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1.
Nutrients ; 16(9)2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38732559

ABSTRACT

(1) Background: Fortifying maize and wheat flours with folic acid has effectively reduced neural tube defect-affected births. However, maize and wheat flours may not be widely consumed in all countries; further reduction in neural tube defect-affected births could benefit from the identification of alternative food vehicles. We aimed to use dietary intake or apparent consumption data to determine alternative food vehicles for large-scale fortification with folic acid in low-income and lower-middle-income countries (LILMICs) and identify current research related to examining the technological feasibility of fortifying alternative foods with folic acid. (2) Methods: We identified 81 LILMICs, defined by the World Bank's (WB) 2018 income classifications. To identify dietary intake or apparent consumption, we reviewed WB's Microdata Library and Global Health Data Exchange for national surveys from 1997-2018. We reviewed survey reports for dietary intake or apparent consumption data and analyzed survey datasets for population coverage of foods. We defined alternative food vehicles as those that may cover/be consumed by ≥30% of the population or households; cereal grains (maize and wheat flours and rice) were included as an alternative food vehicle if a country did not have existing mandatory fortification legislation. To identify current research on fortification with folic acid in foods other than cereal grains, we conducted a systematic review of published literature and unpublished theses, and screened for foods or food products. (3) Results: We extracted or analyzed data from 18 national surveys and countries. The alternative foods most represented in the surveys were oil (n = 16), sugar (n = 16), and salt (n = 14). The coverage of oil ranged from 33.2 to 95.7%, sugar from 32.2 to 98.4%, and salt from 49.8 to 99.9%. We found 34 eligible studies describing research on alternative foods. The most studied alternative foods for fortification with folic acid were dairy products (n = 10), salt (n = 6), and various fruit juices (n = 5). (4) Conclusions: Because of their high coverage, oil, sugar, and salt emerge as potential alternative foods for large-scale fortification with folic acid. However, except for salt, there are limited or no studies examining the technological feasibility of fortifying these foods with folic acid.


Subject(s)
Edible Grain , Folic Acid , Food, Fortified , Neural Tube Defects , Triticum , Folic Acid/administration & dosage , Humans , Neural Tube Defects/prevention & control , Triticum/chemistry , Edible Grain/chemistry , Flour/analysis , Zea mays/chemistry , Developing Countries
2.
Eye Brain ; 14: 137-147, 2022.
Article in English | MEDLINE | ID: mdl-36531433

ABSTRACT

Introduction: Previous works on experience-dependent brain plasticity have been limited to the cortical structures, overlooking subcortical visual structures such as the lateral geniculate nucleus (LGN). Animal studies have shown substantial experience dependent plasticity and using fMRI, human studies have demonstrated similar properties in patients with cataract surgery. However, in neither animal nor human studies LGN has not been directly assessed, mainly due to its small size, tissue heterogeneity, low contrast/noise ratio, and low spatial resolution. Methods: Utilizing a new algorithm that markedly improves the LGN visibility, LGN was evaluated in a group of low vision patients before and after retinal intervention to reinstate vision and normal sighted matched controls. Results: Between and within groups comparisons showed that patients had significantly smaller left (p< 0.0001) and right (p < 0.00002) LGN volumes at baseline as compared to the one-year follow-up volumes. The same baseline and one year comparison in controls was not significant. Significant positive correlations were observed between the incremental volume increase after gene therapy of the left LGN and the incremental increase in the right (r = 0.71, p < 0.02) and left (r = 0.72, p = 0.018) visual fields. Incremental volume increase of the right LGN also showed a similar positive slope but did not reach significance. Discussion: These results show that despite significantly less volume at baseline, retinal gene therapy promotes robust expansion and increase in LGN volume. Reinstating vision may have facilitated the establishment of new connections between the retina and the LGN and/or unmasking of the dormant connections. The exact trajectory of the structural changes taking place in LGN is unclear but our data shows that even after years of low vision, the LGN in RPE65 patients has the potential for plasticity and expansion to a nearly normal volume one year after gene therapy administration.

