Synthesis of Metallo-β-Lactamase VIM-2 Is Associated with a Fitness Reduction in Salmonella enterica Serovar Typhimurium

Antibiotic resistance, especially due to β-lactamases, has become one of the main obstacles in the correct treatment of Salmonella infections; furthermore, antibiotic resistance determines a gain of function that may encompass a biological cost, or fitness reduction, to the resistant bacteria. The aim of this work was to determine in vitro if the production of the class B β-lactamase VIM-2 determined a fitness cost for Salmonella enterica serovar Typhimurium. To that end the gene bla_VIM-2 was cloned into the virulent strain S. Typhimurium SL1344, using both the tightly regulated pBAD22 vector and the natural plasmid pST12, for inducible and constitutive expression, respectively. Fitness studies were performed by means of motility, growth rate, invasiveness in epithelial cells, and plasmid stability. The expression of bla_VIM-2 was accompanied by alterations in micro- and macroscopic morphology and reduced growth rate and motility, as well as diminished invasiveness in epithelial cells. These results suggest that VIM-2 production entails a substantial fitness cost for S. Typhimurium, which in turn may account for the extremely low number of reports of metallo-β-lactamase-producing Salmonella spp.     

Recreational sport activity after total replacement of the first metatarsophalangeal joint: a prospective study

First metatarsophalangeal joint replacement is an alternative surgical procedure to arthrodesis in the treatment of moderate-to-severe hallux rigidus. However, few studies have been published about functional outcome after joint reconstructive procedures for hallux rigidus. The purpose of this study was to assess clinical, radiological and functional outcome, with special regard to recreational and sports activity, after first metatarsophalangeal joint replacement in patients affected by hallux rigidus grade III. Twenty-three patients who had undergone total joint replacement of the first metatarsophalangeal joint were examined preoperatively and three, six, 12 and 18 months postoperatively. All patients (mean age of 57.0 ± 3.7 years) received a non-cemented TOEFIT-PLUS™ implant by one surgeon. Clinical scores (AOFAS score and VAS), radiological examination, patient satisfaction and sport participation were used to evaluate treatment outcome and radiolucent lines. The mean AOFAS score showed a significant improvement from 44.6 ± 7.2 points preoperatively to an average of 82.5 ± 14.4 points at last follow-up (p < 0.001). The mean total ROM of the first MTP joint increased from 28.1 ± 4.9 degrees preoperatively to 52.7 ± 15.7 degrees postoperatively (p < 0.001). After surgery, 91.3% of the patients were able to resume at least one recreational activity. Total arthroplasty for the treatment of hallux rigidus in an active patient population revealed good clinical and functional results. However, postoperative recreational sport activity showed a decrease in comparison to the pre-arthritic state. Further follow-up is necessary to quantify loosening risk in active patients after total hallux arthroplasty.     

Is neuronal encoding of subject-object distance dependent on learning?

Recordings were made in the intermediate and medial part of the hyperstriatum ventrale of behaving domestic chicks which had been imprinted (trained) by being exposed to a training stimulus. Neurons were tested for responsiveness to the training stimulus and to an alternative stimulus at each of three distances (d = 0.5 m, 1 m, 2 m) from the chick. For responses to the training stimulus 24/78 (31%) responsive neurons were d-sensitive, i.e. responses changed with distance. For responses to the alternative stimulus, a similar proportion of neurons was d-sensitive (16/57, 28%). Six d-invariant neurons responded similarly at each distance: four to the training and two to the alternative stimulus. Thus no effect of learning on d-sensitive or d-invariant neuronal responsiveness was found.     

Combining etanercept with traditional agents in the treatment of psoriasis: a review of the clinical evidence

Psoriasis is a chronic, systemic inflammatory disorder manifesting primarily in skin and potentially in joints, frequently necessitating treatment with conventional systemic therapies, phototherapy or biological agents. Patients with moderate to severe disease suffer a diminished quality of life, experience significant comorbidities and have a higher mortality. Although traditional treatments are effective in the short‐term, their use is often limited by concerns over long‐term toxicity, including end‐organ damage and risk of malignancy. Combination therapy is a commonly used approach and is often more effective than any single agent. Lower doses of two treatments in combination can also minimize potential side effects from a single agent at higher doses. Etanercept is a recombinant human tumour necrosis factor (TNF)α receptor (p75) protein fused with the Fc portion of IgG1 that binds to TNFα. This article reviews the evidence on the efficacy and safety of etanercept in combination with methotrexate, acitretin, narrowband UVB and cyclosporin. The largest body of evidence assesses the combination with methotrexate, although evidence is available for the other combinations. Data suggest that although highly effective as monotherapy, etanercept in combination with a conventional systemic agent can enhance efficacy and allow drug sparing. Potentially, the combination may also result in faster treatment responses and permit safe transitioning from one systemic agent to another. Evidence to date suggests that these benefits can be achieved without significant additional toxicity, although long‐term data on the efficacy and safety of the combination in psoriatic populations is limited and further evaluation is warranted.     

Improving Beverage Choice in Adults with Developmental Disabilities: Implementation of a Token Reinforcement System in a Community Residential Setting

Journal of Autism and Developmental Disorders - Individuals with developmental disabilities (DD) are twice as likely to have obesity than non-disabled individuals. Replacing the consumption of...