Diverse computations in the neocortex are aided by specialized GABAergic interneurons (INs), which selectively target other INs. However, much less is known about how these canonical disinhibitory circuit motifs contribute to network operations supporting spatial navigation and learning in the hippocampus. Using chronic two-photon calcium imaging in mice performing random foraging or goal-oriented learning tasks, we found that vasoactive intestinal polypeptide-expressing (VIP +), disinhibitory INs in hippocampal area CA1 form functional subpopulations defined by their modulation by behavioral states and task demands. Optogenetic manipulations of VIP + INs and computational modeling further showed that VIP + disinhibition is necessary for goaldirected learning and related reorganization of hippocampal pyramidal cell population dynamics. Our results demonstrate that disinhibitory circuits in the hippocampus play an active role in supporting spatial learning.

Functional response models are important in understanding predator-prey interactions. The development of functional response methodology has progressed from mechanistic models to more statistically motivated models that can account for variance and the over-dispersion commonly seen in the datasets collected from functional response experiments. However, little information seems to be available for those wishing to prepare optimal parameter estimation designs for functional response experiments. It is worth noting that optimally designed experiments may require smaller sample sizes to achieve the same statistical outcomes as non-optimally designed experiments. In this paper, we develop a model-based approach to optimal experimental design for functional response experiments in the presence of parameter uncertainty (also known as a robust optimal design approach). Further, we develop and compare new utility functions which better focus on the statistical efficiency of the designs; these utilities are generally applicable for robust optimal design in other applications (not just in functional response). The methods are illustrated using a beta-binomial functional response model for two published datasets: an experiment involving the freshwater predator (an aquatic insect) preying on (a small crustacean), and another experiment involving a ladybird beetle ( L.) preying on the black bean aphid ( Scopoli). As a by-product, we also derive necessary quantities to perform optimal design for beta-binomial regression models, which may be useful in other applications.

BackgroundFew studies have compared technical success and effectiveness of transradial access (TRA) versus transfemoral access (TFA) for mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We compared the two approaches for technical success, effectiveness, and outcomes.MethodsWe retrospectively compared TRA with TFA for AIS MT at our institute. We additionally performed a systematic review and meta-analysis of studies describing the use of TRA alone or in comparison with TFA for MT. Primary outcomes included rate of successful reperfusion (thrombolysis in cerebral infarction (TICI) >2b), number of passes, access-site complications, and 3- month mortality and favorable functional outcomes (modified Rankin Scale (mRS) score 0–2).ResultsA total of 222 consecutive patients (TRA=93, TFA=129) were included in our case series. The rate of successful reperfusion was significantly higher for the TFA cohort (91.4% vs 79.6%, P=0.01) with lower mean number of passes (1.8±1.2 vs 2.4±1.6, P=0.014). Three-month mortality in the TFA group was lower (22.1% vs 40.9% for the TRA cohort (P=0.004), with a higher rate of favorable functional outcomes (51.3% vs 34.1%, P=0.015). A meta-analysis of 10 studies showed significant heterogeneity in rates of successful reperfusion (57.1% to 95.6%, heterogeneity=67.55%, P=0.001). None of the previous comparative studies reported 3-month mortality and functional outcomes.ConclusionsThis case series demonstrate a higher successful reperfusion rate, fewer passes, lower 3-month mortality, and improved 3-month functional outcomes with TFA. The systematic review highlights the inadequacy of existing evidence. Prospective comparative studies are needed before a ‘radial-first’ approach can be adopted for stroke intervention.

Over the past two decades, multiple studies have demonstrated the important role that the autonomic nervous system (ANS) plays in tumorigenesis and cancer progression. However, the mechanisms by which this process occurs have only recently begun to be elucidated. Further, the extent of autonomic innervation in various cancer types and its effects on tumor molecular, immunological, and histopathological features, as well as on patient outcomes, are not yet fully characterized. In this study, we analyzed intratumoral ANS gene expression signatures, including overall intratumoral neuron growth and sympathetic and parasympathetic markers, across 32 cancer types using tumor transcriptomic and clinical annotation data available from The Cancer Genome Atlas (TCGA). Our analysis revealed wide variations in intratumoral ANS expression both within and across cancer types. The association of ANS signatures with tumor histopathological characteristics and survival outcomes also varied by cancer type. We found intratumoral ANS expression to be commonly correlated with angiogenesis, TGF-β signaling, and immunosuppression in the tumor microenvironment of many cancer types, which provide mechanistic insights into the involvement of intratumoral innervation in cancer development and progression. Our findings suggest that the potential benefits of cancer therapies targeting β-adrenergic receptor-mediated stress signaling pathways are likely dependent on cancer type.

Morgellons disease (MD) is a rare dermatopathy characterized by nonspecific symptoms and the production of multicolored fibers and granular tissue from diffuse skin ulcerations which are described as being either pruritic or painful.The etiology of MD is currently unknown; previous studies have suggested both psychiatric and infectious causes, with increasing interest over the previous decade in elaborating a possible pathogenesis for the disease secondary to infection by Borrelia species. We report a middle-aged Caucasian female who developed symptoms of MD in the days following exposure to a tick bite after spending an afternoon hiking through a wooded area. She was subsequently treated with a course of Doxycycline and found on two-week follow-up to have complete remission of her symptoms. This case report further supports the theory for an infectious etiology of MD and encourages future studies into its pathophysiology.