A dual function for a bacterial small RNA: SgrS performs base pairing-dependent regulation and encodes a functional polypeptide

SgrS is a 227-nt small RNA that is expressed in Escherichia coli during glucose-phosphate stress, a condition associated with intracellular accumulation of glucose-6-phosphate caused by disruption of glycolytic flux. Under stress conditions, SgrS negatively regulates translation and stability of the ptsG mRNA, encoding the major glucose transporter, by means of a base pairing-dependent mechanism requiring the RNA chaperone Hfq. SgrS activity mitigates the effects of glucose-phosphate stress, and the present study has elucidated a function of SgrS that is proposed to contribute to the stress response. The 5' end of SgrS, upstream of the nucleotides involved in base pairing with the ptsG mRNA, contains a 43-aa ORF, sgrT, that is conserved in most species that contain SgrS-like small RNAs. The sgrT gene is translated in E. coli under conditions of glucose-phosphate stress. Analysis of alleles that separate the base pairing function of SgrS from the sgrT coding sequence revealed that either of these functions alone are sufficient for previously characterized SgrS phenotypes. SgrS-dependent down-regulation of ptsG mRNA stability does not require SgrT and SgrT by itself has no effect on ptsG mRNA stability. Cells expressing sgrT alone had a defect in glucose uptake even though they had nearly wild-type levels of PtsG (IICB(Glc)). Together, these data suggest that SgrS represents a previously unrecognized paradigm for small RNA (sRNA) regulators as a bifunctional RNA that encodes physiologically redundant but mechanistically distinct functions contributing to the same stress response.     

Patient Presentation and Management of Labial Ulceration Following Uterine Artery Embolization

Uterine artery embolization is a safe and effective procedure for the treatment of symptomatic uterine fibroids. Nontarget embolization of adjacent internal iliac artery branches is a reported complication of uterine artery embolization. The following report describes the presentation and management of ulcerations of the labium minora due to nontarget embolization of the internal pudendal artery.     

Predictors of general quality of life and the mediating role of health related quality of life in patients with schizophrenia

Introduction  The concept ‘quality of life’ (QoL) has become increasingly important as an outcome measure in the evaluation of services and in clinical trials of people with schizophrenia. This study examines the mediating role of health related quality of life (HRQoL) in the prediction of general quality of life (GQoL). Method  QoL and other patient- and illness characteristics (psychopathology, overall functioning, illness history, self-esteem and social integration) were measured in a group of 143 outpatients with schizophrenia. GQoL was measured by the Lancashire Quality of Life Profile and HRQoL was measured by the MOS SF-36. To test the temporal stability of our findings, assessments were performed twice with an 18-month interval. Results  We found that patient’s GQoL is predicted mainly by anxiety and depression and self-esteem and to a lesser extent by global functioning and social integration. At both time intervals HRQoL appeared to be a significant mediator of the relationship between anxiety and depression and self esteem versus patient’s GQoL. Conclusions  The results of this study are important for mental health professionals, as these provide more insight in the mechanisms by which they could improve the GQoL of their patients with schizophrenia. The results confirm that diagnosis and treatment of anxiety and depression in outpatients with schizophrenia deserves careful attention of clinicians. Also strategies and specific interventions to improve self-esteem of patients with schizophrenia are very important to maximise patient’s QoL.     

Task-dependent modulations of prefrontal and hippocampal activity during intrinsic word production

