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1.
Contraception ; 134: 110420, 2024 06.
Article in English | MEDLINE | ID: mdl-38462205

ABSTRACT

OBJECTIVES: To understand patterns in demand for emergency contraception (EC), we characterize the sales of over-the-counter (OTC) levonorgestrel (LNG) EC in the United States from traditional retail outlets. STUDY DESIGN: We describe sales of OTC LNG EC using retail sales data aggregated from traditional retail channels, including grocery stores, drug stores, mass merchandisers, club stores, dollar stores, and military outlets. RESULTS: Sales of OTC LNG EC doubled between 2016 and 2022 (approximately 7.2-14.8 million). CONCLUSIONS: Increasing sales of EC are consistent with increased use and use frequency of EC by those at risk of pregnancy in the United States. IMPLICATIONS: OTC LNG EC sales since 2016 exceed what national survey usage estimates would suggest, indicating that national surveys underreport EC use, those using EC purchase it somewhat frequently, and/or individuals stockpile EC for later use. The role of EC in individual contraceptive strategies, particularly as access to reproductive healthcare is restricted, warrants further study.


Subject(s)
Commerce , Contraception, Postcoital , Levonorgestrel , Nonprescription Drugs , Levonorgestrel/supply & distribution , Levonorgestrel/administration & dosage , United States , Humans , Nonprescription Drugs/supply & distribution , Nonprescription Drugs/economics , Female , Contraception, Postcoital/statistics & numerical data , Commerce/statistics & numerical data , Contraceptives, Postcoital/supply & distribution , Contraceptives, Postcoital/economics , Pregnancy
2.
Womens Health Issues ; 34(1): 66-71, 2024.
Article in English | MEDLINE | ID: mdl-37563061

ABSTRACT

INTRODUCTION: Despite the high potential need for emergency contraception (EC) among college students, lack of accurate knowledge may decrease the likelihood of its use in this population. We examined knowledge about EC methods, potential outcomes of use, and access among college students in the United States. METHODS: We recruited college students from a listserv devoted to EC campus activism for an online survey about EC knowledge (N = 150) and conducted 24 follow-up in-depth interviews. We describe the share of respondents that correctly answered each question and provide additional context and insight from interview respondents. RESULTS: Gaps in EC knowledge were noted in our sample of college student EC activists. Awareness of different methods of EC was not universal; 38% of the sample was unaware of ulipristal acetate (ella®) and 61% was unaware of the intrauterine device inserted after intercourse as EC. Many respondents also incorrectly perceived additional barriers to acquiring EC such as minimum age or an ID requirement to purchase EC (64% and 49%, respectively). Interview respondents describe how medical providers, such as student health services and pharmacists, can pose barriers to EC access through either their actions or how college students expect they will act. CONCLUSIONS: We document several gaps in knowledge surrounding EC in college students, even in an activist sample. Additional efforts to inform students about the variety of available EC methods and address mistaken perceptions about barriers to access may allow college students to better meet their needs for EC.


Subject(s)
Contraception, Postcoital , Intrauterine Devices , Female , Humans , Friends , Health Knowledge, Attitudes, Practice , Students , Surveys and Questionnaires , Universities
4.
BMJ ; 383: e077437, 2023 12 20.
Article in English | MEDLINE | ID: mdl-38123174

