Research gaps and future needs for allergen prediction in food safety.

The allergenicity and protein risk assessments in food safety are facing new challenges. Demands for healthier and more sustainable food systems have led to significant advances in biotechnology, the development of more complex foods, and the search for alternative protein sources. All this has increased the pressure on the safety assessment prediction approaches anchored into requirements defined in the late 90's. In 2022, the EFSA's Panel on Genetically Modified Organisms published a scientific opinion focusing on the developments needed for allergenicity and protein safety assessments of new products derived from biotechnology. Here, we further elaborate on the main elements described in this scientific opinion and prioritize those development needs requiring critical attention. The starting point of any new recommendation would require a focus on clinical relevance and the development of a fit-for-purpose database targeted for specific risk assessment goals. Furthermore, it is imperative to review and clarify the main purpose of the allergenicity risk assessment. An internationally agreed consensus on the overall purpose of allergenicity risk assessment will accelerate the development of fit-for-purpose methodologies, where the role of exposure should be better clarified. Considering the experience gained over the last 25 years and recent scientific developments in the fields of biotechnology, allergy, and risk assessment, it is time to revise and improve the allergenicity safety assessment to ensure the reliability of allergenicity assessments for food of the future.

Western Australian adolescent emotional wellbeing during the COVID-19 pandemic in 2020.

BACKGROUND: The impacts of the COVID-19 pandemic have been vast and are not limited to physical health. Many adolescents have experienced disruptions to daily life, including changes in their school routine and family's financial or emotional security, potentially impacting their emotional wellbeing. In low COVID-19 prevalence settings, the impact of isolation has been mitigated for most young people through continued face-to-face schooling, yet there may still be significant impacts on their wellbeing that could be attributed to the pandemic. METHODS: We report on data from 32,849 surveys from Year 7-12 students in 40 schools over two 2020 survey cycles (June/July: 19,240; October: 13,609), drawn from a study of 79 primary and secondary schools across Western Australia, Australia. The Child Health Utility Index (CHU9D) was used to measure difficulties and distress in responding secondary school students only. Using comparable Australian data collected six years prior to the pandemic, the CHU9D was calibrated against the Kessler-10 to establish a reliable threshold for CHU9D-rated distress. RESULTS: Compared to 14% of responding 12-18-year-olds in 2013/2014, in both 2020 survey cycles almost 40% of secondary students returned a CHU9D score above a threshold indicative of elevated difficulties and distress. Student distress increased significantly between June and October 2020. Female students, those in older Grades, those with few friendships or perceived poor quality friendships, and those with poor connectedness to school were more likely to score above the threshold. CONCLUSIONS: In a large dataset collected during the first year of the COVID-19 pandemic, the proportion of secondary school students with scores indicative of difficulties and distress was substantially higher than a 2013/2014 benchmark, and distress increased as the pandemic progressed, despite the low local prevalence of COVID-19. This may indicate a general decline in social and emotional wellbeing exacerbated by the events of the pandemic. TRIAL REGISTRATION: ANZCTRN (ACTRN12620000922976). Retrospectively registered 17/08/2020. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380429&isReview=true .

Fiscal federalism vs fiscal decentralization in healthcare: a conceptual framework.

INTRODUCTION: Fiscal federalism and fiscal decentralization are distinct policy options in public services in general and healthcare in particular, with possibly opposed effects on equity, effectiveness, and efficiency. However, the pertinent discourse often reflects confusion between the concepts or conflation thereof. METHODS: This paper performs a narrative review of theoretical literature on decentralization. The study offers clear definitions of the concepts of fiscal federalism and fiscal decentralization and provides an overview of the potential implications of each policy for healthcare systems. RESULTS: The interpretation of the literature identified three different dimensions of decentralization: political, administrative, economic. Economic decentralization can be further implemented through two different policy options: fiscal federalism and fiscal decentralization. Fiscal federalism is the transfer of spending authority of a centrally pooled public health budget to local governments or authorities. Countries like the UK, Cuba, Denmark, and Brazil mostly rely on fiscal federalism mechanisms for healthcare financing. Fiscal decentralization consists of transferring both pooling and spending responsibilities from the central government to local authorities. Contrarily to fiscal federalism, the implementation of fiscal decentralization requires as a precondition the fragmentation of the national pool into many local pools. The restructuring of the pooling system may limit the cross-subsidization effect between high- and low-income groups and areas that a central pool guarantees; thus, severely affecting local equality and equity. With the limited availability of local public resources in poorer regions, the quality of services drops, increasing the disparity gap between areas. Evidence from Italy, Spain, China, and Ivory Coast -countries with a strong fiscal decentralization element in their healthcare services- suggests that fiscal decentralization has positive effects on the infant mortality rate. However, it decreases healthcare resources as well as access to services, fostering spatial inequities. CONCLUSION: If public resources are and remain adequate, allocation follows equitable criteria, and local communities are involved in the decision-making debate, fiscal federalism -rather than fiscal decentralization- appear to be an adequate policy option to improve the healthcare services and population's health nationwide and achieve health sector economic decentralization. HIPPOKRATIA 2020, 24(3): 107-113.

Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer.

Background: Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to the first-line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Patients and methods: Eighty-three patients on the first-line AI therapy for metastatic breast cancer were enrolled in a prospective study. Plasma samples were collected every 3 months to disease progression and ctDNA analysed by digital droplet PCR and enhanced tagged-amplicon sequencing (eTAm-Seq). Mutations identified in progression samples by sequencing were tracked back through samples before progression to study the evolution of mutations on therapy. The frequency of novel mutations was validated in an independent cohort of available baseline plasma samples in the Study of Faslodex versus Exemestane with or without Arimidex (SoFEA) trial, which enrolled patients with prior sensitivity to AI. Results: Of the 39 patients who progressed on the first-line AI, 56.4% (22/39) had ESR1 mutations detectable at progression, which were polyclonal in 40.9% (9/22) patients. In serial tracking, ESR1 mutations were detectable median 6.7 months (95% confidence interval 3.7-NA) before clinical progression. Utilising eTAm-Seq ctDNA sequencing of progression plasma, ESR1 mutations were demonstrated to be sub-clonal in 72.2% (13/18) patients. Mutations in RAS genes were identified in 15.4% (6/39) of progressing patients (4 KRAS, 1 HRAS, 1 NRAS). In SoFEA, KRAS mutations were detected in 21.2% (24/113) patients although there was no evidence that KRAS mutation status was prognostic for progression free or overall survival. Conclusions: Cancers progressing on the first-line AI show high levels of genetic heterogeneity, with frequent sub-clonal mutations. Sub-clonal KRAS mutations are found at high frequency. The genetic diversity of AI resistant cancers may limit subsequent targeted therapy approaches.

Biocompatibility and immunogenicity of elastin-like recombinamer biomaterials in mouse models.

Novel thermo-sensitive elastin-like recombinamers (ELRs) containing bioactive molecules were created for use as a biomimetic biomaterial for tissue regeneration. For effective use for in vivo applications, it is essential to ensure that they do not induce adverse inflammatory, immune, or allergic responses that inhibit tissue repair. Therefore, we sought to establish a pre-clinical approach to evaluate biocompatibility in experimental mice using ELRs as a prototype biomaterial. First, we measured in vitro proliferation and cytokine production from BALB/c and C57BL/6 mouse splenocytes incubated with ELRs. Second, we used a rapid, high throughput in vivo approach in which inflammatory cells and cytokines were measured following an intraperitoneal implantation. Lastly, a subchronic in vivo approach was used in which ELRs or positive controls were subcutaneously implanted and the implantation sites were assessed for inflammation and gene expression. We found that ELRs induced mild inflammation and minimal fibrosis compared to the intense response to Vitoss. Additionally, implantation increased antigen-specific antibody titers for both groups and gene expression profiling of the implantation sites revealed the upregulation of inflammation, fibrosis, and wound healing-related genes in ELR and positive control-implanted mice compared to sham controls. These data demonstrate that ELRs appear safe for use in tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 924-934, 2018.

Diagnosis of Lobesia botrana (Lepidoptera: Tortricidae) Using Real-Time PCR.

A real-time PCR assay is reported for identification of Lobesia botrana (Denis and Schiffermüller) collected in California. This assay multiplexes two independent TaqMan probe systems in a single reaction tube to reduce handling time and sample exposure to environmental contaminants. One probe system targets a segment of DNA located in the internal transcribed spacer region 2 (ITS2) that is present in the L. botrana genome but absent in native North American Tortricidae. The second probe system serves as a control for DNA quality by targeting a segment of the 18S rDNA gene that is conserved in L. botrana and all of the tested nontarget species. The assay successfully diagnosed 70 Lobesia botrana specimens and 95 nontarget specimens. No false-positive or false-negative results were observed supporting its application for identification of this pest in California.

