Adipocyte maturation impacts daunorubicin disposition and metabolism.

INTRODUCTION: Acute lymphoblastic leukaemia (ALL) is the most common type of childhood leukaemia with effective chemotherapeutic treatment. However, obesity has been associated with higher ALL chemoresistance rates and lower event-free survival rates. The molecular mechanism of how obesity promotes chemotherapy resistance is not well delineated. OBJECTIVES: This study evaluated the effect of adipocyte maturation on sequestration and metabolism of chemotherapeutic drug daunorubicin (DNR). METHODS: Using targeted LC-MS/MS multi-analyte assay, DNR sequestration and metabolism were studied in human preadipocyte and adipocyte cell lines, where expressions of DNR-metabolizing enzymes aldo-keto reductases (AKR) and carbonyl reductases (CBR) were also evaluated. In addition, to identify the most DNR-metabolizing AKR/CBR isoforms, recombinant human AKR and CBR enzymes were subject to DNR metabolism. The results were further validated by AKR-, CBR-specific inhibitors. RESULTS: This report shows that adipocyte maturation upregulates expressions of AKR and CBR enzymes (by 4- to 60- folds, p < .05), which is positively associated with enhanced sequestration and metabolism of DNR in adipocytes compared to preadipocytes (by ~30%, p < .05). In particular, adipocyte maturation upregulates AKR1C3 and CBR1, which are the predominate metabolic enzyme isoforms responsible for DNR biotransformation to its metabolites. CONCLUSION: Fat is an expandable tissue that can sequester and detoxify DNR when stimulated by obesity, likely through the upregulation of DNR-metabolizing enzymes AKR1C3 and CBR1. Our data partially explains why obese ALL patients may be more likely to become chemoresistant towards DNR, and provides evidence for potential clinical investigation targeting obesity to reduce DNR chemoresistance.

Hydroxypropyl-Beta Cyclodextrin Barrier Prevents Respiratory Viral Infections: A Preclinical Study.

The emergence and mutation of pathogenic viruses have been occurring at an unprecedented rate in recent decades. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global public health crisis due to extensive viral transmission. In situ RNA mapping has revealed angiotensin-converting enzyme 2 (ACE2) expression to be highest in the nose and lower in the lung, pointing to nasal susceptibility as a predominant route for infection and the cause of subsequent pulmonary effects. By blocking viral attachment and entry at the nasal airway using a cyclodextrin-based formulation, a preventative therapy can be developed to reduce viral infection at the site of entry. Here, we assess the safety and antiviral efficacy of cyclodextrin-based formulations. From these studies, hydroxypropyl beta-cyclodextrin (HPBCD) and hydroxypropyl gamma-cyclodextrin (HPGCD) were then further evaluated for antiviral effects using SARS-CoV-2 pseudotypes. Efficacy findings were confirmed with SARS-CoV-2 Delta variant infection of Calu-3 cells and using a K18-hACE2 murine model. Intranasal pre-treatment with HPBCD-based formulations reduced viral load and inflammatory signaling in the lung. In vitro efficacy studies were further conducted using lentiviruses, murine hepatitis virus (MHV), and influenza A virus subtype H1N1. These findings suggest HPBCD may be used as an agnostic barrier against transmissible pathogens, including but not limited to SARS-CoV-2.

Loss of 15-Lipoxygenase in Retinodegenerative RCS Rats.

Retinitis pigmentosa (RP) is a retinal degenerative disease associated with a diversity of genetic mutations. In a natural progression study (NPS) evaluating the molecular changes in Royal College of Surgeons (RCS) rats using lipidomic profiling, RNA sequencing, and gene expression analyses, changes associated with retinal degeneration from p21 to p60 were evaluated, where reductions in retinal ALOX15 expression corresponded with disease progression. This important enzyme catalyzes the formation of specialized pro-resolving mediators (SPMs) such as lipoxins (LXs), resolvins (RvDs), and docosapentaenoic acid resolvins (DPA RvDs), where reduced ALOX15 corresponded with reduced SPMs. Retinal DPA RvD2 levels were found to correlate with retinal structural and functional decline. Retinal RNA sequencing comparing p21 with p60 showed an upregulation of microglial inflammatory pathways accompanied by impaired damage-associated molecular pattern (DAMP) clearance pathways. This analysis suggests that ALXR/FPR2 activation can ameliorate disease progression, which was supported by treatment with an LXA4 analog, NAP1051, which was able to promote the upregulation of ALOX12 and ALOX15. This study showed that retinal inflammation from activated microglia and dysregulation of lipid metabolism were central to the pathogenesis of retinal degeneration in RP, where ALXR/FPR2 activation was able to preserve retinal structure and function.

