Aspirin Metabolites and Mammographic Breast Density in Premenopausal Women.

BACKGROUND: Studies investigating the associations of self-reported aspirin use and mammographic breast density (MBD) have reported conflicting results. We, therefore, investigated the associations of aspirin metabolites, with MBD in premenopausal women. METHODS: We performed this study on 705 premenopausal women who had fasting blood draw for metabolomic profiling. We performed covariate-adjusted linear regression models to calculate the least squares means of volumetric measures of MBD (volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)) by quartiles of aspirin metabolites (salicyluric glucuronide, 2-hydroxyhippurate (salicylurate), salicylate, and 2,6-dihydroxybenzoic acid). RESULTS: Approximately 13% of participants reported taking aspirin in the past 12 months. Aspirin users had higher levels of 2-hydroxyhippurate (salicylurate), salicylate, and salicyluric glucuronide (peak area) than non-users, but only mean peak area of salicyluric glucuronide increased by both dose (1-2 tabs per day=1,140,663.7, and ≥3 tabs per day=1,380,476.0) and frequency (days per week: 1 day=888,129.3, 2-3 days=1,199,897.9 and ≥4 days=1,654,637.0). Aspirin metabolites were not monotonically associated with VPD, DV, or NDV. CONCLUSIONS: Given the null results, additional research investigating the associations of aspirin metabolites in breast tissue and MBD is necessary. IMPACT: Elucidating the determinants of MBD, a strong risk factor for breast cancer, can play an important role in breast cancer prevention. Future studies should determine the associations of non-aspirin non-steroidal anti-inflammatory drug metabolites with MBD.

Bayesian estimation methods for survey data with potential applications to health disparities research.

Understanding how and why certain communities bear a disproportionate burden of disease is challenging due to the scarcity of data on these communities. Surveys provide a useful avenue for accessing hard-to-reach populations, as many surveys specifically oversample understudied and vulnerable populations. When survey data is used for analysis, it is important to account for the complex survey design that gave rise to the data, in order to avoid biased conclusions. The field of Bayesian survey statistics aims to account for such survey design while leveraging the advantages of Bayesian models, which can flexibly handle sparsity through borrowing of information and provide a coherent inferential framework to easily obtain variances for complex models and data types. For these reasons, Bayesian survey methods seem uniquely well-poised for health disparities research, where heterogeneity and sparsity are frequent considerations. This review discusses three main approaches found in the Bayesian survey methodology literature: 1) multilevel regression and post-stratification, 2) weighted pseudolikelihood-based methods, and 3) synthetic population generation. We discuss advantages and disadvantages of each approach, examine recent applications and extensions, and consider how these approaches may be leveraged to improve research in population health equity.

Differences in Serum miRNA Profiles by Race, Ethnicity, and Socioeconomic Status: Implications for Developing an Equitable Ovarian Cancer Screening Test.

Serum miRNAs are promising biomarkers for several clinical conditions, including ovarian cancer. To inform equitable implementation of these tests, we investigated the effects of race, ethnicity, and socioeconomic status on serum miRNA profiles. Serum samples from a large institutional biobank were analyzed using a custom panel of 179 miRNA species highly expressed in human serum, measured using the Abcam Fireplex assay via flow cytometry. Data were log-transformed prior to analysis. Differences in miRNA by race and ethnicity were assessed using logistic regression. Pairwise t tests analyzed racial and ethnic differences among eight miRNAs previously associated with ovarian cancer risk. Pearson correlations determined the relationship between mean miRNA expression and the social deprivation index (SDI) for Massachusetts residents. Of 1,586 patients (76.9% white, non-Hispanic), compared with white, non-Hispanic patients, those from other racial and ethnic groups were younger (41.9 years ± 13.2 vs. 51.3 ± 15.1, P < 0.01) and had fewer comorbidities (3.5 comorbidities ± 2.7 vs. 4.6 ± 2.8, P < 0.01). On logistic regression, miRNAs predicted race and ethnicity at an AUC of 0.69 (95% confidence interval, 0.66-0.72), which remained consistent when stratified by most comorbidities. Among eight miRNAs previously associated with ovarian cancer risk, seven significantly varied by race and ethnicity (all P < 0.01). There were no significant differences in SDI for any of these eight miRNAs. miRNA expression is significantly influenced by race and ethnicity, which remained consistent after controlling for confounders. Understanding baseline differences in biomarker test characteristics prior to clinical implementation is essential to ensure instruments perform comparably across diverse populations. PREVENTION RELEVANCE: This study aimed to understand factors affecting miRNA expression, to ensure we create equitable screening tests for ovarian cancer that perform well in diverse populations. The goal is to ensure that we are detecting ovarian cancer cases earlier (secondary prevention) in women of all races, ethnic backgrounds, and socioeconomic means.