Origin of the hungry caterpillar: Evolution of fasting in slug moths (Insecta: Lepidoptera: Limacodidae).

Studies of caterpillar defense strategy evolution typically focus on aposematic coloration, gregarious behavior, and/or chemical defense. In the slug moth family Limacodidae, the evolution of chemical defense is coupled to the life history trait of first instar feeding behaviors. In nettle caterpillars, the first instars fast and molt into a second instar that feeds. In contrast, gelatines and monkey slug larval forms feed in the first instar. This study focused on whether the evolution of fasting associated with the nettle morphology was a derived trait of single or multiple origins. Twenty-nine species of Limacodidae (including one Chrysopolominae) representing 27 genera and four outgroup species with known first and final instar morphologies and behaviors were included. Four out-group species representing Megalopygidae (1 sp), Dalceridae (1 sp) and Aididae (2 sp) were included. These were sequenced for three molecular markers for a total of 4073 bp, mitochondrial COI (∼1500 bp), 18S (∼1900 bp) and the D2 region of 28S (approximately 670 bp). Maximum likelihood and Bayesian analyses were conducted. The resulting phylogeny and comparative analysis of feeding strategy revealed that the nettle caterpillar morphology and behavior of larval fasting may have a single origin.

Appearance of cholinergic myenteric neurons during enteric nervous system development: comparison of different ChAT fluorescent mouse reporter lines.

BACKGROUND: Cholinergic neurons have been identified with the acetylcholine synthetic enzyme choline acetyltransferase (ChAT). However, ChAT is difficult to localize in newly differentiated peripheral neurons making the study of cholinergic neuronal development problematic. Consequently, researchers have used mouse reporter lines to indicate the presence of ChAT. METHODS: Our objective was to determine which ChAT reporter line was the most sensitive indicator of ChAT expression. We utilized two different fluorescent ChAT reporter lines (ChAT-GFP and ChAT-Cre;R26R:floxSTOP:tdTomato) together with immunolocalization of ChAT protein (ChAT-IR) to characterize the spatial and temporal expression of ChAT in myenteric neurons throughout enteric nervous system (ENS) development. KEY RESULTS: ChAT-IR cells were first seen in the intestine at E10.5, even within the migration wavefront of neural precursors. Myenteric neurons within the distal small intestine (dSI) and proximal colon were first labeled by ChAT-IR, then ChAT-GFP, and finally ChAT-Cre tdTomato. The percentage of ChAT-IR neurons is equivalent to adult levels in the dSI by E13.5 and proximal colon by P0. After these stages, the percentages remained relatively constant throughout development despite dramatic changes in neuronal density. CONCLUSIONS & INFERENCES: These observations indicate that neurotransmitter expression occurs early and there is only a brief gap between neurogenesis and neurotransmitter expression. Our finding that the proportion of ChAT myenteric neurons reached adult levels during embryonic development suggests that the fate of cholinergic neurons is tightly regulated and that their differentiation might influence further neuronal development. ChAT-GFP is a more accurate indicator of early ENS cholinergic neuronal differentiation than the ChAT-Cre;R26R:floxSTOP:tdTomato reporter mouse.

General and substance-specific predictors of young adult nicotine dependence, alcohol use disorder, and problem behavior: replication in two samples.

BACKGROUND: This paper presents two replications of a heuristic model for measuring environment in studies of gene-environment interplay in the etiology of young adult problem behaviors. METHODS: Data were drawn from two longitudinal, U.S. studies of the etiology of substance use and related behaviors: the Raising Healthy Children study (RHC; N=1040, 47% female) and the Minnesota Twin Family Study (MTFS; N=1512, 50% female). RHC included a Pacific Northwest, school-based, community sample. MTFS included twins identified from state birth records in Minnesota. Both studies included commensurate measures of general family environment and family substance-specific environments in adolescence (RHC ages 10-18; MTFS age 18), as well as young adult nicotine dependence, alcohol and illicit drug use disorders, HIV sexual risk behavior, and antisocial behavior (RHC ages 24, 25; MTFS age 25). RESULTS: Results from the two samples were highly consistent and largely supported the heuristic model proposed by Bailey et al. (2011). Adolescent general family environment, family smoking environment, and family drinking environment predicted shared variance in problem behaviors in young adulthood. Family smoking environment predicted unique variance in young adult nicotine dependence. Family drinking environment did not appear to predict unique variance in young adult alcohol use disorder. CONCLUSIONS: Organizing environmental predictors and outcomes into general and substance-specific measures provides a useful way forward in modeling complex environments and phenotypes. Results suggest that programs aimed at preventing young adult problem behaviors should target general family environment and family smoking and drinking environments in adolescence.

