Influence of sodium valproate on medium-late luteal phase pulsatile LH secretion in normal women.

PubMed

Lado Abeal, J; Rey Losada, C; Cabezas Agricola, J M; Cabezas-Cerrato, J

1994-01-01

It is not known whether gamma-aminobutyric acid (GABA) is involved in control of pulsatile LH secretion in human beings. Previous work by our group has shown that manipulation of the GABAergic system with sodium valproate does not affect pulsatile LH secretion in normal women in the late follicular phase. However, it has been suggested that steroid levels are critical for the influence of GABA upon hormone secretion; in particular, progesterone has been said to enhance inhibition by GABA. In this work we studied the effect of sodium valproate on pulsatile LH secretion in medium-late luteal phase of normal women. Six normal young women were studied over an 8-hour period in two successive menstrual cycles. On each occasion blood samples were taken every 10 minutes between 1000 and 1800 h. We administered 400 mg of sodium valproate every 8 hours on the 7 days preceding their second cycle and additional 400 mg at 0900 and 1400 h on the day of the study. Ovulation day was estimated by means of serial ovarian ultrasound examinations and confirmed by serum progesterone concentrations. In each cycle, LH, oestradiol and progesterone were determined by radioimmunoassay and sodium valproate by repolarization fluorescence spectrophotometry. The series of LH levels was smoothed for 1-minute sampling periods by means of a spline function and analysed by means of a program developed in our laboratory and written in Fortran 77. The program deconvolved the signal and calculated the pulse area, pulse duration, interpulse interval and number of pulses. LH pulse identification on the deconvolved signals was performed using our own method based on Friedman's non-parametric statistic. The statistical significance of differences between parameters was estimated using the Mann-Whitney test and Wilcoxon signed rank test. There were no significant differences in LH pulse area, pulse duration, interpulse interval or number of pulses with the administration of sodium valproate. Activation of the GABAergic system with sodium valproate had no biologically significant effect on the mid-late luteal phase pulsatile LH secretion in normal women.

Atm heterozygous mice are more sensitive to radiation-induced cataracts than are their wild-type counterparts

PubMed Central

Worgul, Basil V.; Smilenov, Lubomir; Brenner, David J.; Junk, Anna; Zhou, Wei; Hall, Eric J.

2002-01-01

It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM+/−) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM+/− cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage. PMID:12119422

[The Effects of Neurofeedback Training on Physical, Psychoemotional Stress Response and Self-Regulation for Late Adolescence: A Non-Randomized Trial].

PubMed

Choi, Moon Ji; Park, Wan Ju

2018-04-01

The aim of this study was to analyze the effects of neurofeedback training for reducing stress and enhancing self-regulation in late adolescence to identify the possibility of use for nursing intervention. A nonequivalent control group pre-post quasi-experimental design was used. Participants were 78 late adolescents assigned to the experimental group (n=39) that received the neurofeedback training and the control group (n=39). Data were collected on heart rate variability (HRV) and skin conductance level (SCL) to assess stress-biomarker response. The questionnaire contained 164 items from: Positive and Negative Affect Schedule (PANAS), Symptom Checklist-90-Revised (SCL-90-R) and Self-regulatory Ability scale. The neurofeedback training was based on the general adaptation syndrome and body-mind medicine. The intervention was conducted in a total of 10 sessions for 30 minutes per session with high-beta, theta and sensory motor rhythm training on scalp at central zero. There were significant difference in standard deviation of normal to normal interval (p=.036) in HRV and SCL (p=.029) of stress-biomarker response between the two groups. Negative affect (p=.036) in PANAS and obsessive compulsive (p=.023) and depression (p<.001) in SCL-90-R were statistically significant. Self-regulation mode (p=.004) in self-regulation ability scale showed a significant difference between the two groups. The results indicated that the neurofeedback training is effective in stress-biomarkers, psychoemotional stress response and self-regulation. Therefore, neurofeedback training using neuroscientific approach based on brain-mind-body model can be used as an effective nursing intervention for late adolescents in clinics and communities for effective stress responses. © 2018 Korean Society of Nursing Science.

Continuous glucose profiles in obese and normal-weight pregnant women on a controlled diet: metabolic determinants of fetal growth.

PubMed

Harmon, Kristin A; Gerard, Lori; Jensen, Dalan R; Kealey, Elizabeth H; Hernandez, Teri L; Reece, Melanie S; Barbour, Linda A; Bessesen, Daniel H

2011-10-01

We sought to define 24-h glycemia in normal-weight and obese pregnant women using continuous glucose monitoring (CGM) while they consumed a habitual and controlled diet both early and late in pregnancy. Glycemia was prospectively measured in early (15.7 ± 2.0 weeks' gestation) and late (27.7 ± 1.7 weeks' gestation) pregnancy in normal-weight (n = 22) and obese (n = 16) pregnant women on an ad libitum and controlled diet. Fasting glucose, triglycerides (early pregnancy only), nonesterified fatty acids (FFAs), and insulin also were measured. The 24-h glucose area under the curve was higher in obese women than in normal-weight women both early and late in pregnancy despite controlled diets. Nearly all fasting and postprandial glycemic parameters were higher in the obese women later in pregnancy, as were fasting insulin, triglycerides, and FFAs. Infants born to obese mothers had greater adiposity. Maternal BMI (r = 0.54, P = 0.01), late average daytime glucose (r = 0.48, P < 0.05), and late fasting insulin (r = 0.49, P < 0.05) correlated with infant percentage body fat. However, early fasting triglycerides (r = 0.67, P < 0.001) and late fasting FFAs (r = 0.54, P < 0.01) were even stronger correlates. This is the first study to demonstrate that obese women without diabetes have higher daytime and nocturnal glucose profiles than normal-weight women despite a controlled diet both early and late in gestation. Body fat in infants, not birth weight, was related to maternal BMI, glucose, insulin, and FFAs, but triglycerides were the strongest predictor. These metabolic findings may explain higher rates of infant macrosomia in obese women, which might be targeted in trials to prevent excess fetal growth.

Late Miocene extensional systems in northern Tunisia and their relation with SE directed delamination of the African subcontinental mantle lithosphere

NASA Astrophysics Data System (ADS)

Booth-Rea, Guillermo; Gaidi, Seif; Melki, Fetheddine; Pérez-Peña, Vicente; Marzougui, Wissem; Azañón, Jose Miguel; Galve, Jorge Pedro

2017-04-01

Recent work has proposed the delamination of the subcontinental mantle lithosphere under northern Tunisia during the late Miocene. This process is required to explain the present location of the Tunisian segment of the African slab, imaged by seismic tomography, hanging under the Gulf of Gabes to the south of Tunisia. Thus, having retreated towards the SE several hundred km from its original position under the Tellian-Atlas nappe contact that crops out along the north of Tunisia. However, no tectonic structures have been described which could be related to this mechanism of lithospheric mantle peeling. Here we describe for the first time extensional fault systems in northern Tunisia that strongly thinned the Tellian nappes, exhuming rocks from the Tunisian Atlas in the core of folded extensional detachments. Two normal fault systems with sub-orthogonal extensional transport occur. These were active during the late Miocene associated to the extrusion of 13 Ma granodiorite and 9 Ma rhyodacite in the footwall of the Nefza detachment. We have differentiated an extensional system formed by low-angle normal faults with NE- and SW-directed transport cutting through the Early to Middle Miocene Tellian nappen stack and a later system of low and high-angle normal faults that cuts down into the underlying Tunisian Atlas units with SE-directed transport, which root in the Nefza detachment. Both normal fault systems have been later folded and cut by thrusts during Plio-Quaternary NW-SE directed compression. These findings change the interpretation of the tectonic evolution of Tunisia that has always been framed in a transpressive to compressive setting, manifesting the extensional effects of Late Miocene lithospheric mantle delamination under northern Tunisia.

[Application of the life table method to the estimation of late complications of normal tissues after radiotherapy].

PubMed

Morita, K; Uchiyama, Y; Tominaga, S

1987-06-01

In order to evaluate the treatment results of radiotherapy it is important to estimate the degree of complications of the surrounding normal tissues as well as the frequency of tumor control. In this report, the cumulative incidence rate of the late radiation injuries of the normal tissues was calculated using the modified actuarial method (Cutler-Ederer's method) or Kaplan-Meier's method, which is usually applied to the calculation of the survival rate. By the use of this method of calculation, an accurate cumulative incidence rate over time can be easily obtained and applied to the statistical evaluation of the late radiation injuries.

The prediction of late-onset preeclampsia: Results from a longitudinal proteomics study.

PubMed

Erez, Offer; Romero, Roberto; Maymon, Eli; Chaemsaithong, Piya; Done, Bogdan; Pacora, Percy; Panaitescu, Bogdan; Chaiworapongsa, Tinnakorn; Hassan, Sonia S; Tarca, Adi L

2017-01-01

Late-onset preeclampsia is the most prevalent phenotype of this syndrome; nevertheless, only a few biomarkers for its early diagnosis have been reported. We sought to correct this deficiency using a high through-put proteomic platform. A case-control longitudinal study was conducted, including 90 patients with normal pregnancies and 76 patients with late-onset preeclampsia (diagnosed at ≥34 weeks of gestation). Maternal plasma samples were collected throughout gestation (normal pregnancy: 2-6 samples per patient, median of 2; late-onset preeclampsia: 2-6, median of 5). The abundance of 1,125 proteins was measured using an aptamers-based proteomics technique. Protein abundance in normal pregnancies was modeled using linear mixed-effects models to estimate mean abundance as a function of gestational age. Data was then expressed as multiples of-the-mean (MoM) values in normal pregnancies. Multi-marker prediction models were built using data from one of five gestational age intervals (8-16, 16.1-22, 22.1-28, 28.1-32, 32.1-36 weeks of gestation). The predictive performance of the best combination of proteins was compared to placental growth factor (PIGF) using bootstrap. 1) At 8-16 weeks of gestation, the best prediction model included only one protein, matrix metalloproteinase 7 (MMP-7), that had a sensitivity of 69% at a false positive rate (FPR) of 20% (AUC = 0.76); 2) at 16.1-22 weeks of gestation, MMP-7 was the single best predictor of late-onset preeclampsia with a sensitivity of 70% at a FPR of 20% (AUC = 0.82); 3) after 22 weeks of gestation, PlGF was the best predictor of late-onset preeclampsia, identifying 1/3 to 1/2 of the patients destined to develop this syndrome (FPR = 20%); 4) 36 proteins were associated with late-onset preeclampsia in at least one interval of gestation (after adjustment for covariates); 5) several biological processes, such as positive regulation of vascular endothelial growth factor receptor signaling pathway, were perturbed; and 6) from 22.1 weeks of gestation onward, the set of proteins most predictive of severe preeclampsia was different from the set most predictive of the mild form of this syndrome. Elevated MMP-7 early in gestation (8-22 weeks) and low PlGF later in gestation (after 22 weeks) are the strongest predictors for the subsequent development of late-onset preeclampsia, suggesting that the optimal identification of patients at risk may involve a two-step diagnostic process.

The prediction of late-onset preeclampsia: Results from a longitudinal proteomics study

PubMed Central

Erez, Offer; Romero, Roberto; Maymon, Eli; Chaemsaithong, Piya; Done, Bogdan; Pacora, Percy; Panaitescu, Bogdan; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.

2017-01-01

Background Late-onset preeclampsia is the most prevalent phenotype of this syndrome; nevertheless, only a few biomarkers for its early diagnosis have been reported. We sought to correct this deficiency using a high through-put proteomic platform. Methods A case-control longitudinal study was conducted, including 90 patients with normal pregnancies and 76 patients with late-onset preeclampsia (diagnosed at ≥34 weeks of gestation). Maternal plasma samples were collected throughout gestation (normal pregnancy: 2–6 samples per patient, median of 2; late-onset preeclampsia: 2–6, median of 5). The abundance of 1,125 proteins was measured using an aptamers-based proteomics technique. Protein abundance in normal pregnancies was modeled using linear mixed-effects models to estimate mean abundance as a function of gestational age. Data was then expressed as multiples of-the-mean (MoM) values in normal pregnancies. Multi-marker prediction models were built using data from one of five gestational age intervals (8–16, 16.1–22, 22.1–28, 28.1–32, 32.1–36 weeks of gestation). The predictive performance of the best combination of proteins was compared to placental growth factor (PIGF) using bootstrap. Results 1) At 8–16 weeks of gestation, the best prediction model included only one protein, matrix metalloproteinase 7 (MMP-7), that had a sensitivity of 69% at a false positive rate (FPR) of 20% (AUC = 0.76); 2) at 16.1–22 weeks of gestation, MMP-7 was the single best predictor of late-onset preeclampsia with a sensitivity of 70% at a FPR of 20% (AUC = 0.82); 3) after 22 weeks of gestation, PlGF was the best predictor of late-onset preeclampsia, identifying 1/3 to 1/2 of the patients destined to develop this syndrome (FPR = 20%); 4) 36 proteins were associated with late-onset preeclampsia in at least one interval of gestation (after adjustment for covariates); 5) several biological processes, such as positive regulation of vascular endothelial growth factor receptor signaling pathway, were perturbed; and 6) from 22.1 weeks of gestation onward, the set of proteins most predictive of severe preeclampsia was different from the set most predictive of the mild form of this syndrome. Conclusions Elevated MMP-7 early in gestation (8–22 weeks) and low PlGF later in gestation (after 22 weeks) are the strongest predictors for the subsequent development of late-onset preeclampsia, suggesting that the optimal identification of patients at risk may involve a two-step diagnostic process. PMID:28738067

Effect of foot massage to decrease physiological lower leg oedema in late pregnancy: a randomized controlled trial in Turkey.

PubMed

Coban, Ayden; Sirin, Ahsen

2010-10-01

This study aims to evaluate the effect of foot massage for decreasing physiological lower leg oedema in late pregnancy. Eighty pregnant women were randomly divided into two groups; study group had a 20 min foot massage daily for 5 days whereas the control group did not receive any intervention beyond standard prenatal care. The research was conducted between March and August 2007 in Manisa Province Health Ministry Central Primary Health Care Clinic 1, in Manisa, Western Turkey. Compared with the control group, women in the experimental group had a significantly smaller lower leg circumference (right and left, ankle, instep and metatarsal-phalanges joint) after 5 days of massage. The results obtained from our research show that foot massage was found to have a positive effect on decreasing normal physiological lower leg oedema in late pregnancy. © 2010 Blackwell Publishing Asia Pty Ltd.

Selenoprotein P Inhibits Radiation-Induced Late Reactive Oxygen Species Accumulation and Normal Cell Injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eckers, Jaimee C.; Kalen, Amanda L.; Xiao, Wusheng

2013-11-01

Purpose: Radiation is a common mode of cancer therapy whose outcome is often limited because of normal tissue toxicity. We have shown previously that the accumulation of radiation-induced late reactive oxygen species (ROS) precedes cell death, suggesting that metabolic oxidative stress could regulate cellular radiation response. The purpose of this study was to investigate whether selenoprotein P (SEPP1), a major supplier of selenium to tissues and an antioxidant, regulates late ROS accumulation and toxicity in irradiated normal human fibroblasts (NHFs). Methods and Materials: Flow cytometry analysis of cell viability, cell cycle phase distribution, and dihydroethidium oxidation, along with clonogenic assays,more » were used to measure oxidative stress and toxicity. Human antioxidant mechanisms array and quantitative real-time polymerase chain reaction assays were used to measure gene expression during late ROS accumulation in irradiated NHFs. Sodium selenite addition and SEPP1 overexpression were used to determine the causality of SEPP1 regulating late ROS accumulation and toxicity in irradiated NHFs. Results: Irradiated NHFs showed late ROS accumulation (4.5-fold increase from control; P<.05) that occurs after activation of the cell cycle checkpoint pathways and precedes cell death. The mRNA levels of CuZn- and Mn-superoxide dismutase, catalase, peroxiredoxin 3, and thioredoxin reductase 1 increased approximately 2- to 3-fold, whereas mRNA levels of cold shock domain containing E1 and SEPP1 increased more than 6-fold (P<.05). The addition of sodium selenite before the radiation treatment suppressed toxicity (45%; P<.05). SEPP1 overexpression suppressed radiation-induced late ROS accumulation (35%; P<.05) and protected NHFs from radiation-induced toxicity (58%; P<.05). Conclusion: SEPP1 mitigates radiation-induced late ROS accumulation and normal cell injury.« less

Pain Perception Is Increased in Congenital but Not Late Onset Blindness

PubMed Central

Slimani, Hocine; Danti, Sabrina; Ptito, Maurice; Kupers, Ron

2014-01-01

There is now ample evidence that blind individuals outperform sighted individuals in various tasks involving the non-visual senses. In line with these results, we recently showed that visual deprivation from birth leads to an increased sensitivity to pain. As many studies have shown that congenitally and late blind individuals show differences in their degree of compensatory plasticity, we here address the question whether late blind individuals also show hypersensitivity to nociceptive stimulation. We therefore compared pain thresholds and responses to supra-threshold nociceptive stimuli in congenitally blind, late blind and normally sighted volunteers. Participants also filled in questionnaires measuring attention and anxiety towards pain in everyday life. Results show that late blind participants have pain thresholds and ratings of supra-threshold heat nociceptive stimuli similar to the normally sighted, whereas congenitally blind participants are hypersensitive to nociceptive thermal stimuli. Furthermore, results of the pain questionnaires did not allow to discriminate late blind from normal sighted participants, whereas congenitally blind individuals had a different pattern of responses. Taken together, these results suggest that enhanced sensitivity to pain following visual deprivation is likely due to neuroplastic changes related to the early loss of vision. PMID:25244529

Effects of arginine treatment on nutrition, growth and urea cycle function in seven Japanese boys with late-onset ornithine transcarbamylase deficiency.

PubMed

Nagasaka, Hironori; Yorifuji, Tohru; Murayama, Kei; Kubota, Mitsuru; Kurokawa, Keiji; Murakami, Tomoko; Kanazawa, Masaki; Takatani, Tomozumi; Ogawa, Atsushi; Ogawa, Emi; Yamamoto, Shigenori; Adachi, Masanori; Kobayashi, Kunihiko; Takayanagi, Masaki

2006-09-01

The aim of this study was to investigate the effects of arginine on nutrition, growth and urea cycle function in boys with late-onset ornithine transcarbamylase deficiency (OTCD). Seven Japanese boys with late-onset OTCD enrolled in this study resumed arginine treatment after the cessation of this therapy for a few years. Clinical presentations such as vomiting and unconsciousness, plasma amino acids and urinary orotate excretion were followed chronologically to evaluate urea cycle function and protein synthesis with and without this therapy. In addition to height and body weight, blood levels of proteins, lipids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein -3 (IGFBP-3) were monitored. The frequency of hyperammonemic attacks and urinary orotate excretion decreased significantly following the resumption of arginine treatment. Despite showing no marked change in body weight, height increased gradually. Extremely low plasma arginine increased to normal levels, while plasma glutamine and alanine levels decreased considerably. Except for a slight increase in high-density lipoprotein cholesterol level, blood levels of markers for nutrition did not change. In contrast, low serum IGF-I and IGFBP-3 levels increased to age-matched control levels, and normal urinary GH secretion became greater than the level observed in the controls. Arginine treatment is able to reduces attacks of hyperammonemia in boys with late-onset OTCD and to increase their growth.

Brain levels of high-energy phosphate metabolites and executive function in geriatric depression.

PubMed

Harper, David G; Joe, Elizabeth B; Jensen, J Eric; Ravichandran, Caitlin; Forester, Brent P

2016-11-01

Depression in late life has been associated with difficulties in cognitive processing, particularly in the domains of executive function, processing speed and memory, and increases the risk of developing dementia suggesting a neurodegenerative phenotype. Mitochondrial dysfunction is frequently an early event in neurodegenerative illnesses and may be operative in patients with late life depression. Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the quantification of bioenergetic molecules produced by mitochondria. Ten patients with late life depression and eight normal elderly controls were studied with Stroop color and interference tests, which are widely used measures of processing speed and executive function, respectively, followed by (31P) MRS 3-dimensional chemical-shift imaging measuring levels of adenosine triphosphate, phosphocreatine, inorganic phosphate, and pH over the whole brain. In all subjects, gray matter phosphocreatine was positively associated with Stroop interference. Levels of white matter adenosine triphosphate were associated with Stroop interference in subjects with late life depression but not normal elderly. There was also a complementary association between white matter inorganic phosphate and Stroop interference in late life depression patients. These findings suggest two independent sources of executive function dependence on bioenergetic state in the aging brain. The dependence of executive function performance in subjects with late life depression on ATP in white matter may be associated with mitochondrial impairment and is consistent with predictions of the vascular depression hypothesis. Further research with wider neuropsychological testing targeting bioenergetic markers could help clarify the scope of these effects. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Blindness alters the microstructure of the ventral but not the dorsal visual stream.

PubMed

Reislev, Nina L; Kupers, Ron; Siebner, Hartwig R; Ptito, Maurice; Dyrby, Tim B

2016-07-01

Visual deprivation from birth leads to reorganisation of the brain through cross-modal plasticity. Although there is a general agreement that the primary afferent visual pathways are altered in congenitally blind individuals, our knowledge about microstructural changes within the higher-order visual streams, and how this is affected by onset of blindness, remains scant. We used diffusion tensor imaging and tractography to investigate microstructural features in the dorsal (superior longitudinal fasciculus) and ventral (inferior longitudinal and inferior fronto-occipital fasciculi) visual pathways in 12 congenitally blind, 15 late blind and 15 normal sighted controls. We also studied six prematurely born individuals with normal vision to control for the effects of prematurity on brain connectivity. Our data revealed a reduction in fractional anisotropy in the ventral but not the dorsal visual stream for both congenitally and late blind individuals. Prematurely born individuals, with normal vision, did not differ from normal sighted controls, born at term. Our data suggest that although the visual streams are structurally developing without normal visual input from the eyes, blindness selectively affects the microstructure of the ventral visual stream regardless of the time of onset. We suggest that the decreased fractional anisotropy of the ventral stream in the two groups of blind subjects is the combined result of both degenerative and cross-modal compensatory processes, affecting normal white matter development.

A cognitive neuropsychological approach to the study of delusions in late-onset schizophrenia.

PubMed

Phillips, M L; Howard, R; David, A S

1997-09-01

Hypotheses to explain delusion formation include distorted perceptual processing of meaningful stimuli (e.g. faces), abnormal reasoning, or a combination of both. The study investigated these hypotheses using standardized neuropsychological tests. A three-patient case-study, compared with a small group (n = 8) of age-matched normal control subjects. Hospital in- and outpatients. Age-matched normal controls were from local residential homes. Three subjects with late-onset schizophrenia, two currently deluded and one in remission. Both deluded subjects had persecutory beliefs. One had a delusion of misidentification. All subjects were administered standardized neuropsychological tests of facial processing and tests of verbal reasoning. The test scores of the three patients were compared with published normal values and the age-matched control data. The tests demonstrated impaired matching of unfamiliar faces in deluded subjects, particularly in the subject with delusional misidentification. Increasing the emotional content of logical reasoning problems had a significant effect on the deluded subjects' reasoning but not that of the normal controls. The findings suggest impaired visual processing plus abnormal reasoning in deluded subjects. However, these impairments are relatively subtle given the severity of psychiatric disorder in the patients studied.

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh

2016-01-01

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed themore » dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late RILD are also due to different pathologies. As such, new radiation techniques reducing irradiated volume might change the dose-limiting toxicity of the radiation therapy treatment.« less

CLB5-dependent activation of late replication origins in S. cerevisiae.

PubMed

Donaldson, A D; Raghuraman, M K; Friedman, K L; Cross, F R; Brewer, B J; Fangman, W L

1998-08-01

Replication origins in chromosomes are activated at specific times during the S phase. We show that the B-type cyclins are required for proper execution of this temporal program. clb5 cells activate early origins but not late origins, explaining the previously described long clb5 S phase. Origin firing appears normal in cIb6 mutants. In clb5 clb6 double mutant cells, the late origin firing defect is suppressed, accounting for the normal duration of the phase despite its delayed onset. Therefore, Clb5p promotes the timely activation of early and late origins, but Clb6p can activate only early origins. In clb5 clb6 mutants, the other B-type cyclins (Clb1-4p) promote an S phase during which both early and late replication origins fire.

Early Radiosurgery Improves Hearing Preservation in Vestibular Schwannoma Patients With Normal Hearing at the Time of Diagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akpinar, Berkcan; Mousavi, Seyed H., E-mail: mousavish@upmc.edu; McDowell, Michael M.

Purpose: Vestibular schwannomas (VS) are increasingly diagnosed in patients with normal hearing because of advances in magnetic resonance imaging. We sought to evaluate whether stereotactic radiosurgery (SRS) performed earlier after diagnosis improved long-term hearing preservation in this population. Methods and Materials: We queried our quality assessment registry and found the records of 1134 acoustic neuroma patients who underwent SRS during a 15-year period (1997-2011). We identified 88 patients who had VS but normal hearing with no subjective hearing loss at the time of diagnosis. All patients were Gardner-Robertson (GR) class I at the time of SRS. Fifty-seven patients underwent earlymore » (≤2 years from diagnosis) SRS and 31 patients underwent late (>2 years after diagnosis) SRS. At a median follow-up time of 75 months, we evaluated patient outcomes. Results: Tumor control rates (decreased or stable in size) were similar in the early (95%) and late (90%) treatment groups (P=.73). Patients in the early treatment group retained serviceable (GR class I/II) hearing and normal (GR class I) hearing longer than did patients in the late treatment group (serviceable hearing, P=.006; normal hearing, P<.0001, respectively). At 5 years after SRS, an estimated 88% of the early treatment group retained serviceable hearing and 77% retained normal hearing, compared with 55% with serviceable hearing and 33% with normal hearing in the late treatment group. Conclusions: SRS within 2 years after diagnosis of VS in normal hearing patients resulted in improved retention of all hearing measures compared with later SRS.« less

The short-term effects of cisplatin chemotherapy on bone turnover.

PubMed

Young, D R; Virolainen, P; Inoue, N; Frassica, F J; Chao, E Y

1997-11-01

Cisplatin is an effective agent in the treatment of osteosarcoma of bone but little is known of its effects on normal bone turnover. Twenty-four dogs divided into three study groups were used to study the effect of cisplatin on normal bone turnover at the distant site of surgery. Group 1 served as the control group, group 2 received four cycles of cisplatin every 3 weeks before the surgery, and group 3 received four cycles postoperatively. The bone turnover rate was evaluated by measuring levels of systemic bone markers, osteocalcin, alkaline phospohatase, urine pyridinoline cross-links, and by determination histomorphometric indices. Histomorphological analysis showed poor correlation on bone formation with systemic bone markers at distant sites of surgery. Histomorphometrically normal bone turnover was affected by administration of cisplatin, but the effect was temporary, late, and less significant than what occurred at the surgical site. Our data showed that significant effects of cisplatin are observed at the site of active cellular induction and proliferation, such as implant-host interface, and less effects are seen at the sites of normal bone turnover.

Late complications of pelvic irradiation in 16 dogs.

PubMed

Anderson, Christine R; McNiel, Elizabeth A; Gillette, Edward L; Powers, Barbara E; LaRue, Susan M

2002-01-01

When external beam radiation therapy is administered to the pelvis, normal tissues irradiated may include the colon, small intestine, urethra, bladder, bone, and spinal cord. The objectives of this retrospective study were to determine the incidence and severity of late radiation effects following pelvic irradiation in dogs and to identify factors that increase the risk of these effects. Medical records of all dogs treated with curative intent external beam radiation therapy to the pelvic region between 1993 and 1999 were reviewed. Patients with follow-up longer than 9 months or any patient that developed late complications earlier than 9 months were evaluated. Sixteen dogs met criteria for inclusion in this study. All dogs were treated with a 6-MV linear accelerator with bilaterally opposed beams. Diseases treated included transitional cell carcinoma of the bladder, transitional cell carcinoma of the prostate, and anal sac apocrine gland adenocarcinoma. Four dose/fractionation schemes were used: 49.5 Gy in 3.3 Gy fractions, 54 Gy in 3.0 Gy fractions, 54 Gy in 2.7 Gy fractions, and 18 Gy intraoperative radiation therapy followed by 43 Gy external beam radiation therapy in 2.9 Gy fractions. Implantable chemotherapy in the form of an OPLA-Pt sponge was used in six dogs as a radiation potentiator. Colitis was the major late effect following pelvic irradiation, occurring in nine dogs (56%). Colitis was characterized as mild in three dogs, moderate in one dog, and severe in five dogs. Three of the dogs with severe effects suffered gastrointestinal perforation. All dogs with severe late effects received 3 or 3.3 Gy per fraction, and 80% received radiation potentiators. In the seven dogs that received 2.7 Gy or 2.9 Gy per fraction, late effects were classified as none (n = 5), mild colitis (n = 1), and moderate colitis (n = 1). Radiation therapy can be administered to the pelvic region with a minimal risk of late effects to the colon by giving smaller doses per fraction and avoiding systemic radiation potentiators.

Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension.

PubMed

Moreira-Gonçalves, Daniel; Ferreira, Rita; Fonseca, Hélder; Padrão, Ana Isabel; Moreno, Nuno; Silva, Ana Filipa; Vasques-Nóvoa, Francisco; Gonçalves, Nádia; Vieira, Sara; Santos, Mário; Amado, Francisco; Duarte, José Alberto; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago

2015-11-01

Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

Effect of a prenatal lifestyle intervention on physical activity level in late pregnancy and the first year postpartum

PubMed Central

Sagedal, Linda Reme; Haakstad, Lene Annette Hagen; Lohne-Seiler, Hilde

2017-01-01

Background Despite documented health benefits for mother and baby, physical activity (PA)-level tends to decline in pregnancy. Overweight/obese and physically inactive women are two selected groups at increased risk of pregnancy complications. Thus, efficient strategies to maintain or increase PA-level in pregnancy and the postpartum period, especially among these women, are warranted. This secondary analysis examined the effect of a prenatal lifestyle-intervention on PA-level in late pregnancy and the first year postpartum, with subanalysis on initially physically active versus inactive and normal-weight versus overweight/obese women. Method The Norwegian Fit for Delivery (NFFD) randomized controlled trial included healthy primiparous women with singleton pregnancies and body mass index (BMI) ≥19 kg/m2 assigned to an intervention group, n = 303 (twice weekly group-exercises and dietary counseling) or a control group, n = 303 (standard prenatal care). The International Physical Activity Questionnaire short-form was used to assess PA-levels at inclusion (mean gestational week (GW) 16), GW 36, and six and 12 months postpartum. Results At GW 36, a positive intervention-effect with a significant between-group difference in total PA-level compared to time of inclusion was found for the total group (530 MET-min/week, p = 0.001) and the subgroups of normal-weight (533 MET-min/week, p = 0.003) and initially active women (717 MET-min/week, p<0.001). Intervention-effect was dependent on exercise-adherence among overweight/obese and inactive women. Compared to time of inclusion, the intervention groups maintained total PA-level at GW 36, while total PA-level decreased in the control groups. The PA-levels increased postpartum, but with no significant differences between the randomization groups. Conclusion The NFFD prenatal combined lifestyle intervention had a significant effect on TPA-level in late pregnancy among women entering pregnancy normal-weight or physically active, thereby preventing the downward trend typically seen during pregnancy. Intervention-effect among overweight/obese and physically inactive women was, however, dependent on exercise-adherence. Long-term intervention-effect was not observed in the postpartum period. PMID:29176762

Effect of a prenatal lifestyle intervention on physical activity level in late pregnancy and the first year postpartum.

PubMed

Sanda, Birgitte; Vistad, Ingvild; Sagedal, Linda Reme; Haakstad, Lene Annette Hagen; Lohne-Seiler, Hilde; Torstveit, Monica Klungland

2017-01-01

Despite documented health benefits for mother and baby, physical activity (PA)-level tends to decline in pregnancy. Overweight/obese and physically inactive women are two selected groups at increased risk of pregnancy complications. Thus, efficient strategies to maintain or increase PA-level in pregnancy and the postpartum period, especially among these women, are warranted. This secondary analysis examined the effect of a prenatal lifestyle-intervention on PA-level in late pregnancy and the first year postpartum, with subanalysis on initially physically active versus inactive and normal-weight versus overweight/obese women. The Norwegian Fit for Delivery (NFFD) randomized controlled trial included healthy primiparous women with singleton pregnancies and body mass index (BMI) ≥19 kg/m2 assigned to an intervention group, n = 303 (twice weekly group-exercises and dietary counseling) or a control group, n = 303 (standard prenatal care). The International Physical Activity Questionnaire short-form was used to assess PA-levels at inclusion (mean gestational week (GW) 16), GW 36, and six and 12 months postpartum. At GW 36, a positive intervention-effect with a significant between-group difference in total PA-level compared to time of inclusion was found for the total group (530 MET-min/week, p = 0.001) and the subgroups of normal-weight (533 MET-min/week, p = 0.003) and initially active women (717 MET-min/week, p<0.001). Intervention-effect was dependent on exercise-adherence among overweight/obese and inactive women. Compared to time of inclusion, the intervention groups maintained total PA-level at GW 36, while total PA-level decreased in the control groups. The PA-levels increased postpartum, but with no significant differences between the randomization groups. The NFFD prenatal combined lifestyle intervention had a significant effect on TPA-level in late pregnancy among women entering pregnancy normal-weight or physically active, thereby preventing the downward trend typically seen during pregnancy. Intervention-effect among overweight/obese and physically inactive women was, however, dependent on exercise-adherence. Long-term intervention-effect was not observed in the postpartum period.

Contribution of four lifelong factors of cognitive reserve on late cognition in normal aging and Parkinson's disease.

PubMed

Rouillard, Maud; Audiffren, Michel; Albinet, Cédric; Ali Bahri, Mohamed; Garraux, Gaëtan; Collette, Fabienne

2017-03-01

Cognitive reserve (CR) was proposed to explain how individual differences in brain function help to cope with the effects of normal aging and neurodegenerative diseases. Education, professional solicitations, and engagement in leisure and physical activities across the lifetime are considered as major determinants of this reserve. Using multiple linear regression analyses, we tested separately in healthy elderly and Parkinson's disease (PD) populations to what extent cognitive performance in several domains was explained by (a) any of these four environmental lifespan variables; (b) demographic and clinical variables (age, gender, depression score, and, for the PD group, duration of disease and dopaminergic drugs). We also tested for an interaction, if any, between these lifespan variables and brain pathology indexed by global atrophy measured from high-resolution anatomical magnetic resonance imaging. Age was negatively associated with cognitive performance in the PD group. In healthy elderly participants, we observed significant positive associations between cognitive performance and (a) education, (b) leisure activities, and (c) professional solicitation (decisional latitude). Furthermore, participants with greater brain atrophy benefited more from CR. In PD patients, education and professional solicitations contributed to cognitive performance but to a lesser extent than in controls. CR factors modulated the relationship between cognition and brain atrophy only in patients with a slight or moderate brain atrophy. Education is the CR factor that contributed the most to late cognitive functioning in both groups, closely followed by leisure activity in normal aging and professional solicitations in PD. Our results also provide evidence suggesting that the effects of CR does not express similarly in normal aging and PD. From a broader perspective, these results seem to indicate that CR factors the most consistently practiced across lifespan (education and professional solicitation) are those that are the more strongly associated to late cognitive efficiency.

Sensory and other neurogenic effects of exposures to airborne office dust

NASA Astrophysics Data System (ADS)

Mølhave, L.; Kjærgaard, S. K.; Attermann, J.

This Danish Office Dust Experiment investigated the response of 24 healthy non-sensitive adult subjects to exposure to normal office dust in the air (7 μg m -3 clean air, 136 and 390 μg m -3 TSP). The dust had no major identifiable specific reactive components. The exposure duration was 5 1/4 h and was arranged in a climate chamber in controlled atmospheric conditions. Measurements were made acutely at exposure onset, subacutely at exposure end and next day (late). As secondary aims the time course and threshold of any observed effect of the exposures, and the characteristics of any hyperresponding subgroup were investigated. In a questionnaire with 36 questions the dust exposures caused increased acute, subacute and late perceptions of reduced air quality, acute and subacute increased odor intensity, acute eye irritation, acute and late heavy head, subacute feeling of perspiration, and subacute general irritation. Cough increased subacutely during exposures. In addition, a performance test showed effects of dust exposures which also affected "Mood Scale" ratings. No effect was seen on an addition test for distraction, and objective measurements of skin humidity. The overall conclusion of the study is that healthy subjects without hypersensitivity reactions seem to respond to airborne house dust. The responses are both subjective sensory reactions and other neurogenic effects even at exposure levels within the range found in normal buildings. Some of the effects appeared acutely and decreased through adaptation while others increased during prolonged exposure and remained for more than 17 h after the exposure ended. The findings may indicate for this type of dust a threshold level for the dose-response relationships below 140 μg m -3.

Cannabinoid mitigation of neuronal morphological change important to development and learning: insight from a zebra finch model of psychopharmacology.

PubMed

Soderstrom, Ken; Gilbert, Marcoita T

2013-03-19

Normal CNS development proceeds through late-postnatal stages of adolescent development. The activity-dependence of this development underscores the significance of CNS-active drug exposure prior to completion of brain maturation. Exogenous modulation of signaling important in regulating normal development is of particular concern. This mini-review presents a summary of the accumulated behavioral, physiological and biochemical evidence supporting such a key regulatory role for endocannabinoid signaling during late-postnatal CNS development. Our focus is on the data obtained using a unique zebra finch model of developmental psychopharmacology. This animal has allowed investigation of neuronal morphological effects essential to establishment and maintenance of neural circuitry, including processes related to synaptogenesis and dendritic spine dynamics. Altered neurophysiology that follows exogenous cannabinoid exposure during adolescent development has the potential to persistently alter cognition, learning and memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Interleukin-6 is an essential determinant of on-time parturition in the mouse.

PubMed

Robertson, Sarah A; Christiaens, Inge; Dorian, Camilla L; Zaragoza, Dean B; Care, Alison S; Banks, Anke M; Olson, David M

2010-08-01

IL-6 abundance in amniotic fluid and uterine tissues increases in late gestation or with infection-associated preterm labor. A role in regulation of labor onset is suggested by observations that IL-6 increases expression of genes controlling prostaglandin synthesis and signaling in isolated uterine cells, but whether IL-6 is essential for normal parturition is unknown. To evaluate the physiological role of IL-6 in parturition in mice, we investigated the effect of Il6 null mutation on the timing of parturition and expression of genes associated with uterine activation. Il6 null mutant mice delivered 24 h later than wild-type mice, although circulating progesterone fell similarly in both genotypes during the prepartal period. Il6 null mutant mice were also refractory to low doses of lipopolysaccharide sufficient to induce preterm delivery in wild-type mice. The characteristic late-gestation elevation in uterine expression of Oxtr mRNA encoding oxytocin receptor, and peripartal increases in Ptgfr and Ptgs2 mRNAs regulating prostaglandin synthesis and signaling were delayed by 24 h in Il6 null mutant mice. Conversely, Ptger4 mRNA encoding the prostaglandin E receptor-4 was abnormally elevated in late-gestation in Il6 null mutant mice. Administration of recombinant IL-6 from d 11.5 postcoitum until term restored the normal timing of delivery and normalized Ptger4 mRNA expression in late gestation. We conclude that IL-6 has a key role in controlling the progression of events culminating in parturition and that it acts downstream of luteolysis in the uterus to regulate genes involved in the prostaglandin-mediated uterine activation cascade.

Gating of the late Na+ channel in normal and failing human myocardium.

PubMed

Undrovinas, Albertas I; Maltsev, Victor A; Kyle, John W; Silverman, Norman; Sabbah, Hani N

2002-11-01

We previously reported an ultraslow inactivating late Na+ current (INaL) in left ventricular cardiomyocytes (VC) isolated from normal (NVC) and failing (FVC) human hearts. This current could play a role in heart failure-induced repolarization abnormalities. To identify properties of NaCh contributing to INaL, we examined early and late openings in cell-attached patches of HEK293 cells expressing human cardiac NaCh alpha-subunit (alpha-HEK) and in VC of one normal and three failing human hearts. Two types of the late NaCh openings underlay INaL in all three preparations: scattered late (SLO) and bursts (BO). Amplitude analysis revealed that slope conductance for both SLO and BO was the same compared to the main level of early openings (EO) in both VC (21 vs 22.7pS, NVC; 22.7 vs 22.6pS, FVC) and alpha-HEK (23.2 vs 23pS), respectively. Analysis of SLO latencies revealed voltage-independent ultraslow inactivation in all preparations with tendency to be slower in FVC compared to NCV. EO and SLO render one open voltage-independent state (tau approximately 0.4ms) for NVC and FVC. One open (voltage-dependent) and two closed states (one voltage-dependent and another voltage-independent) were found in BO of both specimens. Burst duration tend to be longer in FVC ( approximately 50ms) than in NVC ( approximately 30ms). In FVC we found both modes SLO and BO at membrane potential of -10mV that is attribute for take-off voltages (from -18 to -2mV) for early afterdepolarizations (EAD's) in FVC. In conclusions, we found a novel gating mode SLO that manifest slow (hundreds of ms), voltage-independent inactivation in both NVC and FVC. We were unable to reliably demonstrate any differences in the properties of the late NaCh in failing vs a normal human heart. Accordingly, the late current appears to be generated by a single population of channels in normal and failing human ventricular myocardium. Both SLO and BO could be implicated in EADs in HF.

Dose-time relationships for post-irradiation cutaneous telangiectasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, L.; Ubaldi, S.E.

1977-01-01

Seventy-five patients who had received electron beam radiation a year or more previously were studied. The irradiated skin portals were photographed and late reactions graded in terms of the number and severity of telangiectatic lesions observed. The skin dose, number of fractions, overall treatment time and irradiated volume were recorded in each case. A Strandqvist-type iso-effect line was derived for this response. A multi-probit search program also was used to derive best-fitting cell population kinetic parameters for the same data. From these parameters a comprehensive iso-effect table could be computed for a wide range of treatment schedules including daily treatmentmore » as well as fractionation at shorter and longer intervals; this provided a useful set of normal tissue tolerance limits for late effects.« less

Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

PubMed

Hoffmann, Aswin L; Nahum, Alan E

2013-10-07

The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

Late Treatment of Syndesmotic Injuries.

PubMed

Swords, Michael P; Sands, Andrew; Shank, John R

2017-03-01

Normal syndesmosis anatomy and alignment are essential to ankle function. Although injuries to the syndesmosis are common with ankle injuries, accurate diagnosis and reduction continue to be a challenge. Late reconstruction for syndesmosis is reviewed. A surgical technique for late reconstruction is outlined in detail. Copyright © 2016 Elsevier Inc. All rights reserved.

Late hematologic toxicity following treatment of rattlesnake envenomation with crotalidae polyvalent immune Fab antivenom.

PubMed

Ruha, Anne-Michelle; Curry, Steven C; Albrecht, Clay; Riley, Brad; Pizon, Anthony

2011-01-01

North American rattlesnake envenomations commonly produce defibrination, coagulopathy and/or thrombocytopenia, which may be reversed following treatment with Crotalidae Polyvalent Immune Fab Ovine (FabAV). Despite initial resolution with FabAV, late onset or recurrence of venom-induced hematologic effects may occur. Time at which onset of late hematotoxicity may first be detected is unknown. The purpose of this study was to identify the incidence and time of onset of recurrent or new late hypofibrinogenemia, coagulopathy, or thrombocytopenia in a cohort of rattlesnake envenomation patients seen in outpatient follow-up after treatment with FabAV, and to report hematologic outcomes in these patients. Review of 66 charts of patients with rattlesnake envenomation who were treated with FabAV, and subsequently had outpatient follow-up evaluation at least 48 h after last FabAV, was performed. Demographic information, rattlesnake and bite characteristics, dose and timing of antivenom administration, adverse events, in-patient laboratory values, length of hospital stay, and follow-up laboratory values were collected. The primary outcome parameters were recurrent or delayed onset coagulopathy, hypofibrinogenemia, or thrombocytopenia identified no sooner than 48 h after last dose of FabAV. Prior to control of the envenomation with FabAV, 42 patients (63.6%) experienced hematologic toxicity. At follow-up, 21 patients (32%) were found to have late coagulopathy, hypofibrinogenemia, or thrombocytopenia. Of twenty-three patients (35%) with more than one follow-up visit, fifteen had normal laboratory findings at the first follow-up visit. Five of these 15 patients (8% of total study group; 33% of this subgroup) with normal hematologic studies at first follow-up exhibited late hematologic toxicity at second follow-up. Severe late hematologic toxicity developed in five of 66 (8%) patients. One patient was retreated with FabAV for late severe thrombocytopenia. Recurrent and delayed onset of hematologic toxicity in rattlesnake envenomation victims treated with FabAV is common. Follow-up more than three days after treatment is necessary to detect all cases of late hematologic toxicity. Copyright © 2010 Elsevier Ltd. All rights reserved.

LLR data analysis and impact on lunar dynamics from recent developments at OCA LLR Station

NASA Astrophysics Data System (ADS)

Viswanathan, Vishnu; Fienga, Agnes; Courde, Clement; Torre, Jean-Marie; Exertier, Pierre; Samain, Etienne; Feraudy, Dominique; Albanese, Dominique; Aimar, Mourad; Mariey, Hervé; Viot, Hervé; Martinot-Lagarde, Gregoire

2016-04-01

Since late 2014, OCA LLR station has been able to range with infrared wavelength (1064nm). IR ranging provides both temporal and spatial improvement in the LLR observations. IR detection also permits in densification of normal points, including the L1 and L2 retroreflectors due to better signal to noise ratio. This contributes to a better modelisation of the lunar libration. The hypothesis of lunar dust and environmental effects due to the chromatic behavior noticed on returns from L2 retroreflector is discussed. In addition, data analysis shows that the effect of retroreflector tilt and the use of calibration profile for the normal point deduction algorithm, contributes to improving the precision of normal points, thereby impacting lunar dynamical models and inner physics.

Changes in postharvest quality of Swiss chard grown using 3 organic preharvest treatments.

PubMed

Daiss, N; Lobo, M G; Gonzalez, M

2008-08-01

Using storage conditions recommended for conventional chard (4 degrees C, 90% RH and 7 d), the chard treated with some organic preharvest treatments [effective microorganisms, a fermented mixture of effective microorganisms with organic matter (EM-Bokashi + EM), and an auxiliary soil product] lost considerable water (> 2%) and weight (> 25%). These results indicate that organic methods tested produce a vegetable that can not sustain its quality when commercialized through the conventional supply chain. Nevertheless, respiration, color, pH, and titratable acidity practically remained constant during conservation. Ascorbic acid content was constant in chard treated with the different preharvest treatments and collected at 8 wk after sowing (normal harvest). However, the ascorbic acid content of the control chard decreased 60% after 7 d of storage. This vitamin diminished (35%) in chard collected after 19 wk after sowing (late harvest) during the postharvest conservation. The greatest difference in chard quality was registered between sampling dates since chard collected during the late harvest had higher levels of dry matter, sugars, acids, proteins, and ascorbic acid than chard collected during the normal harvest.

Early treatment of posterior crossbite - a randomised clinical trial

PubMed Central

2013-01-01

Background The aim of this randomised clinical trial was to assess the effect of early orthodontic treatment in contrast to normal growth effects for functional unilateral posterior crossbite in the late deciduous and early mixed dentition by means of three-dimensional digital model analysis. Methods This randomised clinical trial was assessed to analyse the orthodontic treatment effects for patients with functional unilateral posterior crossbite in the late deciduous and early mixed dentition using a two-step procedure: initial maxillary expansion followed by a U-bow activator therapy. In the treatment group 31 patients and in the control group 35 patients with a mean age of 7.3 years (SD 2.1) were monitored. The time between the initial assessment (T1) and the follow-up (T2) was one year. The orthodontic analysis was done by a three-dimensional digital model analysis. Using the ‘Digimodel’ software, the orthodontic measurements in the maxilla and mandible and for the midline deviation, the overjet and overbite were recorded. Results Significant differences between the control and the therapy group at T2 were detected for the anterior, median and posterior transversal dimensions of the maxilla, the palatal depth, the palatal base arch length, the maxillary arch length and inclination, the midline deviation, the overjet and the overbite. Conclusions Orthodontic treatment of a functional unilateral posterior crossbite with a bonded maxillary expansion device followed by U-bow activator therapy in the late deciduous and early mixed dentition is an effective therapeutic method, as evidenced by the results of this RCT. It leads to three-dimensional therapeutically induced maxillary growth effects. Dental occlusion is significantly improved, and the prognosis for normal craniofacial growth is enhanced. Trial registration Registration trial DRKS00003497 on DRKS PMID:23339736

A qualitative study: Mothers of late preterm infants relate their experiences of community-based care

PubMed Central

Dosani, Aliyah; Oliver, Lynnette May; Lodha, Abhay K; Young, Marilyn

2017-01-01

Purpose In Alberta, the high occurrence of late preterm infants and early hospital discharge of mother-infant dyads has implications for postpartum care in the community. Shortened hospital stay and complexities surrounding the care of biologically and developmentally immature late preterm infants heighten anxiety and fears. Our descriptive phenomenological study explores mothers’ experience of caring for their late preterm infants in the community. Methods Eleven mothers were interviewed using a semi-structured interview guide. Interview transcripts were analysed using an interpretive thematic approach. Findings The mothers’ hospital experience informed their perspective that being a late preterm infant was not a “big deal,” and they tended to treat their infant as normal. “Feeding was really problem,” especially the variability in feeding effectiveness, which was not anticipated. Failing to recognize late preterm infants’ feeding distress exemplified lack of knowledge of feeding cues and tendencies to either rationalize or minimize feeding concerns. Public health nurses represent a source of informational support for managing neonatal morbidities associated with being late preterm; however, maternal experiences with public health nurses varied. Some nurses used a directive style that overwhelmed certain mothers. Seeing multiple public health nurses and care providers was not always effective, given inconsistent and contradictory guidance to care. These new and changing situations increased maternal anxiety and stress and influenced maternal confidence in care. Fathers, family, and friends were important sources of emotional support. Conclusion After discharge, mothers report their lack of preparation to meet the special needs of their late preterm infants. Current approaches to community-based care can threaten maternal confidence in care. New models and pathways of care for late preterm infants and their families need to be responsive to the spectrum of feeding issues encountered, limit duplication of services, and ensure consistent and effective care that parents will accept. PMID:28334033

Otitis Media and Speech/Language Development in Late-Talkers.

ERIC Educational Resources Information Center

Paul, Rhea; And Others

This study examines otitis media as a possible factor associated with increased risk for communicative handicap in a group of children with a possible vulnerability for language delay: "late-talkers." Speech and language outcomes at ages 3 and 4 were examined in 28 late talkers and 24 children with normal language development. Late…

Reference tissue normalization in longitudinal (18)F-florbetapir positron emission tomography of late mild cognitive impairment.

PubMed

Shokouhi, Sepideh; Mckay, John W; Baker, Suzanne L; Kang, Hakmook; Brill, Aaron B; Gwirtsman, Harry E; Riddle, William R; Claassen, Daniel O; Rogers, Baxter P

2016-01-15

Semiquantitative methods such as the standardized uptake value ratio (SUVR) require normalization of the radiotracer activity to a reference tissue to monitor changes in the accumulation of amyloid-β (Aβ) plaques measured with positron emission tomography (PET). The objective of this study was to evaluate the effect of reference tissue normalization in a test-retest (18)F-florbetapir SUVR study using cerebellar gray matter, white matter (two different segmentation masks), brainstem, and corpus callosum as reference regions. We calculated the correlation between (18)F-florbetapir PET and concurrent cerebrospinal fluid (CSF) Aβ1-42 levels in a late mild cognitive impairment cohort with longitudinal PET and CSF data over the course of 2 years. In addition to conventional SUVR analysis using mean and median values of normalized brain radiotracer activity, we investigated a new image analysis technique-the weighted two-point correlation function (wS2)-to capture potentially more subtle changes in Aβ-PET data. Compared with the SUVRs normalized to cerebellar gray matter, all cerebral-to-white matter normalization schemes resulted in a higher inverse correlation between PET and CSF Aβ1-42, while the brainstem normalization gave the best results (high and most stable correlation). Compared with the SUVR mean and median values, the wS2 values were associated with the lowest coefficient of variation and highest inverse correlation to CSF Aβ1-42 levels across all time points and reference regions, including the cerebellar gray matter. The selection of reference tissue for normalization and the choice of image analysis method can affect changes in cortical (18)F-florbetapir uptake in longitudinal studies.

Modulation of in vitro transformation and the early and late modes of DNA replication of uv-irradiation Syrian hamster cells by caffeine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doniger, J.; DiPaolo, J.A.

1981-09-01

The effect of caffeine on post-uv DNA replication was studied to determine its relevance to carcinogenesis. The level of uv-induced transformed colonies of Syrian hamster embryo cells (HEC) was increased up to fivefold when caffeine was added to cells between 0 and 6 h post-uv. The greatest increase was observed when the interval between uv irradiation and caffeine addition was 4 h. Two modes of DNA replication occurred after uv irradiation. During the early mode (0 to 3 h post-uv) the size of nascent strands, as measured by alkaline sucrose sedimentation, was smaller than those in nonirradiated cells, whereas duringmore » the late mode they recovered to normal size. Caffeine inhibited the rate of elongation of nascent strands during the early mode. When caffeine was added immediately after uv irradiation, the conversion of the early mode to the late mode was inhibited. Studies on the effects of caffeine have now been extended to the late mode. While caffeine has little effect with the fd elements beginning from the 10th day after irradiation is connected with their proliferation but not with the migration out from lymphoid organs.« less

Renal dysfunction after total body irradiation: Dose-effect relationship

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kal, Henk B.; Kempen-Harteveld, M. Loes van

2006-07-15

Purpose: Late complications related to total body irradiation (TBI) as part of the conditioning regimen for hematopoietic stem cell transplantation have been increasingly noted. We reviewed and compared the results of treatments with various TBI regimens and tried to derive a dose-effect relationship for the endpoint of late renal dysfunction. The aim was to find the tolerance dose for the kidney when TBI is performed. Methods and Materials: A literature search was performed using PubMed for articles reporting late renal dysfunction. For intercomparison, the various TBI regimens were normalized using the linear-quadratic model, and biologically effective doses (BEDs) were calculated.more » Results: Eleven reports were found describing the frequency of renal dysfunction after TBI. The frequency of renal dysfunction as a function of the BED was obtained. For BED >16 Gy an increase in the frequency of dysfunction was observed. Conclusions: The tolerance BED for kidney tissue undergoing TBI is about 16 Gy. This BED can be realized with highly fractionated TBI (e.g., 6 x 1.7 Gy or 9 x 1.2 Gy at dose rates >5 cGy/min). To prevent late renal dysfunction, the TBI regimens with BED values >16 Gy (almost all found in published reports) should be applied with appropriate shielding of the kidneys.« less

Association between ventricular filling patterns and the extent of late enhancement on magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

PubMed

De Zan, M; Carrascosa, P; Deviggiano, A; Capunay, C; Rodríguez-Granillo, G A

To explore the relationship between ventricular filling curves and the extent of late enhancement on cardiac magnetic resonance imaging (MRI) in patients with hypertrophic cardiomyopathy. We retrospectively included consecutive patients with suspected and/or confirmed hypertrophic cardiomyopathy and a control group of patients matched for age and sex who underwent cardiac MRI with evaluation of late enhancement. Among other determinations, we evaluated the following parameters on cine sequences: peak filling rate, time to the first peak filling rate, and filling rate normalized to the filling volume. Late enhancement was observed in 29 (73%) of the 40 patients with hypertrophic cardiomyopathy. The normalized peak filling rate was significantly lower in patients with late enhancement (4.9 ± 1.6 in those with hypertrophic cardiomyopathy positive for late enhancement vs. 5.8 ± 2.2 in those with hypertrophic cardiomyopathy negative for late enhancement vs. 6.3 ± 1.5 in controls, p = 0.008) and the time to peak filling was longer in patients with late enhancement (540.6 ± 89.7 ms vs. 505.5 ± 99.3 ms in those with hypertrophic cardiomyopathy negative for late enhancement vs. 486.9 ± 86.3 ms in controls, p = 0.02). When the population was stratified into three groups in function of the normalized peak filling rate, significant differences were observed among groups for age (p = 0.002), mean wall thickness (p = 0.036), and myocardial mass (p = 0.046) and atrial dimensions, whereas no significant differences with respect to late enhancement were seen. In patients with hypertrophic cardiomyopathy, we found a significant association between ventricular filling patterns and age, wall thicknesses, and atrial dimensions, but not with the extent of late enhancement. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Right ventricular performance and mass by use of cine MRI late after atrial repair of transposition of the great arteries.

PubMed

Lorenz, C H; Walker, E S; Graham, T P; Powers, T A

1995-11-01

The long-term adaptation of the right ventricle after atrial repair of transposition of the great arteries (TGA) remains a subject of major concern. Cine magnetic resonance imaging (MRI), with its tomographic capabilities, allows unique quantitative evaluation of both right and left ventricular function and mass. Our purpose was to use MRI and an age-matched normal population to examine the typical late adaptation of the right and left ventricles after atrial repair of TGA. Cine MRI was used to study ventricular function and mass in 22 patients after atrial repair of TGA. Images were obtained in short-axis sections from base to apex to derive normalized right and left ventricular mass (RVM and LVM, g/m2), interventricular septal mass (IVSM, g/m2), RV and LV end-diastolic volumes (EDV, mL/m2), and ejection fractions (EF). Results 8 to 23 years after repair were compared with analysis of 24 age- and sex-matched normal volunteers and revealed markedly elevated RVM, decreased LVM and IVSM, normal RV size, and only mildly depressed RVEF. Only 1 of 22 patients had clinical RV dysfunction, and this patient had increased RVM. Cine MRI allows quantitative evaluation of both RV and LV mass and function late after atrial repair of TGA. Longitudinal studies that include these measurements should prove useful in determining the mechanism of late RV failure in these patients. On the basis of these early data, inadequate hypertrophy does not appear to be the cause of late dysfunction in this patient group.

Left ventricular diastolic filling with an implantable ventricular assist device: beat to beat variability with overall improvement

NASA Technical Reports Server (NTRS)

Nakatani, S.; Thomas, J. D.; Vandervoort, P. M.; Zhou, J.; Greenberg, N. L.; Savage, R. M.; McCarthy, P. M.

1997-01-01

OBJECTIVES: We studied the effects of left ventricular (LV) unloading by an implantable ventricular assist device on LV diastolic filling. BACKGROUND: Although many investigators have reported reliable systemic and peripheral circulatory support with implantable LV assist devices, little is known about their effect on cardiac performance. METHODS: Peak velocities of early diastolic filling, late diastolic filling, late to early filling ratio, deceleration time of early filling, diastolic filling period and atrial filling fraction were measured by intraoperative transesophageal Doppler echocardiography before and after insertion of an LV assist device in eight patients. A numerical model was developed to simulate this situation. RESULTS: Before device insertion, all patients showed either a restrictive or a monophasic transmitral flow pattern. After device insertion, transmitral flow showed rapid beat to beat variation in each patient, from abnormal relaxation to restrictive patterns. However, when the average values obtained from 10 consecutive beats were considered, overall filling was significantly normalized from baseline, with early filling velocity falling from 87 +/- 31 to 64 +/- 26 cm/s (p < 0.01) and late filling velocity rising from 8 +/- 11 to 32 +/- 23 cm/s (p < 0.05), resulting in an increase in the late to early filling ratio from 0.13 +/- 0.18 to 0.59 +/- 0.38 (p < 0.01) and a rise in the atrial filling fraction from 8 +/- 10% to 26 +/- 17% (p < 0.01). The deceleration time (from 112 +/- 40 to 160 +/- 44 ms, p < 0.05) and the filling period corrected by the RR interval (from 39 +/- 8% to 54 +/- 10%, p < 0.005) were also significantly prolonged. In the computer model, asynchronous LV assistance produced significant beat to beat variation in filling indexes, but overall a normalization of deceleration time as well as other variables. CONCLUSIONS: With LV assistance, transmitral flow showed rapidly varying patterns beat by beat in each patient, but overall diastolic filling tended to normalize with an increase of atrial contribution to the filling. Because of the variable nature of the transmitral flow pattern with the assist device, the timing of the device cycle must be considered when inferring diastolic function from transmitral flow pattern.

Mesozoic magmatism and timing of epigenetic Pb-Zn-Ag mineralization in the western Fortymile mining district, east-central Alaska: Zircon U-Pb geochronology, whole-rock geochemistry, and Pb isotopes

USGS Publications Warehouse

Dusel-Bacon, Cynthia; Aleinkoff, J.N.; Day, W.C.; Mortensen, J.K.

2015-01-01

Epigenetic Pb-Zn-Ag ± Cu prospects in the western Fortymile district are spatially associated with splays of the northeast-trending Kechumstuk sinistral-normal fault zone and with ca. 68-66 Ma felsic intrusions and dikes. The similarity between Pb isotope compositions of feldspars from the Late Cretaceous igneous bodies and sulfides from the epithermal prospects suggests a Late Cretaceous age for most of the mineralization. Fluid flow along the faults undoubtedly played a major role in mineralization. We interpret displacement on the northeast-trending faults to be a far-field effect of dextral translation along Late Cretaceous plate-scale boundaries and faults that were roughly parallel to the subsequently developed Denali and Tintina fault systems, which currently bound the region.