Transcriptome and biochemical analysis in hexaploid wheat with contrasting tolerance to iron deficiency pinpoints multi-layered molecular process.

Iron (Fe) is an essential plant nutrient that is indispensable for many physiological activities. This study is an effort to identify the molecular and biochemical basis of wheat genotypes with contrasting tolerance towards Fe deficiency. Our physiological experiments performed at the early growth stage in cv. Kanchan (KAN) showed Fe deficiency tolerance, whereas cv. PBW343 (PBW) was susceptible. Under Fe deficient condition, KAN showed delayed chlorosis, high SPAD values, and low malondialdehyde content compared to PBW, indicative of Fe deficient condition. Comparative shoot transcriptomics revealed increased expression of photosynthetic pathway genes in PBW, further suggesting its sensitivity to Fe fluctuations. Under Fe deficiency, both the cultivars showed distinct molecular re-arrangements such as high expression of genes involved in Fe uptake (including membrane transporters) and its remobilization. Specifically, in KAN these changes lead to high root phytosiderophores (PS) biosynthesis and its release, resulting in enhanced Fe translocation index. Utilizing the non-transgenic TILLING (Targeting Induced Lesions in Genomes) technology, we identified TaZIFL4.2D as a putative PS efflux transporter. Characterization of the wheat TILLING lines indicated that TaZIFL4.2 functions in PS release and Fe acquisition, thereby imparting tolerance to Fe deficiency. Altogether, this work highlights the mechanistic insight into Fe deficiency tolerance of hexaploid wheat, thus enabling breeders to select suitable genotypes to utilize nutrients for maximum yields.

Oligosaccharide production and signaling correlate with delayed flowering in an Arabidopsis genotype grown and selected in high [CO2].

Since industrialization began, atmospheric CO2 ([CO2]) has increased from 270 to 415 ppm and is projected to reach 800-1000 ppm this century. Some Arabidopsis thaliana (Arabidopsis) genotypes delayed flowering in elevated [CO2] relative to current [CO2], while others showed no change or accelerations. To predict genotype-specific flowering behaviors, we must understand the mechanisms driving flowering response to rising [CO2]. [CO2] changes alter photosynthesis and carbohydrates in plants. Plants sense carbohydrate levels, and exogenous carbohydrate application influences flowering time and flowering transcript levels. We asked how organismal changes in carbohydrates and transcription correlate with changes in flowering time under elevated [CO2]. We used a genotype (SG) of Arabidopsis that was selected for high fitness at elevated [CO2] (700 ppm). SG delays flowering under elevated [CO2] (700 ppm) relative to current [CO2] (400 ppm). We compared SG to a closely related control genotype (CG) that shows no [CO2]-induced flowering change. We compared metabolomic and transcriptomic profiles in these genotypes at current and elevated [CO2] to assess correlations with flowering in these conditions. While both genotypes altered carbohydrates in response to elevated [CO2], SG had higher levels of sucrose than CG and showed a stronger increase in glucose and fructose in elevated [CO2]. Both genotypes demonstrated transcriptional changes, with CG increasing genes related to fructose 1,6-bisphosphate breakdown, amino acid synthesis, and secondary metabolites; and SG decreasing genes related to starch and sugar metabolism, but increasing genes involved in oligosaccharide production and sugar modifications. Genes associated with flowering regulation within the photoperiod, vernalization, and meristem identity pathways were altered in these genotypes. Elevated [CO2] may alter carbohydrates to influence transcription in both genotypes and delayed flowering in SG. Changes in the oligosaccharide pool may contribute to delayed flowering in SG. This work extends the literature exploring genotypic-specific flowering responses to elevated [CO2].

