Effectiveness of a symptom-clinic intervention delivered by general practitioners with an extended role for people with multiple and persistent physical symptoms in England: the Multiple Symptoms Study 3 pragmatic, multicentre, parallel-group, individually randomised controlled trial.

BACKGROUND: People with multiple and persistent physical symptoms have impaired quality of life and poor experiences of health care. We aimed to evaluate the effectiveness of a community-based symptom-clinic intervention in people with multiple and persistent physical symptoms, hypothesising that this symptoms clinic plus usual care would be superior to usual care only. METHODS: The Multiple Symptoms Study 3 was a pragmatic, multicentre, parallel-group, individually randomised controlled trial conducted in 108 general practices in the UK National Health Service in four regions of England between Dec 6, 2018, and June 30, 2023. Participants were individually randomised (1:1) to the symptom-clinic intervention plus usual care or to usual care only via a computer-generated, pseudo-random list stratified by trial centre. Allocation was done by the trial statistician and concealed with a centralised, web-based randomisation system; masking participants was not possible due to the nature of the intervention. The symptom-clinic intervention was a sequence of up to four medical consultations that aimed to elicit a detailed clinical history, fully hear and validate the participant, offer rational explanations for symptoms, and assist the participant to develop ways of managing their symptoms; it was delivered by general practitioners with an extended role. The primary outcome was Patient Health Questionnaire-15 (PHQ-15) score 52 weeks after randomisation, analysed by intention to treat. The trial is registered on the ISRCTN registry (ISRCTN57050216). FINDINGS: 354 participants were randomly assigned; 178 (50%) were assigned to receive the community-based symptoms clinic plus usual care and 176 (50%) were assigned to receive usual care only. At the primary-outcome point of 52 weeks, PHQ-15 scores were 14·1 (SD 3·7) in the group receiving usual care and 12·2 (4·5) in the group receiving the intervention. The adjusted between-group difference of -1·82 (95% CI -2·67 to -0·97) was statistically significantly in favour of the intervention group (p<0·0001). There were 39 adverse events in the group receiving usual care and 36 adverse events in the group receiving the intervention. There were no statistically significant between-group differences in the proportion of participants who had non-serious adverse events (-0·03, 95% CI -0·11 to 0·05) or serious adverse events (0·02, -0·02 to 0·07). No serious adverse event was deemed to be related to the trial intervention. INTERPRETATION: Our symptom-clinic intervention, which focused on explaining persistent symptoms to participants in order to support self-management, led to sustained improvement in multiple and persistent physical symptoms. FUNDING: UK National Institute for Health and Care Research.

Glucocerebrosidase reduces the spread of protein aggregation in a Drosophila melanogaster model of neurodegeneration by regulating proteins trafficked by extracellular vesicles.

Abnormal protein aggregation within neurons is a key pathologic feature of Parkinson's disease (PD). The spread of brain protein aggregates is associated with clinical disease progression, but how this occurs remains unclear. Mutations in glucosidase, beta acid 1 (GBA), which encodes glucocerebrosidase (GCase), are the most penetrant common genetic risk factor for PD and dementia with Lewy bodies and associate with faster disease progression. To explore how GBA mutations influence pathogenesis, we previously created a Drosophila model of GBA deficiency (Gba1b) that manifests neurodegeneration and accelerated protein aggregation. Proteomic analysis of Gba1b mutants revealed dysregulation of proteins involved in extracellular vesicle (EV) biology, and we found altered protein composition of EVs from Gba1b mutants. Accordingly, we hypothesized that GBA may influence pathogenic protein aggregate spread via EVs. We found that accumulation of ubiquitinated proteins and Ref(2)P, Drosophila homologue of mammalian p62, were reduced in muscle and brain tissue of Gba1b flies by ectopic expression of wildtype GCase in muscle. Neuronal GCase expression also rescued protein aggregation both cell-autonomously in brain and non-cell-autonomously in muscle. Muscle-specific GBA expression reduced the elevated levels of EV-intrinsic proteins and Ref(2)P found in EVs from Gba1b flies. Perturbing EV biogenesis through neutral sphingomyelinase (nSMase), an enzyme important for EV release and ceramide metabolism, enhanced protein aggregation when knocked down in muscle, but did not modify Gba1b mutant protein aggregation when knocked down in neurons. Lipidomic analysis of nSMase knockdown on ceramide and glucosylceramide levels suggested that Gba1b mutant protein aggregation may depend on relative depletion of specific ceramide species often enriched in EVs. Finally, we identified ectopically expressed GCase within isolated EVs. Together, our findings suggest that GCase deficiency promotes accelerated protein aggregate spread between cells and tissues via dysregulated EVs, and EV-mediated trafficking of GCase may partially account for the reduction in aggregate spread.