ABSTRACT

OBJECTIVE: To estimate the increase in sales of emergency contraception following the New Year's Eve/New Year's Day holiday. DESIGN: Time series analysis using autoregressive integrated moving average (ARIMA) model. SETTING: Traditional (that is, "bricks and mortar") retail outlets-grocery stores, drug stores, mass merchandisers, club stores, dollar stores, and military outlets-in the United States from 2016 to 2022. DATA SOURCE: Marketing data on weekly aggregated sales of items classified as emergency contraception gathered between 2016 and 2022 (n=362). On the basis of dates, weeks were classified as following the New Year holiday (n=6) or not (n=356). MAIN OUTCOME MEASURE: Weekly sales of levonorgestrel emergency contraception per 1000 women of reproductive age in the US population. RESULTS: Sales of levonorgestrel emergency contraception significantly increased after the New Year holiday (0.63 (95% confidence interval 0.58 to 0.69) unit increase per 1000 women aged 15-44). Holidays that share some aspects of the elevated risks of unprotected sexual intercourse with the New Year holiday (Valentine's Day, St Patrick's Day, US Independence Day) were associated with increased sales, albeit to a lesser degree, with respective sales increases per 1000 women aged 15-44 of 0.31 (0.25 to 0.38), 0.14 (0.06 to 0.23), and 0.20 (0.11 to 0.29). Holidays without these expectations (Easter, Mother's Day, Father's Day) were not significantly associated with sales of levonorgestrel emergency contraception. CONCLUSIONS: Increased sales of emergency contraception following the New Year's holiday suggest that this period is associated with increased risks of unprotected vaginal intercourse compared with other holidays. Targeting behavioral risks, prevention strategies to mitigate sexual violence, and improving access to contraception around holidays may limit the risks associated with unprotected vaginal intercourse.


Subject(s)
Contraception, Postcoital , Humans , United States/epidemiology , Female , Levonorgestrel/therapeutic use , Holidays , Time Factors , Marketing
5.
Article in English | MEDLINE | ID: mdl-37899592

ABSTRACT

The hydrogenation of metal nanoparticles provides a pathway toward tuning their combustion characteristics. Metal hydrides have been employed as solid-fuel additives for rocket propellants, pyrotechnics, and explosives. Gas generation during combustion is beneficial to prevent aggregation and sintering of particles, enabling a more complete fuel utilization. Here, we discuss a novel approach for the synthesis of magnesium hydride nanoparticles based on a two-step aerosol process. Mg particles are first nucleated and grown via thermal evaporation, followed immediately by in-flight exposure to a hydrogen-rich low-temperature plasma. During the second step, atomic hydrogen generated by the plasma rapidly diffuses into the Mg lattice, forming particles with a significant fraction of MgH2. We find that hydrogenated Mg nanoparticles have an ignition temperature that is reduced by ∼200 °C when combusted with potassium perchlorate as an oxidizer, compared to the non-hydrogenated Mg material. This is due to the release of hydrogen from the fuel, jumpstarting its combustion. In addition, characterization of the plasma processes suggests that a careful balance between the dissociation of molecular hydrogen and heating of the nanoparticles must be achieved to avoid hydrogen desorption during production and achieve a significant degree of hydrogenation.

6.
J Lipid Res ; 64(6): 100374, 2023 06.
Article in English | MEDLINE | ID: mdl-37075982

ABSTRACT

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome, but a predominant subset of HFpEF patients has metabolic syndrome (MetS). Mechanistically, systemic, nonresolving inflammation associated with MetS might drive HFpEF remodeling. Free fatty acid receptor 4 (Ffar4) is a GPCR for long-chain fatty acids that attenuates metabolic dysfunction and resolves inflammation. Therefore, we hypothesized that Ffar4 would attenuate remodeling in HFpEF secondary to MetS (HFpEF-MetS). To test this hypothesis, mice with systemic deletion of Ffar4 (Ffar4KO) were fed a high-fat/high-sucrose diet with L-NAME in their water to induce HFpEF-MetS. In male Ffar4KO mice, this HFpEF-MetS diet induced similar metabolic deficits but worsened diastolic function and microvascular rarefaction relative to WT mice. Conversely, in female Ffar4KO mice, the diet produced greater obesity but no worsened ventricular remodeling relative to WT mice. In Ffar4KO males, MetS altered the balance of inflammatory oxylipins systemically in HDL and in the heart, decreasing the eicosapentaenoic acid-derived, proresolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE), while increasing the arachidonic acid-derived, proinflammatory oxylipin 12-hydroxyeicosatetraenoic acid (12-HETE). This increased 12-HETE/18-HEPE ratio reflected a more proinflammatory state both systemically and in the heart in male Ffar4KO mice and was associated with increased macrophage numbers in the heart, which in turn correlated with worsened ventricular remodeling. In summary, our data suggest that Ffar4 controls the proinflammatory/proresolving oxylipin balance systemically and in the heart to resolve inflammation and attenuate HFpEF remodeling.


