In vitro methods in autophagy research: Applications in neurodegenerative diseases and mood disorders

BackgroundAutophagy is a conserved physiological intracellular mechanism responsible for the degradation and recycling of cytoplasmic constituents (e.g., damaged organelles, and protein aggregates) to maintain cell homeostasis. Aberrant autophagy has been observed in neurodegenerative diseases, including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Huntington’s Disease (HD), and recently aberrant autophagy has been associated with mood disorders, such as depression. Several in vitro methods have been developed to study the complex and tightly regulated mechanisms of autophagy. In vitro methods applied to autophagy research are used to identify molecular key players involved in dysfunctional autophagy and to screen autophagy regulators with therapeutic applications in neurological diseases and mood disorders. Therefore, the aims of this narrative review are (1) to compile information on the cell-based methods used in autophagy research, (2) to discuss their application, and (3) to create a catalog of traditional and novel in vitro methods applied in neurodegenerative diseases and depression.MethodsPubmed and Google Scholar were used to retrieve relevant in vitro studies on autophagy mechanisms in neurological diseases and depression using a combination of search terms per mechanism and disease (e.g., “macroautophagy” and “Alzheimer’s disease”). A total of 37 studies were included (14 in PD, 8 in AD, 5 in ALS, 5 in %, and 5 in depression).ResultsA repertoire of traditional and novel approaches and techniques was compiled and discussed. The methods used in autophagy research focused on the mechanisms of macroautophagy, microautophagy, and chaperone-mediated autophagy. The in vitro tools presented in this review can be applied to explore pathophysiological mechanisms at a molecular level and to screen for potential therapeutic agents and their mechanism of action, which can be of great importance to understanding disease biology and potential therapeutic options in the context of neurodegenerative disorders and depression.ConclusionThis is the first review to compile, discuss, and provide a catalog of traditional and novel in vitro models applied to neurodegenerative disorders and depression

The Effectiveness of Aromatherapy for Depressive Symptoms: A Systematic Review

Background. Depression is one of the greatest health concerns affecting 350 million people globally. Aromatherapy is a popular CAM intervention chosen by people with depression. Due to the growing popularity of aromatherapy for alleviating depressive symptoms, in-depth evaluation of the evidence-based clinical efficacy of aromatherapy is urgently needed. Purpose. This systematic review aims to provide an analysis of the clinical evidence on the efficacy of aromatherapy for depressive symptoms on any type of patients. Methods. A systematic database search was carried out using predefined search terms in 5 databases: AMED, CINHAL, CCRCT, MEDLINE, and PsycINFO. Outcome measures included scales measuring depressive symptoms levels. Results. Twelve randomized controlled trials were included and two administration methods for the aromatherapy intervention including inhaled aromatherapy (5 studies) and massage aromatherapy (7 studies) were identified. Seven studies showed improvement in depressive symptoms. Limitations. The quality of half of the studies included is low, and the administration protocols among the studies varied considerably. Different assessment tools were also employed among the studies. Conclusions. Aromatherapy showed potential to be used as an effective therapeutic option for the relief of depressive symptoms in a wide variety of subjects. Particularly, aromatherapy massage showed to have more beneficial effects than inhalation aromatherapy

Olfactory dysfunction: A plausible source of COVID-19-induced neuropsychiatric symptoms

Olfactory dysfunction and neuropsychiatric symptoms are commonly reported by patients of coronavirus disease 2019 (COVID-19), a respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence from recent research suggests linkages between altered or loss of smell and neuropsychiatric symptoms after infection with the coronavirus. Systemic inflammation and ischemic injury are believed to be the major cause of COVID-19-related CNS manifestation. Yet, some evidence suggest a neurotropic property of SARS-CoV-2. This mini-review article summarizes the neural correlates of olfaction and discusses the potential of trans-neuronal transmission of SARS-CoV-2 or its particles within the olfactory connections in the brain. The impact of the dysfunction in the olfactory network on the neuropsychiatric symptoms associated with COVID-19 will also be discussed