Exploring Undergraduate Nursing Students' Preferences in Psychiatric Nursing Simulation Modalities.

BACKGROUND: The use of high-fidelity simulators (manikins) and standardized patients (SPs) in simulation has been incorporated into many nursing schools throughout the nation to augment the clinical rotation experience. There is little to no data available on comparing undergraduate students' preferences between SPs and manikins in psychiatric nursing. METHODS: A quantitative descriptive exploratory design was used to evaluate pre-licensure nursing students' preferences in both traditional 4-year Bachelor of Science in Nursing (BSN) and accelerated BSN programs (ABSN). RESULTS: Overall, students preferred having an SP over a manikin to learn how to properly perform a nursing assessment on a psychiatric patient. CONCLUSIONS: Standardized patients offer a more realistic experience when assessing various domains of the mental status examination and when practicing therapeutic communication techniques in psychiatric nursing. The growth of SP training programs should be fostered. Well-trained SPs are an asset to simulation, especially in psychiatric nursing.

Cost-utility analysis of shockwave lithotripsy vs ureteroscopic stone treatment in adults.

OBJECTIVES: To assess the cost-effectiveness, resource use implications, quality-adjusted life-years (QALYs) and cost per QALY of care pathways starting with either extracorporeal shockwave lithotripsy (SWL) or with ureteroscopic retrieval (ureteroscopy [URS]) for the management of ureteric stones. PATIENTS AND METHODS: Data on quality of life and resource use for 613 patients, collected prospectively in the Therapeutic Interventions for Stones of the Ureter (TISU) randomized controlled trial (ISRCTN 92289221), were used to assess the cost-effectiveness of two care pathways, SWL and URS. A health provider (UK National Health Service) perspective was adopted to estimate the costs of the interventions and subsequent resource use. Quality-of-life data were calculated using a generic instrument, the EuroQol EQ-5D-3L. Results are expressed as incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. RESULTS: The mean QALY difference (SWL vs URS) was -0.021 (95% confidence interval [CI] -0.033 to -0.010) and the mean cost difference was -£809 (95% CI -£1061 to -£551). The QALY difference translated into approximately 10 more healthy days over the 6-month period for the patients on the URS care pathway. The probabaility that SWL is cost-effective is 79% at a society's willingness to pay (WTP) threshold for 1 QALY of £30,000 and 98% at a WTP threshold of £20,000. CONCLUSION: The SWL pathway results in lower QALYs than URS but costs less. The incremental cost per QALY is £39 118 cost saving per QALY lost, with a 79% probability that SWL would be considered cost-effective at a WTP threshold for 1 QALY of £30 000 and 98% at a WTP threshold of £20 000. Decision-makers need to determine if costs saved justify the loss in QALYs.

Understanding the student's experience of community health nursing simulations.

OBJECTIVES: The purpose of this study was to explore nursing students' experiences after completing community health nursing simulation encounters. METHODS: The study used a descriptive qualitative design. Through conventional content analysis, the research team analyzed the experiences of 73 nursing students after participating in community health nursing simulation encounters. The data come from nursing students' responses to three post-simulation qualitative questions. RESULTS: Nursing students identified both positive aspects (simulation as a great learning method, useful in understanding community health nurses' roles, faculty's role in facilitating an effective learning environment) and opportunities for improvement (needing for clear objectives, expectations, and roles). CONCLUSIONS: Community health nursing simulation encounters can be a powerful educational method to help students experience and understand the roles of community health nurses. IMPLICATIONS FOR INTERNATIONAL AUDIENCE: Augmentation of the pre-brief component will further improve students' simulation experiences.