3.
J Biogeogr ; 49(5): 979-992, 2022 May.
Article in English | MEDLINE | ID: mdl-35506011

ABSTRACT

Aim: Comprehensive, global information on species' occurrences is an essential biodiversity variable and central to a range of applications in ecology, evolution, biogeography and conservation. Expert range maps often represent a species' only available distributional information and play an increasing role in conservation assessments and macroecology. We provide global range maps for the native ranges of all extant mammal species harmonised to the taxonomy of the Mammal Diversity Database (MDD) mobilised from two sources, the Handbook of the Mammals of the World (HMW) and the Illustrated Checklist of the Mammals of the World (CMW). Location: Global. Taxon: All extant mammal species. Methods: Range maps were digitally interpreted, georeferenced, error-checked and subsequently taxonomically aligned between the HMW (6253 species), the CMW (6431 species) and the MDD taxonomies (6362 species). Results: Range maps can be evaluated and visualised in an online map browser at Map of Life (mol.org) and accessed for individual or batch download for non-commercial use. Main conclusion: Expert maps of species' global distributions are limited in their spatial detail and temporal specificity, but form a useful basis for broad-scale characterizations and model-based integration with other data. We provide georeferenced range maps for the native ranges of all extant mammal species as shapefiles, with species-level metadata and source information packaged together in geodatabase format. Across the three taxonomic sources our maps entail, there are 1784 taxonomic name differences compared to the maps currently available on the IUCN Red List website. The expert maps provided here are harmonised to the MDD taxonomic authority and linked to a community of online tools that will enable transparent future updates and version control.

4.
CJC Open ; 4(2): 214-222, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35198939

ABSTRACT

BACKGROUND: Women with physical disabilities are faced with challenges in many aspects of life-education, work, income, relationships, as well as their general health. These women are at a greater risk of developing heart disease. This study aimed to explore the cardiac pain experiences of women with physical disabilities and heart disease within a Canadian healthcare context. METHODS: In this qualitative study, 8 women with physical disabilities and heart disease from across Canada were interviewed. They were asked about their pre-, peri-, and post-diagnostic experiences in the Canadian healthcare system. Transcripts of the interviews were analyzed using a hermeneutic phenomenological approach inspired by Ricoeur. RESULTS: Two main themes were uncovered in the analysis of the transcripts, as follows: (i) the diagnostic journey; and (ii) life with cardiac symptoms and a disability. The women indicated that they had experienced difficulties in utilizing the Canadian healthcare system prior to receiving a cardiac diagnosis, including long waitlists, expensive and unreliable transport, issues with accessibility, and dealing with providers' attitudinal barriers regarding disability. Receiving a diagnosis was challenging due to poor relationships with healthcare providers; however, having a same-sex provider seemed essential to receiving adequate care. Self-managing a disability and heart disease had significant physical and psychological impact, which was lightened by financial and social supports, modified lifestyle choices, and self-advocacy. CONCLUSIONS: Women with physical disabilities are often forgotten in discussions encompassing equity and inclusion. The participants' experiences offer insight into what changes are needed within the Canadian healthcare system in order to improve outcomes for these women.


CONTEXTE: Les femmes qui présentent une incapacité physique doivent composer avec des défis dans de nombreux aspects de leur vie, notamment en ce qui touche l'éducation, le travail, le revenu, les relations et la santé en général. Le risque de cardiopathie est plus important dans leur cas. Cette étude visait à examiner comment la douleur cardiaque est vécue par les femmes présentant une incapacité physique et une cardiopathie dans le contexte des soins de santé au Canada. MÉTHODOLOGIE: Dans le cadre de cette étude qualitative, huit femmes présentant une incapacité physique et une cardiopathie ont participé à des entrevues menées à l'échelle du Canada. Elles ont été interrogées sur leurs expériences au sein du système de santé canadien au cours des périodes précédant, entourant et suivant le diagnostic. Les transcriptions des entrevues ont été analysées en fonction d'une approche phénoménologique herméneutique inspirée par Ricœur. RÉSULTATS: Deux grands thèmes ressortent de l'analyse des transcriptions, à savoir : (i) le parcours diagnostique; (ii) la vie avec des symptômes cardiaques et une incapacité physique. Les femmes interrogées ont indiqué qu'elles avaient éprouvé des difficultés dans leur parcours au sein du système de santé canadien avant de recevoir un diagnostic en cardiologie, évoquant à cet égard les longues listes d'attente, les services de transport coûteux et peu fiables, les problèmes d'accessibilité et les obstacles liés à l'attitude des fournisseurs de soins vis-à-vis de l'incapacité physique. Le fait de recevoir un diagnostic a été éprouvant en raison de rapports difficiles avec les fournisseurs de soins de santé; cependant, le fait d'avoir un fournisseur de soins de sexe féminin semblait être une condition essentielle à une prestation de soins adéquate. L'autoprise en charge d'une incapacité physique et d'une cardiopathie a eu des répercussions physiques et psychologiques importantes qui ont pu être allégées par le soutien financier et social, des modifications des habitudes de vie et l'autonomie sociale. CONCLUSIONS: Les femmes qui présentent une incapacité physique sont souvent laissées pour compte dans les discussions portant sur l'équité et l'inclusion. Le vécu des participantes donne un aperçu des changements qui doivent être apportés au sein du système de santé canadien afin d'améliorer les résultats chez ces femmes.

