Korean Americans' Beliefs about Colorectal Cancer Screening

SummaryPurposeThe purpose of this study was to assess Korean Americans' (KAs) health and cultural beliefs about colorectal cancer (CRC) and their CRC screening utilization in order to understand how health and cultural beliefs play a role in CRC screening utilization and why KAs have a low rate of CRC screening.MethodsFace-to-face, individual interviews with 26 Korean immigrants aged 50 and older were conducted in Korean. A semi-structured interview guide with open-ended questions was used to explore participants' health and cultural beliefs about CRC and CRC screening. Recorded audio interviews were transcribed verbatim in Korean and coded using thematic analysis.ResultsThe themes that emerged from analyzing the individual interview data were: (a) valuing their families before themselves; (b) seeing a doctor only if they have symptoms; (c) believing that they would not get CRC; (d) balancing the will to stay healthy and fatalism; and (e) refusing health information.ConclusionResults show the critical need for in-depth understanding of unique health and cultural beliefs about CRC screening in KAs. These beliefs could be useful for future intervention strategies to change health and cultural beliefs in order to increase CRC screening participation in KAs

Human polyomavirus 6 and 7 are associated with pruritic and dyskeratotic dermatoses

ABSTRACT Background: Human Polyomavirus 6 (HPyV6) and Human Polyomavirus 7 (HPyV7) are shed chronically from human skin. HPyV7, but not HPyV6, has been linked to a pruritic skin eruption of immunosuppression. Objective: We determined whether biopsies showing a characteristic pattern of dyskeratosis and parakeratosis might be associated with polyomavirus infection. Methods: We screened biopsies showing "peacock plumage" histology by PCR for human polyomaviruses. Cases positive for HPyV 6 or 7 were then analyzed by immunohistochemistry, electron microscopy (EM), immunofluorescence, quantitative PCR, and complete sequencing, including unbiased, next generation sequencing (NGS). Results: We identified three additional cases of HPyV6 or 7 skin infections. Expression of T antigen and viral capsid was abundant in lesional skin. Dual immunofluorescence staining experiments confirmed that HPyV7 primarily infects keratinocytes. High viral loads in lesional skin compared to normal skin and the identification of intact virions by both EM and NGS support a role for active viral infections in these skin diseases. Limitation: This was a small case-series of archived materials. Conclusion: We have found that HPyV6 and HPyV7 are associated with rare, pruritic skin eruptions with a unique histologic pattern and describe this entity as "HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatosis (H6PD and H7PD).

Alternative splicing regulation of membrane trafficking genes during myogenesis

Alternative splicing transitions occur during organ development, and, in numerous diseases, splicing programs revert to fetal isoform expression. We previously found that extensive splicing changes occur during postnatal mouse heart development in genes encoding proteins involved in vesicle-mediated trafficking. However, the regulatory mechanisms of this splicing-trafficking network are unknown. Here, we found that membrane trafficking genes are alternatively spliced in a tissue-specific manner, with striated muscles exhibiting the highest levels of alternative exon inclusion. Treatment of differentiated muscle cells with chromatin-modifying drugs altered exon inclusion in muscle cells. Examination of several RNA-binding proteins revealed that the poly-pyrimidine tract binding protein 1 (PTBP1) and quaking regulate splicing of trafficking genes during myogenesis, and that removal of PTBP1 motifs prevented PTBP1 from binding its RNA target. These findings enhance our understanding of developmental splicing regulation of membrane trafficking proteins which might have implications for muscle disease pathogenesis

Systems Analysis of miRNA Biomarkers to Inform Drug Safety

microRNAs (miRNAs or miRs) are short non-coding RNA molecules which have been shown to be dysregulated and released into the extracellular milieu as a result of many drug and non-drug-induced pathologies in different organ systems. Consequently, circulating miRs have been proposed as useful biomarkers of many disease states, including drug-induced tissue injury. miRs have shown potential to support or even replace the existing traditional biomarkers of drug-induced toxicity in terms of sensitivity and specificity, and there is some evidence for their improved diagnostic and prognostic value. However, several pre-analytical and analytical challenges, mainly associated with assay standardization, require solutions before circulating miRs can be successfully translated into the clinic. This review will consider the value and potential for the use of circulating miRs in drug-safety assessment and describe a systems approach to the analysis of the miRNAome in the discovery setting, as well as highlighting standardization issues that at this stage prevent their clinical use as biomarkers. Highlighting these challenges will hopefully drive future research into finding appropriate solutions, and eventually circulating miRs may be translated to the clinic where their undoubted biomarker potential can be used to benefit patients in rapid, easy to use, point-of-care test systems

Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c) (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product) and Levaquin(c) (Janssen-Cilag Farmacêutica Ltda, Brazil, test product) was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c) and Levaquin(c) are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies

A Blood-Based Metabolomic Signature Predictive of Risk for Pancreatic Cancer

Emerging evidence implicates microbiome involvement in the development of pancreatic cancer (PaCa). Here, we investigate whether increases in circulating microbial-related metabolites associate with PaCa risk by applying metabolomics profiling to 172 sera collected within 5 years prior to PaCa diagnosis and 863 matched non-subject sera from participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cohort. We develop a three-marker microbial-related metabolite panel to assess 5-year risk of PaCa. The addition of five non-microbial metabolites further improves 5-year risk prediction of PaCa. The combined metabolite panel complements CA19-9, and individuals with a combined metabolite panel + CA19-9 score in the top 2.5th percentile have absolute 5-year risk estimates of \u3e13%. The risk prediction model based on circulating microbial and non-microbial metabolites provides a potential tool to identify individuals at high risk of PaCa that would benefit from surveillance and/or from potential cancer interception strategies

Smoking, drinking and body weight after re-employment: does unemployment experience and compensation make a difference?

