[Research progress of transcriptomics and proteomics in schizophrenia].

Schizophrenia is a severe psychiatric disorder with an unclear etiology and various clinical manifestations. The diagnosis and consequent treatment of schizophrenia mainly rely on clinical symptoms. Multiple risk sites associated with schizophrenia have been identified, yet objective indicators have not been found to facilitate clinical diagnosis and treatment of schizophrenia. The development of omics technology provides different perspectives on the etiology of schizophrenia and make the early identification, diagnosis and treatment of the disorder possible. This article summarizes the prevalence of schizophrenia, reviews the research results and shortcomings of transcriptomics and proteomics, as well as the latest achievements and prospects of multi-omics, aiming to reveal the use of omics in SZ, provide more comprehensive biological evidence to reveal the complex pathogenesis of schizophrenia and provide a theoretical basis for the early identification, accurate diagnosis, disease progression control, and prognosis improvement of schizophrenia.

Clinical utility of tumour marker velocity of cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) in breast cancer surveillance.

BACKGROUND: Serum tumour markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) are not routinely recommended for detecting breast cancer recurrence and monitoring treatment. In this study, we aim to evaluate the diagnostic accuracy of absolute CA 15-3 and CEA levels and report on the clinical utility of tumour marker velocity in breast cancer surveillance. METHODS: 67 consecutive patients over a 15-year period (1998-2012) with available serial serum CA 15-3 and CEA measurements at recurrence were matched to a control group of patients. Tumour marker velocity was derived from the average change in consecutive tumour marker values over time, expressed in unit/year. Logistic regression analysis was performed to investigate the association between tumour characteristics, tumour marker velocity and disease recurrence. RESULTS: Using the Youden index values, the optimal cut-off values for absolute CA 15-3 and CEA corresponded to the normal assay reference range while tumour marker velocity values were derived to be 2.5U/mL/year and 1.2ng/mL/year respectively. CA 15-3 velocity > 2.5U/mL/year had the highest AUROC value of 0.85 than CEA velocity alone. When either tumour marker velocity exceeded threshold values, the sensitivity, specificity, negative predictive value and positive predictive value were 94.0%, 73.1%, 92.5%, and 77.8% respectively. In the multivariate logistic regression analysis, having both CA 15-3 and CEA velocity exceeding the cut-off values was shown to be a significant predictor for disease recurrence (p = 0.01). CONCLUSION: These findings highlighted the clinical utility of serial tumour markers measurements and its velocity in breast cancer surveillance.

Anti-Voltage-gated Potassium Channel Limbic Encephalitis with Psychiatric Features: a Case Report.

We report a case of anti-voltage-gated potassium channel (VGKC) limbic encephalitis in a 47-year-old man presenting with a 2-year history of psychiatric features. The patient had cognitive impairment, slurred speech, and a mildly unsteady gait but no other neurological deficits or seizures. Results of blood, urine, and cerebrospinal fluid tests and magnetic resonance imaging of the brain were normal. However, electroencephalography showed an epileptogenic focus in the bilateral temporal regions with mild to moderate diffuse encephalopathy. Autoimmune panel results confirmed the diagnosis of anti-VGKC limbic encephalitis, with a serum VGKC concentration of 6730 pmol/L. The patient was treated with Keppra and pulsed intravenous methylprednisolone for 3 days, and his behaviour improved.

Network meta-analysis of novel and conventional sentinel lymph node biopsy techniques in breast cancer.

Background: The aim of this network meta-analysis was to compare the performance of blue dye alone or in combination with radioisotope (technetium-99m, Tc) with three novel techniques for sentinel lymph node detection in breast cancer: indocyanine green fluorescence (ICG), superparamagnetic iron oxide (SPIO) nanoparticles and contrast-enhanced ultrasound imaging (CEUS). Methods: PubMed, Embase, the Cochrane Library, China Knowledge Research Integrated Database, ClinicalTrials.gov and OpenGrey databases were searched up to 31 November 2017, without language restriction. Studies that compared the detection performance of at least one of the novel methods (ICG, SPIO and CEUS) with that of traditional methods (blue dye and/or radioisotope) were included in network meta-analysis. Results: Thirty-five studies were included. Pooled risk ratios (RRs) for Tc (1·09, 95 per cent c.i. 1·04 to 1·15), ICG (1·12, 1·07 to 1·16) and SPIO (1·09, 1·01 to 1·18) showed statistically better performance in detecting sentinel lymph nodes than blue dye alone. ICG had the lowest false-negative rate, with a RR of 0·29 (0·16 to 0·54), followed by Tc (RR 0·44, 0·20 to 0·96) and SPIO (RR 0·45, 0·14 to 1·45), with blue dye alone as the reference group. Conclusion: SPIO or ICG alone are superior to blue dye alone and comparable to the standard dual-modality technique of blue dye with Tc.

