Scientific reports
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SARS-CoV-2 is a newly emergent coronavirus, which has adversely impacted human health and has led to the COVID-19 pandemic. There is an unmet need to develop therapies against SARS-CoV-2 due to its severity and lack of treatment options. A promising approach to combat COVID-19 is through the neutralization of SARS-CoV-2 by therapeutic antibodies. ⋯ In this study we used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs shows favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19.
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Delta opioid receptor (DOR) agonists have been identified as a promising novel therapy for headache disorders. DORs are broadly expressed in several peripheral and central regions important for pain processing and mood regulation; and it is unclear which receptors regulate headache associated symptoms. In a model of chronic migraine-associated pain using the human migraine trigger, nitroglycerin, we observed increased expression of DOR in cortex, hippocampus, and striatum; suggesting a role for these forebrain regions in the regulation of migraine. ⋯ In a model reflecting negative affect associated with migraine, SNC80 was only effective in loxP controls and not Dlx-DOR mice. Similarly, SNC80 was ineffective in the cortical spreading depression model of migraine aura in conditional knockout mice. Taken together, these data indicate that forebrain DORs are necessary for the action of DOR agonists in relieving headache-related symptoms and suggest that forebrain regions may play an important role in migraine modulation.
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The purpose was to review the incidence of in situ carcinoma in Iceland after initiating population-based mammography screening in 1987 and to compare management of ductal carcinoma in situ (DCIS) between Iceland and the Uppsala-Örebro region (UÖR) in Central Sweden. The Icelandic Cancer Registry provided data on in situ breast carcinomas for women between 1957 and 2017. Clinical data for women with DCIS between 2008 and 2014 was extracted from hospital records and compared to women diagnosed in UÖR. In Iceland, in situ carcinoma incidence increased from 7 to 30 per 100 000 women per year, following the introduction of organised mammography screening. ⋯ In Iceland, 49% of all DCIS women underwent mastectomy compared to 40% in UÖR. The incidence of in situ carcinoma in Iceland increased four-fold after the uptake of population-based mammography screening causing considerable risk of overtreatment. Differences in treatment of DCIS were seen between Iceland and UÖR, revealing the importance of quality registration for monitoring patterns of management.
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Developmental Dyslexia (DD) is a learning disorder characterized by specific difficulties in learning to read accurately and fluently, which has been generally explained in terms of phonological deficits. Recent research has shown that individuals with DD experience timing difficulties in the domains of language, music perception and motor control, probably due to impaired rhythmic perception, suggesting that timing deficit might be a key underlying factor to explain such a variety of difficulties. The present work presents two experiments aimed at assessing the anticipatory ability on a given rhythm of 9-year old Italian children and Italian adults with and without DD. ⋯ No difference between participants with and without DD was found in the control condition, in which the uncertain timing of the beat did not permit the extraction of regularities. These results suggest that both children and adults with DD are unable to exploit temporal regularities to efficiently anticipate the next sensory event whereas control participants easily are. By showing that the anticipatory timing system of individuals with Developmental Dyslexia appears affected, this study adds another piece of evidence to the multifaceted reality of Developmental Dyslexia.
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To assess the use of a structured report in the Chest Computed Tomography (CT) reporting of patients with suspicious viral pneumonia by COVID-19 and the evaluation of the main CT patterns. This study included 134 patients (43 women and 91 men; 68.8 years of mean age, range 29-93 years) with suspicious COVID-19 viral infection evaluated by reverse transcription real-time fluorescence polymerase chain reaction (RT-PCR) test. All patients underwent CT examinations at the time of admission. ⋯ Barotrauma sign was absent in all the patients. High percentage (54.8%) of the patients had mediastinal lymphadenopathy. Using a Chest CT structured report, with a standardized language, we identified that the cardinal hallmarks of COVID-19 infection were bilateral, peripheral and multifocal/patching GGO and bilateral consolidation with peripheral and segmental distribution.