The effect of patient-centered communication on medication intake: an experimental study.

It is not only crucial to provide patients with information, but also to communicate this information in a way to enable patient participation in health decisions. Experimental studies investigating the association between the communication style of health professionals and patients' health decisions are rare, which limits causal conclusions. This study investigated the effect of a doctor's patient-centered communication style on the likelihood to take a medication.Healthy women (N = 120) were randomly allocated to one of three groups. They either received a medical consultation characterized by a patient-centered communication style (PC group) or by a doctor-centered communication style (DC group) or they received no consultation at all (control group). All participants were told that the study would investigate the effects of a 'concentration-enhancing medication'. Voluntary intake of the medication (a placebo pill) served as behavioral outcome. Participants' self-rated intention to take the medication was measured at three assessment points. Data were analyzed using a Chi-square-test and a mixed analysis of covariance.In each group, 40 participants were analyzed. Following the consultation, groups did not differ regarding the behavioral outcome, but participants' intention to take the medication was higher in the PC group compared with the control group.Our results indicate that patient-centered communication has a beneficial influence on participants' intention to take medication. Future studies should investigate the role of communication in individuals with health conditions that require a specified treatment plan and taking medication over the long-term.

Glucocerebrosidase deficiency promotes protein aggregation through dysregulation of extracellular vesicles.

Mutations in the glucosylceramidase beta (GBA) gene are strongly associated with neurodegenerative diseases marked by protein aggregation. GBA encodes the lysosomal enzyme glucocerebrosidase, which breaks down glucosylceramide. A common explanation for the link between GBA mutations and protein aggregation is that lysosomal accumulation of glucosylceramide causes impaired autophagy. We tested this hypothesis directly by measuring protein turnover and abundance in Drosophila mutants with deletions in the GBA ortholog Gba1b. Proteomic analyses revealed that known autophagy substrates, which had severely impaired turnover in autophagy-deficient Atg7 mutants, showed little to no overall slowing of turnover or increase in abundance in Gba1b mutants. Likewise, Gba1b mutants did not have the marked impairment of mitochondrial protein turnover seen in mitophagy-deficient parkin mutants. Proteasome activity, microautophagy, and endocytic degradation also appeared unaffected in Gba1b mutants. However, we found striking changes in the turnover and abundance of proteins associated with extracellular vesicles (EVs), which have been proposed as vehicles for the spread of protein aggregates in neurodegenerative disease. These changes were specific to Gba1b mutants and did not represent an acceleration of normal aging. Western blotting of isolated EVs confirmed the increased abundance of EV proteins in Gba1b mutants, and nanoparticle tracking analysis revealed that Gba1b mutants had six times as many EVs as controls. Genetic perturbations of EV production in Gba1b mutants suppressed protein aggregation, demonstrating that the increase in EV abundance contributed to the accumulation of protein aggregates. Together, our findings indicate that glucocerebrosidase deficiency causes pathogenic changes in EV metabolism and may promote the spread of protein aggregates through extracellular vesicles.

Assessing Undergraduate Student Nurses' Performance in Various Public Health Roles Using Simulation.

Purpose: To expose students to various public health roles and complement clinical experience using simulated encounters.Design: This exploratory study assessed students' performance of basic nursing tasks for three public health nurse roles.Methods: 15-guided questions were used to evaluate a convenience sample of 137 students' expected performance compared to their actual performance of basic nursing skills.Findings: Students' performed well in all nurse roles with some significant differences in completing a few critical tasks in the case manager and school nurse roles.Conclusion: Simulation can address gaps in nursing programs and expose student nurses to various public health roles using real-life scenarios.Clinical Evidence: Lack of clinical sites in public health limits students' experience to a myriad of nurse functions within communities.

Genome-wide association study for insect bite hypersensitivity susceptibility in horses revealed novel associated loci on chromosome 1.