Exploring genetic variability, heritability, and trait correlations in gari and eba quality from diverse cassava varieties in Nigeria.

BACKGROUND: Gari (especially in Nigeria) is an important West African food product made from cassava. It is an affordable, precooked, dry, easy to prepare and store food product. Eba is a stiff dough produced by reconstituting gari in hot water. Gari and eba quality is an important driver of varietal acceptance by farmers, processors, and consumers. RESULTS: This study characterized the genetic variability, heritability, and correlations among quality-related traits of fresh roots, gari, and eba. Thirty-three diverse genotypes, including landraces and released and advanced breeding genotypes, were used in this study. In total, 40 traits categorized into fresh root quality, colour, functional, and texture properties trait groups were assessed. We observed broad phenotypic variability among the genotypes used in this study. Dry matter content had a positive (P < 0.05) correlation with gari%, bulk density and a negative correlation with eba hardness and gumminess. Broad-sense heritability across all environments varied considerably among the different trait groups: 62% to 79% for fresh root quality, 0% to 96% for colour, 0% to 79% for functional and 0% to 57% for texture properties. CONCLUSIONS: The stable broad-sense heritability found for gari%, gari and eba colour, bulk density, swelling index, and hardness measured using instrumental texture profile analysis coupled with sufficient variability in the population indicate good potential for genetic improvement of these traits through recurrent selection. Also, it is possible to genetically improve gari%, bulk density, and swelling power by simultaneously improving the dry matter content of fresh roots. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Prevalence and Risk Factors for Intimate Partner Physical Violence-Related Acquired Brain Injury Among Visitors to Justice Center in New York.

OBJECTIVE: The recent United States Government Accountability Office report highlights the need for improved data on the prevalence of intimate partner violence (IPV)-related acquired brain injury (ABI) to help direct Health & Human Services public efforts. This article identifies the prevalence and risk factors for IPV-related ABI among survivors of IPV at a Justice Center in New York. SETTING: Community Justice Center. PARTICIPANTS: Forty survivors of IPV, aged 17 to 73 years (median 32, interquartile range: 25.25, 42) were assessed within 60 days of sustaining physical violence. DESIGN: Retrospective chart review. MAIN MEASURES: The HELPS and the Danger Assessment-Revised were used at the initial Center visit. RESULTS: Of the 40 physical IPV survivors screened, all (100%) reported a prior history of partner-induced ABI within the past 60 days. Thirty-seven (92.5%) survivors also reported sustaining at least 1 potential hypoxic brain injury from strangulation. However, only 16 (40%) survivors screened positive on the HELPS for a history of IPV-related mild traumatic brain injury. Females (95%) and individuals with low income (67.5%) largely comprised our sample. Compared with the County's average, the proportion of African Americans/Blacks and refugees was 227% higher (42.5% vs 13%) and 650% higher (7.5% vs 1.09%), respectively. Refugee status (P = .017) also correlated with number of previous ABIs. On an exploratory binary logistic regression with stepwise selection, only balance difficulties (P = .023) and difficulty concentrating/remembering (P = .009) predicted a positive screen for mild traumatic brain injury. CONCLUSIONS: Consistent with previous findings, our data indicate a high prevalence of IPV-related ABI among visitors to a New York Justice Center. An overrepresentation of African Americans/Blacks and refugees in our sample relative to the region signified a higher prevalence of IPV in these populations and warrants a provision of more trauma-informed ABI resources to these groups/communities. Intimate partner violence survivors visiting Justice Centers should be screened for motor/neurocognitive symptoms suggestive of mild traumatic brain injury. Further research to identify the prevalence and risk factors of IPV-related ABI statewide and nationwide is urgently needed to improve resource allocation and clinical management.

