Propionibacterium acnes bacteriophages display limited genetic diversity and broad killing activity against bacterial skin isolates.

UnlabelledInvestigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne.ImportancePropionibacterium acnes is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11 P. acnes phages, thereby substantially increasing the amount of available genomic information about this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages, P. acnes phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of P. acnes; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne

Response Parameters for SMS Text Message Assessments Among Pregnant and General Smokers Participating in SMS Cessation Trials.

INTRODUCTION: Despite a substantial increase in use of SMS text messages for collecting smoking-related data, there is limited knowledge on the parameters of response. This study assessed response rates, response speed, impact of reminders and predictors of response to text message assessments among smokers. METHODS: Data were from two SMS cessation intervention trials using clinical samples of pregnant (n = 198) and general smokers (n = 293) sent text message assessments during 3-month cessation programs. Response rates were calculated using data from the host web-server. Changes in response over time, impact of reminders and potential demographic (age, gender, ethnicity, parity, and deprivation) and smoking (nicotine dependence, determination to quit, prenatal smoking history, smoking status at follow-up) predictors of response were analyzed. RESULTS: Mean response rates were 61.9% (pregnant) and 67.8% (general) with aggregated median response times of 0.35 (pregnant) and 0.64 (general) hours. Response rate reduced over time (P = .003) for general smokers only. Text message reminders had a significant effect on response (Ps < .001), with observed mean increases of 13.8% (pregnant) and 17.7% (general). Age (odds ratio [OR] = 0.95, 95% confidence interval [CI] 0.90-1.00) and deprivation (OR = 0.98, 95% CI 0.96-1.00) weakly predicted response among pregnant smokers and nonsmoking status at 4 weeks follow-up (OR = 8.63, 95% CI 3.03-24.58) predicted response among general smokers. CONCLUSIONS: Text message assessments within trial-based cessation programs yield rapid responses from a sizable proportion of smokers, which can be increased using text reminders. While few sources of nonresponse bias were identified for general smokers, older and more deprived pregnant women were less likely to respond. IMPLICATIONS: This study demonstrates that most pregnant and general smokers enrolled in a cessation trial will respond to a small number of questions about their smoking sent by text message, mostly within 1 hour of being sent the assessment text message. For those who do not initially respond, our findings suggest that 24- and 48-hour text message reminders are likely to increase response a small but meaningful amount. However, older age and higher deprivation among pregnant smokers and relapse among general smokers is likely to reduce the chance of response.The MiQuit feasibility trial was funded by Cancer Research UK (CR-UK) grant number C1345/A5809. The iQuit in Practice trial was funded by the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR).This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/ntr/ntv26

Environmental influences on affect and cognition: A study of natural and commercial semi-public spaces

Research has consistently shown differences in affect and cognition after exposure to different physical environments. The time course of these differences emerging or fading during exploration of environments is less explored, as most studies measure dependent variables only before and after environmental exposure. In this within-subject study, we used repeated surveys to measure differences in thought content and affect throughout a 1-h environmental exploration of a nature conservatory and a large indoor mall. At each survey, participants reported on aspects of their most recent thoughts (e.g., thinking of the present moment vs. the future; thinking positively vs. negatively) and state affect. Using Bayesian multi-level models, we found that while visiting the conservatory, participants were more likely to report thoughts about the past, more positive and exciting thoughts, and higher feelings of positive affect and creativity. In the mall, participants were more likely to report thoughts about the future and higher feelings of impulsivity. Many of these differences in environments were present throughout the 1-h walk, however some differences were only evident at intermediary time points, indicating the importance of collecting data during exploration, as opposed to only before and after environmental exposures. We also measured cognitive performance with a dual n-back task. Results on 2-back trials replicated results from prior work that interacting with nature leads to improvements in working-memory performance. This study furthers our understanding of how thoughts and feelings are influenced by the surrounding physical environment and has implications for the design and use of public spaces

Evaluating outcomes of therapies offered by occupational therapists in adult mental health

Background: Attitudes towards the use of outcome measures by professionals working in mental health have been shown to be variable. Occupational therapists appear to have difficulty specifying goals and measuring the outcomes of interventions. Aims: To measure the outcomes of therapies offered by occupational therapists and to assess concurrent validity of the Van du Toit Model of Creative Ability (VdT MoCA) assessment. Method: The Global Assessment of Functioning (GAF), VdT MoCA assessment and Canadian Occupational Performance Measure (COPM) were used. Changes in mean scores on the measures were assessed using appropriate tests. Correlations between measures were assessed using Spearman's non-parametric test. Results: Mean post-therapy scores were significantly higher than pre-therapy scores on all three measures. VdT MoCA assessment scores pre- and post-therapy were highly correlated with GAF scores. The COPM outcome scores were uncorrelated with VdT MoCA assessment and GAF scores. Conclusions: The results offer a promising indication that occupational therapy interventions may increase functioning and thus aid clients' recovery. The VdT MoCA assessment is promising as a measure of improvement in functioning. Further research is needed to confirm these results and to further explore issues around occupational therapists' use of outcome measures