Audit of Mental Capacity Assessment by Primary Care Physicians Versus Consultation-liaison Psychiatrists.

OBJECTIVE: To review the mental capacity assessment of in-patients referred to consultation-liaison psychiatrists and to compare the assessment first made by primary care physicians. METHODS: Medical records of in-patients who were referred to consultation-liaison psychiatrists for mental capacity assessment between May and October 2015 were retrospectively reviewed. Assessment was first made by a primary care physician; complex cases were referred to a consultation-liaison psychiatrist. Audit of each case note was conducted independently by at least two of the authors. RESULTS: Medical records of 37 female and 26 male in-patients aged 24 to 91 (mean, 68.2) years were audited. Only 33.3% of these patients had no psychiatric diagnosis. Overall, assessments by primary care physicians were suboptimal. Assessments by consultation-liaison psychiatrists were more detailed, with documentation of mental capacity (93.7%) and psychiatric diagnosis (88.9%). Nonetheless, patient wishes and beliefs were poorly documented (19.0%), as were whether the patient had a lasting power of attorney or a court-appointed deputy (6.3%) and whether the patient had made advance care planning (0%). CONCLUSION: Overall, mental capacity assessment was inadequately performed by primary care physicians and consultation-liaison psychiatrists. More work needs to be done to engage, educate, and empower all stakeholders involved.

Energy transfer rate and electron-phonon coupling properties in Eu3+ -doped nanophosphors.

A series of controllable emissions SrWO4 :Eu3+ and charge-compensated SrWO4 : Eum3+ (m = 0.01 or 0.20) phosphors was successfully prepared via a simple co-precipitation method. The energy transfer mechanism was studied based on the Huang's theory. A low magnitude of Huang-Rhys factor (10-2 ) was calculated using phonon sideband spectra. The Judd-Ofelt parameters Ωλ (λ = 2, 4 and 6) of Eu3+ -activated SrWO4 doped with charge compensation were obtained. The calculated Commission Internationale de l'Eclairage chromaticity coordinates were found to be about (0.67, 0.33) for SrWO4 : Eu0.203+ and charge-compensated SrWO4 : Eu0.203+ phosphors, which coincided with the National Television Standard Committee system standard values for red. A white light emission was obtained under 362 nm excitation. The correlated color temperature was computed by a simple equation to characterize light sources. Thus, warm white light-emitting diodes with higher Ra can be constructed by combining as-prepared high efficiency, low correlated color temperature and high color purity phosphor.

miR-200 promotes the mesenchymal to epithelial transition by suppressing multiple members of the Zeb2 and Snail1 transcriptional repressor complexes.

The miR-200 family promotes the epithelial state by suppressing the Zeb1/Zeb2 epithelial gene transcriptional repressors. To identify other miR-200-regulated genes, we isolated mRNAs bound to transfected biotinylated miR-200c in mouse breast cancer cells. In all, 520 mRNAs were significantly enriched in miR-200c binding at least twofold. Putative miR-200-regulated genes included Zeb2, enriched 3.5-fold in the pull down. However, Zeb2 knockdown does not fully recapitulate miR-200c overexpression, suggesting that regulating other miR-200 targets contributes to miR-200's enhancement of epithelial gene expression. Candidate genes were highly enriched for miR-200c seed pairing in their 3'UTR and coding sequence and for genes that were downregulated by miR-200c overexpression. Epidermal growth factor receptor and downstream MAPK signaling pathways were the most enriched pathways. Genes whose products mediate transforming growth factor (TGF)-ß signaling were also significantly overrepresented, and miR-200 counteracted the suppressive effects of TGF-ß and bone morphogenic protein 2 (BMP-2) on epithelial gene expression. miR-200c regulated the 3'UTRs of 12 of 14 putative miR-200c-binding mRNAs tested. The extent of mRNA binding to miR-200c strongly correlated with gene suppression. Twelve targets of miR-200c (Crtap, Fhod1, Smad2, Map3k1, Tob1, Ywhag/14-3-3γ, Ywhab/14-3-3ß, Smad5, Zfp36, Xbp1, Mapk12, Snail1) were experimentally validated by identifying their 3'UTR miR-200 recognition elements. Smad2 and Smad5 form a complex with Zeb2 and Ywhab/14-3-3ß and Ywhag/14-3-3γ form a complex with Snail1. These complexes that repress transcription assemble on epithelial gene promoters. miR-200 overexpression induced RNA polymerase II localization and reduced Zeb2 and Snail1 binding to epithelial gene promoters. Expression of miR-200-resistant Smad5 modestly, but significantly, reduced epithelial gene induction by miR-200. miR-200 expression and Zeb2 knockdown are known to inhibit cell invasion in in vitro assays. Knockdown of each of three novel miR-200 target genes identified here, Smad5, Ywhag and Crtap, also profoundly suppressed cell invasion. Thus, miR-200 suppresses TGF-ß/BMP signaling, promotes epithelial gene expression and suppresses cell invasion by regulating a network of genes.

