Staging and stratifying cognitive dysfunction in multiple sclerosis

BACKGROUND: The sequence in which cognitive domains become impaired in multiple sclerosis (MS) is yet to be formally demonstrated. It is unclear whether processing speed dysfunction temporally precedes other cognitive impairments, such as memory and executive function. OBJECTIVE: Determine the order in which different cognitive domains become impaired in MS and validate these findings using clinical and vocational outcomes. METHODS: In a longitudinal sample of 1073 MS patients and 306 healthy controls, we measured performance on multiple, consensus-standard, neurocognitive tests. We used an event-based staging approach to model the sequence in which cognitive domains become impaired. Linear and logistic mixed-effects models were used to explore associations between stages of impairment, neurological disability, and employment status. RESULTS: Our model suggested that the order of impairments was as follows: processing speed, visual learning, verbal learning, working memory/attention, and executive function. Stage of cognitive impairment predicted greater neurological disability, β = 0.16, SE = 0.02, p < 0.001, and probability of unemployment, β = 1.14, SE = 0.001, p < 0.001. CONCLUSION: This is the first study to introduce a cognitive staging and stratification system for MS. Findings underscore the importance of using the Symbol Digit Modalities Test in routine screening for cognitive impairment and memory testing to assess patients later in disease evolution

Atom-specific forces and defect identification on surface-oxidized Cu(100) with combined 3D-AFM and STM measurements

Cataloged from PDF version of article.The influence of defects on the local structural, electronic, and chemical properties of a surface oxide on Cu(100) were investigated using atomic resolution three-dimensional force mapping combined with tunneling current measurements and ab initio density functional theory. Results reveal that the maximum attractive force between tip and sample occurs above the oxygen atoms; theory indicates that the tip, in this case, terminates in a Cu atom. Meanwhile, simultaneously acquired tunneling current images emphasize the positions of Cu atoms, thereby, providing species-selective contrast in the two complementary data channels. One immediate outcome is that defects due to the displacement of surface copper are exposed in the current maps, even though force maps only reflect a well-ordered oxygen sublattice. The exact nature of the defects is confirmed by the simulations, which also reveal that the arrangement of the oxygen atoms is not disrupted by the copper displacement. In addition, the experimental force maps uncover a position-dependent modulation of the attractive forces between the surface oxygen and the copper-terminated tips, which is found to reflect the surface's inhomogeneous chemical and structural environment. As a consequence, the demonstrated method has the potential to directly probe how defects affect surface chemical interactions. DOI: 10.1103/PhysRevB.87.15541

Capture and inception of bubbles near line vortices

Motivated by the need to predict vortex cavitation inception, a study has been conducted to investigate bubble capture by a concentrated line vortex of core size rcrc and circulation Γ0Γ0 under noncavitating and cavitating conditions. Direct numerical simulations that solve simultaneously for the two phase flow field, as well as a simpler one-way coupled point-particle-tracking model (PTM) were used to investigate the capture process. The capture times were compared to experimental observations. It was found that the point-particle-tracking model can successfully predict the capture of noncavitating small nuclei by a line vortex released far from the vortex axis. The nucleus grows very slowly during capture until the late stages of the process, where bubble/vortex interaction and bubble deformation become important. Consequently, PTM can be used to study the capture of cavitating nuclei by dividing the process into the noncavitating capture of the nucleus, and then the growth of the nucleus in the low-pressure core region. Bubble growth and deformation act to speed up the capture process.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87832/2/022105_1.pd

Effect of sirolimus on the regression of peritoneal sclerosis in an experimental rat model

