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The purpose of this review is to summarize essential biological, pharmaceutical, and clinical aspects in the field of topically applied medicines that may help scientists when trying to develop new topical medicines. After a brief history of topical drug delivery, a review of the structure and function of the skin and routes of drug absorption and their limitations is provided. The most prevalent diseases and current topical treatment approaches are then detailed, the organization of which reflects the key disease categories of autoimmune and inflammatory diseases, microbial infections, skin cancers, and genetic skin diseases. The complexity of topical product development through to large-scale manufacturing along with recommended risk mitigation approaches are then highlighted. As such topical treatments are applied externally, patient preferences along with the challenges they invoke are then described, and finally the future of this field of drug delivery is discussed, with an emphasis on areas that are more likely to yield significant improvements over the topical medicines in current use or would expand the range of medicines and diseases treatable by this route of administration. SIGNIFICANCE STATEMENT: This review of the key aspects of the skin and its associated diseases and current treatments along with the intricacies of topical formulation development should be helpful in making judicious decisions about the development of new or improved topical medicines. These aspects include the choices of the active ingredients, formulations, the target patient population's preferences, limitations, and the future with regard to new skin diseases and topical medicine approaches.

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Two techniques for analyzing human extracranial neurophysiological signals, namely the periodic/aperiodic parameterization of neural power spectra and the transient events framework of oscillatory activity, have recently emerged in the scientific literature. In this work, we integrate these two analysis perspectives to analyze extracranial neurophysiological signals as a series of transient rhythmic events disambiguated from the background aperiodic activity. We call this novel technique the periodic/aperiodic parametrization of transient oscillations (PAPTO). We demonstrate PAPTO by investigating resting-state sensorimotor magnetoencephalography recordings from the Cambridge Center for Ageing and Neuroscience cross-sectional study on healthy ageing (n = 600, ages 18-88). We show that PAPTO is more sensitive to neocortical transient beta rhythms compared to more conventional transient event detection algorithms and captures more variance in the resting-state occurrence rate of beta events across participants. The improved sensitivity of PAPTO reveals that the beta occurrence rate almost doubles over the adult lifespan which we discuss in terms of thalamocortical beta generation in the somatosensory cortex and the age-related decline of sensory perception.

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Non-invasive neurophysiological recordings, such as those measured by magnetoencelography (MEG), provide insight into the behaviour of neural networks and how these networks change with factors such as task performance, disease state, and age. Recently, there has been a trend in describing neurophysiological recordings as a series of transient bursts of neural activity rather than averaged sustained oscillations as burst characteristics may be more directly correlated with the neurological generators of brain activity. In this work, we investigate how beta burst characteristics change with age in a large open access dataset. The objectives are (1) to detect and characterize transient beta bursts over the ipsilateral and contralateral primary sensorimotor cortices during a unilateral motor task performance and during wakeful resting, and (2) to identify age-related changes in beta burst characteristics, in the context of earlier reports of age-related changes in beta suppression and the post-movement beta rebound. MEG data, acquired at the Cambridge Centre for Ageing and Neuroscience, of roughly 600 participants with a nearly uniform distribution of ages between 18 and 88 years old was used for analysis. We found that burst rate is the predominant factor related to age-related changes in the amplitude of the induced beta rhythm responses associated with a button press task. Furthermore, we present a cross-validation of burst parameters detected at the sensor- (peak sensor and sensor ROI) and source-level (beamformer spatial filter). This work is as an important step in characterizing transient bursts in neuromagnetic signals in the temporal domain, towards a better understanding of the healthy aging human brain.

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Molybdenum disulfide (MoS2) has shown highly attractive superiority as a platform for sensing. However, DNA physisorption on the surface of MoS2 was susceptible to nonspecific probe displacement and false-positive signals. To solve these problems, we have developed a novel MoS2-aptamer nanosheet biosensor for detecting thrombin using a covalently linked aptamer to the MoS2 nanosheet. Ten percent Tween 80 was used to prevent thrombin from nonspecific binding and to rapidly form thiol-DNA/gold nanoparticle (AuNP) conjugates. Furthermore, an MoS2 and exonuclease coassisted signal amplification strategy was developed to improve the detection limit for thrombin. We used the hybridization of the aptamer molecules and the matched strand with a 5' terminal thiol to immobilize the aptamer molecules on the surface of AuNPs in AuNPs@MoS2 nanocomposites. Exonuclease digested the single-strand aptamer and released the thrombin, which was then detected in the next recycle. With the coassisted amplification strategy, a 6 fM detection limit was achieved, showing that this method has higher sensitivity than most reported methods for thrombin detection. The results presented in this work show that this method of covalently attaching the aptamer and using the coassisted amplification is a promising technique for the detection of protein in medical diagnostics.

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Recently, graphene oxide (GO) has shown superiority for disease detection arising from its unique physical and chemical properties. However, proteins adsorbed on the surface of GO prevent sensitivity improvement in fluorescence-based detection methods. In this paper, a label-free method based on aptamer modified gold nanoparticles (GNPs) combined with Tween 80 was shown to solve this problem using the detection of thrombin as an example. An aptamer was designed and bound to thrombin by changing its conformation. Tween 80 was used for rapid and reproducible synthesis of stable DNA-functionalized GNPs and prevented the thrombin from nonspecific binding to GO. Thrombin was detected with a limit of 0.68 pM by taking advantage of the efficient cross-linking effect of aptamer-GNPs to GO. The sensor was validated by determining thrombin concentration in human blood serum samples. The results indicate that this method has promising analytical application in medical diagnostic.

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