Our recent findings link the apolipoprotein E4 (ApoE4)-specific changes in brain phosphoinositol biphosphate (PIP2) homeostasis to the susceptibility of developing Alzheimer’s Disease (AD). In the present study, we have identified miR-195 as a top micro-RNA candidate involved in the ApoE/PIP2 pathway using miRNA profiles in human ROSMAP datasets and mouse microarray studies. Further validation studies have demonstrated that levels of miR-195 are significantly lower in human brain tissue of ApoE4+/− patients with clinical diagnosis of mild cognitive impairment (MCI) or early AD when compared to ApoE4−/− subjects. In addition, brain miR-195 levels are reduced along with disease progression from normal aging to early AD, and cerebrospinal fluid (CSF) miR-195 levels of MCI subjects are positively correlated with cognitive performances as measured by mini-mental status examination (MMSE) and negatively correlated with CSF tau levels, suggesting the involvement of miR-195 in early development of AD with a potential impact on cognition. Similar differences in miR-195 levels are seen in ApoE4+/+ mouse hippocampal brain tissue and cultured neurons when compared to ApoE3+/+ counterparts. Over-expressing miR-195 reduces expression levels of its top predicted target synaptojanin 1 (synj1), a brain PIP2-degrading enzyme. Furthermore, elevating miR-195 ameliorates cognitive deficits, amyloid plaque burden, and tau hyper-phosphorylation in ApoE4+/+ mice. In addition, elevating miR-195 rescues AD-related lysosomal defects in inducible pluripotent stem cells (iPSCs)-derived brain cells of ApoE4+/+ AD subjects while inhibiting miR-195 exacerbates these phenotypes. Together, our data uncover a novel regulatory mechanism of miR-195 targeted at ApoE4-associated brain PIP2 dyshomeostasis, cognitive deficits, and AD pathology.

Despite the increasing large population of COVID-19+ infected patients, knowledge of the disease remains limited. Understanding the effects and long-term implications of COVID-19 will be paramount to implementing the right public health measures and developing future preventive and effective treatments. In this article, we discuss currently available information with COVID-19-related neurological complications, possible routes of virus infection into the central nervous system, and hypothesis about virus-induced cytokine storm syndrome, long-term outcomes, as well as ongoing clinical studies of novel therapies and biomarkers for COVID-19. Understanding the effects of COVID-19 on neurological systems is crucial for properly diagnosing and caring for the disease. We need to be prepared that COVID-19 could cause long-lasting debilitations after the infection has cleared. Investigating long-term effects of the disease will yield insight for providing comprehensive care to the survivors. Understanding these risks will also lead to better treatments as well as inform policies to create a system capable of caring for those affected by COVID-19 long after the pandemic has subsided.

Women have traditionally been excluded from positions of power, specifically in the field of science, technology, engineering, and mathematics (STEM). Believed to diminish the intellectual capabilities of scholars, women were historically barred from many opportunities. The first woman was not admitted to the forefront of scientific developments founded in 1666, the French Academy of Sciences until 1979. Over the past half a century, this situation has gradually improved with changes in the scientific landscape and an increased awareness of gender bias in science. More women are encouraged to pursue careers in science, and their interests in science are being cultivated. However, we have not yet reached equality. Where are we in 2019? Data suggest that female scientists continue to face challenges and hurdles in their career advancement. As to be expected from This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Objective We sought to investigate the prevalence of triptan use among patients with migraine who have contraindications to triptan usage, and to explore specifics of the medication prescribed, dosage, and route of administration. Background Triptan medications are a mainstay of acute migraine therapy, but little is known about prevalence and patterns of triptan prescribing among patients with contraindications in the United States. Methods In this retrospective cohort study, we used data from the IBM Marketscan database to identify patients aged ≥ 18 years with migraine from January 1, 2016, to December 31, 2017, using International Classification of Diseases, Clinical Modification 10 codes. Contraindications to triptan medications were identified by review of package labels as listed on the US Food and Drug Administration website. Triptan medications were identified from the IBM Micromedex Redbook linked to prescription claims along with route of administration and dosage. Results Of 1,038,472 individuals diagnosed with migraine, 400,112 (38.5%) were prescribed triptan medication, and of those who were prescribed a triptan, 55,707 (13.9%) had at least one contraindication, with the most common contraindication being cardiac arrhythmia (33,696/400,112 individuals, 8.4%) followed by cerebrovascular disease (14,787/400,112, 3.7%) and coronary artery disease (10,236/400,112, 2.6%). Sumatriptan was the most prescribed triptan (261,736/1,038,472, 25.2%), and the subcutaneous and intranasal routes were more commonly prescribed among those with contraindications compared with those without contraindications. Discussion A substantial proportion of patients with migraine with contraindications were prescribed triptan medications. These findings call for further research on the outcomes of patients with medical contraindications who are prescribed triptan medications, and for greater clarity in prescribing guidelines about the optimal approach for acute therapy among patients with migraine.