6.
J Rural Health ; 38(1): 93-99, 2022 01.
Article in English | MEDLINE | ID: mdl-33666274

ABSTRACT

PURPOSE: Rural areas of the United States have experienced outbreaks of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections among people who use drugs (PWUD). Pharmacy-based interventions may play a crucial role in prevention and entry into care, especially when traditional health care access is limited. The willingness of rural PWUD to use pharmacies for HIV/HCV-related services remains unknown. The purpose of this study was to describe the factors associated with the perceived likelihood of participating in free pharmacy-based HIV and HCV testing among PWUD living in rural Kentucky. METHODS: Baseline data from the CARE2HOPE study in five Appalachian counties in eastern Kentucky were used. Participants were recruited using respondent-driven sampling and completed interviewer-administered surveys. Guided by the Andersen and Newman Framework of Health Services Utilization, we examined distributions and correlates of items regarding willingness to participate in free pharmacy-based HIV/HCV testing using logistic regression. Analyses included individuals who reported being HIV (N = 304) or HCV (N = 185) negative. FINDINGS: Seventy-five percent of PWUD reported being "very likely" to participate in free pharmacy-based HIV testing and 80% for HCV testing. Two factors were associated with being less willing to participate in free HIV testing: PWUD who previously tested for HIV (OR: 0.47, CI: 0.25-0.88) and PWUD who obtained a high school diploma or equivalent compared to those who completed less (OR: 0.50, CI: 0.26-0.99). CONCLUSION: Free pharmacy-based HIV and HCV testing was invariably acceptable among most of the rural PWUD in our sample, suggesting that pharmacies might be acceptable testing venues for this population.


Subject(s)
HIV Infections , Hepatitis C , Pharmaceutical Preparations , Pharmacies , Pharmacy , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Testing , Hepacivirus , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Humans , Kentucky/epidemiology , Patient Acceptance of Health Care
7.
PLoS Biol ; 19(11): e3001460, 2021 11.
Article in English | MEDLINE | ID: mdl-34780461

ABSTRACT

A vast range of research applications in biodiversity sciences requires integrating primary species, genetic, or ecosystem data with other environmental data. This integration requires a consideration of the spatial and temporal scale appropriate for the data and processes in question. But a versatile and scale flexible environmental annotation of biodiversity data remains constrained by technical hurdles. Existing tools have streamlined the intersection of occurrence records with gridded environmental data but have remained limited in their ability to address a range of spatial and temporal grains, especially for large datasets. We present the Spatiotemporal Observation Annotation Tool (STOAT), a cloud-based toolbox for flexible biodiversity-environment annotations. STOAT is optimized for large biodiversity datasets and allows user-specified spatial and temporal resolution and buffering in support of environmental characterizations that account for the uncertainty and scale of data and of relevant processes. The tool offers these services for a growing set of near global, remotely sensed, or modeled environmental data, including Landsat, MODIS, EarthEnv, and CHELSA. STOAT includes a user-friendly, web-based dashboard that provides tools for annotation task management and result visualization, linked to Map of Life, and a dedicated R package (rstoat) for programmatic access. We demonstrate STOAT functionality with several examples that illustrate phenological variation and spatial and temporal scale dependence of environmental characteristics of birds at a continental scale. We expect STOAT to facilitate broader exploration and assessment of the scale dependence of observations and processes in ecology.