An accelerated technique for irradiation of malignant canine nasal and paranasal sinus tumors.

PubMed

Adams, W M; Miller, P E; Vail, D M; Forrest, L J; MacEwen, E G

1998-01-01

Tumor and normal tissue response was assessed in 21 dogs with malignant nasal tumors given 42 Gy cobalt radiation in 9 or 10 fractions over 11 to 13 days. Local tumor/clinical relapse recurred in 68% of dogs, with a median relapse free interval (RFI) of 270 days. Median survival was 428 days. One year survival for all dogs was 60%. RFI and survival times are better than, or similar to, previous reports of dogs treated with radiotherapy only. Acute radiation effects were severe in one dog. Late effects were severe in six of 15 dogs (40%) with durable tumor control. Late effects included bilateral blindness (3), osteoradionecrosis (3), and seizures (1). These six dogs had a median survival of 705 days. Loss of vision occurred in at least one eye in nine dogs (47%). Tumor staging based on CT findings was predictive for survival duration. Tumor histology was not predictive of outcome. Labrador Retrievers were significantly over-represented. Despite comparable or improved tumor control and survival times provided by this accelerated protocol, relative to other radiotherapy reports, local failure remains the major cause of death, and late radiation effects can be severe in dogs with durable tumor control.

The effect of western juniper on the estrous cycle in beef cattle.

PubMed

Welch, Kevin D; Stonecipher, Clint A; Gardner, Dale R; Panter, Kip E; Parsons, Cory; Deboodt, Tim; Johnson, Bryan

2015-02-01

Numerous evergreen trees and shrubs contain labdane acids, including isocupressic acid, which can cause late-term abortions in cattle. Recent research has shown that the bark from western juniper trees can also cause late-term abortions in cattle. Additionally, ranchers have observed that cattle in western juniper-infested rangelands tend to have decreased conception rates. The objective of this study was to determine if western juniper alters the estrous cycle of cattle. Fourteen heifers (10 treated and 4 control) were monitored for 74 days for signs of normal estrous behavior, with a 21 day feeding trial with western juniper bark from days 28-48, after which the cattle were bred naturally with a bull. The cattle were checked for pregnancy 30 days after all cattle had been bred. The data from this study indicate that exposure to western juniper bark does not affect normal estrus, estrous cycle or conception rates of cattle. Published by Elsevier Ltd.

Locally applied simvastatin improves fracture healing at late period in osteoporotic rat

NASA Astrophysics Data System (ADS)

Tian, Faming; Zhang, Liu; Kang, Yuchuan; Zhang, Junshan; Ao, Jiao; Yang, Fang

effect of simvastatin locally applied from a bioactive polymer coating of implants on osteoporotic fracture healing at late period. Methods:Femur fracture model was established on normal or osteotoporotic mature female SD rats, intramedullary stabilization was achieved with uncoated titanium Kirschnerwires in normal rats(group A),with polymer-only coated vs. polymer plus simvastatin coated titanium Kirschner wires in osteoporotic rats(group B and C, respectively).Femurs were harvested after 12 weeks, and underwent radiographic and histologic analysis, as well as immunohistochemical evaluation for BMP-2 expression. Results:Radiographic results demonstrated progressed callus in the simvastatin-treated groups compared to the uncoated group.The histologic analysis revealed a significantly processed callus with irregular-shaped newly formed bone trabeculae in simvastatin-treated group. Immunohistochemical evaluation showed markedly higher expression levels of B:MP-2 in simvastatin-treated group.Conclusions: The present study revealed a improved fracture healing under local application of simvastatin in osteoporotic rat,which might partially from upregulation of the B:MP-2 expression at fractured site.

Cdc7 is required throughout the yeast S phase to activate replication origins.

PubMed

Donaldson, A D; Fangman, W L; Brewer, B J

1998-02-15

The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7(ts) allele were first arrested in G1 at the cdc7 block by incubation at 37 degrees C, and then were allowed to enter S phase by brief incubation at 23 degrees C. During the S phase, after return to 37 degrees C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.

Hypogonadotropic hypogonadism

MedlinePlus

... lack of sex hormones. This prevents normal sexual maturity in children and normal function of the testicles ... self-esteem due to late start of puberty (emotional support may be helpful) Sexual problems, such as ...

Neural and Muscular Contributions to the Age-Related Reductions in Rapid Strength.

PubMed

Gerstner, Gena R; Thompson, Brennan J; Rosenberg, Joseph G; Sobolewski, Eric J; Scharville, Michael J; Ryan, Eric D

2017-07-01

The purposes of this study were to investigate the age-related differences in absolute and normalized plantarflexion rate of torque development (RTD) at early (0-50 ms) and late (100-200 ms) time intervals and to examine specific neural and muscular mechanisms contributing to these differences. Thirty-two young (20.0 ± 2.1 yr) and 20 older (69.5 ± 3.3 yr) recreationally active men performed rapid plantarflexion isometric muscle actions to examine absolute and normalized RTD and muscle activation using EMG at early and late time intervals. Ultrasonography was used to examine medial gastrocnemius muscle size, echo intensity (EI), and muscle architecture (fascicle length [FL] and pennation angle [PA]). The older men were weaker (23.9%, P < 0.001) and had lower later absolute and normalized RTD (P = 0.001-0.034) variables when compared with the young men. The older men also had higher EI (P < 0.001), smaller PA (P = 0.004), and lower later EMG amplitude values (P = 0.009-0.046). However, there were no differences in early RTD and EMG amplitude values, muscle size, or FL between groups (P = 0.097-0.914). Lower late RTD values were related to higher EI, smaller PA, and lower EMG amplitude values (r = -0.28-0.59, P = 0.001-0.044); however, late RTD values were no longer related to PA after normalizing to peak torque. Age-related alterations in muscle quality (EI), architecture, and muscle activation may influence rapid torque production at late time intervals (≥100 ms) from contraction onset. These findings highlight specific neuromuscular factors that influence the age-related reductions in RTD, which has been shown to significantly influence function and performance in older adults.

Biochemical Response of Late Rickets and Osteomalacia to a Chupatty-free Diet

PubMed Central

Ford, J. A.; Colhoun, E. M.; McIntosh, W. B.; Dunnigan, M. G.

1972-01-01

Eight Pakistani children with late rickets and two Pakistani women with osteomalacia were given a chupatty-free diet for seven weeks, substituting leavened bread of lower extraction. On this diet serum calcium levels rose to normal or near normal, levels of serum inorganic phosphorus rose slightly but significantly, and serum alkaline phosphatase levels showed a definite rise indicative of healing bone disease. It is concluded that the high phytate content of unleavened bread is the major cause of late rickets and osteomalacia in Pakistani and Indian communities in the United Kingdom. The simplest prophylactic measure seems to be the additional fortification with calcium carbonate of the high extraction flour used in preparing unleavened bread. PMID:5069221

The Use of Lexical Neighborhood Test (LNT) in the Assessment of Speech Recognition Performance of Cochlear Implantees with Normal and Malformed Cochlea.

PubMed

Kant, Anjali R; Banik, Arun A

2017-09-01

The present study aims to use the model-based test Lexical Neighborhood Test (LNT), to assess speech recognition performance in early and late implanted hearing impaired children with normal and malformed cochlea. The LNT was administered to 46 children with congenital (prelingual) bilateral severe-profound sensorineural hearing loss, using Nucleus 24 cochlear implant. The children were grouped into Group 1-(early implantees with normal cochlea-EI); n = 15, 31/2-61/2 years of age; mean age at implantation-3½ years. Group 2-(late implantees with normal cochlea-LI); n = 15, 6-12 years of age; mean age at implantation-5 years. Group 3-(early implantees with malformed cochlea-EIMC); n = 9; 4.9-10.6 years of age; mean age at implantation-3.10 years. Group 4-(late implantees with malformed cochlea-LIMC); n = 7; 7-12.6 years of age; mean age at implantation-6.3 years. The following were the malformations: dysplastic cochlea, common cavity, Mondini's, incomplete partition-1 and 2 (IP-1 and 2), enlarged IAC. The children were instructed to repeat the words on hearing them. Means of the word and phoneme scores were computed. The LNT can also be used to assess speech recognition performance of hearing impaired children with malformed cochlea. When both easy and hard lists of LNT are considered, although, late implantees (with or without normal cochlea), have achieved higher word scores than early implantees, the differences are not statistically significant. Using LNT for assessing speech recognition enables a quantitative as well as descriptive report of phonological processes used by the children.

Progressive deformation of the Chugach accretionary complex, Alaska, during a paleogene ridge-trench encounter

USGS Publications Warehouse

Kusky, Timothy M.

1997-01-01

The Mesozoic accretionary wedge of south-central Alaska is cut by an array of faults including dextral and sinistral strike-slip faults, synthetic and antithetic thrust faults, and synthetic and antithetic normal faults. The three fault sets are characterized by quartz ± calcite ± chlorite ± prehnite slickensides, and are all relatively late, i.e. all truncate ductile fabrics of the host rocks. Cross-cutting relationships suggest that the thrust fault sets predate the late normal and strike-slip fault sets. Together, the normal and strike-slip fault system exhibits orthorhombic symmetry. Thrust faulting shortened the wedge subhorizontally perpendicular to strike, and then normal and strike-slip faulting extended the wedge oblique to orogenic strike. Strongly curved slickenlines on some faults of each set reveal that displacement directions changed over time. On dip-slip faults (thrust and normal), slickenlines tend to become steeper with younger increments of slip, whereas on strike-slip faults, slickenlines become shallower with younger strain increments. These patterns may result from progressive exhumation of the accretionary wedge while the faults were active, with the curvature of the slickenlines tracking the change from a non-Andersonian stress field at depth to a more Andersonian system (σ1 or σ2 nearly vertical) at shallower crustal levels.We interpret this complex fault array as a progressive deformation that is one response to Paleocene-Eocene subduction of the Kula-Farallon spreading center beneath the accretionary complex because: (1) on the Kenai Peninsula, ENE-striking dextral faults of this array exhibit mutually cross-cutting relationships with Paleocene-Eocene dikes related to ridge subduction; and (2) mineralized strike-slip and normal faults of the orthorhombic system have yielded 40Ar/39Ar ages identical to near-trench intrusives related to ridge subduction. Both features are diachronous along-strike, having formed at circa 65 Ma in the west and 50 Ma in the east. Exhumation of deeper levels of the southern Alaska accretionary wedge and formation of this late fault array is interpreted as a critical taper adjustment to subduction of progressively younger oceanic lithosphere yielding a shallower basal de´collement dip as the Kula-Farallon ridge approached the accretionary prism. The late structures also record different kinematic regimes associated with subduction of different oceanic plates, before and after ridge subduction. Prior to triple junction passage, subduction of the Farallon plate occurred at nearly right angles to the trench axis, whereas after triple junction migration, subduction of the Kula plate involved a significant component of dextral transpression and northward translation of the Chugach terrane. The changes in kinematics are apparent in the sequence of late structures from: (1) thrusting; (2) near-trench plutonism associated with normal + strike-slip faulting; (3) very late gouge-filled dextral faults.

Struggling to be part of Swedish society: Strategies used by immigrants with late effects of polio.

PubMed

Santos Tavares Silva, Iolanda; Thorén-Jönsson, Anna-Lisa

2015-01-01

To explore and describe strategies in daily occupations among immigrants with late effects of polio. The strategies were explored by interviews with 12 immigrants from Eastern Africa with late effects of polio. Sampling and data analysis was carried out according to grounded theory. The participants struggled for occupational participation and normality in an effort to participate in, and be part of, society. The study identified 14 strategies used by the immigrants in their daily occupations. The strategies can be presented in the following four categories: managing physical capacity; promoting occupational performance; strategies for gaining respect; and preparing the ground for one's existence. The participants struggled to find a balance between physical capacity and meaningful occupations, conception of their own and others' norms and values, and living conditions in Swedish society. The strategies were related to the participants' will to manage daily occupations, maintain social relationships, and be part of society. The strategies revealed that the participants strive to participate in occupations and society. This study reinforces the importance of occupation for immigrants with disability. The results highlight the need for adequate health care and rehabilitation but should also alert other social institutions.

Late-time Cooling of Neutron Star Transients and the Physics of the Inner Crust

NASA Astrophysics Data System (ADS)

Deibel, Alex; Cumming, Andrew; Brown, Edward F.; Reddy, Sanjay

2017-04-01

An accretion outburst onto a neutron star transient heats the neutron star’s crust out of thermal equilibrium with the core. After the outburst, the crust thermally relaxes toward equilibrium with the neutron star core, and the surface thermal emission powers the quiescent X-ray light curve. Crust cooling models predict that thermal equilibrium of the crust will be established ≈ 1000 {days} into quiescence. Recent observations of the cooling neutron star transient MXB 1659-29, however, suggest that the crust did not reach thermal equilibrium with the core on the predicted timescale and continued to cool after ≈ 2500 {days} into quiescence. Because the quiescent light curve reveals successively deeper layers of the crust, the observed late-time cooling of MXB 1659-29 depends on the thermal transport in the inner crust. In particular, the observed late-time cooling is consistent with a low thermal conductivity layer near the depth predicted for nuclear pasta that maintains a temperature gradient between the neutron star’s inner crust and core for thousands of days into quiescence. As a result, the temperature near the crust-core boundary remains above the critical temperature for neutron superfluidity, and a layer of normal neutrons forms in the inner crust. We find that the late-time cooling of MXB 1659-29 is consistent with heat release from a normal neutron layer near the crust-core boundary with a long thermal time. We also investigate the effect of inner crust physics on the predicted cooling curves of the accreting transient KS 1731-260 and the magnetar SGR 1627-41.

Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American rattlesnake bite patients.

PubMed

Bush, Sean P; Seifert, Steven A; Oakes, Jennifer; Smith, Susan D; Phan, Tammy H; Pearl, Sarah R; Reibling, Ellen T

2013-07-01

In patients bitten by North American rattlesnakes and treated with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV), late hematologic abnormalities-persistent, recurrent, or late, new onset of hypofibrinogenemia, prolonged PT/INR, prolonged PTT, and/or thrombocytopenia beyond 48 h post-envenomation-are common, difficult to manage, and may result in morbidity and mortality are common, difficult to manage, and may result in morbidity and mortality. The optimal management of late hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined. The current FabAV treatment regimen is to give antivenom as a bolus dose over a one-hour period. We describe our experience using a continuous intravenous infusion of FabAV for late hematologic effects and/or associated bleeding complications in rattlesnake envenomation. This is a retrospective, observational case series of patients envenomated by North American rattlesnakes at three medical centers managed with a continuous intravenous infusion of FabAV for late hematologic abnormalities and/or associated bleeding complications. Indications, dilution and infusion protocols, and duration of therapy were individualized. Five cases were identified between July 2010 and September 2011. All patients had profound late hematologic abnormalities and/or were associated with bleeding complications. Several patients had received repeat bolus infusions of FabAV, with or without human blood products, with either inadequate or only transient beneficial response. All patients were then managed with a continuous intravenous infusion of FabAV and all appeared to respond to the continuous intravenous infusion of FabAV, titrated to effect, with cessation of progression and, in most cases, improvement in hematologic abnormalities. Rates of infusion varied from 2 to 4 vials per 24 h (mean = 3.1 ± 0.4 vials/day). The termination of FabAV infusion was between day 6 and day 14 from the time of envenomation (mean = 10 ± 3 days), after which hematologic values were normalized or were normalizing in all patients and continued to do so. The use of FabAV as a continuous intravenous infusion, particularly after the acute phase of envenomation has passed, provides a continuous source of circulating antibodies to neutralize venom components reaching circulation from tissue stores and allows natural replenishment of hematologic factors such as platelets and/or fibrinogen. This method is an efficient use of FabAV, avoiding the wasteful excess of a bolus dose, may be more effective, eliminating the potential for destruction of hematologic factors when protective antivenom levels are lost between bolus FabAV doses, and appears to be safe. Further assessments of the stability and sterility of the product during infusion are needed. The need to continue hospitalization is the major drawback, but continued observation and inpatient care may be needed for other indications (e.g. bleeding) in this subset of patients. A continuous intravenous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 6-14 days post-envenomation appeared to be associated with reversal of late hematologic effects of rattlesnake envenomation and, when combined with indicated human blood products, control of significant bleeding. Continuous intravenous infusion of FabAV may be safer, more efficacious, and more cost-effective than observation without FabAV treatment or as-needed bolus dosing in selected patients with late hematologic abnormalities. Copyright © 2013 Elsevier Ltd. All rights reserved.

Factors influencing brain natriuretic peptide levels in healthy pregnant women.

PubMed

Mayama, Michinori; Yoshihara, Masato; Uno, Kaname; Tano, Sho; Takeda, Takehiko; Ukai, Mayu; Kishigami, Yasuyuki; Oguchi, Hidenori

2017-02-01

The normal range of plasma brain natriuretic peptide (BNP) in pregnant women is still unclear. Moreover, pregnant women experience dynamic body weight changes and suffer from anemia, but effects on maternal BNP have not been investigated. This study aimed to reveal the normal plasma BNP range and examine the effects of physiological changes on BNP among pregnant women. Plasma BNP, hemoglobin, plasma creatinine and BMI were measured in 58 non-pregnant control women and in 773 normal pregnant women at late pregnancy, early postpartum and 1-month postpartum. Mean plasma BNP (in pg/mL) was 11.8 (95% confidence interval: 0-27.5) in non-pregnant women, 17.9 (0-44.7, p<0.001) at late pregnancy, 42.5 (0-112.6, p<0.001) early postpartum and 16.1 (0-43.9, p=0.001) 1-month postpartum. Multiple regression analysis revealed that pre-delivery BNP levels were negatively correlated with BMI (p<0.001) and hemoglobin (p=0.002) and positively correlated with creatinine (p<0.001). Post-delivery BNP was positively associated with body weight change during pregnancy (p=0.001) and post-delivery creatinine (p=0.010) but negatively associated with body weight loss at delivery (p<0.001) and post-delivery hemoglobin (p=0.004). Even normal pregnancy affects plasma BNP, particularly in the early postpartum period, indicative of cardiac stress. Plasma BNP levels are affected by BMI, body weight changes, creatinine and hemoglobin levels; therefore, these factors should be considered when analysing cardiac function and the physiological implications of BNP levels in pregnant women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plaga, Alexis; Shields, Lisa B.E.; Sun, David A.

Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority givenmore » to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study may help to stratify patients at risk for late effects to develop strategies to reduce frequency and severity of radiation sequelae.« less

Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation.

PubMed

Plaga, Alexis; Shields, Lisa B E; Sun, David A; Vitaz, Todd W; Spalding, Aaron C

2012-01-01

Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study may help to stratify patients at risk for late effects to develop strategies to reduce frequency and severity of radiation sequelae. Copyright © 2012 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Control of bacteriophage P2 gene expression: analysis of transcription of the ogr gene.

PubMed Central

Birkeland, N K; Lindqvist, B H; Christie, G E

1991-01-01

The bacteriophage P2 ogr gene encodes an 8.3-kDa protein that is a positive effector of P2 late gene transcription. The ogr gene is preceded by a promoter sequence (Pogr) resembling a normal Escherichia coli promoter and is located just downstream of a late transcription unit. We analyzed the kinetics and regulation of ogr gene transcription by using an ogr-specific antisense RNA probe in an S1 mapping assay. During a normal P2 infection, ogr gene transcription starts from Pogr at an intermediate time between the onset of early and late transcription. At late times after infection the ogr gene is cotranscribed with the late FETUD operon; the ogr gene product thus positively regulates its own synthesis from the P2 late promoter PF. Expression of the P2 late genes also requires P2 DNA replication. Complementation experiments and transcriptional analysis show that a nonreplicating P2 phage expresses the ogr gene from Pogr but is unable to transcribe the late genes. A P2 ogr-defective phage makes an increased level of ogr mRNA, consistent with autogenous control from Pogr. Transcription of the ogr gene in the prophage of a P2 heteroimmune lysogen is stimulated after infection with P2, suggesting that Pogr is under indirect immunity control and is activated by a yet-unidentified P2 early gene product during infection. Images FIG. 4 FIG. 5 FIG. 6 FIG. 7 FIG. 8 PMID:1938896

Is 123I-metaiodobenzylguanidine heart-to-mediastinum ratio dependent on age? From Japanese Society of Nuclear Medicine normal database.

PubMed

Nakajima, Kenichi; Okuda, Koichi; Matsuo, Shinro; Wakabayashi, Hiroshi; Kinuya, Seigo

2018-04-01

Heart-to-mediastinum ratios (HMRs) of 123 I-metaiodobenzylguanidine (MIBG) have usually been applied to prognostic evaluations of heart failure and Lewy body disease. However, whether these ratios depend on patient age has not yet been clarified using normal databases. We analyzed 62 patients (average age 57 ± 19 years, male 45%) derived from a normal database of the Japanese Society of Nuclear Medicine working group. The HMR was calculated from early (15 min) and delayed (3-4 h) anterior planar 123 I-MIBG images. All HMRs were standardized to medium-energy general purpose (MEGP) collimator equivalent conditions using conversion coefficients for the collimator types. Washout rates (WR) were also calculated, and we analyzed whether early and late HMR, and WR are associated with age. Before standardization of HMR to MEGP collimator conditions, HMR and age did not significantly correlate. However, late HMR significantly correlated with age after standardization: late HMR = - 0.0071 × age + 3.69 (r 2  = 0.078, p = 0.028), indicating that a 14-year increase in age corresponded to a decrease in HMR of 0.1. Whereas the lower limit (2.5% quantile) of late HMR was 2.3 for all patients, it was 2.5 and 2.0 for those aged ≤ 63 and > 63 years, respectively. Early HMR tended to be lower in subjects with the higher age (p = 0.076), whereas WR was not affected by age. While late HMR was slightly decreased in elderly patients, the lower limit of 2.2-2.3 can still be used to determine both early and late HMR.

The hyper-fluorescent transitional bands in ultra-late phase of indocyanine green angiography in chronic central serous chorioretinopathy.

PubMed

Hua, Rui; Yao, Kai; Xia, Fan; Li, Jun; Guo, Lei; Yang, Guoxing; Tao, Jun

2016-03-01

Chronic central serous chorioretinopathy (CSCR) is regarded as a type of severe diffuse retinal pigment epitheliopathy. There is an atrophic tract at level of retinal pigment epithelium (RPE) due to hyper-permeability of choroidal vessels, along with photoreceptor (PR) atrophy. Indocyanine green angiography (ICGA) is considered a gold standard for diagnosis. The purpose of this work is to investigate the hyper-fluorescent transitional bands (HFTB) between hypo-fluorescent and normal regions of the retina in the ultra-late phase of ICGA in CSCR. 26 chronic CSCR eyes and 12 relative normal eyes received spectral domain optical coherence tomography (SD-OCT), and ICGA at the 24th hour after indocyanine green (ICG) intravenous injection. In the ultra-late phase, images showed homogenous fluorescence in all normal eyes. On the contrary, geographical hypofluorescent lesions with atrophy of RPE was noted in 26 chronic CSCR eyes. Moreover, HFTB with intact RPE and disrupted PR was detected in 20 out of 26 chronic CSCR eyes (76.9%). The HFTB may indicate the early damage in chronic CSCR. Ultra-late ICGA can monitor not only metabolic status by endogenous melanin, but also membrane function in RPE by exogenous ICG molecule. © 2015 Wiley Periodicals, Inc.

Effect of the menstrual cycle on the optic nerve head in diabetes: analysis by confocal scanning laser ophthalmoscopy.

PubMed

Akar, Munire Erman; Yucel, Iclal; Erdem, Uzeyir; Taskin, Omur; Ozel, Alper; Akar, Yusuf

2005-04-01

The purpose of this study was to examine and compare menstrual-cycle-dependent topographic changes in the optic nerve head of normally menstruating women with different grades of type 2 diabetes mellitus. We studied the right eyes of 123 normally menstruating women (36 with severe nonproliferative diabetic retinopathy [NPDR], 42 with mild NPDR and 45 healthy subjects). All subjects underwent a complete ocular examination at baseline. At 4 hormonally distinct phases of the menstrual cycle (early follicular, late follicular, mid-luteal and late luteal), we analysed the topography of the optic nerve head, using a confocal scanning laser ophthalmoscope, and measured the serum levels of estradiol, progesterone and luteinizing hormone. We excluded from analysis the data for 8 patients with severe NPDR, 10 patients with mild NPDR and 15 control subjects who were lost to follow-up examinations during the menstrual cycle. The mean age and optic disc area did not differ significantly among the 3 groups. The duration of diabetes was significantly longer in the patients with severe NPDR than in those with mild NPDR (p < 0.05). The women with severe NPDR had a significantly increased neuroretinal rim area and a significantly decreased cup-shape measure, linear cup/disc ratio, cup/disc area ratio and cup area in the late luteal phase compared with the other phases of the menstrual cycle (p < 0.05). Those with mild NPDR or a normal retina had no significant topographic changes in the optic nerve head during the menstrual cycle. Severe NPDR is associated with significant topographic changes in the rim and cup of the optic nerve head during the menstrual cycle. This must be considered in the evaluation of women with both diabetes and glaucoma. The normal fluctuations in serum sex hormone levels during the menstrual cycle of diabetic women seem to affect the optic nerve head more when the disease is advanced.

Language Outcomes of 7-Year-Old Children with or without a History of Late Language Emergence at 24 Months

ERIC Educational Resources Information Center

Rice, Mabel L.; Taylor, Catherine L.; Zubrick, Stephen R.

2008-01-01

Purpose: The aim of this study was to investigate the language outcomes of 7-year-old children with and without a history of late language emergence at 24 months. Method: One hundred twenty-eight children with a history of late language emergence (LLE) at 24 months and 109 children with a history of normal language emergence (NLE) at 24 months…

Cosmology of a Friedmann-Lamaître-Robertson-Walker 3-brane, late-time cosmic acceleration, and the cosmic coincidence.

PubMed

Doolin, Ciaran; Neupane, Ishwaree P

2013-04-05

A late epoch cosmic acceleration may be naturally entangled with cosmic coincidence--the observation that at the onset of acceleration the vacuum energy density fraction nearly coincides with the matter density fraction. In this Letter we show that this is indeed the case with the cosmology of a Friedmann-Lamaître-Robertson-Walker (FLRW) 3-brane in a five-dimensional anti-de Sitter spacetime. We derive the four-dimensional effective action on a FLRW 3-brane, from which we obtain a mass-reduction formula, namely, M(P)(2) = ρ(b)/|Λ(5)|, where M(P) is the effective (normalized) Planck mass, Λ(5) is the five-dimensional cosmological constant, and ρ(b) is the sum of the 3-brane tension V and the matter density ρ. Although the range of variation in ρ(b) is strongly constrained, the big bang nucleosynthesis bound on the time variation of the effective Newton constant G(N) = (8πM(P)(2))(-1) is satisfied when the ratio V/ρ ≳ O(10(2)) on cosmological scales. The same bound leads to an effective equation of state close to -1 at late epochs in accordance with astrophysical and cosmological observations.

Proximal Femur Mechanical Adaptation to Weight Gain in Late Adolescence: A Six-Year Longitudinal Study

PubMed Central

Petit, Moira A; Beck, Thomas J; Hughes, Julie M; Lin, Hung-Mo; Bentley, Christy; Lloyd, Tom

2008-01-01

The effect of weight gain in late adolescence on bone is not clear. Young women who consistently gained weight (n = 23) from 17 to 22 yr of age had increased BMD but a lack of subperiosteal expansion compared with stable weight peers (n = 48). Bone strength increased appropriately for lean mass in both groups but decreased relative to body weight in weight gainers, suggesting increased bone fragility in weight gainers. Introduction Weight gain leading to obesity often starts in adolescence, yet little is known about its effects on bone. We used longitudinal data to examine the effects of weight gain in late adolescence (from 17 to 22 yr of age) on proximal femur BMD, geometry, and estimates of bending strength. Materials and Methods Participants were classified as either weight gainers (WG, n = 23) or stable weight (SW, n = 48) using a random coefficients model. Weight gainers had positive increases in weight (p < 0.05) at each clinic visit from age 17 onward. Proximal femur DXA scans (Hologic QDR 2000) taken annually from 17 to 22 yr of age were analyzed for areal BMD (g/cm2), subperiosteal width (cm), and bone cross-sectional area (CSA) at the proximal femoral shaft. Cortical thickness was measured, and section modulus (Z, cm3) was calculated as a measure of bone bending strength. Total body lean (g) and fat (g) mass were measured from DXA total body scans. Results Over ages 17–22, height remained stable in both groups. Weight remained static in the SW group but increased 14% on average in the WG group (p < 0.05). After controlling for age 17 baseline values, WG had higher BMD (+2.6%), thicker cortices (+3.6%), and greater bone CSA (+2.3%). Increased BMD did not translate to greater increases in bone bending strength (Z). The SW group achieved similar gains in Z by greater subperiosteal expansion. Bone strength index (SI = Z/height) normalized for body weight remained constant in the SW group but decreased significantly in the WG group. In contrast, SI normalized to lean mass did not change over time in either group. Other variables including physical activity, nutrition, and hormone levels (estradiol, testosterone, cortisol) did not differ significantly between groups. Conclusions These data suggest that weight gain in late adolescence may inhibit the periosteal expansion known to normally occur throughout life in long bones, resulting in decreased bone strength relative to body weight. PMID:17937533

Akron Perkins Normal School: An Institutional History, 1898-1931.

ERIC Educational Resources Information Center

Kline, Melinda J.

The preparation of elementary school teachers in the middle and late 19th century increasingly included city normal training schools. The city school board of Akron, Ohio, reflected this trend and established its own normal training school in 1898. This paper documents the preservice training of teachers within the city training school, the…

The effect of puberty on fat oxidation rates during exercise in overweight and normal-weight girls.

PubMed

Chu, L; Riddell, M C; Schneiderman, J E; McCrindle, B W; Hamilton, J K

2014-01-01

Excess weight is often associated with insulin resistance (IR) and may disrupt fat oxidation during exercise. This effect is further modified by puberty. While studies have shown that maximal fat oxidation rates (FOR) during exercise decrease with puberty in normal-weight (NW) and overweight (OW) boys, the effect of puberty in NW and OW girls is unclear. Thirty-three NW and OW girls ages 8-18 yr old completed a peak aerobic capacity test on a cycle ergometer. FOR were calculated during progressive submaximal exercise. Body composition and Tanner stage were determined. For each participant, a best-fit polynomial curve was constructed using fat oxidation vs. exercise intensity to estimate max FOR. In a subset of the girls, IR derived from an oral glucose tolerance test (n = 20), and leptin and adiponectin levels (n = 11) were assessed in relation to FOR. NW pre-early pubertal girls had higher max FOR [6.9 ± 1.4 mg·kg fat free mass (FFM)(-1)·min(-1)] than NW mid-late pubertal girls (2.2 ± 0.9 mg·kg FFM(-1)·min(-1)) (P = 0.002), OW pre-early pubertal girls (3.8 ± 2.1 mg·kg FFM(-1)·min(-1)), and OW mid-late pubertal girls (3.3 ± 0.9 mg·kg FFM(-1)·min(-1)) (P < 0.05). Bivariable analyses showed positive associations between FOR with homeostatic model assessment of IR (P = 0.001), leptin (P < 0.001), and leptin-to-adiponectin ratio (P = 0.001), independent of percent body fat. Max FOR decreased in NW girls during mid-late puberty; however, this decrease associated with puberty was blunted in OW girls due to lower FOR in pre-early puberty. The presence of IR due to obesity potentially masks the effect of puberty on FOR during exercise in girls.

Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl; Floot, Ben; Russell, Nicola S.

Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, andmore » 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.« less

Fast Mapping in Late-Talking Toddlers

ERIC Educational Resources Information Center

Weismer, Susan Ellis; Venker, Courtney E.; Evans, Julia L.; Moyle, Maura Jones

2013-01-01

This study investigated fast mapping in late-talking (LT) toddlers and toddlers with normal language (NL) development matched on age, nonverbal cognition, and maternal education. The fast-mapping task included novel object labels and familiar words. The LT group scored significantly lower than the NL group on novel word comprehension and…

Myxomatosis: changes in the epidemiology of myxomatosis coincident with the establishment of the European rabbit flea Spilopsyllus cuniculi (Dale) in the Mallee region of Victoria

PubMed Central

Shepherd, Rosamond C. H.; Edmonds, J. W.

1978-01-01

Outbreaks of myxomatosis during the winter or spring have coincided with the establishment of the European rabbit flea in the Mallee region. The severity of these outbreaks has varied from causing complete suppression of the normal spring increase in rabbit numbers to being completely ineffective in a year in which late spring rains allowed rabbit breeding to extend into the early summer. In 1973 and 1974 effective spring myxomatosis caused heavy mortality in kittens before they emerged from the warrens. The age of the population increased as the result of few young rabbits coming into the population and of the lessened stress on old rabbits in a low summer—autumn population. This effect was reversed in the late-breeding year, 1976, when flea numbers were apparently too low to maintain a spring outbreak and rabbit numbers increased rapidly. PMID:569676

Myxomatosis: changes in the epidemiology of myxomatosis coincident with the establishment of the European rabbit flea Spilopsyllus cuniculi (Dale) in the Mallee region of Victoria.

PubMed

Shepherd, R C; Edmonds, J W

1978-12-01

Outbreaks of myxomatosis during the winter or spring have coincided with the establishment of the European rabbit flea in the Mallee region. The severity of these outbreaks has varied from causing complete suppression of the normal spring increase in rabbit numbers to being completely ineffective in a year in which late spring rains allowed rabbit breeding to extend into the early summer.In 1973 and 1974 effective spring myxomatosis caused heavy mortality in kittens before they emerged from the warrens. The age of the population increased as the result of few young rabbits coming into the population and of the lessened stress on old rabbits in a low summer-autumn population. This effect was reversed in the late-breeding year, 1976, when flea numbers were apparently too low to maintain a spring outbreak and rabbit numbers increased rapidly.

Large scale structure formation of the normal branch in the DGP brane world model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Yong-Seon

2008-06-15

In this paper, we study the large scale structure formation of the normal branch in the DGP model (Dvail, Gabadadze, and Porrati brane world model) by applying the scaling method developed by Sawicki, Song, and Hu for solving the coupled perturbed equations of motion of on-brane and off-brane. There is a detectable departure of perturbed gravitational potential from the cold dark matter model with vacuum energy even at the minimal deviation of the effective equation of state w{sub eff} below -1. The modified perturbed gravitational potential weakens the integrated Sachs-Wolfe effect which is strengthened in the self-accelerating branch DGP model.more » Additionally, we discuss the validity of the scaling solution in the de Sitter limit at late times.« less

Effects of education on the progression of early- versus late-stage mild cognitive impairment.

PubMed

Ye, Byoung Seok; Seo, Sang Won; Cho, Hanna; Kim, Seong Yoon; Lee, Jung-Sun; Kim, Eun-Joo; Lee, Yunhwan; Back, Joung Hwan; Hong, Chang Hyung; Choi, Seong Hye; Park, Kyung Won; Ku, Bon D; Moon, So Young; Kim, Sangyun; Han, Seol-Heui; Lee, Jae-Hong; Cheong, Hae-Kwan; Na, Duk L

2013-04-01

Highly educated participants with normal cognition show lower incidence of Alzheimer's disease (AD) than poorly educated participants, whereas longitudinal studies involving AD have reported that higher education is associated with more rapid cognitive decline. We aimed to evaluate whether highly educated amnestic mild cognitive impairment (aMCI) participants show more rapid cognitive decline than those with lower levels of education. A total of 249 aMCI patients enrolled from 31 memory clinics using the standard assessment and diagnostic processes were followed with neuropsychological evaluation (duration 17.2 ± 8.8 months). According to baseline performances on memory tests, participants were divided into early-stage aMCI (-1.5 to -1.0 standard deviation (SD)) and late-stage aMCI (below -1.5 SD) groups. Risk of AD conversion and changes in neuropsychological performances according to the level of education were evaluated. Sixty-two patients converted to AD over a mean follow-up of 1.43 years. The risk of AD conversion was higher in late-stage aMCI than early-stage aMCI. Cox proportional hazard models showed that aMCI participants, and late-stage aMCI participants in particular, with higher levels of education had a higher risk of AD conversion than those with lower levels of education. Late-stage aMCI participants with higher education showed faster cognitive decline in language, memory, and Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores. On the contrary, early-stage aMCI participants with higher education showed slower cognitive decline in MMSE and CDR-SOB scores. Our findings suggest that the protective effects of education against cognitive decline remain in early-stage aMCI and disappear in late-stage aMCI.

The Effects of Phosphatidylserine and Omega-3 Fatty Acid-Containing Supplement on Late Life Depression

PubMed Central

Komori, Teruhisa

2015-01-01

Late life depression is often associated with a poor response to antidepressants; therefore an alternative strategy for therapy is required. Although several studies have reported that phosphatidylserine (PS) may be effective for late life depression and that omega-3 fatty acids DHA and EPA have also proven beneficial for many higher mental functions, including depression, no concrete conclusion has been reached. This study was performed to clarify the effect of PS and omega-3 fatty acid-containing supplement for late life depression by not only clinical evaluation but also salivary cortisol levels. Eighteen elderly subjects with major depression were selected for the study. In all, insufficient improvement had been obtained by antidepressant therapy for at least 6 months. The exclusion criteria from prior brain magnetic resonance images (MRI) included the presence of structural MRI findings compatible with stroke or other gross brain lesions or malformations, but not white matter hypersensitivities. They took a supplement containing PS 100 mg, DHA 119 mg and EPA 70 mg three times a day for 12 weeks. The effects of the supplement were assessed using the 17-item Hamilton depression scale (HAM-D17) and the basal levels and circadian rhythm of salivary cortisol. The study adopted them as indices because: salivary cortisol levels are high in patients with depression, their circadian rhythm related to salivary cortisol is often irregular, and these symptoms are alleviated as depression improves. The mean HAM-D17 in all subjects taking the supplement was significantly improved after 12 weeks of taking the supplement. These subjects were divided into 10 non-responders and 8 responders. The basal levels and circadian rhythm of salivary cortisol were normalized in the responders while not in non-responders. PS and omega-3 fatty acids, or other elements of the supplement, may be effective for late life depression, associated with the correction of basal levels and circadian rhythm of salivary cortisol. PMID:26266022

PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat.

PubMed

Fernández-Blanco, Joan Antoni; Fernández-Blanco, Juan A; Hollenberg, Morley D; Martínez, Vicente; Vergara, Patri

2013-02-15

Proteinase-activated receptor-2 (PAR-2) and mast cell (MC) mediators contribute to inflammatory and functional gastrointestinal disorders. We aimed to characterize jejunal PAR-2-mediated responses and the potential MC involvement in the early and late phases of a rat model of postinfectious gut dysfunction. Jejunal tissues of control and Trichinella spiralis-infected (14 and 30 days postinfection) rats, treated or not with the MC stabilizer, ketotifen, were used. Histopathology and immunostaining were used to characterize inflammation, PAR-2 expression, and mucosal and connective tissue MCs. Epithelial barrier function (hydroelectrolytic transport and permeability) and motility were assessed in vitro in basal conditions and after PAR-2 activation. Intestinal inflammation on day 14 postinfection (early phase) was significantly resolved by day 30 (late phase) although MC counts and epithelial permeability remained increased. PAR-2-mediated ion transport (Ussing chambers, in vitro) and epithelial surface PAR-2 expression were reduced in the early phase, with a trend toward normalization during the late phase. In control conditions, PAR-2 activation (organ bath) induced biphasic motor responses (relaxation followed by excitation). At 14 days postinfection, spontaneous contractility and PAR-2-mediated relaxations were enhanced; motor responses were normalized on day 30. Postinfectious changes in PAR-2 functions were not affected by ketotifen treatment. We concluded that, in the rat model of Trichinella spiralis infection, alterations of intestinal PAR-2 function and expression depend on the inflammatory phase considered. A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction.

Determining the best phenological state for accurate mapping of Phragmites australis in wetlands using time series multispectral satellite data

NASA Astrophysics Data System (ADS)

Rupasinghe, P. A.; Markle, C. E.; Marcaccio, J. V.; Chow-Fraser, P.

2017-12-01

Phragmites australis (European common reed), is a relatively recent invader of wetlands and beaches in Ontario. It can establish large homogenous stands within wetlands and disperse widely throughout the landscape by wind and vehicular traffic. A first step in managing this invasive species includes accurate mapping and quantification of its distribution. This is challenging because Phragimtes is distributed in a large spatial extent, which makes the mapping more costly and time consuming. Here, we used freely available multispectral satellite images taken monthly (cloud free images as available) for the calendar year to determine the optimum phenological state of Phragmites that would allow it to be accurately identified using remote sensing data. We analyzed time series, Landsat-8 OLI and Sentinel-2 images for Big Creek Wildlife Area, ON using image classification (Support Vector Machines), Normalized Difference Vegetation Index (NDVI) and Normalized Difference Water Index (NDWI). We used field sampling data and high resolution image collected using Unmanned Aerial Vehicle (UAV; 8 cm spatial resolution) as training data and for the validation of the classified images. The accuracy for all land cover classes and for Phragmites alone were low at both the start and end of the calendar year, but reached overall accuracy >85% by mid to late summer. The highest classification accuracies for Landsat-8 OLI were associated with late July and early August imagery. We observed similar trends using the Sentinel-2 images, with higher overall accuracy for all land cover classes and for Phragmites alone from late July to late September. During this period, we found the greatest difference between Phragmites and Typha, commonly confused classes, with respect to near-infrared and shortwave infrared reflectance. Therefore, the unique spectral signature of Phragmites can be attributed to both the level of greenness and factors related to water content in the leaves during late summer. Landsat-8 OLI or Sentinel-2 images acquired in late summer can be used as a cost effective approach to mapping Phragmites at a large spatial scale without sacrificing accuracy.

Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sheehan, Megan M.; Karunamuni, Ganga; Pedersen, Cameron J.; Gu, Shi; Doughman, Yong Qiu; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

2017-02-01

Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. Up to 40% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects (CHDs) including life-threatening outflow and valvuloseptal anomalies. Previously we established a PAE model in the avian embryo and used optical coherence tomography (OCT) imaging to assay looping-stage (early) cardiac function/structure and septation-stage (late) cardiac defects. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septae, and aortic vessels. However, supplementation with the methyl donor betaine reduced gross defects, prevented cardiac defects such as ventricular septal defects and abnormal AV valves, and normalized cardiac parameters. Immunofluorescent staining for 5-methylcytosine in transverse embryo sections also revealed that DNA methylation levels were reduced by ethanol but normalized by co-administration of betaine. Furthermore, supplementation with folate, another methyl donor, in the PAE model appeared to normalize retrograde flow levels which are typically elevated by ethanol exposure. Studies are underway to correlate retrograde flow numbers for folate with associated cushion volumes. Finally, preliminary findings have revealed that glutathione, a key endogenous antioxidant which also regulates methyl group donation, is particularly effective in improving alcohol-impacted survival and gross defect rates. Current investigations will determine whether glutathione has any positive effect on PAE-related CHDs. Our studies could have significant implications for public health, especially related to prenatal nutrition recommendations.

Glucose starvation impairs DNA repair in tumour cells selectively by blocking histone acetylation.

PubMed

Ampferl, Rena; Rodemann, Hans Peter; Mayer, Claus; Höfling, Tobias Tim Alexander; Dittmann, Klaus

2018-03-01

Tumour cells are characterized by aerobic glycolysis and thus have high glucose consumption. Because repairing radiation-induced DNA damage is an energy-demanding process, we hypothesized that glucose starvation combined with radiotherapy could be an effective strategy to selectively target tumour cells. We glucose-starved tumour cells (A549, FaDu) in vitro and analysed their radiation-induced cell responses compared to normal fibroblasts (HSF7). Irradiation depleted intracellular ATP levels preferentially in cancer cells. Consequently, glucose starvation impaired DNA double-strand break (DSB) repair and radiosensitized confluent tumour cells but not normal fibroblasts. In proliferating tumour cells glucose starvation resulted in a reduction of proliferation, but failed to radiosensitize cells. Glucose supply was indispensable during the late DSB repair in confluent tumour cells starting approximately 13 h after irradiation, and glucose starvation inhibited radiation-induced histone acetylation, which is essential for chromatin relaxation. Sirtinol - an inhibitor of histone deacetylases - reverted the effects of glucose depletion on histone acetylation and DNA DSB repair in tumour cells. Furthermore, a glucose concentration of 2.8 mmol/L was sufficient to impair DSB repair in tumour cells and reduced their clonogenic survival under a fractionated irradiation regimen. In resting tumour cells, glucose starvation combined with irradiation resulted in the impairment of late DSB repair and the reduction of clonogenic survival, which was associated with disrupted radiation-induced histone acetylation. However, in normal cells, DNA repair and radiosensitivity were not affected by glucose depletion. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of premedication with subcutaneous adrenaline on the pharmacokinetics and immunogenicity of equine whole IgG antivenom in a rabbit model.

PubMed

Herrera, María; Sánchez, Melvin; Machado, Anderson; Ramírez, Nils; Vargas, Mariángela; Villalta, Mauren; Sánchez, Andrés; Segura, Álvaro; Gómez, Aarón; Solano, Gabriela; Gutiérrez, José María; León, Guillermo

2017-06-01

Subcutaneous administration of a low dose of adrenaline is used to prevent the early adverse reactions (EARs) induced by snake antivenoms. We used a rabbit model to study the effect of premedication with adrenaline on the potential of antivenoms to exert therapeutic effects and to induce late adverse reactions. We found that premedication with adrenaline did not change the heart rate or blood pressure of normal rabbits, but reduced the rise in temperature in rabbits previously sensitized with antivenom. Pharmacokinetic studies suggest that premedication with adrenaline does not affect the ability of the antivenom to exert the initial control of envenomation nor the susceptibility of rabbits to develop recurrence of antigenemia and envenomation. Our results also indicate that it is unlikely that premedication with adrenaline decreases the incidence of late reactions induced by the antivenom administration, although it reduces the extent of early reactions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sonic Hedgehog modulates EGFR dependent proliferation of neural stem cells during late mouse embryogenesis through EGFR transactivation

PubMed Central

Reinchisi, Gisela; Parada, Margarita; Lois, Pablo; Oyanadel, Claudia; Shaughnessy, Ronan; Gonzalez, Alfonso; Palma, Verónica

2013-01-01

Sonic Hedgehog (Shh/GLI) and EGFR signaling pathways modulate Neural Stem Cell (NSC) proliferation. How these signals cooperate is therefore critical for understanding normal brain development and function. Here we report a novel acute effect of Shh signaling on EGFR function. We show that during late neocortex development, Shh mediates the activation of the ERK1/2 signaling pathway in Radial Glial cells (RGC) through EGFR transactivation. This process is dependent on metalloprotease activity and accounts for almost 50% of the EGFR-dependent mitogenic response of late NSCs. Furthermore, in HeLa cancer cells, a well-known model for studying the EGFR receptor function, Shh also induces cell proliferation involving EGFR activation, as reflected by EGFR internalization and ERK1/2 phosphorylation. These findings may have important implications for understanding the mechanisms that regulate NSC proliferation during neurogenesis and may lead to novel approaches to the treatment of tumors. PMID:24133411

Clustering and age of onset in familial late onset Alzheimer`s disease are determined at the apoliopoprotein E locus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Houlden, H.; Rossor, M.

1994-09-01

Recent work has demonstrated that the apolipoprotein E (ApoE) genotype is of great importance in the etiology of Alzheimer`s disease (AD). Thus, inheritance of the ApoE4 allele predisposes to the occurrences of late onset disease and decreases the onset age in families with pathogenic mutations in the amyloid precursor protein gene. We analysed ApoE genotypes in 35 families multiply affected by AD and confirm that familial clustering in late onset AD is associated with the ApoE4 allele. This allele occurs in the great majority (82%) of late onset familial Alzheimer cases. Elderly unaffected sibs (80-90 years) have an allele frequencymore » that is not significantly different to that of normal controls. Data presented from our family sets together previously published data is suggestive that the effect of a single ApoE4 allele is to increase the risk of developing AD by an amount equivalent to 5 years and that the effect of ApoE4 homozygosity is to increase the risk of developing AD by an amount equivalent to 10 years of age. Data shows significant difference between the frequency of the ApoE4 allele in the familial AD probands and controls and in both sets of unaffected sibs, p<0.01.« less

Long-Term Positive and Negative Psychological Late Effects for Parents of Childhood Cancer Survivors: A Systematic Review

PubMed Central

Ljungman, Lisa; Cernvall, Martin; Grönqvist, Helena; Ljótsson, Brjánn; Ljungman, Gustaf; von Essen, Louise

2014-01-01

Increasing survival rates in childhood cancer have yielded a growing population of parents of childhood cancer survivors (CCSs). This systematic review compiles the literature on positive and negative long-term psychological late effects for parents of CCSs, reported at least five years after the child's diagnosis and/or two years after the end of the child's treatment. Systematic searches were made in the databases CINAHL, EMBASE, PsycINFO, and PubMed. Fifteen studies, published between 1988 and 2010, from 12 projects were included. Thirteen studies used quantitative methodology, one quantitative and qualitative methodology, and one qualitative methodology. A total of 1045 parents participated in the reviewed studies. Mean scores were within normal ranges for general psychological distress, coping, and family functioning. However, a substantial subgroup reported a clinical level of general psychological distress, and 21–44% reported a severe level of posttraumatic stress symptoms. Worry, disease-related thoughts and feelings, marital strains, as well as posttraumatic growth was reported. Several factors were associated with the long-term late effects, such as parents' maladaptive coping during earlier stages of the childs disease trajectory and children's current poor adjustment. Quality assessments of reviewed studies and clinical implications of findings are discussed and recommendations for future research are presented. PMID:25058607

A neutral effect of testosterone therapy on macroprolactin content in men with macroprolactinemia and late-onset hypogonadism.

PubMed

Krysiak, Robert; Kowalska, Beata; Szkróbka, Witold; Okopień, Bogusław

2016-02-01

In the light of recent studies, macroprolactinemia seems to occur much more frequently than previously thought. In women, oral contraceptive pills exhibit a stimulatory effect on macroprolactin production. No previous study has investigated macroprolactin levels in androgen-treated hypogonadal men. We studied 10 men with isolated macroprolactinemia and 14 men with normal prolactin levels who because of late-onset hypogonadism were treated with intramuscular testosterone enanthate. Serum prolactin, macroprolactin content, serum testosterone and gonadotropin levels were assessed at baseline and after 4 months of therapy. Although baseline levels of testosterone and gonadotropins were similar in men with and without macroprolactinemia, clinical symptoms were more severe in patients with elevated big-big prolactin levels. As expected, testosterone treatment increased serum testosterone, slightly reduced serum gonadotropins, as well as improved clinical condition in both patients with and without macroprolactinemia, with no difference between the groups. However, testosterone therapy did not affect serum prolactin and macroprolactin content, even after replacing intramuscular testosterone enanthate with oral testosterone undecanoate. Our results suggest a negligible effect of testosterone replacement on macroprolactin levels in macroprolactinemic men with late-onset hypogonadism. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Impact of the NTCP modeling on medical decision to select eligible patient for proton therapy: the usefulness of EUD as an indicator to rank modern photon vs proton treatment plans.

PubMed

Chaikh, Abdulhamid; Calugaru, Valentin; Bondiau, Pierre-Yves; Thariat, Juliette; Balosso, Jacques

2018-06-07

The aim of this study is to evaluate the impact of normal tissue complication probability (NTCP)-based radiobiological models on the estimated risk for late radiation lung damages. The second goal is to propose a medical decision-making approach to select the eligible patient for particle therapy. 14 pediatric patients undergoing cranio-spinal irradiation were evaluated. For each patient, two treatment plans were generated using photon and proton therapy with the same dose prescriptions. Late radiation damage to lung was estimated using three NTCP concepts: the Lyman-Kutcher-Burman, the equivalent uniform dose (EUD) and the mean lung dose according to the quantitative analysis of normal tissue effects in the clinic QUANTEC review. Wilcoxon paired test was used to calculate p-value. Proton therapy achieved lower lung EUD (Gy). The average NTCP values were significantly lower with proton plans, p < 0.05, using the three NTCP concepts. However, applying the same TD 50/5 using radiobiological models to compare NTCP from proton and photon therapy, the ΔNTCP was not a convincing method to measure the potential benefit of proton therapy. Late radiation pneumonitis estimated from the mean lung dose model correlated with QUANTEC data better. treatment effectiveness assessed on NTCP reduction depends on radiobiological predictions and parameters used as inputs for in silico evaluation. Since estimates of absolute NTCP values from LKB and GN models are imprecise due to EUD ≪ TD 50/5 , a reduction of the EUD value with proton plans would better predict a reduction of dose/toxicity. The EUD concept appears as a robust radiobiological surrogate of the dose distribution to select the optimal patient's plan.

Variation in Telangiectasia Predisposing Genes Is Associated With Overall Radiation Toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanteles, George A.; Department of Cancer Studies and Molecular Medicine, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester; Murray, Robert J.S.

2012-11-15

Purpose: In patients receiving radiotherapy for breast cancer where the heart is within the radiation field, cutaneous telangiectasiae could be a marker of potential radiation-induced heart disease. We hypothesized that single nucleotide polymorphisms (SNPs) in genes known to cause heritable telangiectasia-associated disorders could predispose to such late, normal tissue vascular damage. Methods and Materials: The relationship between cutaneous telangiectasia as a late normal tissue radiation injury phenotype in 633 breast cancer patients treated with radiotherapy was examined. Patients were clinically assessed for the presence of cutaneous telangiectasia and genotyped at nine SNPs in three candidate genes. Candidate SNPs were withinmore » the endoglin (ENG) and activin A receptor, type II-like 1 (ACVRL1) genes, mutations in which cause hereditary hemorrhagic telangiectasia and the ataxia-telangiectasia mutated (ATM) gene associated with ataxia-telangiectasia. Results: A total of 121 (19.1%) patients exhibited a degree of cutaneous telangiectasiae on clinical examination. Regression was used to examine the associations between the presence of telangiectasiae in patients who underwent breast-conserving surgery, controlling for the effects of boost and known brassiere size (n=388), and individual geno- or haplotypes. Inheritance of ACVRL1 SNPs marginally contributed to the risk of cutaneous telangiectasiae. Haplotypic analysis revealed a stronger association between inheritance of a ATM haplotype and the presence of cutaneous telangiectasiae, fibrosis and overall toxicity. No significant association was observed between telangiectasiae and the coinheritance of the candidate ENG SNPs. Conclusions: Genetic variation in the ATM gene influences reaction to radiotherapy through both vascular damage and increased fibrosis. The predisposing variation in the ATM gene will need to be better defined to optimize it as a predictive marker for assessing radiotherapy late effects.« less

Vortex flow during early and late left ventricular filling in normal subjects: quantitative characterization using retrospectively-gated 4D flow cardiovascular magnetic resonance and three-dimensional vortex core analysis.

PubMed

Elbaz, Mohammed S M; Calkoen, Emmeline E; Westenberg, Jos J M; Lelieveldt, Boudewijn P F; Roest, Arno A W; van der Geest, Rob J

2014-09-27

LV diastolic vortex formation has been suggested to critically contribute to efficient blood pumping function, while altered vortex formation has been associated with LV pathologies. Therefore, quantitative characterization of vortex flow might provide a novel objective tool for evaluating LV function. The objectives of this study were 1) assess feasibility of vortex flow analysis during both early and late diastolic filling in vivo in normal subjects using 4D Flow cardiovascular magnetic resonance (CMR) with retrospective cardiac gating and 3D vortex core analysis 2) establish normal quantitative parameters characterizing 3D LV vortex flow during both early and late ventricular filling in normal subjects. With full ethical approval, twenty-four healthy volunteers (mean age: 20±10 years) underwent whole-heart 4D Flow CMR. The Lambda2-method was used to extract 3D LV vortex ring cores from the blood flow velocity field during early (E) and late (A) diastolic filling. The 3D location of the center of vortex ring core was characterized using cylindrical cardiac coordinates (Circumferential, Longitudinal (L), Radial (R)). Comparison between E and A filling was done with a paired T-test. The orientation of the vortex ring core was measured and the ring shape was quantified by the circularity index (CI). Finally, the Spearman's correlation between the shapes of mitral inflow pattern and formed vortex ring cores was tested. Distinct E- and A-vortex ring cores were observed with centers of A-vortex rings significantly closer to the mitral valve annulus (E-vortex L=0.19±0.04 versus A-vortex L=0.15±0.05; p=0.0001), closer to the ventricle's long-axis (E-vortex: R=0.27±0.07, A-vortex: R=0.20±0.09, p=0.048) and more elliptical in shape (E-vortex: CI=0.79±0.09, A-vortex: CI=0.57±0.06; <0.001) compared to E-vortex. The circumferential location and orientation relative to LV long-axis for both E- and A-vortex ring cores were similar. Good to strong correlation was found between vortex shape and mitral inflow shape through both the annulus (r=0.66) and leaflet tips (r=0.83). Quantitative characterization and comparison of 3D vortex rings in LV inflow during both early and late diastolic phases is feasible in normal subjects using retrospectively-gated 4D Flow CMR, with distinct differences between early and late diastolic vortex rings.

Multiple determinants controlling activation of yeast replication origins late in S phase.

PubMed

Friedman, K L; Diller, J D; Ferguson, B M; Nyland, S V; Brewer, B J; Fangman, W L

1996-07-01

Analysis of a 131-kb segment of the left arm of yeast chromosome XIV beginning 157 kb from the telomere reveals four highly active origins of replication that initiate replication late in S phase. Previous work has shown that telomeres act as determinants for late origin activation. However, at least two of the chromosome XIV origins maintain their late activation time when located on large circular plasmids, indicating that late replication is independent of telomeres. Analysis of the replication time of plasmid derivatives containing varying amounts of chromosome XIV DNA show that a minimum of three chromosomal elements, distinct from each tested origin, contribute to late activation time. These late determinants are functionally equivalent, because duplication of one set of contributing sequences can compensate for the removal of another set. Furthermore, insertion of an origin that is normally early activated into this domain results in a shift to late activation, suggesting that the chromosome XIV origins are not unique in their ability to respond to the late determinants.

Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila.

PubMed

Kuo, Tzu-Hsing; Williams, Julie A

2014-05-01

Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Laboratory. Drosophila melanogaster. Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection.

The Generation of Superficial Cortical Layers Is Regulated by Levels of the Transcription Factor Pax6

PubMed Central

Manuel, Martine; Price, David J.

2011-01-01

The ventricular zone (VZ) of the embryonic dorsal telencephalon is a major site for generating cortical projection neurons. The transcription factor Pax6 is highly expressed in apical progenitors (APs) residing in the VZ from the earliest stages of corticogenesis. Previous studies mainly focused on Pax6−/− mice have implicated Pax6 in regulating cortical progenitor proliferation, neurogenesis, and formation of superficial cortical layers. We analyzed the developing cortex of PAX77 transgenic mice that overexpress Pax6 in its normal domains of expression. We show that Pax6 overexpression increases cell cycle length of APs and drives the system toward neurogenesis. These effects are specific to late stages of corticogenesis, when superficial layer neurons are normally generated, in cortical regions that express Pax6 at the highest levels. The number of superficial layer neurons is reduced in postnatal PAX77 mice, whereas radial migration and lamina specification of cortical neurons are not affected by Pax6 overexpression. Conditional deletion of Pax6 in cortical progenitors at midstages of corticogenesis, by using a tamoxifen-inducible Emx1-CreER line, affected both numbers and specification of late-born neurons in superficial layers of the mutant cortex. Our analyses suggest that correct levels of Pax6 are essential for normal production of superficial layers of the cortex. PMID:20413449

Late myocardial ischemia with ST-segment elevation after negative dobutamine stress echocardiography in a patient with normal coronary arteries.

PubMed

Cabani, Enrico; Lattanzi, Fabio; Paci, Anna Maria; Pieroni, Andrea; Baria, Luca; Tommasi, Salvatore Mario De

2009-04-01

Late complications after pharmacological stress echocardiography are infrequent but potentially dreadful events. We report the case of a 80-year-old woman admitted to hospital for rest chest pain with trivial troponin increase, normal left ventricular function and no significant ECG changes. A dobutamine stress echocardiography was performed for diagnostic purpose, with a negative result. About 30 min after the end of dobutamine infusion, she developed ST-segment elevation in inferior leads associated with chest pain and left ventricular dyssynergy, promptly resolved by sublingual nitrates. Subsequently, angiography documented the absence of significant coronary stenoses. The following clinical course was uneventful. Transient myocardial ischemia was likely due to dobutamine-induced coronary spasm. The case emphasizes the utility of routine, long-lasting monitoring of patients after stress echocardiography, even if negative, to counteract possible late life-threatening complications.

Simulated hypogravity and synaptogenesis in culture

NASA Technical Reports Server (NTRS)

Gruener, R.

