This study addressed the hypothesis that duration and magnitude of applied intermittent hydrostatic pressure (IHP) are critical parameters in regulation of normal human articular chondrocyte aggrecan and type I1 collagen expression. Articular chondrocytes were isolated from knee cartilage and maintained as primary, high-density monolayer cultures. IHP was applied at magnitudes of 1, 5 and 10 MPa at I Hz for durations of either 4 h per day for one day (4 x 1) or 4 h per day for four days (4 x 4). Total cellular RNA was isolated and analyzed for aggrecan and type I1 collagen mRNA signal levels using specific primers and reverse transcription polymerase chain reaction (RT-PCR) nested with beta-actin primers as internal controls. With a 4 x 1 loading regimen, aggrecan mRNA signal levels increased 1.3-and 1.5-fold at 5 and 10 MPa, respectively, relative to beta-actin mRNA when compared to unloaded cultures. Changing the duration of loading to a 4 x 4 regimen increased aggrecan mRNA signal levels by 1.4-, 1.8-and 1.9-fold at loads of 1, 5 and 10 MPa, respectively. In contrast to the effects of IHP on aggrecan, type I1 collagen mRNA signal levels were only upregulated at loads of 5 and 10 MPa with the 4 x 4 loading regimen. Analysis of cell-associated protein by western blotting confirmed that IHP increased aggrecan and type I1 collagen in chondrocyte extracts. These data demonstrate that duration and magnitude of applied IHP differentially alter chondrocyte matrix protein expression. The results show that IHP provides an important stimulus for increasing cartilage matrix anabolism and may contribute to repair and regeneration of damaged or diseased cartilage.

A method for target sequence enrichment from the human genome is described. This hybridization-based approach using oligonucleotide probes in solution has excellent sensitivity and accuracy for calling SNPs

Neisseria gonorrhoeae is the second most common bacterial sexually transmitted infection in the world after Chlamydia trachomatis . The pathogen has developed resistance to every antibiotic currently approved for treatment, and multidrug-resistant strains have been identified globally. The current treatment recommended by the World Health Organization is ceftriaxone and azithromycin dual therapy. However, resistance to azithromycin and ceftriaxone are increasing and treatment failures have been reported. As a result, there is a critical need to develop novel strategies for mitigating the spread of antimicrobial-resistant N. gonorrhoeae through improved diagnosis and treatment of resistant infections. Strategies that are currently being pursued include developing molecular assays to predict resistance, utilizing higher doses of ceftriaxone, repurposing older antibiotics, and developing newer agents. In addition, efforts to discover a vaccine for N. gonorrhoeae have been reignited in recent years with the cross-protectivity provided by the N. meningitidis vaccine, with several new strategies and targets. Despite the significant progress that has been made, there is still much work ahead to combat antimicrobial-resistant N. gonorrhoeae globally.

Acute lung injury/acute respiratory distress syndrome occurred in more than one third of mechanically ventilated neurosciences critical care unit patients. Loss of the cough or gag reflex is strongly predictive of acute lung injury/acute respiratory distress syndrome, while neurologic diagnosis and Glasgow Coma Scale are not. Lower brainstem dysfunction, a clinical marker of neurologic injury not captured by the Glasgow Coma Scale, is a risk factor for acute lung injury/acute respiratory distress syndrome and could inform decisions regarding airway protection and mechanical ventilation.