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Development and characterization of resveratrol fortified bread: effects on dough performance, bread quality, and in vitro starch digestibility
Get PDFThe global increase in type 2 diabetes mellitus (T2DM) has driven research in functional staple foods that reduce postprandial glycemic responses. Bread, a primary carbohydrate source, is characterized by rapid starch digestion and a high glycemic index. Resveratrol (RSV), a dietary polyphenol with antioxidant, anti-inflammatory, and enzyme-inhibitory effects, can lower starch digestibility; however, its sensitivity to heat, light, and oxygen makes baked-food fortification challenging. This thesis study aimed to (i) develop resveratrol-fortified wheat breads using cost-effective protective coatings to improve RSV retention, dough performance, and in-vitro digestibility, and (ii) determine whether RSV and amyloglucosidase (AMG), alone or in combination, can modulate starch digestion while maintaining bread quality.
Mixolab was used to determine thermomechanical characteristics (water absorption, development time, stability, weakening), whereas Rapid Visco Analyzer described pasting behavior. In vitro enzymatic hydrolysis (Box-Lucas modeling) and α-amylase inhibition were used to assess starch digestibility; bread quality and sensory acceptability were evaluated in parallel.
In the first section, RSV was either added as a free compound or encapsulated in gels of corn starch, pea starch, xanthan gum, or locust bean gum (0.5% w/w). Regardless of mixing speed, mixing was the breadmaking step with the highest RSV loss. RSV-enriched gels, especially xanthan gum and corn starch, increased RSV recovery in dough (44.01% and 39.04% vs. 34.97% for free RSV) and restored dough stability relative to free RSV. RSV addition slowed starch hydrolysis, and bread slices with RSV-enriched corn starch gels had lower hardness (1086 g vs 2030 g) and higher cohesiveness (0.84 vs 0.72) than those with free RSV.
The second study involved supplementing white and whole wheat flours with RSV, AMG, or RSV–AMG. In white flour, AMG reduced peak viscosity, but RSV partially reduced this impact and increased setback, indicating improved retrogradation. The combined RSV–AMG treatment had the lowest hydrolysis rate (k = 0.56 min⁻¹), indicating an extensive starch–polyphenol network that limited enzymatic access. In whole-wheat systems, bran and fiber influenced the reaction, with RSV increasing starch retrogradation during cooling and the AMG–RSV combination softening white crumbs while reducing RSV-induced hardness in whole-wheat crumbs.February 202
A permutation-based approach applied to biologically informed neural networks for ontological pathway analysis
Get PDFIntroduction: Pathway analysis is a widespread method for determining actionable insight from high-throughput sequencing experiments. Traditional techniques have limitations, which novel machine learning methods seek to address. Biologically Informed Neural Networks (BINNs) are an emerging technique which applies ontological information built from existing literature, and explainable artificial intelligence metrics to perform biomarker discovery (genetic material of relevance to disease) and pathway analysis. Best practices for the implementation and interpretation of BINNs do not currently exist, and as such, we compare the results produced from a BINN to a traditional approach as a form of validation. We also examine the impact of pre-clustering data, and performing a permutation test on the output of BINNs.
Methods: Using a Python library which implements a BINN, and a traditional hypergeometric overrepresentation analysis, we compare the output of these methods on bulk RNA-sequencing cancer data accessed from the Cancer Cell Line Encyclopedia. Weighted Gene Co-expression Network Analysis was used to pre-cluster the RNA-sequencing data, and a “point estimate” null probability was produced using the explainable AI metrics and a permutation test, was implemented using R and Python.
Results: Using a ROC curve between our approach and the hypergeometric, we are able to achieve a high (>0.80) area under the curve in predicting statistically significant terms using the point estimate metric. This showed an improvement over other interpretations of the BINN output.
