1,466 research outputs found

    Absence of a serum melatonin rhythm under acutely extended darkness in the horse

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    <p>Abstract</p> <p>Background</p> <p>In contrast to studies showing gradual adaptation of melatonin (MT) rhythms to an advanced photoperiod in humans and rodents, we previously demonstrated that equine MT rhythms complete a 6-h light/dark (LD) phase advance on the first post-shift day. This suggested the possibility that melatonin secretion in the horse may be more strongly light-driven as opposed to endogenously rhythmic and light entrained. The present study investigates whether equine melatonin is endogenously rhythmic in extended darkness (DD).</p> <p>Methods</p> <p>Six healthy, young mares were maintained in a lightproof barn under an LD cycle that mimicked the ambient natural photoperiod outside. Blood samples were collected at 2-h intervals for 48 consecutive h: 24-h in LD, followed by 24-h in extended dark (DD). Serum was harvested and stored at -20°C until melatonin and cortisol were measured by commercial RIA kits.</p> <p>Results</p> <p>Two-way repeated measures ANOVA (n = 6/time point) revealed a significant circadian time (CT) x lighting condition interaction (<it>p < .0001</it>) for melatonin with levels non-rhythmic and consistently high during DD (CT 0-24). In contrast, cortisol displayed significant clock-time variation throughout LD and DD (<it>p = .0009</it>) with no CT x light treatment interaction (<it>p </it>= .4018). Cosinor analysis confirmed a significant 24-h temporal variation for melatonin in LD <it>(p = .0002) </it>that was absent in DD <it>(p = .51)</it>, while there was an apparent circadian component in cortisol, which approached significance in LD <it>(p = .076)</it>, and was highly significant in DD <it>(p = .0059).</it></p> <p>Conclusions</p> <p>The present finding of no 24 h oscillation in melatonin in DD is the first evidence indicating that melatonin is not gated by a self-sustained circadian process in the horse. Melatonin is therefore not a suitable marker of circadian phase in this species. In conjunction with recent similar findings in reindeer, it appears that biosynthesis of melatonin in the pineal glands of some ungulates is strongly driven by the environmental light cycle with little input from the circadian oscillator known to reside in the SCN of the mammalian hypothalamus.</p

    in Utero Exposure to antiemetic and Risk of adult-Onset Colorectal Cancer

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    BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (comprising doxylamine, pyridoxine, and dicyclomine), an antiemetic prescribed during pregnancy in the 1960s. METHODS: We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in Oakland, CA, between 1959 and 1966 (n = 14 507 mothers and 18 751 liveborn offspring). We reviewed prescribed medications from mothers\u27 medical records to identify those who received Bendectin during pregnancy. Diagnoses of CRC in adult (aged ≥18 years) offspring were ascertained by linkage with the California Cancer Registry. Cox proportional hazards models were used to estimate adjusted hazard ratios, with follow-up accrued from birth through cancer diagnosis, death, or last contact. RESULTS: Approximately 5% of offspring (n = 1014) were exposed in utero to Bendectin. Risk of CRC was higher in offspring exposed in utero (adjusted hazard ratio = 3.38, 95% confidence interval [CI] = 1.69 to 6.77) compared with unexposed offspring. Incidence rates of CRC were 30.8 (95% CI = 15.9 to 53.7) and 10.1 (95% CI = 7.9 to 12.8) per 100 000 in offspring exposed to Bendectin and unexposed, respectively. CONCLUSIONS: Higher risk of CRC in offspring exposed in utero may be driven by dicyclomine contained in the 3-part formulation of Bendectin used during the 1960s. Experimental studies are needed to clarify these findings and identify mechanisms of risk

    Rapid phase adjustment of melatonin and core body temperature rhythms following a 6-h advance of the light/dark cycle in the horse

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    <p>Abstract</p> <p>Background</p> <p>Rapid displacement across multiple time zones results in a conflict between the new cycle of light and dark and the previously entrained program of the internal circadian clock, a phenomenon known as jet lag. In humans, jet lag is often characterized by malaise, appetite loss, fatigue, disturbed sleep and performance deficit, the consequences of which are of particular concern to athletes hoping to perform optimally at an international destination. As a species renowned for its capacity for athletic performance, the consequences of jet lag are also relevant for the horse. However, the duration and severity of jet lag related circadian disruption is presently unknown in this species. We investigated the rates of re-entrainment of serum melatonin and core body temperature (BT) rhythms following an abrupt 6-h phase advance of the LD cycle in the horse.</p> <p>Methods</p> <p>Six healthy, 2 yr old mares entrained to a 12 h light/12 h dark (LD 12:12) natural photoperiod were housed in a light-proofed barn under a lighting schedule that mimicked the external LD cycle. Following baseline sampling on Day 0, an advance shift of the LD cycle was accomplished by ending the subsequent dark period 6 h early. Blood sampling for serum melatonin analysis and BT readings were taken at 3-h intervals for 24 h on alternate days for 11 days. Disturbances to the subsequent melatonin and BT 24-h rhythms were assessed using repeated measures ANOVA and analysis of Cosine curve fitting parameters.</p> <p>Results</p> <p>We demonstrate that the equine melatonin rhythm re-entrains rapidly to a 6-h phase advance of an LD12:12 photocycle. The phase shift in melatonin was fully complete on the first day of the new schedule and rhythm phase and waveform were stable thereafter. In comparison, the advance in the BT rhythm was achieved by the third day, however BT rhythm waveform, especially its mesor, was altered for many days following the LD shift.</p> <p>Conclusion</p> <p>Aside from the temperature rhythm disruption, rapid resynchronization of the melatonin rhythm suggests that the central circadian pacemaker of the horse may possess a particularly robust entrainment response. The consequences for athletic performance remain unknown.</p