Subject(s)
Heart Failure , Metabolic Syndrome , Male , Female , Mice , Animals , Heart Failure/complications , Heart Failure/metabolism , Oxylipins , Metabolic Syndrome/complications , Stroke Volume/physiology , Ventricular Remodeling , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid , Inflammation/complications
7.
Front Mol Neurosci ; 15: 1007026, 2022.
Article in English | MEDLINE | ID: mdl-36340689

ABSTRACT

The natriuretic peptide receptors NPR1 and NPR2, also known as guanylyl cyclase A and guanylyl cyclase B, have critical functions in many signaling pathways, but much remains unknown about their localization and function in vivo. To facilitate studies of these proteins, we developed genetically modified mouse lines in which endogenous NPR1 and NPR2 were tagged with the HA epitope. To investigate the role of phosphorylation in regulating NPR1 and NPR2 guanylyl cyclase activity, we developed mouse lines in which regulatory serines and threonines were substituted with glutamates, to mimic the negative charge of the phosphorylated forms (NPR1-8E and NPR2-7E). Here we describe the generation and applications of these mice. We show that the HA-NPR1 and HA-NPR2 mice can be used to characterize the relative expression levels of these proteins in different tissues. We describe studies using the NPR2-7E mice that indicate that dephosphorylation of NPR2 transduces signaling pathways in ovary and bone, and studies using the NPR1-8E mice that indicate that the phosphorylation state of NPR1 is a regulator of heart, testis, and adrenal function.

8.
Micromachines (Basel) ; 13(10)2022 Oct 13.
Article in English | MEDLINE | ID: mdl-36296083

ABSTRACT

Cells cultured in three-dimensional scaffolds express a phenotype closer to in vivo cells than cells cultured in two-dimensional containers. Natural polymers are suitable materials to make three-dimensional scaffolds to develop disease models for high-throughput drug screening owing to their excellent biocompatibility. However, natural polymer solutions have a range of viscosities, and none of the currently available liquid dispensers are capable of dispensing highly viscous polymer solutions. Here, we report the development of an automated scaffold dispensing system for rapid, reliable, and homogeneous creation of scaffolds in well-plate formats. We employ computer-controlled solenoid valves to regulate air pressure impinging upon a syringe barrel filled with scaffold solution to be dispensed. Automated dispensing of scaffold solution is achieved via a programmable software interface that coordinates solution extrusion and the movement of a dispensing head. We show that our pneumatically actuated dispensing system can evenly distribute high-viscosity, chitosan-based polymer solutions into 96- and 384-well plates to yield highly uniform three-dimensional scaffolds after lyophilization. We provide a proof-of-concept demonstration of high-throughput drug screening by culturing glioblastoma cells in scaffolds and exposing them to temozolomide. This work introduces a device that can hasten the creation of three-dimensional cell scaffolds and their application to high-throughput testing.