Conclusion: Interpretation of BINNs may be improved with a point estimate when considering a traditional, hypergeometric approach as a ground truth. We also observed interpretations of BINNs that use purely Deep SHAP importances show a low correlation with an existing pathway analysis approach.February 202
Scaling up access to antiretroviral treatment for HIV: lessons from a key populations program in Nigeria
Get PDFAbstract Over the years, Nigeria has recorded significant progress in controlling the HIV epidemic in the country. HIV prevalence has reduced from 4.1% in 2010 to 1.4 in 2019. The number of people acquiring new HIV infections decreased from 120,000 in 2010 to 74,000 in 2021, and HIV-related deaths decreased from 82,000 in 2010 to 51,000 in 2021. However, the country still faces challenges such as high HIV transmission among key populations (KP) who account for 11% of new HIV infections. Over the years, the government and development partners involved in HIV response efforts in Nigeria have been establishing and scaling up access to services to help address the needs of KPs. Initially, services for KPs as with the general population in Nigeria were largely preventive. Treatment of PLHIV in Nigeria commenced in 2002 and has increased from about 15,000 to more than 1.78 million PLHIVs in 2023. Despite this progress in treatment coverage, however, KPs are not equitably covered. To address this gap, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) launched an ambitious initiative—the Key Population Investment Fund (KPIF)—to target the unaddressed HIV-related needs of key populations (KPs) who are disproportionately affected by HIV. The KPIF initiative was implemented through partner organizations such as the Society for Family Health (SFH), a KP-friendly and indigenous non-governmental organization. Earlier, the program implemented by SFH was largely an HIV prevention program. SFH’s transformation, transition, and growth to a comprehensive HIV prevention, care, and treatment service provider was necessary to bridge the gap in the needed expansion of HIV services to adequately meet the care needs of KPs and scale up programs. Therefore, this paper’s aim is to share experiences in the transformation of SFH into a comprehensive HIV prevention, treatment, and care service provider in the hope that it may serve as a lesson for organizations with similar objectives
Examination of the evaluation of negative skin friction on production piles for a major bridge structure
No full textRelative settlement of soil and pile generates negative skin friction (NSF), creating a downward shearing force along the pile’s shaft. The resulting axial force and settlement are called drag force (DF) and downdrag (DD), respectively. The pile's downward movement starts at the top and reaches equilibrium at the neutral plane (NP), where relative settlement is zero. The NP’s location determines the pile’s maximum axial force (MAF). Excessive settlement from external loads, such as embankment filling, can induce DF on the pile in compressible soils. A full-scale field study was conducted on a production H-pile at a bridge construction site in Manitoba, Canada. The pile was driven into clay till to evaluate the NSF and its associated DF and DD under service loads. Field monitoring showed that the pile installation into cooler ground reduced compressive strain along the shaft. Loading and unloading during pile driving create compressive residual stresses in the middle and lower shaft and tensile stresses at the pile top. Ignoring these forces might lead to underestimating the applied loads on the pile. Five code provisions for ultimate limit state (ULS) design of piles subjected to NSF were evaluated. The findings indicated that design codes that include DF in ULS design, such as AASHTO and CEN, tend to result in more conservative and potentially costly designs compared to codes that do not account for DF in ULS design, such as CHBDC, AS2159, and FHWA. Numerical modeling revealed that MAF, NSF, DF, and DD vary among piles within a group due to the geometry of the applied load. The pile in the most critical location experienced 65% higher MAF, 25% more DF, 37.5% more DD, and 32% more NSF compared to the least critical pile. Parametric studies showed that increasing surcharge load, shortening pile length, reducing pile cross-section and decreasing soil-pile friction reduced DF and MAF at the NP. Applying bitumen coating along the shaft reduced MAF and DF by 70% and 90%, respectively, and construction in high plastic clays leads to an increase in MAF and DF. Replacing traditional granular embankment with lightweight cellular concrete reduced by up to 60%. It also DD by 65% to 70%, DF by 35% to 44%, and NSF by 50% to 70%, depending on the pile’s location within the cap. Comparing between the Unified Design Method (UDM) and the obtained results showed that UDM overestimated MAF at the NP, DF and DD for both pile scenarios, however the NP position was almost identical. Additionally, the pile resistance based on this method may not account for the setup effect, leading to a more conservative design. Considering pile capacity derived from restrike measurements versus end of initial driving in dynamic analysis provides higher resistance in geotechnical ULS design in soil with shaft setup potential.May 202
Partnered health research in Canada: a cross-sectional survey of perceptions among researchers and knowledge users involved in funded projects between 2011 and 2019