A latent unknown clustering integrating multi-omics data (LUCID) with phenotypic traits.

MOTIVATION: Epidemiologic, clinical and translational studies are increasingly generating multiplatform omics data. Methods that can integrate across multiple high-dimensional data types while accounting for differential patterns are critical for uncovering novel associations and underlying relevant subgroups. RESULTS: We propose an integrative model to estimate latent unknown clusters (LUCID) aiming to both distinguish unique genomic, exposure and informative biomarkers/omic effects while jointly estimating subgroups relevant to the outcome of interest. Simulation studies indicate that we can obtain consistent estimates reflective of the true simulated values, accurately estimate subgroups and recapitulate subgroup-specific effects. We also demonstrate the use of the integrated model for future prediction of risk subgroups and phenotypes. We apply this approach to two real data applications to highlight the integration of genomic, exposure and metabolomic data. AVAILABILITY AND IMPLEMENTATION: The LUCID method is implemented through the LUCIDus R package available on CRAN (https://CRAN.R-project.org/package=LUCIDus). SUPPLEMENTARY INFORMATION: Supplementary materials are available at Bioinformatics online.

Genome-wide association study of circulating folate one-carbon metabolites.

Experimental, observational, and clinical trials support a critical role of folate one-carbon metabolism (FOCM) in colorectal cancer (CRC) development. In this report, we focus on understanding the relationship between common genetic variants and metabolites of FOCM. We conducted a genome-wide association study of FOCM biomarkers among 1,788 unaffected (without CRC) individuals of European ancestry from the Colon Cancer Family Registry. Twelve metabolites, including 5-methyltetrahydrofolate, vitamin B2 (flavin mononucleotide and riboflavin), vitamin B6 (4-pyridoxic acid, pyridoxal, and pyridoxamine), total homocysteine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, cystathionine, and creatinine were measured from plasma using liquid chromatography-mass spectrometry (LC-MS) or LC-MS/MS. For each individual biomarker, we estimated genotype array-specific associations followed by a fixed-effect meta-analysis. We identified the variant rs35976024 (at 2p11.2 and intronic of ATOH8) associated with total homocysteine (p = 4.9 × 10-8 ). We found a group of six highly correlated variants on chromosome 15q14 associated with cystathionine (all p < 5 × 10-8 ), with the most significant variant rs28391580 (p = 2.8 × 10-8 ). Two variants (rs139435405 and rs149119426) on chromosome 14q13 showed significant (p < 5 × 10-8 ) associations with S-adenosylhomocysteine. These three biomarkers with significant associations are closely involved in homocysteine metabolism. Furthermore, when assessing the principal components (PCs) derived from seven individual biomarkers, we identified the variant rs12665366 (at 6p25.3 and intronic of EXOC2) associated with the first PC (p = 2.3 × 10-8 ). Our data suggest that common genetic variants may play an important role in FOCM, particularly in homocysteine metabolism.

Cyanine Nanocage Activated by Near-IR Light for the Targeted Delivery of Cyclosporine A to Traumatic Brain Injury Sites.

More than 2.8 million annually in the United States are afflicted with some form of traumatic brain injury (TBI), where 75% of victims have a mild form of TBI (MTBI). TBI risk is higher for individuals engaging in physical activities or involved in accidents. Although MTBI may not be initially life-threatening, a large number of these victims can develop cognitive and physical dysfunctions. These late clinical sequelae have been attributed to the development of secondary injuries that can occur minutes to days after the initial impact. To minimize brain damage from TBI, it is critical to diagnose and treat patients within the first or "golden" hour after TBI. Although it would be very helpful to quickly determine the TBI locations in the brain and direct the treatment selectively to the affected sites, this remains a challenge. Herein, we disclose our novel strategy to target cyclosporine A (CsA) into TBI sites, without the need to locate the exact location of the TBI lesion. Our approach is based on TBI treatment with a cyanine dye nanocage attached to CsA, a known therapeutic agent for TBI that is associated with unacceptable toxicities. In its caged form, CsA remains inactive, while after near-IR light photoactivation, the resulting fragmentation of the cyanine nanocage leads to the selective release of CsA at the TBI sites.