9.
Calcif Tissue Int ; 111(5): 506-518, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35947145

ABSTRACT

C-type natriuretic peptide (CNP) activation of guanylyl cyclase-B (GC-B) catalyzes the synthesis of cGMP in chondrocytes and osteoblasts. Elevated cGMP stimulates long bone growth, and inactivating mutations in CNP or GC-B reduce cGMP, which causes dwarfism. GC-B7E/7E mice that express a GC-B mutant that cannot be inactivated by dephosphorylation exhibit increased CNP-dependent GC-B activity, which increases bone length, as well as bone mass and strength. Importantly, how GC-B increases bone mass is not known. Here, we injected 12-week-old, wild type mice once daily for 28 days with or without BMN-111 (Vosoritide), a proteolytically resistant CNP analog. We found that BMN-111 treated mice had elevated levels of osteocalcin and collagen 1 C-terminal telopeptide (CTX) as well as increased osteoblasts and osteoclasts. In BMN-111 injected mice, tibial mRNAs for Rank ligand and osteoprotegrin were increased and decreased, respectively, whereas sclerostin mRNA was elevated 400-fold, consistent with increased osteoclast activity and decreased osteoblast activity. Mineral apposition rates and trabecular bone mass were not elevated in response to BMN-111. Because 9-week-old male GC-B7E/7E mice have increased bone mass but do not exhibit increased mineral apposition rates, we examined 4-week-old male GC-B7E/7E mice and found that these animals had increased serum osteocalcin, but not CTX. Importantly, tibias from these mice had 37% more osteoblasts, 26% fewer osteoclasts as well as 36% and 40% higher mineral apposition and bone formation rates, respectively. We conclude that GC-B-dependent bone formation is coupled to an early juvenile process that requires both increased osteoblasts and decreased osteoclasts.


Subject(s)
Natriuretic Peptide, C-Type , Osteoclasts , Animals , Collagen , Cyclic GMP , Male , Mice , Natriuretic Peptide, C-Type/genetics , Natriuretic Peptide, C-Type/metabolism , Osteoblasts/metabolism , Osteocalcin , Osteoclasts/metabolism , Osteogenesis , RANK Ligand , RNA, Messenger
10.
Child Youth Serv Rev ; 1362022 May.
Article in English | MEDLINE | ID: mdl-35342214

ABSTRACT

Millions of families in the United States are economically vulnerable: one shock can lead to hardship. We use data from the Fragile Families and Child Wellbeing Study to examine the association between acute healthcare utilization - emergency room visits or hospitalizations - and subsequent housing hardships, such as being evicted for financial reasons. Further, we explore whether this association differs by who in the family utilized the care and whether perceived social support protects against hardship when these experiences occur. Using lagged dependent variable regression models, we find that families that visited the emergency room or were hospitalized, regardless if it was a child or parent with this experience, were five percentage points more likely to experience any housing hardship than families that did not use acute care. Among families in which a child utilized acute care, perceived social support buffered the impact of using acute care. That perceived social support is associated with a lower likelihood of housing hardship among families that experienced acute care utilization for a child, but not parent, suggests that social support may be able to offset the challenges arising from children's, but not adults', use of acute care. In the face of economic precarity, informal safety nets may be insufficient to reduce the impact of acute care utilization on housing hardships.

