The IRG1-itaconate axis protects from cholesterol-induced inflammation and atherosclerosis.

Atherosclerosis is fueled by a failure to resolve lipid-driven inflammation within the vasculature that drives plaque formation. Therapeutic approaches to reverse atherosclerotic inflammation are needed to address the rising global burden of cardiovascular disease (CVD). Recently, metabolites have gained attention for their immunomodulatory properties, including itaconate, which is generated from the tricarboxylic acid-intermediate cis-aconitate by the enzyme Immune Responsive Gene 1 (IRG1/ACOD1). Here, we tested the therapeutic potential of the IRG1-itaconate axis for human atherosclerosis. Using single-cell RNA sequencing (scRNA-seq), we found that IRG1 is up-regulated in human coronary atherosclerotic lesions compared to patient-matched healthy vasculature, and in mouse models of atherosclerosis, where it is primarily expressed by plaque monocytes, macrophages, and neutrophils. Global or hematopoietic Irg1-deficiency in mice increases atherosclerosis burden, plaque macrophage and lipid content, and expression of the proatherosclerotic cytokine interleukin (IL)-1ß. Mechanistically, absence of Irg1 increased macrophage lipid accumulation, and accelerated inflammation via increased neutrophil extracellular trap (NET) formation and NET-priming of the NLRP3-inflammasome in macrophages, resulting in increased IL-1ß release. Conversely, supplementation of the Irg1-itaconate axis using 4-octyl itaconate (4-OI) beneficially remodeled advanced plaques and reduced lesional IL-1ß levels in mice. To investigate the effects of 4-OI in humans, we leveraged an ex vivo systems-immunology approach for CVD drug discovery. Using CyTOF and scRNA-seq of peripheral blood mononuclear cells treated with plasma from CVD patients, we showed that 4-OI attenuates proinflammatory phospho-signaling and mediates anti-inflammatory rewiring of macrophage populations. Our data highlight the relevance of pursuing IRG1-itaconate axis supplementation as a therapeutic approach for atherosclerosis in humans.

Exploring the combined effect of heavy metals on accumulation efficiency of Salix alba raised on lead and cadmium contaminated soils.

The present study illustrated that Salix alba can accumulate high level of Pb and Cd in different plant parts, with maximum accumulation in roots followed by stem and leaves in the order Cd > Pb > Cd + Pb. The phytoremediation evaluation factors such as bioconcentration factor (BCF) and translocation factor (TF) was higher for Cd over Pb in all plant parts, further the BCF for both Pb and Cd was maximum in root (BCF > 1) followed by stem and leaves. Higher accumulation of Cd over the Pb was observed inside the plant tissues due to Cd mimics with other elements and gets transported through respective transporters. The combined treatment of Pb and Cd affected the bioaccumulation at every treatment level suggesting the negative effect among both elements. Higher survival rate (>85%) was recorded up to 200mgPb/kg and 15mgCd/kg, while further increase in metal concentration reduced the plant efficiency to remediate contaminated soils, hence results in declined survival rate. The FTIR analysis revealed that Pb and Cd accumulation in plants induced changes in carboxy, amino, hydroxyl and phosphate groups that ultimately caused alteration in physiological and biochemical processes of plant and thus provided an insight to the interaction, binding and accumulation of heavy metals.

The present study conferred that Salix alba is a heavy metal (Pb and Cd) excluder plant on the basis of phytoremediation efficiency evaluation factors such BCF >1 (root) and TF <1. The correlation studies suggested the negative correlation among Pb and Cd accumulation and morphological traits. Physiological studies indicated that Pb and Cd accumulation negatively affect chlorophyll concentration and the antioxidant mechanism of plants gets activated, further these results are confirmed with FTIR studies, which reported the alteration in functional groups and associated compounds in plant tissues under Pb and Cd stress.

Starch-based antibacterial food packaging with ZnO nanoparticle.

