Prolonged focal application of polyethylene glycol induces conduction block in guinea pig spinal cord white matter.

A 2-min focal application of Polyethylene Glycol (PEG) to injured mammalian spinal cords can offer significant yet limited restoration of functional and structural integrity. However, longer application of PEG has not been tested in similar injuries. In this study, isolated spinal cord white matter strips from adult guinea pigs were subjected to a 25 min exposure of PEG (MW: 2000; 50% w/w), with or without prior compression. When applied in a continuous steam, PEG, with a delay of about 6 min, suppressed the compound action potential (CAP) amplitude to 64+/-4% of the pre-PEG level in uninjured cords and to 64+/-7% in compressed cord strips. Both recovered to 70+/-5% (uninjured) and 88+/-11% (compressed) of the pre-PEG level following wash. When PEG was applied in a pulsatile manner, no significant decrease of CAP amplitude was observed. In summary, our results show that focal continuous application of PEG has minimal toxicity if applied for less than 5 min. Pulsatile application could extend this duration to at least 25 min with no toxicity. This study could be useful in determining the optimal protocol for the use of PEG in both animal research and human spinal cord victims.     

Contrasting synaptic actions of the inhalational general anesthetics isoflurane and xenon

BACKGROUND: The mechanisms by which the inhalational general anesthetics isoflurane and xenon exert their effects are unknown. Moreover, there have been surprisingly few quantitative studies of the effects of these agents on central synapses, with virtually no information available regarding the actions of xenon. METHODS: The actions of isoflurane and xenon on gamma-aminobutyric acid-mediated (GABAergic) and glutamatergic synapses were investigated using voltage-clamp techniques on autaptic cultures of rat hippocampal neurons, a preparation that avoids the confounding effects of complex neuronal networks. RESULTS: Isoflurane exerts its greatest effects on GABAergic synapses, causing a marked increase in total charge transfer (by approximately 70% at minimum alveolar concentration) through the inhibitory postsynaptic current. This effect is entirely mediated by an increase in the slow component of the inhibitory postsynaptic current. At glutamatergic synapses, isoflurane has smaller effects, but it nonetheless significantly reduces the total charge transfer (by approximately 30% at minimum alveolar concentration) through the excitatory postsynaptic current, with the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor-mediated components being roughly equally sensitive. Xenon has no measurable effect on GABAergic inhibitory postsynaptic currents or on currents evoked by exogenous application of GABA, but it substantially inhibits total charge transfer (by approximately 60% at minimum alveolar concentration) through the excitatory postsynaptic current. Xenon selectively inhibits the NMDA receptor-mediated component of the current but has little effect on the AMPA/kainate receptor-mediated component. CONCLUSIONS: For both isoflurane and xenon, the most important targets appear to be postsynaptic. The authors' results show that isoflurane and xenon have very different effects on GABAergic and glutamatergic synaptic transmission, and this may account for their differing pharmacologic profiles.     

Cyclin d1 is a valuable prognostic marker in oropharyngeal squamous cell carcinoma.

BACKGROUND: The current tumor-node-metastasis system is inadequate to accurately classify patients in terms of prognosis. Thus, with the availability of recently developed molecular tools, considerable interest lies in discovering prognostic markers in order to guide treatment decisions. In this study, we sought to determine the prognostic significance of the cell cycle regulator cyclin D1 in oropharyngeal squamous cell carcinoma (OSCC). EXPERIMENTAL DESIGN: We studied the protein expression levels of cyclin D1 on a tissue microarray composed of 63 OSCCs with long-term follow-up data available. Protein expression was analyzed with an automated in situ quantitative (AQUA) method which allows preservation of tissue morphology while quantifying protein expression in paraffin-embedded tissue. RESULTS: The mean follow-up time was 35 months. High cyclin D1 nuclear expression was associated with increased 5-year local recurrence rate (48% versus 15%), inferior 5-year disease-free survival (16% versus 58%), and inferior 5-year overall survival (17% versus 53%). In multivariate Cox regression, high nuclear cyclin D1 expression was an independent predictor for local recurrence, disease-free survival, and overall survival at 5 years. CONCLUSIONS: Our results indicate that quantitative assessment of nuclear cyclin D1 expression level by automated in situ quantitative analysis is a strong predictor for outcome in OSCC. Thus, cyclin D1 may be a potential target for molecular intervention in patients with oropharyngeal squamous cell cancer.     

Cathepsins in neuronal plasticity

Proteases comprise a variety of enzymes defined by their ability to catalytically hydrolyze the peptide bonds of other proteins, resulting in protein lysis. Cathepsins, specifically, encompass a class of at least twenty proteases with potent endopeptidase activity. They are located subcellularly in lysosomes, organelles responsible for the cell's degradative and autophagic processes, and are vital for normal lysosomal function. Although cathepsins are involved in a multitude of cell signaling activities, this chapter will focus on the role of cathepsins(with a special emphasis on Cathepsin B) in neuronal plasticity. We will broadly define what is known about regulation of cathepsins in the central nervous system and compare this with their dysregulation after injury or disease. Importantly, we will delineate what is currently known about the role of cathepsins in axon regeneration and plasticity after spinal cord injury. It is well established that normal cathepsin activity is integral to the function of lysosomes. Without normal lysosomal function, autophagy and other homeostatic cellular processes become dysregulated resulting in axon dystrophy. Furthermore, controlled activation of cathepsins at specialized neuronal structures such as axonal growth cones and dendritic spines have been positively implicated in their plasticity. This chapter will end with a perspective on the consequences of cathepsin dysregulation versus controlled, localized regulation to clarify how cathepsins can contribute to both neuronal plasticity and neurodegeneration.     

