Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

We review modeling of astrocyte ion dynamics with a specific focus on the implications of so-called spatial potassium buffering, where excess potassium in the extracellular space (ECS) is transported away to prevent pathological neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for modeling ion dynamics in astrocytes (and brain tissue in general) is outlined and used to study such spatial buffering. We next describe how the ion dynamics of astrocytes may regulate microscopic liquid flow by osmotic effects and how such microscopic flow can be linked to whole-brain macroscopic flow. We thus include the key elements in a putative multiscale theory with astrocytes linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure

Your space or mine? : Mapping self in time

Peer reviewedPublisher PD

Satisfaction with care after total hip or knee replacement predicts self-perceived health status after surgery

<p>Abstract</p> <p>Background</p> <p>Inpatient satisfaction with care is a standard indicator of the quality of care delivered during hospitalization. Total hip and knee replacement (THR/TKR) for osteoarthritis (OA) are among the most successful orthopaedic interventions having a positive impact on health-related quality of life (HRQoL). The aim was to evaluate the effect of satisfaction shortly after hospital discharge on 1-month, 6-month and 1-year Medical Outcomes Study 36-item Short Form (SF-36) scores for OA patients after THR and TKR, controlling for patient characteristics, clinical presentation and preoperative SF-36 scores.</p> <p>Methods</p> <p>A multicenter prospective cohort study recruited 231 patients with OA scheduled to receive THR or TKR. Satisfaction was assessed by the Patients Judgment of Hospital Quality (PJHQ) questionnaire and HRQoL by the SF-36 questionnaire. Linear models for repeated measures assessed the relation between satisfaction (scores were dichotomized) and postoperative SF-36 scores.</p> <p>Results</p> <p>Of 231 participants, 189 were followed up 12 months after discharge (mean age 69 SD = 8; 42.6% male). The mean length of hospital stay was 13.5 (SD = 4) days. After adjustment for preoperative SF-36 scores, sociodemographic and clinical patient characteristics, satisfied patients (PJHQ score > 70) had higher SF-36 scores 1 year after surgery than did less-satisfied patients. Admission, medical care, and nursing and daily care scores mainly predicted bodily pain, mental health, social functioning, vitality and general health scores of the SF-36.</p> <p>Conclusion</p> <p>Besides being a quality-of-care indicator, immediate postoperative patient satisfaction with care may bring a new insight into clinical practice, as a predictor of self-perceived health status after surgery.</p

Selecting short-statured children needing growth hormone testing: Derivation and validation of a clinical decision rule

<p>Abstract</p> <p>Background</p> <p>Numerous short-statured children are evaluated for growth hormone (GH) deficiency (GHD). In most patients, GH provocative tests are normal and are thus in retrospect unnecessary.</p> <p>Methods</p> <p>A retrospective cohort study was conducted to identify predictors of growth hormone (GH) deficiency (GHD) in children seen for short stature, and to construct a very sensitive and fairly specific predictive tool to avoid unnecessary GH provocative tests. GHD was defined by the presence of 2 GH concentration peaks < 10 ng/ml. Certain GHD was defined as GHD and viewing pituitary stalk interruption syndrome on magnetic resonance imaging. Independent predictors were identified with uni- and multi-variate analyses and then combined in a decision rule that was validated in another population.</p> <p>Results</p> <p>The initial study included 167 patients, 36 (22%) of whom had GHD, including 5 (3%) with certain GHD. Independent predictors of GHD were: growth rate < -1 DS (adjusted odds ratio: 3.2; 95% confidence interval [1.3–7.9]), IGF-I concentration < -2 DS (2.8 [1.1–7.3]) and BMI z-score ≥ 0 (2.8 [1.2–6.5]). A clinical decision rule suggesting that patients be tested only if they had a growth rate < -1 DS and a IGF-I concentration < -2 DS achieved 100% sensitivity [48–100] for certain GHD and 63% [47–79] for GHD, and a specificity of 68% [60–76]. Applying this rule to the validation population (n = 40, including 13 patients with certain GHD), the sensitivity for certain GHD was 92% [76–100] and the specificity 70% [53–88].</p> <p>Conclusion</p> <p>We have derived and performed an internal validation of a highly sensitive decision rule that could safely help to avoid more than 2/3 of the unnecessary GH tests. External validation of this rule is needed before any application.</p

