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1.
Afr J Reprod Health ; 28(9): 136-144, 2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39373156

ABSTRACT

complications, infectious diseases, maternal and infant health in disasters, gender-based violence, healthcare access inequities, mental health impacts, and food security issues. Findings reveal an uneven distribution of coverage across continents, with potential language bias in English-dominated sources. Acknowledging limitations, future research directions emphasize a more inclusive approach, incorporating diverse linguistic perspectives and qualitative exploration of community experiences. The study underscores the imperative for global representation in media discourse This research explores the intricate relationship between climate change and reproductive health through an analysis of 1000 global news articles from 2018 onwards. Utilizing Latent Dirichlet Allocation (LDA), key topics in media coverage are identified, encompassing fertility challenges, pregnancy and advocates for comprehensive, evidence-based strategies to address the complex interplay between climate change and reproductive health.


Cette recherche explore la relation complexe entre le changement climatique et la santé reproductive à travers une analyse de 1 000 articles de presse mondiaux à partir de 2018. Grâce à l'allocation de Dirichlet latente (LDA), des sujets clés de la couverture médiatique sont identifiés, englobant les problèmes de fertilité, les complications de la grossesse, les maladies infectieuses, la santé maternelle et infantile en cas de catastrophe, la violence sexiste, les inégalités d'accès aux soins de santé, les impacts sur la santé mentale et les problèmes de sécurité alimentaire. . Les résultats révèlent une répartition inégale de la couverture à travers les continents, avec un biais linguistique potentiel dans les sources à dominante anglaise. Reconnaissant les limites, les futures orientations de recherche mettent l'accent sur une approche plus inclusive, intégrant diverses perspectives linguistiques et une exploration qualitative des expériences communautaires. L'étude souligne l'impératif d'une représentation mondiale dans le discours médiatique et préconise des stratégies globales et fondées sur des preuves pour aborder l'interaction complexe entre le changement climatique et la santé reproductive.


Subject(s)
Climate Change , Journalism , Reproductive Health , Humans , Female , Pregnancy
2.
Clin Psychol Sci ; 12(5): 865-881, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39323941

ABSTRACT

Individual differences in self-control predict many health and life outcomes. Building on twin literature, we used genomic structural equation modeling to test the hypothesis that genetic influences on executive function and impulsivity predict independent variance in mental health and other outcomes. The impulsivity factor (comprising urgency, lack of premeditation, and other facets) was only modestly genetically correlated with low executive function (rg =.13). Controlling for impulsivity, low executive function was genetically associated with increased internalizing (ßg =.15), externalizing (ßg =.13), thought disorders (ßg =.38), compulsive disorders (ßg =.22), and chronotype (ßg =.11). Controlling for executive function, impulsivity was positively genetically associated with internalizing (ßg =.36), externalizing (ßg =.55), body mass index (ßg =.26), and insomnia (ßg =.35), and negatively genetically associated with compulsive disorders (ßg = -.17). Executive function and impulsivity were both genetically correlated with general cognitive ability and educational attainment. This work suggests that executive function and impulsivity are genetically separable and show independent associations with mental health.

