Post-traumatic syringomyelia: a review.

More than a quarter of spinal cord injured patients develop syringes and many of these patients suffer progressive neurological deficits as a result of cyst enlargement. The mechanism of initial cyst formation and progressive enlargement are unknown, although arachnoiditis and persisting cord compression with disturbance of cerebrospinal fluid flow appear to be important aetiological factors. Current treatment options include correction of bony deformity, decompression of the spinal cord, division of adhesions, and shunting. Long-term improvement occurs in fewer than half of patients treated. Imaging evidence of a reduction in syrinx size following treatment does not guarantee symptomatic resolution or even prevention of further neurological loss. A better understanding of the causal mechanisms of syringomyelia is required to develop more effective therapy.     

Correction to: Incidental intracranial meningiomas: a systematic review and meta-analysis of prognostic factors and outcomes

Journal of Neuro-Oncology - Issues with data analysis have recently been highlighted by a reader of our article. These have been addressed with changes to Tables 2&4, as shown below, and...     

The false-negative fraction: a statistical method to measure the efficacy of cervical smear screening laboratories.

The false-negative fraction (FNF) is emerging as a statistical parameter that may be used to evaluate the efficacy of Papanicolaou smear screening laboratories. Our objectives for this paper are to acquaint non-laboratorians with this important measurement and to measure the FNF of the Air Force Cyto-center (AFCC) at the Armed Forces Institute of Pathology in Washington, DC. The FNF is defined as estimated false negatives divided by (true positives plus estimated false negatives). Most often, the number generated is multiplied by 100 and expressed as a percent. We have determined the FNF of the AFCC to be 3.7%. This value compares favorably with most others reported in the medical literature.     

Defining principles that influence antimicrobial peptide activity against capsulated Klebsiella pneumoniae

The extracellular polysaccharide capsule of Klebsiella pneumoniae resists penetration by antimicrobials and protects the bacteria from the innate immune system. Host antimicrobial peptides are inactivated by the capsule as it impedes their penetration to the bacterial membrane. While the capsule sequesters most peptides, a few antimicrobial peptides have been identified that retain activity against encapsulated K. pneumoniae, suggesting that this bacterial defense can be overcome. However, it is unclear what factors allow peptides to avoid capsule inhibition. To address this, we created a peptide analog with strong antimicrobial activity toward several K. pneumoniae strains from a previously inactive peptide. We characterized the effects of these two peptides on K. pneumoniae, along with their physical interactions with K. pneumoniae capsule. Both peptides disrupted bacterial cell membranes, but only the active peptide displayed this activity against capsulated K. pneumoniae. Unexpectedly, the active peptide showed no decrease in capsule binding, but did lose secondary structure in a capsule-dependent fashion compared with the inactive parent peptide. We found that these characteristics are associated with capsule-peptide aggregation, leading to disruption of the K. pneumoniae capsule. Our findings reveal a potential mechanism for disrupting the protective barrier that K. pneumoniae uses to avoid the immune system and last-resort antibiotics.

Multidrug-resistant (MDR) bacterial infections have become a major threat to human health (1–3). Mortality rates from infections caused by gram-negative bacteria, specifically Klebsiella pneumoniae, are on the rise owing to the lack of effective antibiotics to treat the emergent MDR strains (4–7). The capsule of K. pneumoniae is composed of extracellular polysaccharides that promote infection by masking the bacteria from immune recognition and provide an especially potent barrier against peptide-based antimicrobials, including innate host defense peptides and last-resort polymyxin antibiotics (8–14).Antimicrobial peptides are commonly amphipathic, with both a charged and a hydrophobic character (15). The anionic nature of the bacterial capsule promotes an electrostatic attraction to cationic antimicrobial peptides, and peptide hydrophobicity has been proposed to enhance capsule binding through nonionic interactions (9, 12, 16). Interaction with the bacterial capsule is thought to induce structural changes that cause sequestration of antimicrobial peptides to prevent them from reaching their bacterial membrane target (16, 17). While the bacterial capsule inhibits host defense peptides and polymyxins, a few amphipathic antimicrobial peptides have been identified that can retain activity against capsulated K. pneumoniae (18–21). However, it is not known what enables some peptides to avoid sequestration by the capsule of K. pneumoniae while the capsule effectively neutralizes our innate host defense peptides with similar physicochemical properties. This lack of knowledge prevents us from understanding how to bypass the capsule barrier that K. pneumoniae uses to avoid our innate immune response and last-resort treatment options.Here we characterize the synthetic evolution of a peptide inhibited by capsule to a peptide with potent activity against capsulated K. pneumoniae. Remarkably, our results indicate that rather than reduced interactions, our active peptide retains binding to capsule and undergoes conformational changes associated with capsule aggregation. We present a model in which peptide-driven sequestration of capsule disrupts this barrier and reduces its ability to protect K. pneumoniae against antimicrobial attack. These findings provide insight into improving antimicrobial peptide activity against K. pneumoniae and may help strengthen our understanding of the inability of innate host defense peptides to act on capsulated bacteria.     

'Recurrent' glioblastoma multiforme, when should we reoperate?

The surgical management of recurrent glioblastoma multiforme is controversial. Recent publications suggest that re-operation provides 3-5 months median survival, without significant increases in morbidity or mortality. Age (< or =50 years, although older patients may also benefit) and performance status (Karnofsky performance score > or =60-70) are the most important factors. Re-resection not only improves symptoms and maintains quality of life, it can delay symptom progression, reduce corticosteroid doses, and also improve response to (and allow intra-operative) chemotherapy and/or radiotherapy. Surgical treatment of recurrent glioblastoma multiforme in selected patients should always be considered.