Starch-based biofilms with embedded nanoparticles (NPs) are used to wrap food in biodegradable packaging system that has high antibacterial action against a variety of microorganisms. In this study, ZnO NPs were synthesised using both a green synthesis approach utilising Azadirachta indica (Neem) and a chemical synthesis approach using the sol-gel technique. The structural and morphological properties of all synthesized NPs were characterized through XRD, UV-VIS, UV-DRS, FTIR, and FESEM analysis. Further, these NPs were employed in the development of starch-based biodegradable films. A meticulous comparative analysis was performed to evaluate the functional properties of the nanocomposites, encompassing crucial parameters such as film thickness, moisture content, swelling index, opacity, solubility, water vapor permeability, and tensile strength. In comparison to films embedded with chemically synthesised NPs (F1), nanocomposite with green synthesised NPs (F2) showed 15.27% greater inhibition against Escherichia coli growth and 22.05% stronger inhibition against Staphylococcus aureus bacterial strains. Based on the biodegradability analysis, the nanocomposite film-F2 showed a 53.33% faster degradation rate compared to the film-F1. The developed films were utilized to assess the quality of both wrapped and unwrapped grapes, leading to the generalization of the research for the development of starch-based antibacterial and environmentally friendly food packaging material. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05834-9.

Association of blood donor characteristics and in vitro haemolysis of packed red blood cell concentrates during storage.

BACKGROUND AND OBJECTIVES: Blood donor variability can affect the storage properties of packed red blood cells (PRBCs). This study aimed to determine the association of donor characteristics with in vitro storage haemolysis of PRBCs. MATERIALS AND METHODS: In the prospective observational study, a total of 109 whole blood donors were enrolled using the purposive sampling method. A pre-donation sample was collected for haemoglobin (Hb) and serum uric acid (UA) levels. PRBC aliquots were tested for potassium, lactate dehydrogenase (LDH), Hb, haematocrit, plasma Hb and haemolysis on days 1, 21 and 35 of storage. The association of these parameters with donor age, sex, donation status, dietary pattern and body mass index was determined. RESULTS: Mean haemolysis was significantly higher in PRBCs from donors with UA levels ≤6 mg/dL than donors with UA levels >6 mg/dL on day 35 of storage (0.22 ± 0.11 vs. 0.18 ± 0.07, p = 0.03). Median plasma Hb (mg/L) was significantly higher in PRBCs from first-time donors on day 21 (586 vs. 509, p = 0.05) and day 35 (1507 vs. 1358, p = 0.02) of storage in comparison to frequent donors. Significantly higher mean potassium (p = 0.04 day 1; p = 0.02 day 21) and median LDH values (p = 0.02 day 1, p = 0.05 day 21) were observed in PRBCs from male donors. A statistically significant positive association was observed between donor UA and LDH levels of PRBCs on day 35 of storage (ß coefficient: 715.52, p-value: 0.003) on multiple regression analysis. CONCLUSION: In vitro haemolysis of PRBCs is affected by blood donor characteristics.

Physiological and psychological stress response of blood donors during the blood donation process.

BACKGROUND AND OBJECTIVES: Blood donation can be a potentially stressful event, leading to the activation of an acute stress response. Knowing and identifying potential stressors could help in optimizing the donation experience. The present study aimed to measure the physiological and psychological stress changes before, during and after blood donation. MATERIALS AND METHODS: Physiological and psychological stress response was assessed in 70 blood donors. To evaluate physiological stress response, pulse rate, respiratory rate, blood pressure (BP), beat-to-beat BP and lead II electrocardiogram were recorded. Baroreflex sensitivity was calculated using the available software. Psychological stress response was assessed using the State-Trait Anxiety Inventory scale. RESULTS: A significant increase in systolic blood pressure, diastolic blood pressure and mean arterial pressure was observed in the pre-donation period (p < 0.001). Among the time-domain parameters, SDSD (standard deviation of differences between adjacent respiratory rate intervals) and RMSSD (root mean square of the successive differences) were significantly lower during the post-donation period (p < 0.005, p < 0.007, respectively). Among the frequency-domain parameters, LF nu (relative power of the low-frequency band in normalized units), HF nu (relative power of the high-frequency band in normalized units) and LF% (relative power of the low-frequency band in percentage) were significantly lower before donation compared to during donation (p < 0.001, p < 0.001 and p < 0.012, respectively). LF nu, LF% and LF/HF ratio were also significantly lower during donation compared to after donation (p < 0.05, p < 0.016 and p < 0.042, respectively). Baroreflex sensitivity was also statistically higher during the pre-donation period. State score was significantly higher among the blood donors during the pre-donation period. CONCLUSION: Physiological and psychological stress is experienced by blood donors during the pre-donation period. A pre-donation informative conversation should be carried out with each blood donor and potential stressors should be identified in each.

