Sodium Propionate and Sodium Butyrate Promote Fatty Acid Oxidation in HepG2 Cells under Oxidative Stress

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disturbances that includes simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and liver cancer. NAFLD affects individuals that consume the typical Western diet consisting of high levels of fats and carbohydrates. The increase in circulating free fatty acids, palmitate and oleate, or lipopolysaccharides (LPS), induce oxidative stress and pro-inflammatory cytokine production in the liver, which all contribute to NAFLD progression. In this study, we are evaluating the mRNA expression of genes associated with fatty acid oxidation (FAO) and the protein expression of pro-inflammatory cytokines related to NAFLD using the HepG2 human liver hepatocellular carcinoma cells exposed to palmitate/oleate or LPS. The treatment of sodium butyrate (NaB) or sodium propionate (NaP) was used to relieve oxidative stress and inflammation in liver cells. The quantitative real-time polymerase chain reaction (qRT-PCR) results show that NaP or NaB, were able to promote FAO, regulate lipolysis, and reduce reactive oxygen species production by significantly increasing the mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), adipose triglyceride lipase (ATGL), carnitine palmitoyltransferase 1 alpha (CPT1α), fibroblast growth factor 21 (FGF21), and uncoupling protein 2 (UCP2) in HepG2 cells. Together, NaP and NaB may produce synergistic effects by significantly increasing CPT1α, PPARα, and UCP2 mRNA expression in LPS-induced HepG2 cells and by significantly increasing CPT1α and ATGL mRNA expression in palmitate/oleate-induced HepG2 cells. Only NaP treatment may have the ability to reverse hepatic steatosis and increase whole-body energy expenditure by significantly increasing FGF21 mRNA expression in palmitate/oleate-induced HepG2 cells. The ELISA results reveal that only LPS significantly increased Tumor Necrosis Factor alpha (TNF-α) expression in HepG2 cells. At the same time, NaP alone or in combination with NaB significantly decreased TNF-α expression in LPS-induced HepG2 cells. The expression of IL-8 in both models showed no significant differences in all treatments. The Western blot analysis of CPT1α protein expression increased by NaP alone or in combination with NaB in the palmitate/oleate model. In conclusion, this study shows promising results for the use of NaP and NaB as a potential new therapy in NAFLD

Experimental and Numerical Investigation of Mass Transfer in Passive Scaled-up Micromixers

Micromixers are vital components in micro-total analysis systems (μ-TAS) and Lab-on-Chip (LOC) devices, with applications in drug delivery, medical diagnostics, and chemical analyses, amongst others. Traditional macroscale mixing techniques may not be applied at the microscale, where viscous forces become important compared to inertial forces. As such, it remains a challenge to effectively and thoroughly mix liquid species in small characteristic dimensions. The present work aims to analyze flow phenomena and mass transfer in three novel scaled-up micromixers, which make use of variations in channel geometry to induce mixing. Designs based on multi-lamination inlets, obstruction filled channels, Dean vortex inducing curved channels, and helical flow inducing grooves are investigated. Flow visualization is used as a qualitative tool, providing valuable information regarding flow patterns and mixing. Induced fluorescence is applied to assess whole field concentration distribution, and provide quantitative species distribution data. Complex three dimensional flows are analyzed using numerical simulations, which show good agreement with experimental work. The mixers are evaluated over Reynolds numbers ranging from 0.5 to 100, corresponding to Péclet numbers ranging from 1.25 × 103 to 1.25 × 105. Results show a decreasing-increasing trend in the degree of mixing with increasing Reynolds number, as the dominant mixing mechanism changes from mass diffusion to mass advection. Up to 90% mixing is reported. To allow for reasonable mixing performance comparison with published work, an equivalent length parameter is proposed. The present devices offer good mixing in shorter lengths over a wide range of Reynolds numbers compared to numerous published devices

Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis

A 160 kb minimal common region in Xp21 has been determined as the cause of XY gonadal dysgenesis, if duplicated. The region contains the MAGEB genes and the NR0B1 gene; this is the candidate for gonadal dysgenesis if overexpressed. Most patients present gonadal dysgenesis within a more complex phenotype. However, few independent cases have recently been described presenting with isolated XY gonadal dysgenesis caused by relatively small NR0B1 locus duplications. We have identified another NR0B1 duplication in two sisters with isolated XY gonadal dysgenesis with an X-linked inheritance pattern. We performed X-inactivation studies in three fertile female carriers of three different small NR0B1 locus duplications identified by our group. The carrier mothers did not show obvious skewing of X-chromosome inactivation, suggesting that NR0B1 overexpression does not impair ovarian function. We furthermore emphasize the importance to investigate the NR0B1 locus also in patients with isolated XY gonadal dysgenesis