Validation of QuEChERS method for the determination of 36 pesticide residues in fruits and vegetables from Ghana, using gas chromatography with electron capture and pulsed flame photometric detectors.

In this study, "Quick, Easy, Cheap, Effective, Rugged and Safe" 'QuEChERS' method was modified for the determination of 36 pesticides fortified at (0.01-1.0) mg kg(-1) in three vegetables and a fruit (lettuce, carrot, tomatoes and pineapples respectively) from Ghana. The method involved extraction with acetonitrile, phase separation with primary secondary amine and magnesium sulfate; the final injection solution was reconstituted in ethyl acetate. Organochlorine and synthetic pyrethroids residues were detected with electron capture detector whereas organophosphorus, pulsed flame photometric detector was used. The recoveries at different concentration levels (0.01, 0.1 and 1.0 mg kg(-1)) were in the range of 83% and 93% with relative standard deviation ranging from 2% to 10% (n = 5) and the coefficient of determination (R(2)) was greater than 0.99 for all the 36 pesticides. The method was successfully tested on 120 real samples from Accra markets and this proved to be useful for monitoring purposes particularly in laboratories that have no gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry.

Analysis of Contact Allergens in Polyvinyl Chloride Examination Gloves in the United States.

Background: Polyvinyl chloride (PVC) gloves are recommended as a safe alternative for patients with rubber accelerator allergy. However, allergic contact dermatitis to other chemicals in PVC gloves has been reported. Objective: To analyze single-use PVC medical examination gloves in the United States for the presence of potential contact allergens. Methods: Using liquid chromatography-mass spectrometry, 20 unique PVC gloves were analyzed in triplicate for 6 chemicals: benzisothiazolinone, bisphenol A, mono(2-ethylhexyl) maleate, tricresyl phosphate, triphenyl phosphate, and triphenyl phosphite. Results: All 20 PVC gloves contained detectable quantities of benzisothiazolinone (range, 0.001-1.48 parts per million [ppm]), bisphenol A (0.01-0.11 ppm), triphenyl phosphate (0.01-2.11 ppm), and triphenyl phosphite (0.001-0.22 ppm). Eighteen (90%) gloves contained mono(2-ethylhexyl) maleate (0.001-0.14 ppm) and 3 (15%) contained tricresyl phosphate (0.001-0.002 ppm). Conclusions: Known allergens were present in all 20 PVC gloves. However, the detected levels were mostly low and their relationship with sensitization and elicitation thresholds requires further study.

Trade-offs and Synergies between Economic and Environmental Cocoa Farm Management Decisions.

Optimizing sustainability among smallholder farms poses challenges due to inherent trade-offs. In the study of organic and conventional cocoa smallholder farming in Ghana, 398 farms are assessed using the Food and Agriculture Organsation of the United Nations (FAO) Sustainability Assessment of Food and Agriculture systems (SAFA) Guidelines and Sustainability Monitoring and Assessment Routine (SMART)-Farm Tool. Organic farming exhibited synergies in environmental aspects (e.g., soil quality, energy efficiency) and between biodiversity conservation and risk management. Conventional farming showed potential vulnerabilities, including trade-offs with long-range investments (e.g., chemical inputs) and species diversity. Both systems demand tailored approaches for short-term economic and environmental sustainability, aligning with community-wide long-term goals. To mitigate trade-offs in conventional farming, smallholders should adopt practices like material reuse, recycling, and recovery within their operations.

Genome-wide association study for yield and quality of granulated cassava processed product.