Expression analysis of mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2) in more than 300 human tumors and matching normal tissues reveals their co-expression in gynecologic malignancies

BACKGROUND: Mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2), two members of the secretoglobin superfamily, are known to be co-expressed in breast cancer, where their proteins form a covalent complex. Based on the relatively high tissue-specific expression pattern, it has been proposed that the mammaglobin A protein and/or its complex with lipophilin B could be used in breast cancer diagnosis and treatment. In view of these clinical implications, the aim of the present study was to analyze the expression of both genes in a large panel of human solid tumors (n = 309), corresponding normal tissues (n = 309) and cell lines (n = 11), in order to evaluate their tissue specific expression and co-expression pattern. METHODS: For gene and protein expression analyses, northern blot, dot blot hybridization of matched tumor/normal arrays (cancer profiling arrays), quantitative RT-PCR, non-radioisotopic RNA in situ hybridization and immunohistochemistry were used. RESULTS: Cancer profiling array data demonstrated that mammaglobin A and lipophilin B expression is not restricted to normal and malignant breast tissue. Both genes were abundantly expressed in tumors of the female genital tract, i.e. endometrial, ovarian and cervical cancer. In these four tissues the expression pattern of mammaglobin A and lipophilin B was highly concordant, with both genes being down-, up- or not regulated in the same tissue samples. In breast tissue, mammaglobin A expression was down-regulated in 49% and up-regulated in 12% of breast tumor specimens compared with matching normal tissues, while lipophilin B was down-regulated in 59% and up-regulated in 3% of cases. In endometrial tissue, expression of mammaglobin A and lipophilin B was clearly up-regulated in tumors (47% and 49% respectively). Both genes exhibited down-regulation in 22% of endometrial tumors. The only exceptions to this concordance of mammaglobin A/lipophilin B expression were normal and malignant tissues of prostate and kidney, where only lipophilin B was abundantly expressed and mammaglobin A was entirely absent. RNA in situ hybridization and immunohistochemistry confirmed expression of mammaglobin A on a cellular level in endometrial and cervical cancer and their corresponding normal tissues. CONCLUSION: Altogether, these data suggest that expression of mammaglobin A and lipophilin B might be controlled in different tissues by the same regulatory transcriptional mechanisms. Diagnostic assays based on mammaglobin A expression and/or the mammaglobin A/lipophilin B complex appear to be less specific for breast cancer, but with a broader spectrum of potential applications, which includes gynecologic malignancies

Resting-State Quantitative Electroencephalography Reveals Increased Neurophysiologic Connectivity in Depression

Symptoms of Major Depressive Disorder (MDD) are hypothesized to arise from dysfunction in brain networks linking the limbic system and cortical regions. Alterations in brain functional cortical connectivity in resting-state networks have been detected with functional imaging techniques, but neurophysiologic connectivity measures have not been systematically examined. We used weighted network analysis to examine resting state functional connectivity as measured by quantitative electroencephalographic (qEEG) coherence in 121 unmedicated subjects with MDD and 37 healthy controls. Subjects with MDD had significantly higher overall coherence as compared to controls in the delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), and beta (12–20 Hz) frequency bands. The frontopolar region contained the greatest number of “hub nodes” (surface recording locations) with high connectivity. MDD subjects expressed higher theta and alpha coherence primarily in longer distance connections between frontopolar and temporal or parietooccipital regions, and higher beta coherence primarily in connections within and between electrodes overlying the dorsolateral prefrontal cortical (DLPFC) or temporal regions. Nearest centroid analysis indicated that MDD subjects were best characterized by six alpha band connections primarily involving the prefrontal region. The present findings indicate a loss of selectivity in resting functional connectivity in MDD. The overall greater coherence observed in depressed subjects establishes a new context for the interpretation of previous studies showing differences in frontal alpha power and synchrony between subjects with MDD and normal controls. These results can inform the development of qEEG state and trait biomarkers for MDD

