We present X-ray and optical analysis of 188 active galactic nuclei (AGN) identified from 497 hard X-ray (f sub(2.0-8.0 keV) > 2.7 x 10 super(-15) ergs cm super(-2) s super(-1)) sources in 20 Chandra ...fields (1.5 deg super(2)) forming part of the Chandra Multiwavelength Project. These medium depth X-ray observations enable us to detect a representative subset of those sources responsible for the bulk of the 2-8 keV cosmic X-ray background. Brighter than our optical spectroscopic limit, we achieve a reasonable degree of completeness (77% of X-ray sources with counterparts r' < 22.5 have been classified): broad emission-line AGNs (62%), narrow emission-line galaxies (24%), absorption line galaxies (7%), stars (5%), or clusters (2%). We find that most X-ray unabsorbed AGNs (N sub(H) < 10 super(22) cm super(-2)) have optical properties characterized by broad emission lines and blue colors, similar to optically selected quasars from the Sloan Digital Sky Survey but with a slightly broader color distribution. However, we also find a significant population of redder (g' - i' > 1.0) AGNs with broad optical emission lines. Most of the X-ray-absorbed AGNs (10 super(22) cm super(-2) < N sub(H) < 10 super(24) cm super(-2)) are associated with narrow emission-line galaxies, with red optical colors characteristically dominated by luminous, early-type galaxy hosts rather than from dust reddening of an AGN. We also find a number of atypical AGNs; for instance, several luminous AGNs show both strong X-ray absorption (N sub(H) > 10 super(22) cm super(-2)) and broad emission lines. Overall, we find that 81% of X-ray-selected AGNs can be easily interpreted in the context of current AGN unification models. Most of the deviations seem to be due to an optical contribution from the host galaxies of the low-luminosity AGNs.
Protein-protein interactions play a pivotal role in the assembly of the cellulosome, one of nature's most intricate nanomachines dedicated to the depolymerization of complex carbohydrates. The ...integration of cellulosomal components usually occurs through the binding of type I dockerin modules located at the C terminus of the enzymes to cohesin modules located in the primary scaffoldin subunit. Cellulosomes are typically recruited to the cell surface via type II cohesin-dockerin interactions established between primary and cell-surface anchoring scaffoldin subunits. In contrast with type II interactions, type I dockerins usually display a dual binding mode that may allow increased conformational flexibility during cellulosome assembly. Acetivibrio cellulolyticus produces a highly complex cellulosome comprising an unusual adaptor scaffoldin, ScaB, which mediates the interaction between the primary scaffoldin, ScaA, through type II cohesin-dockerin interactions and the anchoring scaffoldin, ScaC, via type I cohesin-dockerin interactions. Here, we report the crystal structure of the type I ScaB dockerin in complex with a type I ScaC cohesin in two distinct orientations. The data show that the ScaB dockerin displays structural symmetry, reflected by the presence of two essentially identical binding surfaces. The complex interface is more extensive than those observed in other type I complexes, which results in an ultra-high affinity interaction (Ka ∼1012m). A subset of ScaB dockerin residues was also identified as modulating the specificity of type I cohesin-dockerin interactions in A. cellulolyticus. This report reveals that recruitment of cellulosomes onto the cell surface may involve dockerins presenting a dual binding mode to incorporate additional flexibility into the quaternary structure of highly populated multienzyme complexes.
Background: Cohesin-dockerin interactions support the binding of multienzyme complexes (cellulosomes) onto the cell surface.
Results: The structures of novel Coh-Doc complexes reveal a dual binding mode.
Conclusion: A dual binding mode is present in Coh-Doc interactions supporting cell-surface attachment.
Significance: The dual binding mode introduces flexibility into highly populated multienzyme complexes attached to the cell surface.