The starchy storage roots of cassava are commonly processed into a variety of products, including cassava granulated processed products (gari). The commercial value of cassava roots depends on the yield and quality of processed products, directly influencing the acceptance of new varieties by farmers, processors, and consumers. This study aims to estimate genetic advance through phenotypic selection and identify genomic regions associated and candidate genes linked with gari yield and quality. Higher single nucleotide polymorphism (SNP)-based heritability estimates compared to broad-sense heritability estimates were observed for most traits highlighting the influence of genetic factors on observed variation. Using genome-wide association analysis of 188 clones, genotyped using 53,150 genome-wide SNPs, nine SNPs located on seven chromosomes were significantly associated with peel loss, gari yield, color parameters for gari and eba, bulk density, swelling index, and textural properties of eba. Future research will focus on validating and understanding the functions of identified genes and their influence on gari yield and quality traits.

Computational optimization of delivery parameters to guide the development of targeted Nasal spray.

Airborne transmission by droplets and aerosols is known to play a critical role in the spread of many viruses amongst which are the common flu and the more recent SARS-CoV-2 viruses. In the case of SARS-CoV-2, the nasal cavity not only constitutes an important viral entry point, but also a primary site of infection (Sungnak W. et al. Nat. Med. 26:681-687. https://doi.org/10.1038/s41591-020-0868-6 , 2020).. Although face masks are a well-established preventive measure, development of novel and easy-to-use prophylactic measures would be highly beneficial in fighting viral spread and the subsequent emergence of variants of concern (Tao K. et al. Nat Rev Genet 22:757-773. https://doi.org/10.1038/s41576-021-00408-x , 2021). Our group has been working on optimizing a nasal spray delivery system that deposits particles inside the susceptible regions of the nasal cavity to act as a mechanical barrier to impede viral entry. Here, we identify computationally the delivery parameters that maximize the protection offered by this barrier. We introduce the computational approach and quantify the protection rate obtained as a function of a broad range of delivery parameters. We also introduce a modified design and demonstrate that it significantly improves deposition, thus constituting a viable approach to protect against nasal infection of airborne viruses. We then discuss our findings and the implications of this novel system on the prevention of respiratory diseases and targeted drug delivery.

Uncovering mechanisms of brain inflammation in Alzheimer's disease with APOE4: Application of single cell-type lipidomics.

A chronic state of unresolved inflammation in Alzheimer's disease (AD) is intrinsically involved with the remodeling of brain lipids. This review highlights the effect of carrying the apolipoprotein E ε4 allele (APOE4) on various brain cell types in promoting an unresolved inflammatory state. Among its pleotropic effects on brain lipids, we focus on APOE4's activation of Ca2+ -dependent phospholipase A2 (cPLA2) and its effects on arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid signaling cascades in the brain. During the process of neurodegeneration, various brain cell types, such as astrocytes, microglia, and neurons, together with the neurovascular unit, develop distinct inflammatory phenotypes that impact their functions and have characteristic lipidomic fingerprints. We propose that lipidomic phenotyping of single cell-types harvested from brains differing by age, sex, disease severity stage, and dietary and genetic backgrounds can be employed to probe mechanisms of neurodegeneration. A better understanding of the brain cellular inflammatory/lipidomic response promises to guide the development of nutritional and drug interventions for AD dementia.

Does COVID-19 Fear Induce Employee Innovation Performance Deficiency? Examining the Mediating Role of Psychological Stress and Moderating Role of Organizational Career Support.

With the immense, short/long-term, and multidirectional effects of the coronavirus disease (COVID-19) pandemic on work performance, industry activities, and the national/global economy, it has adversely affected employees' psychological well-being due to its elevated stress and anxiety that have substantially affected employee innovation performance (deficiency) (EIP(D)). The goal of this empirical paper is to identify how COVID-19 induces EIPD by examining the mediating role of psychological stress (PS) on the relationship between fear of infection with COVID-19 (FIC) and EIPD based on affective events theory (AET) and the moderating effect of organizational career support (OCS) on the relationship between PS and EIPD. Based on 865 survey responses provided by mid-level managers from Chinese manufacturing firms and the covariance-based structural equation modeling (SEM) technique using AMOS 25, we identified that FIC has a positive relationship with EIPD while PS can fully mediate the link between FIC and EIPD and OCS weakens the positive relationship between PS and EIPD (that is, in the presence of OCS, EIPD decreases despite the presence of PS among the employees). The findings of our empirical study will theoretically and practically contribute to the pandemic-related existing literature by providing an in-depth understanding of these variables. Furthermore, policymakers can also benefit by boosting their EIP from the outcomes revealed and suggestions provided.

