Fasting Glucose and the Risk of Depressive Symptoms: Instrumental-Variable Regression in the Cardiovascular Risk in Young Finns Study

Purpose

Type 2 diabetes (T2D) has been associated with depressive symptoms, but the causal direction of this association and the underlying mechanisms, such as increased glucose levels, remain unclear. We used instrumental-variable regression with a genetic instrument (Mendelian randomization) to examine a causal role of increased glucose concentrations in the development of depressive symptoms.

Method

Data were from the population-based Cardiovascular Risk in Young Finns Study (n = 1217). Depressive symptoms were assessed in 2012 using a modified Beck Depression Inventory (BDI-I). Fasting glucose was measured concurrently with depressive symptoms. A genetic risk score for fasting glucose (with 35 single nucleotide polymorphisms) was used as an instrumental variable for glucose.

Results

Glucose was not associated with depressive symptoms in the standard linear regression (B = ?0.04, 95% CI [?0.12, 0.04], p = .34), but the instrumental-variable regression showed an inverse association between glucose and depressive symptoms (B = ?0.43, 95% CI [?0.79, ?0.07], p = .020). The difference between the estimates of standard linear regression and instrumental-variable regression was significant (p = .026)

Conclusion

Our results suggest that the association between T2D and depressive symptoms is unlikely to be caused by increased glucose concentrations. It seems possible that T2D might be linked to depressive symptoms due to low glucose levels.

     

Concordance between Composite International Diagnostic Interview and self‐reports of depressive symptoms: a re‐analysis

Concordance between sum scores of self‐reported depressive symptoms and structured interview diagnoses has been studied extensively, but are these the best attainable self‐report‐based predictions for interview diagnoses? We maximized the cross‐validated concordance between World Health Organization's Composite International Diagnostic Interview (CIDI) diagnosis and Beck's Depression Inventory (BDI), and General Health Questionnaire (GHQ), from the viewpoint of exploratory statistics, re‐analysing Health 2000 general‐population sample of adults over 30 years in mainland Finland (N = 5200–5435). BDI sum‐score prediction of CIDI diagnosis could be superseded by using (1) weighted sums of items, (2) classification trees constructed from items, or (3) a single item. Best solution (2) yielded cross‐validated Youden's Index 0.757 [standard error (SE) = 0.001, sensitivity = 0.907, specificity = 0.851], improving the concordance to 1.07‐fold (1.18‐fold for 12‐month diagnosis). A single‐item solution was best for the GHQ. All positive predictive values remained low (0.09–0.31). Thus, CIDI‐to‐questionnaire concordance can be improved by using all information in the questionnaires instead of just sum scores, but latent‐trait theory for questionnaires is incompatible with interview diagnoses (single item achieved better concordance than summing all). Self‐reports have low predictive value for CIDI diagnoses in the general population, but better in settings with higher major depressive disorder (MDD) base rates. Copyright © 2015 John Wiley & Sons, Ltd.     

Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis

Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency of which causes early-onset and particularly aggressive forms of neuronal ceroid-lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are characterized by severe neurodegeneration, but the molecular mechanisms behind the neuronal death remain poorly understood. In this study, we have systematically mapped the distribution of neuropathologic changes in CTSD-deficient mouse brains by stereologic, immunologic, and electron microscopic methods. We report highly accentuated neuropathologic changes within the ventral posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF), which receive and send information to the thalamic VPM/VPL. These changes included pronounced astrocytosis and microglial activation that begin in the VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced neuronal number and redistribution of presynaptic markers. In addition, loss of synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin were observed in the VPM/VPL. These synaptic alterations are accompanied by changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates formation of the SNARE complex at the synapse. Taken together, these data reveal the somatosensory thalamocortical circuitry as a particular focus of pathologic changes and provide the first evidence for synaptic alterations at the molecular and ultrastructural levels in CTSD deficiency.     

Impaired pre-attentive auditory processing in opioid dependence with and without benzodiazepine co-dependence revealed by combined magnetoencephalography and electroencephalography

Cognitive dysfunctions may be a significant factor in drug-seeking behavior, reducing the efficiency of rehabilitation in opioid dependence. Neurophysiological basis of these dysfunctions is poorly understood. 21 opioid-dependent patients and 15 healthy controls with no experience of illicit drugs were studied with simultaneous electroencephalography (EEG) and magnetoencephalography (MEG). Among opioid dependents 15 were benzodiazepine co-dependent. In a passive oddball paradigm, a train of 700-Hz standard tones (80%), presented to the left ear, was occasionally interrupted by infrequent deviants, which were either 600-Hz or 400-Hz pure tones or complex novel sounds. The auditory evoked potentials (AEP) and fields (AEF) were analyzed. The strength of the N1m dipoles was enhanced in patients with benzodiazepine co-dependence, but the latency of the response or the source location was not changed. A delay of mismatch negativity (MMN) response of novel tones in EEG, and delay of P3am response on the contralateral hemisphere to stimulated ear in MEG in opioid-dependent patients were observed. There were no differences in source locations or strengths of the dipoles for P1m, MMNm, and P3am determined using equivalent current dipoles. There were no group differences in EEG amplitude measures. In conclusion, our results suggest delayed pre-attentive auditory processing of novel information in opioid dependence. Benzodiazepine co-dependence modulated N1m response.     