Subject(s)
Biodiversity , Cloud Computing , Animals , Birds/physiology , Databases as Topic , Satellite Communications , Seasons , Spatio-Temporal Analysis , Species Specificity , Temperature , Time Factors
8.
Cureus ; 13(5): e15242, 2021 May 25.
Article in English | MEDLINE | ID: mdl-34188984

ABSTRACT

We present a rare case in which malignant catatonia led to acute liver failure (ALF). A 19-year-old male was admitted for psychosis and developed ALF with a peak aspartate aminotransferase and alanine aminotransferase of 5,728 U/L and 7,735 U/L, respectively, and a peak international normalized ratio of 7.1. Liver biopsy showed significant confluent necrosis involving >70% of the liver tissue. He was listed for a liver transplant but was ultimately taken off of because of significant improvement with treatment by N-acetylcysteine infusion. Through our research, we found that symptoms of hepatitis can be seen with psychotic disorders, but ALF is rare.

9.
Nutrients ; 13(2)2021 Feb 09.
Article in English | MEDLINE | ID: mdl-33572488

ABSTRACT

Food fortification is designed to improve the nutritional profile of diets. The purpose of this research was to estimate the potential nutrient contribution of fortified maize flour, oil, rice, salt, and wheat flour in 153 countries, using the national intake (or availability) of the food and the nutrient levels required for fortification. This was done under two scenarios-maximum, where 100% of the food is assumed to be industrially processed and fortified, and realistic, where the maximum value is adjusted based on the percent of the food that is industrially processed and fortified. Under the maximum scenario, the median Estimated Average Requirements (EARs) met ranged from 22-75% for 14 nutrients (vitamins A, B1, B2, B3, B6, B12, D, E, folic acid and calcium, fluoride, iron, selenium and zinc), and 338% for iodine. In the realistic scenario, the median EARs met were 181% for iodine and <35% for the other nutrients. In both scenarios, the median Tolerable Upper Intake Levels (ULs) met were <55% for all nutrients. Under the realistic scenario, no country exceeded 100% of the UL for any nutrient. Current fortification practices of the five foods of interest have the global potential to contribute up to 15 nutrients to the diets of people, with minimal risk of exceeding ULs.


Subject(s)
Food, Fortified , Micronutrients/administration & dosage , Oryza , Sodium Chloride, Dietary/analysis , Triticum , Zea mays , Eating , Flour/analysis , Humans , Micronutrients/analysis , No-Observed-Adverse-Effect Level , Nutritional Requirements , Plant Oils/analysis
10.
Sci Total Environ ; 764: 143963, 2021 Apr 10.
Article in English | MEDLINE | ID: mdl-33385644

ABSTRACT

Consumption of licit and/or illicit compounds during sporting events has traditionally been monitored using population surveys, medical records, and law enforcement seizure data. This pilot study evaluated the temporal and geospatial patterns in drug consumption during a university football game from wastewater using liquid chromatography tandem mass spectrometry (LC-MS/MS). Untreated wastewater samples were collected from three locations within or near the same football stadium every 30 min during a university football game. This analysis leveraged two LCMS/ MS instruments (Waters Acquity TQD and a Shimadzu 8040) to analyze samples for 58 licit or illicit compounds and some of their metabolites. Bayesian multilevel models were implemented to estimate mass load and population-level drug consumption, while accounting for multiple instrument runs and concentrations censored at the lower limit of quantitation. Overall, 29 compounds were detected in at least one wastewater sample collected during the game. The 10 most common compounds included opioids, anorectics, stimulants, and decongestants. For compounds detected in more than 50% of samples, temporal trends in median mass load were correlated with the timing of the game; peak loads for cocaine and tramadol occurred during the first quarter of the game and for phentermine during the third quarter. Stadium-wide estimates of the number of doses of drugs consumed were rank ordered as follows: oxycodone (n = 3246) > hydrocodone (n = 2260) > phentermine (n = 513) > cocaine (n = 415) > amphetamine (n = 372) > tramadol (n = 360) > pseudoephedrine (n = 324). This analysis represents the most comprehensive assessment of drug consumption during a university football game and indicates that wastewater-based epidemiology has potential to inform public health interventions focused on reducing recreational drug consumption during large-scale sporting events.