Get PDFAbstract Background Engaging knowledge users in health research is accelerating in Canada. Our objective was to examine perceptions of partnered health research among individuals involved in funded Canadian partnered health research projects between 2011 and 2019. Methods We invited 2155 recipients of 1153 funded projects to answer a questionnaire probing project characteristics and perceptions of partnered health research. We described and compared perceived effects of involving knowledge users in the project, team cohesion, capability, opportunity and motivation for working in partnership between two categories of respondents: project role [nominated principal investigators (NPIs), other researchers and knowledge users] and gender. Findings We analysed data from 589 respondents (42% NPIs, 40% other researchers and 18% knowledge users; 56% women). Among the perceived effects variables, the proportion of ratings of significant influence of involving knowledge users in the project ranged between 12% and 63%. Cohesion, capability, opportunity and motivation variables ranged between 58% and 97% agreement. There were no significant differences between respondent groups for most variables. NPIs and women rated the overall influence of involving knowledge users as significant more than other respondent groups (p < 0.001). NPIs also reported higher agreement with feeling sufficiently included in team activities, pressure to engage and partnerships enabling personal goals (all p < 0.001). Conclusions Most respondents held positive perceptions of working in partnership, although ratings of perceived effects indicated limited effects of involving knowledge users in specific research components and on project outcomes. Continued analysis of project outcomes may identify specific contexts and partnership characteristics associated with greater impact
Determining the role of ZEB1 and ZEB2 in controlling fibroblast activation
Get PDFMyocardial infarction (MI) is a leading cause of death in Canada. The activated fibroblast, also known as myofibroblast, is a key player in extracellular matrix production, remodeling, and fibrosis in the heart following a MI. Previous studies in our lab have shown that the transcription factor ZEB2 is expressed in activated cardiac fibroblasts and that the overexpression of ZEB2 upregulates the expression of the myofibroblast markers -SMA, SMemb and ED-A fibronectin. The Zinc finger transcription factor family proteins ZEB1 and ZEB2 have crucial roles in embryonic development, angiogenesis, Epithelial-Mesenchymal transition (EMT), and Endothelial-Mesenchymal transition (EndoMT). This study was focused on determining the role of both ZEB1 and ZEB2 in cardiac fibroblast activation. We compared the protein levels of ZEB1 and ZEB2 in primary adult male and female rat cardiac fibroblast cells during the process of fibroblast activation in vitro. As well, we analyzed the effect of over-expression and knockdown of ZEB1 and ZEB2 in the mouse NIH3T3 embryonic fibroblast cell line. Our results show that both ZEB1 and ZEB2 are expressed in the activated fibroblasts with their expression being highest at 48 hours and then decreasing. We observed that ectopic expression of ZEB2 in both NIH3T3 cells and rat primary cardiac fibroblasts resulted in a corresponding decrease in endogenous ZEB1 expression. Furthermore, siRNA mediated knockdown of ZEB2 resulted in increased ZEB1 expression in cardiac fibroblasts and NIH3T3 cells. Similarly, ZEB1 knockdown resulted in increased ZEB2 expression. This shows that ZEB1 and ZEB2 may form a negative feedback loop to maintain an optimal level of their expression in cardiac fibroblasts. ZEB1 and ZEB2 may directly compensate for the loss of the other transcription factor in fibroblasts. Interestingly, despite these regulatory interactions, the expression of the myofibroblast markers,
-smooth muscle actin (SMA) and Embryonic smooth muscle heavy chain (SMemb), remain
ZEB1 and ZEB2. This study enhances our understanding of the complex interplay between ZEB1 and ZEB2 in cardiac fibroblast activation and provides new insight into the regulatory mechanism underlying this process. These findings could have significant implications to develop new therapeutic strategies for myocardial infarction and heart failure by targeting ZEB1 and ZEB2 to control fibroblast activation and fibrosis.May 202
Posttraumatic stress disorder and cannabis use: an in-depth examination of a nationally representative sample
Get PDFCannabis is among the top substances used by individuals with PTSD. Research regarding the effects of cannabis use on PTSD symptomatology is largely contradictory and unclear, claiming both the improvement and worsening of PTSD symptoms concurrently. Furthermore, cannabis use disorder (CUD) is increasing in prevalence, due to recent legalization of recreational cannabis use across much of North America. To date, relatively little is known about correlates of comorbid PTSD and CUD (PTSD-CUD), as well as the impact of comorbid PTSD-CUD on various areas of mental health functioning. Individuals with PTSD routinely experience barriers to acceptable and effective treatment, which may be further exacerbated by the co-occurrence of CUD. Three distinct research studies utilized a nationally representative sample of adult civilians (≥18 years) collected during the National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III; N = 36,309) in 2012-2013. The aims of the proposed project were threefold: (1) to examine the sociodemographic profile of individuals with PTSD-CUD, (2) to identify distinct cannabis use profiles among individuals with PTSD, and (3) to examine rates of mental healthcare utilization among individuals with PTSD who use cannabis. This nationally representative sample provides the opportunity to examine the complex relationships between PTSD and cannabis use in comprehensive detail. Comorbid PTSD-CUD represents an increasingly frequent disorder combination that appears to impact treatment course and outcome. Improved understanding regarding the relations between PTSD and cannabis use is fundamental to reduce disorder durations, resolve healthcare disparities, and improve treatment interventions for this complex population.May 202