1985-01-01

A study on the effects of simulated microgravity on spinal neurons and myocytes cultured from X. laevis, is performed. Horizontal clinorotation at 1-10 rpm lasted from 16-36 hours, a sufficient time for cells to proceed through ontogenetic maturation. Late appearance of striations, retarded consumpton of yolk platelets and fewer and thinner neurites indicate subnormal expression of cell functions. Furthermore, these cells do not respond normally to environmental cues like trophic substances or surface contact. The observed delay in cell maturation is consistent with a hypothesis that cellular graviperception may effect the centriole and cytoskeleton.

[Neurophysiological analysis of the development of endocrine and hypertensive reactions in long-term emotional stress].

PubMed

Amiragova, M G; Arkhangel'skaia, M I; Polyntsev, Iu V; Vorontsov, V I

1985-08-01

A study was made of the effect of chronic emotional stress on the formation of hypertension in animals. This was shown to be related to dynamic changes in the function of the CNS, particularly in the hypothalamic apparatus of the neuroendocrine control. The above changes played a role in the formation of hypertensive vascular reactions accompanied by a high hormonal secretion of the adrenal cortex and thyroid. During stabilization of high arterial blood pressure at the late stages of the "after-effect", the hormonal secretion returns to normal.

Effects of transforming growth factor-β1 treatment on muscle regeneration and adipogenesis in glycerol-injured muscle.

PubMed

Mahdy, Mohamed A A; Warita, Katsuhiko; Hosaka, Yoshinao Z

2017-11-01

Transforming growth factor (TGF)-β1 is associated with fibrosis in many organs. Recent studies demonstrated that delivery of TGF-β1 into chemically injured muscle enhances fibrosis. In this study, we investigated the effects of exogenous TGF-β1 on muscle regeneration and adipogenesis in glycerol-injured muscle of normal mice. Tibialis anterior (TA) muscles were injured by glycerol injection. TGF-β1 was either co-injected with glycerol, as an 'early treatment' group, or injected at day 4 after glycerol, as a 'late treatment' group and the TA muscles were collected at day 7 after initial injury. Myotube density was significantly lower in the early treatment group than in the glycerol-injured group (without TGF-β1 treatment). Moreover, the Oil red O-positive area was significantly smaller in the early treatment group than in the late treatment group and glycerol-injured group. Furthermore, TGF-β1 treatment increased endomysial fibrosis and induced immunostaining of α-smooth muscle actin. The greater inhibitory effects of early TGF-β1 treatment than that of late TGF-β1 treatment during regeneration in glycerol-injured muscle suggest a more potent effect of TGF-β1 on the initial stage of muscle regeneration and adipogenesis. Combination of TGF-β1 with glycerol might be an alternative to enhance muscle fibrosis for future studies. © 2017 Japanese Society of Animal Science.

Clinical evolution of post-transplant diabetes mellitus.

PubMed

Porrini, Esteban L; Díaz, Jose M; Moreso, Francisco; Delgado Mallén, Patricia I; Silva Torres, Irene; Ibernon, Meritxell; Bayés-Genís, Beatriz; Benitez-Ruiz, Rocío; Lampreabe, Ildefonso; Lauzurrica, Ricardo; Osorio, Jose M; Osuna, Antonio; Domínguez-Rollán, Rosa; Ruiz, Juan C; Jiménez-Sosa, Alejandro; González-Rinne, Ana; Marrero-Miranda, Domingo; Macía, Manuel; García, Javier; Torres, Armando

2016-03-01

The long-term clinical evolution of prediabetes and post-transplant diabetes mellitus (PTDM) is unknown. We analysed, in this cohort study, the reversibility, stability and progression of PTDM and prediabetes in 672 patients using repeated oral glucose tolerance tests (OGTTs) for ≤5 years. Most patients were on tacrolimus, steroids and mycophenolate. About half developed either PTDM or prediabetes. The incidence of PTDM was 32% and bimodal: early PTDM (≤3 months) and late PTDM. Early PTDM reverted in 31%; late PTDM developed in patients with post-transplant prediabetes. The use of OGTTs was necessary to detect around half of PTDM. Pretransplant obesity was a major risk factor for early PTDM, for its persistence and for late PTDM {odds ratio [OR] 1.18 [95% confidence interval (CI) 1.09-1.28]}. At 3 months, higher HbA1c promoted [OR 2.37 (95% CI 1.38-4.06)], while insulin sensitivity protected against [OR 0.64 (95% CI 0.48-0.86)] late PTDM. At 3 months, 28% had prediabetes; of these, 36% remained stable, 43% normalized and 21% developed late PTDM. Pretransplant obesity [OR 1.20 (95% CI 1.04-1.39)] and higher HbA1c [OR 3.80 (95% CI 1.45-9.94)] at 3 months promoted while insulin sensitivity protected against [OR 0.57 (95% CI 0.34-0.95)] evolution from prediabetes to late PTDM. Immunosuppressive levels or acute rejection did not influence PTDM. Most (84%) of the patients with normal tests at 3 months remained stable without evolving into PTDM; 14% developed prediabetes. PTDM and prediabetes are very common in renal transplantation. Classic metabolic factors like obesity, prediabetes and insulin resistance promote the evolution of PTDM and prediabetes. Patients with normal glucose metabolism rarely develop PTDM. OGTT is necessary to detect PTDM and prediabetes and thus should be included in clinical practice. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

RADIATION THERAPY COMMUNICATION-REIRRADIATION OF A NASAL TUMOR IN A BRACHYCEPHALIC DOG USING INTENSITY MODULATED RADIATION THERAPY.

PubMed

Rancilio, Nicholas J; Custead, Michelle R; Poulson, Jean M

2016-09-01

A 5-year-old spayed female Shih Tzu was referred for evaluation of a nasal transitional carcinoma. A total lifetime dose of 117 Gy was delivered to the intranasal mass in three courses over nearly 2 years using fractionated intensity modulated radiation therapy (IMRT) to spare normal tissues. Clinically significant late normal tissue side effects were limited to bilaterally diminished tear production. The patient died of metastatic disease progression 694 days after completion of radiation therapy course 1. This case demonstrates that retreatment with radiation therapy to high lifetime doses for recurrent local disease may be well tolerated with IMRT. © 2016 American College of Veterinary Radiology.

Posterior cingulate glucose metabolism, hippocampal glucose metabolism, and hippocampal volume in cognitively normal, late-middle-aged persons at 3 levels of genetic risk for Alzheimer disease.

PubMed

Protas, Hillary D; Chen, Kewei; Langbaum, Jessica B S; Fleisher, Adam S; Alexander, Gene E; Lee, Wendy; Bandy, Daniel; de Leon, Mony J; Mosconi, Lisa; Buckley, Shannon; Truran-Sacrey, Diana; Schuff, Norbert; Weiner, Michael W; Caselli, Richard J; Reiman, Eric M

2013-03-01

To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease. Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxyglucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers. Academic medical center. A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume. Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P = .60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P = .001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r = 0.29, P = .0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P < .05, determined by use of pairwise Fisher z tests). Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for Alzheimer disease.

Late-onset rhabdomyolysis in burn patients in the intensive care unit.

PubMed

Bache, Sarah E; Taggart, Ian; Gilhooly, Charlotte

2011-11-01

Rhabdomyolysis (RML), defined as creatine phosphokinase (CPK) >1000 U/L, is relatively common immediately after a significant burn. Late-onset RML, occurring a week or more after a burn, is less well understood and recognised. All patients admitted to the Intensive Care Unit (ICU) following an acute burn between May 2006 and December 2009 were retrospectively identified. Patients with CPK>1000 U/L a week or more after their burn had a detailed notes review. Seventy-six patients were admitted during 43 months. Late-onset RML was demonstrated in 7/76 (9%) patients. They had a similar pattern of normal or mildly raised CPK on admission that resolved over the following days, but suddenly increased sharply to over 1000 U/L, a week or more after their burn, usually around day ten. A severe late-onset RML occurred in 5/76 (7%) patients, with a CPK rise of over 5000 U/L, and all required haemodialysis. Potential triggering factors for late-onset RML include sepsis, nephrotoxic drugs and hypophosphataemia. It is important to consider measuring CPK in all patients with the above complications, even after it has previously been observed to be normal, in order to initiate early treatment. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

The Intellectual Climate of the Late Nineteenth Century and the Fate of American Normal Schools

ERIC Educational Resources Information Center

Diener, David

2008-01-01

In 1839 the first normal school in the United States opened in Lexington, Massachusetts. Heralded as "an instrument of great good" (Everett 1863, 769) and a spring in which was coiled "a vigor whose uncoiling may wheel the spheres" (Ogren 2005, 16), normal schools continued to grow in numbers throughout the nineteenth century and produced…

Variability of Late-Night Salivary Cortisol in Cushing Disease: A Prospective Study.

PubMed

Sandouk, Zahrae; Johnston, Philip; Bunch, Dustin; Wang, Sihe; Bena, James; Hamrahian, Amir; Kennedy, Laurence

2018-03-01

The frequency of variable hormonogenesis in patients with Cushing disease (CD) but without cyclical symptoms is unclear. To assess the frequency of variable hormonogenesis in patients presenting with CD. Over a 6-month period, patients with confirmed or suspected CD provided late-night salivary samples for up to 42 consecutive nights. Of 19 patients confirmed to have CD, 16 provided at least 7 consecutive salivary samples, and 13 provided at least 21; these 16 patients are the subjects of this report. Twelve patients had at least three peak and two trough levels of late-night salivary cortisol (LNSC) but in only two patients were strict criteria for cyclical hormonogenesis fulfilled; variation was assessed as random in the others. Eight patients had de novo CD, and eight had recurrent/persistent disease. All patients with recurrent/persistent CD had two or more normal results, and in four of these patients, >50% of LNSC were normal. In six patients with de novo disease with at least one normal LNSC level, the maximum levels ranged from 1.55 to 15.5 times the upper limit of normal. Extreme fluctuations of cortisol production, measured by sequential LNSC, are common in CD. In newly diagnosed disease, this may only occasionally impair diagnostic ability, whereas in most patients with recurrent/persistent disease after pituitary surgery, LNSC is frequently within the reference range, with potential to cause diagnostic problems.

Efficacy of computerized discrimination between structure-related and non-structure-related echoes in ultrasonographic images for the quantitative evaluation of the structural integrity of superficial digital flexor tendons in horses.

PubMed

van Schie, H T; Bakker, E M; Jonker, A M; van Weeren, P R

2001-07-01

To evaluate effectiveness of computerized discrimination between structure-related and non-structure-related echoes in ultrasonographic images for quantitative evaluation of tendon structural integrity in horses. 4 superficial digital flexor tendons (2 damaged tendons, 2 normal tendons). Transverse ultrasonographic images that precisely matched histologic sections were obtained in fixed steps along the long axis of each tendon. Distribution, intensity, and delineation of structure-related echoes, quantitatively expressed as the correlation ratio and steadiness ratio , were compared with histologic findings in tissue that was normal or had necrosis, early granulation, late granulation, early fibrosis, or inferior repair. In normal tendon, the even distribution of structure-related echoes with high intensity and sharp delineation yielded high correlation ratio and steadiness ratio. In areas of necrosis, collapsed endotendon septa yielded solid but blurred structure-related echoes (high correlation ration and low steadiness ratio). In early granulation tissue, complete lack of organization caused zero values for both ratios. In late granulation tissue, reorganization and swollen endotendon septa yielded poorly delineated structure-related echoes (high correlation ratio, low steadiness ratio). In early fibrosis, rearrangement of bundles resulted in normal correlation ration and slightly low steadiness ratio. In inferior repair, the almost complete lack of structural reorganization resulted in heterogeneous poorly delineated low-intensity echoes (low correlation ratio and steadiness ratio). The combination of correlation ratio and steadiness ratio accurately reflects histopathologic findings, making computerized correlation of ultrasonographic images an efficient tool for quantitative evaluation of tendon structural integrity.

Determination of the radioprotective effects of topical applications of MEA, WR-2721, and N-acetylcysteine on murine skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verhey, L.J.; Sedlacek, R.

1983-01-01

Topical applications of MEA (beta-mercaptoethylamine or cysteamine), WR-2721 (S-2-(3-aminopropylamino)-ethylphosphorothioic acid), and N-acetylcysteine (NAC) were tested for their ability to protect the normal skin of the hind legs of mice against acute and late damage from single doses of /sup 137/Cs radiation. No significant protection was observed with either WR-2721 or NAC. MEA was shown to offer significant protection against acute skin damage in both buffered and unbuffered forms, but no significant protection against late contraction. The use of topical MEA on unanesthetized animals breathing carbogen (95% O2, 5% CO2) appears to give an enhanced level of radioprotection over that shownmore » for anesthetized, air-breathing animals.« less

Action of certain tropine esters on voltage-clamped lobster axon.

PubMed

Blaustein, M P

1968-03-01

Tropine p-tolylacetate (TPTA) and its quaternary analogue, tropine p-tolylacetate methiodide (TPTA MeI) decrease the early transient (Na) and late (K) currents in the voltage-clamped lobster giant axon. These agents, which block the nerve action potential, reduce the maximum Na and K conductance increases associated with membrane depolarization. They also slow the rate at which the sodium conductance is increased and shift the (normalized) membrane conductance vs. voltage curves in the direction of depolarization along the voltage axis. All these effects are qualitatively similar to those resulting from the action of procaine on the voltage-clamped axon. One unusual effect of the tropine esters, noticeable particularly at large depolarization steps, is that they cause the late, K current to reach a peak and then fall off with increasing pulse duration. This effect has not been reported to occur as a result of procaine action. Tropine p-chlorophenyl acetate (TPClphiA), which differs from TPTA only by the substitution of a p-Cl for a p-CH(3) group on the benzene ring, had a negligible effect on axonal excitability.

Action of Certain Tropine Esters on Voltage-Clamped Lobster Axon

PubMed Central

Blaustein, M. P.

1968-01-01

Tropine p-tolylacetate (TPTA) and its quaternary analogue, tropine p-tolylacetate methiodide (TPTA MeI) decrease the early transient (Na) and late (K) currents in the voltage-clamped lobster giant axon. These agents, which block the nerve action potential, reduce the maximum Na and K conductance increases associated with membrane depolarization. They also slow the rate at which the sodium conductance is increased and shift the (normalized) membrane conductance vs. voltage curves in the direction of depolarization along the voltage axis. All these effects are qualitatively similar to those resulting from the action of procaine on the voltage-clamped axon. One unusual effect of the tropine esters, noticeable particularly at large depolarization steps, is that they cause the late, K current to reach a peak and then fall off with increasing pulse duration. This effect has not been reported to occur as a result of procaine action. Tropine p-chlorophenyl acetate (TPClφA), which differs from TPTA only by the substitution of a p-Cl for a p-CH3 group on the benzene ring, had a negligible effect on axonal excitability. PMID:5648830

THE EFFECT OF ANTISERUM, ALONE AND WITH HYDROCORTISONE, ON FOETAL MOUSE BONES IN CULTURE

PubMed Central

Fell, Honor B.; Weiss, L.

1965-01-01

1. The effects of normal rabbit serum and of rabbit antiserum to whole foetal mouse tissues, on the isolated limb bones of late foetal mice were studied in organ culture, and the influence of hydrocortisone on these effects was investigated. 2. Unheated normal serum caused slight loss of metachromatic material from the cartilage matrix, and some resorption of both cartilage and bone. 3. In unheated antiserum to foetal mouse tissues, the terminal cartilage was smaller and less metachromatic than in paired controls in normal serum, while osteoclasis was so intense that in many explants the bone had almost disappeared. The amount of necrosis varied with different batches of antiserum. 4. The changes produced by normal serum and antiserum could be largely prevented by heating the sera to 57°C for 45 minutes. 5. The effects could also be inhibited by the addition of hydrocortisone to the unheated sera; as little as 0.1 µg hydrocortisone per ml of medium had a well marked protective action. 6. It is suggested that (a) unheated antiserum causes a release of lysosomal enzymes with consequent breakdown of intercellular material, (b) this release is due to an indirect action on the lysosome via an increased permeability of the cell membrane, (c) hydrocortisone does not affect the antigen-antibody reaction, but inhibits the autolytic changes that normally follow this reaction, possibly by stabilising both the lysosomal and cell membranes. PMID:14276776

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan.

PubMed

Ashpole, Nicole M; Logan, Sreemathi; Yabluchanskiy, Andriy; Mitschelen, Matthew C; Yan, Han; Farley, Julie A; Hodges, Erik L; Ungvari, Zoltan; Csiszar, Anna; Chen, Sixia; Georgescu, Constantin; Hubbard, Gene B; Ikeno, Yuji; Sonntag, William E

2017-04-01

Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igf f/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Wei; Fu, Jianfang; Zhang, Shun

Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from themore » elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment disrupted AJs dynamics. • BTZ treatment stimulated AMPK activity during late phase of testicular recovery. • AMPK-dependent mechanisms counteract FSH proliferative effects in BTZ-exposed SCs.« less

Genome-wide transcriptome analyses of developing seeds from low and normal phytic acid soybean lines.

PubMed

Redekar, Neelam R; Biyashev, Ruslan M; Jensen, Roderick V; Helm, Richard F; Grabau, Elizabeth A; Maroof, M A Saghai

2015-12-18

Low phytic acid (lpa) crops are potentially eco-friendly alternative to conventional normal phytic acid (PA) crops, improving mineral bioavailability in monogastric animals as well as decreasing phosphate pollution. The lpa crops developed to date carry mutations that are directly or indirectly associated with PA biosynthesis and accumulation during seed development. These lpa crops typically exhibit altered carbohydrate profiles, increased free phosphate, and lower seedling emergence, the latter of which reduces overall crop yield, hence limiting their large-scale cultivation. Improving lpa crop yield requires an understanding of the downstream effects of the lpa genotype on seed development. Towards that end, we present a comprehensive comparison of gene-expression profiles between lpa and normal PA soybean lines (Glycine max) at five stages of seed development using RNA-Seq approaches. The lpa line used in this study carries single point mutations in a myo-inositol phosphate synthase gene along with two multidrug-resistance protein ABC transporter genes. RNA sequencing data of lpa and normal PA soybean lines from five seed-developmental stages (total of 30 libraries) were used for differential expression and functional enrichment analyses. A total of 4235 differentially expressed genes, including 512-transcription factor genes were identified. Eighteen biological processes such as apoptosis, glucan metabolism, cellular transport, photosynthesis and 9 transcription factor families including WRKY, CAMTA3 and SNF2 were enriched during seed development. Genes associated with apoptosis, glucan metabolism, and cellular transport showed enhanced expression in early stages of lpa seed development, while those associated with photosynthesis showed decreased expression in late developmental stages. The results suggest that lpa-causing mutations play a role in inducing and suppressing plant defense responses during early and late stages of seed development, respectively. This study provides a global perspective of transcriptomal changes during soybean seed development in an lpa mutant. The mutants are characterized by earlier expression of genes associated with cell wall biosynthesis and a decrease in photosynthetic genes in late stages. The biological processes and transcription factors identified in this study are signatures of lpa-causing mutations.

Brain-Derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study

PubMed Central

Diniz, Breno Satler; Reynolds, Charles F.; Begley, Amy; Dew, Mary Amanda; Anderson, Stewart J.; Lotrich, Francis; Erickson, Kirk I.; Lopez, Oscar; Aizenstein, Howard; Sibille, Etienne L.; Butters, Meryl A.

2014-01-01

Changes in brain-derived neurotrophic factor (BDNF) level are implicated in the pathophysiology of cognitive decline in depression and neurodegenerative disorders in older adults. We aimed to evaluate the longitudinal association over two years between BDNF and persistent cognitive decline in individuals with remitted late-life depression and Mild Cognitive Impairment (LLD+MCI) compared to either individuals with remitted LLD and no cognitive decline (LLD+NCD) or never-depressed, cognitively normal, elderly control participants. We additionally evaluated the effect of double-blind, placebo-controlled donepezil treatment on BDNF levels in all of the remitted LLD participants (across the levels of cognitive function). We included 160 elderly participants in this study (72 LLD+NCD, 55 LLD+MCI and 33 never-depressed cognitively normal elderly participants). At the same visits, cognitive assessments were conducted and blood sampling to determine serum BDNF levels were collected at baseline assessment and after one and two years of follow-up. We utilized repeated measure, mixed effect models to assess: (1) the effects of diagnosis (LLD+MCI, LLD+NCD, and controls), time, and their interaction on BDNF levels; and (2) the effects of donepezil treatment (donepezil vs. placebo), time, baseline diagnosis (LLD+MCI vs. LLD+NCD), and interactions between these contrasts on BDNF levels. We found a significant effect of time on BDNF level (p=0.02) and a significant decline in BDNF levels over 2 years of follow-up in participants with LLD+MCI (p=0.004) and controls (p=0.04). We found no effect of donepezil treatment on BDNF level. The present results suggest that aging is an important factor related to decline in BDNF level. PMID:24290367

Does Human Milk Modulate Body Composition in Late Preterm Infants at Term-Corrected Age?

PubMed

Giannì, Maria Lorella; Consonni, Dario; Liotto, Nadia; Roggero, Paola; Morlacchi, Laura; Piemontese, Pasqua; Menis, Camilla; Mosca, Fabio

2016-10-23

(1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at  term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(β = -47.9, 95% confidence interval (CI) = -95.7; -0.18; p = 0.049; β = -89.6, 95% CI = -131.5; -47.7; p < 0.0001; β = -104.1, 95% CI = -151.4; -56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants.

Longitudinal Development of Phonology and Morphology in Children with Late-Identified Mild-Moderate Sensorineural Hearing Loss

PubMed Central

Moeller, Mary Pat; McCleary, Elizabeth; Putman, Coille; Tyler-Krings, Amy; Hoover, Brenda; Stelmachowicz, Patricia

2010-01-01

Objective Studies of language development in children with mild-moderate hearing loss are relatively rare. Longitudinal studies of children with late-identified hearing loss have not been conducted, and they are relevant for determining how a period of unaided mild-moderate hearing loss impacts development. In recent years, newborn hearing screening programs have effectively reduced the ages of identification for most children with permanent hearing loss. However, some children continue to be identified late and research is needed to guide management decisions. Further, studies of this group may help to discern if language normalizes following intervention, and/or if certain aspects of language might be vulnerable to persistent delays. The current study examines the impact of late identification and reduced audibility on speech and language outcomes via a longitudinal study of four children with mild-moderate sensorineural hearing loss. Design Longitudinal outcomes of four children with late-identified mild-moderate sensorinueral hearing loss were studied using standardized measures and language sampling procedures, from at or near the point of identification (28 – 41 months) through 84 months of age. The children with hearing loss were compared to ten age-matched children with normal hearing on a majority of the measures through 60 months of age. Spontaneous language samples were collected from mother-child interaction sessions, recorded at consistent intervals in a laboratory-based play setting. Transcripts were analyzed using computer-based procedures (Systematic Analysis of Language Transcripts) and the Index of Productive Syntax. Possible influences of audibility were explored by examining the onset and productive use of a set of verb tense markers, and by monitoring the children’s accuracy in use of morphological endings. Phonological samples at baseline were transcribed and analyzed using Computerized Profiling. Results At entry to the study, the four children with hearing loss demonstrated language delays, with pronounced delays in phonological development. Three of the four children demonstrated rapid progress with development and interventions, and performed within the average range on standardized speech and language measures compared to age-matched children by 60-months of age. However, persistent differences from children with normal hearing were observed in the areas of morphosyntax, speech intelligibility in conversation, and production of fricatives. Children with mild-moderate hearing loss demonstrated later than typical emergence of certain verb tense markers, which may be related to reduced or inconsistent audibility. Conclusions The results of this study suggest that early communication delays will resolve for children with late-identified mild-moderate hearing loss, given appropriate amplification and intervention services. A positive result is that three of four children demonstrated normalization of broad language behaviors by 60-months of age, in spite of significant delays at baseline. However, these children are at risk for persistent delays in phonology at the conversational level and for accuracy in use of morphological markers. The ways in which reduced auditory experiences and audibility may contribute to these delays are explored, along with implications for evaluation of outcomes. PMID:20548239

Structural Features of the Western Taiwan Foreland Basin in the Eastern Taiwan Strait since Late Miocene

NASA Astrophysics Data System (ADS)

WANG, J. H.; Liu, C. S.; Chang, J. H.; Yang, E. Y.

2017-12-01

The western Taiwan Foreland Basin lies on the eastern part of Taiwan Strait. The structures in this region are dominated by crustal stretch and a series of flexural normal faults have been developed since Late Miocene owing to the flexural of Eurasia Plate. Through deciphering multi-channel seismic data and drilling data, these flexural features are observed in the offshore Changhua coastal area. The flexure normal faults are important features to realize structural activity in the western Taiwan Foreland Basin. Yang et al. (2016) mention that the reactivated normal faults are found north of the Zhushuixi estuary. It should be a significant issue to decipher whether these faults are still active. In this study, we have analyzed all the available seismic reflections profiles in the central part of the Taiwan Strait, and have observed many pre-Pliocene normal faults that are mainly distributed in the middle of the Taiwan Strait to Changyun Rise, and we tentatively suggest that the formation of these faults may be associated with the formation of the foreland basal unconformity. Furthermore, we will map the distribution of these normal faults and examine whether the reactivated normal faults have extended to south of the Zhushuixi estuary. Finally, we discuss the relation between the reactivated normal faults in the Taiwan Strait and those faults onshore. Key words: Multichannel seismic reflection profile, Taiwan Strait, Foreland basin, normal fault.

Early and late effects of Ibuprofen on mouse sperm parameters, chromatin condensation, and DNA integrity in mice.

PubMed

Roodbari, Fatemeh; Abedi, Nahid; Talebi, Ali Reza

2015-11-01

There are few studies indicating the detrimental effects of ibuprofen on sperm fertility potential and DNA integrity. To determine the effects of Ibuprofen on sperm parameters, chromatin condensation and DNA integrity of mice. In this experimental study, 36 adult male mice with average weight 37 gr were divided into three groups, including control (group I, n=12), normal dosage of ibuprofen (group II, n=12) and high dosage (group III, n=12). Ibuprofen with different doses was dissolved in daily water of animals. After 35, 70 and 105 days, the cauda epididymis of mice were cut and incubated in Ham's F10 media. Sperm samples were analyzed for parameters (motility, morphology and count), DNA integrity (SCD test) and chromatin condensation (chromomycin A3 and Aniline blue staining). After 35 days, in addition to above mentioned sperm parameters, all of the treated mice showed statistically significant increase in spermatozoa with immature chromatin (P<0.05). However, after 70 days, the rate of sperm DNA fragmentation assessed by SCD was increased in group II (66.5±0.7) and the percentage of immature spermatozoa (AB(+) and CMA3(+)) was higher in group III (77.5±0.7 and 49.5±6.3 respectively) than other groups. After 105 days, the AB(+) spermatozoa were increased in both normal dose and high dose groups. Ibuprofen may cause a significant reduction in sperm parameters and sperm chromatin/DNA integrity in mice. It should be noted that these deleterious effects are dose-dependent and can be seen in early and late stage of drug treatments.

Photodynamic therapy mediated by acai oil (Euterpe oleracea Martius) in nanoemulsion: A potential treatment for melanoma.

PubMed

Monge-Fuentes, Victoria; Muehlmann, Luis Alexandre; Longo, João Paulo Figueiró; Silva, Jaqueline Rodrigues; Fascineli, Maria Luiza; de Souza, Paulo; Faria, Fernando; Degterev, Igor Anatolievich; Rodriguez, Anselmo; Carneiro, Fabiana Pirani; Lucci, Carolina Madeira; Escobar, Patricia; Amorim, Rivadávio Fernandes Batista; Azevedo, Ricardo Bentes

2017-01-01

Melanoma is the most aggressive and lethal form of skin cancer, responsible for >80% of deaths. Standard treatments for late-stage melanoma usually present poor results, leading to life-threatening side effects and low overall survival. Thus, it is necessary to rethink treatment strategies and design new tools for the treatment of this disease. On that ground, we hereby report the use of acai oil in nanoemulsion (NanoA) as a novel photosensitizer for photodynamic therapy (PDT) used to treat melanoma in in vitro and in vivo experimental models. NIH/3T3 normal cells and B16F10 melanoma cell lines were treated with PDT and presented 85% cell death for melanoma cells, while maintaining high viability in normal cells. Flow cytometry indicated that cell death occurred by late apoptosis/necrosis. Tumor bearing C57BL/6 mice treated five times with PDT using acai oil in nanoemulsion showed tumor volume reduction of 82% in comparison to control/tumor group. Necrotic tissue per tumor area reached its highest value in PDT-treated mice, supporting PDT efficacy. Overall, acai oil in nanoemulsion was an effective photosensitizer, representing a promising source of new photosensitizing molecules for PDT treatment of melanoma, a tumor with an inherent tendency to be refractory for this type of therapy. Copyright © 2016. Published by Elsevier B.V.

Hypofractionated intensity modulated irradiation for localized prostate cancer, results from a phase I/II feasibility study

PubMed Central

Junius, Sara; Haustermans, Karin; Bussels, Barbara; Oyen, Raymond; Vanstraelen, Bianca; Depuydt, Tom; Verstraete, Jan; Joniau, Steven; Van Poppel, Hendrik

2007-01-01

Background To assess acute (primary endpoint) and late toxicity, quality of life (QOL), biochemical or clinical failure (secondary endpoints) of a hypofractionated IMRT schedule for prostate cancer (PC). Methods 38 men with localized PC received 66 Gy (2.64 Gy) to prostate,2 Gy to seminal vesicles (50 Gy total) using IMRT. Acute toxicity was evaluated weekly during radiotherapy (RT), at 1–3 months afterwards using RTOG acute scoring system. Late side effects were scored at 6, 9, 12, 16, 20, 24 and 36 months after RT using RTOG/EORTC criteria. Quality of life was assessed by EORTC-C30 questionnaire and PR25 prostate module. Biochemical failure was defined using ASTRO consensus and nadir+2 definition, clinical failure as local, regional or distant relapse. Results None experienced grade III-IV toxicity. 10% had no acute genito-urinary (GU) toxicity, 63% grade I; 26% grade II. Maximum acute gastrointestinal (GI) scores 0, I, II were 37%, 47% and 16%. Maximal acute toxicity was reached weeks 4–5 and resolved within 4 weeks after RT in 82%. Grade II rectal bleeding needing coagulation had a peak incidence of 18% at 16 months after RT but is 0% at 24–36 months. One developed a urethral stricture at 2 years (grade II late GU toxicity) successfully dilated until now. QOL urinary symptom scores reached a peak incidence 1 month after RT but normalized 6 months later. Bowel symptom scores before, at 1–6 months showed similar values but rose slowly 2–3 years after RT. Nadir of sexual symptom scores was reached 1–6 months after RT but improved 2–3 years later as well as physical, cognitive and role functional scales. Emotional, social functional scales were lowest before RT when diagnosis was given but improved later. Two years after RT global health status normalized. Conclusion This hypofractionated IMRT schedule for PC using 25 fractions of 2.64 Gy did not result in severe acute side effects. Until now late urethral, rectal toxicities seemed acceptable as well as failure rates. Detailed analysis of QOL questionnaires resulted in the same conclusion. PMID:17686162

Effects of dry period length and concentrate protein content in late lactation on body condition score change and subsequent lactation performance of thin high genetic merit dairy cows.

PubMed

Dale, A J; Purcell, P J; Wylie, A R G; Gordon, A W; Ferris, C P

2017-03-01

Improving body condition score of thin cows in late lactation is necessary, because cows that are thin at drying off exhibit decreased fertility postpartum and are at increased risk of disease and of being culled in the subsequent lactation. Offering a diet low in crude protein (CP) content in late lactation may help to improve body condition score (BCS) at drying off, whereas imposing an extended dry period (EDP) has been advocated as another way to increase BCS at calving. To test these hypotheses, 65 thin cows (mean BCS 2.25 at 14 wk precalving) were managed on 1 of 3 treatments between 13 and 9 wk prepartum: normal protein control {NP; grass silage + 5 kg/d of a normal protein concentrate [228 g of CP/kg of dry matter (DM)]}, low protein [LP; grass silage + 5 kg/d of a low-protein concentrate (153 g of CP/kg of DM)], or EDP (cows dried off at 13 wk precalving and offered a grass silage-only diet). Both NP and LP cows were dried off at wk 8 prepartum, after which all cows were offered a grass silage-only diet until calving. After calving, all cows were offered a common diet (supplying 11.1 kg of concentrate DM/cow per day) for 19 wk. Between 13 and 9 wk prepartum, LP cows had lower DM intake, milk yield, and body weight than NP cows. Whereas EDP cows had lower serum β-hydroxybutyrate and fatty acid concentrations than those of NP cows, BCS at wk 9 prepartum did not differ between treatments. Cows on the LP treatment continued to have lower DMI and BW than those of NP and EDP cows between 8 wk prepartum and calving, but only EDP cows had a higher BCS at calving. Treatment did not affect calving difficulty score or calf birth weight. Although all cows were offered a common diet postpartum, cows on the LP treatment had lower DM intake and milk fat + plus protein yield than cows on any other treatment during the 19-wk period postpartum, but we found no differences in any postpartum indicator of body tissue reserves. The treatments imposed from wk 13 to 9 prepartum had no effect on any fertility or health parameters examined postpartum. Extending the dry period for thin cows improved their BCS at calving but did not allow these cows to achieve the target BCS of 2.75, and we found no beneficial effects of this treatment on cow performance postpartum. Offering a lower-protein diet to thin cows in late lactation did not improve BCS at calving above that of cows on a normal protein diet, but had unexplained long-term negative effects on cow performance. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Process of infection with bacteriophage phi chi 174. XL. Viral DNA replication of phi chi 174 mutants blocked in progeny single-stranded DNA synthesis.

PubMed Central

Fukuda, A; Sinsheimer, R L

1976-01-01

Mutation in several different cistrons of bacteriophage phi chi 174 blocks net progeny single-stranded DNA synthesis at the late period of infection (15). For the study of the functions of these cistrons in single-stranded DNA synthesis, asymmetric replication of replicative form DNA was examined at the late period of infection with amber mutants of these cistrons. While the normal, rapid process of asymmetric single-stranded viral DNA synthesis is blocked at the late period of these mutant infections, an asymmetric synthesis of the viral strand of replicative-form DNA is observed in this period, though at a reduced level, together with degradation of prelabeled viral strand. Some intermediate replicative-form molecules were also detected. Asymmetric synthesis of the viral strand of replicative-form DNA at the late period of phi chi infection is completely inhibited in the presence of a low concentration (35mug/ml) of chloramphenicol (which also blocks net single-stranded viral DNA synthesis). These results are discussed in terms of the possible role of the specific viral proteins for normal single-stranded DNA synthesis. PMID:1255871

Strike-slip structural styles and petroleum system evolution, northeast Sakhalin Island

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meisling, K.E.; Wagner, J.B.

1996-12-31

The primary petroleum system of northeast Sakhalin Island and adjacent shelfal areas is comprised of a system of Late Miocene to Quaternary faulted transpressional anticlines that trap oil and gas in Early Miocene to Pliocene deltaic reservoirs sourced from Late Oligocene to Early Miocene diatomaceous shales. Existing production has been limited to onshore anticlines, and offshore structural trends remain undeveloped, despite several discoveries. The regional tectonic evolution of Sakhalin Island can be divided into five major phases: (1) Late Cretaceous to Early Eocene subduction, (2) Middle-Eocene collision and uplift, (3) Late Eocene to Early Oligocene oblique rifting, (4) Late Oligocenemore » to Middle Miocene thermal subsidence, and (5) Late Miocene to Quaternary transpression and inversion. Oil-prone source rocks were deposited during rapid post-rift thermal subsidence of transtensional rift basins and adjacent highs, which provided an ideal sediment-starved setting for source rock accumulation. Reservoir facies were supplied by prograding post-rift Miocene deltaics of the paleo-Amur river, which built a shelf across the thermally subsiding basin and intrabasin highs. Traps were formed when the basin was later inverted during Late Miocene to Pleistocene transpression, which reactivated both Paleogene normal faults and structural trends of the Mesozoic accretionary prism to create a broad zone of distributed shear. Strike-slip structural styles are evidenced by linear, en echelon alignments of doubly-plunging anticlines characterized by numerous small-displacement, transverse normal faults. Strike slip on individual structures is relatively small, however, based on a lack of thorough going faults. Strike-slip structures on Sakhalin Island are considered active, in light of the earthquake of May 27, 1995 (M=7.6) and uplift of Pleistocene marine terraces.« less

Strike-slip structural styles and petroleum system evolution, northeast Sakhalin Island

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meisling, K.E.; Wagner, J.B.

1996-01-01

The primary petroleum system of northeast Sakhalin Island and adjacent shelfal areas is comprised of a system of Late Miocene to Quaternary faulted transpressional anticlines that trap oil and gas in Early Miocene to Pliocene deltaic reservoirs sourced from Late Oligocene to Early Miocene diatomaceous shales. Existing production has been limited to onshore anticlines, and offshore structural trends remain undeveloped, despite several discoveries. The regional tectonic evolution of Sakhalin Island can be divided into five major phases: (1) Late Cretaceous to Early Eocene subduction, (2) Middle-Eocene collision and uplift, (3) Late Eocene to Early Oligocene oblique rifting, (4) Late Oligocenemore » to Middle Miocene thermal subsidence, and (5) Late Miocene to Quaternary transpression and inversion. Oil-prone source rocks were deposited during rapid post-rift thermal subsidence of transtensional rift basins and adjacent highs, which provided an ideal sediment-starved setting for source rock accumulation. Reservoir facies were supplied by prograding post-rift Miocene deltaics of the paleo-Amur river, which built a shelf across the thermally subsiding basin and intrabasin highs. Traps were formed when the basin was later inverted during Late Miocene to Pleistocene transpression, which reactivated both Paleogene normal faults and structural trends of the Mesozoic accretionary prism to create a broad zone of distributed shear. Strike-slip structural styles are evidenced by linear, en echelon alignments of doubly-plunging anticlines characterized by numerous small-displacement, transverse normal faults. Strike slip on individual structures is relatively small, however, based on a lack of thorough going faults. Strike-slip structures on Sakhalin Island are considered active, in light of the earthquake of May 27, 1995 (M=7.6) and uplift of Pleistocene marine terraces.« less

Acute Sleep Deprivation Enhances Post-Infection Sleep and Promotes Survival during Bacterial Infection in Drosophila

PubMed Central

Kuo, Tzu-Hsing; Williams, Julie A.

2014-01-01

Study Objectives: Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Setting: Laboratory. Participants: Drosophila melanogaster. Methods and Results: Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Conclusions: Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection. Citation: Kuo TH, Williams JA. Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila. SLEEP 2014;37(5):859-869. PMID:24790264

Inherited partial direct duplication of 11q: First report and possible association with a midline developmental field defect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witt, D.R.; Jenkins, L.; Pinheiro, S.

1994-09-01

A 36-year-old woman underwent amniocentesis for advanced maternal age. The fetal karyotype had an extra dark staining G band on the long arm of chromosome 11 with no other identifiable abnormalities. FISH studies using a chromosome 11 paint probe confirmed the origin of the extra band. The abnormality was identified as a partial duplication of 11q: 46,XX dir dup (11)(q13.5q21) or (q21q23.1). The specific duplicated band could not be identified with certainty. Detailed fetal sonograms were normal. Family studies revealed the identical duplication in the mother but normal karyotypes in both maternal grandparents. The mother had strabismus and a shortmore » tongue frenulum which required surgical correction. Menses occurred late in adolescence and complete development of secondary sexual characteristics was delayed until adulthood. An infertility evaluation revealed duplication of the uterus, cervix, and vagina. An evaluation for metorrhagia identified a pituitary adenoma which was resected. Her intelligence was normal. To our knowledge this is the first report of a heritable direct duplication of 11q. It is possible that one or more gene in the duplicated segment played a causal role in the pathophysiology of the patient`s anomalies through a disturbance of the so-called {open_quotes}midline developmental field{close_quotes}. Alternatively, the cytogenetic findings could be unrelated to the malformations. Rare instances of partial gain or loss of specific late-replicating heterochromatic regions without phenotypic effect have been reported. This region of 11q is also relatively late-replicating. This is consistent with previous reports suggesting a paucity of expressed genes in this 11q region. Molecular studies of the duplication are underway to determine the specific location and extent of duplication. Phenotypic evaluation of the patient`s baby will also be reported.« less

Phasic Contractions of the Mouse Vagina and Cervix at Different Phases of the Estrus Cycle and during Late Pregnancy

PubMed Central

Gravina, Fernanda S.; van Helden, Dirk F.; Kerr, Karen P.; de Oliveira, Ramatis B.; Jobling, Phillip

2014-01-01

Background/Aims The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking. Methodology/Principal Findings Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina. Conclusions/Significance Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges. PMID:25337931

Phasic contractions of the mouse vagina and cervix at different phases of the estrus cycle and during late pregnancy.

PubMed

Gravina, Fernanda S; van Helden, Dirk F; Kerr, Karen P; de Oliveira, Ramatis B; Jobling, Phillip

2014-01-01

The pacemaker mechanisms activating phasic contractions of vaginal and cervical smooth muscle remain poorly understood. Here, we investigate properties of pacemaking in vaginal and cervical tissues by determining whether: 1) functional pacemaking is dependent on the phase of the estrus cycle or pregnancy; 2) pacemaking involves Ca2+ release from sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) -dependent intracellular Ca2+ stores; and 3) c-Kit and/or vimentin immunoreactive ICs have a role in pacemaking. Vaginal and cervical contractions were measured in vitro, as was the distribution of c-Kit and vimentin positive interstitial cells (ICs). Cervical smooth muscle was spontaneously active in estrus and metestrus but quiescent during proestrus and diestrus. Vaginal smooth muscle was normally quiescent but exhibited phasic contractions in the presence of oxytocin or the K+ channel blocker tetraethylammonium (TEA) chloride. Spontaneous contractions in the cervix and TEA-induced phasic contractions in the vagina persisted in the presence of cyclopiazonic acid (CPA), a blocker of the SERCA that refills intracellular SR Ca2+ stores, but were inhibited in low Ca2+ solution or in the presence of nifedipine, an inhibitor of L-type Ca2+channels. ICs were found in small numbers in the mouse cervix but not in the vagina. Cervical smooth muscle strips taken from mice in estrus, metestrus or late pregnancy were generally spontaneously active. Vaginal smooth muscle strips were normally quiescent but could be induced to exhibit phasic contractions independent on phase of the estrus cycle or late pregnancy. Spontaneous cervical or TEA-induced vaginal phasic contractions were not mediated by ICs or intracellular Ca2+ stores. Given that vaginal smooth muscle is normally quiescent then it is likely that increases in hormones such as oxytocin, as might occur through sexual stimulation, enhance the effectiveness of such pacemaking until phasic contractile activity emerges.

Emerging issues among adolescent and young adult cancer survivors.

PubMed

Patterson, Pandora; McDonald, Fiona E J; Zebrack, Brad; Medlow, Sharon

2015-02-01

To review the characteristics of cancer in the adolescence and young adult age group; the medical, psychosocial and behavioral late effects; survivorship care planning and transition; current research priorities; and practice implications. Published articles, research studies and position statements. Survivors of cancers that occurred during adolescence and young adulthood (AYA) are confronted with the dual demands of managing their transition to independent adulthood, concurrently with their transition from cancer patient to cancer survivors, with an associated reduction in support from medical services. AYA survivors also face complex medical, psychosocial and behavioral late effects, including fertility and mental health issues. An understanding of the impact of cancer diagnoses among this age group, including survivors' abilities to reintegrate into 'normal' life and potential long term consequences, is necessary to provide the best support. This care and support can be enhanced through multidisciplinary teams who work together to address the medical and psychosocial needs of AYAs diagnosed with cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Precursors to speech in infancy: the prediction of speech and language disorders.

PubMed

Oller, D K; Eilers, R E; Neal, A R; Schwartz, H K

1999-01-01

During the canonical stage of infant babbling, infants produce well-formed syllables, often in reduplicated sequences such as "bababa." Although nearly all infants with normal hearing begin the canonical stage by 10 months of age, a few are delayed, and these infants may be of special interest. Recent studies indicate that late onset of canonical babbling may be a predictor of disorders. A simple screening procedure that focuses on canonical babbling was used to evaluate over 3400 infants at risk who were about 10 months of age. Among infants who showed late onset of canonical babbling, fewer than half had been previously diagnosed as having a significant medical problem that might have accounted for the delay. A follow-up study indicated that infants with delayed canonical babbling had smaller production vocabularies at 18, 24, and 30 months than did infants in the control group. The results suggest that late onset of canonical babbling, a factor that can be monitored effectively through an interview with a parent, can predict delay in the onset of speech production.

Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy—A Hypothesis-Driven Review

PubMed Central

Laube, Markus; Kniess, Torsten; Pietzsch, Jens

2016-01-01

Radiation therapy (RT) evolved to be a primary treatment modality for cancer patients. Unfortunately, the cure or relief of symptoms is still accompanied by radiation-induced side effects with severe acute and late pathophysiological consequences. Inhibitors of cyclooxygenase-2 (COX-2) are potentially useful in this regard because radioprotection of normal tissue and/or radiosensitizing effects on tumor tissue have been described for several compounds of this structurally diverse class. This review aims to substantiate the hypothesis that antioxidant COX-2 inhibitors are promising radioprotectants because of intercepting radiation-induced oxidative stress and inflammation in normal tissue, especially the vascular system. For this, literature reporting on COX inhibitors exerting radioprotective and/or radiosensitizing action as well as on antioxidant COX inhibitors will be reviewed comprehensively with the aim to find cross-points of both and, by that, stimulate further research in the field of radioprotective agents. PMID:27104573

X-Ray Luminosity Functions of Normal Galaxies in the Great Observatories Origins Deep Survey

NASA Astrophysics Data System (ADS)

Ptak, Andrew; Mobasher, Bahram; Hornschemeier, Ann; Bauer, Franz; Norman, Colin

2007-10-01

We present soft (0.5-2 keV) X-ray luminosity functions (XLFs) in the Great Observatories Origins Deep Survey (GOODS) fields derived for galaxies at z~0.25 and 0.75. SED fitting was used to estimate photometric redshifts and separate galaxy types, resulting in a sample of 40 early-type galaxies and 46 late-type galaxies. We estimate k-corrections for both the X-ray/optical and X-ray/NIR flux ratios, which facilitates the separation of AGNs from the normal/starburst galaxies. We fit the XLFs with a power-law model using both traditional and Markov-Chain Monte Carlo (MCMC) procedures. A key advantage of the MCMC approach is that it explicitly takes into account upper limits and allows errors on ``derived'' quantities, such as luminosity densities, to be computed directly (i.e., without potentially questionable assumptions concerning the propagation of errors). The slopes of the early-type galaxy XLFs tend to be slightly flatter than the late-type galaxy XLFs, although the effect is significant at only the 90% and 97% levels for z~0.25 and 0.75. The XLFs differ between z<0.5 and z>0.5 at >99% significance levels for early-type, late-type, and all (early- and late-type) galaxies. We also fit Schechter and lognormal models to the XLFs, fitting the low- and high-redshift XLFs for a given sample simultaneously assuming only pure luminosity evolution. In the case of lognormal fits, the results of MCMC fitting of the local FIR luminosity function were used as priors for the faint- and bright-end slopes (similar to ``fixing'' these parameters at the FIR values, except here the FIR uncertainty is included). The best-fit values of the change in logL* with redshift were ΔlogL*=0.23+/-0.16 dex (for early-type galaxies) and 0.34+/-0.12 dex (for late-type galaxies), corresponding to (1+z)1.6 and (1+z)2.3. These results were insensitive to whether the Schechter or lognormal function was adopted.

Cognitive functioning in healthy aging: the role of reserve and lifestyle factors early in life.

PubMed

Fritsch, Thomas; McClendon, McKee J; Smyth, Kathleen A; Lerner, Alan J; Friedland, Robert P; Larsen, Janet D

2007-06-01

According to the reserve perspective on cognitive aging, individuals are born with or can develop resources that help them resist normal and disease-related cognitive changes that occur in aging. The reserve perspective is becoming more sophisticated, but gaps in knowledge persist. In the present research, we considered three understudied questions about reserve: Is reserve primarily static (unchangeable) throughout the life course or dynamic (changeable, in terms of increases or decreases)? Can reserve be increased at any point in life, or are there optimal time periods--such as early life, midlife, or late life--to increase it? Does participation in different types of leisure and occupational activities in early life and midlife have different effects depending on specific domains of late-life cognitive functioning? Here we link early cognitive and activity data--gathered from archival sources--with cognitive data from older adults to examine these issues. 349 participants, all mid-1940s graduates of the same high school, underwent telephone cognitive screening. All participants provided access to adolescent IQ scores; we determined activity levels from yearbooks. We used path analysis to evaluate the complex relationships between early life, midlife, and late-life variables. Adolescent IQ had strong direct effects on global cognitive functioning, episodic memory, verbal fluency, and processing speed. Participants' high school mental activities had direct effects on verbal fluency, but physical and social activities did not predict any cognitive measure. Education had direct effects on global cognitive functioning, episodic memory, and, most strongly, processing speed, but other midlife factors (notably, occupational demands) were not significant predictors of late-life cognition. There were weak indirect effects of adolescent IQ on global cognitive functioning, episodic memory, and processing speed, working through high school mental activities and education. Verbal fluency, in contrast, was affected by adolescent IQ through links with high school mental activities, but not education. Our study suggests that reserve is dynamic, but it is most amenable to change in early life. We conclude that an active, engaged lifestyle, emphasizing mental activity and educational pursuits in early life, can have a positive impact on cognitive functioning in late life.

Effects of microbeam radiation therapy on normal and tumoral blood vessels.

PubMed

Bouchet, Audrey; Serduc, Raphäel; Laissue, Jean Albert; Djonov, Valentin

2015-09-01

Microbeam radiation therapy (MRT) is a new form of preclinical radiotherapy using quasi-parallel arrays of synchrotron X-ray microbeams. While the deposition of several hundred Grays in the microbeam paths, the normal brain tissues presents a high tolerance which is accompanied by the permanence of apparently normal vessels. Conversely, the efficiency of MRT on tumor growth control is thought to be related to a preferential damaging of tumor blood vessels. The high resistance of the healthy vascular network was demonstrated in different animal models by in vivo biphoton microscopy, magnetic resonance imaging, and histological studies. While a transient increase in permeability was shown, the structure of the vessels remained intact. The use of a chick chorioallantoic membrane at different stages of development showed that the damages induced by microbeams depend on vessel maturation. In vivo and ultrastructural observations showed negligible effects of microbeams on the mature vasculature at late stages of development; nevertheless a complete destruction of the immature capillary plexus was found in the microbeam paths. The use of MRT in rodent models revealed a preferential effect on tumor vessels. Although no major modification was observed in the vasculature of normal brain tissue, tumors showed a denudation of capillaries accompanied by transient increased permeability followed by reduced tumor perfusion and finally, a decrease in number of tumor vessels. Thus, MRT is a very promising treatment strategy with pronounced tumor control effects most likely based on the anti-vascular effects of MRT. Copyright © 2015. Published by Elsevier Ltd.

Luteal phase deficiency: abnormal gonadotropin and progesterone secretion patterns.

PubMed

Soules, M R; Clifton, D K; Cohen, N L; Bremner, W J; Steiner, R A

1989-10-01

Luteal phase deficiency (LPD) is a reproductive disorder associated with infertility and spontaneous abortion. This study was undertaken to determine whether LPD might be related to an abnormal pattern of gonadotropin secretion. We tested this hypothesis by evaluating the pattern of pulsatile LH secretion in both the follicular and luteal phases of the menstrual cycle in normal women (n = 21) and women with LPD (n = 20), which was diagnosed on the basis of two out of phase endometrial biopsies. In addition, we sought to determine whether changes in progesterone (P) pulse patterns could account for the decrease in average serum P levels in women with LPD. To this end, we examined the pulse patterns of P and compared these patterns between normal women and those with LPD. Frequent blood sampling was performed in both groups to determine their respective hormone secretion patterns. In the follicular phase, blood samples were obtained every 10 min for 12 h; in the luteal phase the samples were obtained every 10 min for 12 h; in the luteal LH, FSH, and P were assayed in each sample. Pulse detection was performed by an adaptive threshold method of pulse analysis. The LH pulse frequency was significantly higher in the women with LPD than in the normal women in the early follicular phase [P less than 0.05; LPD, 12.8 +/- 1.4 (+/- SE); normal, 8.2 +/- 0.7 pulses/12 h]. LH pulse frequency was similar in the early and late follicular phases in the women with LPD, whereas it was higher in the late follicular phase in normal women. Mean serum FSH levels were not different between groups in both the early and late follicular phases. In the luteal phase the P pulse amplitude and mean serum P level were significantly lower in the LPD group than in the normal women (P less than 0.01). We conclude that 1) a too rapid LH pulse pattern in the early follicular phase may lead to inadequate LH support of the corpus luteum and become manifest as LPD; 2) the mechanism for inadequate P secretion in LPD is decreased P pulse amplitude; 3) the finding of similar serum FSH levels in the two groups in both the early and late follicular phases did not support compromised folliculogenesis as an etiological factor for LPD.

Oxfordian magnetostratigraphy of the Aguilón and Tosos sections (Iberian Range, Spain) and evidence of a pre-Oligocene overprint

NASA Astrophysics Data System (ADS)

Juárez, M. T.; Osete, M. L.; Meléndez, G.; Langereis, C. G.; Zijderveld, J. D. A.

1994-08-01

A composite magnetic polarity sequence has been constructed for the middle and late Oxfordian (late Jurassic) from four overlapping sections situated in both limbs of an anticline. Two stable magnetisation components could be isolated in every sample analyzed. Both components pass the fold test: a low-temperature secondary component, with Dec. = 340.9° and Inc. = 44.9° ( α95 = 1.7°), of pre-Oligocene age, showing always normal polarity, and a high-temperature primary component, with Dec. = 324.1° and Inc. = 40.6° (α 95 = 2.9°). The latter shows both normal and reversed polarities and provides the geomagnetic record for the late Jurassic. The magnetostratigraphy of the four overlapping sections has given consistent results and indicates that a high frequency of reversals characterises the pattern of the geomagnetic field during the middle to upper Oxfordian. The corresponding Oxfordian paleopole is Plat = 251.2°, Plong = 55.9° ( α95 = 3.1).

Effect of Late Planting and Shading on Cellulose Synthesis during Cotton Fiber Secondary Wall Development

PubMed Central

Chen, Ji; Lv, Fengjuan; Liu, Jingran; Ma, Yina; Wang, Youhua; Chen, Binglin; Meng, Yali; Zhou, Zhiguo; Oosterhuis, Derrick M.

2014-01-01

Cotton-rapeseed or cotton-wheat double cropping systems are popular in the Yangtze River Valley and Yellow River Valley of China. Due to the competition of temperature and light resources during the growing season of double cropping system, cotton is generally late-germinating and late-maturing and has to suffer from the coupling of declining temperature and low light especially in the late growth stage. In this study, late planting (LP) and shading were used to fit the coupling stress, and the coupling effect on fiber cellulose synthesis was investigated. Two cotton (Gossypium hirsutum L.) cultivars were grown in the field in 2010 and 2011 at three planting dates (25 April, 25 May and 10 June) each with three shading levels (normal light, declined 20% and 40% PAR). Mean daily minimum temperature was the primary environmental factor affected by LP. The coupling of LP and shading (decreased cellulose content by 7.8%–25.5%) produced more severe impacts on cellulose synthesis than either stress alone, and the effect of LP (decreased cellulose content by 6.7%–20.9%) was greater than shading (decreased cellulose content by 0.7%–5.6%). The coupling of LP and shading hindered the flux from sucrose to cellulose by affecting the activities of related cellulose synthesis enzymes. Fiber cellulose synthase genes expression were delayed under not only LP but shading, and the coupling of LP and shading markedly postponed and even restrained its expression. The decline of sucrose-phosphate synthase activity and its peak delay may cause cellulose synthesis being more sensitive to the coupling stress during the later stage of fiber secondary wall development (38–45 days post-anthesis). The sensitive difference of cellulose synthesis between two cultivars in response to the coupling of LP and shading may be mainly determined by the sensitiveness of invertase, sucrose-phosphate synthase and cellulose synthase. PMID:25133819

Expression and effects of modulation of the K2P potassium channels TREK-1 (KCNK2) and TREK-2 (KCNK10) in the normal human ovary and epithelial ovarian cancer.

PubMed

Innamaa, A; Jackson, L; Asher, V; van Schalkwyk, G; Warren, A; Keightley, A; Hay, D; Bali, A; Sowter, H; Khan, R

2013-11-01

Aberrant expression of potassium (K(+)) channels contributes to cancer cell proliferation and apoptosis, and K(+) channel blockers can inhibit cell proliferation. TREK-1 and -2 belong to the two-pore domain (K2P) superfamily. We report TREK-1 and -2 expression in ovarian cancer and normal ovaries, and the effects of TREK-1 modulators on cell proliferation and apoptosis. The cellular localisation of TREK-1 and -2 was investigated by immunofluorescence in SKOV-3 and OVCAR-3 cell lines and in cultured ovarian surface epithelium and cancer. Channel expression in normal ovaries and cancer was quantified by western blotting. Immunohistochemical analysis demonstrated the association between channel expression and disease prognosis, stage, and grade. TREK-1 modulation of cell proliferation in the cell lines was investigated with the MTS-assay and the effect on apoptosis determined using flow cytometry. Expression was identified in both cell lines, ovarian cancer (n = 22) and normal ovaries (n = 6). IHC demonstrated positive staining for TREK-1 and -2 in 95.7 % of tumours (n = 69) and 100 % of normal ovaries (n = 9). A reduction in cell proliferation (P < 0.05) was demonstrated at 96 h in SKOV-3 and OVCAR-3 cells incubated TREK-1 modulating agents. Curcumin caused a significant reduction in early apoptosis in SKOV-3 (P < 0.001) and OVCAR-3 (P < 0.0001) cells and a significant increase in late apoptosis in SKOV-3 (P < 0.01) and OVCAR-3 cells (P < 0.0001). TREK-1 and -2 are expressed in normal ovaries and ovarian cancer. TREK-1 modulators have a significant effect on cell proliferation and apoptosis. We propose investigation of the therapeutic potential of TREK-1 blockers is warranted.

Characterization of estrogens, testosterone, and cortisol in normal bottlenose dolphin (Tursiops truncatus) pregnancy.

PubMed

Steinman, Karen J; Robeck, Todd R; O'Brien, Justine K

2016-01-15

The goal of this study was to describe profiles of serum estrogens, testosterone and cortisol during normal pregnancy in bottlenose dolphins. Predominant estrogens in all categories of dolphin sera pools during estrus and pregnancy (EARLY: Days 0-120; MID: Days 121-240; LATE: Days 241 to parturition; Day 0=day of conception) were estrone/estrone conjugates (E1-C) and estriol (E3). Serum samples collected throughout 101 normal pregnancies were analyzed for E1-C, E3, testosterone (T) and cortisol (CORT). E1-C was higher (P<0.05) during LATE compared to EARLY and MID, and higher (P<0.05) in nulliparous than multiparous females. E1-C concentrations were also inversely associated with maternal age (P=0.05). E3 was higher (P<0.05) in EARLY than MID and LATE, and higher overall for nulliparous than multiparous females, but concentrations were similar among gestational stages when parity was excluded from analyses. Analysis by indexed month post-conception (IMPC) demonstrated that E1-C increased from IMPC 9 and peaked at IMPC 11. E3 was significantly elevated during IMPC 1, decreased until IMPC 6 and peaked at IMPC 11. T increased (P<0.05) at IMPC 3 and continued to increase throughout gestation (P<0.05). CORT was higher (P<0.05) during LATE compared to EARLY and MID (P<0.05), peaked during IMPC 12, and was not affected by parity. Hormone profiles were not influenced by fetal sex. Copyright © 2015 Elsevier Inc. All rights reserved.

The temporal requirement for vitamin A in the developing eye: mechanism of action in optic fissure closure and new roles for the vitamin in regulating cell proliferation and adhesion in the embryonic retina.

PubMed

See, Angela Wai-Man; Clagett-Dame, Margaret

2009-01-01

Mammalian eye development requires vitamin A (retinol, ROL). The role of vitamin A at specific times during eye development was studied in rat fetuses made vitamin A deficient (VAD) after embryonic day (E) 10.5 (late VAD). The optic fissure does not close in late VAD embryos, and severe folding and collapse of the retina is observed at E18.5. Pitx2, a gene required for normal optic fissure closure, is dramatically downregulated in the periocular mesenchyme in late VAD embryos, and dissolution of the basal lamina does not occur at the optic fissure margin. The addition of ROL to late VAD embryos by E12.5 restores Pitx2 expression, supports dissolution of the basal lamina, and prevents coloboma, whereas supplementation at E13.5 does not. Surprisingly, ROL given as late as E13.5 completely prevents folding of the retina despite the presence of an open fetal fissure, showing that coloboma and retinal folding represent distinct VAD-dependent defects. Retinal folding due to VAD is preceded by an overall reduction in the percentage of cyclin D1 positive cells in the developing retina, (initially resulting in retinal thinning), as well as a dramatic reduction in the cell adhesion-related molecules, N-cadherin and beta-catenin. Reduction of retinal cell number combined with a loss of the normal cell-cell adhesion proteins may contribute to the collapse and folding of the retina that occurs in late VAD fetuses.