Equine insect bite hypersensitivity (IBH) is a pruritic skin allergy caused primarily by biting midges, Culicoides spp. IBH susceptibility has polygenic inheritance and occurs at high frequencies in several horse breeds worldwide, causing increased costs and reduced welfare of affected horses. The aim of this study was to identify and validate single nucleotide polymorphisms (SNPs) associated with equine IBH susceptibility. After quality control, 33,523 SNPs were included in a Bayesian genome-wide association study on 177 affected and 178 unaffected Icelandic horses. We report associated regions in E. caballus (ECA) 1, 3, 15 and 18, overlapping with known IBH QTLs in horses, and novel regions containing several genes, together explaining 11.46% of the total genetic variance. For validation, three SNPs on ECA 1 and ECA X (explaining the largest percentage of genetic variance) within 1-mb genomic windows for IBH were genotyped in an independent population of 280 Exmoor ponies. The associated genomic region (152-153 mb) on ECA 1 was confirmed in Exmoor ponies and contains the AQR gene involved in splicing processes and a long non-coding RNA. This study confirms the polygenic nature of IBH susceptibility and suggests a role of transcriptional regulatory mechanisms (e.g., alternative splicing) for IBH predisposition in these horse breeds.

Using simulation to evaluate exam scores in a public health nursing course.

OBJECTIVE: Public health nursing courses typically incorporate clinical components but rarely offer simulation education as part of clinical practice. There is limited research examining the impact of simulation for public health nursing courses on final exam scores. The objective of this study was to determine the impact of simulation training on final exam scores in a public health nursing course. DESIGN: Public health scenarios were created to provide hands-on experience in two settings. Home and school environments were used with discussion of students' performance during debriefing. SAMPLE: Using a convenience sample, final exam scores were compared between nursing students (n = 79) who participated in a public health nursing simulation and two similar student groups (n = 97) that did not participate in simulation. RESULTS: Students with simulation training scored higher in both public health domains (Community Health; Clinical Prevention and Population Health). A significant difference in total mean final scores (p = .04; p = .02) was noted between groups of students with simulation training and those without. CONCLUSION: The difference in mean final scores suggests that simulation may be an effective educational modality in preparing students toward their state board or end of semester exams.

Targeted Use of Alcohol-Based Hand Rub on Gloves During Task Dense Periods: One Step Closer to Pathogen Containment by Anesthesia Providers in the Operating Room.

BACKGROUND: Anesthesia providers' hand hygiene practices in the operating room may contribute to the transmission of bacteria. There is a debate, however, over the best approaches for pathogen containment during task dense periods (induction and extubation) of anesthesia care. A novel approach to reducing pathogen spread during these task dense periods is the use of alcohol-based hand rub on gloves when it may be difficult to either change gloves or clean hands. METHODS: To evaluate the impact of alcohol-based hand rub on gloves, we estimated perforation rates of 50 gloves that were worn as pairs by volunteers for 2 hours at a time applying alcohol-based hand rub every 15 minutes (total of 8 alcohol-based hand rub applications per pair of gloves). We also identified perforation rates of 50 new, unused gloves. To evaluate the ability to perform routine anesthesia functions, volunteers were asked to pick up a coin from a table top and document whether the gloves felt normal or sticky at each 15-minute period. RESULTS: Fifty new gloves (not exposed to alcohol-based hand rub) were tested for integrity using the Food and Drug Administration-approved process, and one was found to have a microperforation. Of the 50 gloves that had been applied with alcohol-based hand rub 8 times, no microperforations were identified. All volunteers demonstrated tactile competence by picking up a coin from a table top after 8 alcohol-based hand rub applications; in addition, as the number of alcohol-based hand rub applications progressed, the volunteers reported increased stickiness. CONCLUSIONS: This study suggests that the use of alcohol-based hand rub on commonly used nitrile examination gloves does not compromise glove integrity or hamper the ability to safely perform routine anesthesia functions.

Does Adherence to World Health Organization Hand Hygiene Protocols in the Operating Room Have the Potential to Produce Irritant Contact Dermatitis in Anesthesia Providers?

