Notes

Growth and development of an optimistic Choice Large Throughput Innate Monitor inside Dictyostelium discoideum.
h as CGRP antagonists for migraine.
Our findings provide recent rates of vascular disease in patients with migraine. In the future, this information will be useful to help inform clinical riskbenefit decision making when assessing the use of therapies such as CGRP antagonists for migraine.Working memory (WM) is vulnerable to age-related decline, particularly under high loads. Visual alpha oscillations contribute to WM performance in younger adults, and although alpha decreases in power and frequency with age, it is unclear if alpha activity supports WM in older adults. We recorded electroencephalography (EEG) while 24 younger (aged 18-35 years) and 30 older (aged 50-86) adults performed a modified Sternberg task with varying load conditions. Older adults demonstrated slower reaction times at all loads, but there were no significant age differences in WM capacity. Regardless of age, alpha power decreased and alpha frequency increased with load during encoding, and the magnitude of alpha suppression during retention was larger at higher loads. While alpha power during retention was lower than fixation in older, but not younger adults, the relative change from fixation was not significantly different between age groups. Individual differences in alpha power did not predict performance for either age groups or at any WM loads. We demonstrate that alpha power and frequency are modulated in a similar task- and load-dependent manner during WM in both older and younger adults when WM performance is comparable across age groups. IMPACT STATEMENT Aging is associated with a marked decrease in the power and frequency of alpha oscillations. Here, we demonstrate that when verbal working memory performance is matched across age groups, alpha power and frequency are modulated in a similar task- and load-dependent manner in both young and older adults.Recently, our group used exosomes from mesenchymal stromal/stem cells (MSCs) to simulate an M2 macrophage phenotype, that is, exosome-educated macrophages (EEMs). These EEMs, when delivered in vivo, accelerated healing in a mouse Achilles tendon injury model. For the current study, we first tested the ability of EEMs to reproduce the beneficial healing effects in a different rodent model, that is, a rat medial collateral ligament (MCL) injury model. We hypothesized that treatment with EEMs would reduce inflammation and accelerate ligament healing, similar to our previous tendon results. Second, because of the translational advantages of a cell-free therapy, exosomes alone were also examined to promote MCL healing. We hypothesized that MSC-derived exosomes could also alter ligament healing to reduce scar formation. Similar to our previous Achilles tendon results, EEMs improved mechanical properties in the healing ligament and reduced inflammation, as indicated via a decreased endogenous M1/M2 macrophage ratio. We also showed that exosomes improved ligament remodeling as indicated by changes in collagen production and organization, and reduced scar formation but without improved mechanical behavior in healing tissue. Overall, our findings suggest EEMs and MSC-derived exosomes improve healing but via different mechanisms. EEMs and exosomes each have attractive characteristics as therapeutics. EEMs as a cell therapy are terminally differentiated and will not proliferate or differentiate. Alternatively, exosome therapy can be used as a cell free, shelf-stable therapeutic to deliver biologically active components. Results herein further support using EEMs and/or exosomes to improve ligament healing by modulating inflammation and promoting more advantageous tissue remodeling.Developing novel therapeutics for primary mitochondrial disease is likely to require significant academia-industry collaboration. Translational assessments, a tool often used in industry at target validation stage, can highlight disease specific development challenges which requires focused collaborative effort. For PMD, definition of pivotal trial populations and primary endpoints is challenging given lack of clinical precedence, high numbers of subgroups with overlapping symptoms despite common genetics. Disease pathophysiology has not been systematically assessed simultaneously with outcomes in available natural history studies, resulting in a lack of pathophysiology biomarker utilization in clinical trials. Preclinical model systems are available to assist drug development efforts, although these may require better standardization and access. Multistakeholder precompetitive efforts have been used to progress disease pathophysiology biomarker and confirmatory clinical trial endpoint readiness in neurological disease with limited treatment options, such as rare familial Parkinson's disease. This type of approach may be beneficial for PMD therapeutic development, although requires significant funding and time, supported by industry and other funding bodies. Industry expertise on chemistry, data quality and drug development know-how is available to support academic drug development efforts. A combination of industry mindset-reduction of uncertainty to provide an indication statement supportable by evidence-together with academic approach-question-based studies to understand disease mechanisms and patients-has great potential to deliver novel PMD therapeutics.Invited for the cover of this issue is Alberto Fernández-Alarcón and co-workers at The Institute of Chemistry of the National Autonomous University of Mexico and The School of Chemistry of the University of Oviedo. The image depicts the real space analysis of the excitation energies in the double blue and red shift of the water dimer. Read the full text of the article at 10.1002/chem.202002854.
The role of locoregional radiotherapy for metastatic oropharyngeal squamous cell cancer (OPSCC) is unclear. We investigated the impact of head and neck radiotherapy on survival in de novo metastatic OPSCC patients who received systemic therapy.