Stereoselective Reductive Coupling Reactions Utilizing [1,2]-Phospha-Brook Rearrangement: A Powerful Umpolung Approach.

[1,2]-Phospha-Brook rearrangement entails the generation of α-oxygenated carbanions via the umpolung process. Recently, these anionic species have been widely utilized for several C-C bond forming strategies, providing various useful frameworks that are difficult to access through conventional approaches. However, the application of this powerful methodology in the development of chiral strategies is still at the nascent stage due to challenges involved in controlling chemoselectivity and enantioselectivity. This synopsis provides a detailed summary of diastereo- and/or enantioselective chemical transformations using [1,2]-phospha-Brook rearrangement.

Synthesis of a trinuclear zinc(II) cluster composed of [4.4.3.01,5]tridecane cages: a rapid detection and degradation probe for the chemical warfare agent simulant diethyl cyanophosphonate in protein-rich food products.

Diethyl cyanophosphonate (DCNP), a simulant of Tabun, is a common pollutant in pharmaceutical waste and poses a high risk to living organisms. Herein, we demonstrate a compartmental ligand-derived trinuclear zinc(II) cluster [Zn3(LH)2(CH3COO)2] as a probe for the selective detection and degradation of DCNP. It consists of two pentacoordinated Zn(II) [4.4.3.01,5]tridecane cages bridged through a hexacoordinated Zn(II) acetate unit. The structure of the cluster has been elucidated by spectrometric, spectroscopic, and single-crystal X-ray diffraction studies. The cluster shows a two-fold increased emission as compared to the compartmental ligand (at λexc = 370 nm and λem = 463 nm) due to the chelation-enhanced fluorescence effect and acts as a turn-off signal in the presence of DCNP. It can detect DCNP at nano levels up to 186 nM (LOD). The direct bond formation between DCNP and Zn(II) via the -CN group degrades it to inorganic phosphates. The mechanism of the interaction and degradation is supported by spectrofluorimetric experiments, NMR titration (1H and 31P), time of flight mass spectrometry and density functional theory calculations. The applicability of the probe has been further tested by the bio-imaging of zebrafish larvae, analysis of high-protein food products (meat and fish) and vapour phase detection by paper strips.

Association of blood donor characteristics with in vitro platelet storage properties.

BACKGROUND AND OBJECTIVE: The study was planned to determine the association of blood donor characteristics with in vitro quality of platelets. MATERIAL AND METHODS: In the prospective observational study, a total of 85 male whole blood donors in the age group of 18-30 and 45-65 years were enrolled using purposive sampling method. Serum total cholesterol, glycosylated hemoglobin (HbA1c), and LDH levels were performed on donor pre-donation sample. Buffy coat platelet concentrates were prepared from 450 mL quadruple blood bags. Samples from platelets were taken on day one and five of storage and biochemical properties were observed. RESULTS: Median MPV was higher in platelets from older blood donors on day five (9.8 vs 9.4, p = 0.037). Median LDH levels were also higher in platelets on day one and five from older donors (Day one: 204.5 vs 147, p = <0.000; day five: 278 vs 224, p = 0.001 respectively). Platelets from donors with high HbA1c levels had lower median pH (Day one: 7.31 vs 7.37, p = 0.024) and higher median glucose levels on day one of storage (Day one: 358 vs 311, p = 0.001). Higher median lactate levels throughout the storage period were also seen in platelets from donors with higher HbA1c levels (Day one: 7 vs 5.7, p = 0.037; Day five: 16 vs 12.2, p = 0.032). Glucose consumption (108 vs 66, p = 0.025) and lactate production (9 vs 6.4, p = 0.019) was higher in platelets from donors with higher HbA1c levels. CONCLUSION: In vitro platelet storage properties are affected by blood donor characteristics.

Evaluation of chemiluminescence immunoassay as a screening test for syphilis on blood donor samples.

