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The excellent surgical results obtained with transnasal endoscopic approach to the anterior skull base (ASB) are universally recognized; less is known about the quality of life of patients after surgery. The aim of this study is to analyze the quality of life of patients after endoscopic transnasal surgery for the treatment of neoplasms of the ASB. We conducted a retrospective review of patients who underwent transnasal endoscopic surgery for treatment of ASB tumors at the Tertiary Referral Center University Hospital of Verona. All patients were asked to complete the Anterior Skull Base Questionnaire (ASBQ), the Skull Base Inventory (SBI), and the Sino-nasal Outcome Test - 22 Items (SNOT-22) after surgical treatment. The study population was divided into subgroups; a statistical analysis of the overall results and of the different questionnaire domains was performed. 51 patients were enrolled in this study. The average score was 3.04 for ASBQ, 4.05 for SBI and 28.88 for SNOT-22. Analysis of the overall results for the ASBQ showed a lower quality of life in patients after recurrent surgery and in female patients. The SBI showed similar results in relation to recurrent surgery and radiotherapy. Similarly, the results for SNOT-22 highlighted the negative impact of recurrent surgery and radiotherapy. Our results confirmed that the endoscopic transnasal approach shows excellent results not only in terms of surgical outcome, but also for the possibility of ensuring a good QoL after treatment. Recurrent surgery and radiation treatments were the most important negative prognostic factors. Our results confirmed that the endoscopic transnasal approach shows excellent results not only in terms of surgical outcome, but also for the possibility of ensuring a good QoL after treatment. Recurrent surgery and radiation treatments were the most important negative prognostic factors. Acute medication overuse is prevalent in patients with migraine. In three phase 3, double-blind, randomized, placebo-controlled studies, patients with episodic migraine (EVOLVE-1 and EVOLVE-2) or chronic migraine (REGAIN) were randomized 211 to monthly subcutaneous injections of placebo or galcanezumab 120 or 240 mg for 3 or 6 months. This subgroup analysis evaluated mean changes in the number of monthly migraine headache days in each treatment among patients with versus without baseline acute medication overuse via mixing modelling with repeated measures. The percentages of patients with baseline medication overuse in placebo, galcanezumab 120-mg and 240-mg groups, respectively, were 19.4%, 17.3%, and 19.3% for EVOLVE-1/-2 (pooled; ), and 63.4%, 64.3%, and 64.1% for REGAIN ( ). Both galcanezumab doses demonstrated significant improvement compared with placebo for overall least squares mean change in monthly migraine headache days in patients with baseline medication overuse in both the episodic and chronic migraine studies ( ≤ 0.001). Furthermore, both galcanezumab doses reduced average monthly medication overuse rates compared to placebo ( < 0.001) in both patient populations with medication overuse at baseline. Galcanezumab appears to be effective for the preventive treatment of episodic and chronic migraine in patients who overuse acute medications. ClinicalTrials.gov Identifiers NCT02614183, NCT02614196, and NCT02614261. Galcanezumab appears to be effective for the preventive treatment of episodic and chronic migraine in patients who overuse acute medications.Trial registration ClinicalTrials.gov Identifiers NCT02614183, NCT02614196, and NCT02614261.Significance Genomic instability, a hallmark of cancer, renders cancer cells susceptible to genomic stress from both endogenous and exogenous origins, resulting in the increased tendency to accrue DNA damage, chromosomal instability, or aberrant DNA localization. Apart from the cell autonomous tumor-promoting effects, genomic stress in cancer cells could have a profound impact on the tumor microenvironment. Recent Advances Recently, it is increasingly appreciated that harnessing genomic stress could provide a promising strategy to revive antitumor immunity, and thereby offer new therapeutic opportunities in cancer treatment. https://www.selleckchem.com/products/AZD2281(Olaparib).html Critical Issues Genomic stress is closely intertwined with antitumor immunity via mechanisms involving the direct crosstalk with DNA damage response components, upregulation of immune-stimulatory/inhibitory ligands, release of damage-associated molecular patterns, increase of neoantigen repertoire, and activation of DNA sensing pathways. A better understanding of these mechanisms will provide molecular basis for exploiting the genomic stress to boost antitumor immunity. Future Directions Future research should pay attention to the heterogeneity between individual cancers in the genomic instability and the associated immune response, and how to balance the toxicity and benefit by specifying the types, potency, and treatment sequence of genomic stress inducer in therapeutic practice. Autism spectrum disorders and Williams syndrome are complex cognitive conditions exhibiting quite opposite features in the social domain whereas people with autism spectrum disorders are mostly hyposocial, subjects with Williams syndrome are usually reported as hypersocial. At the same time, autism spectrum disorders and Williams syndrome share some common underlying behavioral and cognitive deficits. It is not clear, however, which genes account for the attested differences (and similarities) in the socio-cognitive domain. In this article, we adopted a comparative molecular approach and looked for genes that might be differentially (or similarly) regulated in the blood of people with these conditions. We found a significant overlap between genes dysregulated in the blood of patients compared to neurotypical controls, with most of them being upregulated or, in some cases, downregulated. Still, genes with similar expression trends can exhibit quantitative differences between conditions, with most of them beinces between the autism spectrum disorder and the Williams syndrome socio-cognitive profiles.
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