Phase I DAVIO Trial: EYP-1901 Bioerodible, Sustained-Delivery Vorolanib Insert in Patients With Wet Age-Related Macular Degeneration.

Purpose: To evaluate safety and tolerability of EYP-1901, an intravitreal insert containing vorolanib, a pan-VEGF receptor inhibitor packaged in a bioerodible delivery technology (Durasert E™) for sustained delivery, in patients with wet age-related macular degeneration (wAMD) previously treated with anti-VEGF therapy. Design: Phase I, multicenter, prospective, open-label, dose-escalation trial. Participants: Patients with wAMD and evidence of prior anti-VEGF therapy response. Methods: Patients received a single intravitreal injection of EYP-1901. Main Outcome Measures: The primary objective was to evaluate safety and tolerability of EYP-1901. Secondary objectives assessed biologic activity of EYP-1901 including best-corrected visual acuity (BCVA) and central subfield thickness (CST). Exploratory analyses included reduction in anti-VEGF treatment burden and supplemental injection-free rates. Results: Seventeen patients enrolled in the 440 µg (3 patients), 1030 µg (1 patient), 2060 µg (8 patients), and 3090 µg (5 patients) dose cohorts. No dose-limiting toxicity, ocular serious adverse events (AEs), or systemic AEs related to EYP-1901 were observed. There was no evidence of ocular or systemic toxicity related to vorolanib or the delivery technology. Moderate ocular treatment-emergent AEs (TEAEs) included reduced visual acuity (2/17) and retinal exudates (3/17). One patient with reduced BCVA had 3 separate reductions of 17, 18, and 16 letters, and another had a single drop of 25 letters. One severe TEAE, neovascular AMD (i.e., worsening/progressive disease activity), was reported in 1 of 17 study eyes but deemed unrelated to treatment. Mean change from baseline in BCVA was -1.8 letters and -5.4 letters at 6 and 12 months. Mean change from baseline in CST was +1.7 µm and +2.4 µm at 6 and 12 months. Reduction in treatment burden was 74% and 71% at 6 and 12 months. Of 16 study eyes, 13, 8, and 5 were injection-free up to 3, 6, and 12 months. Conclusion: In the DAVIO trial (ClinicalTrials.gov identifier, NCT04747197), EYP-1901 had a favorable safety profile and was well tolerated in previously treated eyes with wAMD. Measures of biologic activity remained relatively stable following a single EYP-1901 injection. These preliminary data support ongoing phase II and planned phase III trials to assess efficacy and safety. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Confined within a sugarcane monoculture: A participatory assessment of water pollution and potential health risks in the community of El Tiple, Colombia.

Communities neighboring monoculture plantations are vulnerable to different forms of pollution associated with agro-industrial operations. Herein, we examine the case of El Tiple, a rural Afro descendant community embedded within one of the largest sugarcane plantations in the Americas. We implemented a participatory approach to assess water pollution, exposure via water ingestion, and non-carcinogenic health risks associated with the use of local water sources available to the community. We conducted household surveys to unveil demographic characteristics and family dynamics linked to water consumption. Additionally, we measured water quality parameters and assessed the concentration glyphosate, its major metabolite (aminomethylphosphonic acid) and metals and metalloids. Drinking water El Tiple households is sourced from three primary sources: the local aqueduct system, water delivery trucks, and private deep wells. Tests on water samples from both the local aqueduct and delivery trucks showed no traces of pesticides, metals, or metalloids surpassing regulatory limits set by Colombian or EPA standards. However, we found concentration of contaminants of primary concern, including mercury (up to 0.0052 ppm) and lead (up to 0.0375 ppm) that exceed the permissible regulatory thresholds in water from groundwater wells. Residents of the peripheric subdivisions of El Tiple are four times more reliant on well water extraction than residents of the central area of the town due to lack of access to public drinking water and sanitation infrastructure. Finally, adult women and school-age children have a higher health risk associated with exposure to local pollutants than adult men due to their constant presence in the town. We conclude that expanding the coverage of clean water and sanitation infrastructure to include all households of the community would be the most recommended measure to minimize exposure and risk via ingestion of water pollutants.

