Science and Technology Applications (United States)

Abstract Loss of GABAergic and glycinergic inhibitory efficacy in the spinal dorsal horn is associated with neuropathic pain and opioid-induced hyperalgesia in rodent models. Downregulation of the KCC2 chloride extrusion transporter is a key mechanism underlying this decreased inhibitory efficacy, but to-date there is no evidence supporting or opposing this hypothesis in humans. Here we demonstrate that KCC2 expression is decreased in superficial dorsal horn neurons of organ donors who died with a documented history of pain, or of long-term opioid use. We show profoundly decreased KCC2 dorsal horn membrane expression in a primary cohort associated with either chronic pain or opioid use, and in a replication cohort of mixed chronic pain and opioid use history. These results show that decreased dorsal horn inhibitory efficacy likely promotes chronic pain in humans and support the development of therapeutics augmenting KCC2 function as a treatment for chronic pain and opioid use disorders.

O presente artigo pretende discutir a relação entre Tempo e Direito, especialmente no que tange ao tempo processual. A discussão, centra-se na necessária (re)adequação do tempo no/do processo ao tempo social, tornando possível a tutela efetiva dos direitos albergados constitucionalmente. Para tal, crê-se necessária a re-inserção do processo – da jurisdição – no mundo-da-vida, eminentemente histórico e temporal, o que se dará por meio da hermenêutica filosófica.

The approach taken was to analyze the results in a manner consistent with application by design engineers to new and existing applications, while providing some insight into the processes that are occurring. This paper deals with predicting the initiation of cavitation, cavitation impacts on the contraction coefficient (Cc), as well as noncavitation impacts on discharge coefficient (Cd) from L/D of five sharp-edge orifices over a turning angle range between 60 deg and 120 deg. The results show that in the cavitation regime, Cc is controlled by the cavitation parameter (Kcav), where the data follow the 1∕2 power with Kcav, and inception of cavitation occurs at a Kcav of 1.8. In the noncavitation regime for conditions where the cross velocity is 0 the data are consistent with the first order equation relating head loss (HL) to the dynamic pressure where KL is constant and is consistent with in-line orifices. Cross flow has a significant impact on loss coefficient and depends on both the turning angle and manifold inlet to orifice exit velocity ratio.

Prompt establishment