Infectious meningitis and encephalitis is caused by invasion of circulating pathogens into the brain. It is unknown how the circulating pathogens dynamically interact with brain endothelium under shear stress, leading to invasion into the brain. Here, using intravital microscopy, we have shown that Cryptococcus neoformans, a yeast pathogen that causes meningoencephalitis, stops suddenly in mouse brain capillaries of a similar or smaller diameter than the organism, in the same manner and with the same kinetics as polystyrene microspheres, without rolling and tethering to the endothelial surface. Trapping of the yeast pathogen in the mouse brain was not affected by viability or known virulence factors. After stopping in the brain, C. neoformans was seen to cross the capillary wall in real time. In contrast to trapping, viability, but not replication, was essential for the organism to cross the brain microvasculature. Using a knockout strain of C. neoformans, we demonstrated that transmigration into the mouse brain is urease dependent. To determine whether this could be amenable to therapy, we used the urease inhibitor flurofamide. Flurofamide ameliorated infection of the mouse brain by reducing transmigration into the brain. Together, these results suggest that C. neoformans is mechanically trapped in the brain capillary, which may not be amenable to pharmacotherapy, but actively transmigrates to the brain parenchyma with contributions from urease, suggesting that a therapeutic strategy aimed at inhibiting this enzyme could help prevent meningitis and encephalitis caused by C. neoformans infection.

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Anthropogenic noise is now recognized as a major global pollutant. Rapidly burgeoning research has identified impacts on individual behaviour and physiology through to community disruption. To date, however, there has been an almost exclusive focus on vertebrates. Not only does their central role in food webs and in fulfilling ecosystem services make imperative our understanding of how invertebrates are impacted by all aspects of environmental change, but also many of their inherent characteristics provide opportunities to overcome common issues with the current anthropogenic noise literature. Here, we begin by explaining why invertebrates are likely to be affected by anthropogenic noise, briefly reviewing their capacity for hearing and providing evidence that they are capable of evolutionary adaptation and behavioural plasticity in response to natural noise sources. We then discuss the importance of quantifying accurately and fully both auditory ability and noise content, emphasizing considerations of direct relevance to how invertebrates detect sounds. We showcase how studying invertebrates can help with the behavioural bias in the literature, the difficulties in drawing strong, ecologically valid conclusions and the need for studies on fitness impacts. Finally, we suggest avenues of future research using invertebrates that would advance our understanding of the impact of anthropogenic noise.

Climbing frequency and technical difficulty are associated with climbing injuries occurring at both indoor and outdoor venues, particularly cumulative trauma to the upper extremities.

Natural killer (NK) cells are a subset of immune effectors that directly bind and kill fungi via a perforin-dependent mechanism. The receptor mediating this activity and its potential role in disease remain unknown. Using an unbiased approach, we determined that NKp30 is responsible for recognition and killing of the fungal pathogens Cryptococcus and Candida. NKp30 was required for NK cell-fungal conjugate formation, phosphatidylinositol 3-kinase (PI3K) signaling, and perforin release. Because fungal infections are a leading cause of death in AIDS patients, we examined NKp30 expression in HIV-infected patients. NK cells from these patients had diminished NKp30 expression, defective perforin release, and blunted microbicidal activity. Surprisingly, interleukin-12 (IL-12) restored NKp30 expression and fungal killing. Thus, the NKp30 receptor plays a critical role in NK cell antifungal cytotoxicity, and diminished expression of NKp30 is responsible for defective antifungal activity of NK cells from HIV-infected patients, which can be corrected with IL-12.

Protease inhibitor exposure is an unrecognized risk factor for the development of HIV-SN, which may potentiate neuronal damage in HIV-infected DRGs, possibly through the loss of macrophage-derived trophic factors.

Query-expansion is an effective Relevance Feedback technique for improving performance in Information Retrieval. In general query-expansion methods select terms from the complete contents of relevant documents. One problem with this approach is that expansion terms unrelated to document relevance can be introduced into the modified query due to their presence in the relevant documents and distribution in the document collection. Motivated by the hypothesis that queryexpansion terms should only be sought from the most relevant areas of a document, this investigation explores the use of document summaries in query-expansion. The investigation explores the use of both context-independent standard summaries and query-biased summaries. Experimental results using the Okapi BM25 probabilistic retrieval model with the TREC-8 ad hoc retrieval task show that query-expansion using document summaries can be considerably more effective than using full-document expansion. The paper also presents a novel approach to term-selection that separates the choice of relevant documents from the selection of a pool of potential expansion terms. Again, this technique is shown to be more effective that standard methods.

Background Fibromyalgia is characterised by persistent, widespread pain; sleep problems; and fatigue. Transcutaneous electrical nerve stimulation (TENS) is the delivery of pulsed electrical currents across the intact surface of the skin to stimulate peripheral nerves and is used extensively to manage painful conditions. TENS is inexpensive, safe, and can be self-administered. TENS reduces pain during movement in some people so it may be a useful adjunct to assist participation in exercise and activities of daily living. To date, there has been only one systematic review in 2012 which included TENS, amongst other treatments, for fibromyalgia, and the authors concluded that TENS was not e ective. Objectives To assess the analgesic e icacy and adverse events of TENS alone or added to usual care (including exercise) compared with placebo (sham) TENS; no treatment; exercise alone; or other treatment including medication, electroacupuncture, warmth therapy, or hydrotherapy for fibromyalgia in adults. Search methods We searched the following electronic databases up to 18 January 2017: CENTRAL (CRSO); MEDLINE (Ovid); Embase (Ovid); CINAHL (EBSCO); PsycINFO (Ovid); LILACS; PEDRO; Web of Science (ISI); AMED (Ovid); and SPORTDiscus (EBSCO). We also searched three trial registries. There were no language restrictions. Selection criteria We included randomised controlled trials (RCTs) or quasi-randomised trials of TENS treatment for pain associated with fibromyalgia in adults. We included cross-over and parallel-group trial designs. We included studies that evaluated TENS administered using non-invasive techniques at intensities that produced perceptible TENS sensations during stimulation at either the site of pain or over nerve bundles proximal (or near) to the site of pain. We included TENS administered as a sole treatment or TENS in combination with other treatments, and TENS given as a single treatment or as a course of treatments. Data collection and analysis Two review authors independently determined study eligibility by assessing each record and reaching agreement by discussion. A third review author acted as arbiter. We did not anonymise the records of studies before assessment. Two review authors independently extracted data and assessed risk of bias of included studies before entering information into a 'Characteristics of included studies' table. Transcutaneous electrical nerve stimulation (TENS) for fibromyalgia in adults (Review)