Effects of Herbal Tea (Non-Camellia sinensis) on Glucose Homeostasis and Serum Lipids in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

CONTEXT: Hyperglycemia and hyperlipidemia increase the risk for diabetes and its complications, atherosclerosis, heart failure, and stroke. Identification of safe and cost-effective means to reduce risk factors is needed. Herbal teas may be a vehicle to deliver antioxidants and polyphenols for prevention of complications. OBJECTIVE: This systematic review and meta-analysis were conducted to evaluate and summarize the impact of herbal tea (non-Camellia sinensis) on glucose homeostasis and serum lipids in individuals with type 2 diabetes (T2D). DATA SOURCES: PubMed, FSTA, Web of Science, CINAHL, MEDLINE, and Cochrane Library databases were searched from inception through February 2023 using relevant keyword proxy terms for diabetes, serum lipids, and "non-Camellia sinensis" or "tea." DATA EXTRACTION: Data from 14 randomized controlled trials, totaling 551 participants, were included in the meta-analysis of glycemic and serum lipid profile end points. RESULTS: Meta-analysis suggested a significant association between drinking herbal tea (prepared with 2-20 g d-1 plant ingredients) and reduction in fasting blood glucose (FBG) (P = .0034) and glycated hemoglobin (HbA1c; P = .045). In subgroup analysis based on studies using water or placebo as the control, significant reductions were found in serum total cholesterol (TC; P = .024), low-density lipoprotein cholesterol (LDL-C; P = .037), and triglyceride (TG; P = .043) levels with a medium effect size. Meta-regression analysis suggested that study characteristics, including the ratio of male participants, trial duration, and region, were significant sources of FBG and HbA1c effect size heterogeneity; type of control intervention was a significant source of TC and LDL-C effect size heterogeneity. CONCLUSIONS: Herbal tea consumption significantly affected glycemic profiles in individuals with T2D, lowering FBG levels and HbA1c. Significance was seen in improved lipid profiles (TC, TG, and LDL-C levels) through herbal tea treatments when water or placebo was the control. This suggests water or placebo may be a more suitable control when examining antidiabetic properties of beverages. Additional research is needed to corroborate these findings, given the limited number of studies.

Cycloaddition of Phenyltriazolinedione with Carbazole-Alkynes and Yne-Carbamates to Access Diazacyclobutenes.

Previously, we described the synthesis of stable, bicyclic examples of the rather rare diazacyclobutene (DCB) motif by means of a cycloaddition between triazolinediones and electron-rich thiolated alkynes. Here, we report the investigation of the cycloaddition of triazolinediones with related electron-rich yne-carbamates and carbazole-alkynes. Bicyclic DCBs arising from yne-carbamates were isolated in 8-65% yield, while those arising from carbazole-alkynes were isolated in 28-59% yield. Mechanistic studies and characterization of isolable byproducts shed light on the underlying issues leading to poor to moderate yields.

Phytophthora Root and Crown Rot of Lavender: New Host-Pathogen Relationships Involving Six Species of Phytophthora and Three Species of Lavandula.

Phytophthora root and crown rot has become a major threat to the lavender industry worldwide. Isolations from symptomatic plants between 2015 and 2019 revealed a number of potential causal agents in the United States. In this study, we tested nine species of Phytophthora and four species of Lavandula and used Koch's Postulates to prove pathogenicity for six new host-pathogen relationships and confirm two pathogenic relationships for the first time in the United States. A total of 10 experiments were conducted with each consisting of two independent trials. Only host-pathogen combinations that occurred in the field were evaluated. All isolates used in these experiments were recovered from diseased lavender plants or, for one isolate, soil associated with a diseased plant sent to our lab or the Clemson University Plant and Pest Diagnostic Clinic for diagnosis. Experiments were conducted over 3 years, 2017 to 2019, in a research greenhouse under relatively uniform environmental conditions following a standard protocol. Plants were evaluated weekly for foliage symptom severity, and, at the end of each trial, plants were scored for final foliage symptom severity and root rot severity, area under the disease progress curve was calculated, fresh plant mass was weighed, and isolation of pathogens from roots was attempted. These studies successfully demonstrated for the first time pathogenicity of Phytophthora nicotianae, P. palmivora, and P. cinnamomi to hybrid lavender (Lavandula × intermedia), P. nicotianae to sweet lavender (L. heterophylla), and P. cryptogea and P. drechsleri to English lavender (L. angustifolia). In addition, a soil isolate of P. tropicalis was shown to be potentially pathogenic to L. × intermedia. Our results also documented for the first time in the United States pathogenicity of P. palmivora and P. citrophthora to L. angustifolia. We were not able to confirm pathogenicity for three host-pathogen relationships: P. megasperma on English lavender, P. cactorum on hybrid lavender, and P. nicotianae on Spanish lavender (L. stoechas). Results from this study expand the list of Phytophthora species causing root rot on lavender (Lavandula species) in the United States and elsewhere.

