Interface analysis between GSVML and HL7 version 3

In order to realize gene-based medicine, a number of key challenges must be overcome. Construction of infrastructure capable of integrating genetic and clinical information is one of those challenges. The Genomic Sequence Variation Markup Language (GSVML) and the Health Level Seven Version 3 (HL7v3) are important electronic data exchange standards for clinical genome infrastructure, and compatibility between these two standards will promote the above integration. In this study, we analyzed the interface between GSVML and HL7v3, primarily for the Clinical Genomics Domain, from a view of the GSVML, and were able to create a blueprint for a functional interface between GSVML and HL7v3. We expect that these analytical results will help accelerate the realization of gene-based medicine.     

Second-look US Using Real-time Virtual Sonography,a Coordinated Breast US and MRI System with Electromagnetic Tracking Technology: A Pilot Study

Our aim was to retrospectively evaluate the utility of second-look ultrasound (US) using real-time virtual sonography (RVS) for detection of conventional B-mode (cB-mode) occult magnetic resonance imaging (MRI)-detected breast lesions. Between July 2011 and May 2015, 53 consecutive patients who underwent second-look US to identify lesions detected by prone MRI were enrolled in this study. Second-look US using RVS was performed for cB-mode occult MRI-detected breast lesions after an additional supine MRI. In the 53 patients, 59 lesions were initially detected by prone MRI, followed by second-look US. Of the 59 lesions, 20 (34%) were identified by second-look US using cB-mode. Of the 39 (66%) cB-mode occult lesions, 38 (97%) were detected in supine MRI and 33 (85%) were detected by second-look US using RVS. MRI morphology types of the 33 lesions were as follows: mass, 16; non-mass enhancement, 5; and focus, 12. US-guided biopsy under RVS or excisional biopsy demonstrated that of the 33 lesions, 8 (24%) were malignant and the remaining 25 (76%) were benign. A total of 53 (90%) MRI-detected lesions were sonographically identified using both cB-mode and RVS (p < 0.001). All five remaining US-occult lesions could be followed up under RVS after the enhancing area was marked on the breast surface using RVS. Although further prospective studies are required, the findings of our pilot study suggest that second-look US using RVS with additional supine MRI may improve the sonographic and histopathologic detection rate of cB-mode occult MRI-detected breast lesions.     

Characteristics of disability pensioners returning to work: An interview study among individuals with musculoskeletal disorders

Purpose. To explore adaptation patterns among disability pensioners with musculoskeletal disorders returning to work by means of the Swedish law on ‘resting disability pension’.

Method. Qualitative analyses of interviews with 17 individuals going back to work.

Results. Three adaptation patterns were identified: The Go-getter, the Realist and the Indifferent. These differed regarding influence factors, own expectations, motive, morals and mentality.

Conclusion. Several actors may support a return to work for individuals who received a disability pension due to musculoskeletal disorders. In order to succeed, however, it is essential that the disability pensioner is motivated for a reconstruction of his/her life.     

The development of peripartum depressive symptoms is associated with gene polymorphisms of MAOA, 5-HTT and COMT

Background

Polymorphisms of monoamine-related genes have been associated with depression following life events. The peripartum is a physiologically and psychologically challenging period, characterized by fluctuations in depressive symptoms, therefore facilitating prospective investigations in this gene × environment (G × E) interaction.

Methods

Eighty nine pregnant women filled in two Edinburgh Postpartum Depression Scale (EPDS) questionnaires during pregnancy and two in the postpartum period. MAOA, COMT and 5-HTT polymorphisms were analyzed.

Results

We found a significant interaction between the development of depressive symptoms in the course of pregnancy and polymorphisms in 5-HTT (p = 0.019); MAOA (p = 0.044) and COMT (p = 0.026), and MAOA × COMT (p < 0.001). Particularly, women carrying the combination of low activity variants of MAOA and COMT showed increased EPDS scores at week 36 of pregnancy and 6 weeks postpartum, but not during early pregnancy or 12 weeks postpartum.