Comparação entre os Efeitos da Ingestão de Sal do Himalaia e de Sal Comum sobre os Valores de Sódio Urinário e Pressão Arterial em Indivíduos Hipertensos

Background The Himalayan salt (HS) has become a popular alternative for the traditional table salt (TS) due to its health benefit claims, particularly for individuals with arterial hypertension. However, despite the increase in HS consumption, there is still a lack of clinical evidence to support a recommendation for its consumption by health professionals.Objective This cross-over study aimed to compare the impact of HS and TS intake on systolic blood pressure (SBP) and diastolic blood pressure (DBP), and urinary sodium concentration in individuals with arterial hypertension.Methods This study recruited 17 female patients with arterial hypertension who ate out no more than once a week. Participants were randomized into two groups, to receive and consume either HS or TS. Before and after each intervention, participants had their blood pressure measured and urine collected for mineral analysis. A p-value < 0.05 was considered statistically significant.Results There were no statistically significant differences before and after the HS intervention for DBP (70mmHg vs. 68.5mmHg; p=0.977), SBP (118.5 mmHg vs. 117.5 mmHg; p= 0.932) and sodium urinary concentration (151 mEq/24h vs. 159 mEq/24; p=0.875). Moreover, the between-group analysis showed no significant differences after the intervention regarding SBP (117mmHg vs 119 mmHg; p=0.908), DBP (68.5 mmHg vs. 71mmHg; p= 0,645) or sodium urinary concentration (159 mEq/24h vs. 155 mEq/24h; p=0.734).Conclusion This study suggests that there are no significant differences on the impact of HS consumption compared to TS on blood pressure and sodium urinary concentration in individuals with arterial hypertension.     

Participatory Systems Mapping for Municipal Prioritization and Planning

Rapidly growing cities face new and compounding health challenges, leading governments and donors to seek innovative ways to support healthier, more resilient urban growth. One such approach is the systems mapping process developed by Engaging Inquiry (EI) for the USAID-funded Building Healthy Cities project (BHC) in four cities in Asia. This paper provides details on the theory and methods of the process. While systems mapping is not new, the approach detailed in this paper has been uniquely adapted to the purpose of municipal planning. Strategic stakeholder engagement, including participatory workshops with a diverse group of stakeholders, is at the core of this approach and led to deeper insights, greater buy-in, and shared understanding of the city’s unique opportunities and challenges. This innovative mapping process is a powerful tool for defining municipal priorities within growing cities across the globe, where the situation is rapidly evolving. It can be used to provide evidence-based information on where to invest to gain the biggest impact on specific goals. This paper is part of a collection in this issue providing a detailed accounting of BHC’s systems mapping approach across four project cities.     

Melanotic Neuroectodermal Tumor of Infancy: the Use of Immunohistochemical Analysis

The Melanotic Neuroectodermal Tumor of Infancy (MNTI) is an asymptomatic, pigmented neoplasm characterized by a fast and locally aggressive growth along with a rare tissue formation. In the diagnostic process, the use of imaging exams can suggest a local destruction suggestive of malignancy, a sign of bone remodeling and expansion. Therefore, as any early diagnosis minimizes risks and improves the prognosis of treatment for the patient, the aim of this study was, based on a clinical case report, to corroborate the use of histopathological analysis associated with immunohistochemistry. Thus, we conclude that the immunohistochemical exam is of great importance for a better complementation of the MNTI diagnosis process. In addition, it can reveal signs of possible aggressive growth.     

Body Fat Moderates the Association of Olfactory Dysfunction with Dietary Intake in U.S. Middle-Aged and Older Adults: A Cross-Sectional Analysis of NHANES 2013–2014

Background: Obesity relates to impaired olfactory function. Abnormal olfactory function is also associated with poor diet; however, whether obesity-related markers shape this relationship is unknown. Methods: Cross-sectional analysis (n = 1415, age > 40 years) of NHANES 2013–2014 examined body fat percent (BF%) and waist circumference (WC) as moderators of the relationship between olfactory function and diet. The olfactory function test identified adults with olfactory dysfunction (OD) or normal olfaction (NO). Validated 24 h recall captured nutrient intake and Healthy Eating Index-2010 scores. BF% and WC were measured. We tested adjusted linear regression models, with an interaction term between olfactory function and BF%/WC, for each nutrient or HEI score, and reported coefficients (β), standard errors (SE), and p-values for significant interaction terms. Results: In OD (9.5%; mean age 50.9 years, 95% CI 49.6, 52.2) compared with NO (mean age 49.3 years, 95% CI 48.8, 49.9), higher BF% was associated with higher intake of saturated fat (β (SE): 0.2 (0.1) g; p = 0.06) and percent of total calories from total fat (0.2 (0.1); p = 0.07), saturated (0.1 (0.004); p = 0.02), and monounsaturated fat (0.1 (0.1); p = 0.08); lower percent of total calories from carbohydrates (−0.2 (0.1); p = 0.09) and mg of sodium (−17.8 (09.6); p = 0.08); and a higher (healthier) refined grain score (0.1 (0.1); p = 0.04). Higher WC was associated with higher refined grain scores (0.01 (0.02); p = 0.01) in OD. Conclusion: BF% may shape dietary intake and quality in OD. Longitudinal studies are needed to elucidate the directionality of these relationships and develop strategies to improve dietary intake among OD.