4.
Environ Health ; 23(1): 70, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39232744

ABSTRACT

BACKGROUND: Epidemiological and toxicological studies indicate that increased exposure to air pollutants can lead to neurodegenerative diseases. To further confirm this relationship, we evaluated the association between exposure to ambient air pollutants and corneal nerve measures as a surrogate for neurodegeneration, using corneal confocal microscopy. METHODS: We used population-based observational cross-sectional data from The Maastricht Study including N = 3635 participants (mean age 59.3 years, 51.6% were women, and 19.9% had type 2 diabetes) living in the Maastricht area. Using the Geoscience and hEalth Cohort COnsortium (GECCO) data we linked the yearly average exposure levels of ambient air pollutants at home address-level [particulate matter with diameters of ≤ 2.5 µm (PM2.5), and ≤ 10.0 µm (PM10), nitrogen dioxide (NO2), and elemental carbon (EC)]. We used linear regression analysis to study the associations between Z-score for ambient air pollutants concentrations (PM2.5, PM10, NO2, and EC) and Z-score for individual corneal nerve measures (corneal nerve bifurcation density, corneal nerve density, corneal nerve length, and fractal dimension). RESULTS: After adjustment for potential confounders (age, sex, level of education, glucose metabolism status, corneal confocal microscopy lag time, inclusion year of participants, smoking status, and alcohol consumption), higher Z-scores for PM2.5 and PM10 were associated with lower Z-scores for corneal nerve bifurcation density, nerve density, nerve length, and nerve fractal dimension [stß (95% CI): PM2.5 -0.10 (-0.14; -0.05), -0.04 (-0.09; 0.01), -0.11 (-0.16; -0.06), -0.20 (-0.24; -0.15); and PM10 -0.08 (-0.13; -0.03), -0.04 (-0.09; 0.01), -0.08 (-0.13; -0.04), -0.17 (-0.21; -0.12)], respectively. No associations were found between NO2 and EC and corneal nerve measures. CONCLUSIONS: Our population-based study demonstrated that exposure to higher levels of PM2.5 and PM10 are associated with higher levels of corneal neurodegeneration, estimated from lower corneal nerve measures. Our results suggest that air pollution may be a determinant for neurodegeneration assessed in the cornea and may impact the ocular surface health as well.


Subject(s)
Air Pollutants , Cornea , Environmental Exposure , Particulate Matter , Humans , Female , Particulate Matter/analysis , Particulate Matter/adverse effects , Male , Cross-Sectional Studies , Middle Aged , Cornea/innervation , Air Pollutants/analysis , Air Pollutants/adverse effects , Environmental Exposure/adverse effects , Aged , Netherlands/epidemiology , Adult , Microscopy, Confocal
5.
Community Health Equity Res Policy ; : 2752535X241273820, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39235954

ABSTRACT

According to the life course perspective (LCP), optimal human development and healthy aging are key goals that must start preconceptionally and continue later in life. However, older adult health and family health across generations have received very little attention in maternal and child health (MCH). Community-based participatory research (CBPR) is an important strategy for putting the LCP into action by engaging those communities most affected by health disparities. We conducted six CBPR focus groups using the LCP as the theoretical framework to capture community members' perspectives of risk and protective factors for older adult health. Perceived protective factors for older adults included socialization, support systems, and practicing wellness. Perceived risk factors included caretaking responsibilities, isolation, medical issues, and lack of support. The identified risk and protective factors for older adult health must be considered when developing public health interventions that promote health equity in aging and MCH.

6.
Article in English | MEDLINE | ID: mdl-39299657

ABSTRACT

CONTEXT: The critical role of hospice and palliative care in response to the COVID-19 pandemic is well recognized, but there is limited evidence to guide healthcare leadership through future crises. OBJECTIVES: Our goal was to support future organizational resilience by exploring hospice and palliative team members' perspectives on crisis leadership during the COVID-19 pandemic in New York City (NYC). METHODS: This qualitative descriptive study used individual, semi-structured interviews of purposively sampled interdisciplinary team members. Enrollment sites were two large NYC metro hospice care organizations and one outpatient palliative care practice. We asked participants to complete a demographic form and a 45-60 minute interview. We used descriptive statistics and thematic analysis, respectively, for data analysis. We triangulated the data by presenting preliminary study findings to a group of clinicians (n=21) from one of the referring organizations. RESULTS: Participants (n=30) were professionally diverse (e.g., nurses, physicians, social workers, chaplains, administrators), experienced (mean=17 years; 10 years in hospice), and highly educated (83% ≥ master's degree). About half (n=15) self-identified as white, non-Hispanic, and nearly half (n=13) self-identified as being from a racial/ethnic minoritized group. Two (n=2) did not wish to self-identify. We identified four themes that reflected challenges and adaptive responses to providing care during a crisis: Stay Open and Stay Safe; Act Flexibly; Lead Adaptively; and Create a Culture of Solidarity. CONCLUSION: While additional work is indicated, findings offer direction for a crisis management playbook to guide leadership in hospice, palliative care, and other healthcare settings in future crises.