Heart Failure Burden in Oman as a Mid-East Exemplar Versus Global Perspectives: An Integrative Review.

Heart failure (HF), a clinical syndrome caused by a structural and functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and pulmonary congestion. This study intends to investigate the state of heart failure (HF) in Oman and assess it in comparison of global trends. Ten published literatures from the past 20 years were included after a thorough search of databases (Arab World Research Source, EBSCOhost, Medline, and Google Scholar). These studies were reviewed considering the global literature. We have observed an increase in HF cases especially in older adults, over the past two decades in Oman. Acute coronary syndrome and non-compliance with medication are two factors that contribute to acute HF, according to recent research. Ischemic heart disease is the leading cause of HF in the Omani population. The mortality rate for HF patients in Oman was reported to be 25% after a one-year follow-up. The younger population that is diagnosed with HF in Oman is significantly worse than in other nations, according to these data, which are consistent with global trends. The lack of published studies and data sets hampered our understanding of heart failure (HF); yet prevalence of HF is rising and is anticipated to surge with the rise in diabetes mellitus and hypertension and other related cardiovascular precursors. Therefore, HF requires more investigation. In terms of worldwide trends, HF in Oman appears to be even worse; additional information is required to grasp the full picture on HF.

Regulation of steroid production and key genes in catfish Heteropneustes fossilis using recombinant gonadotropins.

The two gonadotropins, FSH and LH, stimulate growth and development of the gonads through gonadal biosynthesis of steroid hormones and growth factors. To date, cDNA sequences encoding gonadotropin subunits have been isolated and characterized from a large number of fish species. Recently, we successfully cloned and characterized gonadotropins (LHß, FSHß, and GPα) from the pituitary glands of the catfish, Heteropneustes fossilis. In the present study, we describe herein the production of recombinant stinging catfish, H. fossilis (hf) FSH (rhfFSH) and LH (rhfLH) using the methylotrophic yeast P. pastoris expression system. We further explored the hypothesis that the recombinant gonadotropins can modulate the hypothalamus-pituitary-ovarian (HPO) axis genes (avt, it, gnrh2, kiss2, and cyp19a1a) and regulate their transcriptional profile and steroid levels in relation to their annual developmental stage during preparatory and pre-spawning phases under in-vitro conditions. We found that the different concentrations of recombinant rhfFSH and rhfLH significantly stimulated E2 levels in the preparatory and prespawning season, and also upregulated gonadal aromatase gene expression in a dose dependent manner. Our results demonstrate that the yeast expression system produced biologically active recombinant catfish gonadotropins, enabling the study of their function in the catfish.

FLOWERING LOCUS C drives delayed flowering in Arabidopsis grown and selected at elevated CO 2.

Altered flowering time at elevated [CO 2 ] is well documented, although mechanisms are not well understood. An Arabidopsis genotype previously selected for high fitness at elevated [CO 2 ] (SG) showed delayed flowering and larger size at flowering when grown at elevated (700 ppm) versus current (380 ppm) [CO 2 ]. This response was correlated with prolonged expression of FLOWERING LOCUS C ( FLC ), a vernalization-responsive floral repressor gene. To determine if FLC directly delays flowering at elevated [CO 2 ] in SG, we used vernalization (extended cold) to downregulate FLC expression. We hypothesized that vernalization would eliminate delayed flowering at elevated [CO 2 ] through the direct reduction of FLC expression, eliminating differences in flowering time between current and elevated [CO 2 ]. We found that with downregulation of FLC expression via vernalization, SG plants grown at elevated [CO 2 ] no longer delayed flowering compared to current [CO 2 ]. Thus, vernalization returned the earlier flowering phenotype, counteracting effects of elevated [CO 2 ] on flowering. This study indicates that elevated [CO 2 ] can delay flowering directly through FLC , and downregulation of FLC under elevated [CO 2 ] reverses this effect. Moreover, this study demonstrates that increasing [CO 2 ] may potentially drive major changes in development through FLC .

