A history of opioid exposure in females increases the risk of metabolic disorders in their future male offspring

© 2019 Society for the Study of Addiction Worldwide consumption of opioids remains at historic levels. Preclinical studies report intergenerational effects on the endogenous opioid system of future progeny following preconception morphine exposure. Given the role of endogenous opioids in energy homeostasis, such effects could impact metabolism in the next generation. Thus, we examined diet-induced modifications in F1 male progeny of morphine-exposed female rats (MORF1). When fed a high fat-sugar diet (FSD) for 6 weeks, MORF1 males display features of emerging metabolic syndrome; they consume more food, gain more weight, and develop fasting-induced hyperglycemia and hyperinsulinemia. In the hypothalamus, proteins involved in energy homeostasis are modified and RNA sequencing revealed down-regulation of genes associated with neuronal plasticity, coupled with up-regulation of genes associated with immune, inflammatory, and metabolic processes that are specific to FSD-maintained MORF1 males. Thus, limited preconception morphine exposure in female rats increases the risk of metabolic syndrome/type 2 diabetes in the next generation

Renormalization of QCD_2

The low energy infrared scaling of the multi-color 2-dimensional quantum chromodynamics is determined in the framework of its bosonized model by using the functional renormalization group method with gliding sharp cut-off k in momentum space in the local potential approximation. The model exhibits a single phase with a superuniversal effective potential.Comment: 15 pages, 3 figures, final versio

Plasticity in neurological disorders and challenges for noninvasive brain stimulation (NBS)

There has been considerable interest in trialing NBS in a range of neurological conditions, and in parallel the range of NBS techniques available continues to expand. Underpinning this is the idea that NBS modulates neuroplasticity and that plasticity is an important contributor to functional recovery after brain injury and to the pathophysiology of neurological disorders. However while the evidence for neuroplasticity and its varied mechanisms is strong, the relationship to functional outcome is less clear and the clinical indications remain to be determined. To be maximally effective, the application of NBS techniques will need to be refined to take into account the diversity of neurological symptoms, the fundamental differences between acute, longstanding and chronic progressive disease processes, and the differential part played by functional and dysfunctional plasticity in diseases of the brain and spinal cord

Utility of a thematic network in primary health care: a controlled interventional study in a rural area

BACKGROUND: UniNet is an Internet-based thematic network for a virtual community of users (VCU). It supports a virtual multidisciplinary community for physicians, focused on the improvement of clinical practice. This is a study of the effects of a thematic network such as UniNet on primary care medicine in a rural area, specifically as a platform of communication between specialists at the hospital and doctors in the rural area. METHODS: In order to study the effects of a thematic network such as UniNet on primary care medicine in a rural area, we designed an interventional study that included a control group. The measurements included the number of patient displacements due to disease, number of patient hospital stays and the number of prescriptions of drugs of low therapeutic utility and generic drug prescriptions by doctors. These data were analysed and compared with those of the control center. RESULTS: Our study showed positive changes in medical practice, reflected in the improvement of the evaluated parameters in the rural health area where the interventional study was carried out, compared with the control area. We discuss the strengths and weaknesses of UniNet as a potential medium to improve the quality of medical care in rural areas. CONCLUSION: The rural doctors had an effective, useful, user-friendly and cheap source of medical information that may have contributed to the improvement observed in the medical quality indices

Individualized Cost-Effectiveness Analysis

John Ioannidis and Alan Garber discuss how to use incremental cost-effectiveness ratios (ICER) and related metrics so they can be useful for decision-making at the individual level, whether used by clinicians or individual patients