The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation

Independent of its known role in NF-κB transcription, the HOIL-1L containing LUBAC is required for assembly and activation of the NLRP3 inflammasome via linear ubiquitination of ASC.Linear ubiquitination is a newly discovered posttranslational modification that is currently restricted to a small number of known protein substrates. The linear ubiquitination assembly complex (LUBAC), consisting of HOIL-1L, HOIP, and Sharpin, has been reported to activate NF-κB–mediated transcription in response to receptor signaling by ligating linear ubiquitin chains to Nemo and Rip1. Despite recent advances, the detailed roles of LUBAC in immune cells remain elusive. We demonstrate a novel HOIL-1L function as an essential regulator of the activation of the NLRP3/ASC inflammasome in primary bone marrow–derived macrophages (BMDMs) independently of NF-κB activation. Mechanistically, HOIL-1L is required for assembly of the NLRP3/ASC inflammasome and the linear ubiquitination of ASC, which we identify as a novel LUBAC substrate. Consequently, we find that HOIL-1L−/− mice have reduced IL-1β secretion in response to in vivo NLRP3 stimulation and survive lethal challenge with LPS. Together, these data demonstrate that linear ubiquitination is required for NLRP3 inflammasome activation, defining the molecular events of NLRP3 inflammasome activation and expanding the role of LUBAC as an innate immune regulator. Furthermore, our observation is clinically relevant because patients lacking HOIL-1L expression suffer from pyogenic bacterial immunodeficiency, providing a potential new therapeutic target for enhancing inflammation in immunodeficient patients

Total smoking bans in psychiatric inpatient services: a survey of perceived benefits, barriers and support among staff

Background: The introduction of total smoking bans represents an important step in addressing the smoking and physical health of people with mental illness. Despite evidence indicating the importance of staff support in the successful implementation of smoking bans, limited research has examined levels of staff support prior to the implementation of a ban in psychiatric settings, or factors that are associated with such support. This study aimed to examine the views of psychiatric inpatient hospital staff regarding the perceived benefits of and barriers to implementation of a successful total smoking ban in mental health services. Secondly, to examine the level of support among clinical and non-clinical staff for a total smoking ban. Thirdly, to examine the association between the benefits and barriers perceived by clinicians and their support for a total smoking ban in their unit. Methods: Cross-sectional survey of both clinical and non-clinical staff in a large inpatient psychiatric hospital immediately prior to the implementation of a total smoking ban. Results: Of the 300 staff, 183 (61%) responded. Seventy-three (41%) of total respondents were clinical staff, and 110 (92%) were non-clinical staff. More than two-thirds of staff agreed that a smoking ban would improve their work environment and conditions, help staff to stop smoking and improve patients' physical health. The most prevalent clinician perceived barriers to a successful total smoking ban related to fear of patient aggression (89%) and patient non-compliance (72%). Two thirds (67%) of all staff indicated support for a total smoking ban in mental health facilities generally, and a majority (54%) of clinical staff expressed support for a ban within their unit. Clinical staff who believed a smoking ban would help patients to stop smoking were more likely to support a smoking ban in their unit. Conclusions: There is a clear need to more effectively communicate to staff the evidence that consistently applied smoking bans do not increase patient aggression. There is also a need to communicate the benefits of smoking bans in aiding the delivery of smoking cessation care, and the benefits of both smoking bans and such care in aiding patients to stop smoking

A Field Trial of Alternative Targeted Screening Strategies for Chagas Disease in Arequipa, Peru

In the wake of emerging T. cruzi infection in children of periurban Arequipa, Peru, we conducted a prospective field trial to evaluate alternative targeted screening strategies for Chagas disease across the city. Using insect vector data that is routinely collected during Ministry of Health insecticide application campaigns in 3 periurban districts of Arequipa, we separated into 4 categories those households with 1) infected vectors; 2) high vector densities; 3) low vector densities; and 4) no vectors. Residents of all infected-vector households and a random sample of those in the other 3 categories were invited for serological screening for T. cruzi infection. Subsequently, all residents of households within a 15-meter radius of detected seropositive individuals were invited to be screened in a ring case-detection scheme. Of 923 participants, 21 (2.28%) were seropositive. There were no significant differences in prevalence across the 4 screening strategies, indicating that household entomologic factors alone could not predict the risk of infection. Indeed, the most predictive variable of infection was the number of years a person lived in a location with triatomine insects. Therefore, a simple residence history questionnaire may be a useful screening tool in large, diverse urban environments with emerging Chagas disease

