Physiological reviews最新文献

Ion channels play a central role in the regulation of nearly every cellular process. Dating back to the classic 1952 Hodgkin-Huxley model of the generation of the action potential, ion channels have always been thought of as independent agents. A myriad of recent experimental findings exploiting advances in electrophysiology, structural biology, and imaging techniques, however, have posed a serious challenge to this long-held axiom, as several classes of ion channels appear to open and close in a coordinated, cooperative manner. Ion channel cooperativity ranges from variable-sized oligomeric cooperative gating in voltage-gated, dihydropyridine-sensitive Ca_V1.2 and Ca_V1.3 channels to obligatory dimeric assembly and gating of voltage-gated Na_V1.5 channels. Potassium channels, transient receptor potential channels, hyperpolarization cyclic nucleotide-activated channels, ryanodine receptors (RyRs), and inositol trisphosphate receptors (IP₃Rs) have also been shown to gate cooperatively. The implications of cooperative gating of these ion channels range from fine-tuning excitation-contraction coupling in muscle cells to regulating cardiac function and vascular tone, to modulation of action potential and conduction velocity in neurons and cardiac cells, and to control of pacemaking activity in the heart. In this review, we discuss the mechanisms leading to cooperative gating of ion channels, their physiological consequences, and how alterations in cooperative gating of ion channels may induce a range of clinically significant pathologies.

Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological function of salivary glands, as well as how they are affected by disease and injury, will direct the development of therapy to repair and regenerate them. Significant recent advances, particularly in the OMICS field, increase our understanding of how salivary glands develop at the cellular, molecular, and genetic levels: the signaling pathways involved, the dynamics of progenitor cell lineages in development, homeostasis, and regeneration, and the role of the extracellular matrix microenvironment. These provide a template for cell and gene therapies as well as bioengineering approaches to repair or regenerate salivary function.

Objective: Treatment of degenerative lumbar diseases has been shown to be clinically effective with open transforaminal lumbar interbody fusion (O-TLIF) or minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). Despite this, a substantial proportion of patients do not meet minimal clinically important differences (MCIDs) in patient-reported outcomes (PROs). The objectives of this study were to compare the proportions of patients who did not meet MCIDs after O-TLIF and MIS-TLIF and to determine potential clinical factors associated with failure to achieve MCID.

Methods: The authors performed a retrospective analysis of consecutive patients who underwent O-TLIF or MIS-TLIF for lumbar degenerative disorders and had been prospectively enrolled in the Canadian Spine Outcomes and Research Network. The authors analyzed the Oswestry Disability Index (ODI) scores, physical and mental component summary scores of SF-12, numeric rating scale (NRS) scores for leg and back pain, and EQ-5D scores of the patients in each group who did not meet the MCID of ODI at 2 years postoperatively.

Results: In this study, 38.8% (137 of 353) of patients in the O-TLIF cohort and 41.8% (51 of 122) of patients in the MIS-TLIF cohort did not meet the MCID of ODI at 2 years postoperatively (p = 0.59). Demographic variables and baseline PROs were similar between groups. There were improvements across the PROs of both groups through 2 years, and there were no differences in any PROs between the O-TLIF and MIS-TLIF cohorts. Multivariable logistic regression analysis demonstrated that higher baseline leg pain score (p = 0.017) and a diagnosis of spondylolisthesis (p = 0.0053) or degenerative disc disease (p = 0.022) were associated with achieving the MCID at 2 years after O-TLIF, whereas higher baseline leg pain score was associated with reaching the MCID after MIS-TLIF (p = 0.038).

Conclusions: Similar proportions of patients failed to reach the MCID of ODI at 2 years after O-TLIF or MIS-TLIF. Higher baseline leg pain score was predictive of achieving the MCID in both cohorts, whereas a diagnosis of spondylolisthesis or degenerative disc disease was predictive of reaching the MCID after O-TLIF. These data provide novel insights for patient counseling and suggest that either MIS-TLIF or O-TLIF does not overcome specific patient factors to mitigate clinical success or failure in terms of the intermediate-term PROs associated with 1- to 2-level lumbar fusion surgical procedures for degenerative pathologies.