Conclusion

We found that MAOA in combination with COMT appears to regulate not only the stress response in laboratory experiments, but also seems to influence the stress-evoked onset of mood during normal, mild, stressful events, such as experienced in the peripartum period. These findings support the G × E concept for depression, but they underline the complexity of this concept, as the cumulating effects of these polymorphic genes (i.e. MAOA + COMT) might be needed and the effects of these polymorphic genes becomes apparent in special environmental or physiological conditions (i.e. the peripartum period). We therefore suggest that G × E interactions become especially noticeable from longitudinal study designs in specific physiological or social challenging periods.     

Low plasma tryptophan in carcinoid patients is associated with increased urinary cortisol excretion

BACKGROUND: Previously we observed in patients suffering from a metastatic carcinoid tumor that irritability, aggression and lack of impulse control are associated with low levels of plasma tryptophan and presumably with low brain serotonin function. In rats we showed that a diet of low tryptophan resulted in higher stress responses and higher corticosterone production. Here we tested in carcinoid patients whether tryptophan depletion due to tumor 5-HT overproduction is associated with high cortisol production. METHODS: Urinary excretion of cortisol, serotonin, 5-hydroxyindole acetic acid (the main metabolite of serotonin a marker of tumor activity), plasma levels of tryptophan and platelet content of serotonin (index of peripheral serotonin synthesis) were determined in metastatic midgut carcinoid patients. Patients (N=25) were divided into two groups based on their plasma tryptophan levels (/=49mumol/l, n=13). RESULTS: Carcinoid patients with low plasma tryptophan levels had significantly higher urinary excretion of free cortisol (p<0.01), independent of tumor activity. The inter-individual differences in the low tryptophan group, however, were substantial. CONCLUSIONS: In a subgroup of the patients suffering from metastatic carcinoid disease the cerebral access of plasma tryptophan is impaired, thus rendering cerebral serotonin neurotransmission suboptimal and leading to hypercortisolism. The present study provides further support to the idea that low serotonergic function is a risk for developing stress-associated psychopathology.     

Thin-film assembly of diethanolamine-based lipidic material as potential gene carrier in mouse embryonic neural stem cells

Understanding of lipidic materials used for gene delivery system is essential for the effective design and development of potential applications in basic and therapeutic research. This study aimed to evaluate the biological activity of totally synthesized ditetradecylacetyldiethanolaminetrimethylammonium (TMA-C2-DEA-C14) as gene carriers for neural stem cells. The transfer abilities were estimated by expressing green fluorescent protein (GFP) in mouse embryonic neural stem cells. Here, we demonstrate that lipidic assembly of TMA-C2-DEA-C14, which was self-organized by incubation in water for a month at 25 degrees C, can provide an efficient gene delivery with low cytotoxicity ( approximately 40% of GFP-expressed neural stem cells). However, when dispersed by ultrasonication, TMA-C2-DEA-C14 showed low effect ( approximately 4%). Moreover, electron microscopic analysis showed that TMA-C2-DEA-C14 assembly is characterized by thin-film structures with polygonal shapes ( approximately 2.7 mum), and after association with DNA, their structures dramatically changes to form liposome complexes that can effectively deliver DNA into the cellular cytoplasm of neural stem cells. Thus, TMA-C2-DEA-C14 assembly identified in this study was determined to have an effective activity as gene carriers for primary neural stem cells. Our findings suggest that this approach can serve as a novel model for the development of lipidic materials on nonviral gene delivery system.     

Clinical significance of alanine aminotransferase levels and the effect of ursodeoxycholic acid in hemodialysis patients with chronic hepatitis C

Background

The natural history of hepatitis C virus (HCV) carriers and the effect of ursodeoxycholic acid (UDCA) have not been fully elucidated among hemodialysis (HD) patients.

Methods

Eighty-four anti-HCV antibody- and HCV RNA-positive and 154 anti-HCV antibody-negative HD patients who were retrospectively observed for at least 3 years were analyzed. We investigated the factors associated with thrombocytopenia (< 1.3 × 10⁵/μL) and decreased platelet count (PLT) (more than 20% decrease during the follow-up period), which were considered to be indicators of hepatic fibrosis. In addition, another 16 HD patients with HCV who received 300 mg/day UDCA orally for at least 6 months were investigated. Changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT) and PLT were assessed.