Purpose Immunosuppressive and anti-inflammatory agents have recently become increasingly popular in the treatment of encapsulating peritoneal sclerosis (EPS). The aim of our study was to investigate the effects of sirolimus on EPS in a rat model. Methods We separated 32 non-uremic rats into four groups: 1 control group, 2 ml isotonic saline injected IP daily for 3 weeks; 2 chlorhexidine gluconate (CG) group, 2 ml 0,1 % CG and 15 % ethanol dissolved in saline injected IP daily for 3 weeks; 3 resting group, CG (weeks 0-3) plus peritoneal rest (weeks 3-6); 4 sirolimus group, CG (weeks 0-3), plus 0.2 ml (1 mg/ml) sirolimus (weeks 3-6). Pathological samples were examined by using hematoxylin eosin (HE) and Masson's trichrome stains. Peritoneal thickness, fibrosis, vascular changes, and inflammation were evaluated by light microscopy. Finally, tissue metalloproteinase (MMP)-2 levels were measured by enzyme-linked immunoassay. Results In the CG group, there was a significant increase in peritoneal thickness, inflammatory activity, and fibrosis score compared to the control group (p<0.05). We also observed a lower fibrosis score and less peritoneal thickening in the sirolimus group compared to the resting and CG groups (p<0.05). There was no difference in histopathologic findings, except for the inflammatory activity in the sirolimus group, compared to the control group. Although the CG group had higher tissue MMP-2 levels than the control group, the tissue MMP-2 levels were not significantly different from the other groups. Conclusions Sirolimus has a beneficial effect on peritoneal fibrosis induced by CG. This suggests that sirolimus may have therapeutic value in the management of EPS. © Springer Science+Business Media, B.V. 2011

Effect of Local Polyhexanide Application in Preventing Exit-Site Infection and Peritonitis: A Randomized Controlled Trial

Topical antibiotic and antiseptic agents have been documented to reduce exit-site infection (ESI) and peritonitis in PD. The aim of this randomized controlled study was to evaluate the efficacy of polyhexanide in the prevention of ESI and peritonitis. Patients were excluded if they had active infection, > 18 years of age, ESI and peritonitis within the previous 4 weeks, received PD for less than 3-months and history of allergy to either drug. All patients were followed up until catheter removal, death, switch to dialysis, transplantation or the end of the study. ESI, tunnel infection, peritonitis, catheter removal and microorganism cause of catheter-related infection were recorded prospectively during clinic follow-up. A total of 88 patients (41 povidone-iodine group; 47 polyhexanide group) were enrolled with a total follow-up duration of 480 and 555 patient-months for povidone-iodine and alternating group, respectively. There were no significant differences in the age, sex, BMI, time of PD, rate of DM, and S. aureus carriage state. A total of 8 ESI and 25 peritonitis episodes were detected during the study. ESI and peritonitis rates tended to be lower in polyhexanide group compared with the povidone-iodine group (0.06 episodes/patient-year vs. 0.12 episodes/patient-year; 0.26 episodes/patient-year vs. 0.32 episodes/patient-year, respectively), but were not significant statistically. Moreover, catheter removal was similar in both groups (0.04 / patient-year vs. 0.05 / patient-year). Polyhexanide is efficient and safe for the prevention of ESI and peritonitis and it may be used as an alternative procedure for the care of healthy exit sites. © 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therap

Mediterranean Fever

BackgroundCirculating levels of Pentraxin-3 (PTX3) have been shown to increase in several inflammatory conditions. However, there is no information about the levels of PTX3 in patients with familial Mediterranean fever (FMF). This study was designed to evaluate the serum PTX3 levels in patients with FMF during attack and free-attack periods.MethodsTwenty FMF patients in attack and free-attack period, and 20 age-, sex-, and body mass index-matched healthy controls were included in the study. Blood samples were obtained within the first 24 h of the attack period and between attacks, and levels of white blood cell, erythrocyte sedimentation rate, Fibrinogen, high sensitive CRP, and PTX3 were determined.ResultsPTX3 levels during the attack period were not significantly different from those in free-attack patients (4.9 4.6 ng/ml vs. 2.8 +/- 1.4 ng/ml, P > 0.05). However, both attack and free-attack patients had significantly higher PTX3 levels than healthy controls (4.9 +/- 4.6 ng/ml vs. 1.8 +/- 0.8 ng/ml, P < 0.001; 2.8 +/- 1.4 ng/ml vs. 1.8 +/- 0.8 ng/ml, P < 0.025, respectively).ConclusionsPTX3 levels were not markedly affected from FMF attacks, but high level of PTX3 in free-attack period of FMF patients shows ongoing subclinical inflammation. However, further studies are needed to determine its usefulness as a marker in clinical practice