Lack of sigma-1 receptor exacerbates ALS progression in mice.

The function of the sigma-1 receptor (S1R) has been implicated in modulating the activity of various ion channels. In the CNS S1R is enriched in cholinergic postsynaptic densities in spinal cord motoneurons (MNs). Mutations in S1R have been found in familial cases of amyotrophic lateral sclerosis (ALS). In this study we show that a knockout of S1R in the SOD1*G93A mouse model of ALS significantly reduces longevity (end stage). Electrophysiological experiments demonstrate that MN of mice lacking S1R exhibit increased excitability. Taken together the data suggest the S1R acts as a brake on excitability, an effect that might enhance longevity in an ALS mouse model.

Altered neuronal density and neurotransmitter expression in the ganglionated region of Ednrb null mice: implications for Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HSCR) is a congenital condition in which enteric ganglia, formed from neural crest cells (NCC), are absent from the terminal bowel. Dysmotility and constipation are common features of HSCR that persist following surgical intervention. This persistence suggests that the portion of the colon that remains postoperatively is not able to support normal bowel function. To elucidate the defects that underlie this condition, we utilized a murine model of HSCR. METHODS: Mice with NCC-specific deletion of Ednrb were used to measure the neuronal density and neurotransmitter expression in ganglia. KEY RESULTS: At the site located proximal to the aganglionic region of P21 Ednrb null mice, the neuronal density is significantly decreased and the expression of neurotransmitters is altered compared with het animals. The ganglia in this colonic region are smaller and more isolated while the size of neuronal cell bodies is increased. The percentage of neurons expressing neuronal nNOS and VIP is significantly increased in Ednrb nulls. Conversely, the percentage of choline acetyltransferase (ChAT) expressing neurons is decreased, while Substance P is unchanged between the two genotypes. These changes are limited to the colon and are not detected in the ileum. CONCLUSIONS & INFERENCES: We demonstrate changes in neuronal density and alterations in the balance of expression of neurotransmitters in the colon proximal to the aganglionic region in Ednrb null mice. The reduced neuronal density and complementary changes in nNOS and ChAT expression may account for the dysmotility seen in HSCR.

Household fuels, low birth weight, and neonatal death in India: the separate impacts of biomass, kerosene, and coal.

We examined the impact of maternal use of different household cooking fuels in India on low birth weight (LBW<2500g), and neonatal mortality (death within 28 days of birth). Using cross-sectional data from India's National Family Health Survey (NFHS-3), we separately analyzed the prevalence of these two outcomes in households utilizing three types of high-pollution fuels for cooking - biomass, coal, and kerosene - using low-pollution fuels (gas and biogas) as the comparison "control" group. Taking socioeconomic and child-specific factors into account, we employed logistic regression to examine the impact of fuel use on fetal and infant health. The results indicate that household use of high-pollution fuels is significantly associated with increased odds of LBW and neonatal death. Compared to households using cleaner fuels (in which the mean birth weight is 2901g), the primary use of coal, kerosene, and biomass fuels is associated with significant decreases in mean birth weight (of -110g for coal, -107g for kerosene, and -78g for biomass). Kerosene and biomass fuel use are also associated with increased risk of LBW (p<0.05). Results suggest that increased risk of neonatal death is strongly associated with household use of coal (OR 18.54; 95% CI: 6.31-54.45), and perhaps with kerosene (OR 2.30; 95% CI: 0.95-5.55). Biomass is associated with increased risk of neonatal death among infants born to women with no more than primary education (OR 7.56; 95% CI: 2.40-23.80). These results are consistent with a growing literature showing health impacts of household air pollution from these fuels.

Expectancy-related modulations of neural oscillations in continuous performance tasks.

