Novel Biomarkers Distinguishing Active Tuberculosis from Latent Infection Identified by Gene Expression Profile of Peripheral Blood Mononuclear Cells

BACKGROUND: Humans infected with Mycobacterium tuberculosis (MTB) can delete the pathogen or otherwise become latent infection or active disease. However, the factors influencing the pathogen clearance and disease progression from latent infection are poorly understood. This study attempted to use a genome-wide transcriptome approach to identify immune factors associated with MTB infection and novel biomarkers that can distinguish active disease from latent infection. METHODOLOGY/PRINCIPAL FINDINGS: Using microarray analysis, we comprehensively determined the transcriptional difference in purified protein derivative (PPD) stimulated peripheral blood mononuclear cells (PBMCs) in 12 individuals divided into three groups: TB patients (TB), latent TB infection individuals (LTBI) and healthy controls (HC) (n = 4 per group). A transcriptional profiling of 506 differentially expressed genes could correctly group study individuals into three clusters. Moreover, 55- and 229-transcript signatures for tuberculosis infection (TB&LTBI) and active disease (TB) were identified, respectively. The validation study by quantitative real-time PCR (qPCR) performed in 83 individuals confirmed the expression patterns of 81% of the microarray identified genes. Decision tree analysis indicated that three genes of CXCL10, ATP10A and TLR6 could differentiate TB from LTBI subjects. Additional validation was performed to assess the diagnostic ability of the three biomarkers within 36 subjects, which yielded a sensitivity of 71% and specificity of 89%. CONCLUSIONS/SIGNIFICANCE: The transcription profiles of PBMCs induced by PPD identified distinctive gene expression patterns associated with different infectious status and provided new insights into human immune responses to MTB. Furthermore, this study indicated that a combination of CXCL10, ATP10A and TLR6 could be used as novel biomarkers for the discrimination of TB from LTBI

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version

predicting treatment response in major depression

Objective: Is it possible to predict the antidepressant treatment response in patients with major depressive disorder? For the antidepressant treatment, the common belief is to wait 6 weeks for deciding its effectiveness. It seem to be crucial to shorten this period for the patients with depressive symptoms in order to make earlier interventions. The aim of this survey is to find the association between early symptomatic improvement and the clinical response to antidepressant treatment in depression.Method: Eighty-seven participants who met the DSM-IV criteria for major depressive disorder in both inpatient and outpatient clinics were included in this study. During the initial, second, fourth and sixth weeks of the treatment Hamilton Depression Scale (HDS) were applied; the % 50 reduction of the HDS score achieved in the sixth week was defined as treatment response. The relation between the degree of decrease in second and fourth week HDS scores with the response in the sixth week were investigated.Results: At the end of sixth week, 73 (% 83.9) of 87 patients responded to their treatment, whereas 14 (% 16.1) of them did not. The correlation between the degree of reductions in HDS scores at the second and sixth weeks was not statistically significant, whereas statistically significant results were found between the decreases in HDS scores at fourth and sixth weeks.Discussion: The findings of this study suggest that the patients who did not respond to their treatment in the early stage did not show satisfactory response to their treatment afterwards. Based on the results, increasing the doses and switching the drugs may well be considered even in the early stages of the disorder

Treatment and outcome of traumatic elbow dislocation in children

Background. Isolated elbow dislocations are uncommon injuries in children. Especially the extent of ligamentous lesions and additional bony injuries are predictive for an unfavorable functional outcome; thus, these lesions must be given special consideration during the diagnostic workup. The aim of this case report is the presentation of treatment and outcome of an isolated traumatic elbow dislocation in a child. Case report. We present a 6-year-old girl with a traumatic elbow dislocation after a fall on the outstretched arm. No additional bony lesions were seen in the diagnostic workup. After closed reduction, isolated medial instability was discovered with tendency for subluxation. The MRI showed a tear of the medial collateral ligament. After immobilization for 6 days in an upper-arm cast, early functional treatment was started. The follow-up examination 6 weeks after trauma showed no pain with a full range of motion. Conclusion. The treatment of isolated elbow dislocation without additional bony injuries in children with plaster immobilization and early functional treatment showed an excellent functional outcome in our case. Detection of additional bony injuries of the elbow joint is crucial for the treatment of these injuries. In the long-term follow-up, restriction of the range of motion or persistent joint instability are rare