    Spitzer IRAC observations of newly-discovered planetary nebulae from the Macquarie-AAO-Strasbourg H-alpha Planetary Nebula Project

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    We compare H-alpha, radio continuum, and Spitzer Space Telescope (SST) images of 58 planetary nebulae (PNe) recently discovered by the Macquarie-AAO-Strasbo- urg H-alpha PN Project (MASH) of the SuperCOSMOS H-alpha Survey. Using InfraRed Array Camera (IRAC) data we define the IR colors of PNe and demonstrate good isolation between these colors and those of many other types of astronomical object. The only substantive contamination of PNe in the color-color plane we illustrate is due to YSOs. However, this ambiguity is readily resolved by the unique optical characteristics of PNe and their environs. We also examine the relationships between optical and MIR morphologies from 3.6 to 8.0um and explore the ratio of mid-infrared (MIR) to radio nebular fluxes, which is a valuable discriminant between thermal and nonthermal emission. MASH emphasizes late evolutionary stages of PNe compared with previous catalogs, enabling study of the changes in MIR and radio flux that attend the aging process. Spatially integrated MIR energy distributions were constructed for all MASH PNe observed by the GLIMPSE Legacy Project, using the H-alpha morphologies to establish the dimensions for the calculations of the Midcourse Space Experiment (MSX), IRAC, and radio continuum (from the Molonglo Observatory Synthesis Telescope and the Very Large Array) flux densities. The ratio of IRAC 8.0-um to MSX 8.3-um flux densities provides a measure of the absolute diffuse calibration of IRAC at 8.0 um. We independently confirm the aperture correction factor to be applied to IRAC at 8.0um to align it with the diffuse calibration of MSX. The result agrees with the recommendations of the Spitzer Science Center and with results from a parallel study of HII regions. These PNe probe the diffuse calibration of IRAC on a spatial scale of 9-77 arcsec.Comment: 48 pages, LaTeX (aastex), incl. 18 PostScript (eps) figures and 3 tables. Accepted by Astrophysical Journa

    in-Utero Exposure to antibiotics and Risk of Colorectal Cancer in a Prospective Cohort of 18 000 adult offspring

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    BACKGROUND: Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring. METHODS: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers\u27 medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides and long-acting sulfonamides. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2021 by linkage with the California Cancer Registry. Cox proportional models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death or last contact. RESULTS: Of 18 751 liveborn offspring, about 15% (n = 2635) were exposed in utero to antibiotics: 5.4% (n = 1016) to tetracyclines, 4.9% (n = 918) to penicillins, 4.2% (n = 785) to short-acting sulfonamides and 1.5% (n = 273) to long-acting sulfonamides. Compared with offspring not exposed, associations between in-utero exposure and CRC in adult offspring were: aHR 1.03 (95% CI 0.32, 3.31) for tetracyclines; aHR 1.12 (95% CI 0.35, 3.58) for penicillins; aHR 0.83 (95% CI 0.20, 3.42) for short-acting sulfonamides; and aHR 4.40 (95% CI 1.63, 11.88) for long-acting sulfonamides. CONCLUSION: Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood

    Stillbirth after adolescent and Young adult Cancer: a Population-Based Study

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    BACKGROUND: Gonadotoxic effects of cancer treatment may increase risk of adverse birth outcomes in adolescent and young adult (AYA, aged 15-39 years) women diagnosed with cancer. We estimated risk of stillbirth (fetal death of gestational age ≥20 weeks or weighing ≥350 grams) in a population-based sample of AYA women. METHODS: AYA women diagnosed with cancer between January 1, 1995, and December 31, 2015, were identified using the Texas Cancer Registry and linked to live birth and fetal death certificates through December 31, 2016. Among AYA women, cumulative incidence of stillbirth was estimated by gestational age, and Poisson regression models identified factors associated with stillbirth. Standardized fetal mortality ratios (SMR) compared the observed fetal mortality rate in AYA women with the expected fetal mortality rate in the general population. RESULTS: A total of 11 628 live births and 68 stillbirths occurred to 8402 AYA women after diagnosis. Cumulative incidence of stillbirth in AYA women was 0.70% (95% confidence interval [CI] = 0.51% to 0.96%) at 40 weeks of gestation. Risk of stillbirth was higher among Hispanic (risk ratio [RR] = 2.64, 95% CI = 1.29 to 5.41) and non-Hispanic Black (RR = 4.13, 95% CI = 1.68 to 10.16) women compared with non-Hispanic White women; there was no association with receipt of chemotherapy or time since diagnosis. Age- and race and ethnicity-adjusted fetal mortality rate in AYA women was similar to the general population (SMR = 0.99, 95% CI = 0.77 to 1.26). CONCLUSIONS: AYA women may be counseled that overall risk of stillbirth is low, and for most, cancer does not appear to confer additional risk