Analysis of neural oscillations in the electroencephalogram (EEG) during cognitive tasks provides valuable information about underlying neuronal processing not accessible by other methods such as event-related potentials (ERPs) and the BOLD signal in fMRI. We investigated neural substrates of motor preparation and expectancy by analyzing neural oscillations of healthy subjects performing the AX continuous performance task (AX-CPT), a task widely used to evaluate processes such as cognitive control, motor preparation and anticipatory and sustained attention. The task consists of letters presented sequentially on a monitor, and subjects are required to respond only when they see the letter A (cue) followed by the letter X (target). In this study, to emphasize expectation and motor preparation, three versions of AX-CPT were used in which the overall propensity to respond was differentially modulated, by changing the probability of the letter sequences. Neural activity was investigated in three time windows following presentation of the cue: sensory, evaluation and preparation. Alpha power was reduced following cue onset similarly in all versions of the task in both the sensory and evaluation periods, but in the later preparation period there were task dependent modulations. Alpha was decreased when an infrequent cue increased the chance of a response, and increased when a propensity to respond had to be overcome, possibly reflecting an anticipatory attentional mechanism to gate visuo-motor processing. Beta power was modulated by task and cue in both evaluation and preparation periods. In the latter, beta power reflected the propensity to respond and correlated both with amplitude of the contingent negative variation (CNV), an ERP that reflects response preparation, and with reaction time. Some clinical populations such as patients with schizophrenia or attention-deficit disorder show specific deficits when performing the AX-CPT. These results provide a basis for investigating the differential neural underpinnings of oscillatory cognitive control deficits observed in various patient populations.

Selection against small males in utero: a test of the Wells hypothesis.

BACKGROUND: The argument that women in stressful environments spontaneously abort their least fit fetuses enjoys wide dissemination despite the fact that several of its most intuitive predictions remain untested. The literature includes no tests, for example, of the hypothesis that these mechanisms select against small for gestational age (SGA) males. METHODS: We apply time-series modeling to 4.9 million California male term births to test the hypothesis that the rate of SGA infants in 1096 weekly birth cohorts varies inversely with labor market contraction, a known stressor of contemporary populations. RESULTS: We find support for the hypothesis that small size becomes less frequent among term male infants when the labor market contracts. CONCLUSIONS: Our findings contribute to the evidence supporting selection in utero. They also suggest that research into the association between maternal stress and adverse birth outcomes should acknowledge the possibility that fetal loss may affect findings and their interpretation. Strengths of our analyses include the large number and size of our birth cohorts and our control for autocorrelation. Weaknesses include that we, like nearly all researchers in the field, have no direct measure of fetal loss.

Development of the sigma-1 receptor in C-terminals of motoneurons and colocalization with the N,N'-dimethyltryptamine forming enzyme, indole-N-methyl transferase.

The function of the sigma-1 receptor (S1R) has been linked to modulating the activities of ion channels and G-protein-coupled receptors (GPCR). In the CNS, the S1R is expressed ubiquitously but is enriched in mouse motoneurons (MN), where it is localized to subsurface cisternae of cholinergic postsynaptic densities, also known as C-terminals. We found that S1R is enriched in mouse spinal MN at late stages of embryonic development when it is first visualized in the endoplasmic reticulum. S1Rs appear to concentrate at C-terminals of mouse MN only on the second week of postnatal development. We found that indole-N-methyl transferase (INMT), an enzyme that converts tryptamine into the sigma-1 ligand dimethyltryptamine (DMT), is also localized to postsynaptic sites of C-terminals in close proximity to the S1R. This close association of INMT and S1Rs suggest that DMT is synthesized locally to effectively activate S1R in MN.

Association of a polymorphism in the indoleamine- 2,3-dioxygenase gene and interferon-α-induced depression in patients with chronic hepatitis C.

Interferon (IFN)-α treatment for infectious diseases and cancer is associated with significant depressive symptoms that can limit therapeutic efficacy. Multiple mechanisms have been implicated in IFN-α-induced depression including immune, neuroendocrine and neurotransmitter pathways. To further explore mechanisms of IFN-α-induced depression and establish associated genetic risk factors, single nucleotide polymorphisms in genes encoding proteins previously implicated in IFN-α-induced depression were explored in two self-reported ethnic groups, Caucasians (n=800) and African Americans (n=232), participating in a clinical trial on the impact of three pegylated IFN-α treatment regimens on sustained viral response in patients with chronic hepatitis C. Before treatment, all subjects were free of psychotropic medications and had a score ≤20 on the Center for Epidemiologic Studies Depression Scale (CES-D), which was used to assess depressive symptom severity throughout the study. In Caucasians, a polymorphism (rs9657182) in the promoter region of the gene encoding indoleamine-2,3-dioxygenase (IDO1) was found to be associated with moderate or severe IFN-α-induced depressive symptoms (CES-D>20) at 12 weeks of IFN-α treatment (P=0.0012, P<0.05 corrected). Similar results were obtained for treatment weeks 24, 36 and 48. In subjects homozygous for the risk allele (CC, n=150), the odds ratio for developing moderate or severe depressive symptoms at treatment week 12 was 2.91 (confidence interval: 1.48-5.73) compared with TT homozygotes (n=270). rs9657182 did not predict depression in African Americans, who exhibited a markedly lower frequency of the risk allele at this locus. The findings in Caucasians further support the notion that IDO has an important role in cytokine-induced behavioral changes.

