Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress.

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr increased both respiration and fermentation but decreased ATP levels and growth, suggesting that Δagr cells assume a hyperactive metabolic state in response to reduced metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δagr strains to lethal H2O2 doses. Increased survival of wild-type agr cells during H2O2 exposure required sodA, which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δagr cells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived "memory" of agr-mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Nox2-/-) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.

Quorum-sensing agr system of Staphylococcus aureus primes gene expression for protection from lethal oxidative stress.

The agr quorum-sensing system links Staphylococcus aureus metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of H2O2, a crucial host defense against S. aureus. We now report that protection by agr surprisingly extends beyond post-exponential growth to the exit from stationary phase when the agr system is no longer turned on. Thus, agr can be considered a constitutive protective factor. Deletion of agr resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δagr cells undergo a shift towards a hyperactive metabolic state in response to diminished metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the agr mutant than in wild-type cells, thereby explaining elevated susceptibility of Δagr strains to lethal H2O2 doses. Increased survival of wild-type agr cells during H2O2 exposure required sodA, which detoxifies superoxide. Additionally, pretreatment of S. aureus with respiration-reducing menadione protected Δagr cells from killing by H2O2. Thus, genetic deletion and pharmacologic experiments indicate that agr helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived 'memory' of agr-mediated protection, which is uncoupled from agr activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient (Cybb-/-) mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.

Crash Performance of Strength Gradient Tube Induced by Selective Laser Patterning.

This paper presents an investigation of the performance of a 22 MnB5 tube after local heat treatment according to a patterning shape under dynamic crash test conditions to propose the patterning shape with the best energy absorption efficiency. Numerical simulations support experimental results to validate the deformation mode during dynamic crash test as well as the strain distribution of the specimen. The helical patterning not only demonstrates the highest axial loading force and energy absorbance in both static and dynamic crash tests, but also can be easily fabricated in a short time. The helical pattern can optimize different pitch sizes according to the thickness and diameter of the cylindrical tube, and it has the highest energy absorption rate with 83.0% in dynamic conditions.

Hydroxychloroquine-induced myopathy.

A 70-year-old woman with a history of undifferentiated connective tissue disease was admitted for work-up of shortness of breath and progressive weakness over the course of 1 year. She had been treated with hydroxychloroquine (HCQ) for last 5 years. Her evaluation revealed diffuse muscle weakness and hyperpigmentation of the skin consistent with HCQ deposition, although this did not entirely explain the patient's dyspnea. The patient underwent cardiac evaluation because of occasional substernal chest pain and persistent elevation in serum troponin I, but her ECG and adenosine thallium study did not show any signs of ischemic heart disease. The diagnosis of HCQ-induced myopathy was made with electromyography and muscle biopsy. HCQ was discontinued, with improvement of the patient's signs and symptoms over the course of the next 18 months.We propose that this patient was experiencing myocardial toxicity as a consequence of HCQ deposition disease with her clinical picture of skeletal muscle myopathy and HCQ deposition in the skin. A Medline search yielded several case reports as well as a case series of patients with antimalarial-induced myopathy. HCQ-induced myopathy may be less recognized because of its presentation with signs, symptoms, and laboratory results which suggest other critical diseases. Moreover, this medication is often prescribed to treat illnesses whose clinical manifestations may include myopathy.

Characteristics of Myofascial Pain Syndrome of the Infraspinatus Muscle.

OBJECTIVE: To report the characteristics of myofascial trigger points (MTrPs) in the infraspinatus muscle and evaluate the therapeutic effect of trigger-point injections. METHODS: Medical records of 297 patients (221 women; age, 53.9±11.3 years) with MTrPs in the infraspinatus muscle were reviewed retrospectively. Because there were 83 patients with MTrPs in both infraspinatus muscles, the characteristics of total 380 infraspinatus muscles with MTrPs (214 one side, 83 both sides) were investigated. Specific characteristics collected included chief complaint area, referred pain pattern, the number of local twitch responses, and distribution of MTrPs in the muscle. For statistical analysis, the paired t-test was used to compare a visual analogue scale (VAS) before and 2 weeks after the first injection. RESULTS: The most common chief complaint area of MTrPs in the infraspinatus muscle was the scapular area. The most common pattern of referred pain was the anterolateral aspect of the arm (above the elbow). Active MTrPs were multiple rather than single in the infraspinatus muscle. MTrPs were frequently in the center of the muscle. Trigger-point injection of the infraspinatus muscle significantly decreased the pain intensity. Mean VAS score decreased significantly after the first injection compared to the baseline (7.11 vs. 3.74; p<0.001). CONCLUSION: Characteristics of MTrPs and the therapeutic effects of trigger-point injections of the infraspinatus muscle were assessed. These findings could provide clinicians with useful information in diagnosing and treating myofascial pain syndrome of the infraspinatus muscle.