7.
G3 (Bethesda) ; 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39250761

ABSTRACT

Genome-wide association studies typically evaluate the autosomes and sometimes the X Chromosome, but seldom consider the Y or mitochondrial Chromosomes. We genotyped the Y and mitochondrial Chromosomes in heterogeneous stock rats (Rattus norvegicus), an outbred population created from eight inbred strains. We identified 8 distinct Y and 4 distinct mitochondrial Chromosomes among the 8 founders. However, only two types of each nonrecombinant chromosome were observed in our modern heterogeneous stock rat population (generations 81-97). Despite the relatively large sample size, there were virtually no significant associations for behavioral, physiological, metabolome, or microbiome traits after correcting for multiple comparisons. However, both Y and mitochondrial Chromosomes were strongly associated with expression of a few genes located on those chromosomes, which provided a positive control. Our results suggest that within modern heterogeneous stock rats there are no Y and mitochondrial Chromosomes differences that strongly influence behavioral or physiological traits. These results do not address other ancestral Y and mitochondrial Chromosomes that do not appear in modern heterogeneous stock rats, nor do they address effects that may exist in other rat populations, or in other species.

8.
Cureus ; 16(7): e65072, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39171067

ABSTRACT

A 29-year-old male presented with acute left-sided weakness in both the upper extremity (UE) and lower extremity (LE), an atypical symptom for testicular cancer but not uncommon for brain metastasis. Testicular cancer usually manifests as a testicular mass or discomfort. His medical history included a previously resected testicular mass, with pathology results unknown due to the patient being lost to follow-up. Upon examination, he exhibited significant neurological deficits and multiple subcutaneous nodules. Imaging revealed multiple enhancing brain lesions and widespread metastases to the lungs and other regions. Laboratory tests showed elevated alpha-fetoprotein and lactate dehydrogenase levels, supporting a diagnosis of advanced non-seminomatous germ cell tumor. He received multidisciplinary treatment, including dexamethasone, levetiracetam, and chemotherapy. The patient responded well to the treatment, showing significant improvement in neurological function and stabilization of his condition. This case underscores the diagnostic and therapeutic challenges of metastatic testicular cancer, particularly with rare presentations such as cutaneous involvement, and highlights the importance of comprehensive diagnostic evaluations and multidisciplinary care.

9.
Hypertension ; 81(10): 2162-2172, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39136128

ABSTRACT

BACKGROUND: Blood-brain barrier (BBB) integrity is presumed to be impaired in hypertension, resulting from cerebral endothelial dysfunction. Hypertension precedes various cerebrovascular diseases, such as cerebral small vessel disease, and is a risk factor for developing neurodegenerative diseases for which BBB disruption is a preceding pathophysiological process. In this cross-sectional study, we investigated the relation between hypertension, current blood pressure, and BBB leakage in human subjects. METHODS: BBB leakage was determined in 22 patients with hypertension and 19 age- and sex-matched normotensive controls (median age [range], 65 [45-80] years; 19 men) using a sparsely time-sampled contrast-enhanced 7T magnetic resonance imaging protocol. Structural cerebral small vessel disease markers were visually rated. Multivariable regression analyses, adjusted for age, sex, cardiovascular risk factors, and cerebral small vessel disease markers, were performed to determine the relation between hypertension status, systolic and diastolic blood pressure, mean arterial pressure, drug treatment, and BBB leakage. RESULTS: Both hypertensive and normotensive participants showed mild scores of cerebral small vessel disease. BBB leakage did not differ between hypertensive and normotensive participants; however, it was significantly higher for systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the cortex, and diastolic blood pressure and mean arterial pressure in the gray matter. Effectively treated patients showed less BBB leakage than those with current hypertension. CONCLUSIONS: BBB integrity in the total and cortical gray matter decreases with increasing blood pressure but is not related to hypertension status. These findings show that BBB disruption already occurs with increasing blood pressure, before the presence of overt cerebral tissue damage. Additionally, our results suggest that effective antihypertensive medication has a protective effect on the BBB. REGISTRATION: URL: https://trialsearch.who.int/; Unique identifier: NL7537.