BACKGROUND AND OBJECTIVE: Global re-emergence of syphilis among blood donors necessitates novel diagnostic and prevention approaches that encourage timely intervention. Thus, the present study was planned to evaluate the efficiency of Chemiluminescence immunoassay (CLIA) as a screening test for syphilis. MATERIAL AND METHODS: This prospective cross-sectional observational study was conducted from October 2021 to September 2022. A total of 344 donors were enrolled by purposive sampling method, including additional 16 donors who were reactive by the Rapid plasma reagin test (RPR) during the study period. Data from three screening tests - RPR test, Treponema pallidum haemagglutination assay (TPHA) and CLIA for 360 blood donors were analysed. TPHA was considered the gold standard test. RESULTS: Of the total 360 samples tested, 21 (5.8 %) were reactive by the RPR test. Of these 21 RPR reactive samples, 19 (90.5 %) were reactive by both TPHA and CLIA, while 2 (9.5 %) RPR reactive samples were non-reactive by both TPHA and CLIA. Of the remaining 339 RPR non-reactive samples, 1 (0.3 %) sample was reactive by both TPHA and CLIA, and 1 (0.3 %) was reactive by CLIA alone. CLIA was found to have sensitivity and specificity of 100 % and 99.7 % and positive predictive value (PPV) and negative predictive values (NPV) of 95.2 % and 100 % respectively, while it was 95 %, 99.4 %, 90 %, and 99.7 %, respectively, with the RPR test. CONCLUSION: CLIA was found to have a higher sensitivity, specificity, PPV and NPV than the RPR test. Thus, CLIA can be an acceptable alternative for syphilis screening in blood donors.

Otolith microchemistry of freshwater indigenous minor carp (Bangana dero) as a biomonitoring tool to trace heavy metals in River Sutlej, Ropar Wetland (Ramsar site), Punjab, India.

The elemental composition of the fish otolith may represent a permanent record of the environmental condition the fish inhabited. Fish otolith grows incrementally from the core to a marginal region that acts as a repository of trace metal signatures. The present study explores the potential application of otolith microchemistry of the benthopelagic indigenous minor carp Bangana dero sampled from the Ropar wetland on River Sutlej, Punjab. The concentration of sixteen metals was evaluated in the otolith (n = 42) and water (n = 48) for the post-monsoon and pre-monsoon season from 2020 to 2022 using inductively coupled plasma mass spectrometry (ICP-MS) followed by element detection in the core and marginal region of whole otolith, using energy-dispersive mass spectroscopy (EDS). All the heavy metals exhibited an increase in metal concentrations in fish otolith than water during the post-monsoon season. By indices approach, the otolith was found to have a high bioaccumulation factor for Se in the post-monsoon and Hg in the pre-monsoon. Certain trace metals like As and Hg exhibited fluctuations in their core and marginal region. Thus, trace metal patterns in the otolith could act as a potential tool for monitoring the seasonal changes of metals in water bodies. The EFHg, EFSe and EFAs in the fish otolith predicted its anthropogenic source, while the remaining studied elements showed ambient water origin. Thus, using the otoliths of Bangana dero as a long-term monitoring tool in the future may be helpful for environmental assessments and the reconstruction of historical exposure for safeguarding of water bodies.

Efficacy of packed red blood cell transfusions based on weight versus formula in thalassemic children: An open-label randomized control trial.

BACKGROUND: Protocols for transfusion therapy in transfusion-dependent thalassemia (TDT) children differ among various medical centers. In India, most centers consider only the patient's weight while calculating the volume of packed red blood cells (PRBCs) to be transfused. This study aimed to compare the efficacy of PRBC transfusions of different volumes calculated either by weight or by a formula using weight and pretransfusion hemoglobin of patient and hematocrit of PRBC. STUDY DESIGN AND METHODS: Sixty TDT patients in the age group of 3-9 years were enrolled and randomly allocated to two groups. Group A received PRBC transfusion volume based on the patient's weight, and Group B received PRBC volume calculated using a formula for 6 months. RESULTS: Average pretransfusion hemoglobin in Group A and Group B (9 ± 0.4 vs. 8.9 ± 0.4 g/dl) was not significantly different (p = .353). Although the average number of visits in 6 months was less for Group A compared to Group B (7 ± 1 vs. 8 ± 1; p = .001); the average volume transfused per visit was more (351 ± 78 vs. 287 ± 68 ml; p = .003). The calculated average annual pure red cell requirement of the patients was 178 ml/kg/year for Group A and 154 ml/kg/year for Group B (p = .000). Total donor exposures were significantly lower in Group B than Group A (11 ± 3 vs. 14 ± 3; p = .006). CONCLUSION: The number of donor exposures and annual pure red cell requirement was significantly lower in the formula-based group. Transfusions based on formula are recommended in TDT patients.