Does high family support protect against substance use in adolescents who perceive high disordered neighborhood stress, border community and immigration stress or normalization of drug trafficking at the US-Mexico border? Analysis of the BASUS survey.

Background: Adolescent substance use is a significant issue which occurs during a critical period of life of youth. Perceived stress is a risk factor for adolescent substance use, and life events such as low family support, and community and familial turmoil often lead to ongoing feelings of stress and uncertainty. Similarly, structural factors such as poverty, local neighborhood disinvestment and disrepair, and exposure to racism and discrimination are linked to feelings of stress. The US-Mexico border region is favorable for drug smuggling. Such a context exacerbates stressful life events during adolescence and increases the risk of adolescent substance use. This study aims to investigate the impact family support has on substance use in adolescents living on either side of the U.S./Mexico border who self-reported high perceptions of disordered neighborhood stress, border community and immigration stress, or normalization of drug trafficking. Methods: This study used data from the cross-sectional BASUS survey. Logistic regression was used to study the association between family support and past 30-day use of alcohol, tobacco, marijuana, and any substance in a sample restricted to students who self-reported high perceptions of disordered neighborhood stress, border community and immigration stress, or normalization of drug trafficking. Results: Participants with low family support were at higher risk of using any substance compared to participants with high family support (aOR= 1.58, 95% CI: 1.02; 2.45). Similar results were found for alcohol (aOR= 1.79, 95% CI: 1.13, 2.83). While the odds of using tobacco were higher for those with low social support as compared to participants with higher social support, this association was not statistically significant (aOR = 1.74, 95% CI: 0.93, 3.27). Conclusion: Prevention programs tailored to the U.S.-Mexico border region should emphasize strengthening family support as a preventive factor against adolescent substance use. Family support should be considered in school counseling assessments, healthcare screenings and other social services.

Comparative analysis of VMT genes/proteins in selected plant species with emphasis on bread wheat (Triticum aestivum L.).

BACKGROUND: In recent years, the study of molecular basis of uptake, transport and utilization of grain Fe/Zn (GFe/GZn) in wheat has been an active area of research. As a result, it has been shown that a number of transporters are involved in uptake and transport of Fe. In a recent study, knockout of a transporter gene OsVMT (VACUOLAR MUGINEIC ACID TRANSPORTER) in rice was shown to be involved in Fe homoeostasis. OBJECTIVE: In this study, we analysed VMT genes among six monocots and three dicots with major emphasis on wheat VMT genes (TaVMTs), taking OsVMT gene as a reference. METHODS AND RESULTS: Using OsVMT gene as a reference, VMT genes were identified and sequence similarities were examined among six monocots and three dicots. Each VMT protein carried one functional domain and 7 to 10 distinct motifs (including 9 novel motifs). The qRT-PCR analysis showed differential expression by all the six TaVMT genes in pairs of contrasting wheat genotypes with high (FAR4 and WB02) and low (K8027 and HD3226) GFe/GZn at two different grain filling stages (14 DAA and 28 DAA). TaVMT1 genes showed up-regulation in high GFe/Zn genotypes relative to low GFe/Zn genotypes, whereas the TaVMT2 genes showed down-regulation or nonsignificant up-regulation in a few cases. CONCLUSIONS: At 14 DAA, each of the six TaVMT genes exhibited higher expression in wheat genotypes with high GFe and GZn relative to those with low GFe and GZn, suggesting major role of VMT genes in improvement of grain Fe/Zn homoeostasis, thus making TaVMT genes useful for improvement in Fe/Zn in wheat grains.