Subject(s)
Wastewater , Water Pollutants, Chemical , Bayes Theorem , Chromatography, Liquid , Humans , Pilot Projects , Substance Abuse Detection , Tandem Mass Spectrometry , Universities , Wastewater/analysis , Water Pollutants, Chemical/analysis
11.
Sci Rep ; 10(1): 18229, 2020 10 26.
Article in English | MEDLINE | ID: mdl-33106580

ABSTRACT

A major limitation hindering the widespread use of synthetic phages in medical and industrial settings is the lack of an efficient phage-engineering platform. Classical T4 phage engineering and several newly proposed methods are often inefficient and time consuming and consequently, only able to produce an inconsistent range of genomic editing rates between 0.03-3%. Here, we review and present new understandings of the CRISPR/Cas9 assisted genome engineering technique that significantly improves the genomic editing rate of T4 phages. Our results indicate that crRNAs selection is a major rate limiting factor in T4 phage engineering via CRISPR/Cas9. We were able to achieve an editing rate of > 99% for multiple genes that functionalizes the phages for further applications. We envision that this improved phage-engineering platform will accelerate the fields of individualized phage therapy, biocontrol, and rapid diagnostics.


Subject(s)
Bacteria/virology , Bacteriophage T4/genetics , CRISPR-Cas Systems/genetics , Gene Editing/methods , Genetic Engineering/standards , Viral Plaque Assay/methods , Bacteria/metabolism , Bacteriophage T4/metabolism , Gene Editing/standards , Genetic Engineering/methods
12.
Analyst ; 145(19): 6291-6297, 2020 Sep 28.
Article in English | MEDLINE | ID: mdl-32945826

ABSTRACT

Phage-based biosensors have shown significant promise in meeting the present needs of the food and agricultural industries due to a combination of sufficient portability, speed, ease of use, sensitivity, and low production cost. Although current phage-based methods do not meet the bacteria detection limit imposed by the EPA, FDA, and USDA, a better understanding of phage genetics can significantly increase their sensitivity as biosensors. In the current study, the signal sensitivity of a T4 phage-based detection system was improved via transcriptional upregulation of the reporter enzyme Nanoluc luciferase (Nluc). An efficient platform to evaluate the promoter activity of reporter T4 phages was developed. The ability to upregulate Nluc within T4 phages was evaluated using 15 native T4 promoters. Data indicates a six-fold increase in reporter enzyme signal from integration of the selected promoters. Collectively, this work demonstrates that fine tuning the expression of reporter enzymes such as Nluc through optimization of transcription can significantly reduce the limits of detection.


Subject(s)
Bacteriophage T4 , Biosensing Techniques , Bacteriophage T4/genetics , Luciferases , Promoter Regions, Genetic
13.
ACS Appl Bio Mater ; 3(9): 5824-5831, 2020 Sep 21.
Article in English | MEDLINE | ID: mdl-34179727

ABSTRACT

Advances in synthetic biology, nanotechnology, and genetic engineering are allowing parallel advances in areas such as drug delivery and rapid diagnostics. Although our current visions of nanobots may be far off, a generation of nanobots synthesized by engineering viruses is approaching. Such tools can be used to solve complex problems where current methods do not meet current demands. Assuring safe drinking water is crucial for minimizing the spread of waterborne illnesses. Although extremely low levels of fecal contamination in drinking water are sufficient to cause a public health risk, it remains challenging to rapidly detect Escherichia coli, the standard fecal indicator organism. Current methods sensitive enough to meet regulatory standards suffer from either prohibitively long incubation times or requirement of expensive, impractical equipment. Bacteriophages, tuned by billions of years of evolution to bind viable bacteria and readily engineered to produce custom proteins, are uniquely suited to bacterial detection. We have developed a biosensor platform based on magnetized phages encoding luminescent reporter enzymes. This system utilizes bio-orthogonally functionalized phages to enable site-specific conjugation to magnetic nanoparticles. The resulting phage-based nanobots, when combined with standard, portable field equipment, allow for detection of <10 cfu/100 mL of viable E. coli within 7 h, faster than any methods published to date.