Binge eating, purging and non-purging compensatory behaviours decrease from adolescence to adulthood: A population-based, longitudinal study

Background Subclinical forms of eating disorders (ED) are highly prevalent, but relatively little is known about age trends, gender differences and distinctions among symptoms. This study investigates age trends and gender difference in binge eating, purging and non-purging compensatory behaviours (CB) and the relationship of such behaviours to psychosocial problems. Methods Data from the national representative longitudinal study "Young in Norway" (ages 14-34 years) were analysed using χ 2 tests, logistic random intercept models and analyses of covariance. Results For both genders, a decrease was found in the prevalence of CB from age 14-16 years to 23 years and over. For binging, however, a significant decrease was found only for females, whose binge eating also declined more markedly over time than did males'. A significant gender difference was detected for purging, with females at higher risk. Purging was related to particularly serious symptoms of psychosocial problems: Those who purged had significantly higher levels of appearance dissatisfaction, anxiety and depressive symptoms, alcohol consumption, self-concept instability and loneliness than those with symptoms of other forms of disordered eating. Conclusions Individuals affected by purging need to be targeted as a high-risk group. The distinction in severity among the subclinical ED may indicate the need for the reformulation of the eating disorder not otherwise specified category in the Diagnostic and Statistical Manual of Mental Disorders-V

Regulation of Intestinal Immune Response by Selective Removal of the Anterior, Posterior, or Entire Pituitary Gland in Trichinella spiralis Infected Golden Hamsters

The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals has been previously reported. Hypophysectomy (HYPOX) in the rat causes atrophy of the intestinal mucosa, and reduction of gastric secretion and intestinal absorption, as well as increased susceptibility to bacterial and viral infections. However, to our knowledge, no findings have been published concerning the immune response following HYPOX during worm infection, particularly that which is caused by the nematode Trichinella spiralis. The aim of this work was to analyze the effects of total or partial HYPOX on colonization of T. spiralis in the intestinal lumen, together with duodenal and splenic cytokine expression. Our results indicate that 5 days post infection, only neurointermediate pituitary lobectomy (NIL) reduces the number of intestinally recovered T. spiralis larvae. Using semiquantitative inmunofluorescent laser confocal microscopy, we observed that the mean intensity of all tested Th1 cytokines was markedly diminished, even in the duodenum of infected controls. In contrast, a high level of expression of these cytokines was noted in the NIL infected hamsters. Likewise, a significant decrease in the fluorescence intensity of Th2 cytokines (with the exception of IL-4) was apparent in the duodenum of control and sham infected hamsters, compared to animals with NIL surgeries, which showed an increase in the expression of IL-5 and IL-13. Histology of duodenal mucosa from NIL hamsters showed an exacerbated inflammatory infiltrate located along the lamina propria, which was related to the presence of the parasite. We conclude that hormones from each pituitary lobe affect the gastrointestinal immune responses to T. spiralis through various mechanisms

Genome-Wide Association Studies in Atherosclerosis

Cardiovascular disease remains the major cause of worldwide morbidity and mortality. Its pathophysiology is complex and multifactorial. Because the phenotype of cardiovascular disease often shows a marked heritable pattern, it is likely that genetic factors play an important role. In recent years, large genome-wide association studies have been conducted to decipher the molecular mechanisms underlying this heritable and prevalent phenotype. The emphasis of this review is on the recently identified 17 susceptibility loci for coronary artery disease. Implications of their discovery for biology and clinical medicine are discussed. A description of the landscape of human genetics in the near future in the context of next-generation sequence technologies is provided at the conclusion of this review