Late Cenozoic extension and crustal doming in the NE Chinese Pamir

NASA Astrophysics Data System (ADS)

Thiede, Rasmus C.; Sobel, Edward R.; Chen, Jie; Schoenbohm, Lindsay; Stockli, Daniel; Sudo, Masafumi; Strecker, Manfred

2013-04-01

The northward motion of the Pamir indenter with respect to Eurasia has resulted in coeval thrusting, strike-slip and normal faulting. The eastern Pamir is currently deformed by east-west oriented extension, accompanied by uplift and exhumation of the Kongur Shan (7719 m) and Muztagh Ata (7546 m) gneiss domes. Both domes are an integral part of the footwall of the Kongur Shan Extensional System (KES), a 250-km-long, north-south oriented graben. Why active normal faulting within the Pamir is primarily localized along the KES and not distributed more widely throughout the orogen, has remained unclear. In addition, relatively little is known about how deformation has evolved throughout the Cenozoic, despite refined estimates on present-day crustal deformation rates and microseismicity, which indicate where crustal deformation is presently being accommodated. To better constrain the spatiotemporal evolution of faulting along the KES, we present 39 new apatite fission-track, zircon U-Th-Sm/He, and 40Ar/39Ar cooling ages from a series of footwall transects along the KES graben shoulder. Combining this data with, present day topographic relief, 1D thermo-kinematic and exhumational modeling documents successive stages, rather than synchronous deformation and gneiss dome exhumation. While Kongur-Shan-exhumation started during the late Miocene, Muztagh Ata began earlier and has slowed down since the late Miocene. We present a new model, suggesting that thermal and density effects associated with a lithospheric tear fault along the eastern margin of the subducting Alai slab localizes extensional upper-plate deformation along the KES and decouples crustal motion between the Central/Western Pamir and Eastern Pamir/Tarim basin.

Does a functional activity programme improve function, quality of life, and falls for residents in long term care? Cluster randomised controlled trial

PubMed Central

Peri, Kathy; Robinson, Elizabeth; Wilkinson, Tim; von Randow, Martin; Kiata, Liz; Parsons, John; Latham, Nancy; Parsons, Matthew; Willingale, Jane; Brown, Paul; Arroll, Bruce

2008-01-01

Objective To assess the effectiveness of an activity programme in improving function, quality of life, and falls in older people in residential care. Design Cluster randomised controlled trial with one year follow-up. Setting 41 low level dependency residential care homes in New Zealand. Participants 682 people aged 65 years or over. Interventions 330 residents were offered a goal setting and individualised activities of daily living activity programme by a gerontology nurse, reinforced by usual healthcare assistants; 352 residents received social visits. Main outcome measures Function (late life function and disability instruments, elderly mobility scale, FICSIT-4 balance test, timed up and go test), quality of life (life satisfaction index, EuroQol), and falls (time to fall over 12 months). Secondary outcomes were depressive symptoms and hospital admissions. Results 473 (70%) participants completed the trial. The programme had no impact overall. However, in contrast to residents with impaired cognition (no differences between intervention and control group), those with normal cognition in the intervention group may have maintained overall function (late life function and disability instrument total function, P=0.024) and lower limb function (late life function and disability instrument basic lower extremity, P=0.015). In residents with cognitive impairment, the likelihood of depression increased in the intervention group. No other outcomes differed between groups. Conclusion A programme of functional rehabilitation had minimal impact for elderly people in residential care with normal cognition but was not beneficial for those with poor cognition. Trial registration Australian Clinical Trials Register ACTRN12605000667617. PMID:18845605

Myocardial late gadolinium enhancement in specific cardiomyopathies by cardiovascular magnetic resonance: a preliminary experience.

PubMed

Silva, Caterina; Moon, James C; Elkington, Andrew G; John, Anna S; Mohiaddin, Raad H; Pennell, Dudley J

2007-12-01

Late gadolinium enhancement cardiovascular magnetic resonance (CMR) can visualize myocardial interstitial abnormalities. The aim of this study was to assess whether regions of abnormal myocardium can also be visualized by late enhancement gadolinium CMR in the specific cardiomyopathies. A retrospective review of all referrals for gadolinium CMR with specific cardiomyopathy over 20 months. Nine patients with different specific cardiomyopathies were identified. Late enhancement was demonstrated in all patients, with a mean signal intensity of 390 +/- 220% compared with normal regions. The distribution pattern of late enhancement was unlike the subendocardial late enhancement related to coronary territories found in myocardial infarction. The affected areas included papillary muscles (sarcoid), the mid-myocardium (Anderson-Fabry disease, glycogen storage disease, myocarditis, Becker muscular dystrophy) and the global sub-endocardium (systemic sclerosis, Loeffler's endocarditis, amyloid, Churg-Strauss). Focal myocardial late gadolinium enhancement is found in the specific cardiomyopathies, and the pattern is distinct from that seen in infarction. Further systematic studies are warranted to assess whether the pattern and extent of late enhancement may aid diagnosis and prognostic assessment.

Late Quaternary faulting along the Death Valley-Furnace Creek fault system, California and Nevada

USGS Publications Warehouse

Brogan, George E.; Kellogg, Karl; Slemmons, D. Burton; Terhune, Christina L.

1991-01-01

The Death Valley-Furnace Creek fault system, in California and Nevada, has a variety of impressive late Quaternary neotectonic features that record a long history of recurrent earthquake-induced faulting. Although no neotectonic features of unequivocal historical age are known, paleoseismic features from multiple late Quaternary events of surface faulting are well developed throughout the length of the system. Comparison of scarp heights to amount of horizontal offset of stream channels and the relationships of both scarps and channels to the ages of different geomorphic surfaces demonstrate that Quaternary faulting along the northwest-trending Furnace Creek fault zone is predominantly right lateral, whereas that along the north-trending Death Valley fault zone is predominantly normal. These observations are compatible with tectonic models of Death Valley as a northwest-trending pull-apart basin. The largest late Quaternary scarps along the Furnace Creek fault zone, with vertical separation of late Pleistocene surfaces of as much as 64 m (meters), are in Fish Lake Valley. Despite the predominance of normal faulting along the Death Valley fault zone, vertical offset of late Pleistocene surfaces along the Death Valley fault zone apparently does not exceed about 15 m. Evidence for four to six separate late Holocene faulting events along the Furnace Creek fault zone and three or more late Holocene events along the Death Valley fault zone are indicated by rupturing of Q1B (about 200-2,000 years old) geomorphic surfaces. Probably the youngest neotectonic feature observed along the Death Valley-Furnace Creek fault system, possibly historic in age, is vegetation lineaments in southernmost Fish Lake Valley. Near-historic faulting in Death Valley, within several kilometers south of Furnace Creek Ranch, is represented by (1) a 2,000-year-old lake shoreline that is cut by sinuous scarps, and (2) a system of young scarps with free-faceted faces (representing several faulting events) that cuts Q1B surfaces.

The Experiences of Late-Diagnosed Women with Autism Spectrum Conditions: An Investigation of the Female Autism Phenotype

ERIC Educational Resources Information Center

Bargiela, Sarah; Steward, Robyn; Mandy, William

2016-01-01

We used Framework Analysis to investigate the female autism phenotype and its impact upon the under-recognition of autism spectrum conditions (ASC) in girls and women. Fourteen women with ASC (aged 22-30 years) diagnosed in late adolescence or adulthood gave in-depth accounts of: "pretending to be normal"; of how their gender led various…

The Course of Neuropsychological Functions in Children with Attention Deficit Hyperactivity Disorder from Late Childhood to Early Adolescence

ERIC Educational Resources Information Center

Drechsler, Renate; Brandeis, Daniel; Foldenyi, Monika; Imhof, Katrin; Steinhausen, Hans-Christoph

2005-01-01

Objective: The aim of this follow-up study was to investigate the course of performance in attentional tasks in children with ADHD and normal controls in late childhood and preadolescence over short periods of time. The development of two dimensions of attention was compared: alertness/arousal and inhibitory control. Method: Children with ADHD (N…

Bedtime and sleep timing but not sleep duration are associated with eating habits in primary school children.

PubMed

Thivel, David; Isacco, Laurie; Aucouturier, Julien; Pereira, Bruno; Lazaar, Nordine; Ratel, Sébastien; Doré, Eric; Duché, Pascale

2015-04-01

In the context of childhood obesity progression, sleep patterns have been associated with unhealthy eating habits and energy intake. The association between several eating habits and sleep patterns in children has been recently studied. The aim of this study was to explore the association between sleep patterns, eating habits, and physical fitness in primary school children. A total of 236 children of 6 to 10 years old were recruited. Anthropometric characteristics and body composition were measured, and cardiorespiratory (20-m shuttle run test) and musculoskeletal (squat jump and cycling peak power) fitness tests were performed. Parents were asked to fill out an eating habits questionnaire, and children were classified into 4 categories as a function of the number of eating risk factors they presented. Parents completed a questionnaire about their child's bedtime and waking hours during weekdays and weekends. Weight (p < .01), waist circumference, and fat mass (p < .05) were significantly higher in late sleepers (27.6 ± 6.3 kg; 60.1 ± 7.6 cm; 19.52 ± 7.44) compared with normal sleepers (25.4 ± 3.7 kg; 58.2 ± 4.9 cm; 17.44% ± 6.23%). None of the physical fitness parameters were associated with sleep duration, bedtime, wake-up time, nor were they significantly different between late and normal sleepers. Bedtime was significantly earlier in children consuming breakfast everyday (08:30 vs. 09:00 PM, p < .01); later in children snacking (09:15 vs. 09:30 PM, p < .05) or watching TV at lunch (10:00 vs 09:30 PM, p < .05). There is an association between the proportion of normal and late sleepers and the accumulation of healthy eating habits (p < .001). Bedtime and sleep timings (normal or late sleepers) are associated with eating habits in primary school children. It seems necessary to consider the number of unhealthy eating habits adopted by children when studying these associations.

Second diastolic pulmonary venous flow and isolated late diastolic mitral valve regurgitation in first-degree atrioventricular block.

PubMed

Leibundgut, Gregor; Bernheim, Alain M

2010-04-01

The authors report the case of a 77-year-old male patient with sinus rhythm and a first-degree atrioventricular (AV) block who was referred for echocardiographic follow-up 18 years after aortic valve replacement. Left ventricular systolic function as well as the function of the aortic prosthesis was normal. Systolic mitral regurgitation (MR) was virtually absent, but isolated late diastolic MR was detected by colour Doppler imaging. Coincidental to the occurrence of diastolic MR, a second late diastolic forward flow in the pulmonary veins was observed. Therefore, during the prolonged left atrial relaxation caused by first-degree AV block, the left atrial pressure drops below the pressure in both adjacent chambers in late diastole, resulting in both late diastolic MR and a second diastolic pulmonary venous forward flow.

Extensive Gravity Sliding of Late Jurassic-Cretaceous Age along the Northern Yucatan Margin of the Gulf of Mexico

NASA Astrophysics Data System (ADS)

Steier, A.; Mann, P.

2017-12-01

Gravity slides on salt or shale detachment surfaces linking updip extension with down dip compression have been described from several margins of the Gulf of Mexico (GOM). In a region 250 km offshore from the southwestern coast of Florida, the late Jurassic section near Destin Dome and Desoto Canyon has undergone late Jurassic to Cretaceous gravity sliding and downdip dispersion of rigid blocks along the top of the underlying Louann salt. Yet there has been no previous study of similar structural styles on the slope and deep basin of its late Jurassic conjugate margin located 200 km offshore of the northern margin of the Yucatan Peninsula. This study describes an extensive area of Mesozoic gravity sliding from the northern Yucatan slope using a grid of 2D seismic data covering a 134,000 km2 area of the northern Yucatan margin tied to nine wells. These data allow the northern Yucatan margin to be divided into three slope and basinal provinces: 1) a 225 km length of the northeastern margin consisting of late Jurassic-Cretaceous section that is not underlain by salt, exhibits no gravity sliding features, and has sub-horizontal dips; 2) a 120 km length of the north-central Yucatan margin with gravity slide features characterized by an 80-km-wide updip zone of normal faults occupying the shelf edge and upper slope and a 50-km-wide downdip zone of folds and thrust faults at the base of the slope; the slide area exhibits multiple detached slide blocks composed of late Jurassic sandstones and marine mudstones separated by intervening salt rollers; growth wedges adjacent to listric, normal faults suggest a gradual and long-lived downdip motion of rigid fault blocks throughout much of the late Jurassic and Cretaceous rather than a catastrophic and instantaneous collapse of the shelf edge; the basal, normal detachment fault averages 3° in dip and is overlain by salt that varies from 0-500 ms in time thickness; by the end of the Cretaceous, most gravity sliding and vertical salt movement off the north-central Yucatan had ceased and was capped by the post-sliding Cretaceous-Paleocene boundary deposit (KPBD); and 3) a 150 km length of the southwestern margin with the largest thicknesses of salt; smaller salt rollers are less common as large diapirs are frequent and extensively deform the late Mesozoic section as well as overlying younger strata.

Comparison of characteristics of aerosol during rainy weather and cold air-dust weather in Guangzhou in late March 2012

NASA Astrophysics Data System (ADS)

Chen, Huizhong; Wu, Dui; Yu, Jianzhen

2016-04-01

Using the data on aerosol observed hourly by Marga ADI 2080 and Grimm 180, we compared the characteristics of aerosol during rainy weather and cold air-dust weather in Guangzhou in late March 2012. The mass concentration of aerosol appeared distinct between the two weather processes. During rainy weather, the mass concentration of PM and total water-soluble components decreased obviously. During cold air-dust weather, the cleaning effect of cold air occurred much more suddenly and about a half day earlier than the dust effect. As a result, the mass concentration of PM and total water-soluble components first dropped dramatically to a below-normal level and then rose gradually to an above-normal level. The ratio of PM2.5/PM10 and PM1/PM10 decreased, suggesting that dust-storm weather mainly brought in coarse particles. The proportion of Ca2+ in the total water-soluble components significantly increased to as high as 50 % because of the effect of dust weather. We further analysed the ionic equilibrium during rainy and cold air-dust weather, and compared it with that during hazy weather during the same period. The aerosol during rainy weather was slightly acidic, whereas that during hazy weather and cold air-dust weather was obviously alkaline, with that during cold air-dust weather being significantly more alkaline. Most of the anions, including SO4 2- and NO3 -, were neutralised by NH4 + during rainy and hazy weather, and by Ca2+ during cold air-dust weather.

Esophagus and Contralateral Lung-Sparing IMRT for Locally Advanced Lung Cancer in the Community Hospital Setting.

PubMed

Kao, Johnny; Pettit, Jeffrey; Zahid, Soombal; Gold, Kenneth D; Palatt, Terry

2015-01-01

The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue-sparing IMRT can allow safe dose escalation resulting in decreased acute and late toxicity. We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of three-dimensional conformal radiotherapy or IMRT without specific esophagus or contralateral lung constraints (standard RT). From 5/12 to 9/14, 38 patients were treated with normal tissue-sparing IMRT with selective sparing of contralateral lung and esophagus. The study endpoints were dosimetry, toxicity, and overall survival. Despite higher mean prescribed radiation doses in the normal tissue-sparing IMRT cohort (64.5 vs. 60.8 Gy, p = 0.04), patients treated with normal tissue-sparing IMRT had significantly lower lung V20, V10, V5, mean lung, esophageal V60, and mean esophagus doses compared to patients treated with standard RT (p ≤ 0.001). Patients in the normal tissue-sparing IMRT group had reduced acute grade ≥3 esophagitis (0 vs. 11%, p < 0.001), acute grade ≥2 weight loss (2 vs. 16%, p = 0.04), and late grade ≥2 pneumonitis (7 vs. 21%, p = 0.02). The 2-year overall survival was 52% with normal tissue-sparing IMRT arm compared to 28% for standard RT (p = 0.015). These data provide proof of principle that suboptimal radiation dose distributions are associated with significant acute and late lung and esophageal toxicity that may result in hospitalization or even premature mortality. Strict attention to contralateral lung and esophageal dose-volume constraints are feasible in the community hospital setting without sacrificing disease control.

Posterior Cingulate Glucose Metabolism, Hippocampal Glucose Metabolism, and Hippocampal Volume in Cognitively Normal, Late-Middle-Aged Persons at 3 Levels of Genetic Risk for Alzheimer Disease

PubMed Central

Protas, Hillary D.; Chen, Kewei; Langbaum, Jessica B. S.; Fleisher, Adam S.; Alexander, Gene E.; Lee, Wendy; Bandy, Daniel; de Leon, Mony J.; Mosconi, Lisa; Buckley, Shannon; Truran-Sacrey, Diana; Schuff, Norbert; Weiner, Michael W.; Caselli, Richard J.; Reiman, Eric M.

2013-01-01

Objective To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease. Design Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxy-glucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers. Setting Academic medical center. Participants A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. Main Outcome Measures The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume. Results Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P=.60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P=.001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r=0.29, P=.0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P<.05, determined by use of pairwise Fisher z tests). Conclusions Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for Alzheimer disease. PMID:23599929

The E7 Open Reading Frame Acts in cis and in trans To Mediate Differentiation-Dependent Activities in the Human Papillomavirus Type 16 Life Cycle▿†

PubMed Central

Bodily, Jason M.; Mehta, Kavi P. M.; Cruz, Linda; Meyers, Craig; Laimins, Laimonis A.

2011-01-01

Human papillomaviruses (HPVs) are the causative agents of several important genital and other mucosal cancers. The HPV16 E7 gene encodes a viral oncogene that is necessary for the continued growth of cancer cells, but its role in the normal, differentiation-dependent life cycle of the virus is not fully understood. The function of E7 in the viral life cycle was examined using a series of mutations of E7 created in the context of the complete HPV16 genome. The effect of these E7 mutations on key events of the viral life cycle, including immortalization, episomal maintenance, late promoter activation, and infectious virion synthesis, was examined. Our studies show that the pRb binding domain is indispensable for early viral activities, whereas the C-terminal zinc finger domain contributed primarily to very late events. Mutations of the casein kinase II phosphorylation site caused a complex phenotype involving both the function of E7 protein and a cis element necessary for the activation of the late promoter, identifying for the first time a promoter element important for late promoter function in the context of the viral genome. All mutant genomes tested showed reduced viral titers following growth in organotypic raft cultures. These studies clarify the role of E7 as a regulator of late events in the differentiation-dependent HPV life cycle. PMID:21697473

Sports in pediatric oncology: the role(s) of physical activity for children with cancer.

PubMed

Götte, Miriam; Taraks, Silke; Boos, Joachim

2014-03-01

Malignant disease and anticancer therapy dramatically affect daily life activities and participation in grassroots and high-performance sports. Specifically in childhood and adolescence such activities are relevant factors of individual development and social life. This review focuses on the inherent reduction of normal physical activity in pediatric oncology because this cutback additionally contributes to the level of burden of malignancies. Maintaining normality requires detailed analyses of disease-related and therapy-related restrictions and their justification. Relevant efforts should be stepped up to maintain physical activity levels during pediatric cancer therapy. Another aspect addresses direct therapeutic implications. Feasibility studies, nonrandomized as well as randomized investigations addressed therapeutic effects in acute hospital care, in bone marrow transplant settings, and in outpatient therapy. The overall summary shows positive effects on clinical and psychosocial outcome. Even if the basis of the data for children is still limited, there will be no doubt about a general impact of physical activity on acute side effects as well as late effects. In the areas of tension between context-related restrictions, the right to maintain normality wherever possible and the positive therapeutic and psychosocial perspectives of sports, strong efforts are needed to support physical activity wherever indicated, clarify contraindications, and overcome structural limitations.

Effect of Intrahepatic Cholestasis of Pregnancy on Neonatal Birth Weight: A Meta-Analysis

PubMed Central

Li, Li; Chen, Yuan-Hua; Yang, Yuan-Yuan; Cong, Lin

2018-01-01

Objective: To evaluate the effect of intrahepatic cholestasis of pregnancy (ICP) on neonatal birth weight. Methods: Potential articles were identified by searching PubMed and Web of Science databases on April 30th, 2017. Using the Mantel-Haenszel random-effects or fixed-effects model, outcomes were summarized through weighted mean difference (WMD) and 95% confidence intervals (CI). Potential publication bias was tested using a funnel plot and the methods of Egger’s regression and Begg’s test. Results: A total of eight studies were included in our meta-analysis. Six studies reported data on neonatal birth weight in ICP and control pregnancies. Pooled data from the six studies showed that the birth weight in the ICP group was significantly lighter than in the control group. The overall pooled WMD was -175 g (95% CI: -301, -48). Meanwhile, pooled data from the other two studies indicated that the birth weight in the late-onset ICP group was heavier than in the early-onset ICP group (WMD: 267 g, 95% CI: 168, 366). Conclusion: Neonatal birth weights in ICP pregnancies were lower than in normal pregnancies. Furthermore, early-onset ICP is associated with a lower birth weight than late-onset ICP. PMID:28825589

Effects of simulated weightlessness on fish otolith growth: Clinostat versus Rotating-Wall Vessel

NASA Astrophysics Data System (ADS)

Brungs, Sonja; Hauslage, Jens; Hilbig, Reinhard; Hemmersbach, Ruth; Anken, Ralf

2011-09-01

Stimulus dependence is a general feature of developing sensory systems. It has been shown earlier that the growth of inner ear heavy stones (otoliths) of late-stage Cichlid fish ( Oreochromis mossambicus) and Zebrafish ( Danio rerio) is slowed down by hypergravity, whereas microgravity during space flight yields an opposite effect, i.e. larger than 1 g otoliths, in Swordtail ( Xiphophorus helleri) and in Cichlid fish late-stage embryos. These and related studies proposed that otolith growth is actively adjusted via a feedback mechanism to produce a test mass of the appropriate physical capacity. Using ground-based techniques to apply simulated weightlessness, long-term clinorotation (CR; exposure on a fast-rotating Clinostat with one axis of rotation) led to larger than 1 g otoliths in late-stage Cichlid fish. Larger than normal otoliths were also found in early-staged Zebrafish embryos after short-term Wall Vessel Rotation (WVR; also regarded as a method to simulate weightlessness). These results are basically in line with the results obtained on Swordtails from space flight. Thus, the growth of fish inner ear otoliths seems to be an appropriate parameter to assess the quality of "simulated weightlessness" provided by a particular simulation device. Since CR and WVR are in worldwide use to simulate weightlessness conditions on ground using small-sized specimens, we were prompted to directly compare the effects of CR and WVR on otolith growth using developing Cichlids as model organism. Animals were simultaneously subjected to CR and WVR from a point of time when otolith primordia had begun to calcify both within the utricle (gravity perception) and the saccule (hearing); the respective otoliths are the lapilli and the sagittae. Three such runs were subsequently carried out, using three different batches of fish. The runs were discontinued when the animals began to hatch. In the course of all three runs performed, CR led to larger than normal lapilli, whereas WVR had no effect on the growth of these otoliths. Regarding sagittae, CR resulted in larger than normal stones in one of the three runs. The other CR runs and all WVR runs had no effect on sagittal growth. These results clearly indicate that CR rather than WVR can be regarded as a device to simulate weightlessness using the Cichlid as model organism. Since WVR has earlier been shown to affect otolith growth in Zebrafish, the lifestyle of an animal (mouth-breeding versus egg-laying) seems to be of considerable importance. Further studies using a variety of simulation techniques (including, e.g. magnetic levitation and random positioning) and various species are needed in order to identify the most appropriate technique to simulate weightlessness regarding a particular model organism.

Anti-Nociceptive Effect of Resveratrol During Inflammatory Hyperalgesia via Differential Regulation of pro-Inflammatory Mediators.

PubMed

Singh, Ajeet Kumar; Vinayak, Manjula

2016-07-01

Sensitization of nociceptive neurons by inflammatory mediators leads to hypersensitivity for normal painful stimuli which is termed hyperalgesia. Oxidative stress is an essential factor in pathological pain; therefore, antioxidants qualify as potential anti-hyperalgesic agents. The present study examines the efficacy of the natural antioxidant resveratrol in complete Freund's adjuvant (CFA) induced hyperalgesic rats. Thermal hyperalgesia was measured at different time points by paw withdrawal latency test and confirmed by c-Fos expression in spinal dorsal horn. The impact of resveratrol treatment on inflammatory mediators at peripheral (paw skin) and central (spinal cord) sites was determined during early (6 h) as well as late phase (48 h) of hyperalgesia. Intraplanter injection of CFA increased the level of cytokines IL-1β, TNF-α and IL-6 as well as inflammatory enzymes COX-2 and iNOS in paw skin in both phases. In case of spinal cord, the level of COX-2 was found to be elevated in both phases, whereas iNOS could not be detected. The cytokines were found to be elevated only in late phase in spinal cord. Administration of resveratrol (20 mg/kg) shifted the level of all inflammatory mediators towards normal, except cytokines in paw skin. The present study suggests that the anti-nociceptive effect of resveratrol is implicated at both peripheral and central sites in a tissue specific manner. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Role of extensional structures on the location of folds and thrusts during tectonic inversion (northern Iberian Chain, Spain)

NASA Astrophysics Data System (ADS)

Cortés, Angel L.; Liesa, Carlos L.; Soria, Ana R.; Meléndez, Alfonso

1999-03-01

The Aguilón Subbasin (NE Spain) was originated daring the Late Jurassic-Early Cretaceous rifting due to the action of large normal faults, probably inherited from Late Variscan fracturing. WNW-ESE normal faults limit two major troughs filled by continental deposits (Valanginian to Early Barremian). NE-SW faults control the location of subsidiary depocenters within these troughs. These basins were weakly inverted during the Tertiary with folds and thrusts striking E-W to WNW-ESE involving the Mesozoic-Tertiary cover with a maximum estimated shortening of about 12 %. Tertiary compression did not produce the total inversion of the Mesozoic basin but extensional structures are responsible for the location of major Tertiary folds. Shortening of the cover during the Tertiary involved both reactivation of some normal faults and development of folds and thrusts nucleated on basement extensional steps. The inversion style depends mainly on the occurrence and geometry of normal faults limiting the basin. Steep normal faults were not reactivated but acted as buttresses to the cover translation. Around these faults, affecting both basement and cover, folds and thrusts were nucleated due to the stress rise in front of major faults. Within the cover, the buttressing against normal faults consists of folding and faulting implying little shortening without development of ceavage or other evidence of internal deformation.

A Late Babylonian Normal and ziqpu star text

NASA Astrophysics Data System (ADS)

Roughton, N. A.; Steele, J. M.; Walker, C. B. F.

2004-09-01

The Late Babylonian tablet BM 36609+ is a substantial rejoined fragment of an important and previously unknown compendium of short texts dealing with the use of stars in astronomy. Three of the fragments which constitute BM 36609+ were first identified as containing a catalogue of Babylonian "Normal Stars" (stars used as reference points in the sky to track the movement of the moon and planets) by N. A. Roughten. C. B. F. Walker has been able to join several more fragments to the tablet which have revealed that other sections of the compendium concern a group of stars whose culminations are used for keeping time, known as ziqpu-stars after the Akkadian term for culmination, ziqpu. All the preserved sections on the obverse of BM 36609+ concern ziqpu-stars. On the reverse of the tablet we find several sections concerning Normal Stars. This side begins with a catalogue of Normal Stars giving their positions within zodiacal signs. The catalogue is apparently related to the only other Normal Star catalogue previously known, BM 46083 published by Sachs. In the following we present an edition of BM 36609+ based upon Walker's transliteration of the tablet. Since Sachs' edition of BM 46083, the Normal Star catalogue related to BM 36609+, was based upon a photograph and is incomplete we include a fresh edition of the tablet. A list of Akkadian and translated star names with identifications is given.

Clinical Use of Aromatase Inhibitors in Adult Males.

PubMed

Tan, Ronny B W; Guay, Andre T; Hellstrom, Wayne J G

2014-04-01

There is a growing interest in the treatment of late-onset hypogonadism, another name for the study of testosterone deficiency in an older age group. Initial attempts at testosterone replacement have also brought attention to the possible adverse effects on the patients' cardiovascular risk factors and their prostate health. The "female" hormone estradiol is no longer considered as the feminizing hormone, as it has been identified to have an effect on the sexual and general well-being of adult males. Urologists and endocrinologists alike have started to pay attention to the serum T/E 2 (testosterone : estradiol) ratio that appears to be more important than the respective individual hormonal levels. Therein lies the possible role of aromatase inhibitors (AIs) in restoring the normal balance of serum testosterone and estradiol levels for the adequate treatment of late-onset hypogonadism, while limiting the potential adverse effects. Currently, other established clinical indications of AIs include the treatment of breast cancer in female patients and developmental growth problems in pediatric patients. This review evaluates the role of AIs as a treatment option for late-onset hypogonadism and the evidence for its other clinical uses in men, including its possible adverse effects. A literature review was performed with regards to the use of aromatase inhibitors in adult males, the role of estrogens in adult males, as well as adverse effect of AIs on bone health in adult males. To evaluate the evidence for the use of AIs in adult males to treat late-onset hypogonadism, obesity-related hypogonadotropic hypogonadism, gynecomastia, and male subfertility. To evaluate the evidence for the possible adverse effects on the bone health of adult males with the use of AIs. Currently there is no literature to recommend the use of AIs in adult males to treat late-onset hypogonadism, obesity-related hypogonadotropic hypogonadism, gynecomastia, or male subfertility, although some positive effects have been reported. The adverse effects on bone health seen in females treated with AIs are not seen in males. With the better understanding of the T/E 2 ratio in adult males, the lack of scientific data to show that bone health is adversely affected by AI usage in adult males, the positive effects of AIs on the treatment of conditions like late-onset hypogonadism and male subfertility encourages conducting large-scale, multicenter, randomized controlled trials for the clinical use of AIs in adult males. Tan RBW, Guay AT, and Hellstrom WJG. Clinical use of aromatase inhibitors in adult males. Sex Med Rev 2014;2:79-90. Copyright © 2014 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Sleep and Premenstrual Syndrome

PubMed Central

Jehan, Shazia; Auguste, Evan; Hussain, Mahjabeen; Pandi-Perumal, Seithikurippu R.; Brzezinski, Amon; Gupta, Ravi; Attarian, Hrayr; Jean-Louis, Giradin; McFarlane, Samy I.

2016-01-01

The etiology of premenstrual syndrome (PMS) is unknown; it may be due to the normal effect of hormones during the menstrual cycle as it occurs in the late luteal phase of the menstrual cycle.PMS affects women of childbearing age and remits with the onset of menstruation. The menstrual phase is known to influence stage 2 and REM sleep in women, irrespective of premenstrual dysphoric disorder (PMDD). Women with PMDD showed a decreased response to melatonin in their luteal phase as compared to the follicular phase of the menstrual cycle. However, melatonin duration or timing of offset in the morning has not been reported to correlate with the mood. Rather, improvement in mood-related symptoms of PMDD has been found to be influenced by sleep deprivation, be it sleep restrictions in early or late night. Sleep disturbance and decreased melatonin secretions due to hormonal fluctuations during the luteal phase of the menstrual cycle could explain the sleep complaints of PMDD. PMID:28239684

Left ventricular remodeling and change of systolic function after closure of patent ductus arteriosus in adults: device and surgical closure.

PubMed

Jeong, Young-Hoon; Yun, Tae-Jin; Song, Jong-Min; Park, Jung-Jun; Seo, Dong-Man; Koh, Jae-Kon; Lee, Se-Whan; Kim, Mi-Jeong; Kang, Duk-Hyun; Song, Jae-Kwan

2007-09-01

Left ventricular (LV) remodeling and predictors of LV systolic function late after closure of patent ductus arteriosus (PDA) in adults remain to be clearly demonstrated. In 45 patients with PDA, including 28 patients who received successful occlusion using the Amplatzer device (AD group) (AGA, Golden Valley, MN) and 17 patients who received surgical closure (OP group), echocardiography studies were performed before closure and 1 day (AD group) or within 7 days (OP group) after closure, and then were repeated at > or = 6 months (17 +/- 13 months). In both groups, LV ejection fraction (EF) and end-diastolic volume index were significantly decreased immediately after closure, whereas end-systolic volume index did not change. During the long-term follow-up period, end-systolic as well as end-diastolic volume indices decreased significantly in both groups and LV EF recovered compared to the immediate postclosure state. However, LV EF remained low compared to the preclosure state. Five patients (11.1%) including 3 patients in the AD group and 2 patients in the OP group showed persistent late LV systolic dysfunction (EF <50%). In stepwise, multiple logistic regression analysis, preclosure EF was the only independent predictor of late normal postclosure EF (odds ratio, 1.230; 95% CI, 1.054-1.434; P = .008). Receiver operating characteristic curve analysis showed that preclosure EF > or = 62% had a sensitivity of 72% and a specificity of 83% for predicting late normal LV EF after closure. Left ventricular EF remains low late after PDA closure compared with preclosure state in adults. Preclosure LV EF is the best index to predict late postclosure LV EF.

Early intervention for late-onset ornithine transcarbamylase deficiency.

PubMed

Fujisawa, Daisuke; Mitsubuchi, Hiroshi; Matsumoto, Shirou; Iwai, Masanori; Nakamura, Kimitoshi; Hoshide, Ryuji; Harada, Nawomi; Yoshino, Makoto; Endo, Fumio

2015-01-01

We report the case of a family with late-onset ornithine transcarbamylase deficiency (OTCD). Several family members had died from OTCD, and the c.221G>A, p.Lys221Lys mutation was detected at the 3' end of exon 6 of OTC in the X-chromosome of some members. We provided genetic counseling on pregnancy, delivery, and neonate management to a 4th-generation female carrier and decided on metabolic management of her child from birth. Two male patients were diagnosed with late-onset OTCD on the basis of blood amino acid and genetic analysis, and they received arginine supplementation from the asymptomatic, early neonatal period. These children grew and developed normally, without decompensation. Patients with late-onset OTCD can and should be diagnosed and treated in the early neonatal period, especially those from families already diagnosed with late-onset OTCD, and family members must be provided with genetic counseling. © 2015 Japan Pediatric Society.

[The relationship of ECG and pregnancy outcome of older pregnant woman in late pregnancy].

PubMed

Zhao, Xiao-Qin; Wang, Chun-Guang; Song, Yu-Xia; Jiao, Hong

2014-01-01

To observe the changes of electrocardiogram (ECG) and pregnancy outcome of the late pregnancy women. Late pregnancy women were divided into two groups by age: over 35 group and under 35 group. The incidence of abnormal electrocardiogram was recorded when the patients were subjected to routine ECG examination. Then the pregnancy, delivery outcome and if there's low birth weight newborn were recorded later. The incidence of abnormal ECG in over 35 group was significantly higher than that in under 35 group (P < 0.05). And the incidence of ST segment changes, arrhythmia in the group of former was higher than that in the group of latter (P < 0.05). Among the different type of arrhythmia, the incidence of sinus bradycardia and ventricular premature beat in the group of former were higher than those in the group of latter (P < 0.05). But the incidence of sinus tachycardia in the former group was obviously lower than that in the latter group (P < 0.05). The incidence of pregnancy loss in over 35 with abnormal ECG group was significantly higher than that in under 35 with normal or abnormal ECG groups (P < 0.05). The incidence of premature birth in over 35 with abnormal ECG group was significantly higher than that in over 35 with normal ECG group (P < 0.05). The incidence of low body weight in over 35 with abnormal ECG group was significantly higher than that in under 35 with normal ECG group (P < 0.05). The late pregnancy women with the age of over 35 are more likely to have ECG abnormalities, such as arrhythmia, myocardial ischemia and so on. The older pregnant women with abnormal ECG easily suffer from pregnancy losing, premature birth and having a low birth weight baby.

Direct evidence that prostate tumors show high sensitivity to fractionation (low alpha/beta ratio), similar to late-responding normal tissue.

PubMed

Brenner, David J; Martinez, Alvaro A; Edmundson, Gregory K; Mitchell, Christina; Thames, Howard D; Armour, Elwood P

2002-01-01

A direct approach to the question of whether prostate tumors have an atypically high sensitivity to fractionation (low alpha/beta ratio), more typical of the surrounding late-responding normal tissue. Earlier estimates of alpha/beta for prostate cancer have relied on comparing results from external beam radiotherapy (EBRT) and brachytherapy, an approach with significant pitfalls due to the many differences between the treatments. To circumvent this, we analyze recent data from a single EBRT + high-dose-rate (HDR) brachytherapy protocol, in which the brachytherapy was given in either 2 or 3 implants, and at various doses. For the analysis, standard models of tumor cure based on Poisson statistics were used in conjunction with the linear-quadratic formalism. Biochemical control at 3 years was the clinical endpoint. Patients were matched between the 3 HDR vs. 2 HDR implants by clinical stage, pretreatment prostate-specific antigen (PSA), Gleason score, length of follow-up, and age. The estimated value of alpha/beta from the current analysis of 1.2 Gy (95% CI: 0.03, 4.1 Gy) is consistent with previous estimates for prostate tumor control. This alpha/beta value is considerably less than typical values for tumors (> or =8 Gy), and more comparable to values in surrounding late-responding normal tissues. This analysis provides strong supporting evidence that alpha/beta values for prostate tumor control are atypically low, as indicated by previous analyses and radiobiological considerations. If true, hypofractionation or HDR regimens for prostate radiotherapy (with appropriate doses) should produce tumor control and late sequelae that are at least as good or even better than currently achieved, with the added possibility that early sequelae may be reduced.

Nailfold capillaroscopy for prediction of novel future severe organ involvement in systemic sclerosis.

PubMed

Smith, Vanessa; Riccieri, Valeria; Pizzorni, Carmen; Decuman, Saskia; Deschepper, Ellen; Bonroy, Carolien; Sulli, Alberto; Piette, Yves; De Keyser, Filip; Cutolo, Maurizio

2013-12-01

Assessment of associations of nailfold videocapillaroscopy (NVC) scleroderma (systemic sclerosis; SSc) ("early," "active," and "late") with novel future severe clinical involvement in 2 independent cohorts. Sixty-six consecutive Belgian and 82 Italian patients with SSc underwent NVC at baseline. Images were blindly assessed and classified into normal, early, active, or late NVC pattern. Clinical evaluation was performed for 9 organ systems (general, peripheral vascular, skin, joint, muscle, gastrointestinal tract, lung, heart, and kidney) according to the Medsger disease severity scale (DSS) at baseline and in the future (18-24 months of followup). Severe clinical involvement was defined as category 2 to 4 per organ of the DSS. Logistic regression analysis (continuous NVC predictor variable) was performed. The OR to develop novel future severe organ involvement was stronger according to more severe NVC patterns and similar in both cohorts. In simple logistic regression analysis the OR in the Belgian/Italian cohort was 2.16 (95% CI 1.19-4.47, p = 0.010)/2.33 (95% CI 1.36-4.22, p = 0.002) for the early NVC SSc pattern, 4.68/5.42 for the active pattern, and 10.14/12.63 for the late pattern versus the normal pattern. In multiple logistic regression analysis, adjusting for disease duration, subset, and vasoactive medication, the OR was 2.99 (95% CI 1.31-8.82, p = 0.007)/1.88 (95% CI 1.00-3.71, p = 0.050) for the early NVC SSc pattern, 8.93/3.54 for the active pattern, and 26.69/6.66 for the late pattern versus the normal pattern. Capillaroscopy may be predictive of novel future severe organ involvement in SSc, as attested by 2 independent cohorts.

Reirradiation of recurrent canine nasal tumors.

PubMed

Bommarito, David A; Kent, Michael S; Selting, Kim A; Henry, Carolyn J; Lattimer, Jimmy C

2011-01-01

Canine nasal tumors are typically treated with radiation therapy but most patients develop local recurrence. Our purpose was to evaluate tumor and normal tissue response to reirradiation in nine dogs. The median dose delivered with the first protocol was 50 Gy (range 44-55 Gy) and the median fraction number was 18 (range 15-20). For the second protocol, the median dose was lower intentionally, median of 36 Gy (range 23-44 Gy), without changing the median fraction number of 18 (range 14-20) to avoid late effects. The median time between protocols was 539 days (range 258-1652 days). Median survival was 927 days (95% confidence interval [CI] 423-1767 days). Median time to progression following the first and second courses was 513 days (95% CI 234-1180 days) and 282 days (95% CI 130-453 days), respectively. These were not significantly different (P=0.086). The qualitative response assessment was better for the first course compared with the second (P=0.018). Severity and timing of skin, mucous membrane, and ocular effects were similar for early side effects between the two courses (P>0.05 for all comparisons). All dogs experienced some late side effects, with two out of nine being classified as severe. These severe effects were blindness in each dog, possibly related to tumor recurrence. Reirradiation of canine nasal tumors resulted in a second clinical remission in eight of nine dogs, although the second response was less complete. Acute and late effects for seven of nine patients were not life threatening, indicating that reirradiation of canine nasal tumors may be a viable treatment option after recurrence. © 2010 Veterinary Radiology & Ultrasound.

The growth rate of bone sarcomas and survival after radiotherapy with tourniquet-induced hypoxia: a clinical study. [/sup 60/Co

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balmukhanov, S.B.; Turdugulov, I.; Karibjanova, Z.

1982-04-15

The volume doubling time of primary bone sarcomas and lung metastases was determined by measurements made on serial radiographs. For the primary tumors, the volume doubling times were lognormal distributed and varied in the range of 20-200 days with a mean around 50 days. The volume doubling times of the metastases also showed a log-normal distribution in the range of 10-100 days, but with a mean twice as short as that of the primaries. Radiation therapy was given with three-four doses of 20-25 Gy to the tumors that, together with the surrounding normal tissues, had been made hypoxic by themore » application of a tourniquet. Amputations were not performed unless required eventually by some serious late radiation damage, such as grave functional deficiency, and/or painful fibrosis and ankyloses. In no case did microscopic examination of the amputated tissues reveal the persistance of any viable, neoplastic cell. The five-year survival of a total of 69 patients was 26%. Survival expectancy was found to be closely related to the volume doubling time of the tumors, as was the incidence of the metastases. The data stress the importance of volume doubling time as a predictive factor and indicate, furthermore, that treatment with a few massive radiation doses in combination with tourniquet-induced hypoxia is effective in the local control of bone sarcomas. The severe late reaction of the normal tissues to the treatment will, however, require amputations in most of the five-year survivors.« less

Macrophage Blockade Using CSF1R Inhibitors Reverses the Vascular Leakage Underlying Malignant Ascites in Late-Stage Epithelial Ovarian Cancer

PubMed Central

Moughon, Diana L.; He, Huanhuan; Schokrpur, Shiruyeh; Jiang, Ziyue Karen; Yaqoob, Madeeha; David, John; Lin, Crystal; Iruela-Arispe, M. Luisa; Dorigo, Oliver; Wu, Lily

2015-01-01

Malignant ascites is a common complication in the late stages of epithelial ovarian cancer (EOC) that greatly diminishes the quality of life of patients. Malignant ascites is a known consequence of vascular dysfunction, but current approved treatments are not effective in preventing fluid accumulation. In this study, we investigated an alternative strategy of targeting macrophage functions to reverse the vascular pathology of malignant ascites using fluid from human patients and an immunocompetent murine model (ID8) of EOC that mirrors human disease by developing progressive vascular disorganization and leakiness culminating in massive ascites. We demonstrate that the macrophage content in ascites fluid from human patients and the ID8 model directly correlates with vascular permeability. To further substantiate macrophages’ role in the pathogenesis of malignant ascites, we blocked macrophage function in ID8 mice using a colony-stimulating factor 1 receptor kinase inhibitor (GW2580). Administration of GW2580 in the late stages of disease resulted in reduced infiltration of protumorigenic (M2) macrophages and dramatically decreased ascites volume. Moreover, the disorganized peritoneal vasculature became normalized and sera from GW2580-treated ascites protected against endothelial permeability. Therefore, our findings suggest that macrophage-targeted treatment may be a promising strategy toward a safe and effective means to control malignant ascites of EOC. PMID:26471360

Effective myotube formation in human adipose tissue-derived stem cells expressing dystrophin and myosin heavy chain by cellular fusion with mouse C2C12 myoblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eom, Young Woo; Biomedical Research Institute, Lifeliver Co., Ltd., Suwon; Lee, Jong Eun

2011-04-29

Highlights: {yields} hASCs were differentiated into skeletal muscle cells by treatment with 5-azacytidine, FGF-2, and the supernatant of cultured hASCs. {yields} Dystrophin and MyHC were expressed in late differentiation step by treatment with the supernatant of cultured hASCs. {yields} hASCs expressing dystrophin and MyHC contributed to myotube formation during co-culture with mouse myoblast C2C12 cells. -- Abstract: Stem cell therapy for muscular dystrophies requires stem cells that are able to participate in the formation of new muscle fibers. However, the differentiation steps that are the most critical for this process are not clear. We investigated the myogenic phases of humanmore » adipose tissue-derived stem cells (hASCs) step by step and the capability of myotube formation according to the differentiation phase by cellular fusion with mouse myoblast C2C12 cells. In hASCs treated with 5-azacytidine and fibroblast growth factor-2 (FGF-2) for 1 day, the early differentiation step to express MyoD and myogenin was induced by FGF-2 treatment for 6 days. Dystrophin and myosin heavy chain (MyHC) expression was induced by hASC conditioned medium in the late differentiation step. Myotubes were observed only in hASCs undergoing the late differentiation step by cellular fusion with C2C12 cells. In contrast, hASCs that were normal or in the early stage were not involved in myotube formation. Our results indicate that stem cells expressing dystrophin and MyHC are more suitable for myotube formation by co-culture with myoblasts than normal or early differentiated stem cells expressing MyoD and myogenin.« less

Late Cenozoic extension and crustal doming in the India-Eurasia collision zone: New thermochronologic constraints from the NE Chinese Pamir

NASA Astrophysics Data System (ADS)

Thiede, Rasmus C.; Sobel, Edward R.; Chen, Jie; Schoenbohm, Lindsay M.; Stockli, Daniel F.; Sudo, Masafumi; Strecker, Manfred R.

2013-06-01

northward motion of the Pamir indenter with respect to Eurasia has resulted in coeval thrusting, strike-slip faulting, and normal faulting. The eastern Pamir is currently deformed by east-west oriented extension, accompanied by uplift and exhumation of the Kongur Shan (7719 m) and Muztagh Ata (7546 m) gneiss domes. Both domes are an integral part of the footwall of the Kongur Shan extensional fault system (KES), a 250 km long, north-south oriented graben. Why active normal faulting within the Pamir is primarily localized along the KES and not distributed more widely throughout the orogen has remained unclear. In addition, relatively little is known about how deformation has evolved throughout the Cenozoic, despite refined estimates on present-day crustal deformation rates and microseismicity, which indicate where crustal deformation is presently being accommodated. To better constrain the spatiotemporal evolution of faulting along the KES, we present 39 new apatite fission track, zircon U-Th-Sm/He, and 40Ar/39Ar cooling ages from a series of footwall transects along the KES graben shoulder. Combining these data with present-day topographic relief, 1-D thermokinematic and exhumational modeling documents successive stages, rather than synchronous deformation and gneiss dome exhumation. While the exhumation of the Kongur Shan commenced during the late Miocene, extensional processes in the Muztagh Ata massif began earlier and have slowed down since the late Miocene. We present a new model of synorogenic extension suggesting that thermal and density effects associated with a lithospheric tear fault along the eastern margin of the subducting Alai slab localize extensional upper plate deformation along the KES and decouple crustal motion between the central/western Pamir and eastern Pamir/Tarim basin.

Late Quaternary Normal Faulting and Hanging Wall Basin Evolution of the Southwestern Rift Margin from Gravity and Geology, B.C.S., MX and Exploring the Influence of Text-Figure Format on Introductory Geology Learning

ERIC Educational Resources Information Center

Busch, Melanie M. D.

2011-01-01

An array of north-striking, left-stepping, active normal faults is situated along the southwestern margin of the Gulf of California. This normal fault system is the marginal fault system of the oblique-divergent plate boundary within the Gulf of California. To better understand the role of upper-crustal processes during development of an obliquely…

Spiroplasma infection causes either early or late male killing in Drosophila, depending on maternal host age

NASA Astrophysics Data System (ADS)

Kageyama, Daisuke; Anbutsu, Hisashi; Shimada, Masakazu; Fukatsu, Takema

2007-04-01

Symbiont-induced male-killing phenotypes have been found in a variety of insects. Conventionally, these phenotypes have been divided into two categories according to the timing of action: early male killing at embryonic stages and late male killing at late larval stages. In Drosophila species, endosymbiotic bacteria of the genus Spiroplasma have been known to cause early male killing. Here, we report that a spiroplasma strain normally causing early male killing also induces late male killing depending on the maternal host age: male-specific mortality of larvae and pupae was more frequently observed in the offspring of young females. As the lowest spiroplasma density and occasional male production were also associated with newly emerged females, we proposed the density-dependent hypothesis for the expression of early and late male-killing phenotypes. Our finding suggested that (1) early and late male-killing phenotypes can be caused by the same symbiont and probably by the same mechanism; (2) late male killing may occur as an attenuated expression of early male killing; (3) expression of early and late male-killing phenotypes may be dependent on the symbiont density, and thus, could potentially be affected by the host immunity and regulation; and (4) early male killing and late male killing could be alternative strategies adopted by microbial reproductive manipulators.

Discovery of specific ligands for oral squamous carcinoma to develop anti-cancer drug loaded precise targeting nanotherapeutics.

PubMed

Yang, Fan; Liu, Ruiwu; Kramer, Randall; Xiao, Wenwu; Jordan, Richard; Lam, Kit S

2012-12-01

Oral squamous cell carcinoma has a low five-year survival rate, which may be due to late detection and a lack of effective tumor-specific therapies. Using a high throughput drug discovery strategy termed one-bead one-compound combinatorial library, the authors identified six compounds with high binding affinity to different human oral squamous cell carcinoma cell lines but not to normal cells. Current work is under way to develop these ligands to oral squamous cell carcinoma specific imaging probes or therapeutic agents.

Evaluation of a speaker identification system with and without fusion using three databases in the presence of noise and handset effects

NASA Astrophysics Data System (ADS)

S. Al-Kaltakchi, Musab T.; Woo, Wai L.; Dlay, Satnam; Chambers, Jonathon A.

2017-12-01

In this study, a speaker identification system is considered consisting of a feature extraction stage which utilizes both power normalized cepstral coefficients (PNCCs) and Mel frequency cepstral coefficients (MFCC). Normalization is applied by employing cepstral mean and variance normalization (CMVN) and feature warping (FW), together with acoustic modeling using a Gaussian mixture model-universal background model (GMM-UBM). The main contributions are comprehensive evaluations of the effect of both additive white Gaussian noise (AWGN) and non-stationary noise (NSN) (with and without a G.712 type handset) upon identification performance. In particular, three NSN types with varying signal to noise ratios (SNRs) were tested corresponding to street traffic, a bus interior, and a crowded talking environment. The performance evaluation also considered the effect of late fusion techniques based on score fusion, namely, mean, maximum, and linear weighted sum fusion. The databases employed were TIMIT, SITW, and NIST 2008; and 120 speakers were selected from each database to yield 3600 speech utterances. As recommendations from the study, mean fusion is found to yield overall best performance in terms of speaker identification accuracy (SIA) with noisy speech, whereas linear weighted sum fusion is overall best for original database recordings.

Alterations in late endocytic trafficking related to the pathobiology of LRRK2-linked Parkinson's disease.

PubMed

Rivero-Ríos, Pilar; Gómez-Suaga, Patricia; Fernández, Belén; Madero-Pérez, Jesús; Schwab, Andrew J; Ebert, Allison D; Hilfiker, Sabine

2015-06-01

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene comprise the most common cause of familial Parkinson's disease (PD), and variants increase the risk for sporadic PD. LRRK2 displays kinase and GTPase activity, and altered catalytic activity correlates with neurotoxicity, making LRRK2 a promising therapeutic target. Despite the importance of LRRK2 for disease pathogenesis, its normal cellular function, and the mechanism(s) by which pathogenic mutations cause neurodegeneration remain unclear. LRRK2 seems to regulate a variety of intracellular vesicular trafficking events to and from the late endosome in a manner dependent on various Rab proteins. At least some of those events are further regulated by LRRK2 in a manner dependent on two-pore channels (TPCs). TPCs are ionic channels localized to distinct endosomal structures and can cause localized calcium release from those acidic stores, with downstream effects on vesicular trafficking. Here, we review current knowledge about the link between LRRK2, TPC- and Rab-mediated vesicular trafficking to and from the late endosome, highlighting a possible cross-talk between endolysosomal calcium stores and Rab proteins underlying pathomechanism(s) in LRRK2-related PD.

Glutaric aciduria type 2, late onset type in Thai siblings with myopathy.

PubMed

Wasant, Pornswan; Kuptanon, Chulaluck; Vattanavicharn, Nithiwat; Liammongkolkul, Somporn; Ratanarak, Pisanu; Sangruchi, Tumtip; Yamaguchi, Seiji

2010-10-01

Reported here is a novel presentation of late onset glutaric aciduria type 2 in two Thai siblings. A 9-year-old boy presented with gradual onset of proximal muscle weakness for 6 weeks. The initial diagnosis was postviral myositis, and then polymyositis. Electromyography and nerve conduction velocity testing indicated a myopathic pattern. Muscle biopsy revealed excessive accumulation of fat. Acylcarnitine profiling led to the diagnosis of glutaric aciduria type 2. Immunoblot analysis of electron-transferring-flavoprotein and its dehydrogenase electron-transferring-flavoprotein dehydrogenase led to mutation analysis of the ETFDH gene, which revealed two different pathogenic mutations in both alleles and confirmed the diagnosis of glutaric aciduria type 2 caused by electron-transferring-flavoprotein dehydrogenase deficiency. The boy recovered completely after treatment. Later, his younger sibling became symptomatic; the same diagnosis was confirmed, and treatment was similarly effective. Acylcarnitine profiling was a crucial investigation in making this diagnosis in the presence of normal urine organic acid findings. Late onset glutaric aciduria type 2, a rare cause of muscle weakness in children, should be included in the differential diagnosis of myopathy. Copyright © 2010 Elsevier Inc. All rights reserved.

How the early sporulation sigma factor sigmaF delays the switch to late development in Bacillus subtilis.

PubMed

Karmazyn-Campelli, Céline; Rhayat, Lamya; Carballido-López, Rut; Duperrier, Sandra; Frandsen, Niels; Stragier, Patrick

2008-03-01

Sporulation in Bacillus subtilis is a primitive differentiation process involving two cell types, the forespore and the mother cell. Each cell implements two successive transcription programmes controlled by specific sigma factors. We report that activity of sigma(G), the late forespore sigma factor, is kept in check by Gin, the product of csfB, a gene controlled by sigma(F), the early forespore sigma factor. Gin abolishes sigma(G) transcriptional activity when sigma(G) is artificially synthesized during growth, but has no effect on sigma(F). Gin interacts strongly with sigma(G) but not with sigma(F) in a yeast two-hybrid experiment. The absence of Gin allows sigma(G) to be active during sporulation independently of the mother-cell development to which it is normally coupled. Premature sigma(G) activity leads to the formation of slow-germinating spores, and complete deregulation of sigma(G) synthesis is lethal when combined with gin inactivation. Gin allows sigma(F) to delay the switch to the late forespore transcription programme by preventing sigma(G) to take over before the cell has reached a critical stage of development. A similar strategy, following a completely unrelated route, is used by the mother cell.

Using virtual reality to improve the efficacy of cognitive-behavioral therapy (CBT) in the treatment of late-life anxiety: preliminary recommendations for future research.

PubMed

Grenier, Sébastien; Forget, Hélène; Bouchard, Stéphane; Isere, Sébastien; Belleville, Sylvie; Potvin, Olivier; Rioux, Marie-Ève; Talbot, Mélissa

2015-07-01

Cognitive-behavioral therapy (CBT) using traditional exposure techniques (i.e. imaginal and in vivo) seems less effective to treat anxiety in older adults than in younger ones. This is particularly true when imaginal exposure is used to confront the older patient to inaccessible (e.g. fear of flying) or less tangible/controllable anxiety triggers (e.g. fear of illness). Indeed, imaginal exposure may become less effective as the person gets older since normal aging is characterized by the decline in cognitive functions involved in the creation of vivid/detailed mental images. One way to circumvent this difficulty is to expose the older patient to a virtual environment that does not require the ability to imagine the frightening situation. In virtuo exposure has proven to be efficient to treat anxiety in working-age people. In virtuo exposure could be employed to improve the efficacy of CBT with exposure sessions in the treatment of late-life anxiety? The current paper explores this question and suggests new research avenues.

Prenatal diagnosis of left isomerism with normal heart: a case report

PubMed Central

De Paola, Nico; Ermito, Santina; Nahom, Antonella; Dinatale, Angela; Pappalardo, Elisa Maria; Carrara, Sabina; Cavaliere, Alessandro; Brizzi, Cristiana

2009-01-01

Objective: Left isomerism, also called polysplenia, is a laterality disturbance associated with with paired leftsidedness viscera and multiple small spleens. Left isomerism, heart congenital abnormalities and gastrointestinal malformation are strongly associated. Methods: We present a case of prenatal diagnosis of left isomerism in a fetus with a structurally normal heart. Conclusion: Left isomerism syndrone may coesist with a structurally normal heart. If prenatal left isomerism is suspected, even in presence of a normal heart, is mandatory to esclude sign of gastrointestinal abnormalities, as late poly hy dramnios, and cardiac rhytm disturbance during the pregnancy and neonatal age. PMID:22439041

Retrospective 25-year follow-up of treatment outcomes in angle Class III patients : Early versus late treatment.

PubMed

Wendl, B; Muchitsch, A P; Winsauer, H; Walter, A; Droschl, H; Jakse, N; Wendl, M; Wendl, T

2017-05-01

To assess early versus late treatment of Class III syndrome for skeletal and dental differences. Thirty-eight Class III patients treated with a chincup were retrospectively analyzed. Baseline data were obtained by reviewing pretreatment (T0) anamnestic records, cephalograms, and casts. The cases were assigned to an early or a late treatment group based on age at T0 (up to 9 years or older than 9 years but before the pubertal growth spurt). Both groups were further compared based on posttreatment data (T1) and long-term follow-up data collected approximately 25 years after treatment (T2). Early treatment was successful in 74% and late treatment in 67% of cases. More failures were noted among male patients. The late treatment group was characterized post therapeutically by significantly more pronounced skeletal parameters of jaw size relative to normal Class I values; in addition, a greater skeletal discrepancy between maxilla and mandible, higher values for mandibular length, Cond-Pog, ramus height, overjet, anterior posterior dysplasia indicator (APDI), lower anterior face height, and gonial angle were measured at T1. The angle between the AB line and mandibular plane was found to be larger at T0, T1, and T2, as well as more pronounced camouflage positions of the lower anterior teeth at T0. The early treatment group was found to exhibit greater amounts of negative overjet at T0 but more effective correction at T1. Early treatment of Class III syndrome resulted in greater skeletal changes with less dental compensation.

New Agents, Emerging Late Effects, and the Development of Precision Survivorship.

PubMed

Chow, Eric J; Antal, Zoltan; Constine, Louis S; Gardner, Rebecca; Wallace, W Hamish; Weil, Brent R; Yeh, Jennifer M; Fox, Elizabeth

2018-06-06

Incremental improvements in the treatment of children and adolescents with cancer have led to 5-year survival rates reaching nearly 85%. In the past decade, impressive progress has been made in understanding the biology of many pediatric cancers. With that understanding, multiple new agents have become available that offer the promise of more-effective and less-toxic treatment. These include agents that target various cell surface antigens and engage the adaptive immune system, as well as those that interfere with key signaling pathways involved in tumor development and growth. For local control, surgery and radiation techniques also have evolved, becoming less invasive or featuring new techniques and particles that more precisely target the tumor and limit the dose to normal tissue. Nevertheless, targeted agents, like conventional chemotherapy, radiotherapy, and surgery, may have off-target effects and deserve long-term follow-up of their safety and efficacy. These include injury to the endocrine, cardiovascular, and immunologic systems. New radiation and surgical techniques that theoretically reduce morbidity and improve long-term quality of life must also be validated with actual patient outcomes. Finally, with advances in genomics, information on host susceptibility to late effects is beginning to emerge. Such knowledge, coupled with improved metrics that better describe the spectrum of potential late effects across the entire lifespan, can lead to the development of decision models that project the potential long-term health outcomes associated with various treatment and follow-up strategies. These developments will help extend the current focus on precision medicine to precision survivorship, where clinicians, patients, and families will have a better grasp of the potential risks, benefits, and tradeoffs associated with the growing number of cancer treatment options.

No increase in toxicity of pelvic irradiation when intensity modulation is employed: clinical and dosimetric data of 208 patients treated with post-prostatectomy radiotherapy.