Functional imaging studies of single word production have consistently reported activation of the lateral prefrontal and cingulate cortex. Its contribution has been shown to be sensitive to task demands, which can be manipulated by the degree of response specification. Compared with classical verbal fluency, free word association relies less on response restrictions but to a greater extent on associative binding processes, usually subserved by the hippocampus. To elucidate the relevance of the frontal and medial-temporal areas during verbal retrieval tasks, we applied varying degrees of response specification. During fMRI data acquisition, 18 subjects performed a free verbal association (FVA), a semantic verbal fluency (SVF) task, and a phonological verbal fluency (PVF) task. Externally guided word production served as a baseline condition to control for basic articulatory and reading processes. As expected, increased brain activity was observed in the left lateral and bilateral medial frontal cortices for SVF and PVF. The anterior cingulate gyrus was the only structure common to both fluency tasks in direct comparison to the less restricted FVA task. The hippocampus was engaged during associative and semantic retrieval. Interestingly, hippocampal activity was selectively evident during FVA in direct comparison to SVF when it was controlled for stimulus-response relations. The current data confirm the role of the left prefrontal-cingulate network in constrained word production. Hippocampal activity during spontaneous word production is a novel finding and seems to be dependent on the retrieval process (free vs. constrained) rather than the variety of stimulus-response relationships that is involved.     

Critical review of economic evaluations in multiple myeloma: an overview of the economic evidence and quality of the methodology

Continued expansion in the availability of costly alternative therapies in multiple myeloma will enhance the role of economic evaluations in reimbursement decisions and amendments to the treatment guidelines. The quality of economic evaluations should be taken into account by clinicians involved in decision-making. A systematic review and critique of the methodology was performed to assess the trends and quality in economic evaluations in multiple myeloma to date. A literature search was conducted to identify full economic evaluations in multiple myeloma as of December 2009. Details of the economic evaluation methods applied were extracted. Each study underwent a quality assessment based on the Drummond checklist for appraisal of high-quality economic evaluations in health care. Eighteen published economic evaluations were identified. Stem cell transplantation in combination with intensive chemotherapy has been demonstrated to be cost-effective, while interferon alpha is generally ineffective at additional costs. Evaluations have become less frequent in the last decade, especially for newer therapies despite their important contribution to improvements in outcomes. The quality of the methodology applied and its documentation can be improved in many aspects. As users of the results of economic evaluations, clinicians involved in guiding decision-making should be critical of the quality of economic evaluations in multiple myeloma. To ensure access to and identification of high-quality studies, researchers conducting economic evaluations of future advances should strive towards evaluations that fulfil the Drummond criteria and are properly documented.     

A review of similarities between domain-specific determinants of four health behaviors among adolescents

Schools are overloaded with health promotion programs that, altogether, focus on a broad array of behavioral domains, including substance abuse, sexuality and nutrition. Although the specific content of programs varies according to the domain focus, programs usually address similar concepts: knowledge, attitudinal beliefs, social influences and skills. This apparent conceptual overlap between behaviors and programs provides opportunities for a transfer-oriented approach which will stimulate students to apply the knowledge and skills they have learned in one domain (e.g. skills for resisting tobacco use) to other domains (e.g. alcohol, sex). A requirement for such an approach is that behaviors share at least some determinants. This review addresses this issue by examining similarities between domain-specific determinants of smoking, drinking, safe sex and healthy nutrition among adolescents. Recent empirical studies and reviews were examined. The results show that the following determinants are relevant to all four behaviors: beliefs about immediate gratification and social advantages, peer norms, peer and parental modeling and refusal self-efficacy. Several other determinants have been found to relate to at least two behaviors, e.g. health risk beliefs and parental norms. These results can be used for the development of a transfer-oriented school health promotion curriculum.     