<p>Abstract</p> <p>Background</p> <p>The impact of unemployment on behaviours such as smoking, drinking and body weight has been extensively researched. However, little is known about the possible protective effects of social assistance programs on these behavioural changes. This study examines the impact of unemployment periods on smoking, drinking and body weight changes among re-employed individuals and investigates whether the receipt of unemployment benefits influences these behaviours.</p> <p>Methods</p> <p>This study used panel data provided by the Panel Study of Income Dynamics. Logistic regression models were used to analyze whether a period of unemployment in 2000 resulted in an increase in smoking and drinking or fluctuations in body weight among 2001 re-employed individuals in comparison with 1999 baseline levels. A total of 3,451 respondents who had been initially healthy and who had been continuously employed between 1998 and 1999 were included in the analysis.</p> <p>Results</p> <p>Compared to stably employed respondents, those who had experienced periods of unemployment in 2000 and did not receive unemployment benefits were more likely than continuously employed individuals to report an increase in alcohol consumption (OR 1.8, 95% CI 1.0–3.1) and a decrease in body weight (OR 1.7, 95% CI 1.1–2.8) when they were already re-employed in 2001.</p> <p>Conclusion</p> <p>Our findings suggest that the receipt of unemployment benefits confers a protective effect on health behavioural changes following periods of unemployment. These findings underscore the need to monitor the impact of unemployment assistance programs on health, particularly in light of the rapidly changing structure of employment and unemployment benefits.</p

Nasal Iodophor Antiseptic vs Nasal Mupirocin Antibiotic in the Setting of Chlorhexidine Bathing to Prevent Infections in Adult ICUs: A Randomized Clinical Trial

IMPORTANCE: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization. OBJECTIVE: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing. DESIGN, SETTING, AND PARTICIPANTS: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included. INTERVENTION: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline). MAIN OUTCOMES AND MEASURES: ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%. RESULTS: Among the 801 668 admissions in 233 ICUs, the participants\u27 mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P \u3c .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]). CONCLUSIONS AND RELEVANCE: Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03140423

Automated deep learning segmentation of high-resolution 7 T postmortem MRI for quantitative analysis of structure-pathology correlations in neurodegenerative diseases

Postmortem MRI allows brain anatomy to be examined at high resolution and to link pathology measures with morphometric measurements. However, automated segmentation methods for brain mapping in postmortem MRI are not well developed, primarily due to limited availability of labeled datasets, and heterogeneity in scanner hardware and acquisition protocols. In this work, we present a high resolution of 135 postmortem human brain tissue specimens imaged at 0.3 mm$^{3}$ isotropic using a T2w sequence on a 7T whole-body MRI scanner. We developed a deep learning pipeline to segment the cortical mantle by benchmarking the performance of nine deep neural architectures, followed by post-hoc topological correction. We then segment four subcortical structures (caudate, putamen, globus pallidus, and thalamus), white matter hyperintensities, and the normal appearing white matter. We show generalizing capabilities across whole brain hemispheres in different specimens, and also on unseen images acquired at 0.28 mm^3 and 0.16 mm^3 isotropic T2*w FLASH sequence at 7T. We then compute localized cortical thickness and volumetric measurements across key regions, and link them with semi-quantitative neuropathological ratings. Our code, Jupyter notebooks, and the containerized executables are publicly available at: https://pulkit-khandelwal.github.io/exvivo-brain-upennComment: Preprint submitted to NeuroImage Project website: https://pulkit-khandelwal.github.io/exvivo-brain-upen

Development of a GIS-based knowledge hub for contaminants of emerging concern in South African water resources using open-source software : lessons learnt

SUPPLEMENTARY INFORMATION : The development of the CEC Knowledge Hub.DATA AVAILABILITY STATEMENT : Data will be made available on request.With population growth and dwindling freshwater sources, protecting such sources has come to the forefront of water resource management. Historically, society’s response to a problem is based on funding availability, current threat, and public outcry. Achieving this is largely dependent on the knowledge of the factors that are resulting in compromised water sources. These factors are constantly changing as novel contaminants are introduced into surface water sources. As we are in the information age, the interest in contaminants of emerging concern (CEC) is gaining ground. Whilst research is being conducted to identify contaminants in South African water sources, the research outputs and available information is not collated and presented to the science community and stakeholders in readily available formats and platforms. Current research outcomes need to be made known to regulators in order to develop environmental laws. By using fourth industrial revolution technology, we were able to collate available data in literature and display these in a user-friendly online format to regulatory bodies as well as researchers. A standardized excel spreadsheet was developed and uploaded to a PostgreSQL, running a PostGIS extension and was then processed in the GeoServer to allow for visualization on an interactive map which can be continuously updated. The near real-time access to information will reduce the possibility of duplication of research efforts, enhance collaboration in the discipline, and act as a CEC early warning system.Water Research Commissionhttps://www.cell.com/heliyon/homePlant Production and Soil Scienc