The Ped (preimplantation embryonic development) gene influences the rate of preimplantation embryonic development and subsequent embryonic survival. The protein product of the Ped gene, the Qa-2 protein, is a major histocompatibility complex (MHC) class Ib protein. There are two alleles of the Ped gene, fast (Qa-2 [+]) and slow (Qa-2 [-]). Qa-2 is encoded by four very similar MHC class Ib genes: Q6, Q7, Q8, and Q9. Recent research in our laboratory has shown that the Ped phenotype is potentially encoded by the Q7 and/or Q9 gene because the Q7 and Q9 genes, but not the Q6 or Q8 gene, are expressed during preimplantation mouse embryonic development. In this study we utilized microinjection of transgenes to assess the functional roles of both the Q7 and Q9 genes in control of the rate of preimplantation development. The Q7 gene, the Q9 gene, and a combination of the Q7 and Q9 genes were microinjected into Ped slow zygotes, and the Ped phenotype and cell surface expression of Qa-2 protein were assayed after a 72-h or 96-h incubation period. We found that the microinjected individual Q7 and Q9 genes increased the rate of preimplantation development. Simultaneous injection of the Q7 and Q9 genes did not have a synergistic effect on the Ped phenotype. Microinjection of the Q7 and/or Q9 genes resulted in protein expression in 10-25% of the microinjected embryos. These results show that both the Q7 and Q9 genes encode the mouse Ped phenotype.
Background: Chronic pain is frequently treated with opioid analgesics, but there is limited evidence for efficacy for chronic use of opioids and the drugs pose significant risks to patients' physical and mental health. Spinal cord stimulation delivered at a frequency of 10,000 Hertz (10 kHz SCS) is a minimally invasive therapy with demonstrated efficacy and safety in treating chronic pain that has also been associated with decreased opioid use. Objective: To evaluate opioid reduction and pain relief in real-world cohort. Study Design: Retrospective review. Setting: Single center. Patients and Methods: Consecutive patients who were implanted with 10 kHz SCS devices from December 1, 2015, to June 30, 2020 for the treatment of chronic pain in the trunk or lower limbs were included. Changes in opioid use following 10 kHz SCS treatment were extracted from electronic medical records, and patient-reported pain relief, improvement in function and sleep were extracted from manufacturer's database. Responder rate was defined as the proportion of patients with at least 50% pain relief. Anonymised results from descriptive analysis of the data are reported. Results: At last follow-up (median 21.4 months), mean daily opioid dose fell by 48.4 morphine milligram equivalents (MME), and fewer patients used opioids. Mean pain relief in these patients was 57% ± 4%, and responder rate was 68% at last recorded follow-up. Interestingly, pain relief (66%) and responder rate (86%) were higher in patients with 1 year or more. Finally, 50% of patients reported improved sleep, and 73% reported improvement in function at last recorded follow-up after treatment with 10 kHz SCS. Conclusion: These results support 10 kHz SCS as a safe and effective treatment of chronic pain in real-world patients with secondary benefits to opioid consumption and measures of patients' quality of life.
There are limited treatment options for patients with foot drop and associated lower back and/or leg pain. We present a case series of three patients who received permanent implantation of 10 kHz spinal cord stimulation (10 kHz SCS) devices. Following treatment, all patients reported sustained improvements in lower back and leg pain, foot mechanics and function which resulted in increased mobility and cessation of opioid use for pain management. Patients were followed up for approximately four years. Treatment with 10 kHz SCS may be a promising alternative to other interventional procedures commonly used for these patients.
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