Anesthesia providers have the burden of constant hand hygiene during task dense periods. The requirement for hand hygiene often demands frequent application of alcohol-based hand rub. To assess whether frequent alcohol-based hand rub use leads to skin changes or irritant contact dermatitis, volunteers cleaned their hands with alcohol-based hand rub every 15 minutes for 8 hours for 5 sequential days. They were examined by a dermatologist before and after and asked about subjective skin changes. Results suggest an increase in irritant contact dermatitis scores and subjective complaints.

Glucocerebrosidase Deficiency in Drosophila Results in α-Synuclein-Independent Protein Aggregation and Neurodegeneration.

Mutations in the glucosidase, beta, acid (GBA1) gene cause Gaucher's disease, and are the most common genetic risk factor for Parkinson's disease (PD) and dementia with Lewy bodies (DLB) excluding variants of low penetrance. Because α-synuclein-containing neuronal aggregates are a defining feature of PD and DLB, it is widely believed that mutations in GBA1 act by enhancing α-synuclein toxicity. To explore this hypothesis, we deleted the Drosophila GBA1 homolog, dGBA1b, and compared the phenotypes of dGBA1b mutants in the presence and absence of α-synuclein expression. Homozygous dGBA1b mutants exhibit shortened lifespan, locomotor and memory deficits, neurodegeneration, and dramatically increased accumulation of ubiquitinated protein aggregates that are normally degraded through an autophagic mechanism. Ectopic expression of human α-synuclein in dGBA1b mutants resulted in a mild enhancement of dopaminergic neuron loss and increased α-synuclein aggregation relative to controls. However, α-synuclein expression did not substantially enhance other dGBA1b mutant phenotypes. Our findings indicate that dGBA1b plays an important role in the metabolism of protein aggregates, but that the deleterious consequences of mutations in dGBA1b are largely independent of α-synuclein. Future work with dGBA1b mutants should reveal the mechanism by which mutations in dGBA1b lead to accumulation of protein aggregates, and the potential influence of this protein aggregation on neuronal integrity.

PINK1-Parkin pathway activity is regulated by degradation of PINK1 in the mitochondrial matrix.

Loss-of-function mutations in PINK1, which encodes a mitochondrially targeted serine/threonine kinase, result in an early-onset heritable form of Parkinson's disease. Previous work has shown that PINK1 is constitutively degraded in healthy cells, but selectively accumulates on the surface of depolarized mitochondria, thereby initiating their autophagic degradation. Although PINK1 is known to be a cleavage target of several mitochondrial proteases, whether these proteases account for the constitutive degradation of PINK1 in healthy mitochondria remains unclear. To explore the mechanism by which PINK1 is degraded, we performed a screen for mitochondrial proteases that influence PINK1 abundance in the fruit fly Drosophila melanogaster. We found that genetic perturbations targeting the matrix-localized protease Lon caused dramatic accumulation of processed PINK1 species in several mitochondrial compartments, including the matrix. Knockdown of Lon did not decrease mitochondrial membrane potential or trigger activation of the mitochondrial unfolded protein stress response (UPRmt), indicating that PINK1 accumulation in Lon-deficient animals is not a secondary consequence of mitochondrial depolarization or the UPRmt. Moreover, the influence of Lon on PINK1 abundance was highly specific, as Lon inactivation had little or no effect on the abundance of other mitochondrial proteins. Further studies indicated that the processed forms of PINK1 that accumulate upon Lon inactivation are capable of activating the PINK1-Parkin pathway in vivo. Our findings thus suggest that Lon plays an essential role in regulating the PINK1-Parkin pathway by promoting the degradation of PINK1 in the matrix of healthy mitochondria.

Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. METHODS: For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 µg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. FINDINGS: Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain). INTERPRETATION: Tamsulosin 400 µg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

A community empowerment approach to the HIV response among sex workers: effectiveness, challenges, and considerations for implementation and scale-up.