Abstract Objective To compare the early health status of people who sustained injuries during road traffic crashes (RTC) in which they were at fault (AF), with people who sustained injuries in RTC in ...which they were not at fault (NAF). Design Prospective cohort study. Subjects People presenting to the emergency department with mild to moderate musculoskeletal injuries following RTC. Main outcome measures Physical Component Score (PCS) and Mental Component Score (MCS) of the Short Form 36 (SF-36) health status measure; Hospital Anxiety and Depression Scale (HADS) and the Functional Rating Index (FRI) recorded immediately post-crash. Results 193 people participated in the study and were enrolled a mean of 9.3 days following the crash. The mean age was 37 years and 60% were female. 71% were NAF. There was a significantly higher number of females in the NAF group (65% compared with 35% males; p < 0.001). Neck and back injuries were reported by 90.4% of the NAF group compared to 69.1% of the AF group ( p < 0.001). There were no significant differences in PCS, FRI or pain intensity between the two groups at a mean of 9.3 days after the crash. The mean MCS for the NAF group was significantly worse than for the AF group (31.4 compared to 37.3; p = 0.005). The SF-36 domain revealed a significantly worse adjusted mean role emotional score for the NAF group (23.4 compared to 32.5, p = 0.002). Females had significantly worse MCS score than males (30.6 and 38.1 respectively; p < 0.001) and worse adjusted mean anxiety and depression scores (10 compared to 7.8; p = 0.002 and 7.6 compared to 5.5; p = 0.002 respectively). Conclusions Despite there being no difference in physical health status, the NAF group demonstrated more emotional and mental disturbance than the AF group; and this was significantly worse for females. Treatment strategies should focus on addressing early pain and disability as well as providing appropriate psychological interventions, particularly for people not at fault following RTC.
Vaccine safety surveillance is a core component of vaccine pharmacovigilance. In Canada, active, participant-centered vaccine surveillance is available for influenza vaccines and has been used for ...COVID-19 vaccines.
The objective of this study is to evaluate the effectiveness and feasibility of using a mobile app for reporting participant-centered seasonal influenza adverse events following immunization (AEFIs) compared to a web-based notification system.
Participants were randomized to influenza vaccine safety reporting via a mobile app or a web-based notification platform. All participants were invited to complete a user experience survey.
Among the 2408 randomized participants, 1319 (54%) completed their safety survey 1 week after vaccination, with a higher completion rate among the web-based notification platform users (767/1196, 64%) than among mobile app users (552/1212, 45%; P<.001). Ease-of-use ratings were high for the web-based notification platform users (99% strongly agree or agree) and 88.8% of them strongly agreed or agreed that the system made reporting AEFIs easier. Web-based notification platform users supported the statement that a web-based notification-only approach would make it easier for public health professionals to detect vaccine safety signals (91.4%, agreed or strongly agreed).
Participants in this study were significantly more likely to respond to a web-based safety survey rather than within a mobile app. These results suggest that mobile apps present an additional barrier for use compared to the web-based notification-only approach.
ClinicalTrials.gov NCT05794113; https://clinicaltrials.gov/show/NCT05794113.
Abstract Objective To compare health outcomes among claimants compared to those who were ineligible or choose not to lodge a compensation claim. We also evaluated the effect of an early intervention ...programme on the health outcomes of the participants. Design Prospective comparative study using sequential cohorts. Subjects People presenting to hospital emergency departments with mild to moderate musculoskeletal injuries following road traffic crashes. Intervention referral to an early intervention programme for assessment by musculoskeletal physician, pain management education, promotion of self-management and encouragement of early activity. Main outcomes The 36-Item Short-Form Survey (SF-36); Hospital Anxiety and Depression Scale (HADS) and Functional Rating Index (FRI) scores were assessed at post-crash and at 12 months. Results At 12 months, mean scores in six and five of the SF-36 domains were significantly lower among participants who claimed compensation versus those who chose not to claim or were ineligible, respectively. Differences in mean SF-36 scores ranged from 3.0 (‘general health perception’) to 8.0 units (‘role limitations due to physical problems’). Participants who claimed compensation had 6.3- and 4.6-units lower SF-36 physical component score compared to those who were ineligible ( p = 0.001) or chose not to claim ( p = 0.01), respectively. Participants who claimed compensation reported a worse HADS-depression score of 6.46 versus 4.97 and 4.69 observed in those who were ineligible ( p = 0.04) or did not claim ( p = 0.01). Claimants had worse FRI scores compared to non-claimants ( p = 0.01) and those who were ineligible ( p = 0.01). The early intervention did not improve health outcomes, 12 months after injury. Conclusions Claiming compensation was associated with a worse health status for people with soft tissue injuries caused by road traffic crashes. The health status in people claiming compensation was not altered by an early intervention programme.
Purpose
To review the available data on non-surgical management for neurogenic bladder in patients with spinal cord injury (SCI). Before the introduction of urinary catheters and antibiotics, ...neurogenic bladder was one of the main culprits for death in those patients with SCI. Currently, the management of neurogenic bladder is focused in improving quality of life and preserving renal function.