Associations among computed tomographic measures of bone and muscle quality and biomechanical measures of tibiotarsal bone quality in laying hens.

OBJECTIVE: The objectives of the current study were to quantify laying hen sternal carina (keel) and tibiotarsal bone and muscle quality using clinical CT, tissue level, and biomechanical measures; test associations among muscle transverse sectional area, bone mineral density, and biomechanical measures of bone quality; and determine whether CT measures of bone and muscle quality would be predictive of biomechanical measures of tibiotarsal bone quality. ANIMALS: 60 40-week-old Hy-Line brown laying hens were used. METHODS: Associations among CT imaging, tissue level, and biomechanical measures of tibiotarsal and keel bone and muscle quality were tested using multivariate correlational analyses. Bivariate and generalized regressions were performed to determine whether CT measures were predictive of biomechanical measures of tibiotarsal bone quality. RESULTS: Low positive correlations were identified between tibiotarsal muscle transverse-sectional area (cross-sectional area [CSA]) and bone mineral density (BMD) in the proximal location of the bone (r = -0.11 to 0.31). Tibiotarsal muscle CSA was also low to moderately correlated with biomechanical measures of bone quality (r = 0.20 to 0.41). Keel muscle CSA values were not correlated with keel BMD values, but they were correlated with biomechanical measures of tibiotarsal bone quality (r = 0.18 to 0.40). Keel CT measures of bone quality were not correlated with tibiotarsal CT measures of bone quality. At the proximal location, muscle CSA and tibiotarsal BMD were predictive of biomechanical failure load (F = 9.68, P = .0003muscle CSA; F = 9.13, P = .004tibiotarsal BMD). CLINICAL RELEVANCE: Findings supported using noninvasive CT measures of muscle and bone quality in longitudinal research studies evaluating the effects of interventions on laying hen welfare.

Genetic architecture of source-sink-regulated senescence in maize.

Source and sink interactions play a critical but mechanistically poorly understood role in the regulation of senescence. To disentangle the genetic and molecular mechanisms underlying source-sink-regulated senescence (SSRS), we performed a phenotypic, transcriptomic, and systems genetics analysis of senescence induced by the lack of a strong sink in maize (Zea mays). Comparative analysis of genotypes with contrasting SSRS phenotypes revealed that feedback inhibition of photosynthesis, a surge in reactive oxygen species, and the resulting endoplasmic reticulum (ER) stress were the earliest outcomes of weakened sink demand. Multienvironmental evaluation of a biparental population and a diversity panel identified 12 quantitative trait loci and 24 candidate genes, respectively, underlying SSRS. Combining the natural diversity and coexpression networks analyses identified 7 high-confidence candidate genes involved in proteolysis, photosynthesis, stress response, and protein folding. The role of a cathepsin B like protease 4 (ccp4), a candidate gene supported by systems genetic analysis, was validated by analysis of natural alleles in maize and heterologous analyses in Arabidopsis (Arabidopsis thaliana). Analysis of natural alleles suggested that a 700-bp polymorphic promoter region harboring multiple ABA-responsive elements is responsible for differential transcriptional regulation of ccp4 by ABA and the resulting variation in SSRS phenotype. We propose a model for SSRS wherein feedback inhibition of photosynthesis, ABA signaling, and oxidative stress converge to induce ER stress manifested as programed cell death and senescence. These findings provide a deeper understanding of signals emerging from loss of sink strength and offer opportunities to modify these signals to alter senescence program and enhance crop productivity.