Monosomy 1p36: Report of a cohort of 13 Asian Indian patients.

Monosomy 1p36 is one of the common microdeletion syndromes with a recognizable facial phenotype. Failure to thrive, developmental delay, congenital heart disease, and other abnormalities are common in these patients. This is the first study on Asian Indian patients with monosomy 1p36, documenting the phenotypic characteristics of 13 patients, indicating phenotypic similarities in a diverse population and broadening the clinical spectrum.

Utility of reticulocyte haemoglobin content and immature reticulocyte fraction in early diagnosis of latent iron deficiency in whole blood donors.

BACKGROUND AND OBJECTIVES: The present study was planned to assess the clinical utility of reticulocyte haemoglobin content (CHr) and immature reticulocyte fraction (IRF) in the early detection of latent iron deficiency in blood donors. MATERIALS AND METHODS: The prospective longitudinal observational study was conducted using the purposive sampling method. Written informed consent was obtained and donors were allocated into the first-time (FTD) and regular donor (RD) group. The enrolled blood donors (n = 205 in each group) were followed up for two subsequent whole blood donations. Haemoglobin (Hb), CHr, IRF and serum ferritin values were recorded at enrolment and two follow-ups. RESULTS: The sensitivity of CHr in detecting iron-deficient erythropoiesis (serum ferritin values ≤ 26 µg/dl) was 45% and 56.7%, specificity 96.7%, positive predictive value (PPV) 85.6% and 90.8% and negative predictive value (NPV) 80.1% and 78.7%, respectively in FTD and RD cohorts. The sensitivity of IRF was 45.1% and 44.8%, specificity 93.4% and 97.1%, PPV 74.8% and 90.4% and NPV 79.6% and 74.5%, respectively in both the cohorts. The sensitivity of CHr in detecting absent iron stores (serum ferritin values ≤ 15 µg/dl) was 66.2% and 74.4%, specificity 92% and 90.6%, PPV 56.7% and 68.7% and NPV 94.5% and 92.8% among FTD and RD cohort, respectively. The sensitivity of IRF was 72.7% and 65.3%, specificity 90.3% and 94.3%, PPV 54.4% and 76% and NPV 95.4% and 90.8%, respectively in both the cohorts. CONCLUSION: Reticulocyte hemoglobin content and IRF can be used along with complete blood count for early detection of iron deficiency in blood donors using the same blood sample at no extra cost.

A Novel Homozygous HAX1 Mutation in a Child With Cyclic Neutropenia: A Case Report and Review.

BACKGROUND: Cyclic neutropenia is a rare genetic disorder causing the arrest of neutrophil function and is characterized by periodic neutropenia and recurrent infections. Patients with cyclic neutropenia with autosomal dominant, sporadic, and X-linked may have mutations in the ELANE gene, and autosomal recessive cases have homozygous/compound heterozygous variants in the HAX1 gene primarily. OBSERVATION: The authors describe a novel variant in the HAX1 gene, which was detected by next-generation sequencing in an 8-year-old male child who presented with recurrent infections and neutropenia. CONCLUSION: The patient extends the clinical variability associated with HAX1 variants and highlights the importance of genetic investigations in patients with suspected cyclic neutropenia.

A prospective interventional study to assess the impact of a 'structured compact training' on knowledge and skills of safe blood transfusion practices among nurses working in a tertiary care institute.