Nonsurgical airway management training for surgeons

PURPOSE: Airway management occupies a crucial component of surgical education. As such, it can be difficult to provide adequate training within the hospital setting alone. To be facile in all aspects of nonsurgical airway management, the surgical resident must have thorough cognitive understanding of the process as well as technical mastery. The Department of Surgery at the Methodist Hospital in Houston has developed a curriculum for nonsurgical airway management that uses multiple modalities for education, reinforcement, and testing. Didactic lectures based on established national guidelines are provided as a foundation. This method is supplemented by hands-on group scenarios that use inanimate models. Throughout the course, faculty leaders provide guidance and skills assessment. Residents are tested for competency using core value checklists based on knowledge and technical proficiency. During its pilot year, the curriculum has proven its need and success in residency education. Future improvements include development of specific clinical scenarios as well as integration of more advanced educational equipment and models for use in nonsurgical airway management. DEVELOPMENT OF THE ACTIVITY AND MATERIALS: Materials used for this program include an article by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway, the New England Journal of Medicine article entitled "Videos in clinical medicine. Orotracheal intubation" by Kabrhel et al,(2) "Management of the difficult and failed airway" by Hung and Murphy,(3) the American Heart Association Airway Management course 2007,(4) and the Manual of Emergency Airway Management by Walls et al.(5) EVALUATION COMPONENT: Before participating in the module, residents completed a written pretest and performed an initial simulation to establish a baseline. Residents then worked through a series of skills that provided experience in both the cognitive and the procedural aspects of airway management. To complete the module successfully, residents were required to attend three 3-hour sessions. After supervised practice, residents were tested on the procedural techniques via a procedural checklist and cognitive aspects with respect to emergency, crash, difficult, and failed airway algorithms.(1,5) The simulations are based on the 2003 American Society of Anesthesiologists Task Force on Management of the Difficult Airway Algorithms(1) and emergency, crash, difficult, and failed airway algorithms.(2,5) PROPOSED OUTCOME MEASURES: Proposed long-term outcome measures will include evaluations from faculty on a resident's noninvasive airway management skills and the resident's self-evaluation in actual noninvasive airway management situations. Resident performance will be evaluated by faculty using standardized checklists, review of simulation parameters, and review of audio-video recording of the simulation. EXPERIENCE TO DATE: This article describes our first implementation in the evolution of this module. The module was introduced to residents at all postgraduate levels in September 2007. Scores on pretests and performance on initial simulations were similar in all postgraduate years, with minimally superior pretest and initial simulation performance from the senior residents. Correct procedural adoption occurred rapidly after prebriefing and initial hands-on demonstration and supervised practice in simulated patient scenarios on airway mannequins. CONCLUSIONS AND NEXT STEPS: Our preliminary experience with a nonsurgical airway management training module for surgical residents has shown that a need for training exists in this critical area. Correct procedural adoption occurred rapidly after a didactic and procedural hands-on experience. Time intervals needed for review to maintain competence will also be studied. Improvements to the proficiency criteria and simulations are underway.     

Hippocampal dysfunction during free word association in male patients with schizophrenia

In schizophrenia, speech production deficits in patients with positive formal thought disorder (FTD e.g. loosening of associations and derailment) have been attributed to impairments in the semantic network. The brain area implicated in the retrieval of associated (i.e. relational) concepts is the hippocampus, a key region in the psychopathology of schizophrenia. However, its role in schizophrenic speech production and FTD in particular is yet little understood.

To investigate the neural correlates of associative verbal retrieval, twelve patients with schizophrenia with varying degrees of FTD and twelve matched healthy control subjects underwent a free verbal association (FVA), a semantic (SVF) and a phonological verbal fluency (PVF) task while brain activity was measured with fMRI. The tasks varied in the relational binding operations needed for linking the stimulus to the respective response.

Compared to control subjects, patients revealed attenuated left hippocampal activity during both semantic word generation tasks (FVA, SVF). Contrasting verbal fluency with FVA, a failure in recruiting the anterior cingulate gyrus emerged in the patient group. A negative correlation was found between right middle temporal activity and the severity of FTD during FVA.

The hippocampus seems to play a major role in word generation. In schizophrenia, attenuated hippocampal activity during semantic tasks strengthens the hypothesis of impaired relational memory processes, affecting thought and language.     

Awake insertion of the Bonfils Retromolar Intubation Fiberscope in five patients with anticipated difficult airways

Traditionally, an awake intubation is performed by flexible fiberoptic laryngoscopy. However, many new devices have been developed to assist anesthesiologists with both routine and difficult airway management, one of which is the Bonfils Retromolar Intubation Fiberscope. This device may be more beneficial than the flexible fiberoptic laryngoscope since it can readily navigate through soft tissue and physically lift airway structures, is more affordable, durable, and easier to clean. This case series demonstrates successful use of the Bonfils Scope in five patients for awake orotracheal intubation with anticipated difficult airways.