Subject(s)
Blood Pressure , Blood-Brain Barrier , Hypertension , Magnetic Resonance Imaging , Humans , Blood-Brain Barrier/physiopathology , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/diagnostic imaging , Male , Female , Middle Aged , Hypertension/physiopathology , Hypertension/drug therapy , Magnetic Resonance Imaging/methods , Aged , Cross-Sectional Studies , Blood Pressure/physiology , Cerebral Small Vessel Diseases/physiopathology , Cerebral Small Vessel Diseases/diagnostic imaging , Aged, 80 and over , Contrast Media
10.
Gerontologist ; 64(10)2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39187989

ABSTRACT

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic severely disrupted hospice care, yet there is little research regarding how widespread disruptions affected clinician and family decision-making. We aimed to understand how the pandemic affected structures, processes, and outcomes of end-of-life care. RESEARCH DESIGN AND METHODS: Retrospective narrative chart review of electronic health records of 61 patients referred and admitted to hospice from 3 New York City geriatrics practices who died between March 1, 2020, and March 31, 2021. We linked longitudinal, unstructured medical, and hospice electronic health record notes to create a real-time, multiperspective trajectory of patients' interactions with providers using directed content analysis. RESULTS: Most patients had dementia and were enrolled in hospice for 11 days. Care processes were shaped by structural factors (staffing, supplies, and governmental/institutional policies), and outcomes were prioritized by care teams and families (protecting safety, maintaining high-touch care, honoring patient values, and supporting patients emotionally and spiritually). Processes used to achieve these outcomes were decision-making, care delivery, supporting a "good death," and emotional and spiritual support. DISCUSSION AND IMPLICATIONS: Care processes were negotiated throughout the end of life, with clinicians and families making in-the-moment decisions. Some adaptations were effective but also placed extraordinary pressure on paid and family caregivers. Healthcare teams' and families' goals to meet patients' end-of-life priorities can be supported by ongoing assessment of patient goals and process changes needed to support them, stronger structural supports for paid and family caregivers, incentivizing relationships across primary care and hospice teams, and extending social work and spiritual care.


Subject(s)
COVID-19 , Electronic Health Records , Hospice Care , SARS-CoV-2 , Terminal Care , Humans , COVID-19/epidemiology , Female , Male , Retrospective Studies , Aged , Terminal Care/organization & administration , Aged, 80 and over , New York City/epidemiology , Decision Making
11.
Genes Brain Behav ; 23(4): e12909, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39119916

ABSTRACT

Delay discounting refers to the behavioral tendency to devalue rewards as a function of their delay in receipt. Heightened delay discounting has been associated with substance use disorders and multiple co-occurring psychopathologies. Human and animal genetic studies have established that delay discounting is heritable, but only a few associated genes have been identified. We aimed to identify novel genetic loci associated with delay discounting through a genome-wide association study (GWAS) using Heterogeneous Stock (HS) rats, a genetically diverse outbred population derived from eight inbred founder strains. We assessed delay discounting in 650 male and female HS rats using an adjusting amount procedure in which rats chose between smaller immediate sucrose rewards or a larger reward at various delays. Preference switch points were calculated and both exponential and hyperbolic functions were fitted to these indifference points. Area under the curve (AUC) and the discounting parameter k of both functions were used as delay discounting measures. GWAS for AUC, exponential k, and one indifference point identified significant loci on chromosomes 20 and 14. The gene Slc35f1, which encodes a member of the solute carrier family, was the sole gene within the chromosome 20 locus. That locus also contained an eQTL for Slc35f1, suggesting that heritable differences in the expression might be responsible for the association with behavior. Adgrl3, which encodes a latrophilin subfamily G-protein coupled receptor, was the sole gene within the chromosome 14 locus. These findings implicate novel genes in delay discounting and highlight the need for further exploration.