INTRODUCTION: There is scarce information on the baseline knowledge and practices of nursing officers in relation to administration of blood components. We set out to evaluate the influence of training on their knowledge and skills through Kirkpatrick's levels of Training Evaluation. MATERIALS AND METHODS: This interventional cross sectional study of 7 months duration conducted in a tertiary care teaching institute involved 200 nursing officers. Hundred were assigned to study/intervention group and 100 were assigned to control/ comparison group by systematic random sampling. Knowledge was tested in different domains-blood components, pre-transfusion checks, transfusion process, post-transfusion process and blood administration practice. RESULTS: The baseline knowledge scores of intervention and control group were similar-15.16 ± 4.11 and 15.02 ± 4.75 (p = 0.831). Post-intervention (phase I) after 1 month, the scores improved significantly for domain A, B, C, D and E to 4.3 ± 2.21 (p = 0.0001), 3.46 ± 2.15 (p = 0.0001), 7.02 ± 3.55 (p = 0.0001), 2.51 ± 1.46 (p = 0.0012), and 5.86 ± 3.61 (p = 0.0018) respectively. In phase II, after 3 months of training, and the scores were significantly better from baseline for all domains except E. For domain A, B, C, D and E, scores were 3.82 ± 2.46 (p = 0.0001), 3.53 ± 1.98 (p = 0.0001), 7.38 ± 3.87 (p = 0.0001), 2.48 ± 1.55 (p = 0.0035), and 5.86 ± 3.61 (p = 0.95) respectively. CONCLUSIONS: Our study showed that baseline scores were low in the nursing officers. No significant difference was found in baseline scores in subject and control population. However, post-intervention, a significant improvement in scores was observed in the study group across all domains.

Pilot study of a culturally sensitive intervention to promote genetic counseling for breast cancer risk.

BACKGROUND: Despite the benefits of genetic counseling and testing, uptake of cancer genetic services is generally low and Black/African American (Black) women are substantially less likely to receive genetic services than non-Hispanic White women. Our team developed a culturally sensitive, narrative decision aid video to promote uptake of genetic counseling among Black women at risk for a hereditary breast cancer syndrome that can be incorporated in conjunction with population-based cancer risk assessment in a clinical setting. We report here a pilot study to demonstrate changes in intention to access genetic counseling and intervention satisfaction. METHODS: Black women who were personally unaffected by breast cancer and were recommended for genetic counseling based on family history screening in a mammography center were recruited at the time of the mammogram. A prospective, pre-post survey study design, guided by theoretical constructs, was used to evaluate baseline and immediate post-intervention psychosocial factors, including intention to participate in genetic counseling and intervention satisfaction. RESULTS: Pilot recruitment goals were met (n = 30). Pre-intervention, 50% of participants indicated that they were extremely likely to make a genetic counseling appointment, compared with 70% post-intervention (p = 0.05). After watching the intervention, 50% of participants indicated that the video changed their mind regarding genetic counseling. CONCLUSIONS: This study demonstrated cultural satisfaction with a decision aid intervention designed to motivate Black women with hereditary breast cancer risk to attend a genetic counseling appointment. Our study showed that intention may be a specific and key construct to target in interventions designed to support decision-making about genetic services. Study results informed the design of a subsequent large scale, randomized implementation study. TRIAL REGISTRATION: Trial registration: Clinicaltrials.gov NCT04082117 . Registered September 9, 2019. Retrospectively registered.

Dose and time response study to develop retinal degenerative model of zebrafish with lead acetate.

Objective: Animal models are the silent scouts that help to understand the complex biological processes and gather data that aid our understanding of how organisms function. Various animal models are being sacrificed to assess the impact of toxic chemicals. Mortality calculations should be minimised and much data should be collected on the basis of clinical signs that can contribute to identifying robust humane endpoints linked to mortality. This study was designed to calculate the lowest possible dose of PbAc (lead acetate), a neurotoxicant, that can have a toxicological impact on the zebrafish retina and to minimise animal usage. Dose and time-dependent changes were observed in the zebrafish retina following PbAc exposure with zero mortality. Vision and visual behaviour response are the foremost indicators that can be recorded to mark the risk assessment of any chemical. Therefore, the present study aims at dose and time response to find the lowest dose of PbAc affecting the zebrafish retina and its visual behaviour.Materials and methods: Zebrafish were treated for 3 weeks with four concentrations of 0.04, 0.06, 0.08, and 0.1 mg/L of PbAc for a dose-response study. Then for the time response study, two doses 0.08 and 0.1 mg/L were selected and zebrafish were exposed to those concentrations for 2 and 4 weeks.Results: The results of qualitative and quantitative analyses of retinal histology showed that 15 days of treatment with 0.08 mg/L concentration can cause appropriate damage to the photoreceptor layer. At the ultrastructural level, it was further observed that PbAc induces damage to the photoreceptors, especially the rod cells. Escape response sbehaviour showed a significant decrease in visual response to changing contrasts in an increasing dose-dependent manner.Conclusion: In conclusion, it has been shown that 15 days treatment with 0.08 mg/L lead acetate induce retinal degeneration in zebrafish without causing any mortality.

