Effects of spatial smoothing on functional brain networks

Graph‐theoretical methods have rapidly become a standard tool in studies of the structure and function of the human brain. Whereas the structural connectome can be fairly straightforwardly mapped onto a complex network, there are more degrees of freedom in constructing networks that represent functional connections between brain areas. For functional magnetic resonance imaging (fMRI) data, such networks are typically built by aggregating the blood‐oxygen‐level dependent signal time series of voxels into larger entities (such as Regions of Interest in some brain atlas) and determining their connection strengths from some measure of time‐series correlations. Although it is evident that the outcome must be affected by how the voxel‐level time series are treated at the preprocessing stage, there is a lack of systematic studies of the effects of preprocessing on network structure. Here, we focus on the effects of spatial smoothing, a standard preprocessing method for fMRI. We apply various levels of spatial smoothing to resting‐state fMRI data and measure the changes induced in functional networks. We show that the level of spatial smoothing clearly affects the degrees and other centrality measures of functional network nodes; these changes are non‐uniform, systematic, and depend on the geometry of the brain. The composition of the largest connected network component is also affected in a way that artificially increases the similarity of the networks of different subjects. Our conclusion is that wherever possible, spatial smoothing should be avoided when preprocessing fMRI data for network analysis.     

HRQoL after coronary artery bypass grafting and percutaneous coronary intervention for stable angina

Objectives. To assess the health related quality of life (HRQoL) and the change in the NYHA class after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in the management of stable coronary artery disease (CAD). The study was non-randomized. CABG group consisted of 240 patients and 229 patients were treated with PCI. HRQoL was measured prospectively by the 15D instrument. Results. Three-year survival was 95.0 and 95.6% (NS). The HRQoL improved statistically in both groups until 6 months after treatment but deteriorated towards the end of the follow-up of 36 months. Clinically evident improvement of the HRQoL and decrease of the NYHA class took place more frequently among CABG patients. Conclusions. Despite initially more serious preoperative state and more demanding procedure CABG patients achieve equal level of HRQoL when compared with PCI patients. CABG patients may also obtain better relief from symptoms in mid-term follow-up. HRQoL cannot be the only factor to determine outcome after invasive treatment of CAD but it has to be placed in the context of the overall situation.     

Intestinal Depletion of NaPi‐IIb/Slc34a2 in Mice: Renal and Hormonal Adaptation

The Na⁺‐dependent phosphate‐cotransporter NaPi‐IIb (SLC34A2) is widely expressed, with intestine, lung, and testis among the organs with highest levels of mRNA abundance. In mice, the intestinal expression of NaPi‐IIb is restricted to the ileum, where the cotransporter localizes specifically at the brush border membrane (BBM) and mediates the active transport of inorganic phosphate (Pi). Constitutive full ablation of NaPi‐IIb is embryonically lethal whereas the global but inducible removal of the transporter in young mice leads to intestinal loss of Pi and lung calcifications. Here we report the generation of a constitutive but intestinal‐specific NaPi‐IIb/Slc34a2–deficient mouse model. Constitutive intestinal ablation of NaPi‐IIb results in viable pups with normal growth. Homozygous mice are characterized by fecal wasting of Pi and complete absence of Na/Pi cotransport activity in BBM vesicles (BBMVs) isolated from ileum. In contrast, the urinary excretion of Pi is reduced in these animals. The plasma levels of Pi are similar in wild‐type and NaPi‐IIb–deficient mice. In females, the reduced phosphaturia associates with higher expression of NaPi‐IIa and higher Na/Pi cotransport activity in renal BBMVs, as well as with reduced plasma levels of intact FGF‐23. A similar trend is found in males. Thus, NaPi‐IIb is the only luminal Na⁺‐dependent Pi transporter in the murine ileum and its absence is fully compensated for in adult females by a mechanism involving the bone‐kidney axis. The contribution of this mechanism to the adaptive response is less apparent in adult males. © 2015 American Society for Bone and Mineral Research.     

Clinical presentations and epidemiology of β-haemolytic streptococcal bacteraemia: a population-based study

In this population-based study, all 314 episodes of β-haemolytic streptococcal bacteraemia in adult patients in the Pirkanmaa area, Finland, during the 10-year period 1995–2004 were retrospectively reviewed. Altogether, 92 cases of bacteraemia caused by Lancefield group A β-haemolytic streptococci (GAS), 76 caused by group B β-haemolytic streptococci (GBS), 18 caused by group C β-haemolytic streptococci (GCS) and 128 caused by group G β-haemolytic streptococci (GGS) were identified. The most important finding was that the incidence of GGS increased during the study period. Disruption of the cutaneous barrier was a very common predisposing factor in GAS and GGS bacteraemias. Skin infections were the presenting clinical manifestations in two-thirds of GAS and GGS bacteraemias.     

Suspicious urine cytology (class III) in patients with bladder cancer: should it be considered as negative or positive?