14.
Antioxidants (Basel) ; 8(1)2019 Jan 04.
Article in English | MEDLINE | ID: mdl-30621138

ABSTRACT

The reactions of antioxidants with superoxide radical were studied by cyclic voltammetry (CV)-and hydrodynamic voltammetry at a rotating ring-disk electrode (RRDE). In both methods, the superoxide is generated in solution from dissolved oxygen and then measured after being allowed to react with the antioxidant being studied. Both methods detected and measured the radical scavenging but the RRDE was able to give detailed insight into the antioxidant behavior. Three flavonoids, chrysin, quercetin and eriodictyol, were studied, their scavenging activity of superoxide was assessed and the molecular structure of each flavonoid was related to its scavenging capability. From our improved and novel RRDE method, we determine the ability of these 3 antioxidants to react with superoxide radical in a more quantitative manner than the classical CV. Density Functional Theory (DFT) and single crystal X-ray diffraction data provide structural information that assists in clarifying the scavenging molecular mechanism. Hydroxyls associated with the A ring, as found in chrysin, scavenge superoxide in a different manner than those found in the B ring of flavonoids, as those in quercetin and eriodictyol.

15.
J Immunol Methods ; 451: 118-121, 2017 12.
Article in English | MEDLINE | ID: mdl-28890365

ABSTRACT

B cell depletion by rituximab treatment might be inefficient in patients suffering from nephrotic syndrome. Due to the impaired glomerular filtration barrier a significant portion of the therapeutic antibody might be lost into the urinary space. In order to determine the amount of rituximab in the urine of such patients, CD20+ Daudi cells were stained with the patients' urine followed by a fluorochrome-labeled secondary antibody. Mean fluorescence intensity of that way labeled Daudi cells was determined by flow cytometry. Control samples with defined rituximab concentrations were used to create standard curves. The analyses revealed that all nephelometric IgG+ urine samples tested also manifested rituximab at concentrations between 100 and 46,707µg/L. The flow cytometry-based approach is an easy and reliable method to assess rituximab in patients' urine samples for monitoring individual rituximab treatment courses in all patients co-presenting impaired renal filtration. Presence of such antibodies in the urine could be considered as criteria to modify the formulation or modality of rituximab delivery in order to prevent the loss of the therapeutic antibodies and thereby ensuring efficacy of the therapy.


Subject(s)
Drug Monitoring/methods , Flow Cytometry , Immunologic Factors/urine , Nephrotic Syndrome/urine , Rituximab/urine , B-Lymphocytes/drug effects , Biomarkers/urine , Case-Control Studies , Cell Line, Tumor , Cell Survival/drug effects , Drug Monitoring/standards , Flow Cytometry/standards , Glomerular Filtration Rate , Humans , Immunologic Factors/pharmacology , Kidney/physiopathology , Nephrotic Syndrome/physiopathology , Predictive Value of Tests , Reference Standards , Reproducibility of Results , Rituximab/pharmacology , Urinalysis
16.
J Biol Chem ; 292(29): 12100-12110, 2017 07 21.
Article in English | MEDLINE | ID: mdl-28539358

ABSTRACT

Kidney disease has been linked to dysregulated signaling via PKC in kidney cells such as podocytes. PKCα is a conventional isoform of PKC and a well-known binding partner of ß-catenin, which promotes its degradation. ß-Catenin is the main effector of the canonical Wnt pathway and is critical in cell adhesion. However, whether other PKC isoforms interact with ß-catenin has not been studied systematically. Here we demonstrate that PKCϵ-deficient mice, which develop proteinuria and glomerulosclerosis, display lower ß-catenin expression compared with PKC wild-type mice, consistent with an altered phenotype of podocytes in culture. Remarkably, ß-catenin showed a reversed subcellular localization pattern: Although ß-catenin exhibited a perinuclear pattern in undifferentiated wild-type cells, it predominantly localized to the nucleus in PKCϵ knockout cells. Phorbol 12-myristate 13-acetate stimulation of both cell types revealed that PKCϵ positively regulates ß-catenin expression and stabilization in a glycogen synthase kinase 3ß-independent manner. Further, ß-catenin overexpression in PKCϵ-deficient podocytes could restore the wild-type phenotype, similar to rescue with a PKCϵ construct. This effect was mediated by up-regulation of P-cadherin and the ß-catenin downstream target fascin1. Zebrafish studies indicated three PKCϵ-specific phosphorylation sites in ß-catenin that are required for full ß-catenin function. Co-immunoprecipitation and pulldown assays confirmed PKCϵ and ß-catenin as binding partners and revealed that ablation of the three PKCϵ phosphorylation sites weakens their interaction. In summary, we identified a novel pathway for regulation of ß-catenin levels and define PKCϵ as an important ß-catenin interaction partner and signaling opponent of other PKC isoforms in podocytes.