11.
Cardiovasc Res ; 118(4): 1061-1073, 2022 03 16.
Article in English | MEDLINE | ID: mdl-33752243

ABSTRACT

AIMS: Free fatty acid receptor 4 (Ffar4) is a G-protein-coupled receptor for endogenous medium-/long-chain fatty acids that attenuates metabolic disease and inflammation. However, the function of Ffar4 in the heart is unclear. Given its putative beneficial role, we hypothesized that Ffar4 would protect the heart from pathologic stress. METHODS AND RESULTS: In mice lacking Ffar4 (Ffar4KO), we found that Ffar4 is required for an adaptive response to pressure overload induced by transverse aortic constriction (TAC), identifying a novel cardioprotective function for Ffar4. Following TAC, remodelling was worsened in Ffar4KO hearts, with greater hypertrophy and contractile dysfunction. Transcriptome analysis 3-day post-TAC identified transcriptional deficits in genes associated with cytoplasmic phospholipase A2α signalling and oxylipin synthesis and the reduction of oxidative stress in Ffar4KO myocytes. In cultured adult cardiac myocytes, Ffar4 induced the production of the eicosapentaenoic acid (EPA)-derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Furthermore, the activation of Ffar4 attenuated cardiac myocyte death from oxidative stress, while 18-HEPE rescued Ffar4KO myocytes. Systemically, Ffar4 maintained pro-resolving oxylipins and attenuated autoxidation basally, and increased pro-inflammatory and pro-resolving oxylipins, including 18-HEPE, in high-density lipoproteins post-TAC. In humans, Ffar4 expression decreased in heart failure, while the signalling-deficient Ffar4 R270H polymorphism correlated with eccentric remodelling in a large clinical cohort paralleling changes observed in Ffar4KO mice post-TAC. CONCLUSION: Our data indicate that Ffar4 in cardiac myocytes responds to endogenous fatty acids, reducing oxidative injury, and protecting the heart from pathologic stress, with significant translational implications for targeting Ffar4 in cardiovascular disease.


Subject(s)
Fatty Acids, Nonesterified , Heart Failure , Animals , Eicosapentaenoic Acid/pharmacology , Fatty Acids , Heart Failure/genetics , Heart Failure/prevention & control , Humans , Mice , Mice, Inbred C57BL , Oxylipins , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism
12.
FASEB J ; 36(1): e22069, 2022 01.
Article in English | MEDLINE | ID: mdl-34859913

ABSTRACT

Atrial natriuretic peptide (NP) and BNP increase cGMP, which reduces blood pressure and cardiac hypertrophy by activating guanylyl cyclase (GC)-A, also known as NPR-A or Npr1. Although GC-A is highly phosphorylated, and dephosphorylation inactivates the enzyme, the significance of GC-A phosphorylation to heart structure and function remains unknown. To identify in vivo processes that are regulated by GC-A phosphorylation, we substituted glutamates for known phosphorylation sites to make GC-A8E/8E mice that express an enzyme that cannot be inactivated by dephosphorylation. GC-A activity, but not protein, was increased in heart and kidney membranes from GC-A8E/8E mice. Activities were threefold higher in female compared to male cardiac ventricles. Plasma cGMP and testosterone were elevated in male and female GC-A8E/8E mice, but aldosterone was only increased in mutant male mice. Plasma and urinary creatinine concentrations were decreased and increased, respectively, but blood pressure and heart rate were unchanged in male GC-A8E/8E mice. Heart weight to body weight ratios for GC-A8E/8E male, but not female, mice were 12% lower with a 14% reduction in cardiomyocyte cross-sectional area. Subcutaneous injection of fsANP, a long-lived ANP analog, increased plasma cGMP and decreased aldosterone in male GC-AWT/WT and GC-A8E/8E mice at 15 min, but only GC-A8E/8E mice had elevated levels of plasma cGMP and aldosterone at 60 min. fsANP reduced ventricular ERK1/2 phosphorylation to a greater extent and for a longer time in the male mutant compared to WT mice. Finally, ejection fractions were increased in male but not female hearts from GC-A8E/8E mice. We conclude that increased phosphorylation-dependent GC-A activity decreases cardiac ERK activity, which results in smaller male hearts with improved systolic function.


Subject(s)
Cardiomegaly , MAP Kinase Signaling System , Phosphorylation , Receptors, Atrial Natriuretic Factor , Sex Characteristics , Animals , Cardiomegaly/enzymology , Cardiomegaly/genetics , Female , Male , Mice , Mice, Transgenic , Receptors, Atrial Natriuretic Factor/genetics , Receptors, Atrial Natriuretic Factor/metabolism
13.
JCI Insight ; 6(9)2021 05 10.
Article in English | MEDLINE | ID: mdl-33784257

