Collateralization of descending spinal pathways from red nucleus and other brainstem cell groups in rat, cat and monkey

The somatotopically organized rubrospinal pathway is the major component of the laterally descending brainstem pathways, and is especially involved in steering of fractionated movements of the distal parts of the limbs. Electrophysiological studies in cat showed that this fiber system, in contrast to the medially descending pathways, has a limited degree of collateralization in the spinal cord (Abzug et al., 1973 and 1974; Shinoda et al., 1977). The red nucleus projects also to the contralateral cerebellum (Brodal and Gogstad, 1954; Courville and Brodal, 1966). The collateralization of the rubrospinal neurons to the contralateral cerebellar interpositus nucleus is relatively high as indicated by anatomical and electrophysiological findings (Anderson, 1971; Brodal and Gogstad, 1954). Thus, the findings in these studies suggested that almost all rubrocerebellar fibers are collaterals from rubrospinal neurons. In view of the above data it appears that the rubrospinal pathway represents a focussed system, which distributes its fibers to specific groups of spinal segments. On the other hand, the rubrocerebellar pathway probably represents a direct, tightly coupled return projection to the interpositus nucleus, which is the main source of afferents to the rubrospinal neurons (Courville, 1966b; Dekker, 1981; Flumerfelt et al., 1973; King et al., 1973; Tsukahara et al., 1967). In the present anatomical study an attempt has been made to demonstrate anatomically the existence of collaterals in the rubrospinal pathway and to compare quantitatively the degree of this collateralization in rat, cat and monkey. This was done with the aid of the multiple retrograde fluorescent tracer technique. This technique will be described in chapter II. In this anatomical study one fluorescent tracer was injected in the cervical grey and another in more caudal segments of the cord. In these experiments the distribution of sin3le and double labeled neurons in red nucleus was studied. The descending pathways from the ventrolateral pontine tegmentum and from the raphe magnus, including the adjoining ventral reticular formation, also descend in the dorsolateral funiculus in rat, cat and monkey and also terminate in the dorsal grey (Basbaum and Fields, 1978, 1979; Holstege et al., 1979; Kuypers and Maisky, 1977; R.F. Martinet al., 1978; G.F. Martinet al., 1979 and 1981a; Tohyama et al., 1979a+b). Therefore, in these retrograde fluorescent double labeling studies the degree of the collateralization ~n these descending tracts was compared to that of the rubrospinal pathway ~n each of three mammalian species (i.e. rat, cat and monkey). In addition, in cat an attempt was made to determine the location of the rubro-olivary neurons in relation to the rubrospinal ones and to establish whether the rubro-olivary neurons give collaterals to the spinal cord. These studies will be presented in Chapter III and IV. In these studies attention was also paid to the rubrocerebellar connections. Specifically an attempt has been made to determine whether these connections are established by collaterals of rubrospinal neurons. These findings will be presented ~n Chapter V. Electron microscopic studies in rat, combining the anterograde and retrograde intra-axonal transport techniques, showed that many rubrospinal neurons receive afferents from the cerebellar interpositus nucleus (Dekker, 1981). Some of the fluorescent tracers used in the present study can be employed both retrogradely to demonstrate parent cell bodies as well as anterogradely to demonstrate the fiber terminals. Using the fluorescent tracers in this fashion it could be demonstrated in light microsc0py that the cerebellar interposito-rubral fibers establish contact with rubrospinal neurons. These data are also presented ~n Chapter V

Development of the stria vascularis and potassium regulation in the human fetal cochlea : insights into hereditary sensorineural hearing loss

Sensorineural hearing loss (SNHL) is one of the most common congenital disorders in humans, afflicting one in every thousand newborns. The majority is of heritable origin and can be divided in syndromic and nonsyndromic forms. Knowledge of the expression profile of affected genes in the human fetal cochlea is limited, and as many of the gene mutations causing SNHL likely affect the stria vascularis or cochlear potassium homeostasis (both essential to hearing), a better insight into the embryological development of this organ is needed to understand SNHL etiologies. We present an investigation on the development of the stria vascularis in the human fetal cochlea between 9 and 18 weeks of gestation (W9–W18) and show the cochlear expression dynamics of key potassium‐regulating proteins. At W12, MITF+/SOX10+/KIT+ neural‐crest‐derived melanocytes migrated into the cochlea and penetrated the basement membrane of the lateral wall epithelium, developing into the intermediate cells of the stria vascularis. These melanocytes tightly integrated with Na(+)/K(+)‐ATPase‐positive marginal cells, which started to express KCNQ1 in their apical membrane at W16. At W18, KCNJ10 and gap junction proteins GJB2/CX26 and GJB6/CX30 were expressed in the cells in the outer sulcus, but not in the spiral ligament. Finally, we investigated GJA1/CX43 and GJE1/CX23 expression, and suggest that GJE1 presents a potential new SNHL associated locus. Our study helps to better understand human cochlear development, provides more insight into multiple forms of hereditary SNHL, and suggests that human hearing does not commence before the third trimester of pregnancy. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1219–1240, 201