EXPERIMENTAL INVESTIGATION OF A SCALED-UP PASSIVE INTERDIGITAL MICROMIXER WITH CIRCULAR-SECTOR MIXING ELEMENTS

ABSTRAC

Behavioural and psychological symptoms of dementia : a new framework for holistic understanding and non-pharmacological management

The National Institute for Health and Care Excellence (NICE) informs us that the first-line treatments for behavioural and psychological symptoms of dementia (BPSD) are non-pharmacological. Although psychotropics used to be the main strategy in the management of behaviours that challenge, there has been an increase in the use of biopsychosocial formulations since 2010, and there are now over a dozen to choose from. However, many are overly focused on obtaining information about the agitation, and less specific about providing details of the actions required to manage the behaviours. The NICE guidelines too fail to provide specific guidance on which non-pharmacological approaches to use. This article argues for giving equal weight to both the collection of meaningful information and the development of 'informed actions', because it is the actions that lead to change. The article outlines a management programme providing a framework for the assessment, formulation and treatment of agitation in dementia. The work draws on theory, evidence-based practice and practice-based evidence to provide a model with sufficient structure and flexibility to be useful for clinicians across a range of settings and professional groups

A mixed methods investigation of how young adults in Virginia received, evaluated, and responded to COVID-19 public health messaging

The purpose of this study was to investigate how young adults in Virginia received, evaluated, and responded to messages related to the coronavirus/COVID-19, a major disruptor of our time, and to understand how and when these messages influenced behavior. This was a sequential explanatory mixed methods study, including an online survey (quantitative) and virtual focus groups (qualitative). We surveyed a convenience sample of 3,694 Virginia residents by distributing a link to complete the survey online. Only data from18-24 year old adults (n=207) were included in the analysis for this study. Focus group participants were recruited from the survey participants as well as from a college-level introductory health class. Most (83%) young adult respondents reported national science and health organizations as a trusted source for COVID-19 information and over 50% of respondents reported getting information from state/local health departments (72%), healthcare professionals (71%), and online news sources (51%). Focus group participants emphasized social media as an additional major source of COVID-19 information. Focus group data revealed that young adults struggled with deciphering contradictory messaging, had a mix of logical and emotional reasons for deciding whether to adhere to guidelines, had a desire for consistent, fact-based public health messaging at the national level. The findings from this study underscore the importance of consistent, positive public health messaging in a public health crisis

Early surgical intervention among patients with acute central cord syndrome is not associated with higher mortality and morbidity

Background: Conflicting reports exist regarding mortality and morbidity of early surgical decompression in the setting of acute central cord syndrome (ACS) in multisystem trauma despite evidence of improved neurological outcomes. Consequently, optimal decompression timing in ACS in multisystem trauma patients remains controversial. This study aims to determine the association between early surgery for acute traumatic central cord and all-cause mortality among multisystem trauma patients in the National Trauma Data Bank (NTDB) using propensity score matching. Methods: We used the NTDB (years 2011-2014) to perform a retrospective cohort study, which included patients \u3e18 years, with ACS (identified using ICD-9 coding). Collected patient data included demographics, surgery timing (≤24 hours, \u3e24 hours), injury mechanism, Charlson comorbidity index (CCI), injury severity score (ISS), serious adverse events (SAE). Logistic regression and propensity matching were used to investigate the relationship between surgery timing and subsequent inpatient mortality. Results: We identified 2,379 traumatic ACS patients. This group was 79.3% male with an average age of 56.3±15.2. They had an average ISS of 19.5±9.0 and mortality rate of 3.0% (n=72). A total of 731 (30.7%) patients underwent surgery for ACS within 24 hours. Univariate analysis did not show a significantly higher mortality rate in the early versus late surgery groups (3.8% Conclusions: Early surgical intervention does not appear to be associated with increased mortality among ACS patients unlike previously suggested. We theorize that survival noted within the NTDB is confounded by factors including existing comorbidities and multisystem trauma, rather than surgical timing. Delaying definitive surgical care may predispose patients to worsened greater neurological morbidity