Subject(s)
Podocytes/metabolism , Protein Kinase C-epsilon/metabolism , Protein Processing, Post-Translational , beta Catenin/metabolism , Active Transport, Cell Nucleus/drug effects , Amino Acid Substitution , Animals , Biological Assay , Carcinogens/toxicity , Cell Line, Transformed , Gene Expression Regulation/drug effects , Glycogen Synthase Kinase 3 beta/metabolism , HEK293 Cells , Humans , Mice, Knockout , Mutagenesis, Site-Directed , Mutation , Phosphorylation/drug effects , Podocytes/cytology , Podocytes/drug effects , Protein Kinase C-epsilon/antagonists & inhibitors , Protein Kinase C-epsilon/genetics , Protein Processing, Post-Translational/drug effects , Protein Stability/drug effects , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Tetradecanoylphorbol Acetate/analogs & derivatives , Tetradecanoylphorbol Acetate/toxicity , Tissue Culture Techniques , beta Catenin/antagonists & inhibitors , beta Catenin/chemistry , beta Catenin/genetics
17.
Case Rep Nephrol ; 2017: 1372859, 2017.
Article in English | MEDLINE | ID: mdl-28243475

ABSTRACT

Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty's syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

18.
J Racial Ethn Health Disparities ; 4(3): 455-461, 2017 06.
Article in English | MEDLINE | ID: mdl-27352114

ABSTRACT

After decades of resistance, there is now a genuine consensus that disease cannot be prevented or even successfully treated unless the role of stress is addressed alongside traditionally recognized factors such as genes and the environment. Measurement of allostatic load, which is quantified by the allostatic load score (ALS), is one of the most frequently used methods to assess the physiologic response to stress. Even though there is universal agreement that in the calculation of ALS, biomarkers from three categories should be included (cardiovascular, metabolic and immune), enormous variation exists in how ALS is calculated. Specifically, there is no consensus on which biomarkers to include or the method which should be used to determine whether the value of a biomarker represents high risk. In this perspective, we outline the approach taken in 21 different NHANES studies.


Subject(s)
Allostasis/physiology , Health Surveys/methods , Allostasis/immunology , Biomarkers/metabolism , Blood Pressure/immunology , Blood Pressure/physiology , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , Humans , RNA-Binding Proteins/immunology , RNA-Binding Proteins/metabolism , Stress, Psychological/immunology , Stress, Psychological/metabolism , United States
19.
Front Public Health ; 4: 265, 2016.
Article in English | MEDLINE | ID: mdl-27933289