An analytical approach towards attaining leave no one behind using patterns and distributions of inequalities in antenatal and facility delivery coverage in Uttar Pradesh, India
Get PDFAbstract Background Leave No One Behind (LNOB) is a central, transformative promise of the 2030 Agenda for Sustainable Development Goals. To attain LNOB, systematic analysis of patterns and distributions of inequalities in coverage of health outcomes on a continuous basis at different program delivery layers is required to design tailored health interventions. We analysed the patterns of change and geographic distribution of inequalities in coverage of antenatal care and facility-based delivery in Uttar Pradesh (UP), India and developed a framework to guide health programmers to understand inequalities better, to accelerate progress by reaching those left behind. Methods Data from five-rounds of National Family Health Survey (1992–2021) and two-rounds of Community Behaviour Tracking Survey (2014–2018) is used. Education and wealth have been used as stratifiers. Three measures of inequality- mean difference from mean, slope index of inequality, and inequality pattern index are used to depict the state, district and sub-district level inequalities. Results UP observed a substantial reduction in the education-related inequality in ANC and facility-delivery during 1992–2021. The slope index of inequality declined from 65.3 [95%CI:60.0-70.6] to 9.3 [95%CI:7.8–10.8] for ANC and from 44.7 [95%CI:38.5–50.9] to 29.9 [95%CI:27.8–32.0] for facility-delivery during 1992–2021. The inequality pattern index showed that, with improved reach of interventions, many districts moved towards bottom inequality from top inequality for any ANC while fewer districts for facility-delivery. Even in districts with high coverage and low inequality, sub-district level(blocks) inequality persisted. Similarly, in blocks with high coverage and low inequality, Accredited Social Health Activist (ASHA) level inequality persisted. Interestingly, for the same ASHA area, the patterns of inequality differed for any ANC and facility delivery; in some districts, inequality direction changed based on the stratifier chosen. Conclusions The proposed health equity framework suggests that to achieve LNOB status, understanding inequality with the coverage status is important. If coverage is high and inequality persists, identify the program layer at which maximum inequality persists to identify the left behinds. Whereas, if coverage is poor, programs are required to improve coverage first. Findings also call for a systematic way of collecting and organizing granular data to understand inequality and identify the left-behinds
Establishment of a regional Mpox surveillance network in Central Africa: shared experiences in an endemic region
Get PDFAbstract To address the underreporting of mpox cases in endemic regions, a regional surveillance network, known as the Mpox Threat Reduction Network (MPX-TRN), was established between five neighboring countries in Central and West Africa in 2022. One direct outcome of the MPX-TRN has been the strengthening of regional mpox surveillance. This consortium has facilited open communication channels, detection of cross-border mpox cases, and improvements of the detection and diagnosis of mpox in Central Africa and worldwide. Importantly, the MPX-TRN provides a scalable model for addressing underreporting of diseases, such as mpox
The integrated stress response in neurodegenerative diseases
Get PDFAbstract The integrated stress response (ISR) is a conserved network in eukaryotic cells that mediates adaptive responses to diverse stressors. The ISR pathway ensures cell survival and homeostasis by regulating protein synthesis in response to internal or external stresses. In recent years, the ISR has emerged as an important regulator of the central nervous system (CNS) development, homeostasis and pathology. Dysregulation of ISR signaling has been linked to several neurodegenerative diseases. Intriguingly, while acute ISR provide neuroprotection through the activation of cell survival mechanisms, prolonged ISR can promote neurodegeneration through protein misfolding, oxidative stress, and mitochondrial dysfunction. Understanding the molecular mechanisms and dynamics of the ISR in neurodegenerative diseases aids in the development of effective therapies. Here, we will provide a timely review on the cellular and molecular mechanisms of the ISR in neurodegenerative diseases. We will highlight the current knowledge on the dual role that ISR plays as a protective or disease worsening pathway and will discuss recent advances on the therapeutic approaches that have been developed to target ISR activity in neurodegenerative diseases