The Enantiomers of Trinorbornane and Derivatives Thereof

Herein, we report the synthesis of the enantiomers of trinorbornane, a tetracyclic saturated hydrocarbon with the chemical formula C11H16. The preparation of these rigid carbon scaffolds was enabled by the successful chiral separation of its tricyclic precursor, thus allowing the enantiomers to be synthesized through a reductive radical cyclization reaction. Assignment of the absolute conformation of the enantiomers was achieved through VCD experiments. Further, we report an alternative cyclization procedure providing access to hydroxyl and phenyl sulfone functionalized trinorbornanes

Loss of penicillin tolerance by inactivating the carbon catabolite repression determinant CcpA in Streptococcus gordonii

Objectives Antibiotic tolerance is a phenomenon allowing bacteria to withstand drug-induced killing. Here, we studied a penicillin-tolerant mutant of Streptococcus gordonii (Tol1), which was shown to be deregulated in the expression of the arginine deiminase operon (arc). arc was not directly responsible for tolerance, but is controlled by the global regulator CcpA. Therefore, we sought whether CcpA might be implicated in tolerance. Methods The ccpA gene was characterized and subsequently inactivated by PCR ligation mutagenesis in both the susceptible wild-type (WT) and Tol1. The minimal inhibitory concentration and time-kill curves for the strains were determined and the outcome of penicillin treatment in experimental endocarditis assessed. Results ccpA sequence and expression were similar between the WT and Tol1 strains. In killing assays, the WT lost 3.5 ± 0.6 and 5.3 ± 0.6 log10 cfu/mL and Tol1 lost 0.4 ± 0.2 and 1.4 ± 0.9 log10 cfu/mL after 24 and 48 h of penicillin exposure, respectively. Deletion of ccpA almost totally restored Tol1 kill susceptibility (loss of 2.5 ± 0.7 and 4.9 ± 0.7 log10 cfu/mL at the same endpoints). In experimental endocarditis, penicillin treatment induced a significant reduction in vegetation bacterial densities between Tol1 (4.1 log10 cfu/g) and Tol1ΔccpA (2.4 log10 cfu/g). Restitution of ccpA re-established the tolerant phenotype both in vitro and in vivo. Conclusions CcpA, a global regulator of the carbon catabolite repression system, is implicated in penicillin tolerance both in vitro and in vivo. This links antibiotic survival to bacterial sugar metabolism. However, since ccpA sequence and expression were similar between the WT and Tol1 strains, other factors are probably involved in toleranc

Vancomycin-intermediate Staphylococcus aureus selected during vancomycin therapy of experimental endocarditis are not detected by culture-based diagnostic procedures and persist after treatment arrest

Objectives Laboratory detection of vancomycin-intermediate Staphylococcus aureus (VISA) and their heterogeneous VISA (hVISA) precursors is difficult. Thus, it is possible that vancomycin failures against supposedly vancomycin-susceptible S. aureus are due to undiagnosed VISA or hVISA. We tested this hypothesis in experimental endocarditis. Methods Rats with aortic valve infection due to the vancomycin-susceptible (MIC 2 mg/L), methicillin-resistant S. aureus M1V2 were treated for 2 days with doses of vancomycin that mimicked the pharmacokinetics seen in humans following intravenous administration of 1 g of the drug every 12 h. Half of the treated animals were killed 8 h after treatment arrest and half 3 days thereafter. Population analyses were done directly on vegetation homogenates or after one subculture in drug-free medium to mimic standard diagnostic procedures. Results Vancomycin cured 14 of 26 animals (54%; P < 0.05 versus controls) after 2 days of treatment. When vegetation homogenates were plated directly on vancomycin-containing plates, 6 of 13 rats killed 8 h after treatment arrest had positive cultures, 1 of which harboured hVISA. Likewise, 6 of 13 rats killed 3 days thereafter had positive valve cultures, 5 of which harboured hVISA. However, one subculture of vegetations in drug-free broth was enough to revert all the hVISA phenotypes to the susceptible pattern of the parent. Thus, vancomycin selected for hVISA during therapy of experimental endocarditis due to vancomycin-susceptible S. aureus. These hVISA were associated with vancomycin failure. The hVISA phenotype persisted in vivo, even after vancomycin arrest, but was missed in vitro after a single passage of the vegetation homogenate on drug-free medium. Conclusions hVISA might escape detection in clinical samples if they are subcultured before susceptibility test

Applicability of a Change of Direction Ability Field Test in Soccer Assistant Referees

The aim of this study was to examine the applicability of a test for change of direction ability (10-8-8-10 test, involving line and sideward sprinting, 36 m) in elite-level soccer assistant referees (ARs). One hundred AR of the first-second and third Italian Championships (ARA-B and ARC, n = 50, respectively) performed the 10-8-8-10 on 3 separate occasions. Twenty AR authorities scored test relevance (1-5 scale, from trivial to very large) for logical validity using a questionnaire. Construct validity was examined comparing ARA-B and ARC for the 10-8-8-10 performance. Short-term reliability was assessed testing a random selection of ARs (n = 64) over 3 separate occasions every other day. Performance in the 10-8-8-10 test was assumed as total coverage time using telemetric photocells. Results showed that the 10-8-8-10 test was perceived as possessing from large (n = 4/20) to very-large (n = 16/20) relevance to AR physical match performance. No significant performance difference was found between competitive levels (p = 0.57). Area under the curve (= 0.49; p = 0.87) showed no significant sensitivity of 10-8-8-10 in detecting competitive-level difference. The intraclass correlation coefficient (n = 64) and typical error of measurement (test 2 vs. 3) values were 0.90 (p < 0.0001) and 0.18 seconds, respectively. This study showed that the 10-8-8-10 test possesses logical validity, good reliability, and it is independent of the competitive level. As such, this original investigation represents the first step in the identification and assessment of a valid and reliable AR change of direction test. Given the strength of our findings, governing bodies should look to integrate the 10-8-8-10 test into the fitness test protocols devised for ARs, with scores 65 9.67 being considered as a starting point for the empirical validation of minimum selection criteria for elite-level ARs

