Antimicrobial peptide capsids of de novo design

The spread of bacterial resistance to antibiotics poses the need for antimicrobial discovery. With traditional search paradigms being exhausted, approaches that are altogether different from antibiotics may offer promising and creative solutions. Here, we introduce a de novo peptide topology that-by emulating the virus architecture-assembles into discrete antimicrobial capsids. Using the combination of high-resolution and real-time imaging, we demonstrate that these artificial capsids assemble as 20-nm hollow shells that attack bacterial membranes and upon landing on phospholipid bilayers instantaneously (seconds) convert into rapidly expanding pores causing membrane lysis (minutes). The designed capsids show broad antimicrobial activities, thus executing one primary function-they destroy bacteria on contact

A cross sectional evaluation of a total smoking ban at a large Australian university

Background: Total smoking bans have been found to contribute positively to the health of non-smokers by reducing exposure to second-hand smoke, and to enhance the likelihood of cessation among smokers. Methods: Two cross-sectional electronic surveys of staff and students at a large Australian university were conducted prior (n = 969) and 1 year post (n = 670) the implementation of a smoke free campus policy. Demographics, tobacco use, intention to quit, attitudes towards smoking and smoking restrictions and awareness of and attitudes towards the campus smoking policy were measured. Results: Exposure to second-hand smoke (SHS) reduced significantly (p < 0.001) one year after policy implementation. Smoking prevalence was similar at both time periods (T1 9.3 %; T2 8.4 %) and over half of smokers indicated they were planning to quit smoking in the future (T1 65.5 vs T2 62.3 %). There was a significant increase in positive responses to the statement the campus should be totally smoke free including all outdoor areas at T2 compared to T1 (T1 60.8 vs T2 71.4 %; p < 0.001), however respondents felt there should be places on campus for smokers to smoke (T1 53.6 vs T2 47 %; p < 0.05). Conclusions: This study found a significant positive difference in exposure SHS after implementation of the total ban. Although prevalence of smoking in this study was low, the proportion of respondents who were contemplating smoking cessation suggests support for smokers would be beneficial. Continued awareness raising, education and enforcement is likely to enhance the long term outcomes of the total ban

TALPID3/KIAA0586 Regulates Multiple Aspects of Neuromuscular Patterning During Gastrointestinal Development in Animal Models and Human

TALPID3/KIAA0586 is an evolutionary conserved protein, which plays an essential role in protein trafficking. Its role during gastrointestinal (GI) and enteric nervous system (ENS) development has not been studied previously. Here, we analyzed chicken, mouse and human embryonic GI tissues with TALPID3 mutations. The GI tract of TALPID3 chicken embryos was shortened and malformed. Histologically, the gut smooth muscle was mispatterned and enteric neural crest cells were scattered throughout the gut wall. Analysis of the Hedgehog pathway and gut extracellular matrix provided causative reasons for these defects. Interestingly, chicken intra-species grafting experiments and a conditional knockout mouse model showed that ENS formation did not require TALPID3, but was dependent on correct environmental cues. Surprisingly, the lack of TALPID3 in enteric neural crest cells (ENCC) affected smooth muscle and epithelial development in a non-cell-autonomous manner. Analysis of human gut fetal tissues with a KIAA0586 mutation showed strikingly similar findings compared to the animal models demonstrating conservation of TALPID3 and its necessary role in human GI tract development and patterning

Psychological morbidity as a moderator of intention to quit smoking : a study of smokers and former smokers

