Quality-Adjusted Life Year Proxies for Caries in Primary Dentition: A Discrete Choice Experiment.

INTRODUCTION: Cost-utility analysis (CUA)-a method to evaluate intervention cost-effectiveness-transforms benefits of alternatives into a measure of quantity and quality of life, such as quality-adjusted life year (QALY), to enable comparison across heterogeneous programs. Measurement challenges prevent directly estimating utilities and calculating QALYs for caries in primary dentition. Proxy disease QALYs are often used as a substitute; however, there lacks quantitative evidence that these proxy diseases are comparable to caries. OBJECTIVE: To employ a discrete choice experiment (DCE) to quantitatively determine the most comparable proxy disease for different levels of caries in primary dentition. METHODS: A cross-sectional DCE survey was administered to respondents (N = 461) who resided in California, were aged ≥18 y, and were primary caretakers for ≥1 child aged 3 to 12 y. Four attributes were included: pain level, disease duration, treatment cost, and family life impacts. Mixed effects logistic regression and conditional logistic regression were used to analyze the survey data. RESULTS: Respondents from the overall sample preferred no pain over mild (odds ratio [OR] = 0.50, P < 0.05), moderate (OR = 0.57, P < 0.05), and severe pain (OR = 0.48, P < 0.05). Acute gastritis (OR = 0.44, P < 0.05), chronic gastritis (OR = 0.31, P < 0.01), and cold sore (OR = 0.38, P < 0.05) were less preferred than stage 1 caries. Acute tonsilitis (OR = 0.43, P < 0.05), acute gastritis (OR = 0.38, P < 0.05), chronic gastritis (OR = 0.26, P < 0.01), and cold sore (OR = 0.33, P < 0.01) were less preferred than stage 2 caries. Chronic gastritis (OR = 0.42,P < 0.05) was less preferred than stage 4 caries. CONCLUSIONS: Parents viewed the characteristics of many diseases with similar QALYs differently. Findings suggest that otitis media and its QALY-as commonly used in CUAs-may be a suitable proxy disease and substitute. However, other disease states with slightly different QALYs may be suitable. As such, the recommendation is to consider a range of proxy diseases and their QALYs when conducting a CUA for child caries interventions. KNOWLEDGE TRANSFER STATEMENT: This study reviews and systematically compares pediatric diseases that are comparable to caries in primary dentition. The findings may inform future research using cost-utility analysis to examine the incremental cost-effectiveness ratio of interventions to prevent and treat caries as compared with an alternative.

How Does Environmental Noise Impact Collaborative Activities at the Main Library of Tecnologico de Monterrey?

Environmental noise is an important social issue that directly affects the efficiency of the students. The aim of this study is to investigate how environmental noise generated in the library affects the performance at learning commons. For this study, the noise of the library was recorded and sixteen students of Tecnologico de Monterrey, were recruited. They were divided into four groups, and two collaborative activities were undertaken with and without noise. In both scenarios, the performance and the physiological reaction of students were investigated. The results showed that the students had a 4% higher performance in a quiet environment than in a noisy one, in the same way, the heart rate increased by 3.48% and the blink rate by 22.91%. Finally, the neural electrical activity was reduced by at least 3%. The findings of the present study suggest that collaborative work is difficult to undertake in noise scenarios such as learning commons, where no appropriated policies are established and followed. Cognitive performance is lower in noisy than in quiet conditions.

Myo1g is required for efficient adhesion and migration of activated B lymphocytes to inguinal lymph nodes.

Cell migration is a dynamic process that involves adhesion molecules and the deformation of the moving cell that depends on cytoskeletal remodeling and actin-modulating proteins such as myosins. In this work, we analyzed the role of the class I Myosin-1 g (Myo1g) in migratory processes of LPS + IL-4 activated B lymphocytes in vivo and in vitro. In vivo, the absence of Myo1g reduced homing of activated B lymphocytes into the inguinal lymph node. Using microchannel chambers and morphology analysis, we found that the lack of Myo1g caused adhesion and chemotaxis defects. Additionally, deficiency in Myo1g causes flaws in adopting a migratory morphology. Our results highlight the importance of Myo1g during B cell migration.

Phase II study of single-agent panitumumab in patients with incurable cutaneous squamous cell carcinoma.

