Focal segmental glomerulosclerosis, Coats’-like retinopathy, sensorineural deafness and chromosome 4 duplication: a new association

We describe the novel association in a girl of nephrotic syndrome due to focal segmental glomerulosclerosis, bilateral sensorineural deafness, basal ganglia calcification, bilateral retinopathy similar to that seen in Coats’ disease, with de novo duplication of a subtelomeric region of chromosome 4q35. The chromosomal duplication was identified during investigation of a possible association with features of fascio-scapulo-humeral dystrophy (FSHD). This duplication has not previously been reported with FSGS and adds to the expanding number of genetic associations with steroid-resistant nephrotic syndrome

Influence of country and city images on students’ perception of host universities and their satisfaction with the assigned destination for their exchange programmes

ABSTRACT: This research focuses on the effect that country image, city image and university image has on students’ a priori satisfaction with the assigned destination for their international exchange programme (Bachelor and Master). In particular, this study establishes six hypotheses related to the causal relationships among the different typologies of image and their effects on students’ satisfaction with the assigned destination to study at least one semester in a host university. In order to contrast these hypotheses, a quantitative research was carried out in the Spanish city of Santander (Spain), by obtaining a sample of 245 international students who participated in an exchange programme at the University of Cantabria. The research findings are: (1) students’ satisfaction with the assigned destination is positively influenced by the university image; (2) the university image is positively influenced by the city image; and (3) the city image is positively influenced by the country image

Global Transcriptional Programs in Peripheral Nerve Endoneurium and DRG Are Resistant to the Onset of Type 1 Diabetic Neuropathy in Ins2Akita/+ Mice

While the morphological and electrophysiological changes underlying diabetic peripheral neuropathy (DPN) are relatively well described, the involved molecular mechanisms remain poorly understood. In this study, we investigated whether phenotypic changes associated with early DPN are correlated with transcriptional alterations in the neuronal (dorsal root ganglia [DRG]) or the glial (endoneurium) compartments of the peripheral nerve. We used Ins2Akita/+ mice to study transcriptional changes underlying the onset of DPN in type 1 diabetes mellitus (DM). Weight, blood glucose and motor nerve conduction velocity (MNCV) were measured in Ins2Akita/+ and control mice during the first three months of life in order to determine the onset of DPN. Based on this phenotypic characterization, we performed gene expression profiling using sciatic nerve endoneurium and DRG isolated from pre-symptomatic and early symptomatic Ins2Akita/+ mice and sex-matched littermate controls. Our phenotypic analysis of Ins2Akita/+ mice revealed that DPN, as measured by reduced MNCV, is detectable in affected animals already one week after the onset of hyperglycemia. Surprisingly, the onset of DPN was not associated with any major persistent changes in gene expression profiles in either sciatic nerve endoneurium or DRG. Our data thus demonstrated that the transcriptional programs in both endoneurial and neuronal compartments of the peripheral nerve are relatively resistant to the onset of hyperglycemia and hypoinsulinemia suggesting that either minor transcriptional alterations or changes on the proteomic level are responsible for the functional deficits associated with the onset of DPN in type 1 DM

Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole-Body Physiology

Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a “virtual population” from which “virtual individuals” can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the “virtual individuals” that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models

Use of non-invasive NIRS during a vascular occlusion test to assess dynamic tissue O<inf>2</inf> saturation response

Introduction: We assessed tissue O2 saturation (StO2) and total hemoglobin (HbT) changes during a vascular occlusion test (VOT) as markers of O2 consumption and cardiovascular reserve. Methods: Using the non-invasive InSpectra® near infrared spectrometer, we studied the effect of VOT to StO2 < 40% then release on thenar eminence StO2 and HbT in 15 normal volunteers (controls) and 10 trauma patients. We repeated the VOT four times in controls and twice in patients, with controls exercising during the last VOT, and correlated StO 2 with HbT changes by linear regression analysis. Results: StO 2 started to decrease 3-28 s post-occlusion (latency) in controls and then decreased in a linear fashion (-0.18 ± 0.04% O2/s, mean ± SD), while post-occlusion StO2 recovery was rapid (5.20 ± 1.19% O2/s). Exercise decreased latency (0-5 s) and increased desaturation rate (-0.18 and -0.69% O2/s, P < 0.005) without altering recovery. Trauma patients showed similar StO2 desaturation rates, but slower recovery (5.20 ± 1.19 vs. 2.88 ± 1.71%/s, P < 0.0001). Repeated VOT gave similar recovery results within study groups. The hyperemic response was variable in both groups and, if present, was associated with an increased HbT. HbT pre- and post-VOT were significantly different within each subject. Although HbT slope of recovery correlated significantly with StO2 recovery in trauma patients (rho 0.76), it was not in controls. Conclusions: One VOT defines StO2 deoxygenation and recovery. That StO2 and HbT recovery co-vary only in trauma patients suggests that pre-existing vasoconstriction was unmasked by the ischemic challenge consistent with increased sympathetic tone. © 2008 Springer-Verlag

Thresholded area over the curve of spectrometric tissue oxygen saturation as an indicator of volume resuscitability in porcine hemorrhagic shock

A rapid, reliable, and noninvasive functional measure of responsiveness to resuscitation in posttraumatic hemorrhagic shock could prove useful in guiding therapy, especially under circumstances such as the battlefield and civilian mass casualties. Tissue oxygen saturation (Sto2) is a promising c and idate for this application. We therefore explored the value of peripheral muscle Sto2 in predicting systemic responsiveness to colloid volume resuscitation in a porcine model of hemorrhagic shock. Fourteen isoflurane-anesthetized piglets were subjected to a st and ardized hemorrhage protocol that maintained mean arterial pressure (MAP) between 30 and 40 mm Hg. Asanguineous resuscitation with a volume of Hextend equal to the total volume bled was initiated when compensation was exhausted (MAP <30 mm Hg). We recorded continuous MAP and Sto2 values, and calculated the contiguous area over the Sto2 curve yet below a given threshold of Sto2 (TAOC) as a function of this threshold before the selected timepoint for timepoints up to 30 minutes before resuscitation. Hemorrhage resulted in significant fluctuations of MAP and high interindividual variability of disease dynamics and outcome: 4 nonsurvivors and 10 survivors at 2 hours postresuscitation. Sto2 measurements reflected hemodynamic conditions in most animals, with a pronounced drop preceding final decompensation in 7 of 14 animals. TAOC discriminated three of four nonresuscitable (nonsurvivor) animals from the survivors, with group differences reaching significance even for the earliest examined timepoint (30 minutes before resuscitation), depending on the choice of TAOC threshold. Sto2 may serve as a marker of decompensation, whereas TAOC, a physiologically motivated correlate of perfusion debt and cumulative hypoperfusion injury, may be a useful early indicator of responsiveness to volume resuscitation in hemorrhagic shock. © rofessor of Surgery and Critical Care, Director Applied Research, Innovative Medical and Information Technology Center, UPMC, F1265 Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213-2536; email: [email protected]