The impact of daylight and window views on length of stay among patients with heart disease: A retrospective study in a cardiac intensive care unit.

Background: Heart disease is the leading cause of death in the United States. The length of stay (LOS) is a well-established parameter used to evaluate health outcomes among critically ill patients with heart disease in cardiac intensive care units (CICUs). While evidence suggests that the presence of daylight and window views can positively influence patients' LOS, no studies to date have differentiated the impact of daylight from window views on heart disease patients. Also, existing research studies on the impact of daylight and window views have failed to account for key clinical and demographic variables that can impact the benefit of such interventions in CICUs. Methods: This retrospective study investigated the impact of access to daylight vs. window views on CICU patients' LOS. The study CICU is located in a hospital in the southeast United States and has rooms of the same size with different types of access to daylight and window views, including rooms with daylight and window views (with the patient bed located parallel to full-height, south-facing windows), rooms with daylight and no window views (with the patient bed located perpendicular to the windows), and windowless rooms. Data from electronic health records (EHRs) for the time-period September 2015 to September 2019 (n=2936) were analyzed to investigate the impact of room type on patients' CICU LOS. Linear regression models were developed for the outcome of interest, controlling for potential confounding variables. Results: Ultimately, 2319 patients were finally included in the study analysis. Findings indicated that patients receiving mechanical ventilation in rooms with access to daylight and window views had shorter LOS durations (16.8 h) than those in windowless rooms. Sensitivity analysis for a subset of patients with LOS ≤3 days revealed that parallel bed placement to the windows and providing access to both daylight and window views significantly reduced their LOS compared to windowless rooms in the unit (P=0.007). Also, parallel bed placement to the window significantly reduced LOS in this patient subset for those with an experience of delirium (P=0.019), dementia (P=0.008), anxiety history (P=0.009), obesity (P=0.003), and those receiving palliative care (P=0.006) or mechanical ventilation (P=0.033). Conclusions: Findings from this study could help architects make design decisions and determine optimal CICU room layouts. Identifying the patients who benefit most from direct access to daylight and window views may also help CICU stakeholders with patient assignments and hospital training programs.

IBA Delivery Technique and Media Salts Affected In Vitro Rooting and Acclimatization of Eight Prunus Genotypes.

Difficult-to-root plants often perform poorly during acclimatization and in vitro rooting can increase the survival and quality of plants. The influence of auxin application and mineral nutrition on in vitro rooting and subsequent effects on plant quality in eight Prunus genotypes were investigated. Microshoots were rooted in vitro on Murashige and Skoog (MS), ½ MS, Driver and Kuniyuki (DKW), or New Prunus Medium (NPM) media formulations in combination with 15 µM indole-3-butyric acid (IBA), 4-day 15 µM IBA pulse, 1 mM 30 s quick-dip, or IBA-free treatments. Shoots were observed pre- and post-acclimatization to determine rooting methods to maximize quality and minimize labor. A genotype-specific response to auxin application was observed with seven of eight genotypes achieving 100% survival when paired with the recommended IBA treatment. Peaches performed best when treated with 4-day IBA pulse or 30 s quick-dip. Rooting of P. cerasifera, it's hybrid to P. persica, and P. munsoniana all benefitted from IBA application. Shoots rooted with 15 µM IBA were smaller and lower quality in most genotypes. DKW maximized size and quality in six genotypes. Better shoots and larger root systems during in vitro rooting produced better plants in the greenhouse with no detrimental effect of callus growth. Rooting techniques to maximize plant quality while reducing labor are specified.

Intraobserver repeatability for a standardized protocol to quantify keel bone damage in laying hens using discrete and continuous radiographic measures.

