Sensitizing Staphylococcus aureus to antibacterial agents by decoding and blocking the lipid flippase MprF.

The pandemic of antibiotic resistance represents a major human health threat demanding new antimicrobial strategies. Multiple peptide resistance factor (MprF) is the synthase and flippase of the phospholipid lysyl-phosphatidylglycerol that increases virulence and resistance of methicillin-resistant Staphylococcus aureus (MRSA) and other pathogens to cationic host defense peptides and antibiotics. With the aim to design MprF inhibitors that could sensitize MRSA to antimicrobial agents and support the clearance of staphylococcal infections with minimal selection pressure, we developed MprF-targeting monoclonal antibodies, which bound and blocked the MprF flippase subunit. Antibody M-C7.1 targeted a specific loop in the flippase domain that proved to be exposed at both sides of the bacterial membrane, thereby enhancing the mechanistic understanding of bacterial lipid translocation. M-C7.1 rendered MRSA susceptible to host antimicrobial peptides and antibiotics such as daptomycin, and it impaired MRSA survival in human phagocytes. Thus, MprF inhibitors are recommended for new antivirulence approaches against MRSA and other bacterial pathogens.

Desires for beverages and liking of skin care product odors in imaginative and immersive virtual reality beach contexts.

Immersive technologies simulating real-life environments allow repeated simulation of complex real-life situations at one location and, therefore, bear potential for consumer product evaluations and food behavior studies. This study aimed to assess whether a contextual exposure by immersive virtual reality (VR) or a photo-enhanced imaginative (PIC) condition could induce effects on desires and liking aligning with the situation. A total of 60 subjects (30 females) were presented to VR and PIC beach settings in a randomized balanced design performed in a laboratory one week apart. A follow-up test in the same room but without the contextual exposure was also performed (Neutral). Subjects rated their desires for hot and cold beverages during and just after the contextual exposure. Liking for skin care samples (sun screen and regular lotion) were assessed during exposure. The retention of the contextual exposure was further explored in a food choice behavior test. A similar test setup was followed in the Neutral condition. Engagement by presence dimensions (e.g., felt like being on a beach) and level of excitement was scored following the contextual exposure. The VR condition induced a significantly stronger engagement, compared with the PIC condition. During each beach exposure a significantly stronger desire for cold beverages compared to hot beverages was induced. The desire for cold versus hot beverages was, however, significantly larger in the VR simulation compared to the PIC context. Results from the Neutral condition provided no significant difference in the desires for hot versus cold beverages. A significant shift in desires was observed after the completion of the contextual beach exposures, as desire scores became aligned with scores assessed in the Neutral condition. The shift in desires was, however, more pronounced after VR. Variations in the contextual settings had little effect on odor liking and no retention effect on choice behavior was observed. Immersive VR induced a positive sensation of presence less dependent on the level of excitement and had a stronger effect on beverage-related desires. The VR technology seems to be a promising tool for evaluating contextual influences in food consumer research.

Diagnostic performance of volume and limited oblique MRI of the anterior cruciate ligament compared to knee arthroscopy.

BACKGROUND: Many strategies have been used to improve the visualisation of the ACL including sagittal, coronal oblique sequences, and 3D volume imaging. Nevertheless, the ACL may not always be visualised. METHODS: Two hundred and thirty-one consecutive patients (77 females; 154 males; average age 43.5, range 18 to 82 years; 205 with chronic, 20 acute, and 6 acute on chronic symptoms) underwent knee arthroscopy for mechanical symptoms within a week of MRI. After routine orthogonal sequences, if general MRI radiographers, with over four years experience, were not able to identify the presence of the ACL, then two 3D volume sequences and 2D limited sagittal oblique T1 sequences were performed. Patients requiring extra sequences, missed by the radiography technicians, were recalled. The MRI sequences were evaluated in a blinded fashion by three radiologists, and compared to the knee arthroscopy findings, with the normal ACL acting as internal controls. The radiography technicians performed additional ACL sequences in 63 patients (27%); of these, 10 patients had a partial and 12 patients had a complete ACL tear. Only 2 patients (0.6%) were recalled (one with a normal, and one with a full thickness ACL tear). RESULTS: The filmed ACL evaluation for complete tears and a normal ACL had a sensitivity of 100%, specificity of 97.1% and accuracy of 97.3%, slightly higher than evaluating on the monitor. Volume sequences had specificities and accuracies over 95%, with good intraobserver reliability (Kappa 0.859, 95% CI 0.705-1.0). Experienced radiographers identified most cases requiring supplementary MRI ACL sequences. An additional volume sequence was beneficial when filmed. Use of the monitor can offer some benefits. Limited oblique T1 sequence of the intercondylar notch was unreliable.

The Effects of Aerobic and Resistance Exercise on Markers of Large Joint Health in Stable Rheumatoid Arthritis Patients: A Pilot Study.