Objective: To analyze psychological morbidity as a moderator of the relationship between smoking representations and quality of life in smokers and former smokers, as well as to determine which psychological variables discriminate between smokers with and without the intention to quit smoking. Methods: This was a quantitative, correlational cross-sectional study involving a convenience sample of 224 smokers and 169 former smokers. Results: In smokers and former smokers, psychological morbidity had a moderating effect on the relationship between mental/physical quality of life and smoking representations (cognitive representations, emotional representations, and comprehensibility). Smokers with the intention to quit smoking more often presented with low comprehensibility, threatening emotional representations, behavioral beliefs, and perceived behavioral control, as well as with normative/control beliefs, than did those without the intention to quit. Conclusions: The results of this study underscore the importance of the moderating effect exerted by psychological morbidity, as well as that of sociocognitive variables, among smokers who have the intention to quit smoking.ResumoObjetivo: Analisar a morbidade psicológica como um moderador na relação entre as representações do tabaco e a qualidade de vida em fumantes e ex-fumantes, assim como conhecer as variáveis psicológicas que discriminam os fumantes com e sem intenção para deixar de fumar. Métodos: Estudo quantitativo, correlacional e transversal com uma amostra de conveniência constituída por 224 fumantes e 169 ex-fumantes. Resultados: Verificou-se um efeito moderador da morbidade psicológica na relação entre a qualidade de vida (física e mental) e as representações do tabaco (representações cognitivas e emocionais e compreensão) nos fumantes e nos ex-fumantes. Os fumantes com intenção para deixar de fumar apresentavam menor compreensão, representações emocionais mais ameaçadoras, mais crenças de comportamento, maior controle comportamental percebido e mais crenças normativas/controle do que aqueles sem essa intenção. Conclusões: Os resultados deste estudo enfatizam a importância da morbidade psicológica como moderadora, bem como das variáveis sociocognitivas, junto dos fumantes que querem deixar de fumar

Temporal Variability of Atomic Hydrogen From the Mesopause to the Upper Thermosphere

We investigate atomic hydrogen (H) variability from the mesopause to the upper thermosphere, on time scales of solar cycle, seasonal, and diurnal, using measurements made by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) instrument on the Thermosphere Ionosphere Mesosphere Energetics Dynamics satellite, and simulations by the National Center for Atmospheric Research Whole Atmosphere Community Climate Model‐eXtended (WACCM‐X). In the mesopause region (85 to 95 km), the seasonal and solar cycle variations of H simulated by WACCM‐X are consistent with those from SABER observations: H density is higher in summer than in winter, and slightly higher at solar minimum than at solar maximum. However, mesopause region H density from the Mass‐Spectrometer‐Incoherent‐Scatter (National Research Laboratory Mass‐Spectrometer‐Incoherent‐Scatter 00 (NRLMSISE‐00)) empirical model has reversed seasonal variation compared to WACCM‐X and SABER. From the mesopause to the upper thermosphere, H density simulated by WACCM‐X switches its solar cycle variation twice, and seasonal dependence once, and these changes of solar cycle and seasonal variability occur in the lower thermosphere (~95 to 130 km), whereas H from NRLMSISE‐00 does not change solar cycle and seasonal dependence from the mesopause through the thermosphere. In the upper thermosphere (above 150 km), H density simulated by WACCM‐X is higher at solar minimum than at solar maximum, higher in winter than in summer, and also higher during nighttime than daytime. The amplitudes of these variations are on the order of factors of ~10, ~2, and ~2, respectively. This is consistent with NRLMSISE‐00

A New Model of Delirium Care in the Acute Geriatric Setting: Geriatric Monitoring Unit

<p>Abstract</p> <p>Background</p> <p>Delirium is a common and serious condition, which affects many of our older hospitalised patients. It is an indicator of severe underlying illness and requires early diagnosis and prompt treatment, associated with poor survival, functional outcomes with increased risk of institutionalisation following the delirium episode in the acute care setting. We describe a new model of delirium care in the acute care setting, titled Geriatric Monitoring Unit (GMU) where the important concepts of delirium prevention and management are integrated. We hypothesize that patients with delirium admitted to the GMU would have better clinical outcomes with less need for physical and psychotropic restraints compared to usual care.</p> <p>Methods/Design</p> <p>GMU models after the Delirium Room with adoption of core interventions from Hospital Elder Life Program and use of evening bright light therapy to consolidate circadian rhythm and improve sleep in the elderly patients. The novelty of this approach lies in the amalgamation of these interventions in a multi-faceted approach in acute delirium management. GMU development thus consists of key considerations for room design and resource planning, program specific interventions and daily core interventions. Assessments undertaken include baseline demographics, comorbidity scoring, duration and severity of delirium, cognitive, functional measures at baseline, 6 months and 12 months later. Additionally we also analysed the pre and post-GMU implementation knowledge and attitude on delirium care among staff members in the geriatric wards (nurses, doctors) and undertook satisfaction surveys for caregivers of patients treated in GMU.</p> <p>Discussion</p> <p>This study protocol describes the conceptualization and implementation of a specialized unit for delirium management. We hypothesize that such a model of care will not only result in better clinical outcomes for the elderly patient with delirium compared to usual geriatric care, but also improved staff knowledge and satisfaction. The model may then be transposed across various locations and disciplines in the acute hospital where delirious patients could be sited.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN52323811">ISRCTN52323811</a></p