A multiplex real-time polymerase chain reaction assay to diagnose Epiphyas postvittana (Lepidoptera: Tortricidae).

A molecular assay for diagnosis of light brown apple moth, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae), in North America is reported. The assay multiplexes two TaqMan real-time polymerase chain reaction (RT-PCR) probe systems that are designed to target DNA segments of the internal transcribed spacer region 2 (ITS2) and 18S rRNA gene. The RT-PCR probe designed for the 18S target recognizes a DNA sequence conserved in all of the moths included in the study and functions as a control in the assay. The second probe recognizes a segment of the ITS2 specifically found in E. postvittana and not found in the other moths included in the study, i.e., this segment is not conserved. Inclusion of the two markers in a single multiplex reaction did not affect assay performance. The assay was tested against 637 moths representing > 90 taxa in 15 tribes in all three subfamilies in the Tortricidae. The assay generated no false negatives based on analysis of 355 E. postvittana collected from California, Hawaii, England, New Zealand, and Australia. Analysis of a data set including 282 moths representing 41 genera generated no false positives. Only three inconclusive results were generated from the 637 samples. Spike experiments demonstrated that DNA contamination in the assay can affect samples differently. Contaminated samples analyzed with the ITS2 RT-PCR assay and DNA barcode methodology by using the cytochrome oxidase I gene can generate contradictory diagnoses.

If I were a rich man could I sell a pancreas? A study in the locus of oppression.

Dan Brock argues that since the unexploitable rich could sell their kidneys too, exploitation could not be an essential feature of organ vending. This paper takes his claim as the point of departure for a discussion on the locus of organ vending-associated oppression. While it accepts Brock's conclusion, it explores the possibility that such oppression is invariably found rather outside the sphere of exchange. It then analyses the implications of this possibility for the discourse surrounding the ethics of organ vending.

Probing the high momentum component of the deuteron at high Q2.

The (2)H(e,e'p)n cross section at a momentum transfer of 3.5 (GeV/c)(2) was measured over a kinematical range that made it possible to study this reaction for a set of fixed missing momenta as a function of the neutron recoil angle θ(nq) and to extract missing momentum distributions for fixed values of θ(nq) up to 0.55 GeV/c. In the region of 35°≤θ(nq)≤45° recent calculations, which predict that final-state interactions are small, agree reasonably well with the experimental data. Therefore, these experimental reduced cross sections provide direct access to the high momentum component of the deuteron momentum distribution in exclusive deuteron electrodisintegration.

Associations of progesterone receptor polymorphisms with age at menarche and menstrual cycle length.

BACKGROUND: Age at menarche and menstrual cycle characteristics are indicators of endocrine function and may be risk factors for diseases such as reproductive cancers. The progesterone receptor gene (PGR) has been identified as a candidate gene for age at menarche and menstrual function. METHODS: Women office workers ages 19-41 self-reported age at menarche and participated in a prospective study of menstrual function and fertility. First-morning urine was used as the DNA source. 444 women were genotyped for a functional variant in PGR, rs1042838 (Val660Leu), and 264 women were also genotyped for 29 other SNPs across the extended gene region. RESULTS: Genetic variation across PGR was associated with age at menarche using a global score statistic (p = 0.03 among non-Hispanic whites). Women carrying two copies of the Val660Leu variant experienced menarche 1 year later than women carrying one or no copies of the variant (13.6 ± 0.5 vs. 12.6 ± 0.1; p = 0.03). The Val660Leu variant was also associated with decreased odds of short menstrual cycles (17-24 days) (OR, 95% CI: 0.54 [0.36, 0.80]; p = 0.002). CONCLUSION: Genetic variation in PGR was associated with age at menarche and menstrual cycle length in this population. Further investigation of these associations in a replication dataset is warranted.