The everpresent eta-problem: knowledge of all hidden sectors required

We argue that the eta-problem in supergravity inflation cannot be solved without knowledge of the ground state of hidden sectors that are gravitationally coupled to the inflaton. If the hidden sector breaks supersymmetry independently, its fields cannot be stabilized during cosmological evolution of the inflaton. We show that both the subsequent dynamical mixing between sectors as well as the lightest mass of the hidden sector are set by the scale of supersymmetry breaking in the hidden sector. The true cosmological eta-parameter arises from a linear combination of the lightest mode of the hidden sector with the inflaton. Generically, either the true eta deviates considerably from the na\"ive eta implied by the inflaton sector alone, or one has to consider a multifield model. Only if the lightest mass in the hidden sector is much larger than the inflaton mass and if the inflaton mass is much larger than the scale of hidden sector supersymmetry breaking, is the effect of the hidden sector on the slow-roll dynamics of the inflaton negligible.Comment: 27 pages, 6 figures; v2, published version, minor adjustments to the introduction, minor corrections to section 2.2 for improved clarity, references adde

Effect of Ultrasonic-Assisted Blanching on Size Variation, Heat Transfer, and Quality Parameters of Mushrooms

The main aim of this work was to assess the influence of the application of power ultrasound during blanching of mushrooms (60 90 °C) on the shrinkage, heat transfer, and quality parameters. Kinetics of mushroom shrinkage was modeled and coupled to a heat transfer model for conventional (CB) and ultrasonic-assisted blanching (UB). Cooking value and the integrated residual enzymatic activity were obtained through predicted temperatures and related to the hardness and color variations of mushrooms, respectively. The application of ultrasound led to an increase of shrinkage and heat transfer rates, being this increase more intense at low process temperatures. Consequently, processing time was decreased (30.7 46.0 %) and a reduction in hardness (25.2 40.8 %) and lightness (13.8 16.8 %) losses were obtained. The best retention of hardness was obtained by the UB at 60 °C, while to maintain the lightness it was the CB and UB at 90 °C. For enhancing both quality parameters simultaneously, a combined treatment (CT), which consisted of a CB 0.5 min at 90 °C and then an UB 19.9min at 60 °C, was designed. In this manner, compared with the conventional treatment at 60 °C, reductions of 39.1, 27.2, and 65.5 % for the process time, hardness and lightness losses were achieved, respectively. These results suggest that the CT could be considered as an interesting alternative to CB in order to reduce the processing time and improve the overall quality of blanched mushrooms.The authors acknowledge the financial support of Consejo Nacional de Investigaciones Cientificas y Tecnicas and Universidad Nacional de La Plata from Argentina, Erasmus Mundus Action 2-Strand 1 and EuroTango II Researcher Training Program and Ministerio de Economia y Competitividad (SPAIN) and the FEDER (project DPI2012-37466-CO3-03).Lespinard, A.; Bon Corbín, J.; Cárcel Carrión, JA.; Benedito Fort, JJ.; Mascheroni, RH. (2015). 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A., Quintero-Ramos, A., Barnard, J., Balandrán-Quintana, R. R., Talamás-Abbud, R., & Jiménez-Castro, J. (2007). Effect of ultrasound on the mass transfer and physical changes in brine bell pepper at different temperatures. Journal of Food Engineering, 81, 374–379.Gallego-Juárez, J. A., Riera, E., De la Fuente, S., Rodríguez-Corral, G., Acosta-Aparicio, V. M., & Blanco, A. (2007). Application of high-power ultrasound for dehydration of vegetables: processes and devices. Drying Technology, 25, 1893–1901.Gamboa-Santos, J., Montilla, A., Soria, A. C., & Villamiel, M. (2012). Effects of conventional and ultrasound blanching on enzyme inactivation and carbohydrate content of carrots. European Food Research and Technology, 234, 1071–1079.García-Pérez, J. V., Cárcel, J. A., De la Fuente, S., & Riera, E. (2006). Ultrasonic drying of foodstuff in a fluidized bed. Parametric study. Ultrasonics, 44, 539–543.García-Pérez, J. V., Cárcel, J. A., Riera, E., Rosselló, C., & Mulet, A. (2012). 