Subjective and objective interpretation of tear film interferometry images

Background: Assessment of the tear film is necessary in routine clinical practice because an unstable tear film can hamper the quality of life by causing vision-related problems and compromising the ocular surface. One of the major concerns related to an unstable tear film is dry eye. Many of dry eye patients suffer from a lack of meibum which forms the lipid layer of the tear film. The lipid layer can be graded and interpreted by using interferometry. However, interpretation and grading of this dynamic layer may be inconsistent in terms of inter- and intra- observations. This study investigated the difficulty of consistent, subjective grading of clinical findings, in general.Methods: The interferometry images of 30 subjects captured from different equipment were analyzed subjectively. The agreement between intra-observer repeatability was also measured.Results: A positive Spearman’s correlation of 0.81 was found among different grading patterns observed using the Tearsope to compare right and left eyes. Similarly, a positive Spearman’s correlation of 0.63 was found among different grading patterns observed under interferometer in right and left eye. Correlations were statistically significant, p<0.001. The agreement between intra-observer repeatability calculated using Cohen’s kappa values were also statistically significant, p<0.001.Conclusions: A correlation between the findings of different equipment could not be made due to the differences in wavelengths of incident light and the image details. However, a new grading pattern has been proposed to describe the thickness of various lipid layer patterns observed under Doane’s interferometer

The Role of PPARgamma in the Cyclooxygenase Pathway in Lung Cancer.

Decreased expression of peroxisome proliferator activated receptor-gamma (PPARgamma) and high levels of the proinflammatory enzyme cyclooxygenase-2 (COX-2) have been observed in many tumor types. Both reduced (PPARgamma) expression and elevated COX-2 within the tumor are associated with poor prognosis in lung cancer patients, and recent work has indicated that these signaling pathways may be interrelated. Synthetic (PPARgamma) agonists such as the thiazolidinedione (TZD) class of anti-diabetic drugs can decrease COX-2 levels, inhibit growth of non-small-cell lung cancer (NSCLC) cells in vitro, and block tumor progression in xenograft models. TZDs alter the expression of COX-2 and consequent production of the protumorigenic inflammatory molecule prostaglandin E2 (PGE2) through both (PPARgamma) dependent and independent mechanisms. Certain TZDs also reduce expression of PGE2 receptors or upregulate the PGE2 catabolic enzyme 15-prostaglandin dehydrogenase. As several COX-2 enzymatic products have antitumor properties and specific COX-2 inhibition has been associated with increased risk of adverse cardiac events, directly reducing the effects or concentration of PGE2 may provide a more safe and effective strategy for lung cancer treatment. Understanding the mechanisms underlying these effects may be helpful for designing anticancer therapies. This article summarizes recent research on the relationship between (PPARgamma), TZDs, and the COX-2/PGE2 pathways in lung cancer

Incorporating genetic selection into individual‐based models of malaria and other infectious diseases

Introduction Control strategies for human infections are often investigated using individual‐based models (IBMs) to quantify their impact in terms of mortality, morbidity and impact on transmission. Genetic selection can be incorporated into the IBMs to track the spread of mutations whose origin and spread are driven by the intervention and which subsequently undermine the control strategy; typical examples are mutations which encode drug resistance or diagnosis‐ or vaccine‐escape phenotypes. Methods and results We simulated the spread of malaria drug resistance using the IBM OpenMalaria to investigate how the finite sizes of IBMs require strategies to optimally incorporate genetic selection. We make four recommendations. Firstly, calculate and report the selection coefficients, s, of the advantageous allele as the key genetic parameter. Secondly, use these values of “s” to calculate the wait time until a mutation successfully establishes itself in the pathogen population. Thirdly, identify the inherent limits of the IBM to robustly estimate small selection coefficients. Fourthly, optimize computational efficacy: when “s” is small, fewer replicates of larger IBMs may be more efficient than a larger number of replicates of smaller size. Discussion The OpenMalaria IBM of malaria was an exemplar and the same principles apply to IBMs of other diseases

An interprofessional urban health elective focused on the social determinants of health

Background: More than half of the world’s population now lives in cities. Health professionals should understand how social factors and processes in urban spaces determine individual and population health. We report on lessons from an interprofessional urban health elective developed to focus on the social determinants of health (SDOH).                Methods: An interprofessional committee developed an urban health elective based in downtown Toronto. Course objectives included promoting collaboration to address SDOH, identifying barriers to care, accessing community-based resources, and learning to advocate at individual- and community-levels.Results: Seventeen students from eight disciplines participated during the 2011-2012 academic year. Sessions were co-facilitated with community partners and community members identified as experts based on their personal experience. Topics included housing, income and food security, Indigenous communities in urban spaces, and advocacy. Students collaborated on self-directed projects, which ranged from literature reviews to policy briefs for government. Students particularly valued learning about community agencies and hearing from people with lived experience.Conclusion: The specific health challenges faced in urban settings can benefit from an interprofessional approach informed by the experiences and needs of patient communities. This elective was innovative in engaging students in interprofessional learning on how health and social agencies collaborate to tackle social determinants in urban spaces.