Development of Moderate Intensity Focused Ultrasound (MIFU) for Ocular Drug Delivery.

The purpose of this study is to develop a method for delivering antiinflammatory agents of high molecular weight (e.g., Avastin) into the posterior segment that does not require injections into the eye (i.e., intravitreal injections; IVT). Diseases affecting the posterior segment of the eye are currently treated with monthly to bimonthly intravitreal injections, which can predispose patients to severe albeit rare complications like endophthalmitis, retinal detachment, traumatic cataract, and/or increased intraocular. In this study, we show that one time moderate intensity focused ultrasound (MIFU) treatment can facilitate the penetration of large molecules across the scleral barrier, showing promising evidence that this is a viable method to deliver high molecular weight medications not invasively. To validate the efficacy of the drug delivery system, IVT injections of vascular endothelial growth factor (VEGF) were used to create an animal model of retinopathy. The creation of this model allowed us to test anti-VEGF medications and evaluate the efficacy of the treatment. In vivo testing showed that animals treated with our MIFU device improved on the retinal tortuosity and clinical dilation compared to the control group while evaluating fluorescein angiogram (FA) Images.

Lipidomics in Understanding Pathophysiology and Pharmacologic Effects in Inflammatory Diseases: Considerations for Drug Development.

The lipidome has a broad range of biological and signaling functions, including serving as a structural scaffold for membranes and initiating and resolving inflammation. To investigate the biological activity of phospholipids and their bioactive metabolites, precise analytical techniques are necessary to identify specific lipids and quantify their levels. Simultaneous quantification of a set of lipids can be achieved using high sensitivity mass spectrometry (MS) techniques, whose technological advancements have significantly improved over the last decade. This has unlocked the power of metabolomics/lipidomics allowing the dynamic characterization of metabolic systems. Lipidomics is a subset of metabolomics for multianalyte identification and quantification of endogenous lipids and their metabolites. Lipidomics-based technology has the potential to drive novel biomarker discovery and therapeutic development programs; however, appropriate standards have not been established for the field. Standardization would improve lipidomic analyses and accelerate the development of innovative therapies. This review aims to summarize considerations for lipidomic study designs including instrumentation, sample stabilization, data validation, and data analysis. In addition, this review highlights how lipidomics can be applied to biomarker discovery and drug mechanism dissection in various inflammatory diseases including cardiovascular disease, neurodegeneration, lung disease, and autoimmune disease.

Induced variations of ethyl methane sulfonate mutagenized cowpea (Vigna unguiculata L. walp) plants.

Unique variants are desired in the development of genetically improved crops to meet farmer and market needs hence ethyl methane sulfonate (EMS) was used to induce genetic variability in cowpea (Vigna unguiculata cv. Asontem). The main objective of this research was to characterize induced variations in EMS chemically mutagenized population of cowpea (Vigna unguiculata L. Walp Var. Asontem) in the M1 and M2 generations. The optimum concentration (LD50) of EMS for generating the mutagenized population was determined by treating seeds with different concentrations of EMS (0.0, 0.2, 0.4, 0.6, and 0.8% v/v) and observing the germination count after 5 days of planting the seeds in Petri dishes. Three thousand cowpea seeds were treated with the 0.4% EMS to generate the M1 and M2 populations that were evaluated for agronomic and morphological traits with untreated seeds serving as control. Data analysis involved distribution of qualitative and quantitative traits. Germination was significantly reduced in the mutagenized population (17.8%) and compared with that of the wild type (61.6%). Percentage survival was significantly higher in wild type (98.38%) as compared with the M1 population (78.46%). Percentage germination in the M2 population (74.03%) was lower than the wild type (80%). A wide spectrum of agro-morphological abnormalities was observed in the M2 population. Wide variations and uniquely different phenotypic classes were observed in leaf color, leaf shape, growth habit, plant pigmentation, twining tendency, pod curvature, seed shape, and seed coat color. M2 individuals were widely distributed for days to flowering, number of pods per plant, number of seeds per pod, number of locules per pods, percentage seed set, pod length and number of seeds per plant. In conclusion, the EMS mutagenesis was effective in inducing the unique variations that will be useful for breeding and development of new farmer preferred varieties.