OBJECTIVES: Urine cytology is the gold standard in the diagnosis and follow-up of bladder cancer. Cytology, however, exhibits variable sensitivity depending on tumour grade and interpretation of urine specimens is highly dependent on the skill of the examiner. Positive cytology, classes IV and V by Papanicolaou classification, is a strong predictor for coexisting or subsequent malignancy, while the role of suspicious cytology, class III, is controversial. The objective of the study was to evaluate the role of the suspicious finding in cytological analysis, and whether it should be considered as a negative or positive sign for coexisting malignancy. MATERIAL AND METHODS: Six hundred and fifty-two consecutive patients with bladder cancer were studied in a prospective multicenter trial. One hundred and fifty-one of the patients were newly diagnosed, and the remaining 501 patients were under follow-up. A voided urine sample was obtained prior to TURB or prior to routine follow-up cystoscopy in those under the surveillance and split for culture and cytology. The cytopathological results were analyzed by a central review and only patients with samples available for review analysis were included. Sensitivity and specificity, as well as positive (PPV) and negative (NPV) predictive values of urine cytology were calculated by classifying the class III samples as negative or positive. RESULTS: A total of 570 patients were evaluable. One hundred and twenty nine (22.6%) were newly diagnosed and 441 were under follow-up, of whom 117 (26.5%) had recurrence. Cytology was classified as suspicious in 33/129 (25.6%) patients with primary tumour, and in 41/441 (9.3%) of those under the follow-up, of whom 20 (48.8%) had recurrence. Sensitivity increased from to 31.0% to 56.6% in primary tumours (p < 0.001) and from 17.8% to 34.7% in recurrent tumours (p < 0.001) if class III was determined as positive, whereas the specificity decreased from 96.6% to 90.1% (p < 0.001). Accordingly, the NPV increased from 76.3% to 79.1% and the PPV decreased from 65.6% to 56.2%. CONCLUSIONS: The poor sensitivity of voided urine cytology improved significantly when suspicious samples were determined as positive while the specificity remained high, a clear advantage compared with most of the new tumour marker tests. In addition, nearly half of the follow-up patients with suspicious class III cytology had recurrence implying that this patient category is at substantial risk for co-existing malignancy. Therefore, it is recommended that suspicious class III cytology together with class IV and V specimens should be considered positive.     

Ultrastructural changes of the capillaries of the cat iris in experimental neuroparalytic keratitis

Summary In order to study the morphological basis of the increased permeability of the capillaries of the iris in neuroparalytic keratitis the ophthalmic division of the trigeminal nerve in the cat was denervated using a stereotactic method. The homolateral iris was studied by electron microscopy three days after denervation. Abnormally large pinocytotic vacuoles were observed in the endothelial cells of the iris capillaries and the intercellular junctions of the endothelial cells showed widened inter-cellular space and macula occludens. These ultrastructural changes may explain the protein leakage into the anterior chamber in neuropyralytic keratitis.

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Zusammenfassung Um die morphologische Grundlage der erhöhten Permeabilität der Iriskapillaren bei Keratitis neuroparalytica zu untersuchen, wurde der Augenast des Trigeminus bei der Katze stereotaktisch denerviert. Drei Tage danach zeigten sich im Elektronenmikroskop abnorm umfangreiche pinocytotische Vakuolen in den Endothelien der Kapillaren der Regenbogenhaut und erweiterte Intercellulärräume mit Macula occludens. Hierin kann der Übertritt von Protein in das Kammerwasser bei Keratitis neuroparalytica erklärt werden.

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Submitted in part to the meeting of the European Club for Ophthalmic Fine Structure in London, April 19, 1974 (M. S.).

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Supported by a grant from the Finnish Medical Foundation and the Instrumentariumin Tiedesäätiö Foundation (M. S.).     

The apolipoprotein E polymorphism is not associated with response to electroconvulsive therapy in major depressive disorder

The apolipoprotein E (APOE) polymorphism is associated with neurodegenerative diseases. Its role regarding psychiatric disorders is controversial. It has been suggested to affect antidepressant treatment response and response to electroconvulsive therapy (ECT). In the present study, the association between APOE polymorphism and response to ECT in 119 patients with major depressive disorder was investigated. Moreover, a relation between APOE polymorphism and the age of onset of depression as well as the cognitive outcome of ECT was studied. In the whole population, no association was found between APOE polymorphism and response to ECT. However, in nonpsychotic patients, the epsilon2 allele tended to be more frequent in responders than nonresponders. Earlier onset of depression was observed in the patients with epsilon4 allele in late-life depression. There was no association between the APOE genotype and the cognitive change caused by ECT in the population as a whole. In women, however, epsilon2 allele may play a protective and epsilon4 allele a deleterious role in cognition during ECT.     

PDZ proteins and proximal ion transport

PURPOSE OF REVIEW: PDZ proteins are major structural components of protein assembly. This review covers the implications of these proteins in the regulation of transport systems expressed in renal proximal tubules. RECENT FINDINGS: In the last few years, many reports have highlighted the implication of PDZ proteins in two aspects of proximal tubule physiology, namely the generation and maintenance of epithelial polarity and the formation of regulatory complexes that provide spatial and molecular specificity to the intracellular signalling. SUMMARY: PDZ-mediated interactions are involved in a wide range of cellular functions, from cell division to cell polarity to intracellular signalling. Consistent with this functional spectrum, ablation of PDZ protein genes generates a wide panel of pathological phenotypes, some of which link directly to human syndromes. In proximal tubules, PDZ proteins are thought to play a major role in epithelial polarity and transport regulation.