HIVAN and medication use in chronic dialysis patients in the United States: analysis of the USRDS DMMS Wave 2 study

BACKGROUND: The use and possible effects of factors known to improve outcomes in patients with human immunodeficiency virus associated nephropathy (HIVAN), namely of angiotensin converting enzyme inhibitors (ACE) and antiretroviral therapy, has not been reported for a national sample of dialysis patients. METHODS: We conducted a historical cohort study of the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Study (DMMS) Wave 2 to identify risk factors associated with increased mortality in these patients. Data were available for 3374 patients who started dialysis and were followed until March 2000. Cox Regression analysis was used to model adjusted hazard ratios (AHR) with HIVAN as a cause of end stage renal disease (ESRD) and its impact on mortality during the study period, adjusted for potential confounders. RESULTS: Of the 3374 patients who started dialysis, 36 (1.1%) had ESRD as a result of HIVAN. Only 22 (61%) of patients with HIVAN received antiretroviral agents, and only nine patients (25%) received combination antiretroviral therapy, and only 14% received ACE inhibitors. Neither the use of multiple antiretroviral drugs (AHR, 0.62, 95% CI, 0.10, 3.86, p = 0.60), or ACE inhibitors were associated with a survival advantage. Patients with HIVAN had an increased risk of mortality (adjusted hazard ratio, 4.74, 95% Confidence Interval, 3.12, 7.32, p < 0.01) compared to patients with other causes of ESRD. CONCLUSIONS: Medications known to improve outcomes in HIV infected patients were underutilized in patients with HIVAN. Adjusted for other factors, a primary diagnosis of HIVAN was associated with increased mortality compared with other causes of ESRD

Structurally plastic peptide capsules for synthetic antimicrobial viruses

A conceptual design for artificial antimicrobial viruses is described. The design emulates viral assembly and function to create self-assembling peptide capsules that promote efficient gene delivery and silencing in mammalian cells. Unlike viruses, however, the capsules are antimicrobial, which allows them to exhibit a dual biological function: gene transport and antimicrobial activity. Unlike other antimicrobials, the capsules act as pre-concentrated antimicrobial agents that elicit rapid and localised membrane-disrupting responses by converting into individual pores at their precise landing positions on membranes. The concept holds promise for engineering virus-like scaffolds with biologically tuneable properties

Utilization of health services in relation to mental health problems in adolescents: A population based survey

BACKGROUND: Only a minority of adolescents reporting symptoms above case-levels on screenings for mental health seeks and receives help from specialist health services. The objective of this study was to a) examine help-seeking for symptoms of anxiety and depression in relation to symptom load dimensionally, b) identify the level of specialization in mental health among service-providers, and c) identify associations between mental health problems and contact with different types of health services. METHODS: This cross-sectional school-based study (response-rate 88%, n = 11154) is based on Norwegian health surveys among 15 and 16 year olds. RESULTS: We found a dose-response association between symptom-load and help seeking. Only 34% of individuals with mental symptom-load above 99(th )percentile reported help-seeking in the last 12 months. Forty percent of help seekers were in contact with specialists (psychiatrists or psychologists), the remaining were mainly in contact with GPs. Mental health problems increased help seeking to all twelve service providers examined. CONCLUSION: It might not be reasonable to argue that all adolescents with case-level mental health problems are in need of treatment. However, concerning the 99(th )percentile, claiming treatment need is less controversial. Even in the Norwegian context where mental health services are relatively available and free of charge, help-seeking in individuals with the highest symptom-loads is still low. Most help seekers achieved contact with health care providers, half of them at a non specialized level. Our results suggest that adolescents' recognition of mental health problems or intention to seek help for these are the major "filters" restricting treatment