PubMed

Jereczek-Fossa, Barbara A; Ciardo, Delia; Ferrario, Silvia; Fossati, Piero; Fanetti, Giuseppe; Zerini, Dario; Zannoni, Davide; Fodor, Cristiana; Gerardi, Marianna A; Surgo, Alessia; Muto, Matteo; Cambria, Raffaella; De Cobelli, Ottavio; Orecchia, Roberto

2016-07-01

To compare the toxicity of image-guided intensity-modulated radiotherapy (IG-IMRT) to the pelvis or prostate bed (PB) only. To test the hypothesis that the potentially injurious effect of pelvic irradiation can be counterbalanced by reduced irradiated normal tissue volume using IG-IMRT. Between February 2010 and February 2012, 208 patients with prostate cancer were treated with adjuvant or salvage IG-IMRT to the PB (102 patients, Group PB) or the pelvis and prostate bed (P) (106 patients, Group P). The Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria were used to evaluate toxicity. Median follow-up was 27 months. Toxicity G ≥ 2 in Group PB: in the bowel acute and late toxicities were 11.8% and 10%, respectively; urinary acute and late toxicities were 10.8% and 15%, respectively. Toxicity G ≥ 2 in Group P: in the bowel acute and late toxicities were both 13.2%; urinary acute and late toxicities were 13.2% and 15.1%, respectively. No statistical difference in acute or late toxicity between the groups was found (bowel: p = 0.23 and p = 0.89 for acute and late toxicity, respectively; urinary: p = 0.39 and p = 0.66 for acute and late toxicity, respectively). Of the clinical variables, only previous abdominal surgery was correlated with acute bowel toxicity. Dosimetric parameters that correlated with bowel toxicity were identified. The toxicity rates were low and similar in both groups, suggesting that IG-IMRT allows for a safe post-operative irradiation of larger volumes. Further investigation is warranted to exclude bias owing to non-randomized character of the study. Our report shows that modern radiotherapy technology and careful planning allow maintaining the toxicity of pelvic lymph node treatment at the acceptable level, as it is in the case of PB radiotherapy.

Inherited discontinuities and fault kinematics of a multiphase, non-colinear extensional setting: Subsurface observations from the South Flank of the Golfo San Jorge basin, Patagonia

NASA Astrophysics Data System (ADS)

Paredes, José Matildo; Aguiar, Mariana; Ansa, Andrés; Giordano, Sergio; Ledesma, Mario; Tejada, Silvia

2018-01-01

We use three-dimensional (3D) seismic reflection data to analyze the structural style, fault kinematics and growth fault mechanisms of non-colinear normal fault systems in the South Flank of the Golfo San Jorge basin, central Patagonia. Pre-existing structural fabrics in the basement of the South Flank show NW-SE and NE-SW oriented faults. They control the location and geometry of wedge-shaped half grabens from the "main synrift phase" infilled with Middle Jurassic volcanic-volcaniclastic rocks and lacustrine units of Late Jurassic to Early Cretaceous age. The NE-striking, basement-involved normal faults resulted in the rapid establishment of fault lenght, followed by gradual increasing in displacement, and minor reactivation during subsequent extensional phases; NW-striking normal faults are characterized by fault segments that propagated laterally during the "main rifting phase", being subsequently reactivated during succesive extensional phases. The Aptian-Campanian Chubut Group is a continental succession up to 4 km thick associated to the "second rifting stage", characterized by propagation and linkage of W-E to WNW-ESE fault segments that increase their lenght and displacement in several extensional phases, recognized by detailed measurement of current throw distribution of selected seismic horizons along fault surfaces. Strain is distributed in an array of sub-parallel normal faults oriented normal to the extension direction. A Late Cretaceous-Paleogene (pre-late Eocene) extensional event is characterized by high-angle, NNW-SSE to NNE-SSW grabens coeval with intraplate alkali basaltic volcanism, evidencing clockwise rotation of the stress field following a ∼W-E extension direction. We demonstrate differences in growth fault mechanisms of non-colinear fault populations, and highlight the importance of follow a systematic approach to the analysis of fault geometry and throw distribution in a fault network, in order to understand temporal-spatial variations in the coeval topography, potential structural traps, and distribution of oil-bearing sandstone reservoirs.

Normal faulting and mass movement during ridge subduction inferred from porosity transition and zeolitization in the Costa Rica subduction zone

NASA Astrophysics Data System (ADS)

Hamahashi, Mari; Screaton, Elizabeth; Tanikawa, Wataru; Hashimoto, Yoshitaka; Martin, Kylara; Saito, Saneatsu; Kimura, Gaku

2017-07-01

Subduction of the buoyant Cocos Ridge offshore the Osa Peninsula, Costa Rica substantially affects the upper plate structure through a variety of processes, including outer forearc uplift, erosion, and focused fluid flow. To investigate the nature of a major seismic reflector (MSR) developed between slope sediments (late Pliocene-late Pleistocene silty clay) and underlying higher velocity upper plate materials (late Pliocene-early Pleistocene clayey siltstone), we infer possible mechanisms of sediment removal by examining the consolidation state, microstructure, and zeolite assemblages of sediments recovered from Integrated Ocean Drilling Program Expedition 344 Site U1380. Formation of Ca-type zeolites, laumontite and heulandite, inferred to form in the presence of Ca-rich fluids, has caused porosity reduction. We adjust measured porosity values for these pore-filling zeolites and evaluated the new porosity profile to estimate how much material was removed at the MSR. Based on the composite porosity-depth curve, we infer the past burial depth of the sediments directly below the MSR. The corrected and uncorrected porosity-depth curves yield values of 800 ± 70 m and 900 ± 70 m, respectively. We argue that deposition and removal of this entire estimated thickness in 0.49 Ma would require unrealistically large sedimentation rates and suggest that normal faulting at the MSR must contribute. The porosity offset could be explained with maximum 250 ± 70 m of normal fault throw, or 350 ± 70 m if the porosity were not corrected. The porosity correction significantly reduces the amount of sediment removal needed for the combination of mass movement and normal faulting that characterize the slope in this margin.

Knockdown of prothrombin in zebrafish.

PubMed

Day, Kenneth; Krishnegowda, Naveen; Jagadeeswaran, Pudur

2004-01-01

Thrombin is a serine protease generated from its zymogen, prothrombin, and plays a central role in the coagulation cascade. It is also important for mammalian development. The zebrafish has now been established as an excellent genetic model for studies on mammalian hemostasis and development. In this report, we used prothrombin-specific antisense morpholinos to knock down the levels of prothrombin to characterize the effects of prothrombin deficiency in the zebrafish embryo. Prothrombin morpholino-injected zebrafish embryos yielded an early phenotype exhibiting severe abnormalities that later showed occasional bleeding. In a second late phenotype, the embryos had no observable morphological abnormalities in early stages, but showed occasional bleeding at later stages. These phenotypes resembled characteristics shown by prothrombin knockout mice. Laser-induced vascular injury on some of the normal appearing phenotypic larvae showed a prolonged time to occlusion, and recombinant zebrafish prothrombin injected into these larvae restored a normal time to occlusion thus showing the specificity of the morpholino effect. The system developed here should be useful for investigation of the role of thrombin in vertebrate development.

Targeted Vaccination against Human α-Lactalbumin for Immunotherapy and Primary Immunoprevention of Triple Negative Breast Cancer

PubMed Central

Tuohy, Vincent K.; Jaini, Ritika; Johnson, Justin M.; Loya, Matthew G.; Wilk, Dennis; Downs-Kelly, Erinn; Mazumder, Suparna

2016-01-01

We have proposed that safe and effective protection against the development of adult onset cancers may be achieved by vaccination against tissue-specific self-proteins that are “retired” from expression at immunogenic levels in normal tissues as we age, but are overexpressed in emerging tumors. α-Lactalbumin is an example of a “retired” self-protein because its expression in normal tissues is confined exclusively to the breast during late pregnancy and lactation, but is also expressed in the vast majority of human triple negative breast cancers (TNBC)—the most aggressive and lethal form of breast cancer and the predominant form that occurs in women at high genetic risk including those with mutated BRCA1 genes. In anticipation of upcoming clinical trials, here we provide preclinical data indicating that α-lactalbumin has the potential as a vaccine target for inducing safe and effective primary immunoprevention as well as immunotherapy against TNBC. PMID:27322324

Insufficient cervix

MedlinePlus

... vagina. In a normal pregnancy, the cervix stays firm, long, and closed until late in the 3rd ... and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Cervix Disorders Health Problems in ...

Mental Illness in Children: Know the Signs

MedlinePlus

... the normal mood swings common in many people. Schizophrenia. This chronic mental illness causes a child to lose touch with reality (psychosis). Schizophrenia most often appears in the late teens through ...

Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency.

PubMed

la Marca, Giancarlo; Canessa, Clementina; Giocaliere, Elisa; Romano, Francesca; Duse, Marzia; Malvagia, Sabrina; Lippi, Francesca; Funghini, Silvia; Bianchi, Leila; Della Bona, Maria Luisa; Valleriani, Claudia; Ombrone, Daniela; Moriondo, Maria; Villanelli, Fabio; Speckmann, Carsten; Adams, Stuart; Gaspar, Bobby H; Hershfield, Michael; Santisteban, Ines; Fairbanks, Lynette; Ragusa, Giovanni; Resti, Massimo; de Martino, Maurizio; Guerrini, Renzo; Azzari, Chiara

2013-06-01

Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear. We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life. We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency. The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 μmol/L (normal value, <1.5 μmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 μmol/L (normal value, <0.07 μmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis. Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Normal Tissue Complication Probability (NTCP) modeling of late rectal bleeding following external beam radiotherapy for prostate cancer: A Test of the QUANTEC-recommended NTCP model.

PubMed

Liu, Mitchell; Moiseenko, Vitali; Agranovich, Alexander; Karvat, Anand; Kwan, Winkle; Saleh, Ziad H; Apte, Aditya A; Deasy, Joseph O

2010-10-01

Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 = 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ(2) test (p = 0.44). Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose distribution characteristics do not vary greatly within this patient cohort.

Complex basin evolution in the Gökova Gulf region: implications on the Late Cenozoic tectonics of southwest Turkey

NASA Astrophysics Data System (ADS)

Gürer, Ömer Feyzi; Sanğu, Ercan; Özburan, Muzaffer; Gürbüz, Alper; Sarica-Filoreau, Nuran

2013-11-01

Southwestern Turkey experienced a transition from crustal shortening to extension during Late Cenozoic, and evidence of this was recorded in four distinct basin types in the Muğla-Gökova Gulf region. During the Oligocene-Early Miocene, the upper slices of the southerly moving Lycian Nappes turned into north-dipping normal faults due to the acceleration of gravity. The Kale-Tavas Basin developed as a piggyback basin along the fault plane on hanging wall blocks of these normal faults. During Middle Miocene, a shift had occurred from local extension to N-S compression/transpression, during which sediments in the Eskihisar-Tınaz Basins were deposited in pull-apart regions of the Menderes Massif cover units, where nappe slices were already eroded. During the Late Miocene-Pliocene, a hiatus occurred from previous compressional/transpressional tectonism along intermountain basins and Yatağan Basin fills were deposited on Menderes Massif, Lycian Nappes, and on top of Oligo-Miocene sediments. Plio-Quaternary marked the activation of N-S extension and the development of the E-W-trending Muğla-Gökova Grabens, co-genetic equivalents of which are common throughout western Anatolia. Thus, the tectonic evolution of the western Anotolia during late Cenozoic was shifting from compressional to extensional with a relaxation period, suggesting a non-uniform evolution.

Caveolin targeting to late endosome/lysosomal membranes is induced by perturbations of lysosomal pH and cholesterol content

PubMed Central

Mundy, Dorothy I.; Li, Wei Ping; Luby-Phelps, Katherine; Anderson, Richard G. W.

2012-01-01

Caveolin-1 is an integral membrane protein of plasma membrane caveolae. Here we report that caveolin-1 collects at the cytosolic surface of lysosomal membranes when cells are serum starved. This is due to an elevation of the intralysosomal pH, since ionophores and proton pump inhibitors that dissipate the lysosomal pH gradient also trapped caveolin-1 on late endosome/lysosomes. Accumulation is both saturable and reversible. At least a portion of the caveolin-1 goes to the plasma membrane upon reversal. Several studies suggest that caveolin-1 is involved in cholesterol transport within the cell. Strikingly, we find that blocking cholesterol export from lysosomes with progesterone or U18666A or treating cells with low concentrations of cyclodextrin also caused caveolin-1 to accumulate on late endosome/lysosomal membranes. Under these conditions, however, live-cell imaging shows cavicles actively docking with lysosomes, suggesting that these structures might be involved in delivering caveolin-1. Targeting of caveolin-1 to late endosome/lysosomes is not observed normally, and the degradation rate of caveolin-1 is not altered by any of these conditions, indicating that caveolin-1 accumulation is not a consequence of blocked degradation. We conclude that caveolin-1 normally traffics to and from the cytoplasmic surface of lysosomes during intracellular cholesterol trafficking. PMID:22238363

Exclusion of particulate allergens by window air conditioners.

PubMed

Solomon, W R; Burge, H A; Boise, J R

1980-04-01

Effects of window air-conditioner operation on intramural particle levels were assessed in the bedrooms of 20 homes and in 10 outpatient clinic examining rooms during late summer periods. At each site, pollen and spore collections in the mechanically cooled room and a normally ventilated counterpart were compared using volumetric impactors. Substantially lower particle recoveries (median = 16/m3) were found in air-conditioned rooms than in those with open windows alone (median = 253 particles/m3). Furthermore, substantial exclusion of small (e.g., Ganoderma spores) as well as large (ragweed pollens) aerosol components were found by window units. Control studies within normally ventilated rooms and outside their open windows showed a marked but variable inward flux of particles. Window units appear to substantially reduce indoor allergan levels by maintaining the isolation of enclosed spaces from particle-bearing outdoor air.

Effects of pioglitazone mediated activation of PPAR-γ on CIDEC and obesity related changes in mice.

PubMed

Shamsi, Bilal Haider; Ma, Chaofeng; Naqvi, Saima; Xiao, Yanfeng

2014-01-01

Obesity is a metabolic disorder that can lead to high blood pressure, increased blood cholesterol and triglycerides, insulin resistance, and diabetes mellitus. The aim was to study the effects of pioglitazone mediated sensitization of peroxisome proliferator-activated receptor gamma (PPAR-γ) on the relationship of Cell death-inducing DFFA-like effector C (CIDEC) with obesity related changes in mice. Sixty C57B/L6 mice weighing 10-12g at 3 weeks of age were randomly divided into 3 groups. Mice in Group 1 were fed on normal diet (ND) while Group 2 mice were given high fat diet (HFD), and Group 3 mice were given high fat diet and treated with Pioglitazone (HFD+P). Body weight, length and level of blood sugar were measured weekly. Quantitative real-time PCR, fluorescence microscopy, and ELISA were performed to analyze the expression of CIDEC and PPAR-γ in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Body weight and length of mice increased gradually with time in all groups. Blood sugar in HFD mice started to increase significantly from the mid of late phase of obesity while pioglitazone attenuated blood sugar level in HFD+P mice. The mRNA expressions and protein levels of PPAR-γ and CIDEC genes started to increase in HFD mice as compared to ND mice and decreased gradually during the late phase of obesity in VAT. Pioglitazone enhanced the expression of PPAR-γ and CIDEC genes in HFD+P mice even during the late phase of obesity. It is insinuated that VAT is associated with late phase obesity CIDEC decrease and insulin resistance, while pioglitazone enhances CIDEC through activation of PPAR-γ, increases its expression, and decreases lipolysis, hence preventing an increase of blood sugar in mice exposed to HFD.

Can Transcranial Direct Current Stimulation Augment Extinction of Conditioned Fear?

PubMed Central

van ’t Wout, Mascha; Mariano, Timothy Y.; Garnaat, Sarah L.; Reddy, Madhavi K.; Rasmussen, Steven A.; Greenberg, Benjamin D.

2016-01-01

Background Exposure-based therapy parallels extinction learning of conditioned fear. Prior research points to the ventromedial prefrontal cortex as a potential site for the consolidation of extinction learning and subsequent retention of extinction memory. Objective/hypothesis The present study aimed to evaluate whether the application of non-invasive transcranial direct current stimulation (tDCS) during extinction learning enhances late extinction and early recall in human participants. Methods Forty-four healthy volunteers completed a 2-day Pavlovian fear conditioning, extinction, and recall paradigm while skin conductance activity was continuously measured. Twenty-six participants received 2 mA anodal tDCS over EEG coordinate AF3 during extinction of a first conditioned stimulus. The remaining 18 participants received similar tDCS during extinction of a second conditioned stimulus. Sham stimulation was applied for the balance of extinction trials in both groups. Normalized skin conductance changes were analyzed using linear mixed models to evaluate effects of tDCS over late extinction and early recall trials. Results We observed a significant interaction between timing of tDCS during extinction blocks and changes in skin conductance reactivity over late extinction trials. These data indicate that tDCS was associated with accelerated late extinction learning of a second conditioned stimulus after tDCS was combined with extinction learning of a previous conditioned stimulus. No significant effects of tDCS timing were observed on early extinction recall. Conclusions Results could be explained by an anxiolytic aftereffect of tDCS and extend previous studies on tDCS-induced modulation of fear and threat related learning processes. These findings support further exploration of the clinical use of tDCS. PMID:27037186

Longterm effects of cardiac mediastinal nerve cryoablation on neural inducibility of atrial fibrillation in canines.

PubMed

Leiria, Tiago Luiz Luz; Glavinovic, Tamara; Armour, J Andrew; Cardinal, René; de Lima, Gustavo Glotz; Kus, Teresa

2011-04-26

In canines, excessive activation of select mediastinal nerve inputs to the intrinsic cardiac nervous system induces atrial fibrillation (AF). Since ablation of neural elements is proposed as an adjunct to circumferential pulmonary vein ablation for AF, we investigated the short and long-term effects of mediastinal nerve ablation on AF inducibility. Under general anesthesia, in 11 dogs several mediastinal nerve sites were identified on the superior vena cava that, when stimulated electrically during the atrial refractory period, reproducibly initiated AF. Cryoablation of one nerve site was then performed and inducibility retested early (1-2 months post Cryo; n=7) or late (4 months post Cryo; n=4). Four additional dogs that underwent a sham procedure were retested 1 to 2 months post-surgery. Stimulation induced AF at 91% of nerve sites tested in control versus 21% nerve sites early and 54% late post-ablation (both P<0.05). Fewer stimuli were required to induce AF in controls versus the Early Cryo group; this capacity returned to normal values in the Late Cryo group. AF episodes were longer in control versus the Early or Late Cryo groups. Heart rate responses to vagal or stellate ganglion stimulation, as well as to local nicotine infusion into the right coronary artery, were similar in all groups. In conclusion, focal damage to intrinsic cardiac neuronal inputs causes short-term stunning of neuronal inducibility of AF without major loss of overall adrenergic or cholinergic efferent neuronal control. That recovery of AF inducibility occurs rapidly post-surgery indicates the plasticity of intrathoracic neuronal elements to focal injury. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of hen age and maternal vitamin D source on performance, hatchability, bone mineral density, and progeny in vitro early innate immune function.

PubMed

Saunders-Blades, J L; Korver, D R

2015-06-01

The metabolite 25-hydroxy vitamin D3 (25-OHD) can complement or replace vitamin D3 in poultry rations, and may influence broiler production and immune function traits. The effect of broiler breeder dietary 25-OHD on egg production, hatchability, and chick early innate immune function was studied. We hypothesized that maternal dietary 25-OHD would support normal broiler breeder production and a more mature innate immune system of young chicks. Twenty-three-week-old Ross 308 hens (n=98) were placed in 4 floor pens and fed either 2,760 IU vitamin D3 (D) or 69 μg 25-OHD/kg feed. Hen weights were managed according to the primary breeder management guide. At 29 to 31 wk (Early), 46 to 48 wk (Mid), and 61 to 63 wk (Late), hens were artificially inseminated and fertile eggs incubated and hatched. Chicks were placed in cages based on maternal treatment and grown to 7 d age. Innate immune function and plasma 25-OHD were assessed at 1 and 4 d post-hatch on 15 chicks/treatment. Egg production, hen BW, and chick hatch weight were not affected by diet (P>0.05). Total in vitro Escherichia coli (E. coli) killing by 25-OHD chicks was greater than the D chicks at 4 d for the Early and Mid hatches, and 1 and 4 d for the Late hatch. This can be partly explained by the 25-OHD chicks from the Late hatch also having a greater E. coli phagocytic capability. No consistent pattern of oxidative burst response was observed. Chicks from the Mid hatch had greater percent phagocytosis, phagocytic capability, and E. coli killing than chicks from Early and Late hatches. Overall, maternal 25-OHD increased hatchability and in vitro chick innate immunity towards E. coli. Regardless of treatment, chicks from Late and Early hens had weaker early innate immune responses than chicks from Mid hens. The hen age effect tended to be the greatest factor influencing early chick innate immunity, but maternal 25-OHD also increased several measures relative to D. © 2015 Poultry Science Association Inc.

A Feasibility Study of Expanding the F404 Aircraft Engine Repair Capability at the Aircraft Intermediate Maintenance Department

DTIC Science & Technology

1993-06-01

1 A. OBJECTIVES ............. .... .................. 1 B. HISTORY ................... .................... 2 C...utilization, and any additional manpower requirements at the "selected" AIMD’s. B. HISTORY Until late 1991 both NADEP JAX and NADEP North Island (NORIS...TRIANGULAR OR ALL LOG NORMAL DISTRIBUTIONS FOR SERVICE TIMES AT AIND CECIL FIELD maintenance/ Triangular Log Normal MAZDA Difference Differe•ce Supply

Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages.

PubMed

Borghammer, Per; Chakravarty, Mallar; Jonsdottir, Kristjana Yr; Sato, Noriko; Matsuda, Hiroshi; Ito, Kengo; Arahata, Yutaka; Kato, Takashi; Gjedde, Albert

2010-05-01

Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD.

A chemical screen for medulloblastoma identifies quercetin as a putative radiosensitizer.

PubMed

Lagerweij, Tonny; Hiddingh, Lotte; Biesmans, Dennis; Crommentuijn, Matheus H W; Cloos, Jacqueline; Li, Xiao-Nan; Kogiso, Mari; Tannous, Bakhos A; Vandertop, W Peter; Noske, David P; Kaspers, Gertjan J L; Würdinger, Tom; Hulleman, Esther

2016-06-14

Treatment of medulloblastoma in children fails in approximately 30% of patients, and is often accompanied by severe late sequelae. Therefore, more effective drugs are needed that spare normal tissue and diminish long-term side effects. Since radiotherapy plays a pivotal role in the treatment of medulloblastoma, we set out to identify novel drugs that could potentiate the effect of ionizing radiation.Thereto, a small molecule library, consisting of 960 chemical compounds, was screened for its ability to sensitize towards irradiation. This small molecule screen identified the flavonoid quercetin as a novel radiosensitizer for the medulloblastoma cell lines DAOY, D283-med, and, to a lesser extent, D458-med at low micromolar concentrations and irradiation doses used in fractionated radiation schemes. Quercetin did not affect the proliferation of neural precursor cells or normal human fibroblasts. Importantly, in vivo experiments confirmed the radiosensitizing properties of quercetin. Administration of this flavonoid at the time of irradiation significantly prolonged survival in orthotopically xenografted mice. Together, these findings indicate that quercetin is a potent radiosensitizer for medulloblastoma cells that may be a promising lead for the treatment of medulloblastoma in patients.

Have You Given Blood Lately?

MedlinePlus

... physical assessment that includes measuring vital signs and hemoglobin levels donating the blood (This takes about 15 ... per applicable state law have a normal blood hemoglobin level be free of infections that can be ...

Noninvasive beat-by-beat registration of ventricular late potentials using high resolution electrocardiography.

PubMed

Hombach, V; Kebbel, U; Höpp, H W; Winter, U; Hirche, H

1984-08-01

We have developed a new high resolution ECG equipment for recording cardiac microvolt potentials from the body surface. Noise reduction has been achieved by specially designed suction electrodes, by spatial averaging of the electrocardiograms from four electrode pairs, using extremely low noise amplifiers, by performing registrations within a Faraday cage, and by teaching the patient to relax during end expiratory breath holding. Fourteen young males (controls) and 30 patients with various cardiac diseases (27 with CHD) were studied. In normals ventricular late potentials were not seen, but in 12/30 patients clearcut diastolic potentials were found. In 7/12 patients with positive findings, late potentials appeared beat-by-beat, in 5/12 patients those signals occurred intermittently, in 11/30 patients questionably, and in the remaining 5/30 patients no late potentials were recorded. One patient with the Romano-Ward syndrome revealed phases with stable beat-by-beat and intermittently occurring ventricular late potentials. These results demonstrate the feasibility of continuous non-invasive recording of ventricular late potentials, whose clinical and prognostic significance remains to be established.

Maternal and fetal blood lipid concentrations during pregnancy differ by maternal body mass index: findings from the ROLO study.

PubMed

Geraghty, Aisling A; Alberdi, Goiuri; O'Sullivan, Elizabeth J; O'Brien, Eileen C; Crosbie, Brenda; Twomey, Patrick J; McAuliffe, Fionnuala M

2017-10-16

Pregnancy is a time of altered metabolic functioning and maternal blood lipid profiles change to accommodate the developing fetus. While these changes are physiologically necessary, blood lipids concentrations have been associated with adverse pregnancy outcomes such as gestational diabetes, pregnancy-induced hypertension and high birth weight. As blood lipids are not routinely measured during pregnancy, there is limited information on what is considered normal during pregnancy and in fetal blood. Data from 327 mother-child pairs from the ROLO longitudinal birth cohort study were analysed. Fasting total cholesterol and triglycerides were measured in early and late pregnancy and fetal cord blood. Intervals were calculated using the 2.5th, 50th and 97.5th centile. Data was stratified based on maternal body mass index (BMI) measured during early pregnancy. Differences in blood lipids between BMI categories were explored using ANOVA and infant outcomes of macrosomia and large-for-gestational-age (LGA) were explored using independent student T-tests and binary logistic regression. All maternal blood lipid concentrations increased significantly from early to late pregnancy. In early pregnancy, women with a BMI < 25 kg/m 2 had lower concentrations of total cholesterol compared to women with a BMI of 25-29.9 kg/m 2 (P = 0.02). With triglycerides, women in the obese category (BMI > 30 kg/m 2 ) had higher concentrations than both women in the normal-weight and overweight category in early and late pregnancy (P < 0.001 and P = 0.03, respectively). In late pregnancy, triglyceride concentrations remained elevated in women in the obese category compared to women in the normal-weight category (P = 0.01). Triglyceride concentrations were also elevated in late pregnancy in mothers that then gave birth to infants with macrosomia and LGA (P = 0.01 and P = 0.03, respectively). Blood lipid concentrations increase during pregnancy and differ by maternal BMI. These intervals could help to inform the development of references for blood lipid concentrations during pregnancy. ROLO Study - ISRCTN54392969 . Date of registration: 22/04/2009.

CpG methylation patterns and decitabine treatment response in acute myeloid leukemia cells and normal hematopoietic precursors

PubMed Central

Negrotto, Soledad; Ng, Kwok Peng; Jankowska, Ania M.; Bodo, Juraj; Gopalan, Banu; Guinta, Kathryn; Mulloy, James C.; Hsi, Eric; Maciejewski, Jaroslaw; Saunthararajah, Yogen

2011-01-01

The DNA hypomethylating drug decitabine maintains normal hematopoietic stem cell (HSC) self-renewal but induces terminal differentiation in acute myeloid leukemia (AML) cells. The basis for these contrasting cell-fates, and for selective CpG hypomethylation by decitabine, is poorly understood. Promoter CpGs, with methylation measured by microarray, were classified by the direction of methylation change with normal myeloid maturation. In AML cells, the methylation pattern at maturation-responsive CpG suggested at least partial maturation. Consistent with partial maturation, in gene expression analyses, AML cells expressed high levels of the key lineage-specifying factor CEBPA, but relatively low levels of the key late-differentiation driver CEBPE. In methylation analysis by mass-spectrometry, CEBPE promoter CpG that are usually hypomethylated during granulocyte maturation were significantly hypermethylated in AML cells. Decitabine treatment induced cellular differentiation of AML cells, and the largest methylation decreases were at CpG that are hypomethylated with myeloid maturation, including CEBPE promoter CpG. In contrast, decitabine-treated normal HSC retained immature morphology, and methylation significantly decreased at CpG that are less methylated in immature cells. High expression of lineage-specifying factor and aberrant epigenetic repression of some key late-differentiation genes distinguishes AML cells from normal HSC and could explain the contrasting differentiation and methylation responses to decitabine. PMID:21836612

The effect of the menstrual cycle on optic nerve head analysis in healthy women.

PubMed

Akar, Munire Erman; Taskin, Omur; Yucel, Iclal; Akar, Yusuf

2004-12-01

To determine the effect of the menstrual cycle on optic nerve head topographic analysis in normally menstruating, healthy women. The study included single eyes selected randomly from each of 52 healthy women with regular menstrual cycles. All subjects underwent a complete ocular examination. Optic nerve head topographic analyses were performed using a confocal scanning laser ophthalmoscope, the Heidelberg Retinal Tomograph II (HRT II, software version 1.6). The analyses were repeated three times during the menstrual cycle: in the follicular phase (days 7-10 of the cycle), at ovulation, and in the late luteal phase (days 1-3 before menstrual bleeding). Serum oestradiol, progesterone and luteinizing hormone levels were measured at each menstrual phase. Fourteen subjects were excluded from the study. The mean age of the subjects (n = 38) was 25.6 +/- 3.7 years (range 21-34 years). Blood oestradiol levels were significantly lower in the late luteal phase (35.8 pg/ml) (p < 0.0001). The mean disc area of the subjects was 1.94 +/- 0.33 mm(2). The neuroretinal rim area decreased significantly during the luteal phase (p < 0.001). However, the linear cup : disc ratio, cup : disc area ratio and the cup area were significantly higher during the luteal phase (p < 0.001). These observations raise the possibility that sex hormone fluctuations which occur during a normal menstrual cycle in healthy women significantly alter neuroretinal rim area and cup variables of the optic nerve head. These findings should be taken into consideration in the clinical follow-up of young women with glaucoma.

Reduced sensitivity of the N400 and late positive component to semantic congruity and word repetition in left temporal lobe epilepsy.

PubMed

Olichney, John M; Riggins, Brock R; Hillert, Dieter G; Nowacki, Ralph; Tecoma, Evelyn; Kutas, Marta; Iragui, Vicente J

2002-07-01

We studied 14 patients with well-characterized refractory temporal lobe epilepsy (TLE), 7 with right temporal lobe epilepsy (RTE) and 7 with left temporal lobe epilepsy (LTE), on a word repetition ERP experiment. Much prior literature supports the view that patients with left TLE are more likely to develop verbal memory deficits, often attributable to left hippocampal sclerosis. Our main objectives were to test if abnormalities of the N400 or Late Positive Component (LPC, P600) were associated with a left temporal seizure focus, or left temporal lobe dysfunction. A minimum of 19 channels of EEG/EOG data were collected while subjects performed a semantic categorization task. Auditory category statements were followed by a visual target word, which were 50% "congruous" (category exemplars) and 50% "incongruous" (non-category exemplars) with the preceding semantic context. These auditory-visual pairings were repeated pseudo-randomly at time intervals ranging from approximately 10-140 seconds later. The ERP data were submitted to repeated-measures ANOVAs, which showed the RTE group had generally normal effects of word repetition on the LPC and the N400. Also, the N400 component was larger to incongruous than congruous new words, as is normally the case. In contrast, the LTE group did not have statistically significant effects of either word repetition or congruity on their ERPs (N400 or LPC), suggesting that this ERP semantic categorization paradigm is sensitive to left temporal lobe dysfunction. Further studies are ongoing to determine if these ERP abnormalities predict hippocampal sclerosis on histopathology, or outcome after anterior temporal lobectomy.

Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism.

PubMed

Mosconi, Lisa; Brys, Miroslaw; Switalski, Remigiusz; Mistur, Rachel; Glodzik, Lidia; Pirraglia, Elizabeth; Tsui, Wai; De Santi, Susan; de Leon, Mony J

2007-11-27

Having a parent affected with late-onset Alzheimer's disease (AD) is a risk factor for developing AD among cognitively normal subjects. We examined whether cognitively normal subjects with a parental family history of AD show cerebral metabolic rate of glucose (CMRglc) reductions consistent with AD as compared with those without a family history and whether there are parent gender effects. Forty-nine 50- to 80-year-old normal subjects were examined who received clinical, neuropsychological, and 2-[(18)F]fluoro-2-deoxy-d-glucose-positron emission tomography examinations, including 16 subjects with a maternal (FHm) and eight with a paternal (FHp) family history of AD and 25 with no family history (FH(-)). FH groups were comparable for demographic and neuropsychological measures. As compared with both FH(-) and FHp groups, FHm subjects showed CMRglc reductions in the same regions as clinically affected AD patients, involving the posterior cingulate cortex/precuneus, parietotemporal and frontal cortices, and medial temporal lobes (P < 0.05, corrected for multiple comparisons). These effects remained significant after accounting for possible risk factors for AD, including age, gender, education, apolipoprotein E genotype, and subjective memory complaints. No CMRglc differences were found between FHp and FH(-) subjects. This study shows a relationship between reduced CMRglc in AD-vulnerable brain regions and a maternal family history of AD in cognitively normal individuals.

Late-onset urea cycle disorder in adulthood unmasked by severe malnutrition.

PubMed

Wells, Diana L; Thomas, Jillian B; Sacks, Gordon S; Zouhary, L Anna

2014-01-01

Urea cycle disorders (UCDs) most often involve inherited deficiencies in genes that code for enzymes normally used by the urea cycle to breakdown nitrogen. UCDs lead to serious metabolic complications, including severe neurologic decompensation related to hyperammonemia. Although the majority of UCDs are revealed soon after birth, stressful events in adulthood can lead to unmasking of a partial, late-onset UCDs. In this report, we describe a late-onset UCD unmasked by severe malnutrition. Early, specialized nutrition therapy is a fundamental aspect of treating hyperammonemic crises in patients with UCD. The case presented here demonstrates the importance of early recognition of UCD and appropriate interventions with nutrition support. Copyright © 2014 Elsevier Inc. All rights reserved.

Perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios.

PubMed

Sahin, Erdem; Madendag, Yusuf; Tayyar, Ahter Tanay; Sahin, Mefkure Eraslan; Col Madendag, Ilknur; Acmaz, Gokhan; Unsal, Deniz; Senol, Vesile

2017-08-16

The purpose of this study is to determine the adverse perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios. A total of 430 pregnant women with an uncomplicated singleton pregnancy at a gestational age of 34 + 0-36 + 6 weeks were included. Borderline oligohydramnios was defined as an amniotic fluid index (AFI) of 5.1-8 cm, which was measured using the four-quadrant technique. Adverse perinatal outcomes were compared between the borderline and normal AFI groups. Approximately 107 of the 430 pregnant women were borderline AFI, and 323 were normal AFI. The demographic and obstetric characteristics were similar in both groups. Delivery <37 weeks, cesarean delivery for non-reassuring fetal heart-rate testing, meconium-stained amniotic fluid, Apgar 5 min <7, transient tachypnea of the newborn, respiratory distress syndrome, neonatal intensive care unit, and hyperbilirubinemia were not statistically different between the groups (p = .054, p = .134, p = .749, p = 0.858, p = .703, p = .320, p = .185, and p = .996, respectively). Although gestational age was full-term, induction of labor rates were significantly higher in the borderline AFI group (p = .040). In addition, fetal renal artery pulsatility index pulsatility index (PI) was significantly lower in the borderline AFI group than in the normal AFI group (p = .014). Our results indicated that borderline AFI was not a risk for adverse perinatal outcomes in uncomplicated, late preterm pregnancies.

Suppression of follicular rupture with meloxicam, a cyclooxygenase-2 inhibitor: potential for emergency contraception.

PubMed

Jesam, Cristián; Salvatierra, Ana María; Schwartz, Jill L; Croxatto, Horacio B

2010-02-01

There is evidence that cyclooxygenase-2 (COX-2) inhibitors can prevent or delay follicular rupture. COX-2 inhibitors, such as meloxicam, may offer advantages over emergency contraception with levonorgestrel, such as extending the therapeutic window for up to 24 h. We assessed the effect of meloxicam administered in the late follicular phase upon ovulation in women. This was a single center, double blind, crossover study designed to assess the effects in 27 eligible women (18-40 years old, surgically sterilized with regular menstrual cycles) of meloxicam, 15 or 30 mg/day, administered orally for five consecutive days during the late follicular phase, starting when the leading follicle reached 18 mm diameter. Volunteers underwent two treatment cycles separated by one resting cycle, with randomization to dose sequence. Main outcomes were follicular rupture; serum LH, progesterone and estradiol (E2) levels; and incidence of adverse events. Twenty-two volunteers completed the study. There were no differences between meloxicam doses in menstrual cycle length. Dysfunctional ovulation was observed in 11/22 (50%) cycles treated with 15 mg/day and 20/22 (90.9%) cycles with 30 mg/day (P = 0.0068). All women had normal luteal phase progesterone levels; mean maximal values +/- SEM were 42 +/- 4.1 and 46.8 +/- 2.6 nmol/l for 15 and 30 mg/day groups, respectively. There were no serious adverse events, and no changes in LH and E2 levels or in cycle length. Meloxicam 30 mg given for five consecutive days in the late follicular phase is safe, effective and may be an alternative form of emergency contraception.

Insulin restores L-arginine transport requiring adenosine receptors activation in umbilical vein endothelium from late-onset preeclampsia.

PubMed

Salsoso, R; Guzmán-Gutiérrez, E; Sáez, T; Bugueño, K; Ramírez, M A; Farías, M; Pardo, F; Leiva, A; Sanhueza, C; Mate, A; Vázquez, C; Sobrevia, L

2015-03-01

Preeclampsia is associated with impaired placental vasodilation and reduced endothelial nitric oxide synthase (eNOS) activity in the foetoplacental circulation. Adenosine and insulin stimulate vasodilation in endothelial cells, and this activity is mediated by adenosine receptor activation in uncomplicated pregnancies; however, this activity has yet to be examined in preeclampsia. Early onset preeclampsia is associated with severe placental vasculature alterations that lead to altered foetus growth and development, but whether late-onset preeclampsia (LOPE) alters foetoplacental vascular function is unknown. Vascular reactivity to insulin (0.1-1000 nmol/L, 5 min) and adenosine (1 mmol/L, 5 min) was measured in KCl-preconstricted human umbilical vein rings from normal and LOPE pregnancies using a wire myograph. The protein levels of human cationic amino acid transporter 1 (hCAT-1), adenosine receptor subtypes, total and Ser¹¹⁷⁷- or Thr⁴⁹⁵-phosphorylated eNOS were detected via Western blot, and L-arginine transport (0-1000 μmol/L L-arginine, 3 μCi/mL L-[³H]arginine, 20 s, 37 °C) was measured in the presence or absence of insulin and adenosine receptor agonists or antagonists in human umbilical vein endothelial cells (HUVECs) from normal and LOPE pregnancies. LOPE increased the maximal L-arginine transport capacity and hCAT-1 and eNOS expression and activity compared with normal conditions. The A(2A) adenosine receptor (A(2A)AR) antagonist ZM-241385 blocked these effects of LOPE. Insulin-mediated umbilical vein ring relaxation was lower in LOPE pregnancies than in normal pregnancies and was restored using the A(2A)AR antagonist. The reduced foetoplacental vascular response to insulin may result from A(2A)AR activation in LOPE pregnancies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biological mechanisms of normal tissue damage: importance for the design of NTCP models.

PubMed

Trott, Klaus-Rüdiger; Doerr, Wolfgang; Facoetti, Angelica; Hopewell, John; Langendijk, Johannes; van Luijk, Peter; Ottolenghi, Andrea; Smyth, Vere

2012-10-01

The normal tissue complication probability (NTCP) models that are currently being proposed for estimation of risk of harm following radiotherapy are mainly based on simplified empirical models, consisting of dose distribution parameters, possibly combined with clinical or other treatment-related factors. These are fitted to data from retrospective or prospective clinical studies. Although these models sometimes provide useful guidance for clinical practice, their predictive power on individuals seems to be limited. This paper examines the radiobiological mechanisms underlying the most important complications induced by radiotherapy, with the aim of identifying the essential parameters and functional relationships needed for effective predictive NTCP models. The clinical features of the complications are identified and reduced as much as possible into component parts. In a second step, experimental and clinical data are considered in order to identify the gross anatomical structures involved, and which dose distributions lead to these complications. Finally, the pathogenic pathways and cellular and more specific anatomical parameters that have to be considered in this pathway are determined. This analysis is carried out for some of the most critical organs and sites in radiotherapy, i.e. spinal cord, lung, rectum, oropharynx and heart. Signs and symptoms of severe late normal tissue complications present a very variable picture in the different organs at risk. Only in rare instances is the entire organ the critical target which elicits the particular complication. Moreover, the biological mechanisms that are involved in the pathogenesis differ between the different complications, even in the same organ. Different mechanisms are likely to be related to different shapes of dose effect relationships and different relationships between dose per fraction, dose rate, and overall treatment time and effects. There is good reason to conclude that each type of late complication after radiotherapy depends on its own specific mechanism which is triggered by the radiation exposure of particular structures or sub-volumes of (or related to) the respective organ at risk. Hence each complication will need the development of an NTCP model designed to accommodate this structure. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Parent perspectives on information about late effects of childhood cancer treatment and their role in initial treatment decision making.

PubMed

Greenzang, Katie A; Dauti, Angela; Mack, Jennifer W

2018-06-01

Though most childhood cancer survivors experience late effects of treatment, we know little about parent preferences for late effects information during therapy, or how parents weigh late effects when making treatment decisions. Our objective was to explore how parents of children with cancer consider late effects in initial treatment decision making and during active cancer treatment. Semistructured interviews were conducted with 12 parents of children with cancer who were actively receiving treatment at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Interviews were audio-recorded, transcribed verbatim, and qualitatively analyzed using thematic analysis. Ten of 12 parents reported that they had to decide between two or more treatment options for their child's cancer. Of those, 50% (5/10) considered late effects to be an important factor in their decision making. Most parents wanted early and detailed information about their child's risk of late effects to make treatment decisions and to feel prepared for the future. However, a few parents felt too overwhelmed to focus on late effects at diagnosis. While many recalled extensive late effects information in informed consent discussions, some parents felt these issues were minimally addressed. Parents desire detailed information about late effects to make informed treatment decisions and prepare for the future. Despite the role of late effects in treatment decision making, some parents feel that late effects are either inadequately addressed or too overwhelming to process at diagnosis. Parents may benefit from early assessment of their information needs and a return to these issues over time. © 2018 Wiley Periodicals, Inc.

Late effects in childhood cancer survivors: a review with a framing effect bias?

PubMed

Fryer, Christopher

2011-12-15

Most publications report the adverse (negative) health issues in childhood cancer survivors. Presenting information to the newly diagnosed patient in a positive manner is advocated, while noting that recurrence is the most likely adverse event. Re-analysis of population-based studies on life-threatening toxicities from Nordic, Dutch, United Kingdom, French, Italian, and N. American publications shows that 5-year survivors have a near normal life expectancy, 75% have no severe or life-threatening treatment related toxicity and 87% remain free of a second malignancy. Children who received radiation or anthracycline >250-300 mg/m(2) are at greatest risk for treatment related life-threatening toxicities. Copyright © 2011 Wiley Periodicals, Inc.

Classical late infantile neuronal ceroid lipofuscinosis fibroblasts are deficient in lysosomal tripeptidyl peptidase I.

PubMed

Vines, D J; Warburton, M J

1999-01-25

Tripeptidyl peptidase I (TPP-I) is a lysosomal enzyme that cleaves tripeptides from the N-terminus of polypeptides. A comparison of TPP-I amino acid sequences with sequences derived from an EST database suggested that TPP-I is identical to a pepstatin-insensitive carboxyl proteinase of unknown specificity which is mutated in classical late infantile neuronal ceroid lipofuscinosis (LINCL), a lysosomal storage disease. Both TPP-I and the carboxyl proteinase have an M(r) of about 46 kDa and are, or are predicted to be, resistant to inhibitors of the four major classes of proteinases. Fibroblasts from LINCL patients have less than 5% of the normal TPP-I activity. The activities of other lysosomal enzymes, including proteinases, are in the normal range. LINCL fibroblasts are also defective at degrading short polypeptides and this defect can be induced in normal fibroblasts by treatment with a specific inhibitor or TPP-I. These results suggest that the cell damage, especially neuronal, observed in LINCL results from the defective degradation and consequent lysosomal storage of small peptides.

The Need for Modernized Operational Snow Models: A Tale of Two Years

NASA Astrophysics Data System (ADS)

Winstral, A. H.; Marks, D. G.

2014-12-01

The Boise River Basin in southwest Idaho, USA contains three major reservoirs totaling nearly 1,000,000 acre-feet of storage capacity. The primary goals for water managers are water supply and flood protection. In terms of observed SWE at monitoring sites throughout the basin, water years 2012 and 2014 were similar and near normal. In WY 2014 inflows into the BRB reservoir system followed historic patterns and reservoir releases were ideally controlled for management goals. WY2012 however was warmer than average and the winter snowpack had uncharacteristically high melt susceptibility. Subsequent energy fluxes produced late winter inflows much higher than normally encountered. The uncharacteristic flow patterns and inability of traditional operational modeling tools to handle this situation challenged water managers. Through late March and early April 2012 near flood stage flows were pushed through the city of Boise in order to increase storage and prevent more catastrophic flooding. While in this case a greater catastrophe was narrowly averted, the shortcomings of the traditional modeling approaches taken by operational agencies were exposed. "Uncharacteristic" events such as these are becoming more and more frequent as the effects of climate change are realized. The need for modernized methods - ones based on the physical controlling processes rather than historic patterns - is imperative. This presentation outlines the latest developments in the application of a physically-based, high-resolution spatial snow model to aid operational water management decisions.

Angiogenic profile and smoking in the Finnish Genetics of Pre-Eclampsia Consortium (FINNPEC) cohort.

PubMed

Jääskeläinen, Tiina; Suomalainen-König, Sanna; Hämäläinen, Esa; Pulkki, Kari; Romppanen, Jarkko; Heinonen, Seppo; Laivuori, Hannele

2017-11-01

The biological mechanism by which smoking reduces the risk of pre-eclampsia (PE) is unresolved. We studied serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and their ratio, in addition to soluble endoglin (sEng) in early and late pregnancy to ascertain whether these factors are altered in women who smoke. First trimester serum samples were available from 217 women who later developed PE and 238 women who did not develop PE. Second/third trimester serum samples were available from 174 PE and 54 non-PE women. PE women who smoked during pregnancy had elevated first trimester concentrations of serum PlGF [geometric mean (95% CI): 39.8 (32.6-48.5) pg/ml, p = .001] and reduced sEng concentration [5.0 (4.6-5.6) ng/ml, p = .047] compared to PE non-smokers [30.0 (28.1-32.1) pg/ml and 6.1 (5.9-6.4) ng/ml, respectively]. Non-smoking women in the PE group had the highest sFlt-1/PlGF ratio in early and late pregnancy. The protective effect of smoking in reducing the risk of PE may be due to the early pregnancy change towards pro-angiogenic marker profile. Also, in late pregnancy, smoking exerted effect in sFlt-1/PlGF ratio in PE pregnancies, and may complicate its use as a prognostic and diagnostic marker. Key messages Smoking appears to have angiogenic effects in early pregnancy with reduced sEng concentrations and elevated PlGF concentrations in both normal and PE pregnancies. Throughout pregnancy, smoking exerted effect in PlGF concentration and sFlt-1/PlGF ratio in PE pregnancies, and thus may complicate its use as a prognostic and diagnostic marker.

Zebrafish msxB, msxC and msxE function together to refine the neural-nonneural border and regulate cranial placodes and neural crest development.

PubMed

Phillips, Bryan T; Kwon, Hye-Joo; Melton, Colt; Houghtaling, Paul; Fritz, Andreas; Riley, Bruce B

2006-06-15

The zebrafish muscle segment homeobox genes msxB, msxC and msxE are expressed in partially overlapping domains in the neural crest and preplacodal ectoderm. We examined the roles of these msx genes in early development. Disrupting individual msx genes causes modest variable defects, whereas disrupting all three produces a reproducible severe phenotype, suggesting functional redundancy. Neural crest differentiation is blocked at an early stage. Preplacodal development begins normally, but placodes arising from the msx expression domain later show elevated apoptosis and are reduced in size. Cell proliferation is normal in these tissues. Unexpectedly, Msx-deficient embryos become ventralized by late gastrulation whereas misexpression of msxB dorsalizes the embryo. These effects appear to involve Distal-less (Dlx) protein activity, as loss of dlx3b and dlx4b suppresses ventralization in Msx-depleted embryos. At the same time, Msx-depletion restores normal preplacodal gene expression to dlx3b-dlx4b mutants. These data suggest that mutual antagonism between Msx and Dlx proteins achieves a balance of function required for normal preplacodal differentiation and placement of the neural-nonneural border.

Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.

1994-07-01

The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through amore » 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses {ge}30 Gy. Radiation changes were present in the aorta and vena cava at doses {ge}40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs.« less

Simulation of late inspiratory rise in airway pressure during pressure support ventilation.

PubMed

Yu, Chun-Hsiang; Su, Po-Lan; Lin, Wei-Chieh; Lin, Sheng-Hsiang; Chen, Chang-Wen

2015-02-01

Late inspiratory rise in airway pressure (LIRAP, Paw/ΔT) caused by inspiratory muscle relaxation or expiratory muscle contraction is frequently seen during pressure support ventilation (PSV), although the modulating factors are unknown. We investigated the effects of respiratory mechanics (normal, obstructive, restrictive, or mixed), inspiratory effort (-2, -8, or -15 cm H2O), flow cycle criteria (5-40% peak inspiratory flow), and duration of inspiratory muscle relaxation (0.18-0.3 s) on LIRAP during PSV using a lung simulator and 4 types of ventilators. LIRAP occurred with all lung models when inspiratory effort was medium to high and duration of inspiratory muscle relaxation was short. The normal lung model was associated with the fastest LIRAP, whereas the obstructive lung model was associated with the slowest. Unless lung mechanics were normal or mixed, LIRAP was unlikely to occur when inspiratory effort was low. Different ventilators were also associated with differences in LIRAP speed. Except for within the restrictive lung model, changes in flow cycle level did not abolish LIRAP if inspiratory effort was medium to high. Increased duration of inspiratory relaxation also led to the elimination of LIRAP. Simulation of expiratory muscle contraction revealed that LIRAP occurred only when expiratory muscle contraction occurred sometime after the beginning of inspiration. Our simulation study reveals that both respiratory resistance and compliance may affect LIRAP. Except for under restrictive lung conditions, LIRAP is unlikely to be abolished by simply lowering flow cycle criteria when inspiratory effort is strong and relaxation time is rapid. LIRAP may be caused by expiratory muscle contraction when it occurs during inspiration. Copyright © 2015 by Daedalus Enterprises.

Normal growth and muscle dysfunction in X-linked hypophosphatemic rickets associated with a novel mutation in the PHEX gene.

PubMed

Makras, Polyzois; Hamdy, Neveen A T; Kant, Sarina G; Papapoulos, Socrates E

2008-04-01

X-linked hypophosphatemic rickets (XLH) is characterized by hypophosphatemia and growth retardation. Early diagnosis and treatment improve growth. Our objective was to describe long-term observations of a family with XLH due to a novel mutation of the PHEX gene with unusual clinical features, including normal growth. The mother and her two sons were followed in the same institution for nearly 30 yr. The mother had hypophosphatemia and normal height (Z score, -0.6) without ever receiving any treatment. Her two sons achieved final heights of 183.7 cm (Z score, -0.01) and 182.7 cm (Z score, -0.18), respectively, despite late initiation of treatment with phosphate and low serum phosphate levels. In addition, they had reversible proximal myopathy that took about 7 yr to resolve in one of them. Direct sequencing of the PHEX gene revealed a new splice site mutation in intron 4 of the gene (IVS4+6T-->C) resulting in skipping of exon 4. Three members of a family with XLH due to a novel mutation of the PHEX gene had a normal growth pattern despite late diagnosis and treatment of the two boys and no treatment at all of their mother. The pathophysiological basis of this phenotype-genotype association warrants further investigation.

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

PubMed

Maruyama, Hiroki; Miyata, Kaori; Mikame, Mariko; Taguchi, Atsumi; Guili, Chu; Shimura, Masaru; Murayama, Kei; Inoue, Takeshi; Yamamoto, Saori; Sugimura, Koichiro; Tamita, Koichi; Kawasaki, Toshihiro; Kajihara, Jun; Onishi, Akifumi; Sugiyama, Hitoshi; Sakai, Teiko; Murata, Ichijiro; Oda, Takamasa; Toyoda, Shigeru; Hanawa, Kenichiro; Fujimura, Takeo; Ura, Shigehisa; Matsumura, Mimiko; Takano, Hideki; Yamashita, Satoshi; Matsukura, Gaku; Tazawa, Ryushi; Shiga, Tsuyoshi; Ebato, Mio; Satoh, Hiroshi; Ishii, Satoshi

2018-03-15

PurposePlasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females.MethodsBetween 1 July 2014 and 31 December 2015, we screened 2,360 patients (1,324 males) referred from 169 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively.ResultsOf 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml -1 ) and low α-Gal A activity (≤4.0 nmol h -1  ml -1 ), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 15 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 8 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance).ConclusionPlasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.Genet Med advance online publication, 15 March 2018; doi:10.1038/gim.2018.31.

Late-onset dietary restriction compensates for age-related increase in oxidative stress and alterations of HSP 70 and synapsin 1 protein levels in male Wistar rats.

PubMed

Sharma, Sandeep; Singh, Rumani; Kaur, Manpreet; Kaur, Gurcharan

2010-04-01

Numerous reports implicate increased oxidative stress in the functional and structural changes occurring in the brain and other organs as a part of the normal aging process. Dietary restriction (DR) has long been shown to be life-prolonging intervention in several species. This study was aimed to assess the potential efficacy of late-onset short term DR when initiated in 21 months old male wistar rats for 3 months on the antioxidant defense system and lipid peroxidation, cellular stress response protein HSP 70 and synaptic marker protein synapsin 1 in discrete brain regions such as cortex, hypothalamus, and hippocampus as well as liver, kidney and heart from 24 month old rats. Age-associated decline in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione, and elevated levels of lipid peroxidation was observed in brain and peripheral organ as well as increased expression of HSP 70 and reduction in synapsin 1 was observed in brain studied. Late-onset short term DR was effective in partially restoring the antioxidant status and in decreasing lipid peroxidation level as well as enhancing the expression of HSP 70 and synapsin 1 in aged rats. Late onset short term DR also prevented age-related neurodegeneration as revealed by Fluoro-Jade B staining in hippocampus and cortex regions of rat brain. Thus our current results suggest that DR initiated even in old age has the potential to improve age related decline in body functions.

Evaluation of the ASOS impact on climatic normals and assessment of variable-length time periods in calculation of normals

NASA Astrophysics Data System (ADS)

Kauffman, Chad Matthew

The temperature and precipitation that describe the norm of daily, monthly, and seasonal climate conditions are ``climate normals.'' They are usually calculated based on climate data covering a 30-year period, and updated in every 10 years. The next update will take place in year 2001. Because of the advent of the Automated Surface Observations Systems (ASOS) beginning in early 1990s and recognized temperature bias between ASOS and the conventional temperature sensors there is an uncertainty of how the ASOS data should be used to calculate the 1971-2000 temperature normal. This study examined the uncertainty and offered a method to minimize it. It showed that the ASOS bias has a measurable impact on the new 30-year temperature normal. The impact varies among stations and climate regions. Some stations with a cooling trend in ASOS temperature have a cooler normal for their temperature, while others with a warming trend have a warmer normal for temperature. These quantitative evaluations of ASOS effect for stations and regions can be used to reduce ASOS bias in temperature normals. This study also evaluated temperature normals for different length periods and compared them to the 30-year normal. It showed that the difference between the normals, is smaller in maritime climate than in continental temperate climate. In the former, the six- year normal describes a similar temperature variation as the 30-year normal does. In the latter, the 18-year normal starts to resemble the temperature variation that the 30-year normal describes. These results provide a theoretical basis for applying different normals in different regions. The study further compared temperature normal for different periods and identified a seasonal shift in climate change in the southwestern U.S. where the summer maximum temperature has shifted to a late summer month and the winter minimum temperature shifted to an early winter month in the past 30 years.

Genetics Home Reference: LAMA2-related muscular dystrophy

MedlinePlus

... weakness of the facial muscles and tongue, but intelligence is usually normal. Heart problems and seizures occasionally ... walk and climb stairs, and life expectancy and intelligence are usually not affected in late-onset LAMA2 - ...

Late Quaternary faulting in the Vallo di Diano basin (southern Apennines, Italy)

NASA Astrophysics Data System (ADS)

Villani, F.; Pierdominici, S.; Cinti, F. R.

2009-12-01

The Vallo di Diano is the largest Quaternary extensional basin in the southern Apennines thrust-belt axis (Italy). This portion of the chain is highly seismic and is currently subject to NE-extension, which triggers large (M> 6) normal-faulting earthquakes along NW-trending faults. The eastern edge of the Vallo di Diano basin is bounded by an extensional fault system featuring three main NW-trending, SW-dipping, right-stepping, ~15-17 km long segments (from north to south: Polla, Atena Lucana-Sala Consilina and Padula faults). Holocene activity has been documented so far only for the Polla segment. We have therefore focused our geomorphological and paleoseismological study on the southern portion of the system, particularly along the ~ 4 km long Atena Lucana-Sala Consilina and Padula faults overlap zone. The latter is characterized by a complex system of coalescent alluvial fans, Middle Pleistocene to Holocene in age. Here we recognized a > 4 km long and 0.5-1.4 km wide set of scarps (ranging in height between 1 m and 2.5 m) affecting Late Pleistocene - Holocene alluvial fans. In the same area, two Late Pleistocene volcanoclastic layers at the top of an alluvial fan exposed in a quarry are affected by ~ 1 m normal displacements. Moreover, a trench excavated across a 2 m high scarp affecting a Holocene fan revealed warping of Late Holocene debris flow deposits, with a total vertical throw of about 0.3 m. We therefore infer the overlap zone of the Atena Lucana-Sala Consilina and Padula faults is a breached relay ramp, generated by hard-linkage of the two fault segments since Late Pleistocene. This ~ 32 km long fault system is active and is capable of generating Mw ≥6.5 earthquakes.

Brain morphological and microstructural features in cryptogenic late-onset temporal lobe epilepsy: a structural and diffusion MRI study.

PubMed

Sone, Daichi; Sato, Noriko; Kimura, Yukio; Watanabe, Yutaka; Okazaki, Mitsutoshi; Matsuda, Hiroshi

2018-06-01

Although epilepsy in the elderly has attracted attention recently, there are few systematic studies of neuroimaging in such patients. In this study, we used structural MRI and diffusion tensor imaging (DTI) to investigate the morphological and microstructural features of the brain in late-onset temporal lobe epilepsy (TLE). We recruited patients with TLE and an age of onset > 50 years (late-TLE group) and age- and sex-matched healthy volunteers (control group). 3-Tesla MRI scans, including 3D T1-weighted images and 15-direction DTI, showed normal findings on visual assessment in both groups. We used Statistical Parametric Mapping 12 (SPM12) for gray and white matter structural normalization and comparison and used Tract-Based Spatial Statistics (TBSS) for fractional anisotropy and mean diffusivity comparisons of DTI. In both methods, p < 0.05 (family-wise error) was considered statistically significant. In total, 30 patients with late-onset TLE (mean ± SD age, 66.8 ± 8.4; mean ± SD age of onset, 63.0 ± 7.6 years) and 40 healthy controls (mean ± SD age, 66.6 ± 8.5 years) were enrolled. The late-onset TLE group showed significant gray matter volume increases in the bilateral amygdala and anterior hippocampus and significantly reduced mean diffusivity in the left temporofrontal lobe, internal capsule, and brainstem. No significant changes were evident in white matter volume or fractional anisotropy. Our findings may reflect some characteristics or mechanisms of cryptogenic TLE in the elderly, such as inflammatory processes.

Products resulting from cleavage of the interglobular domain of aggrecan in samples of synovial fluid collected from dogs with early- and late-stage osteoarthritis.