Hip muscle weakness in patients with symptomatic femoroacetabular impingement

SummaryObjectiveFemoroacetabular impingement (FAI) is a pathomechanical process, which may cause hip pain, disability and early development of hip osteoarthritis (OA) in young and active adults. Patients with FAI experience functional disability during dynamic weight-bearing activities, which could originate from weakness of the hip muscles. The objective of this study was to compare hip muscle strength between patients with symptomatic FAI and healthy controls. It was hypothesized that patients would present overall hip muscle weakness compared to controls.MethodsA total of 22 FAI patients and 22 controls matched for gender, age, and body mass participated in the study. We evaluated isometric maximal voluntary contraction (MVC) strength of all hip muscle groups using hand-held and isokinetic dynamometry, and electromyographic (EMG) activity of the rectus femoris (RF) and tensor fasciae latae (TFL) muscles during active flexion of the hip.ResultsFAI patients had significantly lower MVC strength than controls for hip adduction (28%), flexion (26%), external rotation (18%) and abduction (11%). TFL EMG activity was significantly lower in FAI patients compared with controls (P=0.048), while RF EMG activity did not differ significantly between the two groups (P=0.056).ConclusionsPatients with symptomatic FAI presented muscle weakness for all hip muscle groups, except for internal rotators and extensors. Based on EMG recordings, it was demonstrated that patients with symptomatic FAI have a reduced ability to activate TFL muscle during hip flexion. These findings provide orthopedic surgeons with objective information about the amount and specificity of hip muscle weakness in patients with FAI. Future research should investigate the relationship between hip muscle weakness, functional disability and overuse injury risks, as well as the effects of hip muscle strengthening on clinical outcomes in individuals with symptomatic FAI

Multicenter evaluation of the vitek MS matrix-assisted laser desorption ionization-time of flight mass spectrometry system for identification of gram-positive aerobic bacteria

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF) is gaining momentum as a tool for bacterial identification in the clinical microbiology laboratory. Compared with conventional methods, this technology can more readily and conveniently identify a wide range of organisms. Here, we report the findings from a multicenter study to evaluate the Vitek MS v2.0 system (bioMérieux, Inc.) for the identification of aerobic Gram-positive bacteria. A total of 1,146 unique isolates, representing 13 genera and 42 species, were analyzed, and results were compared to those obtained by nucleic acid sequence-based identification as the reference method. For 1,063 of 1,146 isolates (92.8%), the Vitek MS provided a single identification that was accurate to the species level. For an additional 31 isolates (2.7%), multiple possible identifications were provided, all correct at the genus level. Mixed-genus or single-choice incorrect identifications were provided for 18 isolates (1.6%). Although no identification was obtained for 33 isolates (2.9%), there was no specific bacterial species for which the Vitek MS consistently failed to provide identification. In a subset of 463 isolates representing commonly encountered important pathogens, 95% were accurately identified to the species level and there were no misidentifications. Also, in all but one instance, the Vitek MS correctly differentiated Streptococcus pneumoniae from other viridans group streptococci. The findings demonstrate that the Vitek MS system is highly accurate for the identification of Gram-positive aerobic bacteria in the clinical laboratory setting

Could Public Restrooms Be an Environment for Bacterial Resistomes?

PMCID: PMC3547874This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Hamstring stretch reflex:could it be a reproducible objective measure of functional knee stability?"

Background: The anterior cruciate ligament (ACL) plays an important role in anterior knee stability by preventing anterior translation of the tibia on the femur. Rapid translation of the tibia with respect to the femur produces an ACL-hamstring stretch reflex which may provide an object measure of neuromuscular function following ACL injury or reconstruction. The aim of this study was to determine if the ACL-hamstring stretch reflex could be reliably and consistently obtained using the KT-2000 arthrometer.  Methods: A KT-2000 arthrometer was used to translate the tibia on the femur while recording the electromyography over the biceps femoris muscle in 20 participants, all with intact ACLs. In addition, a sub-group comprising 4 patients undergoing a knee arthroscopy for meniscal pathology, were tested before and after anaesthetic and with direct traction on the ACL during arthroscopy. The remaining 16 participants underwent testing to elicit the reflex using the KT-2000 only.  Results: A total number of 182 trials were performed from which 70 trials elicited stretch reflex (38.5 %). The mean onset latency of the hamstring stretch reflexes was 58.9 ± 17.9 ms. The average pull force was 195 ± 47 N, stretch velocity 48 ± 35 mm/s and rate of force 19.7 ± 6.4 N/s. Conclusions Based on these results, we concluded that the response rate of the anterior cruciate ligament-hamstring reflex is too low for it to be reliably used in a clinical setting, and thus would have limited value in assessing the return of neuromuscular function following ACL injuries

Estudios Filológicos: revisión de las Memorias de grado

El trabajo llevado a cabo por la Red Estudios Filológicos ha consistido en la revisión de las memorias de los siguientes grados: Español: lengua y literaturas; Estudios árabes e islámicos; Estudios franceses; Estudios ingleses y Filología Catalana. Se han corregido erratas evidentes, se han unificado criterios compartidos por todos los grados y se han subsanado yerros tanto de forma como de contenido con el objetivo de proceder a una solicitud de modificación de estas Memorias