A Thalamic Reticular Circuit for Head Direction Cell Tuning and Spatial Navigation.

As we navigate in space, external landmarks and internal information guide our movement. Circuit and synaptic mechanisms that integrate these cues with head-direction (HD) signals remain, however, unclear. We identify an excitatory synaptic projection from the presubiculum (PreS) and the multisensory-associative retrosplenial cortex (RSC) to the anterodorsal thalamic reticular nucleus (TRN), so far classically implied in gating sensory information flow. In vitro, projections to TRN involve AMPA/NMDA-type glutamate receptors that initiate TRN cell burst discharge and feedforward inhibition of anterior thalamic nuclei. In vivo, chemogenetic anterodorsal TRN inhibition modulates PreS/RSC-induced anterior thalamic firing dynamics, broadens the tuning of thalamic HD cells, and leads to preferential use of allo- over egocentric search strategies in the Morris water maze. TRN-dependent thalamic inhibition is thus an integral part of limbic navigational circuits wherein it coordinates external sensory and internal HD signals to regulate the choice of search strategies during spatial navigation

Fractional Microablative CO2 Laser-Related Histological Changes on Vulvar Tissue in Patients With Genitourinary Syndrome of Menopause

Background and Objectives: Fractional CO2 laser has been proposed as an effective treatment for the genitourinary syndrome of menopause (GSM). However, the effects of laser treatment on vulvar tissue have never been assessed. We aimed to assess histological changes related to fractional CO2 laser in vulvar tissue from GSM patients. Study Design/Materials and Methods: A single-center observational prospective cohort study was performed enrolling all GSM patients from July 2017 to October 2018. Patients underwent three outpatient vulvovaginal applications of fractional CO2 laser and vulvar biopsy before and after treatment. Rates of histological changes in vulvar tissue, the difference in means of Vulva Health Index (VuHI), Vaginal Health Index (VHI), Visual Analogue Scale scores for GSM symptoms, and procedure-related pain, and rate of patient's overall satisfaction with treatment were assessed. Univariate comparisons between continuous variables were performed by using the paired t-test (α error = 0.05). Results: Of 20 enrolled patients, 18 underwent all laser applications, and 15 underwent both vulvar biopsies. 93.3% of patients showed remodeling of vulvar connective tissue; 80% showed improvement in vulvar epithelium trophism and 86.7% showed neovascularization. Differences in means between before and after treatment were significant for VuHI, VHI, and all GSM symptoms. Means ± standard deviation of the degree of pain at each laser application were 4.4 ± 0.9, 3.7 ± 1.6, and 2.9 ± 1.9. The rate of overall satisfaction with the treatment was 72.2%. Conclusions: Fractional CO2 laser leads to a restoration of the normal architecture of vulvar tissue, with significant improvement in GSM-related signs and symptoms, and overall satisfaction with the treatment in most GSM patients. Lasers Surg. Med. © 2020 Wiley Periodicals LLC

Circadian rhythms are associated with variation in photosystem II function and photoprotective mechanisms

The circadian clock regulates many aspects of leaf gas supply and biochemical demand for CO2 20 , and is hypothesized to improve plant performance. Yet the extent to which the clock may regulate the efficiency of photosystem II (PSII) and photoprotective mechanisms such as heat dissipation remains largely unexplored. Based on measurements of chlorophyll a fluorescence, we estimated the maximum efficiency of photosystem II in light (Fv'/Fm') and heat dissipation by non-photochemical quenching (NPQ). We further dissected total NPQ into its main components, qE (pH-dependent quenching), qT (state-transition quenching) and qI (quenching related to photoinhibition), in clock mutant genotypes of Arabidopsis thaliana, the cognate wild-type genotypes, and a panel of recombinant inbred lines (RILs) expressing quantitative variation in clock period. Compared to mutants with altered clock function, we observed that wild-type genotypes with clock period lengths of approximately 24 hr had both higher levels of Fv'/Fm ', indicative of improved PSII function, and reduced NPQ, suggestive of lower stress on PSII light harvesting complexes. In the RILs, genetic variances were significant for Fv'/Fm' and all three components of NPQ, with qE explaining the greatest proportion of NPQ. Bivariate tests of association and structural equation models of hierarchical trait relationships showed that quantitative clock variation was empirically associated with Fv'/Fm' and NPQ, with qE mediating the relationship with gas exchange. The results demonstrate significant segregating variation for all photoprotective components, and suggest the adaptive significance of the clock may partly derive from its regulation of the light reactions of photosynthesis and of photoprotective mechanisms. Key words: Arabidopsis thaliana, circadian rhythms, chlorophyll a fluorescence, maximum efficiency of PSII, non-photochemical quenchin