ABSTRACT

INTRODUCTION: Allostatic load score (ALS) summarizes the physiological effect of stress on cardiovascular, metabolic and immune systems. As immigration is stressful, ALS could be affected. OBJECTIVE: Associations between age of immigration, reason for immigration, and unhealthy assimilation behavior and ALS were determined in 238 African immigrants to the United States (age 40 ± 10, mean ± SD, range 21-64 years). METHODS: ALS was calculated using 10 variables from three domains; cardiovascular (SBP, DBP, cholesterol, triglyceride, homocysteine), metabolic [BMI, A1C, albumin, estimated glomerular filtration rate (eGFR)], and immunological [high-sensitivity C-reactive protein (hsCRP)]. Variables were divided into sex-specific quartiles with high-risk defined by the highest quartile for each variable except for albumin and eGFR, which used the lowest quartile. One point was assigned if the variable was in the high-risk range and 0 if not. Unhealthy assimilation behavior was defined by a higher prevalence of smoking, alcohol consumption, or sedentary activity in immigrants who lived in the US for ≥10 years compare to <10 years. RESULTS: Sixteen percent of the immigrants arrived in the US as children (age < 18 years); 84% arrived as adults (age ≥ 18 years). Compared to adulthood immigrants, childhood immigrants were younger (30 ± 7 vs. 42 ± 9, P < 0.01) but had lived in the US longer (20 ± 8 vs. 12 ± 9 years, P < 0.01). Age-adjusted ALS was similar in childhood and adulthood immigrants (2.78 ± 1.83 vs. 2.73 ± 1.69, P = 0.87). For adulthood immigrants, multiple regression analysis (adj R2 = 0.20) revealed older age at immigration and more years in the US were associated with higher ALS (both P < 0.05); whereas, current age, education, income, and gender had no significant influence (all P ≥ 0.4). The prevalence of smoking, alcohol intake, and physical activity did not differ in adulthood immigrants living in the US for ≥10 years vs. <10 years (all P ≥ 0.2). Reason for immigration was available for 77 participants. The reasons included: family reunification, lottery, marriage, work, education, and asylum. Compared to all other reasons combined, immigration for family reunification was associated with the lowest ALS (1.94 ± 1.51 vs. 3.03 ± 1.86, P = 0.03). CONCLUSION: African immigrants do not appear to respond to the stress of immigration by developing unhealthy assimilation behaviors. However, older age at immigration and increased duration of stay in the US are associated with higher ALS; whereas, family reunification is associated with lower ALS. CLINICAL TRIALSGOV IDENTIFIER: NCT00001853.

20.
Clin Chem ; 62(11): 1524-1532, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27624138

ABSTRACT

BACKGROUND: Following immigration to the US, many Africans transition from a low-normal to a high-normal or overweight body mass index (BMI). This weight change is associated with a high rate of prediabetes in the nonobese. Studies in East Asians reveal that glycated albumin is effective in identifying prediabetes in nonobese Asians. Whether this is true in African immigrants is unknown. Therefore, we evaluated the ability of hemoglobin A1c (Hb A1c) and glycated albumin to detect prediabetes in nonobese (BMI <30 kg/m2) and obese (BMI ≥30 kg/m2) African immigrants. METHODS: Oral glucose tolerance tests (OGTTs) were performed in 236 self-identified healthy African immigrants [mean (SD) BMI 27.6 (4.4) kg/m2]. Prediabetes diagnosis was based on glucose criteria for the OGTT. Diagnostic sensitivity of Hb A1c and glycated albumin was determined by thresholds at the upper quartile for each [Hb A1c ≥5.7% (39 mmol/mol), glycated albumin ≥13.77%]. RESULTS: Based on glucose criteria for the OGTT, prediabetes was detected in 36% (85/236). BMI and Hb A1c were positively correlated (r = 0.22, P < 0.001), whereas BMI and glycated albumin were negatively correlated (r = -0.24, P < 0.001). Although the sensitivities of Hb A1c and glycated albumin were similar in nonobese immigrants (37% vs 42%, P = 0.75), prediabetes was detected in 21 nonobese Africans by glycated albumin alone, in 18 by Hb A1c alone, and in 4 by both tests. Therefore, sensitivity of the combined tests was better than for Hb A1c alone(72% vs 37%, P < 0.01). In the obese, Hb A1c was a much better diagnostic test than glycated albumin (64% vs 16%, P < 0.01) and combining the tests did not improve sensitivity (72% vs 64%, P = 0.50). CONCLUSIONS: Glycated albumin contributes by identifying prediabetes not detected by Hb A1c in nonobese African immigrants. ClinicalTrials.gov Identifier: NCT00001853.


Subject(s)
Black or African American , Glycated Hemoglobin/analysis , Prediabetic State/blood , Prediabetic State/diagnosis , Serum Albumin/analysis , Adult , Black People , Body Mass Index , Cohort Studies , Female , Glucose Tolerance Test , Glycation End Products, Advanced , Humans , Male , Middle Aged , Young Adult , Glycated Serum Albumin
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