Sternal carina damage (keel bone damage, KBD) is an important welfare concern for laying hen producers and backyard flock owners. Quantitative radiographic measures of KBD severity are helpful for researchers who study causes for this problem and the effects of novel interventions. The objectives of the current retrospective secondary analysis study were to develop and test intraobserver repeatability for a standardized protocol to quantify three categories of radiographic KBD using open-source image analysis software and discrete and continuous variables. The standardized protocol was developed and evaluated using triplicate measurements of 470 keel bone radiographs that had been previously acquired for a prospective study. Intraobserver repeatability was assessed using intra-class correlation coefficient (ICC) and control chart methods. Based on control chart analyses, measures within the acceptable range of intra-observer variation using the standardized protocol were the number of complete cranial fractures (97.02%), incomplete cranial fractures (96.38%), complete caudal fractures (95.32%), incomplete caudal fractures (98.09%), cranial calluses (99.79%), and caudal calluses (98.09%); proportion of deviation (POD) measurements (97.87%); and angle of displacement (AOD) measurements (93.60%). Findings can be used as background to support future research studies on KBD in laying hens.

Yield, Nutritional Composition, and Digestibility of Conventional and Brown Midrib (BMR) Pearl Millet as Affected by Planting and Harvesting Dates and Interseeded Cowpea.

The objective of this study was to evaluate the yield, nutritional composition, and digestibility of conventional (CON) and brown midrib (BMR) pearl millet (PM) with different establishment dates, maturity at harvest and when mixed with cowpea (CWP). In trial 1, CON and BMR were planted on two different dates. In trial 2, CON and BMR, mixed or not with CWP, were harvested when PM was at the boot or heading stages. In trial 1, dry matter (DM) yield was similar between both PM genotypes but delaying establishment reduced DM yield by 30%. Additionally, BMR had a lower concentration of acid detergent lignin (ADL) and a higher in vitro neutral detergent fiber digestibility (IVNDFD) compared to CON. In Trial 2, the DM yield was 7.3% higher for CON compared to BMR, and PM with the BMR trait had a lower level of ADL and higher IVNDFD compared to CON. Mixing PM with CWP had negligible effects on nutritional composition but reduced DM yield by 8.3%. Results of these studies indicated that fiber from BMR PM is more digestible than CON but, in one of the trials, this occurred at the expense of lower DM yield. Mixing CWP with PM negatively impacted DM yield.

Lipid modulation contributes to heat stress adaptation in peanut.

At the cellular level, membrane damage is a fundamental cause of yield loss at high temperatures (HT). We report our investigations on a subset of a peanut (Arachis hypogaea) recombinant inbred line population, demonstrating that the membrane lipid remodeling occurring at HT is consistent with homeoviscous adaptation to maintain membrane fluidity. A major alteration in the leaf lipidome at HT was the reduction in the unsaturation levels, primarily through reductions of 18:3 fatty acid chains, of the plastidic and extra-plastidic diacyl membrane lipids. In contrast, levels of 18:3-containing triacylglycerols (TGs) increased at HT, consistent with a role for TGs in sequestering fatty acids when membrane lipids undergo remodeling during plant stress. Polyunsaturated acyl chains from membrane diacyl lipids were also sequestered as sterol esters (SEs). The removal of 18:3 chains from the membrane lipids decreased the availability of susceptible molecules for oxidation, thereby minimizing oxidative damage in membranes. Our results suggest that transferring 18:3 chains from membrane diacyl lipids to TGs and SEs is a key feature of lipid remodeling for HT adaptation in peanut. Finally, QTL-seq allowed the identification of a genomic region associated with heat-adaptive lipid remodeling, which would be useful for identifying molecular markers for heat tolerance.

A Phase I, Single Ascending Dose Study of GEM103 (Recombinant Human Complement Factor H) in Patients with Geographic Atrophy.

