Employment among Patients with Multiple Sclerosis-A Population Study

Objective

To investigate demographic and clinical factors associated with employment in MS.

Methods

The study included 213 (89.9%) of all MS patients in Sogn and Fjordane County, Western Norway at December 31^st 2010. The patients underwent clinical evaluation, structured interviews and completed self-reported questionnaires. Demographic and clinical factors were compared between patients being employed versus patients being unemployed and according to disease course of MS. Logistic regression analysis was used to identify factors independently associated with current employment.

Results

After a mean disease duration of almost 19 years, 45% of the population was currently full-time or part- time employed. Patients with relapsing –remitting MS (RRMS) had higher employment rate than patients with secondary (SPMS) and primary progressive (PPMS). Higher educated MS patients with lower age at onset, shorter disease duration, less severe disability and less fatigue were most likely to be employed.

Conclusions

Nearly half of all MS patients were still employed after almost two decades of having MS. Lower age at onset, shorter disease duration, higher education, less fatigue and less disability were independently associated with current employment. These key clinical and demographic factors are important to understand the reasons to work ability in MS. The findings highlight the need for environmental adjustments at the workplace to accommodate individual ’s needs in order to improve working ability among MS patients.     

Cytokinin Profiles in the Conifer Tree <Emphasis Type="Italic">Abies nordmanniana</Emphasis>: Whole-Plant Relations in Year-Round Perspective

Conifer trees are routinely manipulated hormonally to increase flowering, branching, or adjust crown shape for production purposes. This survey of internal cytokinin levels provides a background for such treatments in Abies nordmanniana, a tree of great economic interest. Reference points in the crown and root system were sampled destructively in 4- and 6-year-old trees and analyzed for a range of cytokinins by LC-MS/MS. No seasonal patterns were detected in the root samples, and a major portion of cytokinin was in conjugated forms. Dramatic and consistent seasonal changes occurred in the crown, at levels 17–65 times higher than in the root. Predominant among crown cytokinins was ZR, except in the needles where IPR was also prominent. Within the crown, cytokinin profiles in different organs differed consistently. The leader bud showed a pronounced mid-June minimum, and a maximum later in summer. Subapical buds showed the same June minimum but peaked in mid autumn at a much lower level. Maxima in these buds were preceded by peaks in the subapical stem. Parallel patterns were observed in homologous tissues on branches.This pattern is consistent with two surges beginning in the uppermost stem tissues leading to subsequent accumulation or stimulated production within the buds. Strong differential hormonal profiles between adjacent buds with different fates agree with recent evidence of localized cytokinin production. The data suggest a reduced role of root-derived cytokinins in crown development. Practical cytokinin treatments for crown-shape regulation require close attention to dosage as well as precise timing and positioning.     

The role of changing pH on olfactory success of predator–prey interactions in green shore crabs,Carcinus maenas

Aquatic Ecology - Arguably climate change is one of the biggest challenges faced by many organisms. One of the more significant of these is the decreasing pH level of the ocean, a consequence of...     

Does nociceptin play a role in pain disorders in man?

Nociceptin-immunoreactive cellbodies were detected in the human trigeminal ganglion, while no such fibers were identified in the temporal artery or in dermal tissue from the neck region. In four healthy subjects receiving nociceptin into the temporal muscle in an open labeled design no pain was detected. In 10 healthy subjects who received 200pmol of nociceptin into tender non-dominant trapezius muscles in a placebo-controlled, randomized, balanced, and double-blinded design local tenderness increased (P=0.025) while no pain was noted. Thus, the action of nociceptin should be searched for in the trigeminal ganglion and/or in the central nervous system (CNS).     

CTLs contain and use intracellular stores of FasL distinct from cytolytic granules

CTL lyse target cells through the release of cytolytic granule contents and cell surface expression of Fas ligand (FasL). Current models suggest that FasL is stored in cytolytic granules and that FasL cell surface expression would be subject to the same controls as degranulation. We demonstrate that murine CTLs undergo two waves of FasL cell surface expression after stimulation. The first wave is from a pre-existing pool of FasL, and the second wave requires new protein synthesis. Signaling for FasL expression appears to be finely tuned as a weak signal preferentially induced surface translocation of the stored FasL, whereas a strong signal preferentially triggered the expression of de novo synthesized FasL. The early FasL is differentially regulated from degranulation, as there were multiple circumstances whereby rapid FasL cell surface expression and FasL-dependent killing occurred in the absence of detectable degranulation. Furthermore, we found through confocal microscopy that stored FasL resides in vesicles distinct from cytolytic granules. Our data clearly show that CTL degranulation and FasL lytic mechanisms are fully independent with respect to stored component localization and regulation.     

