements in children frequently generate concern of underlying seizures from parents and lead to professional review. Stigma associated with epilepsy heightens anxiety and a wish to confirm or exclude the diagnosis as soon as possible. These considerations could lead to a wrong diagnosis of epilepsy being given with unwarranted exposure to medications with potential side effects and cost burden to families. This chapter seeks to provide practitioners in pediatric epilepsy with an exploration of practical differential diagnoses for epilepsy in children, particularly for convulsive seizures. Evaluation of all epilepsy mimics requires a precise and relevant history to help arrive at a diagnosis. Epilepsy mimics across various ages will be reviewed, with the most common differential diagnoses presented first. Examples of common potential epilepsy mimics include benign sleep myoclonus, which is frequently observed in infants and may be a challenge to differentiate from myoclonic seizures in infants. It is a very common phenomenon in pre-term infants with an incidence of 57–132 per 1000 live births. Breath-holding spells among toddlers are common and may be mistaken for epilepsy, as can reflex anoxic seizures. Self-gratification phenomena have been observed from infancy onward and may resemble clonic seizures. Inattention in school-going children is a differential diagnosis for absence seizures and both conditions may co-exist. Stressed or traumatized children may present with non-epileptic psychogenic seizures, as can children with established seizures. Lack of concurrent electrophysiological correlates and absence of stereotypic presentation help differentiate inattention and non-epileptic seizures from childhood epilepsy. Sleep-related activity such as hallucinations, parasomnias, and hypnagogic jerks could also be mistaken for epilepsy in children. Video electroencephalogram (video-EEG) telemetry evaluation is invaluable in such cases. Lack of video-EEG services, simple videos, or EEG studies in resource-poor settings makes diagnosis of epilepsy imitators challenging. The differences between epilepsy and common differential diagnoses for practitioners in resource-limited settings who may lack access to requisite investigative tools will be addressed in the following text. The outcome for most epilepsy mimics is excellent with minimal morbidity and mortality. The potential danger posed by unnecessary medical interventions caused by misdiagnosis of epilepsy makes it imperative that this possibility is minimized

Neural circuit interactions between the dorsal raphe nucleus and the lateral hypothalamus: an experimental and computational study

Orexinergic/hypocretinergic (Ox) neurotransmission plays an important role in regulating sleep, as well as in anxiety and depression, for which the serotonergic (5-HT) system is also involved in. However, little is known regarding the direct and indirect interactions between 5-HT in the dorsal raphe nucleus (DRN) and Ox neurons in the lateral hypothalamus (LHA). In this study, we report the additional presence of 5-HT1BR, 5-HT2AR, 5-HT2CR and fast ligand-gated 5-HT3AR subtypes on the Ox neurons of transgenic Ox-enhanced green fluorescent protein (Ox-EGFP) and wild type C57Bl/6 mice using single and double immunofluorescence (IF) staining, respectively, and quantify the colocalization for each 5-HT receptor subtype. We further reveal the presence of 5-HT3AR and 5-HT1AR on GABAergic neurons in LHA. We also identify NMDAR1, OX1R and OX2R on Ox neurons, but none on adjacent GABAergic neurons. This suggests a one-way relationship between LHA's GABAergic and Ox neurons, wherein GABAergic neurons exerts an inhibitory effect on Ox neurons under partial DRN's 5-HT control. We also show that Ox axonal projections receive glutamatergic (PSD-95 immunopositive) and GABAergic (Gephyrin immunopositive) inputs in the DRN. We consider these and other available findings into our computational model to explore possible effects of neural circuit connection types and timescales on the DRN-LHA system's dynamics. We find that if the connections from 5-HT to LHA's GABAergic neurons are weakly excitatory or inhibitory, the network exhibits slow oscillations; not observed when the connection is strongly excitatory. Furthermore, if Ox directly excites 5-HT neurons at a fast timescale, phasic Ox activation can lead to an increase in 5-HT activity; no significant effect with slower timescale. Overall, our experimental and computational approaches provide insights towards a more complete understanding of the complex relationship between 5-HT in the DRN and Ox in the LHA