A History of Chagas Disease Transmission, Control, and Re-Emergence in Peri-Rural La Joya, Peru

The historically rural problem of Chagas disease is increasing in urban areas in Latin America. Peri-rural development may play a critical role in the urbanization of Chagas disease and other parasitic infections. We conducted a cross-sectional study in an urbanizing rural area in southern Peru, and we encountered a complex history of Chagas disease in this peri-rural environment. Specifically, we discovered: (1) long-standing parasite transmission leading to substantial burden of infection; (2) interruption in parasite transmission resulting from an undocumented insecticide application campaign; (3) relatively rapid re-emergence of parasite-infected vector insects resulting from an unsustained control campaign; (4) extensive migration among peri-rural inhabitants. Long-standing parasite infection in peri-rural areas with highly mobile populations provides a plausible mechanism for the expansion of parasite transmission to nearby urban centers. Lack of commitment to control campaigns in peri-rural areas may have unforeseen and undesired consequences for nearby urban centers. Novel methods and perspectives are needed to address the complexities of human migration and erratic interventions

Identifying allosteric fluctuation transitions between different protein conformational states as applied to Cyclin Dependent Kinase 2

BACKGROUND: The mechanisms underlying protein function and associated conformational change are dominated by a series of local entropy fluctuations affecting the global structure yet are mediated by only a few key residues. Transitional Dynamic Analysis (TDA) is a new method to detect these changes in local protein flexibility between different conformations arising from, for example, ligand binding. Additionally, Positional Impact Vertex for Entropy Transfer (PIVET) uses TDA to identify important residue contact changes that have a large impact on global fluctuation. We demonstrate the utility of these methods for Cyclin-dependent kinase 2 (CDK2), a system with crystal structures of this protein in multiple functionally relevant conformations and experimental data revealing the importance of local fluctuation changes for protein function. RESULTS: TDA and PIVET successfully identified select residues that are responsible for conformation specific regional fluctuation in the activation cycle of Cyclin Dependent Kinase 2 (CDK2). The detected local changes in protein flexibility have been experimentally confirmed to be essential for the regulation and function of the kinase. The methodologies also highlighted possible errors in previous molecular dynamic simulations that need to be resolved in order to understand this key player in cell cycle regulation. Finally, the use of entropy compensation as a possible allosteric mechanism for protein function is reported for CDK2. CONCLUSION: The methodologies embodied in TDA and PIVET provide a quick approach to identify local fluctuation change important for protein function and residue contacts that contributes to these changes. Further, these approaches can be used to check for possible errors in protein dynamic simulations and have the potential to facilitate a better understanding of the contribution of entropy to protein allostery and function

A randomised controlled trial linking mental health inpatients to community smoking cessation supports: A study protocol

<p>Abstract</p> <p>Background</p> <p>Mental health inpatients smoke at higher rates than the general population and are disproportionately affected by tobacco dependence. Despite the advent of smoke free policies within mental health hospitals, limited systems are in place to support a cessation attempt post hospitalisation, and international evidence suggests that most smokers return to pre-admission smoking levels following discharge. This protocol describes a randomised controlled trial that will test the feasibility, acceptability and efficacy of linking inpatient smoking care with ongoing community cessation support for smokers with a mental illness.</p> <p>Methods/Design</p> <p>This study will be conducted as a randomised controlled trial. 200 smokers with an acute mental illness will be recruited from a large inpatient mental health facility. Participants will complete a baseline survey and will be randomised to either a multimodal smoking cessation intervention or provided with hospital smoking care only. Randomisation will be stratified by diagnosis (psychotic, non-psychotic). Intervention participants will be provided with a brief motivational interview in the inpatient setting and options of ongoing smoking cessation support post discharge: nicotine replacement therapy (NRT); referral to Quitline; smoking cessation groups; and fortnightly telephone support. Outcome data, including cigarettes smoked per day, quit attempts, and self-reported 7-day point prevalence abstinence (validated by exhaled carbon monoxide), will be collected via blind interview at one week, two months, four months and six months post discharge. Process information will also be collected, including the use of cessation supports and cost of the intervention.</p> <p>Discussion</p> <p>This study will provide comprehensive data on the potential of an integrated, multimodal smoking cessation intervention for persons with an acute mental illness, linking inpatient with community cessation support.</p> <p>Trial Registration</p> <p>Australian and New Zealand Clinical Trials Registry ANZTCN: <a href="http://www.anzctr.org.au/ACTRN12609000465257.aspx">ACTRN12609000465257</a></p