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Comparison of conventional and ultrasound assisted extraction techniques of yellow tea and bioactive composition of obtained extracts. Food and Bioprocess Technology, 5, 2858–2870.Jambrak, A. R., Mason, T. J., Paniwnyk, L., & Lelas, V. (2007a). Ultrasonic effect on pH, electric conductivity, and tissue surface of button mushrooms, brussels sprouts and cauliflower. Czech Journal of Food Science, 25, 90–99.Jambrak, A. R., Mason, T. J., Paniwnyk, L., & Lelas, V. (2007b). Accelerated drying of button mushrooms, Brussels sprouts and cauliflower by applying power ultrasound and its rehydration properties. Journal of Food Engineering, 81, 88–97.Jasinski, E. M., Stemberger, B., Walsh, R., & Kilara, A. (1984). Ultra structural studies of raw and processed tissue of the major cultivated mushroom, Agaricus bisporus. Food Microstructure, 3, 191–196.Jolivet, S., Arpin, N., Wicher, H. J., & Pellon, G. (1998). Agaricus bisporus browning: a review. Mycological Research, 102, 1459–1483.Konanayakam, M., & Sastry, S. K. (1988). Kinetics of shrinkage of mushroom during blanching. Journal of Food Science, 53(5), 1406–1411.Kotwaliwale, N., Bakane, P., & Verma, A. (2007). Changes in textural and optical properties of oyster mushroom during hot air drying. Journal of Food Engineering, 78(4), 1207–1211.Leadley C. & Williams A. (2002). Power ultrasound—current and potential applications for food processing, Review No 32, Campden and Chorleywood Food Research Association.Lespinard, A. R., Goñi, S. M., Salgado, P. R., & Mascheroni, R. H. (2009). Experimental determination and modeling of size variation, heat transfer and quality indexes during mushroom blanching. Journal of Food Engineering, 92, 8–17.Lima, M., & Sastry, S. K. (1990). Influence of fluid rheological properties and particle location on ultrasound-assisted heat transfer between liquid and particles. Journal of Food Science, 55(4), 1112–1115.López, P., & Burgos, J. (1995). 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Journal of Food Science, 39, 1026–1028.Mohapatra, D., Bira, Z. M., Kerry, J. P., Frías, J. M., & Rodrigues, F. A. (2010). Postharvest hardness and color evolution of White button mushrooms (Agaricus bisporus). Journal of Food Science, 75(3), 146–152.Ohlsson, T. (1980). Temperature dependence of sensory quality changes during thermal processing. Journal of Food Science, 45(4), 836–847.Ortuño, C., Martínez-Pastor, M., Mulet, A., & Benedito, J. (2013). Application of high power ultrasound in the supercritical carbon dioxide inactivation of Saccharomyces cerevisiae. Food Research International, 51, 474–481.Peralta-Jimenez, L., & Cañizares-Macías, M. P. (2012). Ultrasound-assisted method for extraction of theobromine and caffeine from cacao seeds and chocolate products. Food and Bioprocess Technology, 6, 3522–3529.Rodríguez-López, J. N., Fenoll, N. G., Tudela, J., Devece, C., Sánchez-Hernández, D., De los Reyes, D., et al. (1999). Thermal inactivation of mushroom polyphenoloxidase employing 2450 MHz microwave radiation. Journal of Agricultural Food Chemistry, 47, 3028–3035.Sala, F., Burgos, J., Condon, S., Lopez, P., & Raso, J. (1995). Effect of heat and ultrasound on microorganisms and enzymes. In G. W. Gould (Ed.), New methods of food preservation (1st ed., pp. 176–204). Glasgow: Blackie Academic and professional.Sanjuán, N., Hernando, I., Lluch, M. A., & Mullet, A. (2005). Effects of low temperature blanching on texture, microstructure and rehydration capacity of carrots. Journal of the Science of Food and Agriculture, 85, 2071–2076.Santos, M. V., & Lespinard, A. R. (2011). Numerical simulation of mushrooms during freezing using the FEM and an enthalpy—Kirchhoff formulation. Heat and Mass Transfer, 47, 1671–1683.Sastry, S. K., Beelman, R. B., & Speroni, J. J. (1985). A three-dimensional finite element model for thermally induced changes in foods: application to degradation of agaritine in canned mushrooms. 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Simvastatin Prevents Dopaminergic Neurodegeneration in Experimental Parkinsonian Models: The Association with Anti-Inflammatory Responses