We queried the NCDB from 2004-2015 for metastatic OPSCC patients at diagnosis with known HPV-status who received systemic therapy. The association of head and neck radiotherapy with overall survival was analyzed using the Kaplan-Meier method, Cox proportional hazards model, and propensity score-matched analysis adjusting for demographic and disease-specific prognostic factors.

Of the 2,139 patients with metastatic OPSCC who presented with metastases and received systemic treatment, we identified 556 patients with known HPV-status. Among these 556 patients, 49% were HPV-positive and 56% received head and neck radiotherapy. With a median follow-up of 17.5 months (IQR 6.0-163.4 months), radiotherapy was associated with significantly improved 1-year OS (67% vs 58%, log-rank P < .001) which remained significant on MVA (HR 0.78 95% CI 0.62-0.97 P = .029). In HPV-status subgroup analysis, a survival benefit was identified in HPV-positive patients (1-year OS 77% vs 67%, log-rank P < .001) but not in HPV-negative patients. Results were consistent on a propensity score-matched analysis of 212 HPV-positive matched patients (HR 0.66, 95% CI 0.49-0.83, P < .001).

The survival of metastatic OPSCC remains limited. In this large series of patients with known HPV-status, head and neck radiotherapy was associated with longer survival in those with HPV-associated disease. These data could guide management of this challenging group of patients for head and neck cancer practitioners.

3 Laryngoscope, 2020.
3 Laryngoscope, 2020.Pluripotent stem cells (PSCs) can differentiate into all cell types in the body, and their differentiation procedures recapitulate the developmental processes of embryogenesis. Focusing on neurodevelopment, we describe here the application of knowledge gained from embryology to the neural induction of PSCs. Furthermore, PSC-based neural modeling provides novel insights into neurodevelopmental processes. In particular, human PSC cultures are a powerful tool for the study of human-specific neurodevelopmental processes and could even enable the elucidation of the mechanisms of human brain evolution. We also discuss challenges and potential future directions in further improving PSC-based neural modeling.
Tinea capitis is the most common pediatric dermatophyte infection. Optimal treatment regimen differs according to the type of the dermatophyte involved.

The aim of this work was to study the trichoscopic signs in relation to isolated organism in a sample of Egyptian patients with tinea capitis and the possibility of using them as a guide for selection of appropriate antifungal.

This study was carried out on 60 subjects with tinea capitis. Patients were mycologically examined, both direct microscopy with KOH preparation and culture of the scraped hair materials on Sabouraud dextrose agar. Culture mounts were used for identification of the organism. PF-573228 Trichoscopic examination of all patients was performed using the Dermlite DLIII dermoscope.

There was significant higher prevalence of both comma and corkscrew hair in endothrix infection and T. violaceum-infected cases. On the other hand, there was significant higher prevalence of zigzag, barcode hairs, and white sheaths in ectothrix infection and M. canis-infected cases.

While some trichoscopic findings are nonspecific, others were found to be more specific. Finding zigzag hairs and barcode hairs points to ectothrix infection (M. canis), and it is recommended to start treatment with griseofulvin. On the other hand, finding comma hairs and corkscrew hairs without zigzag hairs and barcode hairs points to endothrix infection (T. violaceum), and it is recommended to start treatment with terbinafine in the usual dose.
While some trichoscopic findings are nonspecific, others were found to be more specific. link2 Finding zigzag hairs and barcode hairs points to ectothrix infection (M. canis), and it is recommended to start treatment with griseofulvin. On the other hand, finding comma hairs and corkscrew hairs without zigzag hairs and barcode hairs points to endothrix infection (T. link3 violaceum), and it is recommended to start treatment with terbinafine in the usual dose.Actiniae-like carbon nitride (ACN) bundles were synthesized by the pyrolysis of an asymmetric supramolecular precursor prepared from L-arginine (L-Arg) and melamine. ACN has adjustable band gaps (2.25 eV-2.75 eV) and hollow microtubes with ultrathin pore walls, which enrich reaction sites, improve visible-light absorption and enhance charge separation. In the presence of phenylcarbinol, ACN exhibited excellent water-splitting ability (95.3 μmol h-1 ) and in the meanwhile phenylcarbinol was selectively oxidized to benzaldehyde (conversion of 90.9 %, selectivity of 99.7 %) under solar irradiation. For the concurrent reactions, 2 D isotope labeling, separation, and detection were conducted to confirm that the proton source of released hydrogen is water. The mechanism of water splitting and phenylcarbinol oxidation was also investigated.There is limited guidance on how to assess the ethical acceptability of research risks that extend beyond research participants to third parties (or "research bystanders"). Community or stakeholder engagement has been proposed as one way to address potential harms to community members, including bystanders. Despite widespread agreement on the importance of community engagement in biomedical research, this umbrella term includes many different goals and approaches, agreement on which is ethically required or recommended for a particular context. We analyse the case of a potential Zika virus human challenge trial to assess whether and how community engagement can help promote the ethical acceptability of research posing risks to bystanders. We conclude that, in addition to having intrinsic value, community engagement can improve the identification of bystander risks, effective approaches to minimizing them, and transparency about bystander risks for host communities.
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