Diagnostic performance of the ACR/EULAR 2010 criteria for rheumatoid arthritis and two diagnostic algorithms in an early arthritis clinic (REACH)

Introduction: An ACR/EULAR task force released new criteria to classify rheumatoid arthritis at an early stage. This study evaluates the diagnostic performance of these criteria and algorithms by van der Helm and Visser in REACH. Methods: Patients with symptoms ≤12 months from REACH were used. Algorithms were tested on discrimination, calibration and diagnostic accuracy of proposed cut-points. Two patient sets were defi ned to test robustness; undifferentiated arthritis (UA) (n=231) and all patients including those without synovitis (n=513). The outcomes evaluated were methotrexate use and persistent disease at 12 months. Results: In UA patients all algorithms had good areas under the curve 0.79, 95% CI 0.73 to 0.83 for the ACR/EULAR criteria, 0.80, 95% CI 0.74 to 0.87 for van der Helm and 0.83, 95% CI 0.77 to 0.88 for Visser. All calibrated well. Sensitivity and specifi city were 0.74 and 0.66 for the ACR/EULAR criteria, 0.1 and 1.0 for van der Helm and 0.59 and 0.93 for Visser. Similar results were found in all patients indicating robustness. Conclusion: The ACR/EULAR 2010 criteria showed good diagnostic properties in an early arthritis cohort refl ecting daily practice, as did the van der Helm and Visser algorithms. All were robust. To promote uniformity and comparability the ACR/EULAR 2010 criteria should be used in future diagnostic studies. Copyright Article author (or their employer) 2011

Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis

BACKGROUND: Treatment with glucocorticoids is associated with bone loss starting soon after therapy is initiated and an increased risk of fracture. METHODS: We performed a randomized, double-placebo, double-blind clinical trial of 18 months' duration among patients with a rheumatic disease who were starting glucocorticoids at a daily dose that was equivalent to at least 7.5 mg of prednisone. A total of 201 patients were assigned to receive either alendronate (10 mg) and a placebo capsule of alfacalcidol daily or alfacalcidol (1 mu g) and a placebo tablet of alendronate daily. The primary outcome was the change in bone mineral density of the lumbar spine in 18 months; the secondary outcome was the incidence of morphometric vertebral deformities. RESULTS: A total of 100 patients received alendronate, and 101 received alfacalcidol; 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1 percent in the alendronate group (95 percent confidence interval, 1.1 to 3.1 percent) and decreased by 1.9 percent in the alfacalcidol group (95 percent confidence interval, -3.1 to -0.7 percent). At 18 months, the mean difference of change in bone mineral density between the two groups was 4.0 percent (95 percent confidence interval, 2.4 to 5.5 percent). Three patients in the alendronate group had a new vertebral deformity, as compared with eight patients in the alfacalcidol group (of whom three had symptomatic vertebral fractures) (hazard ratio, 0.4; 95 percent confidence interval, 0.1 to 1.4). CONCLUSIONS: During this 18-month trial in patients with rheumatic diseases, alendronate was more effective in the prevention of glucocorticoid-induced bone loss than was alfacalcidol

Cognitive radio network in vehicular ad hoc network (VANET): a survey

Cognitive radio network and vehicular ad hoc network (VANET) are recent emerging concepts in wireless networking. Cognitive radio network obtains knowledge of its operational geographical environment to manage sharing of spectrum between primary and secondary users, while VANET shares emergency safety messages among vehicles to ensure safety of users on the road. Cognitive radio network is employed in VANET to ensure the efficient use of spectrum, as well as to support VANET’s deployment. Random increase and decrease of spectrum users, unpredictable nature of VANET, high mobility, varying interference, security, packet scheduling, and priority assignment are the challenges encountered in a typical cognitive VANET environment. This paper provides survey and critical analysis on different challenges of cognitive radio VANET, with discussion on the open issues, challenges, and performance metrics for different cognitive radio VANET applications

Role of nurses in medication management at the end of life: a qualitative interview study