“They’re in the Shadows”: School Counselors Share the Lived Experiences of Latino/a Undocumented Students

Latino/a undocumented students are among the population of students who are in danger of not graduating or pursuing college due to the unique set of challenges they face navigating education in the U.S. This study aims to understand undocumented students\u27 experiences and the factors that impede them from furthering their education. As professionals in education, school counselors can offer a unique perspective on the barriers that college-bound undocumented students face when pursuing higher education. Using a phenomenological approach, data was gathered from counselors (N=14) across 10 school districts. The findings revealed undocumented students are faced with a myriad of challenges, socio-emotionally, academically, and career-wise, as they prepare to transition from high school to college

Steam-Induced Coarsening of Single-Unit-Cell MFI Zeolite Nanosheets and Its Effect on External Surface Brønsted Acid Catalysis.

Commonly used methods to assess crystallinity, micro-/mesoporosity, Brønsted acid site density and distribution (in micro- vs. mesopores), and catalytic activity suggest nearly invariant structure and function for aluminosilicate zeolite MFI two-dimensional nanosheets before and after superheated steam treatment. Yet, pronounced reaction rate decrease for benzyl alcohol alkylation with mesitylene, a reaction that cannot take place in the zeolite micropores, is observed. Transmission electron microscopy images reveal pronounced changes in nanosheet thickness, aspect ratio and roughness indicating that nanosheet coarsening and the associated changes in the external (mesoporous) surface structure are responsible for the changes in the external surface catalytic activity. Superheated steam treatment of hierarchical zeolites can be used to alter nanosheet morphology and regulate external surface catalytic activity while preserving micro- and mesoporosity, and micropore reaction rates

The effects of physiological and injurious hydrostatic pressure on murine ex vivo articular and growth plate cartilage explants:an RNAseq study

Chondrocytes are continuously exposed to loads placed upon them. Physiological loads are pivotal to the maintenance of articular cartilage health, while abnormal loads contribute to pathological joint degradation. Similarly, the growth plate cartilage is subject to various loads during growth and development. Due to the high-water content of cartilage, hydrostatic pressure is considered one of the main biomechanical influencers on chondrocytes and has been shown to play an important role in the mechano-regulation of cartilage. Herein, we conducted RNAseq analysis of ex vivo hip cap (articular), and metatarsal (growth plate) cartilage cultures subjected to physiological (5 MPa) and injurious (50 MPa) hydrostatic pressure, using the Illumina platform (n = 4 replicates). Several hundreds of genes were shown to be differentially modulated by hydrostatic pressure, with the majority of these changes evidenced in hip cap cartilage cultures (375 significantly upregulated and 322 downregulated in 5 MPa versus control; 1022 upregulated and 724 downregulated in 50 MPa versus control). Conversely, fewer genes were differentially affected by hydrostatic pressure in the metatarsal cultures (5 significantly upregulated and 23 downregulated in 5 MPa versus control; 7 significantly upregulated and 19 downregulated in 50 MPa versus control). Using Gene Ontology annotations for Biological Processes, in the hip cap data we identified a number of pathways that were modulated by both physiological and injurious hydrostatic pressure. Pathways upregulated in response to 50 MPa versus control, included those involved in the generation of precursor metabolites and cellular respiration. Biological processes that were downregulated in this tissue included ossification, connective tissue development, and chondrocyte differentiation. Collectively our data highlights the divergent chondrocyte phenotypes in articular and growth plate cartilage. Further, we show that the magnitude of hydrostatic pressure application has distinct effects on gene expression and biological processes in hip cap cartilage explants. Finally, we identified differential expression of a number of genes that have previously been identified as osteoarthritis risk genes, including Ctsk, and Chadl. Together these data may provide potential genetic targets for future investigations in osteoarthritis research and novel therapeutics. [Abstract copyright: Copyright © 2023 Bourne, Hesketh, Sharma, Bucca, Bush and Staines.

The Role of PPARγ in the Cyclooxygenase Pathway in Lung Cancer

Decreased expression of peroxisome proliferator activated receptor-γ (PPARγ) and high levels of the proinflammatory enzyme cyclooxygenase-2 (COX-2) have been observed in many tumor types. Both reduced (PPARγ) expression and elevated COX-2 within the tumor are associated with poor prognosis in lung cancer patients, and recent work has indicated that these signaling pathways may be interrelated. Synthetic (PPARγ) agonists such as the thiazolidinedione (TZD) class of anti-diabetic drugs can decrease COX-2 levels, inhibit growth of non-small-cell lung cancer (NSCLC) cells in vitro, and block tumor progression in xenograft models. TZDs alter the expression of COX-2 and consequent production of the protumorigenic inflammatory molecule prostaglandin E2 (PGE2) through both (PPARγ) dependent and independent mechanisms. Certain TZDs also reduce expression of PGE2 receptors or upregulate the PGE2 catabolic enzyme 15-prostaglandin dehydrogenase. As several COX-2 enzymatic products have antitumor properties and specific COX-2 inhibition has been associated with increased risk of adverse cardiac events, directly reducing the effects or concentration of PGE2 may provide a more safe and effective strategy for lung cancer treatment. Understanding the mechanisms underlying these effects may be helpful for designing anticancer therapies. This article summarizes recent research on the relationship between (PPARγ), TZDs, and the COX-2/PGE2 pathways in lung cancer