Background: In addition to their original applications to lowering cholesterol, statins display multiple neuroprotective effects. N-methyl-D-aspartate (NMDA) receptors interact closely with the dopaminergic system and are strongly implicated in therapeutic paradigms of Parkinson’s disease (PD). This study aims to investigate how simvastatin impacts on experimental parkinsonian models via regulating NMDA receptors. Methodology/Principal Findings: Regional changes in NMDA receptors in the rat brain and anxiolytic-like activity were examined after unilateral medial forebrain bundle lesion by 6-hydroxydopamine via a 3-week administration of simvastatin. NMDA receptor alterations in the post-mortem rat brain were detected by [3H]MK-801(Dizocilpine) binding autoradiography. 6-hydroxydopamine treated PC12 was applied to investigate the neuroprotection of simvastatin, the association with NMDA receptors, and the anti-inflammation. 6-hydroxydopamine induced anxiety and the downregulation of NMDA receptors in the hippocampus, CA1(Cornu Ammonis 1 Area), amygdala and caudate putamen was observed in 6- OHDA(6-hydroxydopamine) lesioned rats whereas simvastatin significantly ameliorated the anxiety-like activity and restored the expression of NMDA receptors in examined brain regions. Significant positive correlations were identified between anxiolytic-like activity and the restoration of expression of NMDA receptors in the hippocampus, amygdala and CA1 following simvastatin administration. Simvastatin exerted neuroprotection in 6-hydroxydopamine-lesioned rat brain and 6- hydroxydopamine treated PC12, partially by regulating NMDA receptors, MMP9 (matrix metalloproteinase-9), and TNF-a (tumour necrosis factor-alpha). Conclusions/Significance: Our results provide strong evidence that NMDA receptor modulation after simvastatin treatment could partially explain its anxiolytic-like activity and anti-inflammatory mechanisms in experimental parkinsonian models. These findings contribute to a better understanding of the critical roles of simvastatin in treating PD via NMDA receptors

Low diversity Cryptococcus neoformans variety grubii multilocus sequence types from Thailand are consistent with an ancestral African origin.

Published versio

Cryptococcus gattii Virulence Composite: Candidate Genes Revealed by Microarray Analysis of High and Less Virulent Vancouver Island Outbreak Strains

Human and animal cryptococcosis due to an unusual molecular type of Cryptococcus gattii (VGII) emerged recently on Vancouver Island, Canada. Unlike C. neoformans, C. gattii causes disease mainly in immunocompetent hosts, despite producing a similar suite of virulence determinants. To investigate a potential relationship between the regulation of expression of a virulence gene composite and virulence, we took advantage of two subtypes of VGII (a and b), one highly virulent (R265) and one less virulent (R272), that were identified from the Vancouver outbreak. By expression microarray analysis, 202 genes showed at least a 2-fold difference in expression with 108 being up- and 94 being down-regulated in strain R265 compared with strain R272. Specifically, expression levels of genes encoding putative virulence factors (e.g. LAC1, LAC2, CAS3 and MPK1) and genes encoding proteins involved in cell wall assembly, carbohydrate and lipid metabolism were increased in strain R265, whereas genes involved in the regulation of mitosis and ergosterol biosynthesis were suppressed. In vitro phenotypic studies and transcription analysis confirmed the microarray results. Gene disruption of LAC1 and MPK1 revealed defects in melanin synthesis and cell wall integrity, respectively, where CAS3 was not essential for capsule production. Moreover, MPK1 also controls melanin and capsule production and causes a severe attenuation of the virulence in a murine inhalational model. Overall, this study provides the basis for further genetic studies to characterize the differences in the virulence composite of strains with minor evolutionary divergences in gene expression in the primary pathogen C. gattii, that have led to a major invasive fungal infection outbreak