Immunosuppressive drugs for solid organ transplantation are critical dose drugs with a narrow therapeutic index. Many of the most commonly used innovator drugs are off patent and have been replicated by generic counterparts, often at substantial cost-savings to the patient. However, serious adverse events caused by the transition from innovator to generic medications, specifically in pediatric solid organ transplant recipients, have questioned these autosubstitutions. The purpose of this review is to summarize the criteria set forth by the regulatory bodies, and to examine how major immunosuppressive drugs conform to these recommendations. Regulatory bodies have established inconsistent criteria to demonstrate bioequivalence between innovator and generic medications, causing approved generic variations to have varying levels of equivalence with the innovator drugs. In order to minimize the risk for under-immunosuppression, the following recommendations have been concluded. Brand prescribing of cyclosporine and tacrolimus are recommended due to evidence of adverse events after conversion to generic formulations and differences in dissolution parameters. Mycophenolate mofetil (MMF) shows better bioequivalence between innovator and generic formulations, however caution should be advised when switching between formulations. The institution of 'innovator only' policies may be appropriate at this time in order to minimize the risk of under-immunosuppressing patients until the evidence of more stringent bioequivalence has been established.

Introduction: Lung cancer has a high mortality rate mainly due to the lack of early detection or outward signs and symptoms, thereby often progressing to advanced stages (e.g., stage IV) before it is diagnosed. However, if lung cancers can be diagnosed at an early stage and also if clinicians can prospectively identify patients likely to respond to specific treatments, then there is a very high potential to increase patients’ survival. In recent years, several investigations have been conducted to identify cancer biomarkers for lung cancer risk assessment, early detection and diagnosis, the likelihood of identifying the group of patients who will benefit from a particular treatment and monitoring patient response to treatment. Materials and Methods: This paper reports on the review of 19 current clinical and emerging biomarkers used in risk assessment, screening for early detection and diagnosis and monitoring the response of treatment of non-small-cell lung cancers. Conclusion: The future holds promise for personalised and targeted medicine from prevention, diagnosis to treatment, which take into account individual patient’s variability, though it depends on the development of effective biomarkers interrogating the key aberrant pathways and potentially targetable with molecular targeted or immunologic therapies. Lung cancer biomarkers have the potential to guide clinical decision-making since they can potentially detect the disease early, measure the risk of developing the disease and the risk of progression, provide accurate information of patient response to a specific treatment and are capable of informing clinicians about the likely outcome of a cancer diagnosis independent of the treatment received. Moreover, lung cancer biomarkers are increasingly linked to specific molecular pathway deregulations and/or cancer pathogenesis and can be used to justify the application of certain therapeutic or interventional strategies.

Synaptic transmission is the process that underlies most neuronal communication. In the pre-synaptic neuron, membrane depolarization opens calcium channels and the calcium influx triggers exocytosis, in which synaptic vesicles (SVs) fuse with the presynaptic plasma membrane and release neurotransmitters to the synaptic cleft. Membrane added to the presynaptic terminal, via exocytosis, must be recovered by endocytosis to maintain a releasable pool of SVs and to preserve the terminal surface area. That is, exocytosis and endocytosis are coupled. Because at least some endocytosis occurs some distance away from exocytosis sites, SVs turnover implies generation of membrane tension gradients and membrane flow from exocytic sites to endocytic ones. Plasma membrane flows in non-neuronal cells and non-terminal regions of neurons are known to be extremely slow. Such slow flows would impose constraints on the spatio-temporal coupling of exo-and endocytosis. However, membrane tension dynamics and membrane flows have never been quantified at nerve terminals. Here we use goldfish retinal bipolar neurons which possess a giant synaptic terminal to address this issue. We use optical tweezers to pull a thin membrane tether whose restoring force reports membrane tension. We observe that tension can propagate rapidly (seconds) over long distances ($10 mm) in the terminal. In addition, tethers can be dragged around the terminal with little resistance, in sharp contrast to the soma where high friction between the membrane and the cytoskeleton prevents tether sliding. Overall, our results suggest that facile membrane flow and tension equilibration at presynaptic terminals are tuned for rapid turnover of synaptic vesicles, thus playing a key role in neurotransmission.