BACKGROUND: Although advanced cutaneous squamous cell carcinoma (CSCC) is quite common, there are few prospective trials regarding its optimal management. This study evaluated the efficacy and safety of single-agent panitumumab in the treatment of patients with CSCC not suitable for local therapy. PATIENTS AND METHODS: Sixteen patients received single-agent panitumumab at a dose of 6 mg/kg repeated every 2 weeks for a minimum of three cycles and continued until progression, a maximum of nine cycles or dose-limiting toxicity. The primary end point was the best overall response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) criteria. Secondary end points included evaluation of safety, toxicity and progression-free survival (PFS). RESULTS: Between May 2010 and May 2012, 16 patients were recruited. Fourteen patients were male and the median age was 68 years. Fifteen patients had locoregionally advanced or recurrent disease with 14 patients receiving previous radiotherapy and 7 receiving previous cytotoxic chemotherapy. The best ORR [partial (PR) or complete response (CR)] was 31% (3/16 PR, 2/16 CR) with a further 6 of 16 patients achieving SD. The median PFS and overall survival were 8 and 11 months respectively. Grade 3 or 4 events were observed in five patients (four being skin toxicity) with one patient ceasing due to skin toxicity. With a median follow-up of 24 months, 10 patients died due to progressive disease, 6 are alive, one patient with no evidence of disease at the time of analysis. CONCLUSIONS: Single-agent panitumumab is safe and effective in the management of patients with advanced CSCC even in a previously extensively pre-treated cohort.

Hippocampal-sparing radiotherapy: the new standard of care for World Health Organization grade II and III gliomas?

The neurocognitive effects of cranial radiotherapy in patients with gliomas are well-recognised and may be related to the dose delivered to the hippocampi. Intensity modulated radiotherapy (IMRT) is a radiotherapy technique that can be used to selectively spare the hippocampi without compromising the dose delivered to the tumour. This study aimed to evaluate if hippocampal-sparing IMRT is achievable in patients with World Health Organization (WHO) grade II and III gliomas. A retrospective review of consecutive patients with WHO grade II and III gliomas treated with IMRT at our institution between January 2009 and August 2012 was performed. Hippocampal-sparing was defined as a mean dose to at least one hippocampus of less than 30 Gy. The dose delivered to the tumour was never compromised to achieve the hippocampal dose constraint. Logistic regression analyses were performed to identify predictive factors for achieving hippocampal-sparing treatment. Eighteen patients were identified and hippocampal-sparing was achieved in 14 (78%). The median dose prescribed was 59.4 Gy in 33 fractions and 11 patients had WHO grade III gliomas. The mean dose to the contralateral hippocampus was 24.9 Gy. Planning target volumes less than 420.5 cm3 were more likely to enable hippocampal-sparing treatment to be given (hazard ratio 1.7, p=0.03) and there was a trend with oligodendrogliomas and anaplastic oligodendrogliomas. Hippocampal-sparing radiotherapy is feasible in patients with WHO grade II and III gliomas. Oncologic outcomes are yet to be assessed prospectively. The relationship between hippocampal dose and neurocognitive function in adults is currently under investigation.

Overcoming cancer cell resistance to VSV oncolysis with JAK1/2 inhibitors.

Oncolytic vesicular stomatitis virus (VSV) has potent antitumor activity but some cancer cells are resistant to VSV killing, either constitutively or due to type I interferon (IFN) inducing an antiviral state in the cells. Here, we evaluated VSV oncolysis of a panel of human head and neck cancer cells and showed that VSV resistance in SCC25 and SCC15 cells could be reversed with Janus kinase (JAK) 1/2 inhibitors (JAK inhibitor I and ruxolitinib). Pre-treatment of cells with JAK1/2 inhibitors before or in conjunction with VSV enhanced viral infection, spread and progeny yield (100- to 1000-fold increase). In contrast, inhibitors of histone deacetylase (LBH589), phosphatidylinositol 3-kinase (GDC-0941, LY294002), mammalian target of rapamycin (rapamycin) or signal transducer and activator of transcription 3 (STAT3 inhibitor VII) were ineffective. Compared with VSV-sensitive SW579 cells, IFNα/ß responsive antiviral genes (IRF-9, IRF-7, OAS1 but not MxA) are constitutively expressed in SCC25 cells. Pretreatment with JAK inhibitors reduced mRNA levels of these genes, increasing VSV expression in the cells. Interestingly, 1 h of drug exposure was sufficient to reverse SCC25 resistance to VSV and was still effective if virus was added 24 h later. Overall, we show here that JAK inhibitor I and ruxolitinib (Jakafi) can reverse resistance to VSV, supporting the rationale to incorporate JAK1/2 inhibitors in future VSV virotherapy trials.