Subject(s)
Delay Discounting , Genome-Wide Association Study , Animals , Rats , Male , Female , Reward , Quantitative Trait Loci
12.
J Genet Couns ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39189540

ABSTRACT

The goal of this study was to assess the feasibility of using exome (ES) and genome sequencing (GS) in guiding preconception genetic screening (PCGS) for couples who are planning to conceive by creating a workflow for identifying risk alleles for autosomal recessive (AR) and X-linked (XL) disorders without the constraints of a predetermined, targeted gene panel. There were several limitations and challenges related to reporting and the technical aspects of ES and GS, which are listed in the discussion. We selected 150 couples from a cohort of families (trios) enrolled in a research protocol where the goal was to define the genetic etiology of disease in an affected child. Pre-existing, de-identified parental sequencing data were analyzed to define variants that would place the couple at risk of having a child affected by an AR or XL disorder. We identified 17 families who would be selected for counseling about risk alleles. We noted that only 3 of these at-risk couples would be identified if we limited ourselves to the current ACMG-recommended expanded carrier screening gene panel. ES and GS successfully identified couples who are at risk of having a child with a rare AR or XL disorder that would have been missed by the current recommended guidelines. Current limitations of this approach include ethical concerns, difficulties in reporting results including variant calling due to the rare nature of some of the variants, determining which disorders to report, as well as technical difficulties in detecting certain variants such as repeat expansions.

13.
bioRxiv ; 2024 Aug 04.
Article in English | MEDLINE | ID: mdl-39211180

ABSTRACT

Objective: The behavioral and diagnostic heterogeneity within human opioid use disorder (OUD) diagnosis is not readily captured in current animal models, limiting translational relevance of the mechanistic research that is conducted in experimental animals. We hypothesize that a non-linear clustering of OUD-like behavioral traits will capture population heterogeneity and yield subpopulations of OUD vulnerable rats with distinct behavioral and neurocircuit profiles. Methods: Over 900 male and female heterogeneous stock rats, a line capturing genetic and behavioral heterogeneity present in humans, were assessed for several measures of heroin use and rewarded and non-rewarded seeking behaviors. Using a non-linear stochastic block model clustering analysis, rats were assigned to OUD vulnerable, intermediate and resilient clusters. Additional behavioral tests and circuit analyses using c-fos protein activation were conducted on the vulnerable and resilient subpopulations. Results: OUD vulnerable rats exhibited greater heroin taking and seeking behaviors relative to those in the intermediate and resilient clusters. Akin to human OUD diagnosis, further vulnerable rat sub-clustering revealed subpopulations with different combinations of behavioral traits, including sex differences. Lastly, heroin cue-induced neuronal patterns of circuit activation differed between resilient and vulnerable phenotypes. Behavioral sex differences were recapitulated in patterns of circuitry activation, including males preferentially engaging extended amygdala stress circuitry, and females cortico-striatal drug cue-seeking circuitry. Conclusion: Using a non-linear clustering approach in rats, we captured behavioral diagnostic heterogeneity reflective of human OUD diagnosis. OUD vulnerability and resiliency were associated with distinct neuronal activation patterns, posing this approach as a translational tool in assessing neurobiological mechanisms underpinning OUD.

14.
Article in English | MEDLINE | ID: mdl-39031522

ABSTRACT

BACKGROUND: Genome-wide association studies (GWAS) have identified hundreds of common variants associated with alcohol consumption. In contrast, genetic studies of alcohol consumption that use rare variants are still in their early stages. No prior studies of alcohol consumption have examined whether common and rare variants implicate the same genes and molecular networks, leaving open the possibility that the two approaches might identify distinct biology. METHODS: To address this knowledge gap, we used publicly available alcohol consumption GWAS summary statistics (GSCAN, N = 666,978) and whole exome sequencing data (Genebass, N = 393,099) to identify a set of common and rare variants for alcohol consumption. We used gene-based analysis to implicate genes from common and rare variant analyses, which we then propagated onto a shared molecular network using a network colocalization procedure. RESULTS: Gene-based analysis of each dataset implicated 294 (common variants) and 35 (rare variants) genes, including ethanol metabolizing genes ADH1B and ADH1C, which were identified by both analyses, and ANKRD12, GIGYF1, KIF21B, and STK31, which were identified in only the rare variant analysis, but have been associated with other neuropsychiatric traits. Network colocalization revealed significant network overlap between the genes identified via common and rare variants. The shared network identified gene families that function in alcohol metabolism, including ADH, ALDH, CYP, and UGT. Seventy-one of the genes in the shared network were previously implicated in neuropsychiatric or substance use disorders but not alcohol-related behaviors (e.g. EXOC2, EPM2A, and CACNG4). Differential gene expression analysis showed enrichment in the liver and several brain regions. CONCLUSIONS: Genes implicated by network colocalization identify shared biology relevant to alcohol consumption, which also underlie neuropsychiatric traits and substance use disorders that are comorbid with alcohol use, providing a more holistic understanding of two disparate sources of genetic information.

