Assessing the need to update prevention guidelines: a comparison of two methods.

BACKGROUND: An important concern for developers of clinical practice guidelines is how best to determine when guidelines require updating to ensure they remain current and evidence based. Because of the high costs associated with updating guidelines, recent attention has focused on approaches that can reliably assess the extent of updating required. Recently, Shekelle and colleagues proposed a model of limited literature searches with modest expert involvement as a way to reduce the cost and time requirements for assessing whether a guideline needs updating. METHODS: The main objective of this study was to compare the Shekelle et al. assessment model (review approach) and a conventional process using typical systematic review methods (traditional approach) in terms of comprehensiveness and effort. We modeled the review approach on that by Shekelle and colleagues but refined it iteratively over three phases to achieve greater efficiency. Using both methods independently, we assessed the need to update six topics from the 1996 Guide to Clinical Preventive Services from the US Preventive Services Task Force. Main outcomes included completeness of study identification, importance of missed studies and the effort involved. RESULTS: Although the review approach identified fewer eligible studies than the traditional approach, none of the studies missed was rated as important by task force members acting as liaisons to the project with respect to whether the topic required an update. On average, the review approach produced substantially fewer citations to review than the traditional approach. The effort involved and potential time saving depended largely on the scope of the topic. CONCLUSIONS: The revised review approach provides an efficient and acceptable method for judging whether a guideline requires updating.     

Reported use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors was not associated with reduced recurrence of colorectal adenomas.

We did a secondary analysis of data from three large colorectal adenoma chemoprevention trials to assess the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor use and reduced risk of recurrent colorectal adenomas. Reported use of HMG-CoA reductase inhibitors was not associated with a reduced recurrence of colorectal adenomas, multiple adenomas, or advanced adenomas. Lack of statistical power from limited exposure to HMG-CoA reductase inhibitors might be responsible for the lack of association.     

Functional characterization of the Sporothrix schenckii Ktr4 and Ktr5, mannosyltransferases involved in the N-linked glycosylation pathway

Sporothrix schenckii is one of the causative agents of the deep-seated mycosis sporotrichosis, a fungal infection with worldwide distribution. Fungus-specific molecules and biosynthetic pathways are potential targets for the development of new antifungal drugs. The MNT1/KRE2 gene family is a group of genes that encode fungus-specific Golgi-resident mannosyltransferases that participate in the synthesis of O-linked and N-linked glycans. While this family is composed of five and nine members in Candida albicans and Saccharomyces cerevisiae, respectively, the S. schenckii genome contains only three putative members. MNT1 has been previously characterized as an enzyme that participates in the synthesis of both N-linked and O-linked glycans. Here, we aimed to establish the functional role of the two remaining family members, KTR4 and KTR5, in the protein glycosylation pathways by using heterologous complementation in C. albicans mutants lacking genes of the MNT1/KRE2 family. The two S. schenckii genes restored defects in the elaboration of N-linked glycans, but no complementation of mutants that synthesize truncated O-linked glycans was observed. Therefore, our results suggest that MNT1 is the sole member with a role in O-linked glycan elaboration, whereas the three family members have redundant activity in the S. schenckii N-linked glycan synthesis.     

Factors Associated with Tobacco Use among Iranian Adolescents: An Application of Protection Motivation Theory

Background: Tobacco use is a significant predisposing factor to many diseases. Protection motivation theory is a well-suited theory, since fear can motivate individuals to change their unhealthy behaviors. Objective: This study was conducted to examine the associations between the constructs of this theory with intention and tobacco use behavior. Method: The present cross-sectional study was conducted in Noshahr, Iran. The participants were 440 high school boys selected using a stratified random sampling in 2016. A questionnaire about tobacco use based on protection motivation theory was developed and its validity and reliability were assessed. The questionnaire included the demographic information, the constructs of theory, and tobacco use behavior. Structural equation modeling was used to test the associations between the constructs with intention and tobacco use. Results: The variables of perceived vulnerability (β = 0/137, P < 0.001), fear (β = 0/149, P < 0.001), self-efficacy (β = 0/249, P < 0.001), perceived intrinsic reward (β = ?0.285, P < 0.001), threat appraisal (β = ?0.25, P < 0.001), and coping appraisal (β = 0.358, P < 0.001) had direct effect and are significant with intention. Moreover, perceived vulnerability (β = ?0.158, P < 0.001), fear (β = ?0.172, P < 0.001), self-efficacy (β = ?0.288, P < 0.001), perceived intrinsic reward (β = 0.329, P < 0.001), threat appraisal (β = 0.265, P < 0.001), and coping appraisal (β = ?0.379, P < 0.001) affected tobacco use indirectly through intention and were significantly associated with behavior. Also, intention had direct effect and is significant with tobacco use (β = ?1.156, P < 0.001). Conclusions: The protection motivation theory provides a useful framework for investigating factors of tobacco use among male students. Future tobacco prevention interventions should focus on increasing the vulnerability and fear, decreasing intrinsic reward, and improving self-efficacy to reduce tobacco use.     

Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix

During the process of tumor progression, cancer cells can produce the requisite growth- and invasion-promoting factors and can also rely on noncancerous cells in the tumor microenvironment as an alternative, cell-extrinsic source. However, whether the cellular source influences the function of such tumor-promoting factors remains an open question. Here, we examined the roles of the cathepsin Z (CtsZ) protease, which is provided by both cancer cells and macrophages in pancreatic neuroendocrine tumors in humans and mice. We found that tumor proliferation was exclusively regulated by cancer cell-intrinsic functions of CtsZ, whereas tumor invasion required contributions from both macrophages and cancer cells. Interestingly, several of the tumor-promoting functions of CtsZ were not dependent on its described catalytic activity but instead were mediated via the Arg–Gly–Asp (RGD) motif in the enzyme prodomain, which regulated interactions with integrins and the extracellular matrix. Together, these results underscore the complexity of interactions within the tumor microenvironment and indicate that cellular source can indeed impact molecular function.     

High and Low Stimulus-Driven Conflict Engage Segregated Brain Networks,Not Quantitatively Different Resources

Task-irrelevant information is constantly present in our environment and may interfere with the processing of the information necessary to achieve goal-directed behavior. While task goals determine which information must be suppressed, the demand for inhibitory control depends on the strength of the interference induced by incoming, task-irrelevant information. Whether the same or distinct inhibitory processes are engaged to suppress various degrees of interference from task-irrelevant information remains largely unresolved. We investigated this question by manipulating the strength of the conflict induced by automatic word reading in a classical color Stroop task. High conflict was induced by presenting words in participant’s native language and low conflict by presenting words in a less familiar language. Behavioral performance and electrical neuroimaging analyses of event-related potentials to the words were analyzed following a two-by-two within-subject design with factors conflict strength (high; low) and color word/word ink congruency (congruent; incongruent). Behaviorally, we observed a significant conflict strength × congruency driven by a smaller Stroop effect in the low- than high conflict condition. Electrophysiologically, we observed a significant conflict strength × congruency interaction at the topographic level during the period of the N450 components, indicative of the engagement of distinct configurations of brain networks. No such interaction was found at the level of response strength. Electrical sources analyses localized the topographic effect within the anterior cingulate cortex and basal ganglia, left middle frontal and occipital areas. We interpret our results in terms of qualitatively distinct executive mechanisms for reactive inhibitory control in conditions of high versus low stimulus-driven conflict.     

Well-Being and Perceived Quality of Life in Elderly People Displaced After the Earthquake in L’Aquila,Italy

On 6 April 2009, the city of L’Aquila was hit by a violent earthquake that destroyed almost all of its medieval centre, and the surviving inhabitants were evacuated and relocated in temporary quarters or undamaged homes. The aim of this study was to investigate the perceived quality of life of the elderly population 3 years after the earthquake in relation to the social and logistic issues of new housing. The study was carried out between October 2011 and March 2012, and involved 571 subjects aged over 65 years living in the municipality of L’Aquila. The interviews took place in the surgeries of general practitioners and the city’s Department of Prevention and Vaccination in the anti-influenza immunisation period. The instrument used was a 36-item questionnaire with closed, multiple choice answers divided into the following sections: demographics, everyday activities, health and perceived health, and the quality of life in the city. The results show that, 3 years after the earthquake, the elderly population living in the new towns and temporary housing of L’Aquila have a worse perception of their quality of life than the others. They feel a certain social isolation and wish to live elsewhere. Governments faced with the problems arising from a natural calamity should take into account all of the elements making up a good quality of life and, before making choices whose impact cannot be changed, consider both their immediate and long-term social consequences.     

Effect of Ventilation Systems on Prevalence of Symptoms Associated with “Sick Buildings” in Brazilian Commercial Establishments

In this questionnaire study, the authors compared the prevalence of certain symptoms and signs associated with Sick Building Syndrome and perceptions relative to environmental discomfort of employees in a central-air-conditioned shopping center and in natural-ventilation commercial shops located on the streets of Niteröi, Rio de Janeiro, Brazil. There was a statistically significant higher prevalence of symptoms (e.g., water and itching of eyes, sore throat, nose irritation, difficulty breathing, skin irritation, sneezing) that were characteristic of Sick Building Syndrome in the air-conditioned building than in the naturally ventilated stores. The results indicated that there exists a continuing need for further research in Brazilian work environments.