Late-intervention study with ebselen in an experimental model of type 1 diabetic nephropathy.

BACKGROUND AND AIM: Previous studies have shown that preventive treatment with the antioxidant, ebselen, in experimental models of type 1 diabetic nephropathy resulted in an attenuation of structural and functional damage in the kidney. However, evidence for the effectiveness of ebselen in late-intervention studies is lacking. Thus, we aimed to investigate the effects of ebselen in attenuating established renal injury in type 1 diabetic nephropathy using the Akita mouse model. METHODS: Baseline blood glucose and albumin-to-creatinine ratio (ACR) were measured in wild-type (WT) and heterozygous Akita mice at 9 weeks of age. At 10 weeks of age, WT and Akita mice were randomized to receive either vehicle (5% carboxymethyl cellulose) or ebselen by oral gavage at 10mg/kg twice daily. Kidney and urine were collected after 16 weeks of treatment with ebselen for histological and functional analyses. RESULTS: At 9 weeks of age, Akita mice displayed well-established renal dysfunction with significant increases in ACR and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels when compared with WT controls. After 16 weeks of treatment with ebselen, oxidative stress, as measured by nitrotyrosine immunostaining and urinary 8-OHdG levels, was significantly reduced in the Akita mice. Furthermore, gene expression of the major reactive oxygen species-producing nicotinamide adenine dinucleotide phosphate enzyme, Nox4, was also reduced by ebselen. However, ebselen had no effect on ACR and glomerulosclerosis. CONCLUSION: Chronic treatment with ebselen significantly reduced oxidative stress in the Akita mice. However, ebselen failed to attenuate functional or structural kidney damage in this late-intervention study using the Akita mouse model.

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin.

The use of nanomaterials has raised safety concerns, as their small size facilitates accumulation in and interaction with biological tissues. Here we show that exposure of endothelial cells to TiO2 nanomaterials causes endothelial cell leakiness. This effect is caused by the physical interaction between TiO2 nanomaterials and endothelial cells' adherens junction protein VE-cadherin. As a result, VE-cadherin is phosphorylated at intracellular residues (Y658 and Y731), and the interaction between VE-cadherin and p120 as well as ß-catenin is lost. The resulting signalling cascade promotes actin remodelling, as well as internalization and degradation of VE-cadherin. We show that injections of TiO2 nanomaterials cause leakiness of subcutaneous blood vessels in mice and, in a melanoma-lung metastasis mouse model, increase the number of pulmonary metastases. Our findings uncover a novel non-receptor-mediated mechanism by which nanomaterials trigger intracellular signalling cascades via specific interaction with VE-cadherin, resulting in nanomaterial-induced endothelial cell leakiness.

Ministry of health clinical practice guidelines: screening of cardiovascular disease and risk factors.

The Ministry of Health (MOH) publishes clinical practice guidelines on Screening of Cardiovascular Disease and Risk Factors to provide doctors and patients in Singapore with evidence-based guidance on the screening of cardiovascular disease and risk factors. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Screening of Cardiovascular Disease and Risk Factors, for the information of readers of the Singapore Medical Journal. Page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=25776). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Childhood adversity and adult depressive disorder: a case-controlled study in Malaysia.

OBJECTIVE: To describe the association between childhood adversity and depression in adult depressed patients in a Malaysian population. METHODS: Fifty-two patients, who met the criteria for major depressive disorder or dysthymia according to the Structured Clinical Interview based on the revised 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders, were used as cases and compared with 52 controls matched for age and sex. Cases and controls were assessed using a sexual and physical abuse questionnaire and a Parental Bonding Instrument. RESULTS: There was a positive relationship between childhood abuse in general and childhood physical abuse with adult depressive disorder in particular. Nearly a quarter (23%) of depressed patients reported being abused in childhood compared with none in the control group. There was no significant association between childhood loss and depression in adulthood. Low level of parental care during childhood was significantly correlated with adult depressive disorder. CONCLUSION: Clinicians should assiduously seek a history of childhood adversities in adult patients with depression. This information can influence clinical management by way of implementing secondary preventive measures. In all depressed patients, mental health professionals also need to look out for their poor attachment with parents during childhood. This may enable interventions directed at parenting skills and improved attachment relationships with their own children. These types of interventions together with pharmacotherapy may provide the optimal approach to the management of depression in adults and help prevent the cycle of depression perpetuating itself in the next generation.

