Symptom Profile of Patients With Post-COVID-19 Conditions and Influencing Factors for Recovery.

Background: The aim of the study was to examine the factors that influence the improvement of post-coronavirus disease 2019 (COVID-19) symptoms. Methods: We investigated the biomarkers and post-COVID-19 symptoms status of 120 post-COVID-19 symptomatic outpatients (44 males and 76 females) visiting our hospital. This study was a retrospective analysis, so we analyzed the course of symptoms only for those who could follow the progress of the symptoms for 12 weeks. We analyzed the data including the intake of zinc acetate hydrate. Results: The main symptoms that remained after 12 weeks were, in descending order: taste disorder, olfactory disorder, hair loss, and fatigue. Fatigue was improved in all cases treated with zinc acetate hydrate 8 weeks later, exhibiting a significant difference from the untreated group (P = 0.030). The similar trend was observed even 12 weeks later, although there was no significant difference (P = 0.060). With respect to hair loss, the group treated with zinc acetate hydrate showed significant improvements 4, 8, and 12 weeks later, compared with the untreated group (P = 0.002, P = 0.002, and P = 0.006). Conclusion: Zinc acetate hydrate may improve fatigue and hair loss as symptoms after contracting COVID-19.

Ethical Aspects of Brain Organoid Research in News Reports: An Exploratory Descriptive Analysis.

Background and Objectives: Brain organoids are self-assembled, three-dimensional (3D) aggregates generated from pluripotent stem cells. These models are useful for experimental studies on human brain development and function and are therefore increasingly used for research worldwide. As their increasing use raises several ethical questions, we aimed to assess the current state of the press on brain organoid research using a cross-sectional database to understand the extent of discussion of this subject in the public. Materials and Methods: We conducted a descriptive analysis of news reports obtained from the Nexis Uni database, searched in April 2020. After extracting the news reports, the number of published reports in each year and the included terms were analyzed. Results: Up to April 2020, 332 news reports had been published, with over half of them published in the United States and the United Kingdom, with the numbers gradually increasing every year. In total, 113 (34.0%) news reports included ethics-related keywords, and the ratio of studies before and after the study-period midpoint was significantly increased (21.0% (2013-2016) vs. 38.2% (2017-2020); p = 0.0066, Chi-square test with Yates' continuity correction). Conclusions: Although news reports on the ethical aspects of brain organoid research have been increasing gradually, there was a bias in the region of publication. Additional studies focusing on the ethical aspects of brain organoid research should strive to assess the public perception on the subject in different parts of the world.

Effects of Tea Catechins on Alzheimer's Disease: Recent Updates and Perspectives.

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders worldwide. Its incidence is gradually increasing because of an aging demographic. Therefore, AD prevention and modification is important to improve the health status of older adults. Oxidative stress is a component of the pathological mechanisms underlying AD. It is caused by a disruption of the balance between reactive oxygen species and antioxidant molecules. This imbalance also causes neuroinflammation. Catechins, which are bioactive components of tea, have antioxidative and anti-inflammatory effects. Moreover, other potential properties related to AD prevention and modification have been reported in in vitro and in vivo studies. Several clinical studies have also been conducted to date. The current review summarizes recent updates and perspectives of the effects of catechins on AD based on the molecular mechanisms and related clinical studies.

Prescription of Antidementia Drugs and Antipsychotics for Elderly Patients in Japan: A Descriptive Study Using Pharmacy Prescription Data.

BACKGROUND: Antipsychotics are commonly used for managing behavioral and psychological symptoms of dementia among elderly patients with dementia receiving antidementia drugs (ADDs). However, the use of antipsychotics among these patients has not been investigated since 3 ADDs were approved in 2011 in Japan. METHOD: We conducted a descriptive study using pharmacy prescription data and identified patients aged ≥65 years who were newly prescribed donepezil, memantine, rivastigmine, and galantamine between January 1, 2012, and September 30, 2014. We determined the proportion of antipsychotic prescription and the factors affecting antipsychotic prescription using multivariable Cox proportional hazard models. RESULT: Of 13 876 patients, 1705 were memantine users, and the proportion of antipsychotic prescription among them was the highest (11.1%). Adjusted hazard ratios for donepezil, rivastigmine, and galantamine were 0.66, 0.56, and 0.66, respectively, relative to that for memantine. CONCLUSION: Compared to other ADD users, new memantine users were most likely to be prescribed antipsychotics.

Is the Use of Proton-pump Inhibitors a Risk Factor for Alzheimer's Disease? Molecular Mechanisms and Clinical Implications.