Alterations in Renin-Angiotensin System (RAS) Peptide Levels in Patients with HIV.

Chronic HIV infection has long been associated with an increased risk for cardiovascular diseases. The metabolites of the renin−angiotensin system (RAS) such as angiotensin II (AngII) play an important role in regulating blood pressure and fluid dynamics. Cross-sectional analysis of HIV-positive individuals (n = 71, age > 40 years, stable ART > 3 months with HIV viral load < 50 copies/mL) were compared to a similar HIV seronegative group (n = 72). High-resolution B-mode ultrasound images of the right carotid bifurcation (RBIF) and right common carotid artery (RCCA) were conducted to measure the extent of carotid atherosclerotic vascular disease. Plasma RAS peptide levels were quantified using a liquid chromatography-mass spectrometry-based metabolomics assay. RAS peptide concentrations were compared between persons with HIV and persons without HIV, correlating their association with clinical and cardiac measures. Median precursor peptides (Ang(1-12) and AngI) were significantly higher in the HIV-positive group compared to the HIV-negative. Analyses of the patient subgroup not on antihypertensive medication revealed circulating levels of AngII to be four-fold higher in the HIV-positive subgroup. AngII and TNF-alpha levels were found to have a positive association with RCCA, and AngI/Ang(1-12) ratio and TNF-alpha levels were found to have a positive association with RBIF. In both predictive models, AngIII had a negative association with either RCCA or RBIF, which may be attributed to its ability to bind onto AT2R and thus oppose pro-inflammatory events. These results reveal systemic alterations in RAS as a result of chronic HIV infection, which may lead to the activation of inflammatory pathways associated with carotid thickening. RAS peptide levels and cytokine markers were associated with RCCA and RBIF measurements.

Genetic variability and genotype by environment interaction of two major cassava processed products in multi-environments.

Conversion of cassava (Manihot esculenta) roots to processed products such as gari and fufu before consumption is a common practice worldwide by cassava end-user for detoxification, prolonged shelf life or profitability. Fresh root and processed product yield are supposed to be equivalent for each genotype, however, that is not the case. Developing genotypes with high product conversion rate is an important breeding goal in cassava as it drives the adoption rates of new varieties. The objective of this study was to quantify the contribution of genetic and genotype-by-environment interaction (GEI) patterns on cassava root conversion rate to gari and fufu. Sixty-seven advanced breeding genotypes from the International Institute of Tropical Agriculture (IITA) were evaluated across eight environments in Nigeria. Root conversion rate means across trials ranges from 14.72 to 22.76% for gari% and 16.96-24.24% for fufu%. Heritability estimates range from 0.17 to 0.74 for trial bases and 0.71 overall environment for gari% and 0.03-0.65 for trial bases and 0.72 overall environment for fufu% which implies that genetic improvement can be made on these traits. Root conversion rate for both gari and fufu% showed a negative but insignificant correlation with fresh root yield and significant positive correlation to Dry Matter content. For all fitted models, environment and interaction had explained more of the phenotypic variation observed among genotypes for both product conversion rates showing the presence of a strong GEI. Wrickle ecovalence (Wi) stability analysis and Geometric Adaptability index (GAI) identified G40 (TMS14F1285P0006) as part of top 5 genotypes for gari% but no overlapping genotype was identified by both stability analysis for fufu%. This genotypic performance across environments suggests that it is possible to have genotype with dual-purpose for high gari and fufu conversion rate.