A Large Population Histology Study Showing the Lack of Association between ALT Elevation and Significant Fibrosis in Chronic Hepatitis B

OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319 treatment-naive CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading >/= 7 or fibrosis score >/= 3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2 x upper limit of normal (ULN) and > x 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease. CONCLUSION: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.published_or_final_versio

The No Trade Principle in General Environments

The no trade principle asserts that risk-neutral agents are not prepared to trade if and only if a common prior exists. The purpose of this article is to provide general versions of this principle. We first study the case when no topological assumption is made on the state space. Bets are uniform limits of bounded measurable functions. We then assume that the state space is completely regular Hausdorff and consider two cases in which bets are continuous functions and bounded continuous functions respectivelyNo Trade Principle, common priors, duality, completely regular Hausdorff, Separation Theorem

Help from the parent-teacher association to parenting efficacy: Beyond social status and informal social capital

Objective Empirical research is required to shed light on the issue concerning the support the parent-teacher association (PTA) for parents of schoolchildren. It is to examine if the benefit stems from informal social capital arising from the PTA.Method A telephone survey collected data from parents whose children studied in a grade between Grades 4 and 9 in Hong Kong.Results The benefits of PTA membership and help were significant. However, the contribution of informal social capital to change in parenting efficacy was insignificant.Discussion Consequently, The benefit of the PTA is not attributable to informal social capital.

A rare case of melioidosis presenting as pericarditis and pneumonia in a patient with poorly controlled diabetes mellitus

Abstract Melioidosis is a rare but often fatal tropical infection caused by gram‐negative bacteria Burkholderia pseudomallei. It most commonly manifests as pneumonia and rarely presents as pericarditis. Melioidosis can be difficult to diagnose because of its diverse clinical manifestation and close resemblance to bacteria of the genus Pseudomonas. We report a rare case of melioidosis presenting as pericarditis and pneumonia in a 61‐year‐old male patient with poorly controlled diabetes mellitus. He was initially misdiagnosed with Pseudomonas aeruginosa infection and later treated empirically as tuberculosis pericarditis for 2 months, before reaching the diagnosis of melioidosis

Pharmacokinetics of LB80331 and LB80317 following Oral Administration of LB80380, a New Antiviral Agent for Chronic Hepatitis B (CHB), in Healthy Adult Subjects, CHB Patients, and Mice▿

LB80380, a dipivoxil ester prodrug of LB80331 (metabolite, LB80317), is a novel antiviral agent for chronic hepatitis B (CHB). The pharmacokinetics of LB80331/LB80317 were evaluated in two clinical studies and a study with mice. The clinical studies were dose-escalating pharmacokinetic studies with six healthy subjects per single-dose group and six CHB patients per repeated-dose group. The mouse study was designed to measure the amounts of the phosphorylated portions of LB80331 and LB80317 in the liver. In healthy subjects receiving a single dose of LB80380, the plasma level of LB80331 increased as the dose increased. Although a high-fat diet delayed the time to the maximum concentration in plasma (Tmax) of LB80331, the area under the concentration-time curve from time zero to infinity was similar between the subjects in the fasted group and those in the group who consumed a high-fat diet. In CHB patients, the mean Tmax of LB80331 was 1.0 to 2.0 h postdosing at steady state. The steady-state plasma concentration of LB80331 declined in a monoexponential manner, and the apparent elimination half-life was 2.5 to 3.3 h. The steady-state plasma concentration of LB80317 was maximum at 3 to 8 h postdoing and declined in a monoexponential manner; the apparent elimination half-life was 45 to 62 h at the 30- to 240-mg doses, while LB80317 was measurable in plasma only at higher doses of 120 and 240 mg after the administration of the first dose of LB80380. Forty percent of the amount of LB80331/LB80317 in the mouse liver was detected as the phosphorylated form. In conclusion, LB80380 is rapidly absorbed and converted to LB80331. LB80317 has a long half-life at steady-state, supporting the use of a once-daily dosing regimen. The ingestion of a high-fat diet delays the rate of absorption of LB80380 without affecting the extent of absorption