Proton-pump inhibitors (PPIs), such as omeprazole, lansoprazole and rabeprazole, are used for the treatment of gastroesophageal reflux disease and peptic ulcer disease. The use of PPIs has increased, especially in older individuals, and a pharmacoepidemiological study indicated the use of PPIs peaks in people aged 80 years or older. In this population, Alzheimer's disease (AD) is a common neurological disorder and type of dementia, occurring with a frequency of approximately 10%. Currently, over 45 million people are estimated to have dementia worldwide, and it is a major cause of death in the elderly. Recent clinical studies have indicated that chronic use of PPIs can be a risk factor for increased incidence of dementia, including AD. Potential molecular mechanisms related to the pathophysiology of AD (e.g., modulation of amyloid protein processing) have also been reported in both in vitro and in vivo studies. Although the clinical implications of these results are inconclusive, a literature review of the current knowledge is important for future basic and clinical research. This review summarizes the possible mechanisms connecting the use of PPIs and the incidence of AD. Additionally, we summarize results from clinical studies to highlight the influence in humans.

Cortical spreading depression activates and upregulates MMP-9.

Cortical spreading depression (CSD) is a propagating wave of neuronal and glial depolarization and has been implicated in disorders of neurovascular regulation such as stroke, head trauma, and migraine. In this study, we found that CSD alters blood-brain barrier (BBB) permeability by activating brain MMPs. Beginning at 3-6 hours, MMP-9 levels increased within cortex ipsilateral to the CSD, reaching a maximum at 24 hours and persisting for at least 48 hours. Gelatinolytic activity was detected earliest within the matrix of cortical blood vessels and later within neurons and pia arachnoid (> or =3 hours), particularly within piriform cortex; this activity was suppressed by injection of the metalloprotease inhibitor GM6001 or in vitro by the addition of a zinc chelator (1,10-phenanthroline). At 3-24 hours, immunoreactive laminin, endothelial barrier antigen, and zona occludens-1 diminished in the ipsilateral cortex, suggesting that CSD altered proteins critical to the integrity of the BBB. At 3 hours after CSD, plasma protein leakage and brain edema developed contemporaneously. Albumin leakage was suppressed by the administration of GM6001. Protein leakage was not detected in MMP-9-null mice, implicating the MMP-9 isoform in barrier disruption. We conclude that intense neuronal and glial depolarization initiates a cascade that disrupts the BBB via an MMP-9-dependent mechanism.

Adenovirus-mediated gene transfer of fibroblast growth factor-2 increases BrdU-positive cells after forebrain ischemia in gerbils.

BACKGROUND AND PURPOSE: Progenitor cells continue to generate neurons in the adult mammalian brain, and cerebral ischemia induces neurogenesis. We examined the efficacy of the intraventricular injection of a recombinant adenovirus-expressing fibroblast growth factor-2 (FGF-2) (AxCAMAssbFGF) on neurogenesis in both normal and ischemic brains. METHODS: We used a gerbil model of transient global ischemia and counted the number of BrdU-positive cells after injection of AxCAMAssbFGF into the brain with or without ischemia. RESULTS: Intraventricular AxCAMAssbFGF produced robust FGF-2 protein increases in diverse regions of the brain and markedly increased FGF-2 concentrations in cerebrospinal fluid 2 days after administration and evoked significant proliferation of BrdU-positive cells not only in the subventricular zone and dentate gyrus of the hippocampus but also in the cerebral cortex, and some BrdU-positive cells differentiated into neurons. Continuous intraventricular infusion of FGF-2 protein increased FGF-2 concentration in cerebrospinal fluid but not in brain tissues and produced BrdU-positive cell proliferation only in the subventricular zone of the lateral ventricle. CONCLUSIONS: Adenovirally mediated transfer of the FGF-2 gene promoted progenitor cell proliferation more efficiently in widespread regions of the brain after transient global ischemia than continuous intraventricular infusion of FGF-2 protein.

Overexpression of basic fibroblast growth factor and Bcl-xL with adenoviral vectors protects primarily cultured neurons against glutamate insult.

OBJECTIVE: Excitatory amino acid (EAA) toxicity seems to be an important mechanism of neuronal cell death after cerebral infarction. We examined the inhibitory effects of neuronal cell death caused by EAA in vitro by means of adenoviral gene transfer of neurotrophic basic fibroblast growth factor (bFGF) and antiapoptotic Bcl-xL. METHODS: Recombinant adenoviral vectors expressing human bFGF gene with secretory signals of interleukin-2 and human Bcl-xL gene were constructed. Primarily cultured rat neuronal cells were treated with glutamate to cause EAA, and the neuroprotective effects of gene transfer by these adenoviral vectors were investigated at several time points of infection. RESULTS: Each adenoviral infection to primarily cultured neuronal cells exhibited neuroprotective effects against EAA caused by glutamate. Both gene transfer of bFGF with secretory signal and Bcl-xL transfer to neuronal cells exhibited the synergistic neuroprotective effects against EAA. These effects were most prominent with gene transfer 4 hours before glutamate insult; gene transfer performed simultaneously with and up to 4 hours after the insult exhibited definite neuroprotective effects. CONCLUSION: These experiments revealed marked neuroprotective effects of adenoviral gene transfer of bFGF and Bcl-xL into neuronal cells in vitro. The findings may lead to new approaches for treating occlusive cerebrovascular disease.