PubMed

Innes, John F; Little, Chris B; Hughes, Clare E; Caterson, Bruce

2005-10-01

To investigate interglobular domain (IGD) cleavage of aggrecan in dogs with naturally developing osteoarthritis (OA). Samples of synovial fluid (SF) obtained from 3 cubital (elbow) joints and 3 stifle joints of 4 clinically normal dogs, 24 elbow joints of 12 dogs with early-stage OA, 8 stifle joints of 5 dogs with early-stage OA, and 10 stifle joints of 9 dogs with late-stage OA. Fractions of SF were assayed for total glycosaminoglycan (GAG) content and also subjected to Western blot analysis by use of monoclonal antibodies against neoepitopes generated by cleavage of the IGD of the aggrecan protein core by matrix metalloproteinase (MMP; BC-14) and aggrecanase (BC-3). Total GAG content of SF from joints of clinically normal dogs did not differ from that of dogs with early-stage OA. The GAG content of SF from joints of dogs with late-stage OA was significantly lower, compared with GAG content for other SF samples. Aggrecanase-generated fragments were detected in SF from all groups but not in all samples. Matrix metalloproteinase-generated fragments were not detected in any SF samples. In early-stage OA, high-molecular-weight aggrecanase-generated aggrecan catabolites were evident. GAG content of SF obtained from dogs with late-stage OA is significantly decreased, suggesting proteoglycan depletion of cartilage. Aggrecanases, but not MMPs, are the major proteolytic enzymes responsible for IGD cleavage of aggrecan in canine joints. Analyses of SF samples to detect aggrecanase-generated catabolites may provide an early biomarker for discriminating early- and late-stage OA in dogs.

In vitro synthesis of oncogenic human papillomaviruses requires episomal genomes for differentiation-dependent late expression.

PubMed Central

Frattini, M G; Lim, H B; Laimins, L A

1996-01-01

Human papillomavirus (HPV) types 16, 18, 31, and 51 are the etiologic agents of many anogenital cancers including those of the cervix. These "high risk" HPVs specifically target genital squamous epithelia, and their lytic life cycle is closely linked to epithelial differentiation. We have developed a genetic assay for HPV functions during pathogenesis using recircularized cloned HPV 31 genomes that were transfected together with a drug resistance marker into monolayer cultures of normal human foreskin keratinocytes, the natural host cell. After drug selection, cell lines were isolated that stably maintained HPV 31 DNA as episomes and underwent terminal differentiation when grown in organotypic raft cultures. In differentiated rafts, the expression of late viral genes, amplification of viral DNA, and production of viral particles were detected in suprabasal cells. This demonstrated the ability to synthesize HPV 31 virions from transfected DNA templates and allowed an examination of HPV functions during the vegetative viral life cycle. We then used this system to investigate whether an episomal genome was required for the induction of late viral gene expression. When an HPV 31 genome (31E1*) containing a missense mutation in the E1 open reading frame was transfected into normal human keratinocytes, the mutant viral sequences were found to integrate into the host cell chromosomal DNA with both early and late regions intact. While high levels of early viral gene transcription were observed, no late gene expression was detected in rafts of cell lines containing the mutant viral genome despite evidence of terminal differentiation. Therefore, the induction of late viral gene expression required that the viral genomes be maintained as extrachromosomal elements, and terminal differentiation alone was not sufficient. These studies provide the basis for a detailed examination of HPV functions during viral pathogenesis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:8610168

Early metformin therapy (age 8-12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence.

PubMed

Ibáñez, Lourdes; López-Bermejo, Abel; Díaz, Marta; Marcos, Maria Victoria; de Zegher, Francis

2011-08-01

Girls with a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP) are at high risk to develop polycystic ovary syndrome (PCOS). The objective of the study was to compare the capacity of early vs. late metformin treatment to prevent adolescent PCOS. This was a randomized, open-label study over 7 yr. The study was conducted at a university hospital. Thirty-eight LBW-PP girls were followed up from the mean age 8 until age 15 yr. Early metformin (study yr 1-4; age 8-12 yr) vs. late metformin (yr 6; age 13-14 yr). Measures included height; weight; hirsutism score; menstrual cycle; endocrine-metabolic screening (fasting; follicular phase); C-reactive protein; body composition (absorptiometry); abdominal fat partitioning (magnetic resonance imaging); ovarian morphology (ultrasound); PCOS (National Institutes of Health and Androgen Excess Society definitions) after yr 7 (all girls thus untreated for at least 1 yr). None of the girls dropped out of the study. At age 15 yr, early-metformin girls were taller (4 cm), were in a less proinflammatory state, and had less central fat due to reductions in visceral and hepatic fat. Hirsutism, androgen excess, oligomenorrhea, and PCOS were between 2- and 8-fold more prevalent in late- than early-treated girls. Abdominal adiposity was the first variable to diverge (at age 8-10 yr) between girls without vs. with PCOS at age 15 yr. In LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea, and PCOS more effectively than late metformin. The time window of late childhood and early puberty may be more critical for the development, and thus for the prevention, of adolescent PCOS than the first years beyond menarche.

Neuropsychiatric manifestations in late-onset urea cycle disorder patients.

PubMed

Serrano, Mercedes; Martins, Cecilia; Pérez-Dueñas, Belén; Gómez-López, Lilian; Murgui, Empar; Fons, Carmen; García-Cazorla, Angels; Artuch, Rafael; Jara, Fernando; Arranz, José A; Häberle, Johannes; Briones, Paz; Campistol, Jaume; Pineda, Mercedes; Vilaseca, Maria A

2010-03-01

Inherited urea cycle disorders represent one of the most common groups of inborn errors of metabolism. Late-onset urea cycle disorders caused by partial enzyme deficiencies may present with unexpected clinical phenotypes. We report 9 patients followed up in our hospital presenting late-onset urea cycle disorders who initially manifested neuropsychiatric/neurodevelopmental symptoms (the most prevalent neuropsychiatric/neurodevelopmental diagnoses were mental retardation, attention-deficit hyperactivity disorder [ADHD], language disorder, and delirium). Generally, these clinical pictures did not benefit from pharmacological treatment. Conversely, dietary treatment improved the symptoms. Regarding biochemical data, 2 patients showed normal ammonium but high glutamine levels. This study highlights the fact that neuropsychiatric/neurodevelopmental findings are common among the initial symptomatology of late-onset urea cycle disorders. The authors recommend that unexplained or nonresponsive neuropsychiatric/neurodevelopmental symptoms appearing during childhood or adolescence be followed by a study of ammonia and amino acid plasmatic levels to rule out a urea cycle disorder.

Generative Retrieval Improves Learning and Retention of Cardiac Anatomy Using Transesophageal Echocardiography.

PubMed

Kleiman, Amanda M; Forkin, Katherine T; Bechtel, Allison J; Collins, Stephen R; Ma, Jennie Z; Nemergut, Edward C; Huffmyer, Julie L

2017-05-01

Transesophageal echocardiography (TEE) is a valuable monitor for patients undergoing cardiac and noncardiac surgery as it allows for evaluation of cardiovascular compromise in the perioperative period. It is challenging for anesthesiology residents and medical students to learn to use and interpret TEE in the clinical environment. A critical component of learning to use and interpret TEE is a strong grasp of normal cardiovascular ultrasound anatomy. Fifteen fourth-year medical students and 15 post-graduate year (PGY) 1 and 2 anesthesiology residents without prior training in cardiac anesthesia or TEE viewed normal cardiovascular anatomy TEE video clips; participants were randomized to learning cardiac anatomy in generative retrieval (GR) and standard practice (SP) groups. GR participants were required to verbally identify each unlabeled cardiac anatomical structure within 10 seconds of the TEE video appearing on the screen. Then a correctly labeled TEE video clip was shown to the GR participant for 5 more seconds. SP participants viewed the same TEE video clips as GR but there was no requirement for SP participants to generate an answer; for the SP group, each TEE video image was labeled with the correctly identified anatomical structure for the 15 second period. All participants were tested for intermediate (1 week) and late (1 month) retention of normal TEE cardiovascular anatomy. Improvement of intermediate and late retention of TEE cardiovascular anatomy was evaluated using a linear mixed effects model with random intercepts and random slopes. There was no statistically significant difference in baseline score between GR (49% ± 11) and SP (50% ± 12), with mean difference (95% CI) -1.1% (-9.5, 7.3%). At 1 week following the educational intervention, GR (90% ± 5) performed significantly better than SP (82% ± 11), with mean difference (95% CI) 8.1% (1.9, 14.2%); P = .012. This significant increase in scores persisted in the late posttest session at one month (GR: 83% ± 12; SP: 72% ± 12), with mean difference (95% CI) 10.2% (1.3 to 19.1%); P = .026. Mixed effects analysis showed significant improvements in TEE cardiovascular anatomy over time, at 5.9% and 3.5% per week for GR and SP groups respectively (P = .0003), and GR improved marginally faster than SP (P = .065). Medical students and anesthesiology residents inexperienced in the use of TEE showed both improved learning and retention of basic cardiovascular ultrasound anatomy with the incorporation of GR into the educational experience.

The 10:00-11:00 pm urine cortisol/creatinine ratio. An alternative to late-night salivary cortisol for the diagnosis of Cushing's syndrome.

PubMed

Bruno, Oscar D; Rossi, María A; Juárez-Allen, Lea; Serra, Héctor A; Albiero, María C

2015-01-01

The aim of this study was to investigate interchangeability of two tests to diagnose Cushing's syndrome. We compared 10:00-11:00 PM urinary free cortisol/creatinine ratio (UFC/Cr) with late night 11:00 PM salivary cortisol (LNSC) in normal and obese controls vs. patients with Cushing's syndrome. Mean UFC/Cr did not differ between 69 normal and 62 obese controls (9.9 ± 7.9 vs. 9.7 ± 9.3) whereas 116 Cushing's patients had significantly higher values (277.0 ± 318.0; z: -11.1 and -10.2, respectively; p < 0.001). LNSC was 1.9 ± 1.2 nmol/l in 44 normal and 2.5 ± 1.6 in 45 obese subjects with no differences between them, but was significantly higher in 47 Cushing's patients (24.8 ± 23.3; z: -7.22 and -6.96, respectively, p < 0.001). Comparison of UFC/Cr and LNSC in samples obtained simultaneously showed that UFC/Cr was 12.0 ± 8.7 ng cortisol/mg creatinine in 34 normal, 12.3 ± 8.9 in 40 obese and 319.5 ± 333.4 in 35 CS subjects (p < 0.001 vs. normal and obese), whereas LNSC was 1.8 ± 1.2 nmol/l in normal, 2.6 ± 1.7 in obese and 24.6 ± 17.4 in CS patients (p < 0.001 vs. normal and obese); ROC curves showed comparable high sensitivity and specificity figures for the diagnosis of CS. We concluded that UFC/Cr test is easy to perform, readily available in routine laboratories, has high sensitivity and specificity, and offers a valuable alternative to LNSC in the study of Cushing's syndrome.

Testosterone replacement therapy improves health-related quality of life for patients with late-onset hypogonadism: a meta-analysis of randomized controlled trials.

PubMed

Nian, Y; Ding, M; Hu, S; He, H; Cheng, S; Yi, L; Li, Y; Wang, Y

2017-05-01

Although testosterone replacement therapy can restore serum testosterone concentrations to normal level in late-onset hypogonadism patients, whether it can improve patients' quality of life remains uncertain. Therefore, we perform a meta-analysis of randomized controlled trials on this issue. Five randomized controlled trials total 1,212 patients were included. Fixed-effect model was used to calculate the weighted mean difference of score of Aging Males' Symptom rating scale. Our result reveals that testosterone replacement therapy improves patients' health-related quality of life in terms of the decrease in the AMS total score [WMD = -2.96 (-4.21, -1.71), p < .00001] and the psychological [WMD = -0.89 (-1.41, -0.37), p = .0008], somatic [WMD = -0.89 (-1.41, -0.37), p = .0008] and sexual [WMD = -1.29 (-1.75, -0.83), p < .00001] subscale score. © 2016 Blackwell Verlag GmbH.

CSF Flow in the Brain in the Context of Normal Pressure Hydrocephalus.

PubMed

Bradley, W G

2015-05-01

CSF normally flows back and forth through the aqueduct during the cardiac cycle. During systole, the brain and intracranial vasculature expand and compress the lateral and third ventricles, forcing CSF craniocaudad. During diastole, they contract and flow through the aqueduct reverses. Hyperdynamic CSF flow through the aqueduct is seen when there is ventricular enlargement without cerebral atrophy. Therefore, patients presenting with clinical normal pressure hydrocephalus who have hyperdynamic CSF flow have been found to respond better to ventriculoperitoneal shunting than those with normal or decreased CSF flow. Patients with normal pressure hydrocephalus have also been found to have larger intracranial volumes than sex-matched controls, suggesting that they may have had benign external hydrocephalus as infants. While their arachnoidal granulations clearly have decreased CSF resorptive capacity, it now appears that this is fixed and that the arachnoidal granulations are not merely immature. Such patients appear to develop a parallel pathway for CSF to exit the ventricles through the extracellular space of the brain and the venous side of the glymphatic system. This pathway remains functional until late adulthood when the patient develops deep white matter ischemia, which is characterized histologically by myelin pallor (ie, loss of lipid). The attraction between the bare myelin protein and the CSF increases resistance to the extracellular outflow of CSF, causing it to back up, resulting in hydrocephalus. Thus idiopathic normal pressure hydrocephalus appears to be a "2 hit" disease: benign external hydrocephalus in infancy followed by deep white matter ischemia in late adulthood. © 2015 by American Journal of Neuroradiology.

Ionic currents in the guinea-pig taenia coli.

PubMed Central

Inomata, H; Kao, C Y

1976-01-01

Short segments of portions of taenia coli of the guinea-pig averaging 54 mum X 219 mum X ca. 200 mum have been studied by a double sucrose-gap voltage-clamp technique. 2. The average total capacitance was 0-4 muF, corresponding to approximately 10(4) cells, if a specific membrane capacitance of 3 muF/cm2 were assumed. 3. A significant resistance, averaging 11-4omega, was in series with the membrane, and seriously limited the accuracy of the voltage control possible. 4. On depolarization, an early transient inward current was followed by a late maintained outwary current. 5. The late current was carried mainly by K+, because its direction could be reversed if the preparation were first depolarized in isotonic K2SO4 and held back to the original resting potential. 6. After appropriate corrections for residual capacitative and leakage currents, a reversal potential for the late current (Eb) was determined to be 15-20 mV more negative than the natural resting potential. It was not affected by the amplitude or the duration of the activating voltage step, but could be changed by prolonged applications of holding current. 7. At rest, the ratio of PNa:PK was 0-16:1; for Eb it was 0-05:1. 8. The reversal potential for the transient early inward current (Ea) averaged 22 mV in Krebs-bicarbonate solution, but was shifted to about 35 mV when the late current was first suppressed with tetraethylammonium ion. The shift suggested that there was some overlap of the early and late currents. 9. Reduction of [Na+]o to 50% of normal, or replacement of all Na+ with dimethyldiethanol ammonium ion and choline ion, failed to cause any significant shifts in the reversal potential of the early current or reduce the magnitude of the early current. 10. Reduction of [Ca2+]o to 0-25 or 0-1 of the normal caused shifts of the Ea toward the negative and reductions in the early current. These changes can occur without changes in the maximum chord conductance of the early current, such as might happen in ordinary Krebs-bicarbonate solution, or in preparations which had been depolarized by prior treatment with isotonic K2SO4 and then held back to the original membrane voltage. 11. Increase of [Ca2+]o to 5 times normal increased the early inward current, and the maximum chord conductances of the early and late currents, but did not shift the Ea. 12. In preparations pretreated with TEA, increasing [Ca2+]o to 5 times normal shifted Ea toward 45 mV. 13. The various observations are interpreted to mean that the early current in the taenia coli is carried principally by influx of Ca2+, and not by Na+. PMID:1255524

Late effects of childhood leukemia therapy.

PubMed

Fulbright, Joy M; Raman, Sripriya; McClellan, Wendy S; August, Keith J

2011-09-01

As survival rates for children treated for childhood cancers become significantly better, the focus is increasingly on determining the late effects of treatments and the best ways to monitor for them and prevent their occurrence. This review focuses on recent literature discussing the late effects of treatment in patients treated for acute myeloid leukemia and acute lymphoblastic leukemia during childhood. The late effects of therapy for childhood leukemia include secondary malignancy, cardiotoxicity, obesity, endocrine abnormalities, reproductive changes, neurocognitive deficits, and psychosocial effects. As clinicians have become more aware of the late effects of therapy, treatment regimens have been changed to decrease late effects, but patients still require long-term follow-up for their prevention and treatment.

[Effect of tranilast on wound healing and administration time on scar hyperplasia of deep partial-thickness burn in mice].

PubMed

Hu, Zhenzhen; Chen, Bin; Li, Yang; Jiang, Wei; Wen, Lihong; Ji, Fukang; Yang, Xiao; Wang, Jinhuang; Liu, Dalie

2017-04-01

To investigate the effect of tranilast on wound healing and the mechanism of inhibiting scar hyperplasia in mice, and to study the relationship between the inhibiting ability of tranilast on scar hyperplasia and administration time. Sixty-six Kunming mice were selected to build deep II degree burn model, and were randomly divided into the control group (18 mice), the early intervention group (18 mice), the medium intervention group (18 mice), and the late intervention group (12 mice). The mice in the early intervention group, the medium-term intervention group, and the late intervention group were given tranilast 200 mg/(kg·d) by gastrogavage at immediate, 7 days, and 14 days after burn respectively, and the mice in the control group were managed with same amount of normal saline every day. The wound healing was observed regularly. At 14, 28, and 42 days in the early and medium intervention groups and at 28 and 42 days in the late intervention group, fresh tissues were taken from 6 mice to observe the shape of mast cells by toluidine blue staining, collagen content by Masson staining; the collagen type I and collagen type III content were measured to calculate the I/III collagen content ratio by immunohistochemistry method, the contents of transforming growth factor β 1 (TGF-β 1 ) and histamine were detected by ELISA; and the ultrastructure of fibroblasts was observed under transmission electron microscope. There was no significant difference in wound healing time between groups ( F =1.105, P =0.371). The mast cells number, collagen content, TGF-β 1 content, histamine content, and the I/III collagen content ratio in the early intervention group were significantly less than those in the other groups ( P <0.05). Significant difference was found in mast cells number, collagen content, and histamine content between control group and medium or late intervention group at the other time points ( P <0.05) except between control group and late intervention group at 42 days ( P >0.05). Compared with the control group, the activity of fibroblasts in the early intervention group was obviously inhibited, and the arrangement of the fibers was more regular; the fibroblast activity in the medium and late intervention groups was also inhibited obviously. Tranilast has no obvious effect on the wound healing time in mice. Tranilast intervention shows the inhibitory effect on the scar hyperplasia which can significantly reduce the number of mast cells, the content of histamine and TGF-β 1 , inhibit the ability of fibroblasts synthetic collagen and adjust the proportion of collagen synthesis. The immediate tranilast intervention may have the best inhibitory effect on scar hyperplasia.

ASSOCIATION BETWEEN GAB2 HAPLOTYPE AND HIGHER GLUCOSE METABOLISM IN ALZHEIMER'S DISEASE-AFFECTED BRAIN REGIONS IN COGNITIVELY NORMAL APOEε4 CARRIERS

PubMed Central

Liang, Winnie S.; Chen, Kewei; Lee, Wendy; Sidhar, Kunal; Corneveaux, Jason J.; Allen, April N.; Myers, Amanda; Villa, Stephen; Meechoovet, Bessie; Pruzin, Jeremy; Bandy, Daniel; Fleisher, Adam S.; Langbaum, Jessica B.S.; Huentelman, Matthew J.; Jensen, Kendall; Dunckley, Travis; Caselli, Richard J.; Kaib, Susan; Reiman, Eric M.

2010-01-01

In a genome-wide association study (GWAS) of late-onset Alzheimer's disease (AD), we found an association between common haplotypes of the GAB2 gene and AD risk in carriers of the apolipoprotein E (APOE) ε4 allele, the major late-onset AD susceptibility gene. We previously proposed the use of fluorodeoxyglucose positron emission tomography (FDG-PET) measurements as a quantitative presymptomatic endophenotype, more closely related to disease risk than the clinical syndrome itself, to help evaluate putative genetic and non-genetic modifiers of AD risk. In this study, we examined the relationship between the presence or absence of the relatively protective GAB2 haplotype and PET measurements of regional-to-whole brain FDG uptake in several AD-affected brain regions in 158 cognitively normal late-middle-aged APOEε4 homozygotes, heterozygotes, and non-carriers. GAB2 haplotypes were characterized using Affymetrix Genome-Wide Human SNP 6.0 Array data from each of these subjects. As predicted, the possibly protective GAB2 haplotype was associated with higher regional-to-whole brain FDG uptake in AD-affected brain regions in APOEε4 carriers. While additional studies are needed, this study supports the association between the possibly protective GAB2 haplotype and the risk of late-onset AD in APOEε4 carriers. It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk. PMID:20888920

Iron promotes protein insolubility and aging in C. elegans.

PubMed

Klang, Ida M; Schilling, Birgit; Sorensen, Dylan J; Sahu, Alexandria K; Kapahi, Pankaj; Andersen, Julie K; Swoboda, Peter; Killilea, David W; Gibson, Bradford W; Lithgow, Gordon J

2014-11-01

Many late-onset proteotoxic diseases are accompanied by a disruption in homeostasis of metals (metallostasis) including iron, copper and zinc. Although aging is the most prominent risk factor for these disorders, the impact of aging on metallostasis and its role in proteotoxic disease remain poorly understood. Moreover, it is not clear whether a loss of metallostasis influences normal aging. We have investigated the role of metallostasis in longevity ofCaenorhabditis elegans. We found that calcium, copper, iron, and manganese levels increase as a function of age, while potassium and phosphorus levels tend to decrease. Increased dietary iron significantly accelerated the age-related accumulation of insoluble protein, a molecular pathology of aging. Proteomic analysis revealed widespread effects of dietary iron in multiple organelles and tissues. Pharmacological interventions to block accumulation of specific metals attenuated many models of proteotoxicity and extended normal lifespan. Collectively, these results suggest that a loss of metallostasis with aging contributes to age-related protein aggregation.

Faced with a dilemma: Danish midwives' experiences with and attitudes towards late termination of pregnancy.

PubMed

Christensen, Anne Vinggaard; Christiansen, Anne Hjøllund; Petersson, Birgit

2013-12-01

The introduction of prenatal screening for all pregnant women in Denmark in 2004 has lead to an increase in the number of late terminations of pregnancy after the 12th week of pregnancy. Midwives' experiences with late termination of pregnancy (TOP) are still poorly described in the scientific literature. To explore Danish midwives' experiences with and attitudes towards late TOP. Focus was on how midwives perceive their own role in late TOP, and how their professional identity is influenced by working with late TOP in a time where prenatal screening is rapidly developing. A qualitative study consisting of ten individual interviews with Danish midwives, all of whom had taken part in late TOP. Current practice of late TOP resembles the practice of normal deliveries and is influenced by a growing personalisation of the aborted foetus. The midwives strongly supported women's legal right to choose TOP and considerations about the foetus' right to live were suppressed. Midwives experienced a dilemma when faced with aborted foetuses that looked like newborns and when aborted foetuses showed signs of life after a termination. Furthermore, they were critical of how physicians counsel women/couples after prenatal diagnosis. The midwives' practice in relation to late TOP was characterised by an acknowledgement of the growing ethical status of the foetus and the emotional reactions of the women/couples going through late TOP. Other professions as well as structural factors at the hospital highly influenced the midwives' ability to organize their work with late terminations. There is a need for more thorough investigation of how to secure the best possible working conditions for midwives, and how to optimise the care for women/couples going through late TOP. © 2012 The Authors Scandinavian Journal of Caring Sciences © 2012 Nordic College of Caring Science.

Late injury of cancer therapy on the female reproductive tract

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grigsby, P.W.; Russell, A.; Bruner, D.

1995-03-30

The purpose of this article is to review the late effects of cancer therapy on the female reproductive tract. The anatomic sites detailed are the vulva, vagina, cervix, uterus, fallopian tubes, and ovaries. The available pathophysiology is discussed. Clinical syndromes are presented. Tolerance doses of irradiation for late effects are rarely presented in the literature and are reviewed where available. Management strategies for surgical, radiotherapeutic, and chemotherapeutic late effects are discussed. Endpoints for evaluation of therapeutic late effects have been formulated utilizing the symptons, objective, management, and analytic (SOMA) format. Late effects on the female reproductive tract from cancer therapymore » should be recognized and managed appropriately. A grading system for these effects is presented. Endpoints for late effects and tolls for the evaluation need to be further developed. 61 refs., 9 figs., 13 tabs.« less

Late radiation side-effects in three patients undergoing parotid irradiation for benign disease.

PubMed

Armour, A; Ghanna, P; O'Rielly, B; Habeshaw, T; Symonds, P

2000-01-01

We report three patients in whom standard radiation therapy was given and serious late radiation damage was seen. The first patient suffered recurrent parotiditis and a parotid fistula. He was treated initially with 20 Gy in ten fractions via a 300 kV field. Further irradiation was required 1 year later and 40 Gy was given in 2 Gy fractions by an oblique anterior and posterior wedged photon pair. Ten years later he developed localized temporal bone necrosis. The second patient, with pleomorphic salivary adenoma, developed localized temporal bone necrosis 6 years after 60 Gy had been given using standard fractionation and technique. The third patient received 55 Gy in 25 fractions for a pleomorphic salivary adenoma and after 3 years developed temporal bone necrosis. Sixteen years later the same patient developed cerebellar and brainstem necrosis. All patients developed chronic persistent infection during or shortly after the radiation therapy, which increased local tissue sensitivity to late radiation damage. As a result, severe bone, cerebellar and brainstem necrosis was observed at doses that are normally considered safe. We therefore strongly recommend that any infection in a proposed irradiated area should be treated aggressively, with surgical debridement if necessary, before radiotherapy is administered, or that infection developing during or after irradiation is treated promptly.

Imaginal Disc Abnormalities in Lethal Mutants of Drosophila

PubMed Central

Shearn, Allen; Rice, Thomas; Garen, Alan; Gehring, Walter

1971-01-01

Late lethal mutants of Drosophila melanogaster, dying after the larval stage of development, were isolated. The homozygous mutant larvae were examined for abnormal imaginal disc morphology, and the discs were injected into normal larval hosts to test their capacities to differentiate into adult structures. In about half of the mutants analyzed, disc abnormalities were found. Included among the abnormalities were missing discs, small discs incapable of differentiating, morphologically normal discs with limited capacities for differentiation, and discs with homeotic transformations. In some mutants all discs were affected, and in others only certain discs. The most extreme abnormal phenotype is a class of “discless” mutants. The viability of these mutant larvae indicates that the discs are essential only for the development of an adult and not of a larva. The late lethals are therefore a major source of mutants for studying the genetic control of disc formation. Images PMID:5002822

Motor Development of Premature Infants Born between 32 and 34 Weeks

PubMed Central

Prins, S. A.; von Lindern, J. S.; van Dijk, S.; Versteegh, F. G. A.

2010-01-01

Little is known about motor development in late preterm born infants. Our objective was to determine long-term outcome of motor skills of infants born between 32 and 34 weeks. All infants were assessed at corrected ages of 3 and 9 months, using the Alberta Infant Motor Scale. At corrected ages of 4 years, the Movement Assessment Battery for Children was done. Seventy infants were seen at 4 years of age (median of 3 assessments per infant). Abnormal assessment at 3 or 9 months of age resulted in normal outcome in almost 80% at 4 years. On the other hand, a normal outcome in the first year of life resulted in an abnormal outcome at 4 years in 10% of the infants. Our results suggest that long-term followup of these late preterm born infants is necessary, as the assessments in the first year do not predict the long-term outcome. PMID:20885965

Risk of Severe Toxicity According to Site of Recurrence in Patients Treated With Stereotactic Body Radiation Therapy for Recurrent Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ling, Diane C.; Vargo, John A.; Ferris, Robert L.

Purpose: To report a 10-year update of our institutional experience with stereotactic body radiation therapy (SBRT) for reirradiation of locally recurrent head and neck cancer, focusing on predictors of toxicity. Methods and Materials: A retrospective review was performed on 291 patients treated with SBRT for recurrent, previously irradiated head and neck cancer between April 2002 and March 2013. Logistic regression analysis was performed to identify predictors of severe acute and late toxicity. Patients with <3 months of follow-up (n=43) or who died within 3 months of treatment (n=21) were excluded from late toxicity analysis. Results: Median time to death or last clinicalmore » follow-up was 9.8 months among the entire cohort and 53.1 months among surviving patients. Overall, 33 patients (11.3%) experienced grade ≥3 acute toxicity and 43 (18.9%) experienced grade ≥3 late toxicity. Compared with larynx/hypopharynx, treatment of nodal recurrence was associated with a lower risk of severe acute toxicity (P=.03), with no significant differences in severe acute toxicity among other sites. Patients treated for a recurrence in the larynx/hypopharynx experienced significantly more severe late toxicity compared with those with oropharyngeal, oral cavity, base of skull/paranasal sinus, salivary gland, or nodal site of recurrence (P<.05 for all). Sixteen patients (50%) with laryngeal/hypopharyngeal recurrence experienced severe late toxicity, compared with 6-20% for other sites. Conclusions: Salvage SBRT is a safe and effective option for most patients with previously irradiated head and neck cancer. However, patients treated to the larynx or hypopharynx experience significantly more late toxicity compared with others and should be carefully selected for treatment, with consideration given to patient performance status, pre-existing organ dysfunction, and goals of care. Treatment toxicity in these patients may be mitigated with more conformal plans to allow for increased sparing of adjacent normal tissues.« less

Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease.

PubMed

Carrasquillo, Minerva M; Crook, Julia E; Pedraza, Otto; Thomas, Colleen S; Pankratz, V Shane; Allen, Mariet; Nguyen, Thuy; Malphrus, Kimberly G; Ma, Li; Bisceglio, Gina D; Roberts, Rosebud O; Lucas, John A; Smith, Glenn E; Ivnik, Robert J; Machulda, Mary M; Graff-Radford, Neill R; Petersen, Ronald C; Younkin, Steven G; Ertekin-Taner, Nilüfer

2015-01-01

We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM-rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Single dose irradiation response of pig skin: a comparison of brachytherapy using a single, high dose rate iridium-192 stepping source with 200 kV X-rays.

PubMed

Hamm, P C; Bakker, E J; van den Berg, A P; van den Aardweg, G J; Visser, A G; Levendag, P C

2000-07-01

An experimental brachytherapy model has been developed to study acute and late normal tissue reactions as a tool to examine the effects of clinically relevant multifractionation schedules. Pig skin was used as a model since its morphology, structure, cell kinetics and radiation-induced responses are similar to human skin. Brachytherapy was performed using a microSelectron high dose rate (HDR) afterloading machine with a single stepping source and a custom-made template. In this study the acute epidermal reactions of erythema and moist desquamation and the late dermal reactions of dusky mauve erythema and necrosis were evaluated after single doses of irradiation over a follow-up period of 16 weeks. The major aims of this work were: (a) to compare the effects of iridium-192 (192Ir) irradiation with effects after X-irradiation; (b) to compare the skin reactions in Yorkshire and Large White pigs; and (c) to standardize the methodology. For 192Ir irradiation with 100% isodose at the skin surface, the 95% isodose was estimated at the basal membrane, while the 80% isodose covered the dermal fat layers. After HDR 192Ir irradiation of Yorkshire pig skin the ED50 values (95% isodose) for moderate/severe erythema and moist desquamation were 24.8 Gy and 31.9 Gy, respectively. The associated mean latent period (+/- SD) was 39 +/- 7 days for both skin reactions. Late skin responses of dusky mauve erythema and dermal necrosis were characterized by ED50 values (80% isodose) of 16.3 Gy and 19.5 Gy, with latent periods of 58 +/- 7 days and 76 +/- 12 days, respectively. After X-irradiation, the incidence of the various skin reactions and their latent periods were similar. Acute and late reactions were well separated in time. The occurrence of skin reactions and the incidence of effects were comparable in Yorkshire and Large White pigs for both X-irradiation and HDR 192Ir brachytherapy. This pig skin model is feasible for future studies on clinically relevant multifractionation schedules in a brachytherapy setting.

Right Ventricular Tissue Doppler Assessment in Space During Circulating Volume Modification using the Braslet-M Device

NASA Technical Reports Server (NTRS)

Hamilton, D. R.; Sargsyan, A. E.; Fincke, E. M.; Magnus, S. H.; Lonchakov, Y. V.; Alferova, I. V.; Dulchavsky, S. A.; Ebert, D.; Garcia, K.; Martin, D.;

Knowledge and risk perception of late effects among childhood cancer survivors and parents before and after visiting a childhood cancer survivor clinic.

PubMed

Cherven, Brooke; Mertens, Ann; Meacham, Lillian R; Williamson, Rebecca; Boring, Cathy; Wasilewski-Masker, Karen

2014-01-01

Survivors of childhood cancer are at risk for a variety of treatment-related late effects and require lifelong individualized surveillance for early detection of late effects. This study assessed knowledge and perceptions of late effects risk before and after a survivor clinic visit. Young adult survivors (≥ 16 years) and parents of child survivors (< 16 years) were recruited prior to initial visit to a cancer survivor program. Sixty-five participants completed a baseline survey and 50 completed both a baseline and follow-up survey. Participants were found to have a low perceived likelihood of developing a late effect of cancer therapy and many incorrect perceptions of risk for individual late effects. Low knowledge before clinic (odds ratio = 9.6; 95% confidence interval, 1.7-92.8; P = .02) and low perceived likelihood of developing a late effect (odds ratio = 18.7; 95% confidence interval, 2.7-242.3; P = .01) were found to predict low knowledge of late effect risk at follow-up. This suggests that perceived likelihood of developing a late effect is an important factor in the individuals' ability to learn about their risk and should be addressed before initiation of education. © 2014 by Association of Pediatric Hematology/Oncology Nurses.

Report on forest tree seed crop in New England in 1957

Treesearch

A. C. Hart

1958-01-01

Forest tree seed crops were generally poor in 1957 throughout New England, according to reports by observers. Late spring frosts and below-normal precipitation were probably responsible for poor or failing crops of some species.

TRACTOGRAPHY DENSITY AND NETWORK MEASURES IN ALZHEIMER'S DISEASE.

PubMed

Prasad, Gautam; Nir, Talia M; Toga, Arthur W; Thompson, Paul M

2013-04-01

Brain connectivity declines in Alzheimer's disease (AD), both functionally and structurally. Connectivity maps and networks derived from diffusion-based tractography offer new ways to track disease progression and to understand how AD affects the brain. Here we set out to identify (1) which fiber network measures show greatest differences between AD patients and controls, and (2) how these effects depend on the density of fibers extracted by the tractography algorithm. We computed brain networks from diffusion-weighted images (DWI) of the brain, in 110 subjects (28 normal elderly, 56 with early and 11 with late mild cognitive impairment, and 15 with AD). We derived connectivity matrices and network topology measures, for each subject, from whole-brain tractography and cortical parcellations. We used an ODF lookup table to speed up fiber extraction, and to exploit the full information in the orientation distribution function (ODF). This made it feasible to compute high density connectivity maps. We used accelerated tractography to compute a large number of fibers to understand what effect fiber density has on network measures and in distinguishing different disease groups in our data. We focused on global efficiency, transitivity, path length, mean degree, density, modularity, small world, and assortativity measures computed from weighted and binary undirected connectivity matrices. Of all these measures, the mean nodal degree best distinguished diagnostic groups. High-density fiber matrices were most helpful for picking up the more subtle clinical differences, e.g. between mild cognitively impaired (MCI) and normals, or for distinguishing subtypes of MCI (early versus late). Care is needed in clinical analyses of brain connectivity, as the density of extracted fibers may affect how well a network measure can pick up differences between patients and controls.

Activation of the Cannabinoid Type 2 Receptor by a Novel Indazole Derivative Normalizes the Survival Pattern of Lymphoblasts from Patients with Late-Onset Alzheimer's Disease.

PubMed

Del Cerro, Patricia; Alquézar, Carolina; Bartolomé, Fernando; González-Naranjo, Pedro; Pérez, Concepción; Carro, Eva; Páez, Juan A; Campillo, Nuria E; Martín-Requero, Ángeles

2018-05-07

Alzheimer's disease is a multifactorial disorder for which there is no disease-modifying treatment yet. CB2 receptors have emerged as a promising therapeutic target for Alzheimer's disease because they are expressed in neuronal and glial cells and their activation has no psychoactive effects. The aim of this study was to investigate whether activation of the CB2 receptor would restore the aberrant enhanced proliferative activity characteristic of immortalized lymphocytes from patients with late-onset Alzheimer's disease. It is assumed that cell-cycle dysfunction occurs in both peripheral cells and neurons in patients with Alzheimer's disease, contributing to the instigation of the disease. Lymphoblastoid cell lines from patients with Alzheimer's disease and age-matched control individuals were treated with a new, in-house-designed dual drug PGN33, which behaves as a CB2 agonist and butyrylcholinesterase inhibitor. We analyzed the effects of this compound on the rate of cell proliferation and levels of key regulatory proteins. In addition, we investigated the potential neuroprotective action of PGN33 in β-amyloid-treated neuronal cells. We report here that PGN33 normalized the increased proliferative activity of Alzheimer's disease lymphoblasts. The compound blunted the calmodulin-dependent overactivation of the PI3K/Akt pathway, by restoring the cyclin-dependent kinase inhibitor p27 levels, which in turn reduced the activity of the cyclin-dependent kinase/pRb cascade. Moreover, this CB2 agonist prevented β-amyloid-induced cell death in neuronal cells. Our results suggest that the activation of CB2 receptors could be considered a useful therapeutic approach for Alzheimer's disease.

Geomagnetic Reversals of the Late Jurassic and Early Cretaceous Captured in a North China Core

NASA Astrophysics Data System (ADS)

Kuhn, T.; Fu, R. R.; Kent, D. V.; Olsen, P. E.

2016-12-01

The Tuchengzi formation in North China nominally spans nearly 20 million years of the Late Jurassic and Early Cretaceous, an interval during which age calibration of the Geomagnetic Polarity Time Scale (GPTS) based on seafloor magnetic anomalies is poorly known. The overlying Yixian formation is of special paleontological interest due to an abundance of spectacularly preserved macrofossils of feathered non-avian dinosaurs, birds, mammals, and insects. Scarce fossils in the Tuchengzi, sparse accurate radiometric dates on both the Tuchengzi and overlying Yixian formation, and scant previous paleomagnetic studies on these formations motivated our application of magnetostratigraphy as a geochronological tool. We constructed a geomagnetic reversal sequence from the upper 142m of a 200m core extracted in Liaoning Province at Huangbanjigou spanning the lower Yixian Formation and the unconformably underlying Tuchengzi Formation. Thermal demagnetization up to 680°C in steps of 25-50°C revealed predominantly normal overprints consistent with the modern day field with unblocking temperatures between 125°C and as high as 550°C, as well as normal and reverse characteristic components with unblocking temperatures between 500°C and 680°C. Going up from the base of the core, there is a reverse polarity magnetozone >6m thick, followed by a 5m normal magnetozone, a 10m reverse magnetozone, a 25m normal magnetozone, and a 6m reverse magnetozone truncated by the Yixian-Tuchengzi unconformity. Above the unconformity, all 81m of core were normal. These results indicate that a meaningful polarity stratigraphy can be recovered from the Tuchengzi and Yixian formations that will be invaluable for correlations across the Tuchengzi and potentially the Yixian formations, which span thousands of square kilometers and vary in thickness by many hundreds of meters. The results also demonstrate that, in combination with accurate and precise radiometric dates, the Tuchengzi Formation has the potential to provide tight constraints on presently poorly constrained Late Jurassic and Early Cretaceous parts of the GPTS and provide an independent reversal time scale by which seafloor-anomaly based time scales can be refined.

Late onset GM2 gangliosidosis mimicking spinal muscular atrophy.

PubMed

Jamrozik, Z; Lugowska, A; Gołębiowski, M; Królicki, L; Mączewska, J; Kuźma-Kozakiewicz, M

2013-09-25

A case of late onset GM2 gangliosidodis with spinal muscular atrophy phenotype followed by cerebellar and extrapyramidal symptoms is presented. Genetic analysis revealed compound heterozygous mutation in exon 10 of the HEXA gene. Patient has normal intelligence and emotional reactivity. Neuroimaging tests of the brain showed only cerebellar atrophy consistent with MR spectroscopy (MRS) abnormalities. (18)F-fluorodeoxyglucose positron emission tomography (18)F-FDG PET/CT of the brain revealed glucose hypometabolism in cerebellum and in temporal and occipital lobes bilaterally. © 2013 Elsevier B.V. All rights reserved.

Cognitive Impairment and Structural Abnormalities in Late Life Depression with Olfactory Identification Impairment: an Alzheimer's Disease-Like Pattern.

PubMed

Chen, Ben; Zhong, Xiaomei; Mai, Naikeng; Peng, Qi; Wu, Zhangying; Ouyang, Cong; Zhang, Weiru; Liang, Wanyuan; Wu, Yujie; Liu, Sha; Chen, Lijian; Ning, Yuping

2018-03-15

Late-life depression patients are at a high risk of developing Alzheimer's disease, and diminished olfactory identification is an indicator in early screening for Alzheimer's disease in the elderly. However, whether diminished olfactory identification is associated with risk of developing Alzheimer's disease in late-life depression patients remains unclear. One hundred and twenty-five late-life depression patients, 50 Alzheimer's disease patients, and 60 normal controls were continuously recruited. The participants underwent a clinical evaluation, olfactory test, neuropsychological assessment, and neuroimaging assessment. The olfactory identification impairment in late-life depression patients was milder than that in Alzheimer's disease patients. Diminished olfactory identification was significantly correlated with worse cognitive performance (global function, memory language, executive function, and attention) and reduced grey matter volume (olfactory bulb and hippocampus) in the late-life depression patients. According to a multiple linear regression analysis, olfactory identification was significantly associated with the memory scores in late-life depression group (B=1.623, P<.001). The late-life depression with olfactory identification impairment group had worse cognitive performance (global, memory, language, and executive function) and more structural abnormalities in Alzheimer's disease-related regions than the late-life depression without olfactory identification impairment group, and global cognitive function and logical memory in the late-life depression without olfactory identification impairment group was intact. Reduced volume observed in many areas (hippocampus, precuneus, etc.) in the Alzheimer's disease group was also observed in late-life depression with olfactory identification impairment group but not in the late-life depression without olfactory identification impairment group. The patterns of cognitive impairment and structural abnormalities in late-life depression with olfactory identification impairment patients were similar to those in Alzheimer's disease; olfactory identification may help identify late-life depression patients who are at a high risk of developing Alzheimer's disease.

The relationship of the oestrogen and progestin receptors in the abnormal uterus of the adult anovulatory rat. Effects of neonatal treatment with testosterone propionate or clomiphene citrate.

PubMed Central

White, J O; Moore, P A; Elder, M G; Lim, L

1981-01-01

The neonatal administration of testosterone propionate to Wistar rats resulted in anovulatory adults in persistent vaginal oestrus. Clomiphene citrate had a similar effect. In both groups of adults, hyperplasia of the uterine epithelium and occasional metaplasia was observed. The uterine nuclear and cytosol oestrogen and progestin receptors of these anovulatory rats were found to have affinities for their respective ligands similar to those of normal females. The nuclear oestrogen receptor comprised occupied and unoccupied components, as in normal females. The content of the nuclear oestrogen receptor was comparable with that of females in the late dioestrous or pro-oestrous phase. This content was higher in the clomiphene-treated group. Despite the relatively high nuclear oestrogen receptor content the content of progestin receptors, a putative index of the oestrogenic response, was lower in the treated rats than in normal adult females throughout the cycle. Administration of oestradiol to both treatment groups resulted in depletion of cytosol oestrogen receptor content 1 h later, which, however, was not reflected by an increase in the content of nuclear oestrogen receptors. There was no measurable increase in progesterone receptor content in treated rats after daily administration of oestrogen (5 microgram/rat) for 3 days. These changes in sex-hormone-receptor interactions involving an impairment of the normal oestrogenic response may be associated with the abnormal differentiation of the uterus in these sterile, anovulatory animals. Images Fig. 1. Fig. 2. PMID:7316994

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toki, Hideaki; Minowa, Osamu; Inoue, Maki

Dominant mutations in the Serca2 gene, which encodes sarco(endo)plasmic reticulum calcium-ATPase, predispose mice to gastrointestinal epithelial carcinoma [1–4] and humans to Darier disease (DD) [14–17]. In this study, we generated mice harboring N-ethyl-N-nitrosourea (ENU)-induced allelic mutations in Serca2: three missense mutations and one nonsense mutation. Mice harboring these Serca2 mutations developed tumors that were categorized as either early onset squamous cell tumors (SCT), with development similar to null-type knockout mice [2,4] (aggressive form; M682, M814), or late onset tumors (mild form; M1049, M1162). Molecular analysis showed no aberration in Serca2 mRNA or protein expression levels in normal esophageal cells ofmore » any of the four mutant heterozygotes. There was no loss of heterozygosity at the Serca2 locus in the squamous cell carcinomas in any of the four lines. The effect of each mutation on Ca{sup 2+}-ATPase activity was predicted using atomic-structure models and accumulated mutated protein studies, suggesting that putative complete loss of Serca2 enzymatic activity may lead to early tumor onset, whereas mutations in which Serca2 retains residual enzymatic activity result in late onset. We propose that impaired Serca2 gene product activity has a long-term effect on squamous cell carcinogenesis from onset to the final carcinoma stage through an as-yet unrecognized but common regulatory pathway. -- Highlights: •Novel mutations in murine Serca2 caused early onset or late onset of tumorigenesis. •They also caused higher or lower incidence of Darier Disease phenotype. •3D structure model suggested the former mutations led to severer defect on ATPase. •Driver gene mutations via long-range effect on Ca2+ distributions are suggested.« less

Multimodal Characterization of the Late Effects of Traumatic Brain Injury: A Methodological Overview of the Late Effects of Traumatic Brain Injury Project.

PubMed

Edlow, Brian L; Keene, C Dirk; Perl, Daniel P; Iacono, Diego; Folkerth, Rebecca D; Stewart, William; Mac Donald, Christine L; Augustinack, Jean; Diaz-Arrastia, Ramon; Estrada, Camilo; Flannery, Elissa; Gordon, Wayne A; Grabowski, Thomas J; Hansen, Kelly; Hoffman, Jeanne; Kroenke, Christopher; Larson, Eric B; Lee, Patricia; Mareyam, Azma; McNab, Jennifer A; McPhee, Jeanne; Moreau, Allison L; Renz, Anne; Richmire, KatieRose; Stevens, Allison; Tang, Cheuk Y; Tirrell, Lee S; Trittschuh, Emily H; van der Kouwe, Andre; Varjabedian, Ani; Wald, Lawrence L; Wu, Ona; Yendiki, Anastasia; Young, Liza; Zöllei, Lilla; Fischl, Bruce; Crane, Paul K; Dams-O'Connor, Kristen

2018-05-03

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole-mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.

Leuprolide acetate-stimulated androgen response during female puberty.

PubMed

Hernandez, María Isabel; Martinez-Aguayo, Alejandro; Cavada, Gabriel; Avila, Alejandra; Iñiguez, German; Mericq, Veronica

2015-08-01

A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders. The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. To assess circulating levels of ovarian androgens and anti-Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH-a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity. Prospective study of healthy girls (6-12 years) from the local community (n = 63). Tanner I (n = 23) subjects were assessed cross-sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA-S), AMH, sex hormone-binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH-a test (500 μg/m(2) ; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated. Basal and/or stimulated Testosterone DHEA-S and 17-hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian-steroidogenic response was most evident during mid- and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA-S were positively associated with gonadotrophins. In normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with insulin sensitivity in early puberty and with LH only in late puberty. © 2014 John Wiley & Sons Ltd.

Barbiturates Block Sodium and Potassium Conductance Increases in Voltage-Clamped Lobster Axons

PubMed Central

Blaustein, M. P.

1968-01-01

Sodium pentobarbital and sodium thiopental decrease both the peak initial (Na) and late steady-state (K) currents and reduce the maximum sodium and potassium conductance increases in voltage-clamped lobster giant axons. These barbiturates also slow the rate at which the sodium conductance turns on, and shift the normalized sodium conductance vs. voltage curves in the direction of depolarization along the voltage axis. Since pentobarbital (pKa = 8.0) blocks the action potential more effectively at pH 8.5 than at pH 6.7, the anionic form of the drug appears to be active. The data suggest that these drugs affect the axon membrane directly, rather than secondarily through effects on intermediary metabolism. It is suggested that penetration of the lipid layer of the membrane by the nonpolar portion of the barbiturate molecules may cause the decrease in membrane conductances, while electrostatic interactions involving the anionic group on the barbiturate, divalent cations, and "fixed charges" in the membrane could account for the slowing of the rate of sodium conductance turn-on and the shift of the normalized conductance curves along the voltage axis. PMID:5648829

EDITORIAL: Focus on Heavy Ions in Biophysics and Medical Physics FOCUS ON HEAVY IONS IN BIOPHYSICS AND MEDICAL PHYSICS

NASA Astrophysics Data System (ADS)

Durante, Marco

2008-07-01

Interest in energetic heavy ions is rapidly increasing in the field of biomedicine. Heavy ions are normally excluded from radiation protection, because they are not normally experienced by humans on Earth. However, knowledge of heavy ion biophysics is necessary in two fields: charged particle cancer therapy (hadrontherapy), and radiation protection in space missions. The possibility to cure tumours using accelerated heavy charged particles was first tested in Berkeley in the sixties, but results were not satisfactory. However, about 15 years ago therapy with carbon ions was resumed first in Japan and then in Europe. Heavy ions are preferable to photons for both physical and biological characteristics: the Bragg peak and limited lateral diffusion ensure a conformal dose distribution, while the high relative biological effectiveness and low oxygen enhancement ration in the Bragg peak region make the beam very effective in treating radioresistant and hypoxic tumours. Recent results coming from the National Institute of Radiological Sciences in Chiba (see the paper by Dr Tsujii and co-workers in this issue) and GSI (Germany) provide strong clinical evidence that heavy ions are indeed an extremely effective weapon in the fight against cancer. However, more research is needed in the field, especially on optimization of the treatment planning and risk of late effects in normal tissue, including secondary cancers. On the other hand, high-energy heavy ions are present in galactic cosmic radiation and, although they are rare as compared to protons, they give a major contribution in terms of equivalent dose to the crews of manned space exploratory-class missions. Exploration of the Solar System is now the main goal of the space program, and the risk caused by exposure to galactic cosmic radiation is considered a serious hindrance toward this goal, because of the high uncertainty on late effects of energetic heavy nuclei, and the lack of effective countermeasures. Risks include carcinogenesis, late degenerative tissue effects (including damage to the central nervous system), and hereditary effects. For these studies, microbeams represent an essential tool, considering that in space each cell in the human body will not experience more than one heavy-ion traversal. Both NASA and ESA are investing important resources in ground-based space radiation research programs, to reduce risk uncertainty and to develop countermeasures. For both cancer therapy and space radiation protection a better understanding of the effects of energetic heavy ions is needed. Physics should be improved, especially the measurements of nuclear fragmentation cross-sections, and the transport calculations. Biological effects need to be studied in greater detail, and clearly only understanding the mechanisms of heavy-ion induced biological damage will reduce the uncertainty on late effects in humans. This focus issue of New Journal of Physics aims to provide the state-of-the-art of the biophysics of energetic heavy ions and to highlight the areas where more research is urgently needed for therapy and the space program. Focus on Heavy Ions in Biophysics and Medical Physics Contents Heavy ion microprobes: a unique tool for bystander research and other radiobiological applications K O Voss, C Fournier and G Taucher-Scholz Heavy ions light flashes and brain functions: recent observations at accelerators and in spaceflight L Narici Clinical advantages of carbon-ion radiotherapy Hirohiko Tsujii, Tadashi Kamada, Masayuki Baba, Hiroshi Tsuji, Hirotoshi Kato, Shingo Kato, Shigeru Yamada, Shigeo Yasuda, Takeshi Yanagi, Hiroyuki Kato, Ryusuke Hara, Naotaka Yamamoto and Junetsu Mizoe Heavy-ion effects: from track structure to DNA and chromosome damage F Ballarini, D Alloni, A Facoetti and A Ottolenghi Shielding experiments with high-energy heavy ions for spaceflight applications C Zeitlin, S Guetersloh, L Heilbronn, J Miller, N Elkhayari, A Empl, M LeBourgeois, B W Mayes, L Pinsky, M Christl and E Kuznetsov Heavy charged particles in radiation biology and biophysics H Nikjoo, S Uehara, D Emfietzoglou and A Brahme Impact of track structure calculations on biological treatment planning in ion radiotherapy Thilo Elsässer, Richard Cunrath, Michael Krämer and Michael Scholz The physical basis for the biological action of heavy ions Jürgen Kiefer Secondary beam fragments produced by 200 MeV u-1 12C ions in water and their dose contributions in carbon ion radiotherapy K Gunzert-Marx, H Iwase, D Schardt and R S Simon

Cathepsin B expression in colorectal cancer in a Middle East population: Potential value as a tumor biomarker for late disease stages

PubMed Central

Abdulla, Maha-Hamadien; Valli-Mohammed, Mansoor-Ali; Al-Khayal, Khayal; Shkieh, Abdulmalik Al; Zubaidi, Ahmad; Ahmad, Rehan; Al-Saleh, Khalid; Al-Obeed, Omar; McKerrow, James

2017-01-01

Cathepsin B (CTSB), is a cysteine protease belonging to the cathepsin (Clan CA) family. The diagnostic and prognostic significance of increased CTSB in the serum of cancer patients have been evaluated for some tumor types. CTSB serum and protein levels have also been reported previously in colorectal cancer (CRC) with contradictory results. The aim of the present study was to investigate CTSB expression in CRC patients and the association of CTSB expression with various tumor stages in a Middle East population. Serum CTSB levels were evaluated in 70 patients and 20 healthy control subjects using enzyme-linked immunosorbant assay (ELISA) technique. CTSB expression was determined in 100 pairs of CRC tumor and adjacent normal colonic tissue using quantitative PCR for mRNA levels. Detection of CTSB protein expression in tissues was carried out using both immunohistochemistry and western blotting techniques. ELISA analysis showed that in sera obtained from CRC patients, the CTSB concentration was significantly higher in late stage patients with lymph node metastases when compared to early stage patients with values of 2.9 and 0.33 ng/ml, respectively (P=0.001). The majority of tumors studied had detectable CTSB protein expression with significant increased positive staining in tumors cells when compared with matched normal colon subjects (P=0.006). The mRNA expression in early stage CRC compared to late stage CRC was 0.04±0.01 and 0.07±0.02, respectively. Increased mRNA expression was more frequently observed in the advanced cancer stages with lymph node metastases when compared with the control (P=0.002). Mann-Whitney test and paired t-test were used to compare serum CTSB and mRNA levels in early and late tumor stage. A subset of four paired tissue extracts were analyzed by western blotting. The result confirmed a consistent increase in the CTSB protein expression level in tumor tissues compared with that noted in the adjacent normal mucosal cells. These findings indicate that CTSB may be an important prognostic biomarker for late stage CRC and cases with lymph node metastases in the Middle Eastern population. Monitoring serum CTSB in CRC patients may predict and/or diagnose cases with lymph node metastases. PMID:28440429

Early Menarche and Gestational Diabetes Mellitus at First Live Birth.

PubMed

Shen, Yun; Hu, Hui; D Taylor, Brandie; Kan, Haidong; Xu, Xiaohui

2017-03-01

To examine the association between early menarche and gestational diabetes mellitus (GDM). Data from the National Health and Nutrition Examination Survey 2007-2012 were used to investigate the association between age at menarche and the risk of GDM at first birth among 5914 women. A growth mixture model was used to detect distinctive menarche onset patterns based on self-reported age at menarche. Logistic regression models were then used to examine the associations between menarche initiation patterns and GDM after adjusting for sociodemographic factors, family history of diabetes mellitus, lifetime greatest Body Mass Index, smoking status, and physical activity level. Among the 5914 first-time mothers, 3.4 % had self-reported GDM. We detected three groups with heterogeneous menarche onset patterns, the Early, Normal, and Late Menarche Groups. The regression model shows that compared to the Normal Menarche Group, the Early Menarche Group had 1.75 (95 % CI 1.10, 2.79) times the odds of having GDM. No statistically significant difference was observed between the Normal and the Late Menarche Group. This study suggests that early menarche may be a risk factor of GDM. Future studies are warranted to examine and confirm this finding.

Fusion of Ultrasound Tissue-Typing Images with Multiparametric MRI for Image-guided Prostate Cancer Radiation Therapy

DTIC Science & Technology

2014-10-01

work under the guidance of an outstanding mentor team at Emory Winship Cancer Institute. I took three courses ( Medical Health Physics, Radiation...and Late Normal-Tissue Toxicity in Breast- Cancer Radiotherapy”, Medical Physics, 40(6):379, 2013. 5. Yang X, Liu T, Curran W and Torres M...Analysis for Normal-tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast- Cancer Radiotherapy", Medical Physics 41 (6), 482-482

Creb1 regulates late stage mammalian lung development via respiratory epithelial and mesenchymal-independent mechanisms

PubMed Central

Antony, N.; McDougall, A. R.; Mantamadiotis, T.; Cole, T. J.; Bird, A. D.

2016-01-01

During mammalian lung development, the morphological transition from respiratory tree branching morphogenesis to a predominantly saccular architecture, capable of air-breathing at birth, is dependent on physical forces as well as molecular signaling by a range of transcription factors including the cAMP response element binding protein 1 (Creb1). Creb1−/− mutant mice exhibit complete neonatal lethality consistent with a lack of lung maturation beyond the branching phase. To further define its role in the developing mouse lung, we deleted Creb1 separately in the respiratory epithelium and mesenchyme. Surprisingly, we found no evidence of a morphological lung defect nor compromised neonatal survival in either conditional Creb1 mutant. Interestingly however, loss of mesenchymal Creb1 on a genetic background lacking the related Crem protein showed normal lung development but poor neonatal survival. To investigate the underlying requirement for Creb1 for normal lung development, Creb1−/− mice were re-examined for defects in both respiratory muscles and glucocorticoid hormone signaling, which are also required for late stage lung maturation. However, these systems appeared normal in Creb1−/− mice. Together our results suggest that the requirement of Creb1 for normal mammalian lung morphogenesis is not dependent upon its expression in lung epithelium or mesenchyme, nor its role in musculoskeletal development. PMID:27150575

The influence of a reverse-reactivated normal fault on natural fracture geometries and relative chronologies at Castle Cove, Otway Basin

NASA Astrophysics Data System (ADS)

Debenham, Natalie; King, Rosalind C.; Holford, Simon P.

2018-07-01

Despite the ubiquity of normal faults that have undergone compressional inversion, documentation of the structural history of natural fractures around these structures is limited. In this paper, we investigate the geometries and relative chronologies of natural fractures adjacent to a reverse-reactivated normal fault, the Castle Cove Fault in the Otway Basin, southeast Australia. Local variations in strain resulted in greater deformation within the fault damage zone closer to the fault. Structural mapping within the damage zone reveals a complex tectonic history recording both regional and local perturbations in stress and a total of 11 fracture sets were identified, with three sets geometrically related to the Castle Cove Fault. The remaining fracture sets formed in response to local stresses at Castle Cove. Rifting in the late Cretaceous resulted in normal movement of the Castle Cove Fault and associated rollover folding, and the formation of the largest fracture set. Reverse-reactivation of the fault and associated anticlinal folding occurred during late Miocene to Pliocene compression. Rollover folding may have provided structural traps if seals were not breached by fractures, however anticlinal folding likely post-dated the main episodes of hydrocarbon generation and migration in the region. This study highlights the need to conduct careful reconstruction of the structural histories of fault zones that experienced complex reactivation histories when attempting to define off-fault fluid flow properties.

Tectonic evolution of the Fru\\vska Gora (NW Serbia) and implications for the late stage inversion of the Pannonian Basin

NASA Astrophysics Data System (ADS)

Novčić, Novak; Toljić, Marinko; Stojadinović, Uroš; Matenco, Liviu

2017-04-01

Indentation of Adria microplate during latest Miocene to Quaternary times created contraction and transcurrent movements distributed in the Dinarides Mountains and along its margin with the adjacent Pannonian Basin. Fru\\vska Gora of northern Serbia is one of the few areas along the southern margin of the Pannonian Basin where the kinematic effects of this late-stage inversion can be studied. These mountains are located along the Sava-Vardar Suture Zone as an isolated inselberg surrounded by Neogene deposits of the Pannonian Basin, exposing metamorphic rocks, Mesozoic ophiolites and sediments belonging to the Dinarides units. Our field kinematic study demonstrate that deformation structures are related to several Oligocene - Miocene extensional and latest Miocene - Quaternary contractional deformation events. These events took place during the differential rotational stages experienced by Fru\\vska Gora. This has created a gradual change in strike from N-S to E-W of three successive normal faulting episodes (Oligocene-Early Miocene, Early Miocene and Middle-Late Miocene), subsequently inverted by contractional deformation. This latter deformation took place during the continuous latest Miocene - Quaternary Adria indentation and was accompanied by yet another 40 degrees counter clockwise rotation of the entire Fru\\vska Gora. Almost all resulting contractional structures reactivate the pre-existing Oligocene - Miocene normal faults. This is reflected in the present-day morphology of Fruska Gora that has a large-scale flower-type of structural geometry formed during dextral transpression, as demonstrated by field kinematics and seismic interpretations. This overall geometry is significantly different when compared with other areas situated more westwards in a similar structural position in the Dinariders at their contact with the Pannonian Basin, such as Medvednica Mountains or Sava-Drava transpressional systems. The variation in offsets along the strike of the orogen demonstrate that the indentation into the Pannonian basin significantly decrease eastwards towards Fruska Gora, likely accommodating a large-scale variation in indentation mechanics across and along the Dinarides.