Comparison of the suppressing capecitabine and 5-fluorouracil effects on the pronounce of inflammatory cells score in the induction of episcleral fibrosis after trabeculectomy

BACKGROUND/AIM: Trabeculectomy is a filtering antiglaucoma surgery performed to facilitate the formation of a drainage channel for the aqueous humor from the anterior chamber of the eye to the subconjunctival space making a collector, filtering cushion of the eyeliquid. The cause of unfavourable outcome of trabeculectomy is episcleral fibrosis which leads to the obstruction of the drainage channel Inflammatory reaction is an initial, but, also, the key event in the process of fibrosis and directly proportional to it A successful medicamentous suppression of inflammation could stop fibrosis. Arccordingly, the aim of this study was to comparatively evaluate suppressing effects of capecitabine and 5-fluoroaracil upon inflammation, an initial fibrosis process after trabeculectomy. METHODS: This study was performed on an experimental animal model, namely 2 4 rabbits (48 eyes), which were exposed to artificial cause of the tissue changes analogous to human subclinical inflammation. During the trabeculectomy, a 5% solution of 5-fluoroaracil was applied to the right eye sclera of a rabbit, while 2% solution of kapecitabine was applied to the left eye sclera, thus making possible to evaluate the effects of different drugs to the same animal. Two weeks after the surgery the subconjunctival - episcleral tissue cuts were analyzed. Semiquantitative histologic test was used to compare the cellular elements of inflammatory (fibroblasts, mononuclears, plasmocytes, eosinophiles), as well as fibrosing (colagen, reticulin fibers) process, and, based on the differences in histopathologic score, suppressive efficacy of 5-fluoroaracil and kapecitabine was evaluated and compared between the groups of the treated tissues. The results were shown as mean values +/- standard deviation. RESULTS: A statistically significantly lower score was revealed in the initial inflammatory cells - mononudears and plasmocytes in the group of the tissues treated with kapecitabine, while there was no differences between the groups in the score of fibroblasts and colagen fibers. CONCLUSION: The suppression of the initial episcleral fibrosis process obtained by kapecitabine was more significant as compared to the suppression obtained by 5-fluoroaracil, thus providing more favorable outcome of the trabeculectomy.     

Differential diagnosis of acute central nervous system infections in children using modern microbiological methods

Aim:  Except bacterial meningitis, the agents causing acute central nervous system (CNS) infections in children are disclosed in only approximately half of the cases, and even less in encephalitis. We studied the potential of modern microbiological assays to improve this poor situation.
Methods:  In a prospective study during 3 years, all children attending hospital with suspected CNS infection were examined using a wide collection of microbiological tests using samples from the cerebrospinal fluid, serum, nasal swabs and stool.
Results:  Among 213 patients, 66 (31%) cases suggested CNS infection and specific aetiology was identified in 56 patients. Of these microbiologically confirmed cases, viral meningitis/encephalitis was diagnosed in 25 (45%), bacterial meningitis in 21 (38%) and neuroborreliosis in 9 (16%) cases while 1child had fungal infection. In meningitis patients, the causative agent was identified in 85% (35/41) cases and in encephalitis in 75% (12/16). The most common bacteria were Streptococcus agalactiae , Streptococcous pneumonie and Neisseria meningitidis, while the most frequently detected viruses were enteroviruses and varicella zoster virus.
Conclusion:  In 75% to 85% of paediatric CNS infections, specific microbiological diagnosis was obtained with modern laboratory techniques. The results pose a basis for prudent approach to these potentially serious diseases.     

Effect of stable fish oil on arterial thrombogenesis, platelet aggregation, and superoxide dismutase activity

We examined the influence of dietary stable fish oil on aortic thrombosis, platelet aggregation, and superoxide dismutase (SOD) activity in a rat model. Twenty-nine Sprague-Dawley rats were fed regular chow supplemented with stable fish oil preparation (for 1 or 3 weeks), and 37 rats fed regular chow served as controls. The abdominal cavity was opened, and the abdominal aorta isolated. Whatman paper impregnated with 35% FeCl3 was wrapped around the surface of the aorta, and aortic flow was continuously recorded. In control rats, an occlusive platelet-fibrin-rich thrombus was formed in 21 +/- 3 min. Dietary fish oil in a time-dependent fashion delayed time to thrombus formation (24 +/- 2 min in rats fed fish oil for 1 week and 31 +/- 2 min in rats fed fish oil for 3 weeks), inhibited platelet aggregation (21 +/- 5% vs. 45 +/- 6%; p < 0.01) and increased SOD activity (p < 0.01). We conclude that dietary supplementation with stable fish oil delays formation of arterial thrombus, probably by reducing platelet aggregation and oxidative stress-associated arterial injury.     

Serum levels of beta 2-microglobulin in various types of hemodialysis

beta 2-microglobulin (beta 2 m) is the major constituent of amyloid fibrils in dialysis-related amyloidosis (DRA), which is considered to be one of the most severe adverse effect of long-term dialysis. In this study we evaluated the efficiency of beta 2 m removal during different dialysis procedures. A total of 45 patients undergoing hemodialysis were divided in five groups: cuprophane dialysis (n = 10), high-flux polysulphone dialysis (n = 10), postdilutional hemodiafiltration (n = 10), conventional postdilutional hemofiltration (n = 10) and predilutional on-line hemofiltration (n = 5). Serum level of beta 2 m was determined before and after different procedures using ELISA. In the group of patients on cuprophane dialysis was registered an elevation of beta 2 m and of 16.8 +/- 11.4% on the average. Serum level of beta 2 m was decreased following all other procedures on the average of 40.7 +/- 16.4% after high-flux polysulphone dialysis, 42.0 +/- 13.7% after conventional hemofiltration, 64.7 +/- 9% after hemodiafiltration and 67.9 +/- 10.1% after predilutional hemofiltration. The best removal of serum beta 2 m was realized by predilutional hemofiltration. Also, we have noticed that patients treated with high-flux synthetic membranes in the longer time-period have lower predyalisis value of beta 2 m compared to patients treated with cuprophane membrane. Further long-term studies will be necessary to conclude whether these procedures could be successful prophylactic and/or therapeutic regimen for dialysis-related amyloidosis.