ABSTRACT

Activating mutations in the fibroblast growth factor receptor 3 (FGFR3) or inactivating mutations in guanylyl cyclase-B (GC-B), also known as NPR-B or Npr2, cause short-limbed dwarfism. FGFR3 activation causes dephosphorylation and inactivation of GC-B, but the contribution of GC-B dephosphorylation to achondroplasia (ACH) is unknown. GC-B7E/7E mice that express a glutamate-substituted version of GC-B that cannot be inactivated by dephosphorylation were bred with mice expressing FGFR3-G380R, the most common human ACH mutation, to determine if GC-B dephosphorylation is required for ACH. Crossing GC-B7E/7E mice with FGFR3G380R/G380R mice increased naso-anal and long (tibia and femur), but not cranial, bone length twice as much as crossing GC-B7E/7E mice with FGFR3WT/WT mice from 4 to 16 weeks of age. Consistent with increased GC-B activity rescuing ACH, long bones from the GC-B7E/7E/FGFR3G380R/G380R mice were not shorter than those from GC-BWT/WT/FGFR3WT/WT mice. At 2 weeks of age, male but not female FGFR3G380R/G380R mice had shorter long bones and smaller growth plate hypertrophic zones, whereas female but not male GC-B7E/7E mice had longer bones and larger hypertrophic zones. In 2-week-old males, crossing FGFR3G380R/G380R mice with GC-B7E/7E mice increased long bone length and hypertrophic zone area to levels observed in mice expressing WT versions of both receptors. We conclude that preventing GC-B dephosphorylation rescues reduced axial and appendicular skeleton growth in a mouse model of achondroplasia.


Subject(s)
Achondroplasia/genetics , Bone Development/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics , Receptors, Atrial Natriuretic Factor/genetics , Animals , Body Size/genetics , Femur/growth & development , Growth Plate/growth & development , Growth Plate/pathology , Mice , Mice, Transgenic , Organ Size , Phosphorylation , Receptors, Atrial Natriuretic Factor/metabolism , Skull/growth & development , Tibia/growth & development
14.
Gerontologist ; 61(1): 71-77, 2021 01 21.
Article in English | MEDLINE | ID: mdl-33030209

ABSTRACT

BACKGROUND AND OBJECTIVES: Although individual age and preexisting health conditions are well-documented risk factors for coronavirus disease 2019 (COVID-19) mortality, it is unclear whether these 2 factors capture unique dimensions of risk for epidemic severity at the national level. In addition, no studies have examined whether national distributions of these factors are associated with epidemic experiences to date. RESEARCH DESIGN AND METHODS: Drawing on surveys of older adults from 42 countries and estimated case fatality ratios by age and preexisting health conditions, we document and compare national profiles of COVID-19 mortality risks among older adults. We develop 2 measures of national risk profiles: one based on age structures and another based on distributions of preexisting health conditions. Our analysis compares these constructs and documents their associations with national COVID-19 mortality rates. RESULTS: National profiles of COVID-19 mortality risk based on age structure and preexisting health conditions are moderately uncorrelated, capturing different aspects of risk. Both types of national risk profiles correlate meaningfully with countries' COVID-19 mortality experiences to date. DISCUSSION AND IMPLICATIONS: Measures of population age structure are readily available for every country in the world, while cross-national measures of older adult population health are more limited. In the COVID-19 crisis, these factors give different pictures of the countries with high and low risks of COVID-19 mortality. Moreover, our results suggest that both types of national risk profiles based on population health reflect current COVID-19 mortality severity in several countries, highlighting the need for more cross-national comparative data on older adult population health.


