Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain

Gabapentin is a first-line therapy for neuropathic pain but its mechanisms and sites of action remain uncertain. We investigated gabapentin-induced modulation of neuropathic pain following spinal nerve ligation (SNL) in rats. Intravenous or intrathecal gabapentin reversed evoked mechanical hypersensitivity, produced conditioned place preference (CPP) and dopamine release in the nucleus accumbens (NAc) selectively in SNL rats. Spinal gabapentin also significantly inhibited dorsal horn wide dynamic range (WDR) neuronal responses to a range of evoked stimuli in SNL rats. In contrast, gabapentin microinjected bilaterally into the rostral anterior cingulate cortex (rACC), produced CPP and elicited NAc dopamine release selectively in SNL rats but did not reverse tactile allodynia and had marginal effects on WDR neuronal activity. Moreover, blockade of endogenous opioid signaling in the rACC prevented intravenous gabapentin-induced CPP and NAc dopamine release but failed to block its inhibition of tactile allodynia. Gabapentin therefore can potentially act to produce its pain relieving effects by (a) inhibition of injury-induced spinal neuronal excitability, evoked hypersensitivity and ongoing pain and (b) selective supraspinal modulation of affective qualities of pain, without alteration of reflexive behaviors. Consistent with previous findings of pain relief from non-opioid analgesics, gabapentin requires engagement of rACC endogenous opioid circuits and downstream activation of mesolimbic reward circuits reflected in learned pain motivated behaviors. These findings support the partial separation of sensory and affective dimensions of pain in this experimental model and suggest that modulation of affective-motivational qualities of pain may be the preferential mechanism of gabapentin’s analgesic effects in patients

Analysing the Outcomes of the Forestry Sector on the Sustainable Development Goals for Rural Communities: A Case Study of Cabrero, Chile

The forestry sector will play a key role in the achievement of the 2030 Agenda for Sustainable Development. The forestry sector is a pillar of many countries’ economies, including Chile. Despite the many economic benefits of the sector for the country, its contribution to the achievement of the Sustainable Development Goals (SDGs) is not clear, especially for rural communities that co-exist with the sector. This study therefore aimed to identify the impacts of the sector on the sustainable development of rural communities in a Chilean commune, Cabrero, and link these impacts to the SDGs. Based on a mixed-method approach that considers key stakeholders perspectives, the paper finds that the forestry sector has multiple and complex impacts on sustainable development, with both positive and negatives outcomes for rural communities, generating synergies and trade-offs with all of the 17 SDGs. It concludes that while companies play a key role in delivering the 2030 Agenda, the achievement of the SDGs will require collaboration amongst people, government and the private sector to understand and support the delivery of a forestry sector that contributes to the sustainable development of communities in Cabrero and, more generally, in Chile

Current findings for recurring mutations in acute myeloid leukemia

The development of acute myeloid leukemia (AML) is a multistep process that requires at least two genetic abnormalities for the development of the disease. The identification of genetic mutations in AML has greatly advanced our understanding of leukemogenesis. Recently, the use of novel technologies, such as massively parallel DNA sequencing or high-resolution single-nucleotide polymorphism arrays, has allowed the identification of several novel recurrent gene mutations in AML. The aim of this review is to summarize the current findings for the identification of these gene mutations (Dnmt, TET2, IDH1/2, NPM1, ASXL1, etc.), most of which are frequently found in cytogenetically normal AML. The cooperative interactions of these molecular aberrations and their interactions with class I/II mutations are presented. The prognostic and predictive significances of these aberrations are also reviewed

Políticas de racionamiento a través de listas de prioridad

En este trabajo se estudia el racionamiento de un lote de pedido único entre múltiples clases de clientes con demanda estocástica y nivel de servicio diferenciado a través de listas de prioridad. Se propone un modelo para minimizar el lote de pedido único según una política de lista Random, i.e., cuando no existe un criterio preestablecido para definir el orden en que se satisfacerá la demanda de las diferentes clases. Para un caso especial encontramos que la política de lista Random tiene un mejor desempeño que la política de lista Responsive, la cual prioriza a aquellas clases con menor nivel de demanda.Sociedad Argentina de Informática e Investigación Operativa (SADIO

Políticas de racionamiento a través de listas de prioridad

En este trabajo se estudia el racionamiento de un lote de pedido único entre múltiples clases de clientes con demanda estocástica y nivel de servicio diferenciado a través de listas de prioridad. Se propone un modelo para minimizar el lote de pedido único según una política de lista Random, i.e., cuando no existe un criterio preestablecido para definir el orden en que se satisfacerá la demanda de las diferentes clases. Para un caso especial encontramos que la política de lista Random tiene un mejor desempeño que la política de lista Responsive, la cual prioriza a aquellas clases con menor nivel de demanda.Sociedad Argentina de Informática e Investigación Operativa (SADIO