15.
medRxiv ; 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38947071

ABSTRACT

Cannabis is one of the most widely used drugs globally. Decriminalization of cannabis is further increasing cannabis consumption. We performed genome-wide association studies (GWASs) of lifetime (N=131,895) and frequency (N=73,374) of cannabis use. Lifetime cannabis use GWAS identified two loci, one near CADM2 (rs11922956, p=2.40E-11) and another near GRM3 (rs12673181, p=6.90E-09). Frequency of use GWAS identified one locus near CADM2 (rs4856591, p=8.10E-09; r2 =0.76 with rs11922956). Both traits were heritable and genetically correlated with previous GWASs of lifetime use and cannabis use disorder (CUD), as well as other substance use and cognitive traits. Polygenic scores (PGSs) for lifetime and frequency of cannabis use associated cannabis use phenotypes in AllofUs participants. Phenome-wide association study of lifetime cannabis use PGS in a hospital cohort replicated associations with substance use and mood disorders, and uncovered associations with celiac and infectious diseases. This work demonstrates the value of GWASs of CUD transition risk factors.

16.
Front Aging Neurosci ; 16: 1401255, 2024.
Article in English | MEDLINE | ID: mdl-38957542

ABSTRACT

Purpose: Utilizing a participatory approach, we sought to co-design a 12-week Green Activity Program (GAP) with Hispanic/Latino individuals living with memory challenges and their care partners, local outdoor professionals, and healthcare providers. Methods: Participants were recruited via convenience and snowball sampling in the Bronx, New York with Hispanic/Latino persons living with memory challenges and care partners, outdoor activity professionals, and interdisciplinary healthcare providers/dementia experts. Co-design occurred iteratively with 5 focus groups and 4 individual interviews lasting 30-90 min and focused on program and research design. Sessions were recorded and transcribed. Utilizing directed content analysis data was coded using a priori codes program design and research design. Results: 21 participants completed co-design activities: (n = 8 outdoor activity professionals, n = 6 Hispanic/Latino persons living with memory challenges and care partners, and n = 7 interdisciplinary healthcare providers/dementia experts). Participant preferences for program design were captured by subcodes session duration (30-90 min), frequency (4-8 sessions), and delivery modes (in-person and phone). Participants' preferred nature activities included group exercise and outdoor crafts [crocheting], outcomes of social participation, connectedness to nature, decreased loneliness, and stewardship were identified. Preferred language for recruiting and describing the program were "memory challenges," "Hispanic/Latino," and "wellbeing." Referral pathways were identified including community-based organizations and primary care. Conclusion: Co-design was a successful form of engagement for people living with memory challenges that enabled participants to help design key elements of the GAP and research design. Our processes, findings, and recommendations for tailoring co-design to engage Hispanic/Latino people living with memory challenges can inform the development of other programs for this population.

17.
Cureus ; 16(6): e62827, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39040737

ABSTRACT

Lymphoma, a term encompassing tumor masses in the lymph nodes, is often classified into Hodgkin and non-Hodgkin lymphomas, each with distinct subtypes. We present the unique case of an HIV-positive patient diagnosed with Burkitt lymphoma and classical Hodgkin lymphoma simultaneously as a composite lymphoma. Over the course of five years, a variety of dose-adjusted chemotherapy regimens were used that ultimately proved highly effective. The successful management of this rare case reinforces the significance of considering unexpected combinations of neoplastic processes during diagnosis and treatment planning.