Purpose: To establish the safety, tolerability, pharmacokinetics, and pharmacodynamics of an intravitreal injection of recombinant human complement factor H (CFH), GEM103, in individuals with genetically defined age-related macular degeneration (AMD) and geographic atrophy (GA). Design: Phase I single ascending-dose, open-label clinical trial (ClinicalTrials.gov identifier, NCT04246866). Participants: Twelve individuals 50 years of age or older with a confirmed diagnosis of foveal GA in the study eye. Methods: Participants were assigned to the increasing dose cohorts and received 1 50-µl intravitreal injection of GEM103 at doses of 50 µg/eye, 100 µg/eye, 250 µg/eye, or 500 µg/eye; dose escalation was dependent on the occurrence of dose-limiting toxicities. Main Outcome Measures: Safety assessments included ocular and systemic adverse events (AEs), ocular examinations, clinical laboratory and vital signs, and serum antidrug antibody levels. Biomarkers, measured in the aqueous humor (AH), included CFH and complement activation biomarkers factor Ba and complement component 3a. Results: No dose-limiting toxicities were reported, enabling escalation to the maximum study dose. No anti-GEM103 antidrug antibodies were detected during the study. Four participants experienced AEs; these were nonserious, mild or moderate in severity, and unrelated to GEM103. The AEs in 2 of these participants were related to the intravitreal injection procedure. No clinically significant ophthalmic changes and no ocular inflammation were observed. Visual acuity was maintained and stable throughout the 8-week follow-up period. No choroidal neovascularization occurred. CFH levels increased in a dose-dependent manner after GEM103 administration with supraphysiological levels observed at week 1; levels were more than baseline for 8 weeks or more in all participants receiving single doses of 100 µg or more. Complement activation biomarkers were reduced 7 days after dose administration. Conclusions: A single intravitreal administration of GEM103 (up to 500 µg/eye) was well tolerated in individuals with GA. Of the few mild or moderate AEs reported, none were determined to be related to GEM103. No intraocular inflammation or choroidal neovascularization developed. CFH levels in AH were increased and stable for 8 weeks, with pharmacodynamic data suggesting that GEM103 restored complement regulation. These results support further development in a repeat-dose trial in patients with GA with AMD.

Outlook for Implementation of Genomics-Based Selection in Public Cotton Breeding Programs.

Researchers have used quantitative genetics to map cotton fiber quality and agronomic performance loci, but many alleles may be population or environment-specific, limiting their usefulness in a pedigree selection, inbreeding-based system. Here, we utilized genotypic and phenotypic data on a panel of 80 important historical Upland cotton (Gossypium hirsutum L.) lines to investigate the potential for genomics-based selection within a cotton breeding program's relatively closed gene pool. We performed a genome-wide association study (GWAS) to identify alleles correlated to 20 fiber quality, seed composition, and yield traits and looked for a consistent detection of GWAS hits across 14 individual field trials. We also explored the potential for genomic prediction to capture genotypic variation for these quantitative traits and tested the incorporation of GWAS hits into the prediction model. Overall, we found that genomic selection programs for fiber quality can begin immediately, and the prediction ability for most other traits is lower but commensurate with heritability. Stably detected GWAS hits can improve prediction accuracy, although a significance threshold must be carefully chosen to include a marker as a fixed effect. We place these results in the context of modern public cotton line-breeding and highlight the need for a community-based approach to amass the data and expertise necessary to launch US public-sector cotton breeders into the genomics-based selection era.

Analyzing material changes consistent with degradation of explanted polymeric hernia mesh related to clinical characteristics.

BACKGROUND: Proposed mechanisms that potentially contribute to polypropylene mesh degradation after in vivo exposure include oxidizing species and mechanical strains induced by normal healing, tissue integration, muscle contraction, and the immediate and chronic inflammatory responses. METHODS: This study explores these potential degradation mechanisms using 63 mesh implants retrieved from patients after a median implantation time of 24 months following hernia repair surgery (mesh explants) and analysis of multivariate associations between the material changes and clinical characteristics. Specifically, polypropylene mesh degradation was characterized in terms of material changes in surface oxidation, crystallinity and mechanical properties, and clinical characteristics included mesh placement location, medical history and mesh selection. RESULTS: Compared to pristine control samples, subsets of mesh explants had evidence of surface oxidation, altered crystallinity, or changed mechanical properties. Using multivariate statistical approach to control for clinical characteristics, infection was a significant factor affecting changes in mesh stiffness and mesh class was a significant factor affecting polypropylene crystallinity changes. CONCLUSIONS: Highly variable in vivo conditions expose mesh to mechanisms that alter clinical outcomes and potentially contribute to mesh degradation. These PP mesh explants after 0.5 to 13 years in vivo had measurable changes in surface chemistry, crystallinity and mechanical properties, with significant trends associated with factors of mesh placement, mesh class, and infection.