Breast cancer knowledge and screening practices: a survey of 1,000 Asian women.

INTRODUCTION: The incidence of breast cancer in Asia is rapidly rising. Knowledge and perception often influence attendance at screening programmes. However, there has not been any survey to assess the level of knowledge of breast cancer in an Asian population. Singapore has a multiracial population and is the only Asian country with a national screening programme. We conducted a survey on 1,000 women to assess their level of knowledge and screening practices. METHODS: A self-administered questionnaire was used, where one point was given for a correct answer and zero for an incorrect / "not sure" response. The maximum knowledge score was 19. The women were also surveyed for their screening practices. Points were not assigned to questions on practice. RESULTS: The response rate was 100 percent. The mean score was 11.4 and the median was 12 (range 0-19). The scores were high for general knowledge and disease progression, but poor for risk factors, screening, symptoms and treatment. Several myths and misconceptions were prevalent. Only 53 percent did regular breast self-examination (BSE), while 57 percent of women aged 40 years and above had gone for a screening mammogram. Increasing age, Malay race, lower educational level, lower socioeconomic class and not knowing anyone with breast cancer were significant independent predictors of poor knowledge. Higher educational level and knowledge scores were significant independent predictors of BSE practice and screening mammogram attendance. CONCLUSION: Knowledge affects practice. Public education is required to correct misconceptions and focus on women with poor knowledge. This would help to improve screening attendance rates.

CD8+ T-cell responses to tumor-associated antigens correlate with superior relapse-free survival after allo-SCT.

The GVL effect following allo-SCT is one of the most prominent examples showing the ability of the immune system to eliminate malignant hematological diseases. Tumor-associated Ags (TAA), for instance WT1 and proteinase-3, have been proposed as targets for T cells to establish a GVL effect. Here, we examined an additional TAA (MUC1) as a possible T-cell target of GVL-related immune responses. We have defined new peptide epitopes from the MUC1 Ag to broaden patients' screening and to expand the repertoire of immunologic monitoring as well as for therapeutic approaches in the future. Twenty-eight patients after allo-SCT have been screened for T-cell responses toward TAA (proteinase-3, WT1, MUC1). We could detect a significant relationship between relapse and the absence of a TAA-specific T-cell response, whereby only 2/13 (15%) patients with TAA-specific CTL relapsed, in contrast to 9/15 (60%) patients without TAA-specific CTL responses (P<0.05). In conclusion, CD8(+) T-cell responses directed to TAA might contribute to the GVL effect. These observations highlight both the importance and the potential of immunotherapeutic approaches after allo-SCT.

The contrasting presentation and management of pseudoangiomatous stromal hyperplasia of the breast.

Pseudoangiomatous stromal hyperplasia of the breast is a benign entity characterised by dense, collagenous proliferation of mammary stroma, forming interanastomosing capillary-like spaces lined by slender spindle cells. These spaces are not true vascular spaces, hence the term "pseudoangiomatous". We report two 14-year-old girls, who presented to us with pseudoangiomatous stromal hyperplasia of the breast. We believe that our patients represent two of the youngest ethnic Chinese females to be reported with this rare condition. The development of such a rapidly enlarging lesion often leads to anxiety and concern about malignancy, and emphasises the importance in appropriate diagnosis and management. We discuss the aetiology, clinical presentation, radiological and pathological features, as well as management of this unusual condition.

Improving B mode ultrasound evaluation of breast lesions with real-time ultrasound elastography--a clinical approach.

Ultrasound elastography using the extended combined auto-correlation method of tissue elasticity allows for real-time strain image visualisation using a free-hand probe with concurrent conventional B mode imaging. Four hundred and fifteen consecutive women with 550 breast lesions confirmed on B mode ultrasound were assessed with elastography using the elasticity score. There were 119 malignant and 431 benign lesions. The elastography sensitivity was 78.0%, specificity was 98.5% and overall accuracy was 93.8%. The median score for malignancy was 5 and that for benign lesions was 2. There was good correlation with B mode BIRADS category. 98.6% of lesions with an elasticity score of 2 or below (95%CI=96.8-99.4) were benign. BIRADS 3 lesions with an elasticity score of 2 or below may be re-classified as BIRADS 2 lesions. We found that 15.3% of BIRADS 2 and 3 lesions with an elasticity score of 3 were malignant. Real-time ultrasound elastography is user-friendly with a high accuracy rate, thereby improving B mode ultrasound assessment.