A community empowerment-based response to HIV is a process by which sex workers take collective ownership of programmes to achieve the most effective HIV outcomes and address social and structural barriers to their overall health and human rights. Community empowerment has increasingly gained recognition as a key approach for addressing HIV in sex workers, with its focus on addressing the broad context within which the heightened risk for infection takes places in these individuals. However, large-scale implementation of community empowerment-based approaches has been scarce. We undertook a comprehensive review of community empowerment approaches for addressing HIV in sex workers. Within this effort, we did a systematic review and meta-analysis of the effectiveness of community empowerment in sex workers in low-income and middle-income countries. We found that community empowerment-based approaches to addressing HIV among sex workers were significantly associated with reductions in HIV and other sexually transmitted infections, and with increases in consistent condom use with all clients. Despite the promise of a community-empowerment approach, we identified formidable structural barriers to implementation and scale-up at various levels. These barriers include regressive international discourses and funding constraints; national laws criminalising sex work; and intersecting social stigmas, discrimination, and violence. The evidence base for community empowerment in sex workers needs to be strengthened and diversified, including its role in aiding access to, and uptake of, combination interventions for HIV prevention. Furthermore, social and political change are needed regarding the recognition of sex work as work, both globally and locally, to encourage increased support for community empowerment responses to HIV.

The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo.

The accumulation of damaged mitochondria has been proposed as a key factor in aging and the pathogenesis of many common age-related diseases, including Parkinson disease (PD). Recently, in vitro studies of the PD-related proteins Parkin and PINK1 have found that these factors act in a common pathway to promote the selective autophagic degradation of damaged mitochondria (mitophagy). However, whether Parkin and PINK1 promote mitophagy under normal physiological conditions in vivo is unknown. To address this question, we used a proteomic approach in Drosophila to compare the rates of mitochondrial protein turnover in parkin mutants, PINK1 mutants, and control flies. We found that parkin null mutants showed a significant overall slowing of mitochondrial protein turnover, similar to but less severe than the slowing seen in autophagy-deficient Atg7 mutants, consistent with the model that Parkin acts upstream of Atg7 to promote mitophagy. By contrast, the turnover of many mitochondrial respiratory chain (RC) subunits showed greater impairment in parkin than Atg7 mutants, and RC turnover was also selectively impaired in PINK1 mutants. Our findings show that the PINK1-Parkin pathway promotes mitophagy in vivo and, unexpectedly, also promotes selective turnover of mitochondrial RC subunits. Failure to degrade damaged RC proteins could account for the RC deficits seen in many PD patients and may play an important role in PD pathogenesis.

The influence of high fidelity simulation on first responders retention of CPR knowledge.

INTRODUCTION: The purpose of this study was to identify the impact of high-fidelity simulation on the retention of basic life support cardiopulmonary resuscitation (CPR) knowledge among a group of healthcare providers (HCPs). METHODS: A twenty-five question exam was completed by nurses and nurse technicians over a two-year period before and after mandatory CPR training with high-fidelity simulation. RESULTS: Most HCPs scored near 50% or below the passing score (80%) with a mean range of scores between 28% and 84%. HCPs missed questions on the exam that requested specific details related to technique or human physiology during CPR. CONCLUSION: The current teaching method for basic life support may be enhanced by using high-fidelity simulation, but this modality alone is not enough to support HCPs retention of CPR knowledge. Additional studies are needed to identify strategies that will help HCPs remember specific and detailed information in the CPR algorithm.

Synthesis and biological activity of novel mono-indole and mono-benzofuran inhibitors of bacterial transcription initiation complex formation.

Our ongoing research focused on targeting transcription initiation in bacteria has resulted in synthesis of several classes of mono-indole and mono-benzofuran inhibitors that targeted the essential protein-protein interaction between RNA polymerase core and σ(70)/σ(A) factors in bacteria. In this study, the reaction of indole-2-, indole-3-, indole-7- and benzofuran-2-glyoxyloyl chlorides with amines and hydrazines afforded a variety of glyoxyloylamides and glyoxyloylhydrazides. Similarly, condensation of 2- and 7-trichloroacetylindoles with amines and hydrazines delivered amides and hydrazides. The novel molecules were found to inhibit the RNA polymerase-σ(70)/σ(A) interaction as measured by ELISA, and also inhibited the growth of both Gram-positive and Gram-negative bacteria in culture. Structure-activity relationship (SAR) studies of the mono-indole and mono-benzofuran inhibitors suggested that the hydrophilic-hydrophobic balance is an important determinant of biological activity.