Results

After the 60.3-months mean follow-up period, HCV infection was independently associated with both thrombocytopenia [odds ratio (OR) 2.589] and decreased PLT (OR 2.339) in 238 HD patients. In 84 HD patients with HCV, the average ALT levels (≥ 15 IU/L) during the follow-up period was associated with thrombocytopenia (OR 3.882) and decreased PLT (OR 4.470). In addition, ALT, AST and GGT significantly decreased at 6 months after starting UDCA, but PLT did not change in 16 HD patients with HCV.

Conclusions

These results indicate that HCV infection is a risk for thrombocytopenia which should be associated with hepatic fibrosis in HD patients. In addition, the clinical course of ALT levels predicts the progression of thrombocytopenia, and UDCA may effectively lower ALT levels in HD patients with HCV.     

Protein C inhibitor inhibits breast cancer cell growth, metastasis and angiogenesis independently of its protease inhibitory activity

Protein C inhibitor (PCI) regulates the anticoagulant protein C pathway and also inhibits urinary plasminogen activator (uPA), a mediator of tumor cell invasion. In the present study, we evaluated the effect of human PCI and its inactive derivatives on tumor growth and metastasis of human breast cancer (MDA-231) cells, and on angiogenesis in vivo. The invasiveness of MDA-231 cells was inhibited by recombinant intact PCI, but not by reactive site-modified PCI (R354APCI) or by the N-terminal fragment of protease-cleaved PCI (NTPCI). The in vitro invasiveness of MDA-231 cells expressing intact PCI (MDA-PCI) was significantly decreased as compared to MDA-231 cells expressing R354APCI (MDA-R354APCI) or NTPCI (MDA-NTPCI). Further, in vivo growth and metastatic potential of MDA-PCI, MDA-R354APCI and MDA-NTPCI cells in severe combined immunodeficient (SCID) mice were significantly decreased as compared to MDA-Mock cells. Angiogenesis was also significantly decreased in Matrigel implant containing MDA-PCI, MDA-R354APCI or MDA-NTPCI cells as compared to that containing MDA-Mock cells. In vivo angiogenesis in rat cornea and in vitro tube formation were also inhibited by recombinant intact PCI, R354APCI and NTPCI. Furthermore, the anti-angiogenic activity of PCI was strong as cleaved antithrombin (AT), and slightly stronger than that of plasminogen activator inhibitor (PAI)-1 and pigment epithelium-derived factor (PEDF). Overall, this study showed that, in addition to a reactive site-dependent mechanism, PCI may also regulate tumor growth and metastasis independently of its protease inhibitory activity by inhibiting angiogenesis.     

Hoek's formula, a cystatin C-based prediction formula for determining the glomerular filtration rate, is the most effective method for original adjusting the dosage of vancomycin

OBJECTIVE: Some formulas using the serum cystatin C level to estimate the GFR have recently been reported. However, there has been no report of a serum cystatin C-based formula for adjusting the dosage of the drugs cleared by the kidney. In this study, we compared the predictive performance of the serum vancomycin trough concentration predicted using serum cystatin C-based formulas. METHOD: The data were collected from 158 hospitalized patients. Five formulas have been published to predict the GFR using serum cystatin C. The cystatin C-based formulas were divided into two groups, formulas with or without anthropometric data. We predicted the serum vancomycin trough concentrations using VCM-TDM S_edition ver. 1.00 software. RESULTS: In formulas with anthropometric data, the mean absolute error (MAE) using Hoek's formula was 2.38, the MAE using Grubb's 1 formula was 4.13, the MAE using Sj?str?m's formula was 2.90, and the MAE using Cockcroft and Gault formula based on creatinine was 4.42. On the other hand, in formulas without an anthropometric data group, the MAE using Larsson's formula was 3.07, and the MAE using Grubb's 2 formula was 3.63. CONCLUSION: These results suggested that Hoek's formula is the most useful formula for determining the initial dosage settings for vancomycin.