The Herpes Simplex Virus Virion Host Shutoff Protein Enhances Translation of Viral True Late mRNAs Independently of Suppressing Protein Kinase R and Stress Granule Formation.

PubMed

Dauber, Bianca; Poon, David; Dos Santos, Theodore; Duguay, Brett A; Mehta, Ninad; Saffran, Holly A; Smiley, James R

2016-07-01

The herpes simplex virus (HSV) virion host shutoff (vhs) RNase destabilizes cellular and viral mRNAs, suppresses host protein synthesis, dampens antiviral responses, and stimulates translation of viral mRNAs. vhs mutants display a host range phenotype: translation of viral true late mRNAs is severely impaired and stress granules accumulate in HeLa cells, while translation proceeds normally in Vero cells. We found that vhs-deficient virus activates the double-stranded RNA-activated protein kinase R (PKR) much more strongly than the wild-type virus does in HeLa cells, while PKR is not activated in Vero cells, raising the possibility that PKR might play roles in stress granule induction and/or inhibiting translation in restrictive cells. We tested this possibility by evaluating the effects of inactivating PKR. Eliminating PKR in HeLa cells abolished stress granule formation but had only minor effects on viral true late protein levels. These results document an essential role for PKR in stress granule formation by a nuclear DNA virus, indicate that induction of stress granules is the consequence rather than the cause of the translational defect, and are consistent with our previous suggestion that vhs promotes translation of viral true late mRNAs by preventing mRNA overload rather than by suppressing eIF2α phosphorylation. The herpes simplex virus vhs RNase plays multiple roles during infection, including suppressing PKR activation, inhibiting the formation of stress granules, and promoting translation of viral late mRNAs. A key question is the extent to which these activities are mechanistically connected. Our results demonstrate that PKR is essential for stress granule formation in the absence of vhs, but at best, it plays a secondary role in suppressing translation of viral mRNAs. Thus, the ability of vhs to promote translation of viral mRNAs can be largely uncoupled from PKR suppression, demonstrating that this viral RNase modulates at least two distinct aspects of RNA metabolism. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The effect of an acute sleep hygiene strategy following a late-night soccer match on recovery of players.

PubMed

Fullagar, Hugh; Skorski, Sabrina; Duffield, Rob; Meyer, Tim

2016-01-01

Elite soccer players are at risk of reduced recovery following periods of sleep disruption, particularly following late-night matches. It remains unknown whether improving sleep quality or quantity in such scenarios can improve post-match recovery. Therefore, the aim of this study was to investigate the effect of an acute sleep hygiene strategy (SHS) on physical and perceptual recovery of players following a late-night soccer match. In a randomised cross-over design, two highly-trained amateur teams (20 players) played two late-night (20:45) friendly matches against each other seven days apart. Players completed an SHS after the match or proceeded with their normal post-game routine (NSHS). Over the ensuing 48 h, objective sleep parameters (sleep duration, onset latency, efficiency, wake episodes), countermovement jump (CMJ; height, force production), YoYo Intermittent Recovery test (YYIR2; distance, maximum heart rate, lactate), venous blood (creatine kinase, urea and c-reactive protein) and perceived recovery and stress markers were collected. Sleep duration was significantly greater in SHS compared to NSHS on match night (P = 0.002, d = 1.50), with NSHS significantly less than baseline (P < 0.001, d = 1.95). Significant greater wake episodes occurred on match night for SHS (P = 0.04, d = 1.01), without significant differences between- or within-conditions for sleep onset latency (P = 0.12), efficiency (P = 0.39) or wake episode duration (P = 0.07). No significant differences were observed between conditions for any physical performance or venous blood marker (all P > 0.05); although maximum heart rate during the YYIR2 was significantly higher in NSHS than SHS at 36 h post-match (P = 0.01; d = 0.81). There were no significant differences between conditions for perceptual "overall recovery" (P = 0.47) or "overall stress" (P = 0.17). Overall, an acute SHS improved sleep quantity following a late-night soccer match; albeit without any improvement in physical performance, perceptual recovery or blood-borne markers of muscle damage and inflammation.

Argyrophilic grain disease as a neurodegenerative substrate in late-onset schizophrenia and delusional disorders.

PubMed

Nagao, Shigeto; Yokota, Osamu; Ikeda, Chikako; Takeda, Naoya; Ishizu, Hideki; Kuroda, Shigetoshi; Sudo, Koichiro; Terada, Seishi; Murayama, Shigeo; Uchitomi, Yosuke

2014-06-01

To study the relationship between neurodegenerative diseases including argyrophilic grain disease (AGD) and late-onset schizophrenia and delusional disorders (LOSD; onset ≥40 years of age), we pathologically examined 23 patients with LOSD, 71 age-matched normal controls, and 22 psychiatric disease controls (11 depression, six personality disorder, two bipolar disorders, and three neurotic disorders cases). In all LOSD cases (compared to age-matched normal controls), the frequencies of Lewy body disease (LBD), AGD, and corticobasal degeneration (CBD) were 26.1 % (11.3 %), 21.7 % (8.5 %), and 4.3 % (0.0 %), respectively. There was no case of pure Alzheimer's disease (AD). The total frequency of LBD, AGD, and CBD was significantly higher in LOSD cases than in normal controls. Argyrophilic grains were significantly more severe in LOSD than in controls, but were almost completely restricted to the limbic system and adjacent temporal cortex. In LOSD patients whose onset occurred at ≥65 years of age (versus age-matched normal controls), the frequencies of LBD and AGD were 36.4 % (19.4 %) and 36.4 % (8.3 %), respectively, and AGD was significantly more frequent in LOSD patients than in normal controls. In LOSD patients whose onset occurred at <65 years of age, the frequencies of LBD, AGD, and CBD were 16.7, 8.3, and 8.3 %, comparable to those of age-matched normal controls (10.2, 5.1, and 0.0 %). In all psychiatric cases, delusion was significantly more frequent in AGD cases than in cases bearing minimal AD pathology alone. Given these findings, LOSD patients may have heterogeneous pathological backgrounds, and AGD may be associated with the occurrence of LOSD especially after 65 years of age.

Mesozoic and Cenozoic structural evolution of North Oman: New insights from high-quality 3D seismic from the Lekhwair area

NASA Astrophysics Data System (ADS)

Bazalgette, Loïc; Salem, Hisham

2018-06-01

This paper highlights the role of Triassic-Jurassic extension and late Cretaceous compression in the Mesozoic-Cenozoic (Alpine) structuring of North Oman. The syn/post-Mesozoic regional structural evolution is usually documented as a succession of two stages of deformation. The Alpine 1 phase, late Cretaceous in age, occurred in association with two ophiolite obduction stages (Semail and Masirah ophiolites). It was characterised by strike slip to extensional deformation in the North Oman foreland basin sub-surface. The Alpine 2 phase, Miocene in age, was related to the continental collision responsible for both the Zagros orogen and the uplift of the Oman Mountains. The Alpine 2 deformation was transpressional to compressional. Observation and interpretation of good quality 3D seismic in the Lekhwair High area enabled the distinction of two earlier phases. Early Mesozoic extension occurred concomitantly with the regional Triassic to Jurassic rifting, developing Jurassic-age normal faults. Late Cretaceous compression occurred prior to the main Alpine 1 phase and triggered the inversion of Jurassic-seated normal faults as well as the initiation of compressional folds in the Cretaceous overburden. These early phases have been ignored or overlooked as part of the North Oman history although they are at the origin of structures hosting major local and regional hydrocarbon accumulations.

Proton Radiation Therapy for Head and Neck Cancer: A Review of the Clinical Experience to Date

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holliday, Emma B.; Frank, Steven J., E-mail: sjfrank@mdanderson.org

2014-06-01

Proton beam radiation has been used for cancer treatment since the 1950s, but recent increasing interest in this form of therapy and the construction of hospital-based and clinic-based facilities for its delivery have greatly increased both the number of patients and the variety of tumors being treated with proton therapy. The mass of proton particles and their unique physical properties (ie, the Bragg peak) allow proton therapy to spare normal tissues distal to the tumor target from incidental irradiation. Initial observations show that proton therapy is particularly useful for treating tumors in challenging locations close to nontarget critical structures. Specifically,more » improvements in local control outcomes for patients with chordoma, chonodrosarcoma, and tumors in the sinonasal regions have been reported in series using proton. Improved local control and survival outcomes for patients with cancer of the head and neck region have also been seen with the advent of improvements in better imaging and multimodality therapy comprising surgery, radiation therapy, and chemotherapy. However, aggressive local therapy in the proximity of critical normal structures to tumors in the head and neck region may produce debilitating early and late toxic effects. Great interest has been expressed in evaluating whether proton therapy can improve outcomes, especially early and late toxicity, when used in the treatment of head and neck malignancies. This review summarizes the progress made to date in addressing this question.« less

Prediction during language comprehension: benefits, costs, and ERP components.

PubMed

Van Petten, Cyma; Luka, Barbara J

2012-02-01

Because context has a robust influence on the processing of subsequent words, the idea that readers and listeners predict upcoming words has attracted research attention, but prediction has fallen in and out of favor as a likely factor in normal comprehension. We note that the common sense of this word includes both benefits for confirmed predictions and costs for disconfirmed predictions. The N400 component of the event-related potential (ERP) reliably indexes the benefits of semantic context. Evidence that the N400 is sensitive to the other half of prediction--a cost for failure--is largely absent from the literature. This raises the possibility that "prediction" is not a good description of what comprehenders do. However, it need not be the case that the benefits and costs of prediction are evident in a single ERP component. Research outside of language processing indicates that late positive components of the ERP are very sensitive to disconfirmed predictions. We review late positive components elicited by words that are potentially more or less predictable from preceding sentence context. This survey suggests that late positive responses to unexpected words are fairly common, but that these consist of two distinct components with different scalp topographies, one associated with semantically incongruent words and one associated with congruent words. We conclude with a discussion of the possible cognitive correlates of these distinct late positivities and their relationships with more thoroughly characterized ERP components, namely the P300, P600 response to syntactic errors, and the "old/new effect" in studies of recognition memory. Copyright © 2011 Elsevier B.V. All rights reserved.

The relationships between brain structural changes and perceived loneliness in older adults suffering from late-life depression.

PubMed

Sin, Emily L L; Liu, Ho-Ling; Lee, Shwu-Hua; Huang, Chih-Mao; Wai, Yau-Yau; Chen, Yao-Liang; Chan, Chetwyn C H; Lin, Chemin; Lee, Tatia M C

2018-04-01

Late-life depression is a significant health risk factor for older adults, part of which is perceived loneliness. In this voxel-based morphometry study, we examined the relationships between perceived loneliness and depression recurrence. Fifty-two older adults were recruited, and they were split into 3 groups: single episode, multiple episodes, or normal control groups, according to their clinical histories. This result suggests the level of functioning regarding the reward system may be negatively related to the number of depressive episodes. Taken together, the findings of this study offer important insight into the neural underpinnings of the course and chronicity of late-life depression. © 2017 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.

Interactive effects of obesity and physical fitness on risk of ischemic heart disease.

PubMed

Crump, C; Sundquist, J; Winkleby, M A; Sundquist, K

2017-02-01

Obesity and low physical fitness are known risk factors for ischemic heart disease (IHD), but their interactive effects are unclear. Elucidation of interactions between these common, modifiable risk factors may help inform more effective preventive strategies. We examined interactive effects of obesity, aerobic fitness and muscular strength in late adolescence on risk of IHD in adulthood in a large national cohort. We conducted a national cohort study of all 1 547 407 military conscripts in Sweden during 1969-1997 (97-98% of all 18-year-old males each year). Aerobic fitness, muscular strength and body mass index (BMI) measurements were examined in relation to IHD identified from outpatient and inpatient diagnoses through 2012 (maximum age 62 years). There were 38 142 men diagnosed with IHD in 39.7 million person years of follow-up. High BMI or low aerobic fitness (but not muscular strength) was associated with higher risk of IHD, adjusting for family history and socioeconomic factors. The combination of high BMI (overweight/obese vs normal) and low aerobic fitness (lowest vs highest tertile) was associated with highest IHD risk (incidence rate ratio, 3.11; 95% confidence interval (CI), 2.91-3.31; P<0.001). These exposures had no additive and a negative multiplicative interaction (that is, their combined effect was less than the product of their separate effects). Low aerobic fitness was a strong risk factor even among those with normal BMI. In this large cohort study, low aerobic fitness or high BMI at age 18 was associated with higher risk of IHD in adulthood, with a negative multiplicative interaction. Low aerobic fitness appeared to account for a similar number of IHD cases among those with normal vs high BMI (that is, no additive interaction). These findings suggest that interventions to prevent IHD should begin early in life and include not only weight control but aerobic fitness, even among persons of normal weight.

Speech and Speech-Related Quality of Life After Late Palate Repair: A Patient's Perspective.

PubMed

Schönmeyr, Björn; Wendby, Lisa; Sharma, Mitali; Jacobson, Lia; Restrepo, Carolina; Campbell, Alex

2015-07-01

Many patients with cleft palate deformities worldwide receive treatment at a later age than is recommended for normal speech to develop. The outcomes after late palate repairs in terms of speech and quality of life (QOL) still remain largely unstudied. In the current study, questionnaires were used to assess the patients' perception of speech and QOL before and after primary palate repair. All of the patients were operated at a cleft center in northeast India and had a cleft palate with a normal lip or with a cleft lip that had been previously repaired. A total of 134 patients (7-35 years) were interviewed preoperatively and 46 patients (7-32 years) were assessed in the postoperative survey. The survey showed that scores based on the speech handicap index, concerning speech and speech-related QOL, did not improve postoperatively. In fact, the questionnaires indicated that the speech became more unpredictable (P < 0.01) and that nasal regurgitation became worse (P < 0.01) for some patients after surgery. A total of 78% of the patients were still satisfied with the surgery and all of the patients reported that their self-confidence had improved after the operation. Thus, the majority of interviewed patients who underwent late primary palate repair were satisfied with the surgery. At the same time, speech and speech-related QOL did not improve according to the speech handicap index-based survey. Speech predictability may even become worse and nasal regurgitation may increase after late palate repair, according to these results.

Structure, paleogeographic inheritance, and deformation history of the southern Atlas foreland fold and thrust belt of Tunisia

NASA Astrophysics Data System (ADS)

SaïD, Aymen; Baby, Patrice; Chardon, Dominique; Ouali, Jamel

2011-12-01

Structural analysis of the southern Tunisian Atlas was carried out using field observation, seismic interpretation, and cross section balancing. It shows a mix of thick-skinned and thin-skinned tectonics with lateral variations in regional structural geometry and amounts of shortening controlled by NW-SE oblique ramps and tear faults. It confirms the role of the Late Triassic-Early Jurassic rifting inheritance in the structuring of the active foreland fold and thrust belt of the southern Tunisian Atlas, in particular in the development of NW-SE oblique structures such as the Gafsa fault. The Late Triassic-Early Jurassic structural pattern is characterized by a family of first-order NW-SE trending normal faults dipping to the east and by second-order E-W trending normal faults limiting a complex system of grabens and horsts. These faults have been inverted during two contractional tectonic events. The first event occurred between the middle Turonian and the late Maastrichtian and can be correlated with the onset of the convergence between Africa and Eurasia. The second event corresponding to the principal shortening tectonic event in the southern Atlas started in the Serravalian-Tortonian and is still active. During the Neogene, the southern Atlas foreland fold and thrust belt propagated on the evaporitic décollement level infilling the Late Triassic-Early Jurassic rift. The major Eocene "Atlas event," described in hinterland domains and in eastern Tunisia, did not deform significantly the southern Tunisian Atlas, which corresponded in this period to a backbulge broad depozone.

Adenovirus 36, Adiposity, and Bone Strength in Late-Adolescent Females

PubMed Central

Laing, Emma M; Tripp, Ralph A; Pollock, Norman K; Baile, Clifton A; Della-Fera, Mary Anne; Rayalam, Srujana; Tompkins, Stephen M; Keys, Deborah A; Lewis, Richard D

2017-01-01

Adenovirus 36 (Ad36) is the only adenovirus to date that has been linked with obesity in humans. Our previous studies in late-adolescent females suggest that excess weight in the form of fat mass is associated with lower cortical bone strength. The purpose of this study was to assess the relationship between Ad36-specific antibodies, adiposity, and bone strength in our sample of late-adolescent females. A cross-sectional study of 115 females aged 18 to 19 years was performed. Participants were classified according to adiposity by dual-energy X-ray absorptiometry (body fat percentage as normal-fat [<32% body fat; n=93] or high-fat [≥ 32% body fat; n=22]), and according to the presence of Ad36-specific neutralizing antibodies. Peripheral quantitative computed tomography measured bone parameters at the 4% (trabecular bone) and 20% (cortical bone) site, and muscle cross-sectional area (MCSA) at the 66% site, from the distal metaphyses of the radius and the tibia. Bone strength was determined from volumetric bone mineral density and bone geometry to calculate bone strength index (BSI; trabecular site) and polar strength–strain index (SSI; cortical site). After adjustment for MCSA and limb length, radial SSI was lower in Ad36+ versus Ad36− subjects from the high-fat group (p<0.03), but not the normal-fat group. No significant differences were observed between groups in tibial SSI or BSI. These data support an association of adiposity and cortical bone strength at the radius with the presence of neutralizing antibodies to Ad36 in late-adolescent females. PMID:23296755

Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis.

PubMed

Zeydan, Burcu; Lowe, Val J; Schwarz, Christopher G; Przybelski, Scott A; Tosakulwong, Nirubol; Zuk, Samantha M; Senjem, Matthew L; Gunter, Jeffrey L; Roberts, Rosebud O; Mielke, Michelle M; Benarroch, Eduardo E; Rodriguez, Moses; Machulda, Mary M; Lesnick, Timothy G; Knopman, David S; Petersen, Ronald C; Jack, Clifford R; Kantarci, Kejal; Kantarci, Orhun H

2018-05-01

There is growing interest in white matter (WM) imaging with positron emission tomography (PET). We studied the association of cognitive function in late multiple sclerosis (MS) with cortical and WM Pittsburgh compound-B PET (PiB-PET) binding. In the population-based Mayo Clinic Study of Aging, 24 of 4869 participants had MS (12 underwent PiB-PET). Controls were age and sex matched (5:1). We used automated or semi-automated processing for quantitative image analyses and conditional logistic regression for group differences. MS patients had lower memory ( p = 0.03) and language ( p = 0.02) performance; smaller thalamic volumes ( p = 0.003); and thinner temporal ( p = 0.001) and frontal ( p = 0.045) cortices on magnetic resonance imaging (MRI) than controls. There was no difference in global cortical PiB standardized uptake value ratios between MS and controls ( p = 0.35). PiB uptake was lower in areas of WM hyperintensities compared to normal-appearing white matter (NAWM) in MS ( p = 0.0002). Reduced PiB uptake in both the areas of WM hyperintensities ( r = 0.65; p = 0.02) and NAWM ( r = 0.69; p = 0.01) was associated with decreased visuospatial performance in MS. PiB uptake in the cortex in late MS is not different from normal age-matched controls. PiB uptake in the WM in late MS may be a marker of the large network structures' integrity such as those involved in visuospatial performance.

Costs and benefits of late nesting in cliff swallows.

PubMed

Brown, Charles R; Roche, Erin A; O'Brien, Valerie A

2015-02-01

Many organisms of temperate latitudes exhibit declines in reproductive success as the breeding season advances. Experiments can delay the onset of reproduction for early breeders to investigate the consequences of late nesting, but it is rarely possible to observe a distinct second round of nesting in species that normally nest only once. The colonial cliff swallow (Petrochelidon pyrrhonota) is a migratory songbird that has a relatively short breeding season in the western Great Plains, USA, with birds rarely nesting late in the summer. Previous work suggested that ectoparasitism is a primary reason why reproductive success in this species declines over the summer. At colony sites where nests were fumigated to remove ectoparasitic swallow bugs (Oeciacus vicarius), cliff swallows frequently undertook a distinct round of late nesting after previously fledging young that year. Mark-recapture revealed that late-nesting pairs at these colonies produced fewer offspring that survived to the next breeding season, and that survival of late-nesting adults was lower during the next year, relative to pairs nesting earlier in the season. These reproductive costs applied in the absence of ectoparasites and likely reflect other environmental costs of late nesting such as seasonal declines in food availability or a delayed start of fall migration. Despite the costs, the estimated fitness for perennial early-and-late nesters in the absence of ectoparasites was equivalent to that of birds that nested only early in the season. The collective disadvantages of late nesting likely constrain most cliff swallows to raising a single brood in the middle latitudes of North America.

Dynamo Effects in Magnetized Ideal Plasma Cosmologies

NASA Astrophysics Data System (ADS)

Kleidis, Kostas; Kuiroukidis, Apostolos; Papadopoulos, Demetrios; Vlahos, Loukas

The excitation of cosmological perturbations in an anisotropic cosmological model and in the presence of a homogeneous magnetic field has been studied, using the ideal magnetohydrodynamic (MHD) equations. In this case, the system of partial differential equations which governs the evolution of the magnetized cosmological perturbations can be solved analytically. Our results verify that fast-magnetosonic modes propagating normal to the magnetic field, are excited. But, what is most important, is that, at late times, the magnetic-induction contrast (δB/B) grows, resulting in the enhancement of the ambient magnetic field. This process can be particularly favored by condensations, formed within the plasma fluid due to gravitational instabilities.

Perinatal Risks in "Late Motherhood" Defined Based On Parity and Preterm Birth Rate - an Analysis of the German Perinatal Survey (20th Communication).

PubMed

Schure, V; Voigt, M; Schild, R L; Hesse, V; Carstensen, M; Schneider, K T M; Straube, S

2012-01-01

Aim: "Late motherhood" is associated with greater perinatal risks but the term lacks precise definition. We present an approach to determine what "late motherhood" associated with "high risk" is, based on parity and preterm birth rate. Materials and Methods: Using data from the German Perinatal Survey of 1998-2000 we analysed preterm birth rates in women with zero, one, or two previous live births. We compared groups of "late" mothers (with high preterm birth rates) with "control" groups of younger women (with relatively low preterm birth rates). Data of 208 342 women were analysed. For women with zero (one; two) previous live births, the "control" group included women aged 22-26 (27-31; 29-33) years. Women in the "late motherhood" group were aged > 33 (> 35; > 38) years. Results: The "late motherhood" groups defined in this way were also at higher risk of adverse perinatal events other than preterm birth. For women with zero (one; two) previous live births, normal cephalic presentation occurred in 89 % (92.7 %; 93.3 %) in the "control" group, but only in 84.5 % (90 %; 90.4 %) in the "late motherhood" group. The mode of delivery was spontaneous or at most requiring manual help in 71.3 % (83.4 %; 85.8 %) in the "control" group, but only in 51.4 % (72.2 %; 76.4 %) in the "late motherhood" group. Five-minute APGAR scores were likewise worse for neonates of "late" mothers and the proportion with a birth weight ≤ 2499 g was greater. Conclusion: "Late motherhood" that is associated with greater perinatal risks can be defined based on parity and preterm birth rate.

What is the role of a full physical examination in the management of asymptomatic patients with late syphilis?

PubMed

Dabis, R; Radcliffe, K

2012-12-01

According to the British Association for Sexual Health and HIV guidelines, a full physical examination is recommended in patients with possible late syphilis. The aim of this audit was to review all cases of late syphilis diagnosed at our centre since 1994 to see if a full cardiovascular and neurological examination was documented and also to see what a full examination contributed to the management of asymptomatic patients. Of the 480 medical notes audited, 295 patients were asymptomatic of whom 288 (98%) had normal physical examinations; the rest were either not documented, declined or defaulted follow-up. Seven asymptomatic patients had positive clinical findings but these did not lead to a diagnosis of cardiovascular or neurological syphilis. This audit has shown that performing a physical examination in asymptomatic patients added no benefit in diagnosing complications of late syphilis; it would appear that the physical examination did not alter the management.

Effects of temperature variability on community structure in a natural microbial food web.

PubMed

Zander, Axel; Bersier, Louis-Félix; Gray, Sarah M

2017-01-01

Climate change research has demonstrated that changing temperatures will have an effect on community-level dynamics by altering species survival rates, shifting species distributions, and ultimately, creating mismatches in community interactions. However, most of this work has focused on increasing temperature, and still little is known about how the variation in temperature extremes will affect community dynamics. We used the model aquatic community held within the leaves of the carnivorous plant, Sarracenia purpurea, to test how food web dynamics will be affected by high temperature variation. We tested the community response of the first (bacterial density), second (protist diversity and composition), and third trophic level (predator mortality), and measured community respiration. We collected early and late successional stage inquiline communities from S. purpurea from two North American and two European sites with similar average July temperature. We then created a common garden experiment in which replicates of these communities underwent either high or normal daily temperature variation, with the average temperature equal among treatments. We found an impact of temperature variation on the first two, but not on the third trophic level. For bacteria in the high-variation treatment, density experienced an initial boost in growth but then decreased quickly through time. For protists in the high-variation treatment, alpha-diversity decreased faster than in the normal-variation treatment, beta-diversity increased only in the European sites, and protist community composition tended to diverge more in the late successional stage. The mortality of the predatory mosquito larvae was unaffected by temperature variation. Community respiration was lower in the high-variation treatment, indicating a lower ecosystem functioning. Our results highlight clear impacts of temperature variation. A more mechanistic understanding of the effects that temperature, and especially temperature variation, will have on community dynamics is still greatly needed. © 2016 John Wiley & Sons Ltd.

Bioavailability and efficacy of a gap junction enhancer (PQ7) in a mouse mammary tumor model.

PubMed

Shishido, Stephanie N; Prasain, Keshar; Beck, Amanda; Nguyen, Thi D T; Hua, Duy H; Nguyen, Thu Annelise

2013-01-01

The loss of gap junctional intercellular communication is characteristic of neoplastic cells, suggesting that the restoration with a gap junction enhancer may be a new therapeutic treatment option with less detrimental effects than traditional antineoplastic drugs. A gap junction enhancer, 6-methoxy-8-[(2-furanylmethyl) amino]-4-methyl-5-(3-trifluoromethylphenyloxy) quinoline (PQ7), on the normal tissue was evaluated in healthy C57BL/6J mice in a systemic drug distribution study. Immunoblot analysis of the vital organs indicates a reduction in Cx43 expression in PQ7-treated animals with no observable change in morphology. Next the transgenic strain FVB/N-Tg(MMTV-PyVT) 634Mul/J (also known as PyVT) was used as a spontaneous mammary tumor mouse model to determine the biological and histological effects of PQ7 on tumorigenesis and metastasis at three stages of development: Pre tumor, Early tumor, and Late tumor formation. PQ7 was assessed to have a low toxicity through intraperitoneal administration, with the majority of the compound being detected in the heart, liver, and lungs six hours post injection. The treatment of tumor bearing animals with PQ7 had a 98% reduction in tumor growth, while also decreasing the total tumor burden compared to control mice during the Pre stage of development. PQ7 treatment increased Cx43 expression in the neoplastic tissue during Pre-tumor formation; however, this effect was not observed in Late stage tumor formation. This study shows that the gap junction enhancer, PQ7, has low toxicity to normal tissue in healthy C57BL/6J mice, while having clinical efficacy in the treatment of spontaneous mammary tumors of PyVT mice. Additionally, gap junctional intercellular communication and neoplastic cellular growth are shown to be inversely related, while treatment with PQ7 inhibits tumor growth through targeting gap junction expression.

Controlling Cocaine: Supplying Versus Demand Programs

DTIC Science & Technology

1994-01-01

programs are administered to preteens , while cocaine use does not normally start until the late teens and early twenties. 7 A primary activity of...initiation for various drugs. Prevention programs attempt to convince preteens to abstain from marijuana, cigarettes, and alcohol. Therefore, to argue that

Late recurrences of germ cell malignancies: a population-based experience over three decades

PubMed Central

Oldenburg, J; Alfsen, G C; Wæhre, H; Fosså, S D

2006-01-01

The purpose of this study was to explore the incidence of late relapse in patients with malignant germ cell tumour (MGCT) in a population-based series, with emphasis on the mode of detection, survival, and the relevance of histological findings. The clinical records from a population-based cohort of patients with seminoma (n=1123) or non-seminoma (n=826) were evaluated for late relapses. Twenty-five patients developed a late relapse. The cumulative 10-year incidence rate was 1.3%. All 10 seminoma patients, but only eight of 15 non-seminoma patients relapsed with vital malignant tumour (P=0.02). Teratoma or necrosis was found in seven of nine primarily chemotherapy-treated non-seminoma patients with normal tumour markers at late relapse. Six of nine patients operated with limited retroperitoneal lymph node dissection as part of the primary treatment had relapsed retroperitoneally outside the original operation field. The 10-year cause-specific survival was 68% in all patients, 50% in patients relapsing with vital malignant tumour and 100% in those with teratoma/ necrosis before or after salvage chemotherapy. The 10-year incidence rate of late relapses of 1.3% might reflect the true incidence rate in a population-based cohort of MGCT patients, with cure in at least half of them. PMID:16508636

Late cretaceous pelagic sediments, volcanic ASH and biotas from near the Louisville hotspot, Pacific Plate, paleolatitude ∼42°S

USGS Publications Warehouse

Ballance, Peter F.; Barron, John A.; Blome, Charles D.; Bukry, David; Cawood, Peter A.; Chaproniere, George C.H.; Frisch, Robyn; Herzer, Richard H.; Nelson, Campbell S.; Quinterno, Paula; Ryan, Holly F.; Scholl, David W.; Stevenson, Andrew J.; Tappin, David G.; Vallier, Tracy L.

1989-01-01

Dredging on the deep inner slope of the Tonga Trench, immediately north of the intersection between the Louisville Ridge hotspot chain and the trench, recovered some Late Cretaceous (Maestrichtian) slightly tuffaceous pelagic sediments. They are inferred to have been scraped off a recently subducted Late Cretaceous guyot of the Louisville chain. In the vicinity of the Louisville hotspot (present location 50°26′S, 139°09′W; Late Cretaceous location ∼42°S, longitude unknown) Late Cretaceous rich diatom, radiolarian, silicoflagellate, foraminiferal and coccolith biotas, accumulated on the flanks of the guyot and are described in this paper. Rich sponge faunas are not described. ?Inoceramus prisms are present. Volcanic ash is of within-plate alkalic character. Isotope ratios in bulk carbonate δ18O − 2.63 to + 0.85, δ13C + 2.98 to 3.83) are normal for Pacific Maestrichtian sediments. The local CCD may have been shallower than the regional CCD, because of high organic productivity. In some samples Late Cretaceous materials have been mixed with Neogene materials. Mixing may have taken place on the flanks of the guyot during transit across the western Pacific, or on the trench slope during or after subduction and offscraping about 0.5 Ma.

Motor evoked responses from the thigh muscles to the stimulation of the upper limb nerves in patients with late poliomyelitis.

PubMed

Ertekin, Cumhur; On, Arzu Yagiz; Kirazli, Yeşim; Kurt, Tülay; Gürgör, Nevin

2002-04-01

To demonstrate a clear-cut M response recorded from the severely affected thigh muscles to the stimulation of the upper limb nerves in a serial of patients with late poliomyelitis. Fifteen patients with late poliomyelitis, 7 patients with spinal cord disorders and 11 control subjects were included. Evoked muscle responses were investigated in quadriceps femoris and/or thigh adductor muscles to the stimulation of the brachial plexus, median and ulnar nerves. Evoked muscle responses were obtained from the thigh muscles in all 12 late polio patients with proximal lower extremity involvement. The response could not be recorded from the thigh muscles neither in the 3 polio patients with upper extremity involvement nor in the healthy control subjects and in patients with other spinal cord disorders of anterior horn cell. It is proposed that the electrical stimulation of the arm nerves produce interlimb descending muscle responses in the severely affected atrophic thigh muscles of the patients with late polio. This finding suggests that there might be a focal and/or specific loss of inhibitory interneurons between injured and normal motor neurons and increased facilitatory synaptic action at the end of long propriospinal descending fibers in the case of late poliomyelitis.

Treatment for childhood cancer -- long-term risks

MedlinePlus

... and detect any problems early. What Causes Late Effects Some cancer treatments damage healthy cells. The damage ... are more sensitive to treatments) Types of Late Effects There are many types of late effects depending ...

Spatial reversal learning in preclinical scrapie-inoculated mice.

PubMed

Lysons, A M; Woollard, S J

1996-04-10

Acquisition and reversal of a two-choice spatial discrimination were tested in scrapie-inoculated mice. Both acquisition and reversal were normal in mice tested 138 and 103 days prior to the onset of clinical symptoms. At 65 days before onset of clinical symptoms, scrapie-inoculated mice required more trails to criterion in reversal learning, but this effect was not significant in a second experiment (68 days preclinical) and was transient: no effect was seen 33 days before symptoms. However, the course of reversal learning was abnormal in all three late preclinical groups (68, 65 and 33 days before symptoms). Reversal learning in these three groups was characterized by a rapid extinction of the original discrimination, followed by a period, absent in controls, during which performance showed no further improvement. This effect corresponds in time of onset to the appearance of characteristic neuropathological features.

Accelerated partial breast irradiation: An analysis of variables associated with late toxicity and long-term cosmetic outcome after high-dose-rate interstitial brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wazer, David E.; Kaufman, Seth; Department of Radiation Oncology, Rhode Island Hospital, Brown University School of Medicine, Providence, RI

2006-02-01

Purpose: To perform a detailed analysis of variables associated with late tissue effects of high-dose-rate (HDR) interstitial brachytherapy accelerated partial breast irradiation (APBI) in a large cohort of patients with prolonged follow-up. Methods and Materials: Beginning in 1995, 75 women with Stage I/II breast cancer were enrolled in identical institutional trials evaluating APBI as monotherapy after lumpectomy. Patients eligible included those with T1-2, N0-1 ({<=}3 nodes positive), M0 tumors of nonlobular histology with negative surgical margins, no extracapsular nodal extension, and negative results on postexcision mammogram. All patients underwent surgical excision and postoperative irradiation with HDR interstitial brachytherapy. The planningmore » target volume was defined as the excision cavity plus a 2-cm margin. Treatment was delivered with a high-activity Ir-192 source at 3.4 Gy per fraction twice daily for 5 days to a total dose of 34 Gy. Dosimetric analyses were performed with three-dimensional postimplant dose and volume reconstructions. All patients were evaluated at 3-6-month intervals and assessed with a standardized cosmetic rating scale and according to Radiation Therapy Oncology Group late normal tissue toxicity scoring criteria. Clinical and therapy-related features were analyzed for their relationship to cosmetic outcome and toxicity rating. Clinical features analyzed included age, volume of resection, history of diabetes or hypertension, extent of axillary surgery, and systemic therapies. Therapy-related features analyzed included volume of tissue encompassed by the 100%, 150%, and 200% isodose lines (V100, V150, and V200, respectively), the dose homogeneity index (DHI), number of source dwell positions, and planar separation. Results: The median follow-up of all patients was 73 months (range, 43-118 months). The cosmetic outcome at last follow-up was rated as excellent, good, and fair/poor in 67%, 24%, and 9% of patients, respectively. Suboptimal cosmetic outcome was significantly associated with the number of source dwell positions, V150, and V200 and inversely associated with DHI (0.77 vs. 0.73; p = 0.05). Late skin toxicity was rated as Grade 0, 1, or 2 in 77%, 19%, and 4% of patients, respectively. The risk of Grade 1/2 skin toxicity was significantly associated with V150 and V200 and inversely associated with DHI (0.77 vs. 0.71; p = 0.009). Late subcutaneous toxicity was rated as Grade 0, 1, 2, 3, or 4 in 55%, 15%, 12%, 5%, and 13% of patients, respectively. The risk of Grade 0/1 vs. Grade 2-4 subcutaneous toxicity was significantly associated only with a lower value of DHI (0.77 vs. 0.73; p = 0.02). To further explore factors that might contribute to the risk of fat necrosis (symptomatic or asymptomatic), a separate analysis showed that only dose hotspots as reflected in V150 and V200 were significantly associated with elevated risk. The use of adriamycin-based chemotherapy after APBI was found to be associated with a significant increase in the incidence of higher-grade skin toxicity and a higher risk of fat necrosis and suboptimal cosmetic outcome. Patient age, volume of resection, extent of axillary surgery, a history of diabetes or hypertension, and the use of tamoxifen were not found to be significantly associated with cosmetic outcome or late normal tissue complications. Conclusions: Long-term cosmetic results and the risk of late skin and subcutaneous toxicity after APBI with interstitial HDR brachytherapy can be correlated with specific treatment-related variables. These data provide dosimetric parameters that might be used to minimize the risk of normal tissue injury after APBI interstitial brachytherapy.« less

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultheiss, Timothy E.; Wong, Jeffrey; Liu, An

2007-03-15

Purpose: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. Methods and Materials: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribsmore » and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. Results: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. Conclusion: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk.« less

Association between decreased plasma levels of soluble human leukocyte antigen-G and severe pre-eclampsia.

PubMed

He, Yingdong; Chen, Shi; Huang, He; Chen, Qian

2016-04-01

The aim of this study was to investigate the levels of different isoforms of soluble human leukocyte antigen-G (sHLA-G) in maternal plasma during early and late pregnancy, and to investigate the expression of sHLA-G isoforms in women with early or late-onset severe preeclampsia. This prospective, nested, case-control study was performed in 24 early-onset severe preeclamptic, 34 late-onset severe preeclamptic, and 74 uncomplicated pregnant women. Plasma levels of sHLA-G1/5 were measured using ELISA. Plasma sHLA-G1 levels in women with late-onset severe preeclampsia were markedly lower compared with normal controls (median: 0 vs. 1.22 ng/mL) at the first trimester, and plasma sHLA-G1 levels in women with early-onset severe preeclampsia were markedly lower compared with normal controls at the second (median: 0 vs. 1.24 ng/mL) and third (median: 0 vs. 1.34 ng/mL) trimesters. There was no difference between the late-onset and early-onset groups at three trimesters. As for sHLA-G5, there was no difference in concentrations among the three groups at any time point. However, compared with controls, more women with early- or late-onset severe preeclampsia had undetectable sHLA-G5 levels in the first (71.4% and 76.2% vs. 14.1%), second (75.0% and 73.3% vs. 19.0%), and third (100.0% and 70.4% vs. 14.8%, respectively) trimester (all P<0.05). sHLA-G1 levels in the first (odds ratio [OR]=0.254, 95% confidence interval [CI]=0.109-0.591, P=0.010), second (OR=0.315, 95% CI=0.158-0.627, P=0.001), and third (OR=0.170, 95% CI=0.054-0.533, P=0.002) trimester was a risk factor for severe preeclampsia. Severe preeclampsia was associated with low/undetectable maternal plasma levels of sHLA-G. Low sHLA-G1 levels might be a risk marker for severe preeclampsia.

Changing Pattern of Crop Fraction in Late Blight Induced Potato Crops in Potato Bowl of West Bengal by using Multi-temporal Time Series AWiFs Data

NASA Astrophysics Data System (ADS)

Chakrabarty, Abhisek

2016-07-01

Crop fraction is the ratio of crop occupying a unit area in ground pixel, is very important for monitoring crop growth. One of the most important variables in crop growth monitoring is the fraction of available solar radiation intercepted by foliage. Late blight of potato (Solanum tuberosum), caused by the oomycete pathogen Phytophthora infestans, is considered to be the most destructive crop diseases of potato worldwide. Under favourable climatic conditions, and without intervention (i.e. fungicide sprays), the disease can destroy potato crop within few weeks. Therefore it is important to evaluate the crop fraction for monitoring the healthy and late blight affected potato crops. This study was conducted in potato bowl of West Bengal, which consists of districts of Hooghly, Howrah, Burdwan, Bankuara, and Paschim Medinipur. In this study different crop fraction estimation method like linear spectral un-mixing, Normalized difference vegetation index (NDVI) based DPM model (Zhang et al. 2013), Ratio vegetation index based DPM model, improved Pixel Dichotomy Model (Li et al. 2014) ware evaluated using multi-temporal IRS AWiFs data in two successive potato growing season of 2012-13 and 2013-14 over the study area and compared with measured crop fraction. The comparative study based on measured healthy and late blight affected potato crop fraction showed that improved Pixel Dichotomy Model maintain the high coefficient of determination (R2= 0.835) with low root mean square error (RMSE=0.21) whereas the correlation values of NDVI based DPM model and RVI based DPM model is 0.763 and 0.694 respectively. The changing pattern of crop fraction profile of late blight affected potato crop was studied in respect of healthy potato crop fraction which was extracted from the 269 GPS points of potato field. It showed that the healthy potato crop fraction profile maintained the normal phenological trend whereas the late blight affected potato crop fraction profile suddenly fallen after late blight disease affected in potato crops. Therefore, it can be concluded that based on the result of this study the improved Pixel Dichotomy Model is the most convenient method for crop fraction estimation for this region with satisfactory accuracy.

Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis.

PubMed

Gössl, Mario; Mödder, Ulrike I; Atkinson, Elizabeth J; Lerman, Amir; Khosla, Sundeep

2008-10-14

This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype. Increasing evidence indicates a link between bone and the vasculature, and bone marrow and circulating osteogenic cells have been identified by staining for the osteoblastic marker, osteocalcin (OCN). Endothelial progenitor cells contribute to vascular repair, but repair of vascular injury may result in calcification. Using cell surface markers (CD34, CD133, kinase insert domain receptor [KDR]) to identify EPCs, we examined whether patients with coronary atherosclerosis had increases in the percentage of EPCs expressing OCN. We studied 72 patients undergoing invasive coronary assessment: control patients (normal coronary arteries and no endothelial dysfunction, n = 21) versus 2 groups with coronary atherosclerosis-early coronary atherosclerosis (normal coronary arteries but with endothelial dysfunction, n = 22) and late coronary atherosclerosis (severe, multivessel coronary artery disease, n = 29). Peripheral blood mononuclear cells were analyzed using flow cytometry. Compared with control patients, patients with early or late coronary atherosclerosis had significant increases (approximately 2-fold) in the percentage of CD34+/KDR+ and CD34+/CD133+/KDR+ cells costaining for OCN. Even larger increases were noted in the early and late coronary atherosclerosis patients in the percentage of CD34+/CD133-/KDR+ cells costaining for OCN (5- and 2-fold, p < 0.001 and 0.05, respectively). A higher percentage of EPCs express OCN in patients with coronary atherosclerosis compared with subjects with normal endothelial function and no structural coronary artery disease. These findings have potential implications for the mechanisms of vascular calcification and for the development of novel markers for coronary atherosclerosis.

Miocene extension in the East Range, Nevada: A two-stage history of normal faulting in the northern basin and range

USGS Publications Warehouse

Fosdick, J.C.; Colgan, J.P.

2008-01-01

The East Range in northwestern Nevada is a large, east-tilted crustal block bounded by west-dipping normal faults. Detailed mapping of Tertiary stratigraphic units demonstrates a two-phase history of faulting and extension. The oldest sedimentary and volcanic rocks in the area record cumulative tilting of -30??-45??E, whereas younger olivine basalt flows indicate only a 15??-20??E tilt since ca. 17-13 Ma. Cumulative fault slip during these two episodes caused a minimum of 40% extensional strain across the East Range, and Quaternary fault scarps and seismic activity indicate that fault motion has continued to the present day. Apatite fission track and (U-Th)/He data presented here show that faulting began in the East Range ca. 17-15 Ma, coeval with middle Miocene extension that occurred across much of the Basin and Range. This phase of extension occurred contemporaneously with middle Miocene volcanism related to the nearby northern Nevada rifts, suggesting a link between magmatism and extensional stresses in the crust that facilitated normal faulting in the East Range. Younger fault slip, although less well constrained, began after 10 Ma and is synchronous with the onset of low-magnitude extension in many parts of northwestern Nevada and eastern California. These findings imply that, rather than migrating west across a discrete boundary, late Miocene extension in western Nevada is a distinct, younger period of faulting that is superimposed on the older, middle Miocene distribution of extended and unextended domains. The partitioning of such middle Miocene deformation may reflect the influence of localized heterogeneities in crustal structure, whereas the more broadly distributed late Miocene extension may reflect a stronger influence from regional plate boundary processes that began in the late Miocene. ?? 2008 Geological Society of America.

Tissue distribution of very late activation antigens-1/6 and very late activation antigen ligands in the normal thymus and in thymoma.

PubMed Central

Ruco, L. P.; Paradiso, P.; Pittiglio, M.; Diodoro, M. G.; Gearing, A. J.; Mainiero, F.; Gismondi, A.; Santoni, A.; Baroni, C. D.

1993-01-01

The expression of very late activation antigens (VLAs)-1/6 was correlated with that of the VLA ligands fibronectin, laminin, collagen, and vascular cell adhesion molecule-1 in sections of normal thymus, in thymocyte suspensions, and in 10 cases of thymoma. Capsular epithelial cells are VLA-2+, VLA-3+, and VLA-6+ and face the thymic basement membrane, which is rich in fibronectin, laminin, and collagen type IV. Cortical epithelial cells are VLA-2+ and are embedded in a reticular meshwork of nonorganized extracellular matrix (ECM) that is rich in fibronectin. Cortical thymocytes, identified as CD3dim cells by using immunofluorescence in suspension, are highly positive for VLA-4, a fibronectin ligand. Most cortical macrophages are positive for vascular cell adhesion molecule-1, a molecule recognized by VLA-4. Medullary epithelial cells are VLA-2+/VLA-3+ and are codistributed with fibrous strands of organized ECM that are positive for fibronectin, collagen, and laminin. Medullary thymocytes, identified as CD3bright cells, are positive for VLA-4 and VLA-6, a ligand for laminin. Our findings suggest that intrathymic thymocyte maturation is associated with changes in expression of VLA molecules, which are apparently correlated with the presence of VLA ligands in the tissue microenvironment. Thymomas were classified as cortical (three), common (five), or medullary (two) type. Expression of VLA molecules and distribution of ECM in the three histological subtypes were reminiscent of those observed in the respective regions of the normal thymus. All cases of thymoma were characterized by overexpression of VLA molecules on neoplastic cells, which was associated with increased deposition of organized ECM rich in fibronectin, laminin, and collagen. Images Figure 1 Figure 3 PMID:8456937

Multidisciplinary approach for fault detection: Integration of PS-InSAR, geomorphological, stratigraphic and structural data in the Venafro intermontane basin (Central-Southern Apennines, Italy)

NASA Astrophysics Data System (ADS)

Amato, Vincenzo; Aucelli, Pietro P. C.; Bellucci Sessa, Eliana; Cesarano, Massimo; Incontri, Pietro; Pappone, Gerardo; Valente, Ettore; Vilardo, Giuseppe

2017-04-01

A multidisciplinary methodology, integrating stratigraphic, geomorphological and structural data, combined with GIS-aided analysis and PS-InSAR interferometric data, was applied to characterize the relationships between ground deformations and the stratigraphic and the morphostructural setting of the Venafro intermontane basin. This basin is a morphostructural depression related to NW-SE and NE-SW oriented high angle normal faults bordering and crossing it. In particular, a well-known active fault crossing the plain is the Aquae Juliae Fault, whose recent activity is evidenced by archeoseismological data. The approach applied here reveals new evidence of possible faulting, acting during the Lower to Upper Pleistocene, which has driven the morphotectonic and the environmental evolution of the basin. In particular, the tectonic setting emerging from this study highlights the influence of the NW-SE oriented extensional phase during the late Lower Pleistocene - early Middle Pleistocene, in the generation of NE-SW trending, SE dipping, high-angle faults and NW-SE trending, high-angle transtensive faults. This phase has been followed by a NE-SW extensional one, responsible for the formation of NW-SE trending, both NW and SE dipping, high-angle normal faults, and the reactivation of the oldest NE-SW oriented structures. These NW-SE trending normal faults include the Aquae Juliae Fault and a new one, unknown until now, crossing the plain between the Venafro village and the Colle Cupone Mt. (hereinafter named the Venafro-Colle Cupone Fault, VCCF). This fault has controlled deposition of the youngest sedimentary units (late Middle Pleistocene to late Upper Pleistocene) suggesting its recent activity and it is well constrained by PS-InSAR data, as testified by the increase of the subsidence rate in the hanging wall block.

Aksu-Dinar Fault System: Its bearing on the evolution of the Isparta Angle (SW Turkey)

NASA Astrophysics Data System (ADS)

Kaymakci, Nuretdin; Özacar, Arda; Langereis, Cornelis G.; Özkaptan, Murat; Gülyüz, Erhan; van Hinsbergen, Douwe J. J.; Uzel, Bora; McPhee, Peter; Sözbilir, Hasan

2017-04-01

The Isparta Angle is a triangular structure in SW Turkey with NE-SW trending western and NW-SE trending eastern flanks. Aksu Fault is located within the core of this structure and have been taken-up large E-W shortening and sinistral translation since the Late Miocene. It is an inherited structure which emplaced Antalya nappes over the Beydaǧları Platform during the late Eocene to Late Miocene and was reactivated by the Pliocene as a high angle reverse fault to accommodate the counter-clockwise rotation of Beydaǧları and SW Anatolia. On the other hand, the Dinar Fault is a normal fault with slight sinistral component has been active since Pliocene. These two structures are collinear and delimit areas with clockwise and counter-clockwise rotations. The areas to the north and east of these structures rotated clockwise while southern and western areas are rotated counter-clockwise. We claim that the Dinar-Aksu Fault System facilitate rotational deformation in the region as a scissor like mechanism about a pivot point north of Burdur. This mechanism resulted in the normal motion along the Dinar and reverse motion along the Aksu faults with combined sinistral translation component on both structures. We claim that the driving force for the motion of these faults and counter-clockwise rotation of the SW Anatolia seems to be slab-pull forces exerted by the east dipping Antalya Slab, a relic of Tethys oceanic lithosphere. The research for this paper is supported by TUBITAK - Grant Number 111Y239. Key words: Dinar Fault, Aksu Fault, Isparta Angle, SW Turkey, Burdur Pivot, Normal Fault, Reverse Fault

Serum levels of inhibin A and inhibin B in women with normal and abnormal luteal function.

PubMed

Yamoto, M; Imai, M; Otani, H; Nakano, R

1997-05-01

To determine whether serum inhibin A and inhibin B concentrations are lower in patients with luteal dysfunction than in women with normal luteal function. Serum samples were collected from seven healthy women with regular menstrual cycles. Serum samples on days +5 to +9 after the LH surge were collected from patients with luteal dysfunction. The diagnosis of luteal dysfunction was based on a luteal phase duration less than 11 days and a single midluteal progesterone level below 10 ng/mL. Serum levels of inhibin A, inhibin B, progesterone, estradiol (E2), FSH, and LH were measured. The serum inhibin A levels were increased toward the late follicular phase. The levels reached a maximum during the midluteal phase, followed by a fall during the late luteal phase. The serum inhibin B levels were high during the follicular phases and the early luteal phase. The levels decreased during the midluteal and late luteal phases. Serum levels (mean +/- standard error of the mean) of inhibin A in patients with luteal dysfunction were significantly lower than those in women during the midluteal phase (26.2 +/- 2.9 compared to 41.9 +/- 2.8 pg/mL; P < .01) in addition to the expected decrease in serum progesterone levels (6.3 +/- 0.7 compared to 14.7 +/- 1.2 ng/mL; P < .01). Serum inhibin B levels did not differ significantly between normal women and those with luteal dysfunction. There also were no significant differences in the E2, FSH, and LH levels. Levels of inhibin A, but not of inhibin B, may reflect the human luteal function.

New measurements for hadrontherapy and space radiation: biology

NASA Technical Reports Server (NTRS)

Blakely, E. A.

2001-01-01

The dual goals of optimizing clinical efficacy of hadrontherapy and determining radiation risk estimates for space research have intersected to a common focus for investigation of the biological effects of charged particles. This paper briefly highlights recent international progress at accelerator facilities engaged in both biological and clinical studies of the effects of particle beams, primarily protons, carbon and iron ions. Basic mechanisms of molecular, cellular and tissue responses continue under investigation for radiations with a range of ionization densities. Late normal tissue effects, including the risk of cancer in particular, are of importance for both research fields. International cooperation has enhanced the rate of progress as evidenced by recent publications. Specific areas of biomedical research related to the biological radiotoxicity of critical organs (especially the central nervous system), individual radiosensitivities to radiation carcinogenesis, and the analysis of effects in mixed radiation fields still require more research. Recommendations for addressing these issues are made.

Coping – Late Side Effects

Cancer.gov

Cancer treatment can cause late side effects that may not show up for months or years after treatment. These late effects may include heart and lung problems, bone loss, eye and hearing changes, lymphedema, and other problems

Geometry and evolution of low-angle normal faults (LANF) within a Cenozoic high-angle rift system, Thailand: Implications for sedimentology and the mechanisms of LANF development

NASA Astrophysics Data System (ADS)

Morley, Chris K.

2009-10-01

At least eight examples of large (5-35 km heave), low-angle normal faults (LANFs, 20°-30° dip) occur in the Cenozoic rift basins of Thailand and laterally pass into high-angle extensional fault systems. Three large-displacement LANFs are found in late Oligocene-Miocene onshore rift basins (Suphan Buri, Phitsanulok, and Chiang Mai basins), they have (1) developed contemporaneous with, or after the onset of, high-angle extension, (2) acted as paths for magma and associated fluids, and (3) impacted sedimentation patterns. Displacement on low-angle faults appears to be episodic, marked by onset of lacustrine conditions followed by axial progradation of deltaic systems that infilled the lakes during periods of low or no displacement. The Chiang Mai LANF is a low-angle (15°-25°), high-displacement (15-35 km heave), ESE dipping LANF immediately east of the late early Miocene Doi Inthanon and Doi Suthep metamorphic core complexes. Early Cenozoic transpressional crustal thickening followed by the northward motion of India coupled with Burma relative to east Burma and Thailand (˜40-30 Ma) caused migmatization and gneiss dome uplift in the late Oligocene of the core complex region, followed by LANF activity. LANF displacement lasted 4-6 Ma during the early Miocene and possibly transported a late Oligocene-early Miocene high-angle rift system 35 km east. Other LANFs in Thailand have lower displacements and no associated metamorphic core complexes. The three LANFs were initiated as low-angle faults, not by isostatic rotation of high-angle faults. The low-angle dips appear to follow preexisting low-angle fabrics (thrusts, shear zones, and other low-angle ductile foliations) predominantly developed during Late Paleozoic and early Paleogene episodes of thrusting and folding.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Torchia, B.S.; Call, L.M.; Migeon, B.R.

The relationship between the transcriptional state of a locus and the time when it replicates during DNA synthesis is increasingly apparent. Active autosomal genes tend to replicate early, whereas inactive ones are more permissive and frequently replicate later. Although the inactive X chromosome replicates later than its active homologue, little is known about the replication of X-linked genes. The authors have used FISH to examine the replication of loci on the active X chromosome that are not transcribed, either because the tissue analyzed was not the expressing tissue (F8C), because the locus is silent on all active X chromosomes (XIST),more » or because it has been mutated by expansion and methylation of a CpG island (FMR1). In this assay, an unreplicated locus is characterized by a single hybridization signal, and a replicated locus is characterized by a doublet hybridization signal. The percentage of doublets is used as a measure of relative time of replication in S phase. The results show that the FMR1 gene replicates relatively later in fragile X(fraX) males with the full mutation than in normal males, irrespective of the probe used. The F8C locus is late replicating in both normal and fraX males and replicates at nearly the same time on active and inactive X in females. The XIST locus replicates late in all the males studied and asynchronously in female cells. From the late replication of the locus on the active X in males, the authors deduce that the locus on the active X is the later replicating locus in female cells. They conclude that (1) the expansion of the FMR1 locus leads to late replication, (2) silence of the XIST gene in males is associated with late replication of the locus, and (3) this assay will be useful for further studies of the relationship between transcription and replication. 32 refs., 2 figs., 5 tabs.« less

Tree rings reveal a major episode of forest mortality in the late 18th century on the Tibetan Plateau

NASA Astrophysics Data System (ADS)

Fang, Ouya; Alfaro, René I.; Zhang, Qi-Bin

2018-04-01

There is a growing research interest on studying forest mortality in relation to ongoing climate warming, but little is known about such events in past history. The study of past forest mortality provides valuable information for determining baselines that establish the normal parameters of functioning in forest ecosystems. Here we report a major episode of previously undocumented forest mortality in the late 18th century on the northern Tibetan Plateau, China. The event was not spatially uniform, in which a more severe mortality happened in dryer sites. We used dendrochronology to compare radial growth trajectories of individual trees from 11 sites in the region, and found that many trees showed positive growth trend, or growth release, during 1796-1800 CE. Growth releases are a proxy indicator of stand thinning caused by tree mortality. The growth release was preceded by an almost two-decade long growth reduction. Long-term drought related to weakened North Atlantic Oscillation and frequent El Niño events are the likely factors causing the tree mortality in a large area of the plateau. Our findings suggest that, besides the effect of drought in the late 18th century, large-scale forest mortality may be an additional factor that further deteriorated the environment and increased the intensity of dust storms.

Enhanced tethered-flight duration and locomotor activity by overexpression of the human gene SOD1 in Drosophila motorneurons.

PubMed

Petrosyan, Agavni; Hsieh, I-Hui; Phillips, John P; Saberi, Kourosh

2015-03-01

Mutation of the human gene superoxide dismutase (hSOD1) is associated with the fatal neurodegenerative disease familial amyotrophic lateral sclerosis (Lou Gehrig's disease). Selective overexpression of hSOD1 in Drosophila motorneurons increases lifespan to 140% of normal. The current study was designed to determine resistance to lifespan decline and failure of sensorimotor functions by overexpressing hSOD1 in Drosophila's motorneurons. First, we measured the ability to maintain continuous flight and wingbeat frequency (WBF) as a function of age (5 to 50 days). Flies overexpressing hSOD1 under the D42-GAL4 activator were able to sustain flight significantly longer than controls, with the largest effect observed in the middle stages of life. The hSOD1-expressed line also had, on average, slower wingbeat frequencies in late, but not early life relative to age-matched controls. Second, we examined locomotor (exploratory walking) behavior in late life when flies had lost the ability to fly (age ≥ 60 d). hSOD1-expressed flies showed significantly more robust walking activity relative to controls. Findings show patterns of functional decline dissimilar to those reported for other life-extended lines, and suggest that the hSOD1 gene not only delays death but enhances sensorimotor abilities critical to survival even in late life.

Program to analyze aquifer test data and check for validity with the jacob method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Field, M.S.

1993-01-01

The Jacob straight-line method of aquifer analysis deals with the late-time data and small radius of the Theis type curve which plot as a straight line if the drawdown data are plotted on an arithmetic scale and the time data on a logarithmic (base 10) scale. Correct analysis with the Jacob method normally assumes that (1) the data lie on a straight line, (2) the value of the dimensionless time factor is less than 0.01, and (3) the site's hydrogeology conforms to the method's assumptions and limiting conditions. Items 1 and 2 are usually considered for the Jacob method, butmore » item 3 is often ignored, which can lead to incorrect calculations of aquifer parameters. A BASIC computer program was developed to analyze aquifer test data with the Jacob method to test the validity of its use. Aquifer test data are entered into the program and manipulated so that a slope and time intercept of the straight line drawn through the data (excluding early-time and late-time data) can be used to calculate transmissivity and storage coefficient. Late-time data are excluded to eliminate the effects of positive and negative boundaries. The time-drawdown data then are converted into dimensionless units to determine if the Jacob method's assumptions are valid for the hydrogeologic conditions under which the test was conducted.« less

Augmented cell survival in eutopic endometrium from women with endometriosis: Expression of c-myc, TGF-beta1 and bax genes

PubMed Central

Johnson, M Cecilia; Torres, Marisa; Alves, Alessandra; Bacallao, Ketty; Fuentes, Ariel; Vega, Margarita; Boric, M Angélica

2005-01-01

Background Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside of the uterus. The fragments in normal menstruation are composed of necrotic and living cells, which do not survive in ectopic locations because of programmed cell death. The aim of this study was to evaluate if the balance between cell proliferation and apoptosis is changed in eutopic endometrium from women with endometriosis throughout the menstrual cycle by studying bax (pro-apoptotic), c-myc (regulator of cell cycle) and TGF-beta1 (involved in cell differentiation) genes. Methods Eutopic endometrium was obtained from: 30 women with endometriosis (32.8 +/- 5 years) and 34 fertile eumenorrheic women (36 +/- 5.3 years). We analyzed apoptosis (TUNEL: DNA fragmentation); cell proliferation (immunohistochemistry (IHC) for Ki67); c-myc, bax and TGF-beta1 mRNA abundance (RT-PCR) and TGF-beta1 protein (IHC) in endometrial explants. Results Cell proliferation strongly decreased from proliferative to late secretory phases in glands, but not in stroma, in both endometria. Positive staining in glands and stroma from proliferative endometrium with endometriosis was 1.9- and 2.2-fold higher than control endometrium, respectively (p < 0.05). Abundance of c-myc mRNA was 65% higher in proliferative endometrium from endometriosis than normal tissue (p < 0.05). TGF-beta1 (mRNA and protein) augmented during mid secretory phase in normal endometrium, effect not observed in endometrium with endometriosis. In normal endometrium, the percentage of apoptotic epithelial and stromal cells increased more than 30-fold during late secretory phase. In contrast, in endometrium from endometriosis, not only this increase was not observed, besides bax mRNA decreased 63% versus normal endometrium (p < 0.05). At once, in early secretory phase, apoptotic stromal cells increased 10-fold with a concomitant augment of bax mRNA abundance (42%) in endometria from endometriosis (p < 0.05). Conclusion An altered expression of c-myc, TGF-beta1 and bax was observed in eutopic endometrium from endometriosis, suggesting its participation in the regulation of cell survival in this disease. The augmented cell viability in eutopic endometrium from these patients as a consequence of a reduction in cell death by apoptosis, and also an increase in cell proliferation indicates that this condition may facilitate the invasive feature of the endometrium. PMID:16150151

Critical developmental windows for morphology and hematology revealed by intermittent and continuous hypoxic incubation in embryos of quail (Coturnix coturnix).