Chickpea (Cicer arietinum L.) as a Source of Essential Fatty Acids - A Biofortification Approach.

Chickpea is a highly nutritious pulse crop with low digestible carbohydrates (40-60%), protein (15-22%), essential fats (4-8%), and a range of minerals and vitamins. The fatty acid composition of the seed adds value because fats govern the texture, shelf-life, flavor, aroma, and nutritional composition of chickpea-based food products. Therefore, the biofortification of essential fatty acids has become a nutritional breeding target for chickpea crop improvement programs worldwide. This paper examines global chickpea production, focusing on plant lipids, their functions, and their benefits to human health. In addition, this paper also reviews the chemical analysis of essential fatty acids and possible breeding targets to enrich essential fatty acids in chickpea (Cicer arietinum) biofortification. Biofortification of chickpea for essential fatty acids within safe levels will improve human health and support food processing to retain the quality and flavor of chickpea-based food products. Essential fatty acid biofortification is possible by phenotyping diverse chickpea germplasm over suitable locations and years and identifying the candidate genes responsible for quantitative trait loci mapping using genome-wide association mapping.

The epidemiology and etiology of adhesive capsulitis in the U.S. Medicare population.

BACKGROUND: Adhesive capsulitis (AC) of the shoulder, also known as frozen shoulder, causes substantial pain and disability. In cases of secondary AC, the inflammation and fibrosis of the synovial joint can be triggered by trauma or surgery to the joint followed by extended immobility. However, for primary AC the inciting trigger is unknown. The burden of the disorder among the elderly is also unknown leading to this age group being left out of therapeutic research studies, potentially receiving delayed diagnoses, and unknown financial costs to the Medicare system. The purpose of this analysis was to describe the epidemiology of AC in individuals over the age of 65, an age group little studied for this disorder. The second purpose was to investigate whether specific medications, co-morbidities, infections, and traumas are risk factors or triggers for primary AC in this population. METHODS: We used Medicare claims data from 2010-2012 to investigate the prevalence of AC and assess comorbid risk factors and seasonality. Selected medications, distal trauma, and classes of infections as potential inflammatory triggers for primary AC were investigated using a case-control study design with patients with rotator cuff tears as the comparison group. Medications were identified from National Drug codes and translated to World Health Organization ATC codes for analysis. Health conditions were identified using ICD9-CM codes. RESULTS: We found a one-year prevalence rate of AC of approximately 0.35% among adults aged 65 years and older which translates to approximately 142,000 older adults in the United States having frozen shoulder syndrome. Diabetes and Parkinson's disease were significantly associated with the diagnosis of AC in the elderly. Cases were somewhat more common from August through December, although a clear seasonal trend was not observed. Medications, traumas, and infections were similar for cases and controls. CONCLUSIONS: This investigation identified the burden of AC in the US elderly population and applied case-control methodology to identify triggers for its onset in this population. Efforts to reduce chronic health conditions such as diabetes may reduce seemingly unrelated conditions such as AC. The inciting trigger for this idiopathic condition remains elusive.

Synthesis and evaluation of porphyrin glycoconjugates varying in linker length: preliminary effects on the photodynamic inactivation of Mycobacterium smegmatis.

