R7BP Modulates Opiate Analgesia and Tolerance but not Withdrawal

The adaptor protein R7 family binding protein (R7BP) modulates G protein coupled receptor (GPCR) signaling and desensitization by controlling the function of regulator of G protein signaling (RGS) proteins. R7BP is expressed throughout the brain and appears to modulate the membrane localization and stability of three proteins that belong to R7 RGS family: RGS6, RGS7, and RGS9-2. RGS9-2 is a potent negative modulator of opiate and psychostimulant addiction and promotes the development of analgesic tolerance to morphine, whereas the role of RGS6 and RGS7 in addiction remains unknown. Recent studies revealed that functional deletion of R7BP reduces R7 protein activity by preventing their anchoring to the cell membrane and enhances GPCR responsiveness in the basal ganglia. Here, we take advantage of R7BP knockout mice in order to examine the way interventions in R7 proteins function throughout the brain affect opiate actions. Our results suggest that R7BP is a negative modulator of the analgesic and locomotor activating actions of morphine. We also report that R7BP contributes to the development of morphine tolerance. Finally, our data suggest that although prevention of R7BP actions enhances the analgesic responses to morphine, it does not affect the severity of somatic withdrawal signs. Our data suggest that interventions in R7BP actions enhance the analgesic effect of morphine and prevent tolerance, without affecting withdrawal, pointing to R7BP complexes as potential new targets for analgesic drugs.     

Auditory Nerve Fiber Responses to Combined Acoustic and Electric Stimulation

Persons with a prosthesis implanted in a cochlea with residual acoustic sensitivity can, in some cases, achieve better speech perception with “hybrid” stimulation than with either acoustic or electric stimulation presented alone. Such improvements may involve “across auditory-nerve fiber” processes within central nuclei of the auditory system and within-fiber interactions at the level of the auditory nerve. Our study explored acoustic–electric interactions within feline auditory nerve fibers (ANFs) so as to address two goals. First, we sought to better understand recent results that showed non-monotonic recovery of the electrically evoked compound action potential (ECAP) following acoustic masking (Nourski et al. 2007, Hear. Res. 232:87–103). We hypothesized that post-masking changes in ANF temporal properties and responsiveness (spike rate) accounted for the ECAP results. We also sought to describe, more broadly, the changes in ANF responses that result from prior acoustic stimulation. Five response properties—spike rate, latency, jitter, spike amplitude, and spontaneous activity—were examined. Post-masking reductions in spike rate, within-fiber jitter and across-fiber variance in latency were found, with the changes in temporal response properties limited to ANFs with high spontaneous rates. Thus, our results suggest how non-monotonic ECAP recovery occurs for ears with spontaneous activity, but cannot account for that pattern of recovery when there is no spontaneous activity, including the results from the presumably deafened ears used in the Nourski et al. (2007) study. Finally, during simultaneous (electric+acoustic) stimulation, the degree of electrically driven spike activity had a strong influence on spike rate, but did not affect spike jitter, which apparently was determined by the acoustic noise stimulus or spontaneous activity.     

Weight affects survival of primary total knee arthroplasty: study based on the Danish Knee Arthroplasty Register with 67,810 patients and a median follow-up time of 5 years

Background and purpose — Obesity is a rising issue worldwide and growing evidence supports poor outcome amongst obese patients following total knee arthroplasty (TKA). Using nationwide registries we investigated the association between bodyweight and risk of revision of primary TKA.

Patients and methods — All primary TKA performed during 1997–2015, weight at time of primary TKA and subsequent TKA revisions were identified in the Danish Knee Arthroplasty Register (DKR). Data on comorbidities and a priori selected confounding variables were collected from nationwide registries. The association between weight and 1st time TKA revision was calculated as both crude and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) using Cox regression.

Results — Of 67,810 identified primary TKAs, 4.8% were revised within a median follow-up time of 5.4 years. No association between weight and risk of any revision in patients aged 18–54 and 55–70 years was found. Increased risk of any revision was seen in patients >70 years, 80–89?kg (aHR =1.5, CI 1.2–1.8), 90–99?kg (aHR =1.7, CI 1.3–2.1) and patients >99?kg (aHR =1.6, CI 1.3–2.1), as well as those weighing 45–60?kg (aHR =1.4, CI 1.1–1.9) compared with same aged patients weighing 70–79?kg.

Interpretation — We found a complex association between weight and knee arthroplasty survival. There was an increased risk of any revision in patients older than 70 years of age weighing <60?kg and >80?kg. Patients aged 18–55 years weighing 60–69?kg had a lower risk of revision compared with all other weight groups, whereas weight was not found to affect risk of any revision in patients aged 55–70 years.     

Thermopuncture for the Diagnosis,Monitoring, and Treatment of Patients with Type 2 Diabetes

Background

Type 2 diabetes (T2D) is a socially significant disease that affects millions of patients. There were an estimated 366 million people with this disease in 2011, and, according to the forecast, approximately 552 million will be affected by this disease in 2030. It is well known that the primary diagnosis and treatment of a patient with this disease are quite expensive. What should be done to make it possible for a patient to monitor his own state and provide treatment in his own home using telemedicine?To solve this problem, an alternative concept for the diagnosis, monitoring, and treatment at the basis of traditional Chinese medicine combined with mathematical methods of data processing has been used.

Permeability of hyperosmotic agent in normal and atherosclerotic vascular tissues

Noninvasive cardiovascular imaging could lead to the early detection and timely treatment of complex atherosclerotic lesions responsible for major cardiovascular events. Recent investigations have suggested that optical coherence tomography (OCT) is an ideal diagnostic tool due to the high resolution this technology achieves in discriminating the different features of atherosclerotic lesions based on structural imaging. We explore the capability of OCT for functional imaging of normal and atherosclerotic aortic tissues based on time- and depth-resolved quantification of the permeability of biomolecules through these tissues. The permeability coefficient of 20% aqueous solution of glucose was found to be (6.80+/-0.18)x10(-6) cms in normal aortas and (2.69+/-0.42)x10(-5) cms in aortas with atherosclerotic disease. The results suggest that this new OCT functional imaging method-the assessment of the permeability coefficients of various physiologically neutral biomolecules in vascular tissues-could assist in early diagnosing and detecting the different components of atherosclerotic lesions.     

Reproduction of trematodes in the molluscan host: an ultrastructural study of the germinal mass and brood cavity in daughter rediae of Tristriata anatis Belopolskaia, 1953 (Digenea: Notocotylidae)

Parasitology Research - This study describes the fine structure of the germinal mass in daughter rediae of Tristriata anatis. The germinal mass consists of undifferentiated cells, germinal cells...