Subject(s)
COVID-19 , Aged , Humans , Mortality , Risk Factors , SARS-CoV-2
15.
Neuroscience ; 441: 33-45, 2020 08 10.
Article in English | MEDLINE | ID: mdl-32540366

ABSTRACT

The motor features of Parkinson's disease (PD) result from the loss of dopaminergic (DA) neurons in the substantia nigra with autophagy dysfunction being closely linked to this disease. A PD-causing familial mutation in VPS35 (D620N) has been reported to inhibit autophagy. In order to identify signaling pathways responsible for this autophagy defect, we performed an unbiased screen using RNA sequencing (RNA-Seq) of wild-type or VPS35 D620N-expressing retinoic acid-differentiated SH-SY5Y cells. We report that VPS35 D620N-expressing cells exhibit transcriptome changes indicative of alterations in extracellular matrix (ECM)-receptor interaction as well as PI3K-AKT signaling, a pathway known to regulate autophagy. Hyaluronan (HA) is a major component of brain ECM and signals via the ECM receptors CD44, a top RNA-Seq hit, and HA-mediated motility receptor (HMMR) to the autophagy-regulating PI3K-AKT pathway. We find that high (>950 kDa), but not low (15-40 kDa), molecular weight HA treatment inhibits autophagy. In addition, VPS35 D620N facilitated enhanced HA-AKT signaling. Transcriptomic assessment and validation of protein levels identified the differential expression of CD44 and HMMR isoforms in VPS35 D620N mutant cells. We report that knockdown of HMMR or CD44 results in upregulated autophagy in cells expressing wild-type VPS35. However, only HMMR knockdown resulted in rescue of autophagy dysfunction by VPS35 D620N indicating a potential pathogenic role for this receptor and HA signaling in Parkinson's disease.


Subject(s)
Parkinson Disease , Vesicular Transport Proteins , Autophagy , Humans , Hyaluronan Receptors/genetics , Hyaluronic Acid , Phosphatidylinositol 3-Kinases , Vesicular Transport Proteins/genetics
16.
FASEB Bioadv ; 2(3): 160-165, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32161905

ABSTRACT

Human spaceflight endeavors present an opportunity to expand our presence beyond Earth. To this end, it is crucial to understand and diagnose effects of long-term space travel on the human body. Developing tools for targeted, on-site detection of specific DNA sequences will allow us to establish research and diagnostics platforms that will benefit space programs. We describe a simple DNA diagnostic method that utilizes colorimetric loop-mediated isothermal amplification (LAMP) to enable detection of a repetitive telomeric DNA sequence in as little as 30 minutes. A proof of concept assay for this method was carried out using existing hardware on the International Space Station and the results were read instantly by an astronaut through a simple color change of the reaction mixture. LAMP offers a novel platform for on-orbit DNA-based diagnostics that can be deployed on the International Space Station and to the broader benefit of space programs.

17.
Bone ; 135: 115320, 2020 06.
Article in English | MEDLINE | ID: mdl-32179168

ABSTRACT

C-type natriuretic peptide (CNP) activation of guanylyl cyclase (GC)-B, also known as NPR2, stimulates cGMP synthesis and bone elongation. CNP activation requires the phosphorylation of multiple GC-B residues and dephosphorylation inactivates the receptor. GC-B7E/7E knockin mice, expressing a glutamate-substituted, "pseudophosphorylated," form of GC-B, exhibit increased CNP-dependent GC activity. Since mutations that constitutively activate GC-B in the absence of CNP result in low bone mineral density in humans, we determined the skeletal phenotype of 9-week old male GC-B7E/7E mice. Unexpectedly, GC-B7E/7E mice have significantly greater tibial and L5 vertebral trabecular bone volume fraction, tibial trabecular number, and tibial bone mineral density. Cortical cross-sectional area, cortical thickness, periosteal diameter and cortical cross-sectional moment of inertia were also significantly increased in GC-B7E/7E tibiae. Three-point bending measurements demonstrated that the mutant tibias and femurs had greater ultimate load, stiffness, energy to ultimate load, and energy to failure. No differences in microhardness indicated similar bone quality at the tissue level between the mutant and wildtype bones. Procollagen 1 N-terminal propeptide and osteocalcin were elevated in serum, and osteoblast number per bone perimeter and osteoid width per bone perimeter were elevated in tibias from the mutant mice. In contrast to mutations that constitutively activate GC-B, we report that mutations that enhance GC-B activity only in the presence of its natural ligand, increase bone mass, bone strength, and the number of active osteoblasts at the bone surface.