18.
bioRxiv ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39071405

ABSTRACT

Affordable sequencing and genotyping methods are essential for large scale genome-wide association studies. While genotyping microarrays and reference panels for imputation are available for human subjects, non-human model systems often lack such options. Our lab previously demonstrated an efficient and cost-effective method to genotype heterogeneous stock rats using double-digest genotyping-by-sequencing. However, low-coverage whole-genome sequencing offers an alternative method that has several advantages. Here, we describe a cost-effective, high-throughput, high-accuracy genotyping method for N/NIH heterogeneous stock rats that can use a combination of sequencing data previously generated by double-digest genotyping-by-sequencing and more recently generated by low-coverage whole-genome-sequencing data. Using double-digest genotyping-by-sequencing data from 5,745 heterogeneous stock rats (mean 0.21x coverage) and low-coverage whole-genome-sequencing data from 8,760 heterogeneous stock rats (mean 0.27x coverage), we can impute 7.32 million bi-allelic single-nucleotide polymorphisms with a concordance rate >99.76% compared to high-coverage (mean 33.26x coverage) whole-genome sequencing data for a subset of the same individuals. Our results demonstrate the feasibility of using sequencing data from double-digest genotyping-by-sequencing or low-coverage whole-genome-sequencing for accurate genotyping, and demonstrate techniques that may also be useful for other genetic studies in non-human subjects.

19.
J Clin Med ; 13(13)2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38999430

ABSTRACT

Exposure to ionizing radiation (IR) is inevitable in various X-ray imaging examinations, with computed tomography (CT) being a major contributor to increased human radiation exposure. Ionizing radiation may cause structural damage to macromolecules, particularly DNA, mostly through an indirect pathway in diagnostic imaging. The indirect pathway primarily involves the generation of reactive oxygen species (ROS) due to water radiolysis induced by IR, leading to DNA damage, including double-strand breaks (DSB), which are highly cytotoxic. Antioxidants, substances that prevent oxidative damage, are proposed as potential radioprotective agents. This Study Protocol article presents the rationale for selecting vitamin C as a preventive measure against CT-associated IR-induced DNA damage, to be investigated in a randomized placebo-controlled trial, with a full in vivo design, using an oral easy-to-use schedule administration in the outpatient setting, for the single CT examination with the highest total global IR dose burden (contrast-enhanced abdomen and pelvis CT). The study also aims to explore the mediating role of oxidative stress, and it has been written in adherence to the Standard Protocol Items recommendations.

20.
J Hum Hypertens ; 38(9): 649-654, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38898171

ABSTRACT

The purpose of the present study is to identify the impact of the postpartum menstrual cycle on aldosterone, renin, and their ratio of women with and without a preeclamptic pregnancy in the past. To this end, we analysed the data from 59 women with a history of preeclampsia and 39 healthy parous controls. Five to seven months post-partum, we measured aldosterone, renin, and the aldosterone-to-renin ratio during both the follicular and the luteal phase of the menstrual cycle. All measurements were taken in the supine position in the morning. Patients had maintained a standardized sodium diet in the week prior to the measurements. Our results show that in both post-partum women with recent preeclampsia and controls, average levels of renin and aldosterone are significantly elevated in the luteal phase as compared to the follicular phase. The aldosterone-to-renin ratio does not differ between the two phases in either group. Compared to controls, women with recent preeclampsia have significantly lower levels of renin, aldosterone, and aldosterone-to-renin ratio in the follicular phase. This remained consistent in the luteal phase, except for renin. A close correlation existed between the luteal and follicular aldosterone-to-renin ratio in the control group but not in the preeclampsia group. We conclude that both renin and aldosterone are significantly affected by the menstrual cycle whereas the resulting aldosterone-to-renin ratio is not. Post-partum women with recent preeclampsia tend to have lower values for aldosterone and the aldosterone-to-renin ratio than controls.


Subject(s)
Aldosterone , Postpartum Period , Pre-Eclampsia , Renin , Humans , Female , Aldosterone/blood , Renin/blood , Pre-Eclampsia/blood , Pre-Eclampsia/physiopathology , Pregnancy , Adult , Postpartum Period/blood , Luteal Phase/blood , Case-Control Studies , Menstrual Cycle/blood , Menstrual Cycle/physiology , Follicular Phase/blood
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