Development of a culturally sensitive narrative intervention to promote genetic counseling among African American women at risk for hereditary breast cancer.

BACKGROUND: African American women with hereditary breast cancer risk are less likely to undergo genetic counseling and testing compared with non-Hispanic White women. Inequities in the use of precision cancer care are likely to exacerbate racial disparities in cancer outcomes. A culturally sensitive multimedia narrative intervention was developed to motivate African American women at risk for hereditary breast cancer to engage in genetic counseling. METHODS: Development of the intervention was grounded in the Integrative Model of Behavioral Prediction using a phenomenological, deductive approach and employed multiple qualitative methods for data collection, including 1-on-1 interviews and story circles with members of the target audience to identify salient themes and lived experiences. Focus group testing was then conducted with members of the group of focus, primary care providers, and community stakeholders. RESULTS: Six themes that mapped to the theoretical model were identified. Lived experiences were abstracted from story circle data to create a narrative storyline. Educational content and motivational messaging derived from the 6 themes were embedded into the script. Focus group testing with stakeholder groups was used to refine the intervention. Testing of the final multimedia narrative with focus groups indicated that the intervention was culturally sensitive and authentic, and the messaging was effective. CONCLUSIONS: Multiple qualitative data collection methods and a robust theoretical framework of health behavior were key elements for this study to develop a culturally sensitive, narrative intervention that reflects lived experiences and motivates underserved African American women with hereditary breast cancer risk to engage in genetic counseling. This strategy can be applied to mitigate racial inequities in the use of other genomic approaches for personalizing cancer care.

Dissecting the nutrient partitioning mechanism in rice grain using spatially resolved gene expression profiling.

Rice, a staple food worldwide, contains varying amounts of nutrients in different grain tissues. The underlying molecular mechanism of such distinct nutrient partitioning remains poorly investigated. Here, an optimized rapid laser capture microdissection (LCM) approach was used to individually collect pericarp, aleurone, embryo and endosperm from grains 10 days after fertilization. Subsequent RNA-Seq analysis in these tissues identified 7760 differentially expressed genes. Analysis of promoter sequences of tissue-specific genes identified many known and novel cis-elements important for grain filling and seed development. Using the identified differentially expressed genes, comprehensive spatial gene expression pathways were built for accumulation of starch, proteins, lipids, and iron. The extensive transcriptomic analysis provided novel insights about nutrient partitioning mechanisms; for example, it revealed a gradient in seed storage protein accumulation across the four tissue types analysed. The analysis also revealed that the partitioning of various minerals, such as iron, is most likely regulated through transcriptional control of their transporters. We present the extensive analysis from this study as an interactive online tool that provides a much-needed resource for future functional genomics studies aimed to improve grain quality and seed development.

Stereoselective Synthesis of Dihydrocoumarins via [1,2]-Phospha-Brook Rearrangement in Three-Component Coupling Reaction of α-Ketoesters, o-Quinone Methides, and Dialkyl Phosphites.

A highly regio- and diastereoselective approach for the synthesis of phosphate substituted dihydrocoumarins via Brønsted base catalyzed [1,2]-phospha-Brook rearrangement is reported. The two-step, one-pot Michael addition of α-phosphonyloxy enolates proceeds by coupling of dialkyl phosphite and α-ketoesters to o-quinone methides, followed by an intramolecular cyclization, providing 3,4-dihydrocoumarin frameworks.