Direct action of endocrine disrupting chemicals on human sperm

Synthetic endocrine disrupting chemicals (EDCs), omnipresent in food, household, and personal care products, have been implicated in adverse trends in human reproduction, including infertility and increasing demand for assisted reproduction. Here, we study the action of 96 ubiquitous EDCs on human sperm. We show that structurally diverse EDCs activate the sperm‐specific CatSper channel and, thereby, evoke an intracellular Ca²⁺ increase, a motility response, and acrosomal exocytosis. Moreover, EDCs desensitize sperm for physiological CatSper ligands and cooperate in low‐dose mixtures to elevate Ca²⁺ levels in sperm. We conclude that EDCs interfere with various sperm functions and, thereby, might impair human fertilization.     

MicroRNA-196a and -196b as Potential Biomarkers for the Early Detection of Familial Pancreatic Cancer

Screening programs are recommended for individuals at risk (IAR) from families with familial pancreatic cancer (FPC). However, reliable imaging methods or biomarkers for early diagnosis of pancreatic ductal adenocarcinoma (PC) or its precursor lesions are still lacking. The ability of circulating microRNAs (miRNAs) to discriminate multifocal high-grade precursor lesions or PC from normal was examined. The presence of miRNA-21, -155, -196a, -196b and -210 was analyzed in the serum of transgenic KPC mice to test their ability to distinguish mice with different grades of pancreatic intraepithelial neoplasia (mPanIN1–3) or PC from control mice. Serum levels of miR-196a and -196b were significantly higher in mice with PanIN2/3 lesions (n = 10) or PC (n = 8) as compared to control mice (n = 10) or mice with PanIN1 lesions (n = 10; P = .01). In humans, miR-196a and -196b were also diagnostic. Patients with PC, sporadic (n = 9) or hereditary (n = 10), and IAR with multifocal PanIN2/3 lesions (n = 5) had significantly higher serum levels than patients with neuroendocrine pancreatic tumors (n = 10) or chronic pancreatitis (n = 10), IAR with PanIN1 or no PanIN lesions (n = 5), and healthy controls (n = 10). The combination of both miR-196a and -196b reached a sensitivity of 1 and specificity of 0.9 (area under the curve = 0.99) to diagnose PC or high-grade PanIN lesions. In addition, preoperative elevated serum levels of miR-196a and -196b in patients with PC or multifocal PanIN2/3 lesions dropped to normal after potential curative resection. The combination of miR-196a and -196b may be a promising biomarker test for the screening of IAR for FPC.     

Basolateral cholesterol depletion alters Aquaporin-2 post-translational modifications and disrupts apical plasma membrane targeting

Apical plasma membrane accumulation of the water channel Aquaporin-2 (AQP2) in kidney collecting duct principal cells is critical for body water homeostasis. Posttranslational modification (PTM) of AQP2 is important for regulating AQP2 trafficking. The aim of this study was to determine the role of cholesterol in regulation of AQP2 PTM and in apical plasma membrane targeting of AQP2. Cholesterol depletion from the basolateral plasma membrane of a collecting duct cell line (mpkCCD14) using methyl-beta-cyclodextrin (MBCD) increased AQP2 ubiquitylation. Forskolin, cAMP or dDAVP-mediated AQP2 phosphorylation at Ser269 (pS269-AQP2) was prevented by cholesterol depletion from the basolateral membrane. None of these effects on pS269-AQP2 were observed when cholesterol was depleted from the apical side of cells, or when MBCD was applied subsequent to dDAVP stimulation. Basolateral, but not apical, MBCD application prevented cAMP-induced apical plasma membrane accumulation of AQP2. These studies indicate that manipulation of the cholesterol content of the basolateral plasma membrane interferes with AQP2 PTM and subsequently regulated apical plasma membrane targeting of AQP2.