Review article: Non-penetrating neck artery dissection in young adults: Not to be missed!

Young adults who present to the ED with neck pain following non-penetrating, seemingly trivial trauma to the neck, are at risk of neck artery dissection and subsequent stroke. Sport-related neck injury is the chief cause. Physical examination may often be unremarkable, and although there may be reluctance to expose young patients to radiation, radiological imaging is central to making a diagnosis of arterial wall disruption. A comprehensive literature search was performed in relation to neck artery dissection, and the evidence was scrutinised. We discuss the typical mechanism of injury, symptoms, anatomical considerations and clinical aids in diagnosis of neck artery dissection. Although the incidence is low, neck artery dissection has a mortality of 7%. As such, it is important for front-line physicians to have a high suspicion of the diagnosis and a low threshold to organise radiological examinations, specifically computerised tomography. Early detection of neck artery dissection will trigger clinical protocols that call for multi-disciplinary team management of this condition. In general, guideline-based recommendation for the management of neck artery dissection involving an intimal flap is by anti-platelet therapy while treatment of neck artery dissection that results in a pseudo-aneurysm or thrombosis is managed by surgical intervention or endovascular techniques. Close follow up combined with antithrombotic treatment is recommended in these individuals, the goal being prevention of stroke.

Rare presentation of Waldenström's macroglobulinaemia requiring bilateral above-knee amputations: a case report.

BACKGROUND: Waldenström's macroglobulinaemia is a rarely encountered B-lymphocytic malignancy. Waldenström's macroglobulinaemia-associated paraproteinaemia is linked to an increase in serum viscosity, which results in a hypercoagulable state. Burning bilateral foot pain in a man with alcohol dependence and controlled atrial fibrillation presenting to the emergency department was attributed to peripheral neuropathy, given satisfactory angiographic evidence of bilateral foot arterial blood supply. Subsequently, his presentation as an emergency with acute bilateral critical lower limb ischemia that was managed by bilateral above-knee amputations, prompted a wider search for other etiologies. We present a hitherto unreported case of Waldenström's macroglobulinaemia-related acute bilateral lower limb ischemia, which required bilateral above-knee amputations. CASE PRESENTATION: A 50-year-old Caucasian man, who was an alcohol dependent heavy smoker, presented with burning pain in his right foot that was deemed to be related to alcoholic neuropathy. A computerized tomographic angiogram demonstrated an occluded right distal anterior tibial artery but a patent posterior tibial artery supplying the foot arch, findings that were associated with noncritical ischemia. After multiple presentations within a week, he was admitted following sudden clinical deterioration with acute confusion, hyponatremia, and bilateral foot pain. Over the course of 24 hours, the patient deteriorated rapidly, with bilateral lower limb ischemia requiring bilateral above-knee amputations. Subsequent investigations revealed a diagnosis of Waldenström's macroglobulinaemia. CONCLUSIONS: To the best of our knowledge, this is the only reported case of Waldenström's macroglobulinaemia-induced bilateral lower limb ischemia requiring major bilateral amputations.

Proton Pump Inhibitors and Cardiovascular Events: A Systematic Review.

BACKGROUND: Proton pump inhibitors (PPIs) are a commonly prescribed medication that recent data has linked to an increased risk of cardiovascular morbidity and all cause morbidity. The current study sought to perform a systematic review to investigate the link between PPIs and morbidity and mortality METHODS: A systematic review was carried out as per the PRISMA guidelines, with information databases including Pubmed, Medline, and the Cochrane Review Database. English-language studies of all types published from January 1990 to October 2016 were considered. Dichotomous analysis generating odds ratios was performed using RevMan Version 5.3. RESULTS: Thirty-seven studies were considered, of which five directly compared the effect of PPI use on mortality and/or cardiovascular morbidity (including 22,427 patients in mortality datasets, and 354,446 patients in morbidity datasets). For patients taking PPIs, all cause mortality (OR 1.68 [95% CI 1.53-1.84], p<0.001) and rate of major cardiovascular events (OR 1.54 [95% CI 1.11-2.13], p=0.01) were significantly higher. CONCLUSIONS: The current systematic review demonstrates that, in patients using PPIs, there was a significant increase in morbidity due to cardiovascular disease. Careful consideration should be given to the prescription of PPIs while clinical equipoise remains. Further research in the area is required.