Adoptive immunotherapy of HCMV infection.

Human cytomegalovirus (HCMV) infection or reactivation is a frequent cause of morbidity and mortality in immunocompromised individuals such as transplant recipients. Primary HCMV infection or reactivation of HCMV from latency is mostly asymptomatic in immunocompetent individuals and is controlled by the host's cell-mediated immune response. Healthy HCMV seropositive individuals develop high frequencies of HCMV-specific cytotoxic T lymphocytes (CTL) in the peripheral blood. Furthermore, a direct correlation between the recovery of HCMV-specific CTL responses and an improved outcome of HCMV disease could be demonstrated in immunocompromised patients. Deriving from these observations, the strategy of an adoptive transfer of HCMV-specific T cells has been developed. Protective immunity can be transferred successfully by the infusion of donor-derived HCMV-specific CD8+ cytotoxic T-cell clones or cell lines. In addition, several studies have supported the importance of antiviral effector functions of Th cells in maintaining CTL responses after adoptive transfer and their capacity to produce antiviral cytokines. Until today, a broad variety of clinical protocols for HCMV-specific immunotherapy has been published. These protocols vary regarding the isolation procedure, composition of cellular product, number of transferred cells and thus treatment efficacy. In this review, we aim to provide a comprehensive synopsis of the current standard of knowledge concerning cellular HCMV-specific immunotherapeutic approaches.

Delayed fungal infection following augmentation mammoplasty in an immunocompetent host.

We report an unusual case of infection of a breast implant with Trichosporon spp. in an immunocompetent host. There has only been one other reported case in the published literature. The patient was a healthy 27-year-old woman who presented with pain and swelling 17 months after augmentation mammoplasty with a saline implant. Ultrasound-guided aspiration of the effusion surrounding the implant yielded Trichosporon spp. on culture. Oral therapy with fluconazole was commenced, and the implant was salvaged. The nature of this fungi, its mode of transmission and treatment are reviewed. The implications and management of implant infections are also discussed. Physicians should be aware that infection may be delayed, and cultures should be performed for aerobic and anaerobic organisms as well as acid-fast bacilli and fungi. Prompt and appropriate antimicrobial treatment may arrest the infection, sparing the patient the morbidity of a surgical drainage or implant removal.

Am I breast cancer smart? Assessing breast cancer knowledge among health professionals.

INTRODUCTION: Health professionals are a direct source of medical information to the public. Hence, it is crucial that their knowledge is accurate and aids in building awareness. Our aim was to ascertain the level of breast cancer knowledge and screening practices among nurses in a general hospital. METHODS: Between January and April 2004, all registered nurses in a general hospital were surveyed by a self-administered questionnaire for their knowledge of breast cancer and screening practices. One point was given for a correct knowledge answer and zero for wrong/"not sure" answer. The maximum knowledge score was 19. RESULTS: There were 716 (79.4 percent) respondents. The median score was 16 (range 2-19). The scores were high for general knowledge and natural disease progression, fair for knowledge of symptoms and treatment, but dropped when it came to knowledge of risk factors and screening. Nurses also held several common misconceptions held by the public. Those who had managed breast cancer patients had higher total scores (15.7). Only 63 percent did regular breast self-examination (BSE) and only 35 percent had gone for a screening mammogram. Chinese nurses who had managed breast cancer patients were more likely to do regular BSE. CONCLUSION: Nurses working in a general hospital had good knowledge of breast cancer progression, average understanding of symptoms and treatment, but lacked knowledge in risk factors and screening. They had low BSE and mammographic screening rates. Experience in managing breast cancer patients improved their knowledge and practices.

How relevant is breast cancer screening in the Asia/Pacific region?

Nationwide breast cancer screening with mammography is well-established in many western countries. Many studies have shown its benefit in mortality reduction. However, breast cancer screening in Asia has been slow to implement, as it was perceived that the breast cancer incidence was low and the parenchyma of Asian women was difficult to assess mammographically. With changing disease patterns, breast cancer is now one of the most common cancers amongst women in Asia. Breast cancer screening has become an important and relevant health problem. However, apart from biological differences between western and Asian women, cultural and economic considerations need to be addressed. This paper looks at the various issues pertaining to the feasibility and relevance of population-based screening in the Asia/Pacific region.