Exploring the Bottom-Up Growth of Anisotropic Gold Nanoparticles from Substrate-Bound Seeds in Microfluidic Reactors.

We developed an unconventional seed-mediated in situ synthetic method, whereby gold nanostars are formed directly on the internal walls of microfluidic reactors. The dense plasmonic substrate coatings were grown in microfluidic channels with different geometries to elucidate the impacts of flow rate and profile on reagent consumption, product morphology, and density. Nanostar growth was found to occur in the flow-limited regime and our results highlight the possibility of creating shape gradients or incorporating multiple morphologies in the same microreactor, which is challenging to achieve with traditional self-assembly. The plasmonic-microfluidic platforms developed herein have implications for a broad range of applications, including cell culture/sorting, catalysis, sensing, and drug/gene delivery.

Responsiveness to long days for flowering is reduced in Arabidopsis by yearly variation in growing season temperatures.

Conservative flowering behaviours, such as flowering during long days in summer or late flowering at a high leaf number, are often proposed to protect against variable winter and spring temperatures which lead to frost damage if premature flowering occurs. Yet, due the many factors in natural environments relative to the number of individuals compared, assessing which climate characteristics drive these flowering traits has been difficult. We applied a multidisciplinary approach to 10 winter-annual Arabidopsis thaliana populations from a wide climactic gradient in Norway. We used a variable reduction strategy to assess which of 100 climate descriptors from their home sites correlated most to their flowering behaviours when tested for responsiveness to photoperiod after saturation of vernalization; then, assessed sequence variation of 19 known environmental-response flowering genes. Photoperiod responsiveness inversely correlated with interannual variation in timing of growing season onset. Time to flowering appeared driven by growing season length, curtailed by cold fall temperatures. The distribution of FLM, TFL2 and HOS1 haplotypes, genes involved in ambient temperature response, correlated with growing-season climate. We show that long-day responsiveness and late flowering may be driven not by risk of spring frosts, but by growing season temperature and length, perhaps to opportunistically maximize growth.

The measurement of racism in health inequities research.

There is limited literature on the measures and metrics used to examine racism in the health inequities literature. Health inequities research is continuously evolving, with the number of publications increasing over time. However, there is limited knowledge on the best measures and methods to examine the impact of different levels of racism (institutionalized, personally mediated, and internalized) on health inequities. Advanced statistical methods have the potential to be used in new ways to examine the relationship between racism and health inequities. In this review, we conduct a descriptive examination of the measurement of racism in the health inequities epidemiologic literature. We examine the study design, methods used for analysis, types of measures used (e.g., composite, absolute, relative), number of measures used, phase of research (detect, understand, solutions), viewpoint (oppressor, oppressed), and components of structural racism measures (historical context, geographical context, multifaceted nature). We discuss methods (e.g., Peters-Belson, latent class analysis, difference in differences) that have demonstrated potential for future work. The articles reviewed were limited to the detect (25%) and understand (75%) phases, with no studies in the solutions phase. Although the majority (56%) of studies had cross-sectional designs, many authors pointed to the need for longitudinal and multilevel data for further exploration. We examined study design features as mutually exclusive elements. However, racism is a multifaceted system and the measurement of racism in many studies does not fit into a single category. As the literature grows, the significance of methodological and measurement triangulation to assess racism should be investigated.

Excitatory and inhibitory imbalances in the trisynaptic pathway in the hippocampus in schizophrenia: a postmortem ultrastructural study.