Practical intravital two-photon microscopy for immunological research: faster, brighter, deeper.

With its emphasis on minimally invasive high-speed imaging of intact tissues at depth, video-rate two-photon microscopy has revolutionized cell biology. This is particularly true in immunology, where the orchestration of cell migration, cell-cell interactions and intracellular signalling events in multiple distinct anatomical compartments within secondary lymphoid organs is fundamental for achieving an effective immune response. Until recently, access to this powerful tool has been limited to a handful of laboratories with the necessary skills and resources to either custom-build or purchase a commercial two-photon microscope. However, with the entry of more commercial vendors into the market and availability of turnkey solutions, two-photon microscopy is now becoming more accessible. Here, we discuss the practical aspects of establishing a basic intravital two-photon microscopy facility specifically for immunological research and how recent advances in ultrafast lasers, non-linear optics and localized photochemistry can be used to build more sophisticated instruments to support applications such as photoactivation and photobleaching, spectral fingerprinting and automated single-cell tracking. In addition, we discuss the next generation of fluorescent dyes and reporter mice and some of the microsurgical principles required to expose the relevant biology to interrogation by two-photon excitation.

Two-photon imaging of the immune system: a custom technology platform for high-speed, multicolor tissue imaging of immune responses.

Modern imaging approaches are proving important for addressing contemporary issues in the immune system. These approaches are especially useful for characterizing the complex orchestration of immune responses in vivo. Multicolor, two-photon imaging has been proven to be especially enabling for such studies because of its superior tissue penetration, reduced image degradation by light scattering leading to better resolution, and its high image quality deep inside tissues. Here, we examine the functional requirements of two-photon imaging instruments necessary for such immune studies. These requirements include frame rate, spatial resolution and the number of emission channels. We use this discussion as a starting point to compare commercial systems and to introduce a custom technology platform that meets those requirements. This platform is noteworthy because it is very cost-effective, flexible and experimentally useful. Representative data collected with this instrument is used to demonstrate the utility of this platform. Finally, as the field is rapidly evolving, consideration is given to some of the cutting-edge developments in multiphoton microscopy that will likely improve signal strength, depth penetration and/or the experimental usefulness of this approach.

Microscopic imaging techniques for drug discovery.

Microscopic imaging can enhance the drug discovery process by helping to describe how disease processes unfold and how potential therapies might intervene. Recently introduced technologies, and enhancements to existing techniques, are addressing technical issues that have limited the usefulness of microscopic imaging in the past. In particular, these innovations are improving spatial resolution, increasing tissue penetration, overcoming physical access issues and enhancing experimental throughput. Notable recent trends, which are discussed in this article, include the development of super-resolution microscopes, the incorporation of multiphoton techniques into intravital and fibre-optic microscopy and the automation of microscopy and image analysis for high-content screening. Together, these developments are augmenting the existing assays and disease models that are used in early drug discovery and, in some cases, enabling new ones.

Synthesis, spectra, delivery and potentiometric responses of new styryl dyes with extended spectral ranges.

Styryl dyes have been among the most widely used probes for mapping membrane potential changes in excitable cells. However, their utility has been somewhat limited because their excitation wavelengths have been restricted to the 450-550 nm range. Longer wavelength probes can minimize interference from endogenous chromophores and, because of decreased light scattering, improve recording from deep within tissue. In this paper we report on our efforts to develop new potentiometric styryl dyes that have excitation wavelengths ranging above 700 nm and emission spectra out to 900 nm. We have prepared and characterized dyes based on 47 variants of the styryl chromophores. Voltage-dependent spectral changes have been recorded for these dyes in a model lipid bilayer and from lobster nerves. The voltage sensitivities of the fluorescence of many of these new potentiometric indicators are as good as those of the widely used ANEP series of probes. In addition, because some of the dyes are often poorly water soluble, we have developed cyclodextrin complexes of the dyes to serve as efficient delivery vehicles. These dyes promise to enable new experimental paradigms for in vivo imaging of membrane potential.