Methods
A literature review was performed and therapeutic management for neurogenic bladder was divided in six sections: (1) intermittent bladder catheterization; (2) indwelling catheters; (3) condom catheter drainage; (4) reflex voiding and bladder expression with Valsalva or Credé; (5) oral drug therapy of the spinal cord injured bladder; and (6) botulinum neurotoxin (BoNT).
Results
Intermittent catheterization is recommended as the preferable method for management of neurogenic bladder in patients with SCI based on limited high-quality data. However, this may not be feasible or available to all and other alternative options include condom catheter drainage or indwelling catheters such as urethral catheters or suprapubic tube, reflex voiding, and bladder expression with Valsalva or Credé. Non-invasive medical therapies are the key to improve incontinence, urodynamic parameters, and quality of life in this population. Botulinum neurotoxin has revolutionized the management of neurogenic bladder in the last two decades decreasing the need for reconstruction or diversion.
Conclusion
The Joint SIU-ICUD (Société Internationale d’Urologie) (International Consultation on Urological Diseases) International Consultation reviewed the available presented data and provided specific conclusions and recommendations for each non-surgical urologic method to address neurogenic bladder after SCI.
A large body of evidence clearly shows that cancer patients experience significant health benefits with smoking cessation. Cancer Care Ontario, the provincial agency responsible for the quality of ...cancer services in Ontario, has undertaken a province-wide smoking cessation initiative. The strategies used, the results achieved, and the lessons learned are the subject of the present article.
Evidence related to the health benefits of smoking cessation in cancer patients was reviewed. A steering committee developed a vision statement for the initiative, created a framework for implementation, and made recommendations for the key elements of the initiative and for smoking cessation best practices.
New ambulatory cancer patients are being screened for their smoking status in each of Ontario's 14 regional cancer centres. Current or recent smokers are advised of the benefits of cessation and are directed to smoking cessation resources as appropriate. Performance metrics are captured and used to drive improvement through quarterly performance reviews and provincial rankings of the regional cancer centres.
Regional smoking cessation champions, commitment from Cancer Care Ontario senior leadership, a provincial secretariat, and guidance from smoking cessation experts have been important enablers of early success. Data capture has been difficult because of the variety of information systems in use and non-standardized administrative and clinical processes. Numerous challenges remain, including increasing physician engagement; obtaining funding for key program elements, including in-house resources to support smoking cessation; and overcoming financial barriers to access nicotine replacement therapy. Future efforts will focus on standardizing processes to the extent possible, while tailoring the approaches to the populations served and the resources available within the individual regional cancer programs.
Clostridium thermocellum produces the prototypical cellulosome, a large multienzyme complex that efficiently hydrolyzes plant cell wall polysaccharides into fermentable sugars. This ability has ...garnered great interest in its potential application in biofuel production. The core non-catalytic scaffoldin subunit, CipA, bears nine type I cohesin modules that interact with the type I dockerin modules of secreted hydrolytic enzymes and promotes catalytic synergy. Because the large size and flexibility of the cellulosome preclude structural determination by traditional means, the structural basis of this synergy remains unclear. Small angle x-ray scattering has been successfully applied to the study of flexible proteins. Here, we used small angle x-ray scattering to determine the solution structure and to analyze the conformational flexibility of two overlapping N-terminal cellulosomal scaffoldin fragments comprising two type I cohesin modules and the cellulose-specific carbohydrate-binding module from CipA in complex with Cel8A cellulases. The pair distribution functions, ab initio envelopes, and rigid body models generated for these two complexes reveal extended structures. These two N-terminal cellulosomal fragments are highly dynamic and display no preference for extended or compact conformations. Overall, our work reveals structural and dynamic features of the N terminus of the CipA scaffoldin that may aid in cellulosome substrate recognition and binding.
Background: The cellulosome N terminus contains the sole substrate-binding module of the cellulosome scaffoldin.
Results: Two N-terminal cellulosomal fragments are devoid of intermodular interactions, are highly dynamic, and inhabit compact and elongated conformations equally.
Conclusion: The characteristics of the cellulosome N terminus may facilitate its role in substrate binding.
Significance: Information on cellulosome structure and dynamics aids in engineering designer cellulosomes.
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