    Adverse Birth Outcomes of adolescent and Young adult Women Diagnosed With Cancer During Pregnancy

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    BACKGROUND: We examined adverse birth outcomes among adolescent and young adult women diagnosed with cancer (AYA women, ages 15-39 years) during pregnancy. METHODS: We linked data from the Texas Cancer Registry, vital records, and Texas Birth Defects Registry to identify all singleton births to AYA women diagnosed during pregnancy from January 1999 to December 2016. We compared prevalence of adverse live birth outcomes between AYA women and women without cancer (matched 1:4 on age, race and ethnicity, and year). Among AYA women, we used log-binomial regression to identify factors associated with these outcomes. Statistical tests were 2-sided. RESULTS: AYA women had 1271 singleton live births and 20 stillbirths. AYA women (n = 1291) were 33.3% Hispanic and 9.8% non-Hispanic Black and most commonly had breast (22.5%), thyroid (19.8%), and gynecologic (13.3%) cancers. Among live births, AYA women had a higher prevalence of low birth weight offspring (30.1% vs 9.0%), very preterm (5.7% vs 1.2%), and preterm birth (25.1% vs 7.2%); cesarean delivery (44.3% vs 35.2%); and low Apgar score (2.7% vs 1.5%), compared with women without cancer (n = 5084) (all P \u3c .05). Prevalence of any birth defect by age 12 months did not statistically differ (5.2% vs 4.7%; P = .48), but live births to AYA women more often had heart and circulatory system defects (2.2% vs 1.3%; P = .01). In adjusted models, cancer type and chemotherapy were associated with adverse live birth outcomes. CONCLUSIONS: AYA women diagnosed during pregnancy have higher prevalence of adverse birth outcomes and face difficult decisions in balancing treatment risks and benefits

    Characterization of the equine skeletal muscle transcriptome identifies novel functional responses to exercise training

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    <p>Abstract</p> <p>Background</p> <p>Digital gene expression profiling was used to characterize the assembly of genes expressed in equine skeletal muscle and to identify the subset of genes that were differentially expressed following a ten-month period of exercise training. The study cohort comprised seven Thoroughbred racehorses from a single training yard. Skeletal muscle biopsies were collected at rest from the <it>gluteus medius </it>at two time points: T<sub>1 </sub>- untrained, (9 ± 0.5 months old) and T<sub>2 </sub>- trained (20 ± 0.7 months old).</p> <p>Results</p> <p>The most abundant mRNA transcripts in the muscle transcriptome were those involved in muscle contraction, aerobic respiration and mitochondrial function. A previously unreported over-representation of genes related to RNA processing, the stress response and proteolysis was observed. Following training 92 tags were differentially expressed of which 74 were annotated. Sixteen genes showed increased expression, including the mitochondrial genes <it>ACADVL</it>, <it>MRPS21 </it>and <it>SLC25A29 </it>encoded by the nuclear genome. Among the 58 genes with decreased expression, <it>MSTN</it>, a negative regulator of muscle growth, had the greatest decrease.</p> <p>Functional analysis of all expressed genes using FatiScan revealed an asymmetric distribution of 482 Gene Ontology (GO) groups and 18 KEGG pathways. Functional groups displaying highly significant (<it>P </it>< 0.0001) increased expression included mitochondrion, oxidative phosphorylation and fatty acid metabolism while functional groups with decreased expression were mainly associated with structural genes and included the sarcoplasm, laminin complex and cytoskeleton.</p> <p>Conclusion</p> <p>Exercise training in Thoroughbred racehorses results in coordinate changes in the gene expression of functional groups of genes related to metabolism, oxidative phosphorylation and muscle structure.</p

    Two-level system with a thermally fluctuating transfer matrix element: Application to the problem of DNA charge transfer

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    Charge transfer along the base-pair stack in DNA is modeled in terms of thermally-assisted tunneling between adjacent base pairs. Central to our approach is the notion that tunneling between fluctuating pairs is rate-limited by the requirement of their optimal alignment. We focus on this aspect of the process by modeling two adjacent base pairs in terms of a classical damped oscillator subject to thermal fluctuations as described by a Fokker-Planck equation. We find that the process is characterized by two time scales, a result that is in accord with experimental findings.Comment: original file is revtex4, 10 pages, three eps figure
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