Porphyrins have served as common photosensitizing agents in photomedicine due to their unique properties and broad therapeutic potential. While photodynamic therapy (PDT) offers a promising avenue for novel drug development, limitations in application due to selectivity, and the inherent hydrophobicity and poor solubility of porphyrins and other organic photosensitizers has been noted. Porphyrin glycoconjugates have recently gained attention for their potential to overcome these limitations. However, little has been done to explore the effects of the linker between the carbohydrate and porphyrin analog. Here we report the synthesis of over 30 new carbohydrate-porphyrin conjugates which vary in the nature of the sugar (Gal, Glc, GalNAc, GlcNAc, Lac and Tre) and the distance between the porphyrin macrocycle and the carbohydrate. Porphyrin glycoconjugates were synthesized in three steps from a readily available meso-brominated diphenylporphyrin analog by (i) C-O coupling of an appropriate TMS-protected alkynol consisting of two to six carbon spacers (ii) removal of the TMS protecting group, and (iii) CuAAC conjugation with an appropriate glycosyl azide. First studies with trehalose-based glycoporphyrins and M. smeg were used to determine the effects of the linker in photodynamic inactivation (PDI) studies. Preliminary results demonstrated an increase in photodynamic inactivation with a decrease in linker length. Investigations are underway to determine the mechanism for these results.

Average semivariance yields accurate estimates of the fraction of marker-associated genetic variance and heritability in complex trait analyses.

The development of genome-informed methods for identifying quantitative trait loci (QTL) and studying the genetic basis of quantitative variation in natural and experimental populations has been driven by advances in high-throughput genotyping. For many complex traits, the underlying genetic variation is caused by the segregation of one or more 'large-effect' loci, in addition to an unknown number of loci with effects below the threshold of statistical detection. The large-effect loci segregating in populations are often necessary but not sufficient for predicting quantitative phenotypes. They are, nevertheless, important enough to warrant deeper study and direct modelling in genomic prediction problems. We explored the accuracy of statistical methods for estimating the fraction of marker-associated genetic variance (p) and heritability ([Formula: see text]) for large-effect loci underlying complex phenotypes. We found that commonly used statistical methods overestimate p and [Formula: see text]. The source of the upward bias was traced to inequalities between the expected values of variance components in the numerators and denominators of these parameters. Algebraic solutions for bias-correcting estimates of p and [Formula: see text] were found that only depend on the degrees of freedom and are constant for a given study design. We discovered that average semivariance methods, which have heretofore not been used in complex trait analyses, yielded unbiased estimates of p and [Formula: see text], in addition to best linear unbiased predictors of the additive and dominance effects of the underlying loci. The cryptic bias problem described here is unrelated to selection bias, although both cause the overestimation of p and [Formula: see text]. The solutions we described are predicted to more accurately describe the contributions of large-effect loci to the genetic variation underlying complex traits of medical, biological, and agricultural importance.

Genome-wide association mapping of lentil (Lens culinaris Medikus) prebiotic carbohydrates toward improved human health and crop stress tolerance.

Lentil, a cool-season food legume, is rich in protein and micronutrients with a range of prebiotic carbohydrates, such as raffinose-family oligosaccharides (RFOs), fructooligosaccharides (FOSs), sugar alcohols (SAs), and resistant starch (RS), which contribute to lentil's health benefits. Beneficial microorganisms ferment prebiotic carbohydrates in the colon, which impart health benefits to the consumer. In addition, these carbohydrates are vital to lentil plant health associated with carbon transport, storage, and abiotic stress tolerance. Thus, lentil prebiotic carbohydrates are a potential nutritional breeding target for increasing crop resilience to climate change with increased global nutritional security. This study phenotyped a total of 143 accessions for prebiotic carbohydrates. A genome-wide association study (GWAS) was then performed to identify associated variants and neighboring candidate genes. All carbohydrates analyzed had broad-sense heritability estimates (H2) ranging from 0.22 to 0.44, comparable to those reported in the literature. Concentration ranges corresponded to percent recommended daily allowances of 2-9% SAs, 7-31% RFOs, 51-111% RS, and 57-116% total prebiotic carbohydrates. Significant SNPs and associated genes were identified for numerous traits, including a galactosyltransferase (Lcu.2RBY.1g019390) known to aid in RFO synthesis. Further studies in multiple field locations are necessary. Yet, these findings suggest the potential for molecular-assisted breeding for prebiotic carbohydrates in lentil to support human health and crop resilience to increase global food security.