Lung cancer patients in Queensland suffer delays in receiving radiation therapy--but not as a result of distance.

AIM: To determine whether lung cancer radiation therapy waiting times in Queensland public hospitals are associated with distance of residence from the nearest treatment facility. METHODS: Retrospective analysis of radiation therapy waiting times of 1535 Queensland residents who were diagnosed with lung cancer from 2000 to 2004 and received radiation therapy as initial treatment at a public hospital. The effect of distance of residence from treatment centre on median waiting time was analysed by quantile regression controlling for sex, age, lung cancer histology, stage and therapeutic intent. RESULTS: The median waiting time from diagnosis to start of radiation therapy was 33 days for all patients. There was no significant difference (P = 0.141) in median waiting times in relation to distance of residence from a treatment centre. However, in most patients, waiting times were significantly longer than recommended by the Royal Australian and New Zealand College of Radiologists. Curative patients waited longer than palliative patients, while patients with earlier stage cancer waited longer than those with more advanced disease. CONCLUSION: Waiting times for radiation therapy among lung cancer patients in Queensland was not associated with distance from place of residence to the nearest public treatment facility. However, delays overall are excessive and are likely to worsen unless radiation treatment capabilities are enhanced to keep pace with population growth in Queensland.

Aplicaciones de la musicoterapia en la medicina / Medical uses of musical therapy

Music therapy is a science that has been applied since many centuries ago, but it has been organized as a profession during the past century. This science studies the therapeutic effects of music in human beings. Profesionals who practice this science are called "music therapists" and they must be trained not only in music theory and performance, but also in psychology, anatomy, research techniques, and other subjects. Today, we can find music therapy research in many areas such as the effects of music in children with autism, adults with psychiatric illnesses, elderly with Alzheimer and Parkinson disease, people with brain injuries, among others. Numerous studies demonstrate the functionality of music therapy in patients with neurological disorders. These studies show that music helps patients to gain control over their walking patterns after a brain injury, stimulates long and short term memory in patients with Alzheimer disease, and increase self esteem and social interaction in elders

RegulonDB (version 3.2): transcriptional regulation and operon organization in Escherichia coli K-12.

RegulonDB is a database on mechanisms of transcription regulation and operon organization in Escherichia coli K-12. The current version has considerably increased numbers of regulatory elements such as promoters, binding sites and terminators. The complete repertoire of known and predicted DNA-binding transcriptional regulators can be considered to be included in this version. The database now distinguishes different allosteric conformations of regulatory proteins indicating the one active in binding and regulating the different promoters. A new set of operon predictions has been incorporated. The relational design has been modified accordingly. Furthermore, a major improvement is a graphic display enabling browsing of the database with a Java-based graphic user interface with three zoom-levels connected to properties of each chromosomal element. The purpose of these modifications is to make RegulonDB a useful tool and control set for transcriptome experiments. RegulonDB can be accessed on the web at the URL: http://www.cifn.unam.mx/Computational_Biology/++ +regulondb/

RegulonDB (version 3.0): transcriptional regulation and operon organization in Escherichia coli K-12.

RegulonDB is a database on transcription regulation and operon organization in Escherichia coli. The current version describes regulatory signals of transcription initiation, promoters, regulatory binding sites of specific regulators, ribosome binding sites and terminators, as well as information on genes clustered in operons. These specific annotations have been gathered from a constant search in the literature, as well as based on computational sequence predictions. The genomic coordinates of all these objects in the E.coli K-12 chromosome are clearly indicated. Every known object has a link to at least one MEDLINE reference. We have also added direct links to recent expression data of E.coli K-12. The version presented here has important modifications both in the structure of the database, as well as in the amount and type of information encoded in the database. RegulonDB can be accessed on the web at URL: http://www.cifn.unam. mx/Computational_Biology/regulondb/