Subject(s)
Guanylate Cyclase , Natriuretic Peptide, C-Type , Animals , Bone Density , Guanylate Cyclase/genetics , Guanylate Cyclase/metabolism , Male , Mice , Osteoblasts/metabolism , Phosphorylation , Receptors, Atrial Natriuretic Factor/genetics , Receptors, Atrial Natriuretic Factor/metabolism
18.
Socius ; 6: 2378023120980328, 2020.
Article in English | MEDLINE | ID: mdl-34192140

ABSTRACT

In the social upheaval arising from the coronavirus disease 2019 (COVID-19) pandemic, we do not yet know how union formation, particularly marriage, has been affected. Using administration records-marriage certificates and applications-gathered from settings representing a variety of COVID-19 experiences in the United States, the authors compare counts of recorded marriages in 2020 against those from the same period in 2019. There is a dramatic decrease in year-to-date cumulative marriages in 2020 compared with 2019 in each case. Similar patterns are observed for the Seattle metropolitan area when analyzing the cumulative number of marriage applications, a leading indicator of marriages in the near future. Year-to-date declines in marriage are unlikely to be due solely to closure of government agencies that administer marriage certification or reporting delays. Together, these findings suggest that marriage has declined during the COVID-19 outbreak and may continue to do so, at least in the short term.

19.
Biodemography Soc Biol ; 66(3-4): 208-219, 2020.
Article in English | MEDLINE | ID: mdl-34597213

ABSTRACT

Telomere length is often used in studies of adults as a biomarker of cellular aging and an indicator of stress exposure. However, we know little about how telomeres change over time, particularly over the course of the important developmental period of adolescence. We use data on telomere length collected at two points in time spanning adolescence (Years 9 and 15) from the Fragile Families and Child Wellbeing Study to examine longitudinal patterns (n = 1,654) in telomere length. We find a quantitatively small but significant average lengthening in telomere length across adolescence and little evidence of associations between telomere length and pubertal development.


Subject(s)
Cellular Senescence , Telomere , Adolescent , Adult , Biomarkers , Child , Demography , Humans , Telomere/genetics , Telomere Shortening
20.
Women Health ; 60(3): 241-248, 2020 03.
Article in English | MEDLINE | ID: mdl-31284850

ABSTRACT

Emergency contraceptive (EC) pills may be less effective for women with higher body mass index (BMI), but little is known about public response to the fact that EC may lose efficacy as weight increases. In November 2013, European authorities changed the label for a levonorgestrel EC product to warn of a reduction in effectiveness for women with higher BMI, garnering significant media coverage in the United States. Ulipristal acetate (UPA) EC may be more effective than levonorgestrel for women with BMI levels designated as obese. Among 8,019 women who received UPA from the online pharmacy KwikMed from 2011 to 2015 and self-reported their height, weight and reasons for seeking UPA online, we analyzed changes in the proportion of women in different BMI categories before and after the label change. For the 25 month-period after the label change, the proportion of women in the obese category rose by 26.7 percentage points relative to the 35 months before (B = 0.2665, p < .01). Mean BMI (25.5 versus 29.4, p < .001) and average weight (148.6 pounds versus 175.5 pounds, p < .001) of users were higher after the label change. Some women appear to have acted on the information that EC efficacy may be associated with body weight.


Subject(s)
Contraceptives, Postcoital, Hormonal/therapeutic use , Drug Labeling , Levonorgestrel/therapeutic use , Norpregnadienes/therapeutic use , Pharmaceutical Services, Online/statistics & numerical data , Adult , Body Mass Index , Body Weight , Contraception, Postcoital/statistics & numerical data , Female , Humans , Obesity , United States
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