Emerging therapies in pheochromocytoma and paraganglioma: Immune checkpoint inhibitors in the starting blocks

Pheochromocytoma and paraganglioma are neuroendocrine neoplasms, originating in the adrenal medulla and in parasympathetic and sympathetic autonomic nervous system ganglia, respec-tively. They usually present as localized tumours curable with surgery. However, these tumours may exhibit heterogeneous clinical course, ranging from no/minimal progression to aggressive (progres-sive/metastatic) behavior. For this setting of patients, current therapies are unsatisfactory. Immune checkpoint inhibitors have shown outstanding results for several types of solid cancers. We therefore aimed to summarize and discuss available data on efficacy and safety of current FDA-approved immune checkpoint inhibitors in patients with pheochromocytoma and paraganglioma. After an extensive search, we found 15 useful data sources (four full-published articles, four supplements of scientific journals, seven ongoing registered clinical trials). The data we detected, even with the limit of the small number of patients treated, make a great expectation on the therapeutic use of immune checkpoint inhibitors. Besides, the newly detected predictors of response will (hopefully) be of great helps in selecting the subset of patients that might benefit the most from this class of drugs. Finally, new trials are in the starting blocks, and they are expected to shed in the next future new light on a therapy, which is considered a milestone in oncology

Violent video games in virtual reality : re-evaluating the impact and rating of interactive experiences

Bespoke Virtual Reality (VR) laboratory experiences can be differently affecting than traditional display experiences. With the proliferation of at-home VR headsets, these effects need to be explored in consumer media, to ensure the public are adequately informed. As yet, the organizations responsible for content descrip-tions and age-based ratings of consumer content do not rate VR games differently to those played on TV. This could lead to experiences that are more intense or subconsciously affecting than desired. To test whether VR and non-VR games are differently affecting, and so whether game ratings are appropriate, our research examined how participant (n=16) experience differed when playing the violent horror video game “Resident Evil 7”, viewed from a first-person perspective in PlayStation VR and on a 40” TV. The two formats led to meaningfully different experiences, suggesting that current game ratings may be unsuitable for capturing and conveying VR experiences

Machine learning assisted DSC-MRI radiomics as a tool for glioma classification by grade and mutation status

Background: Combining MRI techniques with machine learning methodology is rapidly gaining attention as a promising method for staging of brain gliomas. This study assesses the diagnostic value of such a framework applied to dynamic susceptibility contrast (DSC)-MRI in classifying treatment-naïve gliomas from a multi-center patients into WHO grades II-IV and across their isocitrate dehydrogenase (IDH) mutation status. Methods: Three hundred thirty-three patients from 6 tertiary centres, diagnosed histologically and molecularly with primary gliomas (IDH-mutant = 151 or IDH-wildtype = 182) were retrospectively identified. Raw DSC-MRI data was post-processed for normalised leakage-corrected relative cerebral blood volume (rCBV) maps. Shape, intensity distribution (histogram) and rotational invariant Haralick texture features over the tumour mask were extracted. Differences in extracted features across glioma grades and mutation status were tested using the Wilcoxon two-sample test. A random-forest algorithm was employed (2-fold cross-validation, 250 repeats) to predict grades or mutation status using the extracted features. Results: Shape, distribution and texture features showed significant differences across mutation status. WHO grade II-III differentiation was mostly driven by shape features while texture and intensity feature were more relevant for the III-IV separation. Increased number of features became significant when differentiating grades further apart from one another. Gliomas were correctly stratified by mutation status in 71% and by grade in 53% of the cases (87% of the gliomas grades predicted with distance less than 1). Conclusions: Despite large heterogeneity in the multi-center dataset, machine learning assisted DSC-MRI radiomics hold potential to address the inherent variability and presents a promising approach for non-invasive glioma molecular subtyping and grading

Locative Media and Sociability:Using Location-Based Social Networks to Coordinate Everyday Life

Foursquare was a mobile social networking application that enabled people to share location with friends in the form of “check-ins.” The visualization of surrounding known social connections as well as unknown others has the potential to impact how people coordinate social encounters and forge new social ties. While many studies have explored mobile phones and sociability, there is a lack of empirical research examining location-based social network’s (LSBNs) from a sociability perspective. Drawing on a dataset of original qualitative research with a range of Foursquare users, the paper examines the application in the context of social coordination and sociability in three ways. First, the paper explores if Foursquare is used to organize certain social encounters, and if so, why. Second, the paper examines the visualization of surrounding social connections and whether this leads to “serendipitous encounters.” Lastly, the paper examines whether the use of Foursquare can produce new social relationships