BACKGROUND: A preponderance of evidence suggests that the hippocampus is a key region of dysfunction in schizophrenia. Neuroimaging and other studies indicate a relationship between hippocampal dysfunction and the degree of psychosis. Clinical data indicate hyperactivity in the hippocampus that precedes the onset of psychosis, and is correlated with symptom severity. In this study, we sought to identify circuitry at the electron microscopic level that could contribute to region-specific imbalances in excitation and inhibition in the hippocampus in schizophrenia. We used postmortem tissue from the anterior hippocampus from patients with schizophrenia and matched controls. Using stereological techniques, we counted and measured synapses, postsynaptic densities (PSDs), and evaluated size, number and optical density of mitochondria and parvalbumin-containing interneurons in key nodes of the trisynaptic pathway. Compared to controls, the schizophrenia group had decreased numbers of inhibitory synapses in CA3 and increased numbers of excitatory synapses in CA1; together, this indicates deficits in inhibition and an increase in excitation. The thickness of the PSD was larger in excitatory synapses in CA1, suggesting greater synaptic strength. In the schizophrenia group, there were fewer mitochondria in the dentate gyrus and a decrease in the optical density, a measure of functional integrity, in CA1. The number and optical density of parvalbumin interneurons were lower in CA3. The results suggest region-specific increases in excitatory circuitry, decreases in inhibitory neurotransmission and fewer or damaged mitochondria. These results are consistent with the hyperactivity observed in the hippocampus in schizophrenia in previous studies.

Genome size estimation and its associations with body length, chromosome number and evolution in teleost fishes.

Precise estimation of genome size (GS) is vital for various genomic studies, such as deciding genome sequencing depth, genome assembly, biodiversity documentation, evolution, genetic disorders studies, duplication events etc. Animal Genome Size Database provides GS of over 2050 fish species, which ranges from 0.35 pg in pufferfish (Tetraodon nigroviridis) to 132.83 pg in marbled lungfish (Protopterus aethiopicus). The GS of majority of the fishes inhabiting waters of Indian subcontinent are still missing. In present study, we estimated GS of 51 freshwater teleost (31 commercially important, 7 vulnerable and 13 ornamental species) that ranged from 0.58 pg in banded gourami (Trichogaster fasciata) to 1.92 pg in scribbled goby (Awaous grammepomus). Substantial variation in GS was observed within the same fish orders (0.64-1.45 pg in cypriniformes, 0.70-1.41 pg in siluriformes and 0.58-1.92 pg in perciformes). We examined the relationship between the GS, chromosome number and body length across all the fishes. Body length was found to be associated with GS, whereas no relationship was noticed between the GS and the chromosome number. The analysis using ancestral information revealed haploid chromosome number 25, 27 and 24 for the most recent common ancestor of cypriniformes, siluriformes and perciformes, respectively. The study led to generation of new records on GS of 43 fish species and revalidated records for 8 species. The finding is valuable resource for further research in the areas of fish genomics, molecular ecology and evolutionary conservation genetics.

Racial and ethnic heterogeneity in diets of low-income adult females in the United States: results from National Health and Nutrition Examination Surveys from 2011 to 2018.

BACKGROUND: Poor diet is a major risk factor of cardiovascular and chronic diseases, particularly for low-income female adults. However, the pathways by which race and ethnicity plays a role in this risk factor have not been fully explored. OBJECTIVES: This observational study aimed to identify dietary consumption differences by race and ethnicity of US female adults living at or below the 130% poverty income level from 2011 to 2018. METHODS: A total of 2917 adult females aged 20 to 80 years from the National Health and Nutrition Examination Survey (2011-2018) living at or below the 130% poverty income level with at least one complete 24-hour dietary recall were classified into 5 self-identified racial and ethnic subgroups (Mexican, other Hispanic, non-Hispanic [NH]-White, NH-Black, and NH-Asian). Dietary consumption patterns were defined by 28 major food groups summarized from the Food Pattern Equivalents Database and derived via a robust profile clustering model, which identifies foods that share consumption patterns across all low-income female adults and foods that differ in consumption patterns based on the racial and ethnic subgroups. RESULTS: All food consumption patterns were identified at the local level, defined by racial and ethnic subgroups. Legumes and cured meats were the most differentiating foods identified across all racial and ethnic subgroups. Higher consumption levels of legumes were observed among Mexican-American and other Hispanic females. Higher consumption levels of cured meat were observed among NH-White and Black females. NH-Asian females had the most uniquely characterized patterns with a higher consumption of prudent foods (fruits, vegetables, and whole grains). CONCLUSIONS: Differences among the consumption behaviors of low-income female adults were found along racial and ethnic lines. Efforts to improve the nutritional health of low-income female adults should consider racial and ethnic differences in diets to appropriately focus interventions.