BACKGROUND: Patients in the last phase of their lives often use many medications. Physicians tend to lack awareness that reviewing the useful

Diabetic cardiomyopathy in Zucker diabetic fatty rats: the forgotten right ventricle

<p>Abstract</p> <p>Background</p> <p>In patients with myocardial infarction or heart failure, right ventricular (RV) dysfunction is associated with death, shock and arrhythmias. In patients with type 2 diabetes mellitus, structural and functional alterations of the left ventricle (LV) are highly prevalent, however, little is known about the impact of diabetes on RV characteristics. The purpose of the present study was to investigate whether LV changes are paralleled by RV alterations in a rat model of diabetes.</p> <p>Methods</p> <p>Zucker diabetic fatty (ZDF) and control (ZL) rats underwent echocardiography and positron emission tomography (PET) scanning using [¹⁸F]-2-fluoro-2-deoxy-D-glucose under hyperinsulinaemic euglycaemic clamp conditions. Glucose, insulin, triglycerides and fatty acids were assessed from trunk blood. Another group of rats received an insulin or saline injection to study RV insulin signaling.</p> <p>Results</p> <p>ZDF rats developed hyperglycaemia, hyperinsulinaemia and dyslipidaemia (all p < 0.05). Echocardiography revealed depressed LV fractional shortening and tricuspid annular plane systolic excursion (TAPSE) in ZDF vs. ZL rats (both p < 0.05). A decrease in LV and RV insulin-mediated glucose utilisation was found in ZDF vs. ZL rats (both p < 0.05). LV associated with RV with respect to systolic function (r = 0.86, p < 0.05) and glucose utilisation (r = 0.74, p < 0.05). TAPSE associated with RV MRglu (r = 0.92, p < 0.05) and <it>M</it>-value (r = 0.91, p < 0.0001) and RV MRglu associated with <it>M</it>-value (r = 0.77, p < 0.05). Finally, reduced RV insulin-stimulated phosphorylation of Akt was found in ZDF vs. ZL (p < 0.05).</p> <p>Conclusions</p> <p>LV changes were paralleled by RV alterations in insulin-stimulated glucose utilisation and RV systolic function in a rat model of diabetes, which may be attributed to ventricular interdependence as well as to the uniform effect of diabetes. Since diabetic patients are prone to develop diabetic cardiomyopathy and myocardial ischaemia, it might be suggested that RV dysfunction plays a central role in cardiac abnormalities in this population.</p

Altered myocardial substrate metabolism is associated with myocardial dysfunction in early diabetic cardiomyopathy in rats: studies using positron emission tomography

0.05). CONCLUSION: Using PET and echocardiography, we found increases in myocardial FA oxidation with a concomitant decrease of insulin-mediated myocardial glucose utilisation in early DCM. In addition, the latter was associated with impaired myocardial function. These in vivo data expand previous in vitro findings showing that early alterations in myocardial substrate metabolism contribute to myocardial dysfunctio

Multimodal imaging of hair follicle bulge-derived stem cells in a mouse model of traumatic brain injury

Traumatic brain injury (TBI) is a devastating event for which current therapies are limited. Stem cell transplantation may lead to recovery of function via different mechanisms, such as cell replacement through differentiation, stimulation of angiogenesis and support to the microenvironment. Adult hair follicle bulge-derived stem cells (HFBSCs) possess neuronal differentiation capacity, are easy to harvest and are relatively immune-privileged, which makes them potential candidates for autologous stem cell-based therapy. In this study, we apply in vivo multimodal, optical and magnetic resonance imaging techniques to investigate the behavior of mouse HFBSCs in a mouse model of TBI. HFBSCs expressed Luc2 and copGFP and were examined for their differentiation capacity in vitro. Subsequently, transduced HFBSCs, preloaded with ferumoxytol, were transplanted next to the TBI lesion (cortical region) in nude mice, 2 days after injury. Brains were fixed for immunohistochemistry 58 days after transplantation. Luc2- and copGFP-expressing, ferumoxytol-loaded HFBSCs showed adequate neuronal differentiation potential in vitro. Bioluminescence of the lesioned brain revealed survival of HFBSCs and magnetic resonance imaging identified their localization in the area of transplantation. Immunohistochemistry showed that transplanted cells stained for nestin and neurofilament protein (NF-Pan). Cells also expressed laminin and fibronectin but extracellular matrix masses were not detected. After 58 days, ferumoxytol could be detected in HFBSCs in brain tissue sections. These results show that HFBSCs are able to survive after brain transplantation and suggest that ce