OBJECTIVE: Exercise is beneficial for people with rheumatoid arthritis (RA). However, patients and health professionals have expressed concern about the possible detrimental effects of exercise on joint health. The present study investigated the acute and chronic effects of high-intensity, low-impact aerobic and resistance exercise on markers of large joint health in RA. METHODS: Eight RA patients and eight healthy, matched control (CTL) participants performed 30 minutes' high-intensity, low-impact aerobic and lower-body resistance exercise, one week apart. Primary outcome measures assessing joint health were serum cartilage oligomeric matrix protein (sCOMP) and knee joint synovial inflammation (Doppler ultrasound colour fraction; CF). These measures were taken at baseline, immediately after and 0.5, one, two, six and 24 hours post-exercise. In a separate study, nine RA patients completed eight weeks of progressive exercise training. The same outcome measures were reassessed at baseline, and at one hour post-exercise of training weeks 0, 1, 4 and 8. RESULTS: RA patients showed higher overall sCOMP [RA: 1,347 ± 421, CTL: 1,189 ± 562 ng/mL; p < 0.05; effect size (ES) = 0.32] and CF when scanned longitudinally (RA: 0.489 ± 0.30 × 10(-3) , CTL: 0.101 ± 0.13 × 10(-3) ; p < 0.01; ES = 1.73) and transversely (RA: 0.938 ± 0.69 × 10(-3) , CTL: 0.199 ± 0.36 × 10(-3) ; p < 0.01; ES = 1.33) than CTL. However, no acute effects on joint health were observed post-exercise. Similarly, no chronic effects were observed over eight weeks of combined aerobic and resistance training in RA, with positive effects on physical fitness and function. CONCLUSIONS: RA patients on stable treatment with low disease activity were able to perform an individually prescribed high-intensity, low-impact aerobic and resistance exercise without changes in markers of large joint health. Copyright © 2015 John Wiley & Sons, Ltd.

"Yummy" versus "Yucky"! Explicit and implicit approach-avoidance motivations towards appealing and disgusting foods.

Wanting and rejecting food are natural reactions that we humans all experience, often unconsciously, on a daily basis. However, in the food domain, the focus to date has primarily been on the approach tendency, and researchers have tended not to study the two opposing tendencies in a balanced manner. Here, we develop a methodology with which to understand people's implicit and explicit reactions to both positive (appealing) and negative (disgusting) foods. It consists of a combination of direct and indirect computer-based tasks, as well as a validated food image stimulus set, specifically designed to investigate motivational approach and avoidance responses towards foods. Fifty non-dieting participants varying in terms of their hunger state (hungry vs. not hungry) reported their explicit evaluations of pleasantness, wanting, and disgust towards the idea of tasting each of the food images that were shown. Their motivational tendencies towards those food items were assessed indirectly using a joystick-based approach-avoidance procedure. For each of the food images that were presented, the participants had to move the joystick either towards or away from themselves (approach and avoidance movements, respectively) according to some unrelated instructions, while their reaction times were recorded. Our findings demonstrated the hypothesised approach-avoidance compatibility effect: a significant interaction of food valence and direction of movement. Furthermore, differences between the experimental groups were observed. The participants in the no-hunger group performed avoidance (vs. approach) movements significantly faster; and their approach movements towards positive (vs. negative) foods were significantly faster. As expected, the self-report measures revealed a strong effect of the food category on the three dependent variables and a strong main effect of the hunger state on wanting and to a lesser extent on pleasantness.

NMR findings in patients after wrist trauma with a negative plain radiographs.

BACKGROUND: The purpose was to assess the prevalence and location of the injuries of the carpal bones and soft tissue of the wrist on NMR in patients with negative radiographs. MATERIAL/METHODS: A total of 89 patients (9-81years) were consecutively examined after wrist trauma. Radiograms were performed in four projections: AP, PA, oblique and lateral. In 63 cases of negative radiographs and persistent clinical problem, simplified NMR (T1,T2, STIR; in coronal plane) was conducted with a 1.5 Tesla magnet. Results were evaluated by two independent observers. A positive X-ray result was stated when at least one observer suggested bone fracture. The MR images were viewed for detection of possible bone fracture, bone edema and soft tissue injuries. Cohen's kappa coefficient was calculated to assess the quality of chosen criteria by means of agreement between both observers and both methods. RESULTS: As many as 26 X-ray studies were classified as positive. Substantial agreement between independent observers was found (kappa=0.63). In 17 cases out of 63 with two negative wrist radiogram, the NMR result was positive (19%). The most frequently fractured or injured bone was scaphoid (10 cases) and distal radius (5 cases). Fair agreement was found between X-ray and NMR studies (kappa=0.37) due to different diagnostic information received in both methods. CONCLUSIONS: Simplified NMR imaging of the wrist proved to be strongly efficient in the detection of pathological changes in injured wrists.