Evidence for upregulation of excitatory synaptic transmission in the substantia nigra in Schizophrenia: a postmortem ultrastructural study.

The dopamine hypothesis of schizophrenia suggests that psychotic symptoms originate from dysregulation of dopaminergic activity, which may be controlled by upstream innervation. We hypothesized that we would find anatomical evidence for the hyperexcitability seen in the SN. We examined and quantified synaptic morphology, which correlates with function, in the postmortem substantia nigra (SN) from 15 schizophrenia and 12 normal subjects. Synapses were counted using stereological techniques and classified based on the morphology of the post-synaptic density (PSD) and the presence or absence of a presynaptic density. The density and proportion of excitatory synapses was higher in the schizophrenia group than in controls, while the proportion (but not density) of inhibitory synapses was lower. We also detected in the schizophrenia group an increase in density of synapses with a PSD of intermediate thickness, which may represent excitatory synapses. The density of synapses with presynaptic densities was similar in both groups. The density of synapses with mixed morphologies was higher in the schizophrenia group than in controls. The human SN contains atypical synaptic morphology. We found an excess amount and proportion of excitatory synapses in the SN in schizophrenia that could result in hyperactivity and drive the psychotic symptoms of schizophrenia. The sources of afferent excitatory inputs to the SN arise from the subthalamic nucleus, the pedunculopontine nucleus, and the ventral tegmental area (VTA), areas that could be the source of excess excitation. Synapses with mixed morphologies may represent inputs from the VTA, which release multiple transmitters.

Genome sequencing and assembly of Lathyrus sativus - a nutrient-rich hardy legume crop.

Grass pea (Lathyrus sativus) is a cool-season legume crop tolerant to drought, salinity, waterlogging, insects, and other biotic stresses. Despite these beneficial traits, this crop is not cultivated widely due to the accumulation of a neurotoxin - ß-N-oxalyl-L-α, ß-diaminopropionic acid (ß-ODAP) in the seeds and its association with neurolathyrism. In this study, we sequenced and assembled the genome of Lathyrus sativus cultivar Pusa-24, an elite Indian cultivar extensively used in breeding programs. The assembled genome of Lathyrus was 3.80 Gb in length, with a scaffold N50 of 421.39 Mb. BUSCO assessment indicated that 98.3% of highly conserved Viridiplantae genes were present in the assembly. A total of 3.17 Gb (83.31%) of repetitive sequences and 50,106 protein-coding genes were identified in the Lathyrus assembly. The Lathyrus genome assembly reported here thus provides a much-needed and robust foundation for various genetic and genomic studies in this vital legume crop.

Evergreening of Psychiatric Medications: A Systemic Literature Review of Strategies, Case Examples, and the Implications of Cost.

Evergreening consists of multiple ways that pharmaceutical companies extend patent protection and prolong profitability of brand name drugs past patent expiration. In psychotropic medications, these strategies do not necessarily make more effective drugs, and often increase drug prices, which can result in lower access and utilization. There has not been a systematic literature review of evergreening strategies for psychiatric medications. Based on such a review, 11 strategies were identified and relevant examples were provided. Four case examples of commonly used psychiatric medications indicated evergreen prices 3 to 211 times the cost of the original medication, and the evergreen costs ranging from $132.00 to $10,125.24 higher than the original cost on an annual basis. The higher cost of evergreening medications can create inefficiencies and waste in healthcare resulting in lower-quality patient care. Healthcare providers, patient advocates, health insurance companies, and policy-makers should be aware of these practices to improve healthcare systems.