PubMed

Burggren, Warren W; Elmonoufy, Nourhan A

2017-01-01

Hypoxia during embryonic growth in embryos is frequently a powerful determinant of development, but at least in avian embryos the effects appear to show considerable intra- and inter-specific variation. We hypothesized that some of this variation may arise from different protocols that may or may not result in exposure during the embryo's critical window for hypoxic effects. To test this hypothesis, quail embryos (Coturnix coturnix) in the intact egg were exposed to hypoxia (~15% O2) during "early" (Day 0 through Day 5, abbreviated as D0-D5), "middle" (D6-D10) or "late" (D11-D15) incubation or for their entire 16-18 day incubation ("continuous hypoxia") to determine critical windows for viability and growth. Viability, body mass, beak and toe length, heart mass, and hematology (hematocrit and hemoglobin concentration) were measured on D5, D10, D15 and at hatching typically between D16 and D18 Viability rate was ~50-70% immediately following the exposure period in the early, middle and late hypoxic groups, but viability improved in the early and late groups once normoxia was restored. Middle hypoxia groups showed continuing low viability, suggesting a critical period from D6-D10 for embryo viability. The continuous hypoxia group experienced viability reaching <10% after D15. Hypoxia, especially during late and continuous hypoxia, also inhibited growth of body, beak and toe when measured at D15. Full recovery to normal body mass upon hatching occurred in all other groups except for continuous hypoxia. Contrary to previous avian studies, heart mass, hematocrit and hemoglobin concentration were not altered by any hypoxic incubation pattern. Although hypoxia can inhibit embryo viability and organ growth during most incubation periods, the greatest effects result from continuous or middle incubation hypoxic exposure. Hypoxic inhibition of growth can subsequently be "repaired" by catch-up growth if a final period of normoxic development is available. Collectively, these data indicate a critical developmental window for hypoxia susceptibility during the mid-embryonic period of development.

Oligocene to Recent tectonic history of the Central Solomon intra-arc basin as determined from marine seismic reflection data and compilation of onland geology

NASA Astrophysics Data System (ADS)

Cowley, Shane; Mann, Paul; Coffin, M. F.; Shipley, Thomas H.

2004-10-01

Systematic analysis of a grid of 3450 km of multichannel seismic reflection lines from the Solomon Islands constrains the late Tertiary sedimentary and tectonic history of the Solomon Island arc and its convergent interaction with the Cretaceous Ontong Java oceanic plateau (OJP). The OJP, the largest oceanic plateau on Earth, subducted beneath the northern edge of the Solomon arc in the late Neogene, but the timing and consequences of this obliquely convergent event and its role in the subduction polarity reversal process remain poorly constrained. The Central Solomon intra-arc basin (CSB), which developed in Oligocene to Recent time above the Solomon arc, provides a valuable record of the tectonic environment prior to and accompanying the OJP convergent event and the subsequent arc polarity reversal. Recognition of regionally extensive stratigraphic sequences—whose ages can be inferred from marine sedimentary sections exposed onland in the Solomon Islands—indicate four distinct tectonic phases affecting the Solomon Island arc. Phase 1: Late Oligocene-Late Miocene rifting of the northeast-facing Solomon Island arc produced basal, normal-fault-controlled, asymmetrical sequences of the CSB; the proto-North Solomon trench was probably much closer to the CSB and is inferred to coincide with the trace of the present-day Kia-Kaipito-Korigole (KKK) fault zone; this protracted period of intra-arc extension shows no evidence for interruption by an early Miocene period of convergent "soft docking" of the Ontong Java Plateau as proposed by previous workers. Phase 2: Late Miocene-Pliocene oblique convergence of the Ontong Java Plateau at the proto-North Solomon trench (KKK fault zone) and folding of the CSB and formation of the Malaita accretionary prism (MAP); the highly oblique and diachronous convergence between the Ontong Java plateau and the Solomon arc terminates intra-arc extension first in the southeast (Russell subbasin of the CSB) during the Late Miocene and later during the Pliocene in the northwest (Shortland subbasin of the CSB); folds in the CSB form by inversion of normal faults formed during Phase 1; Phinney et al. [Sequence stratigraphy, structural style, and age of deformation of the Malaita accretionary prism (Solomon arc-Ontong Java Plateau convergent zone)] show a coeval pattern of southeast to northwest younging in folding and faulting of the MAP. Phase 3: Late Pliocene-early Pleistocene arc polarity reversal and subduction initiation at the San Cristobal trench. Effects of this event in the CSB include the formation of a chain of volcanoes above the subducting Australia plate at the San Cristobal trench, the formation of the broad synclinal structure of the CSB with evidence for truncation at the uplifted flanks, and widespread occurrence of slides and "seismites" (deposits formed by seismic shaking). Phase 4: Pleistocene to Recent continued shortening and synclinal subsidence of the CSB. Continued Australia-Pacific oblique plate convergence has led to deepening of the submarine, elongate basin axis of the synclinal CSB and uplift of the dual chain of the islands on its flanks.

Do negative emotions expressed during follow-up consultations with adolescent survivors of childhood cancer reflect late effects?

PubMed

Mellblom, Anneli V; Ruud, Ellen; Loge, Jon Håvard; Lie, Hanne C

2017-11-01

To explore whether negative emotions expressed by adolescent cancer survivors during follow-up consultations were associated with potential late effects (persisting disease or treatment-related health problems). We video-recorded 66 follow-up consultations between 10 pediatricians and 66 adolescent survivors of leukemia, lymphoma or stem-cell transplantations. In transcripts of the recordings, we identified utterances coded as both 1) expressions of negative emotions (VR-CoDES), and 2) late effect-related discussions. Principles of thematic content analysis were used to investigate associations between the two. Of the 66 video-recorded consultations, 22 consultations contained 56 (49%) utterances coded as both emotional concerns and discussions of potential late effects. Negative emotions were most commonly associated with late effects such as fatigue ("I'm struggling with not having energy"), psychosocial distress ("When I touch this (scar) I become nauseous"), pain ("I'm wondering how long I am going to have this pain?"), and treatment-related effects on physical appearance ("Am I growing?"). Negative emotions expressed by adolescent cancer survivors during follow-up consultations were frequently associated with potential late effects. These late effects were not the medically most serious ones, but reflected issues affecting the adolescents' daily life. Eliciting and exploring patients' emotional concerns serve as means to obtain clinically relevant information regarding potential late effect and to provide emotional support. Copyright © 2017 Elsevier B.V. All rights reserved.

Elemental abundance analyses with DAO spectrograms. VII - The late normal B stars Pi Ceti, 134 Tauri, 21 Aquilae, and Nu Capricorni and the use of RETICON spectra

NASA Astrophysics Data System (ADS)

Adelman, Saul J.

1991-09-01

This paper presents elemental abundance analyses of sharp-lined normal late B stars. These stars exhibit mostly near-solar abundances, but each star also shows a few abundances which are a factor of 2 less than solar. The coadded photographic spectrograms are supplemented with Reticon data. A comparison of 261 equivalent widths on 2.4 A/mm spectra of sharp-lined B and A stars shows that the Reticon equivalent widths are about 95 percent of the coadded equivalent mean. The H-gamma profiles of the coadded and Reticon spectra for eight sharp-lined stars show generally good agreement. The generally high quality of the coadded data produced from 10 or more spectrograms is confirmed using the REDUCE graphics-oriented computed reduction code. For five stars, metal lines which fall in the gap between the U and V plates are analyzed using Reticon data.

Elemental abundance analyses with DAO spectrograms. VII - The late normal B stars Pi Ceti, 134 Tauri, 21 Aquilae, and Nu Capricorni and the use of Reticon spectra

NASA Technical Reports Server (NTRS)

Adelman, Saul J.

1991-01-01

This paper presents elemental abundance analyses of sharp-lined normal late B stars. These stars exhibit mostly near-solar abundances, but each star also shows a few abundances which are a factor of 2 less than solar. The coadded photographic spectrograms are supplemented with Reticon data. A comparison of 261 equivalent widths on 2.4 A/mm spectra of sharp-lined B and A stars shows that the Reticon equivalent widths are about 95 percent of the coadded equivalent mean. The H-gamma profiles of the coadded and Reticon spectra for eight sharp-lined stars show generally good agreement. The generally high quality of the coadded data produced from 10 or more spectrograms is confirmed using the REDUCE graphics-oriented computed reduction code. For five stars, metal lines which fall in the gap between the U and V plates are analyzed using Reticon data.

Association between an Alzheimer's Disease-Related Index and APOE ε4 Gene Dose.

PubMed

Schraml, Frank; Chen, Kewei; Ayutyanont, Napatkamon; Auttawut, Roontiva; Langbaum, Jessica B S; Lee, Wendy; Liu, Xiaofen; Bandy, Dan; Reeder, Stephanie Q; Alexander, Gene E; Caselli, Richard J; Fleisher, Adam S; Reiman, Eric M

2013-01-01

We introduced a hypometabolic convergence index (HCI) to characterize in a single measurement the extent to which a person's fluorodeoxyglucose positron emission tomogram (FDG PET) corresponds to that in Alzheimer's disease (AD). Apolipoprotein E ε4 (APOE ε4) gene dose is associated with three levels of risk for late-onset AD. We explored the association between gene dose and HCI in cognitively normal ε4 homozygotes, heterozygotes, and non-carriers. An algorithm was used to characterize and compare AD-related HCIs in cognitively normal individuals, including 36 ε4 homozygotes, 46 heterozygotes, and 78 non-carriers. These three groups differed significantly in their HCIs (ANOVA, p = 0.004), and there was a significant association between HCIs and gene dose (linear trend, p = 0.001). The HCI is associated with three levels of genetic risk for late-onset AD. This supports the possibility of using a single FDG PET measurement to help in the preclinical detection and tracking of AD.

Sex differences in normal age trajectories of functional brain networks.

PubMed

Scheinost, Dustin; Finn, Emily S; Tokoglu, Fuyuze; Shen, Xilin; Papademetris, Xenophon; Hampson, Michelle; Constable, R Todd

2015-04-01

Resting-state functional magnetic resonance image (rs-fMRI) is increasingly used to study functional brain networks. Nevertheless, variability in these networks due to factors such as sex and aging is not fully understood. This study explored sex differences in normal age trajectories of resting-state networks (RSNs) using a novel voxel-wise measure of functional connectivity, the intrinsic connectivity distribution (ICD). Males and females showed differential patterns of changing connectivity in large-scale RSNs during normal aging from early adulthood to late middle-age. In some networks, such as the default-mode network, males and females both showed decreases in connectivity with age, albeit at different rates. In other networks, such as the fronto-parietal network, males and females showed divergent connectivity trajectories with age. Main effects of sex and age were found in many of the same regions showing sex-related differences in aging. Finally, these sex differences in aging trajectories were robust to choice of preprocessing strategy, such as global signal regression. Our findings resolve some discrepancies in the literature, especially with respect to the trajectory of connectivity in the default mode, which can be explained by our observed interactions between sex and aging. Overall, results indicate that RSNs show different aging trajectories for males and females. Characterizing effects of sex and age on RSNs are critical first steps in understanding the functional organization of the human brain. © 2014 Wiley Periodicals, Inc.

Soft-sediment deformation structures interpreted as seismites in the uppermost Aptian to lowermost Albian transgressive deposits of the Chihuahua basin (Mexico)

USGS Publications Warehouse

Blanc, E.J.-P.; Blanc-Aletru, M. -C.; Mojon, P.-O.

1997-01-01

Several levels of soft-sediment deformation structures (s.-s.d.s.) cut by synsedimentary normal faults have been observed in the transition beds between the "Las Vigas" and "La Virgen" formations (Cretaceous) in the northeastern part of the Chihuahua basin in Mexico. These structures consisted of four kinds of motifs (floating breccias, flame-like structures, large pillow structures, and wavy structures). They are restricted to five "stratigraphic" levels (??1-??5) and surrounded by undeformed beds in fluvio-lacustrine and tidal deposits and can be traced over a distance of several hundred meters. This deformation is interpreted to have resulted from the combined effects of liquidization and shear stress in soft-sediments due to local earthquakes in the area which could have been generated during the rifting stage of the Chihuahua basin. New constraints placed on the age of the "Las Vigas" Formation (bracketed by Late Aptian charophytes at the bottom and colomiellids of late Aptian to earliest Albian age at the top) suggest that this synrift tectonism lasted at least until the end of the Aptian.

Doppler ultrasound of the maternal uterine arteries: disappearance of abnormal waveforms and relation to birthweight and pregnancy outcome.

PubMed

Campbell, S; Black, R S; Lees, C C; Armstrong, V; Peacock, J L

2000-08-01

To assess whether the gestation at which abnormal uterine artery waveforms disappear is related to birthweight and complications of pregnancy. A prospective study of outcome of pregnancy after a uterine artery Doppler screening program set in an inner city teaching hospital. One thousand five hundred and twenty-four consecutive women attending the Obstetric Department for a routine anomaly scan at between 19 and 21 weeks gestation had maternal uterine arteries assessed using color wave Doppler. Those women in whom the flow was deemed abnormal were recalled for a further scan at 24-26 weeks gestation. The main outcome measures were birthweight, gestation at delivery and incidence of pre eclampsia. The women in whom the uterine artery blood flow was normal at 20 weeks had babies with significantly higher mean birthweight than those who normalized between 20 and 24-26 weeks gestation ('late normalizers') after adjustment for confounding factors; gestational age, maternal height, parity, ethnic group and smoking (mean difference=173 g, 95% confidence intervals 42 to 303 g). The timing of trophoblast invasion, as reflected by abnormal uterine artery waveforms, may have an effect on birthweight.

A comparison of uterine peristalsis in women with normal uteri and uterine leiomyoma by cine magnetic resonance imaging.

PubMed

Orisaka, Makoto; Kurokawa, Tetsuji; Shukunami, Ken-Ichi; Orisaka, Sanae; Fukuda, Mika T; Shinagawa, Akiko; Fukuda, Shin; Ihara, Noboru; Yamada, Hiroki; Itoh, Harumi; Kotsuji, Fumikazu

2007-11-01

The non-pregnant uterus shows wave-like activity (uterine peristalsis). This pilot study was intended to determine: (1) whether uterine peristalsis during the menstrual cycle is detectable by cine magnetic resonance imaging (MRI); (2) the effects of leiomyoma on uterine peristalsis. Mid-sagittal MRI was performed sequentially with T2-weighted single-shot fast spin-echo (SSFSE) in 3 normal ovulatory volunteers and 19 premenopausal women with uterine leiomyoma. Direction and frequency of movement of the junctional zone were evaluated using a cine mode display. Junctional zone movement was identified in all subjects. Direction of uterine peristalsis in normal volunteers was fundus-to-cervix during menstruation, cervix-to-fundus during the periovulatory phase, and isthmical during the mid- and late-luteal phases. Abnormal peristaltic patterns were detected in three of five patients with uterine leiomyoma during menstruation and in the mid-luteal phase of the cycle, respectively. Cine MRI is a novel method for evaluation of uterine peristalsis. Results of this pilot study suggest that abnormal uterine peristalsis during menstruation and the mid-luteal phase might be one of the causes of hypermenorrhea and infertility associated with uterine leiomyoma.

NOTE: Characterization of cirrhosis and hepatocellular carcinoma using low-angle x-ray scattering signatures of serum

NASA Astrophysics Data System (ADS)

Elshemey, Wael M.; Desouky, Omar S.; Mohammed, Mohammed S.; Elsayed, Anwar A.; El-houseini, Motawa E.

2003-09-01

The diagnosis of hepatocellular carcinoma (HCC) usually occurs at late stages in the disease when there are few effective treatment options. The measurement of the concentration of tumour markers in the serum of patients is a complementary tool frequently used for the interpretation of diagnostic imaging results. It is also used as a prognostic tool for the detection of cancer. Unfortunately, the sensitivity of tumour markers is still low and many times it yields normal results for cirrhotic and HCC patients. In the current work, the detection possibility of the structural changes in serum proteins accompanying cirrhosis and HCC is investigated using a low-angle x-ray scattering (LAXS) technique. The results show that there are significant differences in the LAXS profiles of cirrhosis and HCC lyophilized serum samples compared to normal. The changes in shape, total counts and position of the first scattering peak at 4.8°, which was previously reported to be sensitive to the structural changes in protein, showed the most characteristic deviations from normal serum. The present results are promising and would offer a potentially helpful complementary tool for monitoring cirrhosis and HCC.

Survivors of childhood cancer in South Australia attending a late-effects clinic: a descriptive report of psychological, cognitive, and academic late-effects.

PubMed

Roberts, Rachel M; Robins, Tamara; Gannoni, Anne F; Tapp, Heather

2014-01-01

This study provides a description of psychological late effects among a heterogeneous cohort of pediatric cancer survivors (N = 70) attending the South Australian Late-effects Clinic. Survivors reported more problems on the Strengths and Difficulties Questionnaire and the Child Behavior Checklist compared to normative data but no differences in Sluggish Cognitive Tempo scores. Forty-six percent of the sample reported school difficulties, and 12% of the sample age older than 15 reported smoking. Late-effects clinics should continue to monitor psychological well-being and health behaviors. Further research is recommended to determine whether sluggish cognitive tempo is a useful concept for the assessment of survivors.

Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases.

PubMed

Chen, Qi; Wang, Yao; Zhao, Min; Hyett, Jonathan; da Silva Costa, Fabricio; Nie, Guiying

2016-07-01

Preeclampsia is a pregnancy specific disorder affecting 3-5% of pregnancies worldwide. It is clinically divided into early-onset and late-onset subtypes. Placental factors are involved in the pathogenesis of preeclampsia. Growth differentiation factor 15 (GDF15), a protein of the transforming growth factor beta superfamily, is highly expressed in the placenta. However, it is unclear whether the circulating levels of GDF15 are altered in preeclampsia at the time of or prior to disease presentation. Serum samples across three trimesters from 29 healthy pregnancies, third trimester sera from 34 women presenting with preeclampsia (early-onset n=16, late-onset n=18) and 66 gestation-age-matched controls, and sera at 11-13weeks of pregnancy from women who later did (n=36) or did not (n=33) develop late-onset preeclampsia, were examined for GDF15 by ELISA. Serum GDF15 levels increased significantly with gestation in normal pregnancy. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia compared to their gestation-age-matched controls. This reduction was apparent in both early-onset and late-onset subtypes, but it was more profound in late-onset cases. At 11-13weeks of gestation, however, serum levels of GDF15 were similar between women who subsequently did and did not develop late-onset preeclampsia. Serum GDF15 increased with gestation age, reaching the highest level in the third trimester. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia, especially in late-onset cases. However, serum GDF15 was not altered in the first trimester in women destined to develop late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alterations of resting state networks and structural connectivity in relation to the prefrontal and anterior cingulate cortices in late prematurity.

PubMed

Degnan, Andrew J; Wisnowski, Jessica L; Choi, SoYoung; Ceschin, Rafael; Bhushan, Chitresh; Leahy, Richard M; Corby, Patricia; Schmithorst, Vincent J; Panigrahy, Ashok

2015-01-07

Late preterm birth is increasingly recognized as a risk factor for cognitive and social deficits. The prefrontal cortex is particularly vulnerable to injury in late prematurity because of its protracted development and extensive cortical connections. Our study examined children born late preterm without access to advanced postnatal care to assess structural and functional connectivity related to the prefrontal cortex. Thirty-eight preadolescents [19 born late preterm (34-36 /7 weeks gestational age) and 19 at term] were recruited from a developing community in Brazil. Participants underwent neuropsychological testing. Individuals underwent three-dimensional T1-weighted, diffusion-weighted, and resting state functional MRI. Probabilistic tractography and functional connectivity analyses were carried out using unilateral seeds combining the medial prefrontal cortex and the anterior cingulate cortex. Late preterm children showed increased functional connectivity within regions of the default mode, salience, and central-executive networks from both right and left frontal cortex seeds. Decreased functional connectivity was observed within the right parahippocampal region from left frontal seeding. Probabilistic tractography showed a pattern of decreased streamlines in frontal white matter pathways and the corpus callosum, but also increased streamlines in the left orbitofrontal white matter and the right frontal white matter when seeded from the right. Late preterm children and term control children scored similarly on neuropsychological testing. Prefrontal cortical connectivity is altered in late prematurity, with hyperconnectivity observed in key resting state networks in the absence of neuropsychological deficits. Abnormal structural connectivity indicated by probabilistic tractography suggests subtle changes in white matter development, implying disruption of normal maturation during the late gestational period.

Deletion of the late cornified envelope (LCE) 3B and 3C genes as a susceptibility factor for psoriasis

PubMed Central

de Cid, Rafael; Riveira-Munoz, Eva; Zeeuwen, Patrick L.J.M.; Robarge, Jason; Liao, Wilson; Dannhauser, Emma N.; Giardina, Emiliano; Stuart, Philip E.; Nair, Rajan; Helms, Cynthia; Escaramís, Georgia; Ballana, Ester; Martín-Ezquerra, Gemma; den Heijer, Martin; Kamsteeg, Marijke; Joosten, Irma; Eichler, Evan E.; Lázaro, Conxi; Pujol, Ramón M.; Armengol, Lluís; Abecasis, Gonçalo; Elder, James T.; Novelli, Giuseppe; Armour, John A.L.; Kwok, Pui; Bowcock, Anne; Schalkwijk, Joost; Estivill, Xavier

2011-01-01

Psoriasis is a common inflammatory skin disease with a prevalence of 2% to 3% in Caucasians1. In a genome-wide search for copy number variants (CNV) using a sample pooling approach we have identified a deletion comprising LCE3B and LCE3C, members of the late cornified envelope (LCE) gene cluster2. The absence of LCE3B and LCE3C (LCE3C-LCE3B-del) is significantly associated (p=1.38E-08) with risk of psoriasis in 2,831 samples from Spain, The Netherlands, Italy and the USA, and in a family-based study (p=5.4E-04). LCE3C-LCE3B-del is tagged by rs4112788 (r2=0.93), which is also strongly associated with psoriasis (p<6.6E-09). LCE3C-LCE3B-del shows epistatic effects with the HLA-Cw6 allele on the development of psoriasis in Dutch samples, and multiplicative effects in the other samples. LCE expression can be induced in normal epidermis by skin barrier disruption and is strongly expressed in psoriatic lesions, suggesting that compromised skin barrier function plays a role in psoriasis susceptibility. PMID:19169253

Mast cell phenotypes in the allograft after lung transplantation.

PubMed

Banga, Amit; Han, Yingchun; Wang, Xiaofeng; Hsieh, Fred H

2016-07-01

The burden of mast cell (MC) infiltration and their phenotypes, MC-tryptase (MCT ) and MC-tryptase/chymase (MCTC ), after lung transplantation (LT) has not been evaluated in human studies. We reviewed 20 transbronchial lung biopsy (TBLB) specimen from patients with early normal allograft (<6 months post-LT, n=5), late normal allograft (>6 months, n=5), A2 or worse acute cellular rejection (ACR, n=5), and chronic lung allograft dysfunction (CLAD, n=5). Slides were immunostained for tryptase and chymase. Total MC, MCT , MCTC and MCTC to-MCT ratio were compared between the four groups using a generalized linear mixed model. Irrespective of clinicopathologic diagnosis, MC burden tends to increase with time (r(2) =.56, P=.009). MCTC phenotype was significantly increased in the CLAD group (8.2±4.9 cells per HPF) in comparison with the other three groups (early normal: 1.6±1.7, P=.0026; late normal: 2.5±2.3, P=.048; ACR: 2.7±3.5, P=.021). Further, the ratio of MCTC to MCT was significantly increased in CLAD group as compared to the other three groups (P<.001 for all comparisons). The burden of MC may increase in the allograft as function of time. Patients with CLAD have an increased relative and absolute burden of MCTC phenotype MC. Future studies are needed to confirm these findings and evaluate the potential pathologic role of MCTC in allograft dysfunction. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Navesh K.; Li Tianyu; Chen, David Y.

Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; {>=}6 months, n = 170). The median radiation dosemore » was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. {>=}6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.« less

Classification of oral cancers using Raman spectroscopy of serum

NASA Astrophysics Data System (ADS)

Sahu, Aditi; Talathi, Sneha; Sawant, Sharada; Krishna, C. Murali

2014-03-01

Oral cancers are the sixth most common malignancy worldwide, with low 5-year disease free survival rates, attributable to late detection due to lack of reliable screening modalities. Our in vivo Raman spectroscopy studies have demonstrated classification of normal and tumor as well as cancer field effects (CFE), the earliest events in oral cancers. In view of limitations such as requirement of on-site instrumentation and stringent experimental conditions of this approach, feasibility of classification of normal and cancer using serum was explored using 532 nm excitation. In this study, strong resonance features of β-carotenes, present differentially in normal and pathological conditions, were observed. In the present study, Raman spectra of sera of 36 buccal mucosa, 33 tongue cancers and 17 healthy subjects were recorded using Raman microprobe coupled with 40X objective using 785 nm excitation, a known source of excitation for biomedical applications. To eliminate heterogeneity, average of 3 spectra recorded from each sample was subjected to PC-LDA followed by leave-one-out-cross-validation. Findings indicate average classification efficiency of ~70% for normal and cancer. Buccal mucosa and tongue cancer serum could also be classified with an efficiency of ~68%. Of the two cancers, buccal mucosa cancer and normal could be classified with a higher efficiency. Findings of the study are quite comparable to that of our earlier study, which suggest that there exist significant differences, other than β- carotenes, between normal and cancerous samples which can be exploited for the classification. Prospectively, extensive validation studies will be undertaken to confirm the findings.

Iron promotes protein insolubility and aging in C. elegans

PubMed Central

Klang, Ida M.; Schilling, Birgit; Sorensen, Dylan J.; Sahu, Alexandria K.; Kapahi, Pankaj; Andersen, Julie K.; Swoboda, Peter; Killilea, David W.; Gibson, Bradford W.; Lithgow, Gordon J.

2014-01-01

Many late-onset proteotoxic diseases are accompanied by a disruption in homeostasis of metals (metallostasis) including iron, copper and zinc. Although aging is the most prominent risk factor for these disorders, the impact of aging on metallostasis and its role in proteotoxic disease remain poorly understood. Moreover, it is not clear whether a loss of metallostasis influences normal aging. We have investigated the role of metallostasis in longevity of Caenorhabditis elegans. We found that calcium, copper, iron, and manganese levels increase as a function of age, while potassium and phosphorus levels tend to decrease. Increased dietary iron significantly accelerated the age-related accumulation of insoluble protein, a molecular pathology of aging. Proteomic analysis revealed widespread effects of dietary iron in multiple organelles and tissues. Pharmacological interventions to block accumulation of specific metals attenuated many models of proteotoxicity and extended normal lifespan. Collectively, these results suggest that a loss of metallostasis with aging contributes to age-related protein aggregation. PMID:25554795

Attentional bias modulation by reappraisal in patients with generalized anxiety disorder: an event-related potential study

PubMed Central

Han, H.Y.; Gan, T.; Li, P.; Li, Z.J.; Guo, M.; Yao, S.M.

2014-01-01

Affective states influence subsequent attention allocation. We evaluated emotional negativity bias modulation by reappraisal in patients with generalized anxiety disorder (GAD) relative to normal controls. Event-related potential (ERP) recordings were obtained, and changes in P200 and P300 amplitudes in response to negative or neutral words were noted after decreasing negative emotion or establishing a neutral condition. We found that in GAD patients only, the mean P200 amplitude after negative word presentation was much higher than after the presentation of neutral words. In normal controls, after downregulation of negative emotion, the mean P300 amplitude in response to negative words was much lower than after neutral words, and this was significant in both the left and right regions. In GAD patients, the negative bias remained prominent and was not affected by reappraisal at the early stage. Reappraisal was observed to have a lateralized effect at the late stage. PMID:24863650

Laser treatments of deep-seated brain lesions

NASA Astrophysics Data System (ADS)

Ward, Helen A.

1997-06-01

The five year survival rate of deep-seated malignant brain tumors after surgery/radiotherapy is virtually 100 percent mortality. Special problems include: (1) Lesions often present late. (2) Position: lesion overlies vital structures, so complete surgical/radiotherapy lesion destruction can damage vital brain-stem functions. (3) Difficulty in differentiating normal brain form malignant lesions. This study aimed to use the unique properties of the laser: (a) to minimize damage during surgical removal of deep-seated brain lesions by operating via fine optic fibers; and (b) to employ the propensity of certain lasers for absorption of dyes and absorption and induction of fluorescence in some brain substances, to differentiate borders of malignant and normal brain, for more complete tumor removal. In the method a fine laser endoscopic technique was devised for removal of brain lesions. The results of this technique, were found to minimize and accurately predict the extent of thermal damage and shock waves to within 1-2mm of the surgical laser beam. Thereby it eliminated the 'popcorn' effect.

[Expression and significance of adipocyte fatty acid-binding protein in placenta, serum and umbilical cord blood in preeclampsia].

PubMed

Yan, Jian-Ying; Wang, Xiao-Juan

2010-12-01

To investigate the change of adipocyte fatty acid-binding protein (FABP4) in maternal serum and umbilical cord blood and FABP4 mRNA placental expression in patients with preeclampsia (PE). A total of 60 women with PE and 60 normal pregnant women as control participated in this study.All are admitted to Fujian Maternity and Children Health Hospital for delivery from December 2008 to October 2009. Patients with PE were divided into early-onset group (n = 30, presented at ≤ 34 weeks of gestation) and late-onset group (n = 30, presented at > 34 weeks of gestation), with 30 normal pregnant women as early control group (≤ 34 weeks of gestation) and 30 as late control group (> 34 weeks of gestation). Enzyme-linked immunosorbent assay (ELISA) was used to detect FABP4, fasting serum glucose, fasting insulin (FINS) in maternal serum and FABP4 in umbilical cord blood. Real-time fluorescent quantitative reverse transcription PCR was used to detect placental FABP4 mRNA expression. Furthermore, clinical and biochemical parameters were recorded, such as body mass index (BMI), systolic pressure (SP), diastolic pressure (DP), mean arterial pressure (MAP), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), creatinine (Cr), uric acid (UA), glomerular filtration rate (GFR), 24 hours urine protein in pregnant women and neonatal weight. (1) Maternal serum FABP4 was (176 ± 9) ng/L in early-onset PE group and (170 ± 9) ng/L in late-onset PE group, significantly elevated as compared to (81 ± 13) ng/L in early control group and (94 ± 15) ng/L in late control group. (2) Mean maternal FINS, homeostasis model of assessment for insulin resistence index (HOMA-IR) were significantly elevated in the early-onset PE group and late-onset PE group as compared to control groups, respectively. (3) Mean placental FABP4 mRNA expression were significantly elevated in the early-onset PE group and late-onset PE group as compared to late control group. However, no significant difference was found in placental FABP4 mRNA expression between early-onset and late-onset PE groups. (4) Mean umbilical cord blood FABP4 concentrations were significantly decreased in the early-onset PE group and late-onset PE group as compared to late control group. Furthermore, umbilical cord blood FABP4 concentration correlated negatively with maternal serum FABP4 level and placental FABP4 mRNA expression, but positively with neonatal weight. (5) Mean maternal serum FABP4 concentrations correlated positively with placental FABP4 mRNA expression, TG, FINS, HOMA-IR, Cr, UA; and negatively with HDL, GFR. Increased FABP4 expression in maternal serum and placenta may be involved in the pathogenesis of preeclampsia. Increased FABP4 mRNA expression in placenta may contribute to high serum FABP4 level in women with PE.

Vegetation Cover Change in Yosemite National Park (California) Detected using Landsat Satellite Image Analysis

NASA Technical Reports Server (NTRS)

Potter, Christopher

2015-01-01

Landsat image analysis over the past 20+ years showed that consistent increases in the satellite normalized difference vegetation index (NDVI) during relatively dry years were confined to large wildfire areas that burned in the late 1980s and 1990s.

Differences in neural activation between preterm and full term born adolescents on a sentence comprehension task: implications for educational accommodations.

PubMed

Barde, Laura H F; Yeatman, Jason D; Lee, Eliana S; Glover, Gary; Feldman, Heidi M

2012-02-15

Adolescent survivors of preterm birth experience persistent functional problems that negatively impact academic outcomes, even when standardized measures of cognition and language suggest normal ability. In this fMRI study, we compared the neural activation supporting auditory sentence comprehension in two groups of adolescents (ages 9-16 years); sentences varied in length and syntactic difficulty. Preterms (n=18, mean gestational age 28.8 weeks) and full terms (n=14) had scores on verbal IQ, receptive vocabulary, and receptive language tests that were within or above normal limits and similar between groups. In early and late phases of the trial, we found interactions by group and length; in the late phase, we also found a group by syntactic difficulty interaction. Post hoc tests revealed that preterms demonstrated significant activation in the left and right middle frontal gyri as syntactic difficulty increased. ANCOVA showed that the interactions could not be attributed to differences in age, receptive language skill, or reaction time. Results are consistent with the hypothesis that preterm birth modulates brain-behavior relations in sentence comprehension as task demands increase. We suggest preterms' differences in neural processing may indicate a need for educational accommodations, even when formal test scores indicate normal academic achievement. Copyright © 2011 Elsevier Ltd. All rights reserved.

Research, management, and status of the osprey in North America

USGS Publications Warehouse

Henny, C.J.; Chancellor, R.D.

1977-01-01

Osprey populations were studied throughout North America during the last decade as a result of dramatic declines reported along the North Atlantic Coast in the1950s and early 1960s. Researchers used banding, localized studies, aerial surveys, and pesticide analyses to identify factors influencing regional populations. Declining populations showed extremely poor production, contamination by environmental pollutants (including DDT and its metabolites, dieldrin, and polychlorinated biphenyls) and thin-shelled eggs. Following the reduced use and eventual ban of DDT and dieldrin, productivity began to improve. Improvement in affected populations, mainly those along the Atlantic Coast and in the Great Lakes region, began in the late 1960s and is continuing in the 1970s. Most populations in the South Atlantic region, in Western North America, and in Florida and the Gulf of California appeared to be producing at normal or near-normal rates in the late 1960s and early 1970s. Although some of the most severely affected populations are still not producing at normal rates, the pattern of improvement and an increase in management activities, including provision of nesting platforms and establishment of Osprey management zones, allow cautious optimism about the future of the species in North America. With its low recruitment potential, however, recovery will be slow.

The value of three-dimensional photogrammetry in isolated sagittal synostosis: Impact of age and surgical technique on intracranial volume and cephalic index─a retrospective cohort study.

PubMed

Mertens, Christian; Wessel, Eline; Berger, Moritz; Ristow, Oliver; Hoffmann, Jürgen; Kansy, Katinka; Freudlsperger, Christian; Bächli, Heidrun; Engel, Michael

2017-12-01

The aim of this study was to compare the outcome of intracranial volume (ICV) and cephalic index (CI) between two different techniques for surgical therapy of sagittal synostosis. Between 2011 and 2015, all patients scheduled for surgical therapy of sagittal synostosis were consecutively enrolled. All patients younger than 6 months underwent early extended strip craniectomy (ESC group), and patients older than 6 months underwent late modified pi-procedure (MPP group). To measure ICV and CI, data acquisition was performed via three-dimensional photogrammetry, 1 day before (T0) and between 10 and 12 weeks after surgery (T1). Results were compared with an age-matched reference group of healthy children. Perioperative parameters, as duration of surgery and the amount of blood loss of both surgical procedures were analyzed. A total of 85 patients were enrolled. Of the patients, 48 underwent an extended strip craniotomy with parietal osteotomies and biparietal widening and 37 patients underwent a late modified pi-procedure. There was no significant difference between the ESC group and the MPP group regarding the efficacy of improving CI (p > 0.05). Both techniques were able to normalize CI and to improve head shape. ICV was normal compared to age-matched norm-groups with both techniques, pre- and postoperatively. However, duration of the surgical procedure and calculated blood loss were significantly lower in the ESC group (p < 0.05). ESC and MPP were effective techniques to normalize cephalic index (CI) and improve head shape at their recommended time of surgery. Measurement of ICV and CI with 3D photogrammetry is a valid method to objectively evaluate patients before and after surgery without exposing pediatric patients to ionizing radiation. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Prevalence of Alzheimer's pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives.

PubMed

Lampert, Erika J; Roy Choudhury, Kingshuk; Hostage, Christopher A; Petrella, Jeffrey R; Doraiswamy, P Murali

2013-01-01

A positive family history (FH) is a risk factor for late-onset Alzheimer's disease (AD). Our aim was to examine the effects of FH on pathological and neuronal loss biomarkers across the cognitive spectrum. Cross-sectional analyses of data from a national biomarker study. The Alzheimer's Disease Neuroimaging Initiative national study. 257 subjects (ages 55-89), divided into cognitively normal (CN), mild cognitive impairment (MCI), and AD groups, with CSF and FH data. Cerebrospinal fluid (CSF) Aβ42, tau, and tau/Aβ42 ratio, MRI-measured hippocampal volumes. Univariate and multivariate analyses. In MCI, CSF Aβ42 was lower (p = .005), t-tau was higher (p = 0.02) and t-tau/Aβ42 ratio was higher (p = 0.002) in FH+ than FH- subjects. A significant residual effect of FH on pathologic markers in MCI remained after adjusting for ApoE4 (p<0.05). Among CN, 47% of FH+ exhibited "pathologic signature of AD" (CSF t-tau/Aβ42 ratio >0.39) versus 21% of FH- controls (p = 0.03). The FH effect was not significant in AD subjects. Hippocampal and intracranial volumes did not differ between FH+ and FH- subjects in any group. A positive family history of late-onset AD is associated with a higher prevalence of an abnormal cerebral beta-amyloid and tau protein phenotype in MCI. The unexplained genetic heritability in family history is about the half the size of the ApoE4 effect. Longitudinal studies are warranted to more definitively examine this issue.

THE INFLUENCE OF HYDROCORTISONE ON THE ACTION OF EXCESS VITAMIN A ON LIMB BONE RUDIMENTS IN CULTURE

PubMed Central

Fell, Honor B.; Thomas, Lewis

1961-01-01

The effect of hydrocortisone has been studied in organ cultures of the cartilaginous long bone rudiments from 7-day chick embryos and of the well ossified limb bones from late fetal mice. In the chick rudiments, which grow rapidly in culture, the growth rate was much reduced by hydrocortisone, less intercellular material was formed, and the hypertrophic cells of the shaft were much smaller than in the controls in normal medium. In the late fetal mouse bones, which grow very little in culture, hydrocortisone had no obvious effect on growth but arrested resorption of the cartilage. These effects resemble those described by others in the skeleton of animals treated with cortisone or hydrocortisone. The influence of hydrocortisone on the response of the chick and mouse explants to excess vitamin A was investigated. In the presence of excess vitamin A, cartilage (chick, mouse) and bone (mouse) rapidly disintegrated, but when hydrocortisone also was added to the medium, this dissolution of the intercellular material was much retarded, though not suppressed. The retardative action of hydrocortisone on the changes produced by excess vitamin A in skeletal tissue in culture, contrasts sharply with the strongly additive effect of the two agents on the skeleton in the intact animal (Selye, 1958). It is suggested that this discrepancy between the results obtained in vitro and in vivo is probably due to systemic factors that operate in the body but are eliminated in organ cultures. PMID:13698768

Remagne California margin

USGS Publications Warehouse

Hagstrum, J.T.; Sedlock, R.L.

1998-01-01

Paleomagnetic data for two sections of Cretaceous forearc strata with different structural attitudes on Santa Margarita and Magdalena Islands in Baja California Sur, Mexico, indicate that these rocks have been remagnetized, probably during the late Cenozoic. The in situ paleomagnetic directions, however, are similar to data from other Cretaceous rocks on peninsular California with unexpectedly shallow inclinations and easterly declinations. These data have been interpreted as indicating either northward tectonic transport (10??15?? of latitude) and clockwise rotation (>20??) or compaction shallowing of magnetic inclinations in sedimentary rocks combined with southwestward tilting of plutonic rocks. The available paleomagnetic data for Cretaceous forearc strata in southern and Baja California can be divided into three groups: (1) sections with normal-polarity magnetizations that fail fold tests and are remagnetized, (2) sections with normal-polarity magnetizations with no or inconclusive fold tests that may or may not be remagnetized, and (3) sections with both normaland reversed-polarity intervals where pervasive remagnetization has not occurred. Other rocks of the Mesozoic Great Valley Group, Coast Range ophiolite, and Franciscan Complex in California also have secondary magnetizations with directions similar to younger geomagnetic field directions. Although these widespread remagnetizations could have variable local causes, we propose regional burial and uplift, related to changes in subduction parameters, as a possible explanation. Two episodes of remagnetization are apparent: one in the Late Cretaceous and a second in the late Cenozoic. On the other hand, the unremagnetized and apparently reliable data from sedimentary and plutonic rocks on the Baja Peninsula consistently indicate northward translation (14???? 3??) and clockwise rotation (29???? 8??) with respect to North America since the Late Cretaceous. Copyright 1998 by the American Geophysical Union.

FDG and Amyloid PET in Cognitively Normal Individuals at Risk for Late-Onset Alzheimer’s Disease

PubMed Central

Murray, John; Tsui, Wai H.; Li, Yi; McHugh, Pauline; Williams, Schantel; Cummings, Megan; Pirraglia, Elizabeth; Solnes, Lilja; Osorio, Ricardo; Glodzik, Lidia; Vallabhajosula, Shankar; Drzezga, Alexander; Minoshima, Satoshi; de Leon, Mony J.; Mosconi, Lisa

2014-01-01

Having a parent affected by late-onset Alzheimer’s disease (AD) is a major risk factor for cognitively normal (NL) individuals. This study explores the potential of PET with 18F-FDG and the amyloid- β (Aβ) tracer 11C-Pittsburgh Compound B (PiB) for detection of individual risk in NL adults with AD-parents. Methods FDG− and PiB-PET was performed in 119 young to late-middle aged NL individuals including 80 NL with positive family history of AD (FH+) and 39 NL with negative family history of any dementia (FH−). The FH+ group included 50 subjects with maternal (FHm) and 30 with paternal family history (FHp). Individual FDG and PiB scans were Z scored on a voxel-wise basis relative to modality-specific reference databases using automated procedures and rated as positive or negative (+/−) for AD-typical abnormalities using predefined criteria. To determine the effect of age, the cohort was separated into younger (49 ± 9 y) and older (68 ± 5 y) groups relative to the median age (60 y). Results Among individuals of age >60 y, as compared to controls, NL FH+ showed a higher frequency of FDG+ scans vs. FH− (53% vs. 6% p < 0.003), and a trend for PiB+ scans (27% vs. 11%; p = 0.19). This effect was observed for both FHm and FHp groups. Among individuals of age ≤60 y, NL FHm showed a higher frequency of FDG+ scans (29%) compared to FH− (5%, p = 0.04) and a trend compared to FHp (11%) (p = 0.07), while the distribution of PiB+ scans was not different between groups. In both age cohorts, FDG+ scans were more frequent than PiB+ scans among NL FH+, especially FHm (p < 0.03). FDG-PET was a significant predictor of FH+ status. Classification according to PiB status was significantly less successful. Conclusions Automated analysis of FDG− and PiB-PET demonstrates higher rates of abnormalities in at-risk FH+ vs FH− subjects, indicating potentially ongoing early AD-pathology in this population. The frequency of metabolic abnormalities was higher than that of Aβ pathology in the younger cohort, suggesting that neuronal dysfunction may precede major aggregated Aβ burden in young NL FH+. Longitudinal follow-up is required to determine if the observed abnormalities predict future AD. PMID:25530915

Placental three-dimensional power Doppler indices in mid-pregnancy and late pregnancy complicated by gestational diabetes mellitus.

PubMed

Surányi, A; Kozinszky, Z; Molnár, A; Nyári, T; Bitó, T; Pál, A

2013-10-01

The aim of our study was to evaluate placental three-dimensional power Doppler indices in diabetic pregnancies in the second and third trimesters and to compare them with those of the normal controls. Placental vascularization of pregnant women was determined by three-dimensional power Doppler ultrasound technique. The calculated indices included vascularization index (VI), flow index (FI), and vascularization flow index (VFI). Uncomplicated pregnancies (n = 113) were compared with pregnancies complicated by gestational diabetes mellitus (n = 56) and diabetes mellitus (n = 43). The three-dimensional power Doppler indices were not significantly different between the two diabetic subgroups. All the indices in diabetic patients were significantly reduced compared with those in non-diabetic individuals (p < 0.001). Placental three-dimensional power Doppler indices are slightly diminished throughout diabetic pregnancy [regression coefficients: -0.23 (FI), -0.06 (VI), and -0.04 (VFI)] and normal pregnancy [regression coefficients: -0.13 (FI), -0.20 (VI), and -0.11 (VFI)]. The uteroplacental circulation (umbilical and uterine artery) was not correlated significantly to the three-dimensional power Doppler indices. If all placental indices are low during late pregnancy, then the odds of the diabetes are significantly high (adjusted odds ratio: 1.10). A decreased placental vascularization could be an adjunct sonographic marker in the diagnosis of diabetic pregnancy in mid-gestation and late gestation. © 2013 John Wiley & Sons, Ltd.

Are evoked potentials in patients with adult-onset pompe disease indicative of clinically relevant central nervous system involvement?

PubMed

Wirsching, Andreas; Müller-Felber, Wolfgang; Schoser, Benedikt

2014-08-01

Pompe disease is a multisystem autosomal recessive glycogen storage disease. Autoptic findings in patients with classic infantile and late-onset Pompe disease have proven that accumulation of glycogen can also be found in the peripheral and central nervous system. To assess the functional role of these pathologic findings, multimodal sensory evoked potentials were analyzed. Serial recordings for brainstem auditory, visual, and somatosensory evoked potentials of 11 late-onset Pompe patients were reviewed. Data at the onset of the enzyme replacement therapy with alglucosidase alfa were compared with follow-up recordings at 12 and 24 months. Brainstem auditory evoked potentials showed a delayed peak I in 1/10 patients and an increased I-III and I-V interpeak latency in 1/10 patients, respectively. The III-V interpeak latencies were in the normal range. Visual evoked potentials were completely normal. Median somatosensory evoked potentials showed an extended interpeak latency in 3/9 patients. Wilcoxon tests comparing age-matched subgroups found significant differences in brainstem auditory evoked potentials and visual evoked potentials. We found that the majority of recordings for evoked potentials were within the ranges for standard values, therefore reflecting the lack of clinically relevant central nervous system involvement. Regular surveillance by means of evoked potentials does not seem to be appropriate in late-onset Pompe patients.

Long-term functional health status and exercise test variables for patients with pulmonary atresia with intact ventricular septum: A Congenital Heart Surgeons Society study

PubMed Central

Karamlou, Tara; Poynter, Jeffrey A.; Walters, Henry L.; Rhodes, Jonathan; Bondarenko, Igor; Pasquali, Sara K.; Fuller, Stephanie M.; Lambert, Linda M.; Blackstone, Eugene H.; Jacobs, Marshall L.; Duncan, Kim; Caldarone, Christopher A.; Williams, William G.; McCrindle, Brian W.

2013-01-01

Background A bias favoring biventricular (BV) repair exists regarding choice of repair pathway for patients with pulmonary atresia with intact ventricular septum (PAIVS). We sought to determine the implications of moving borderline candidates down a BV route in terms of late functional health status (FHS) and exercise capacity (EC). Methods Between 1987 and 1997, 448 neonates with PAIVS were enrolled in a multi-institutional study. Late EC and FHS were assessed following repair (mean 14 years) using standardized exercise testing and 3 validated FHS instruments. Relationships between FHS, EC, morphology, and 3 end states (ie, BV, univentricular [UV], or 1.5-ventricle repair [1.5V]) were evaluated. Results One hundred two of 271 end state survivors participated (63 BV, 25 UV, and 14 1.5V). Participants had lower FHS scores in domains of physical functioning (P < .001) compared with age- and sex-matched normal controls, but scored significantly higher in nearly all psychosocial domains. EC was higher in 1.5V-repair patients (P = .02), whereas discrete FHS measures were higher in BV-repair patients. Peak oxygen consumption was low across all groups, and was positively correlated with larger initial tricuspid valve z-score (P < .001), with an enhanced effect within the BV-repair group. Conclusions Late patient-perceived physical FHS and measured EC are reduced, regardless of PAIVS repair pathway, with an important dichotomy whereby patients with PAIVS believe they are doing well despite important physical impediments. For those with smaller initial tricuspid valve z-score, achievement of survival with BV repair may be at a cost of late deficits in exercise capacity, emphasizing that better outcomes may be achieved for borderline patients with a 1.5V- or UV-repair strategy. PMID:23374986

Effectiveness of screening for gestational diabetes during the late gestational period among pregnant Turkish women.

PubMed

Kurtbas, Handan; Keskin, H Levent; Avsar, A Filiz

2011-06-01

To assess the incidence of gestational diabetes mellitus (GDM) beyond 30 gestational weeks (GW) in pregnant Turkish women and to determine the criteria for repeating the test during the late period of gestation when the results were normal after the initial screen. Two hundred pregnant women were enrolled. Maternal age, gravidity, parity and presence of other risk factors (family history of diabetes mellitus, habitual abortions, prior fetal macrosomia, obesity, gestational hypertension history) were collected. First, GDM was evaluated between the 24th and 28th GW by screening (50-g glucose challenge test) and diagnostic tests. This protocol was repeated again at least 1 month from the first screen at the 30th-34th GW in all patients, except those diagnosed with GDM due to an abnormal 3-h test. The results were compared with the clinical risk factors. In total, 19.5% of the cases had positive results in the first screening test. Six patients were diagnosed with GDM. Among the remaining 194 pregnancies, another 10 cases were diagnosed as having GDM with repeated tests, and the incidence of newly diagnosed GDM was 5.2%. Only the mean age (34.2 years) (P = 0.010) and a history of delivering a macrosomic infant (P < 0.010) were significantly high in the late-gestation GDM-positive cases. Even when early screening tests are negative, pregnancies with advanced maternal ages and those with a history of delivering a macrosomic infant should be re-evaluated for GDM during the late gestational period with screening and diagnostic tests. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

Women with breast cancer report substantially more disease- and treatment-related side or late effects than registered by clinical oncologists: a cross-sectional study of a standard follow-up program in an oncological department.

PubMed

Ellegaard, Mai-Britt Bjørklund; Grau, Cai; Zachariae, Robert; Jensen, Anders Bonde

2017-08-01

Follow-up after breast cancer treatment is standard due to the risk of development of new primary cancers and recurrent disease. The aim of the present study was to evaluate a standard follow-up program in an oncological department by assessing: (1) Symptoms or signs of new primary cancer or recurrent disease, (2) Disease- and treatment-related physical and psychosocial side or late effects, and (3) relevant actions by oncology staff. In a cross-sectional study, 194 women who came for follow-up visit after treatment for primary surgery were included. The clinical oncologists registered symptoms and signs of recurrent disease or new primary cancer. Side or late effects were both assessed by patient and the clinical oncologists. Loco-regional or distant signs of recurrent disease were suspected in eight (5%) patients. Further examinations revealed no disease recurrence. Most patients (93%) reported some degree of side or late effects. Statistically significant more side or late effects were reported by the women (average: 6.9) than registered by the clinical oncologists (average: 2.4), p < 0.001. The three most often patient-reported side or late effects were hot flushes (35%), fatigue (32%), and sleep disturbance (31%). None of the scheduled or additional visits resulted in detection of recurrent disease. Furthermore, the majority of patients reported side or late effects. Statistically significant more women reported side or late effects than registered by the clinical oncologists. This suggests the need for rethinking of the follow-up programs with more emphasis upon side or late effects of the treatment.

Late effects awareness website for pediatric survivors of acute lymphocytic leukemia

PubMed Central

Navarro, Ana; Klonoff, Elizabeth A.

2018-01-01

Objectives Every day 43 children are newly diagnosed with cancer. Fortunately, almost 90% of these childhood cancer patients will survive. However, 60–90% of these survivors will experience late effects, health problems that occur months or years after treatment has ended. Late effects could occur as a result of the disease, its treatment, and patient-related factors. The two main objectives of this research are to: 1) Examine the existence of all web-based resources for childhood cancer survivors with acute lymphocytic leukemia which focus on medical and psychological aspects of late effects, and 2) Create an innovative website specifically designed to fill this void. Materials and methods A systematic literature review, followed by input from >20 different organizations, resulted in the creation of LEAP3 AHEAD (Late Effects Awareness for Patients, Physicians and the Public; Advancing Health and Eliminating All Disparities), a multi-dimensional website centering on late effects. Results An extensive review revealed 14 pediatric cancer websites, none of which focused exclusively on late effects. LEAP3 AHEAD is the first interactive website for acute lympocytic leukemia childhood cancer survivors and families, as well as physicians, and the public to: a) increase awareness about risks, detection, diagnosis, treatment, and prevention of medical and psychological late effects, b) provide suggestions to successfully reintegrate into schools, careers, and socially, and c) present opportunities including camps, scholarships, and pet therapy programs. Conclusion LEAP3 AHEAD is the first national website to provide a comprehensive, accessible, affordable, and multi-dimensional resource for pediatricians, internists, nurse practitioners, psychologists, survivors and their families, as well as the public about late effects. PMID:29451924

Style of Cenozoic extensional deformation in the central Beaverhead Mountains, Idaho-Montana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kellogg, K.S.

1993-04-01

Cenozoic extension in the upper Medicine Lodge Creek area in the Beaverhead Mountains was accommodated along numerous low- to high-angle, west-facing normal faults. These faults have repeated moderately east-dipping (by 20--40[degree]) Tertiary rocks that are as old as the Eocene Medicine Lodge Volcanics and that include conformably overlying Miocene and Oligocene conglomerate, tuffaceous sandstone, siltstone, and limestone; a reasonable restoration of Tertiary faulting suggests that the region has extended about 20 percent. At least one normal fault soles into the Late Cretaceous Cabin thrust, one of at least four major Cordilleran thrusts in the Beaverhead Mountains and the Tendoy Mountainsmore » immediately to the east. The Cabin thrust places enigmatic quartzite (age is between Middle Proterozoic and Lower Cambrian) and Archean gneiss above Mississippian to Ordovician rocks. The formation of the north-northwest-trending upper Medicine Lodge Valley was controlled mostly by low-angle normal faults along its east side, where Eocene volcanics and overlying sedimentary rocks dip about 25[degree] eastward against Archean rocks. Faceted spurs are prominent but no scarps are visible, suggesting that last movement is pre-Holocene. Other large-displacement normal faults at higher elevations show relatively little topographic expression. The Late Proterozoic or Cambrian Beaverhead impact structure, defined by wide-spread shatter-coning, pseudotachylite formation, and localized brecciation, make interpretation of some extensive breccia zones in Archean rocks along the east side of Medicine Lodge Valley problematic. The proximity of the breccias to Tertiary normal faults makes a Tertiary age attractive, yet the breccias are older than pseudotachylite interpreted to have been produced by the impact.« less

Research and clinical aspects of the late effects of poliomyelitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Halstead, L.S.; Wiechers, D.O.

1986-01-01

This book contains 32 selections. Some of the titles are: Late effects of Polio: Historical Perspectives; Sleep-Disordered Breathing as a Late Effect of Poliomyelitis; Clinical Subtypes, DNA Repair Efficiency, and Therapeutic Trials in the Post-Polio Syndromes; and Post-Polio Muscle Function.

Doxorubicin-conjugated mesoporous magnetic colloidal nanocrystal clusters stabilized by polysaccharide as a smart anticancer drug vehicle.

PubMed

Li, Dian; Tang, Jing; Wei, Chuan; Guo, Jia; Wang, Shilong; Chaudhary, Deeptangshu; Wang, Changchun

2012-09-10

Fabrication of magnetic nanocarriers that demonstrate enhanced biocompatibility and excellent colloidal stability is critical for the application of magnetic-motored drug delivery, and it remains a challenge. Herein, a novel approach to synthesize mesoporous magnetic colloidal nanocrystal clusters (MMCNCs) that are stabilized by agarose is described; these clusters demonstrate high magnetization, large surface area and pore volume, excellent colloidal stability, enhanced biocompatibility, and acid degradability. The hydroxyl groups of agarose, which cover the surface of the magnetic nanocrystals, are modified with vinyl groups, followed by click reaction with mercaptoacetyl hydrazine to form the terminal hydrazide (-CONHNH(2)). The anticancer agent doxorubicin (DOX) is then conjugated to MMCNCs through a hydrazone bond. The resulting hydrazone is acid cleavable, thereby providing a pH-sensitive drug release capability. This novel carrier provides an important step towards the construction of a new family of magnetic-motored drug-delivery systems. The experimental results show that the release rate of DOX from the DOX-conjugated MMCNCs (MMCNCs-DOX) is dramatically improved at low pH (tumor cell: pH 4-5 in the late stage of endolysosome and pH 5-6 from the early to late endosome), while almost no DOX is released at neutral pH (blood plasma). The cell cytotoxicity of the MMCNCs-DOX measured by MTT assay exhibits a comparable antitumor efficacy but lower cytotoxicity for normal cell lines, when measured against the free drug, thus achieving the aim of reducing side effects to normal tissues associated with controlled drug release. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cardio-renal and metabolic adaptations during pregnancy in female rats born small: implications for maternal health and second generation fetal growth.

PubMed

Gallo, Linda A; Tran, Melanie; Moritz, Karen M; Mazzuca, Marc Q; Parry, Laura J; Westcott, Kerryn T; Jefferies, Andrew J; Cullen-McEwen, Luise A; Wlodek, Mary E

2012-02-01

Intrauterine growth restriction caused by uteroplacental insufficiency increases risk of cardiovascular and metabolic disease in offspring. Cardio-renal and metabolic responses to pregnancy are critical determinants of immediate and long-term maternal health. However, no studies to date have investigated the renal and metabolic adaptations in growth restricted offspring when they in turn become pregnant. We hypothesised that the physiological challenge of pregnancy in growth restricted females exacerbates disease outcome and compromises next generation fetal growth. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on day 18 of gestation in WKY rats and F1 female offspring birth and postnatal body weights were recorded. F1 Control and Restricted females were mated at 4 months and blood pressure, renal and metabolic parameters were measured in late pregnancy and F2 fetal and placental weights recorded. Age-matched non-pregnant Control and Restricted F1 females were also studied. F1 Restricted females were born 10-15% lighter than Controls. Basal insulin secretion and pancreatic β-cell mass were reduced in non-pregnant Restricted females but restored in pregnancy. Pregnant Restricted females, however, showed impaired glucose tolerance and compensatory glomerular hypertrophy, with a nephron deficit but normal renal function and blood pressure. F2 fetuses from Restricted mothers exposed to physiological measures during pregnancy were lighter than Controls highlighting additive adverse effects when mothers born small experience stress during pregnancy. Female rats born small exhibit mostly normal cardio-renal adaptations but altered glucose control during late pregnancy making them vulnerable to lifestyle challenges.

Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use.

PubMed

Ashtari, Manzar; Cervellione, Kelly; Cottone, John; Ardekani, Babak A; Sevy, Serge; Kumra, Sanjiv

2009-01-01

There is growing evidence that adolescence is a key period for neuronal maturation. Despite the high prevalence of marijuana use among adolescents and young adults in the United States and internationally, very little is known about its impact on the developing brain. Based on neuroimaging literature on normal brain developmental during adolescence, we hypothesized that individuals with heavy cannabis use (HCU) would have brain structure abnormalities in similar brain regions that undergo development during late adolescence, particularly the fronto-temporal connection. Fourteen young adult males in residential treatment for cannabis dependence and 14 age-matched healthy male control subjects were recruited. Patients had a history of HCU throughout adolescence; 5 had concurrent alcohol abuse. Subjects underwent structural and diffusion tensor magnetic resonance imaging. White matter integrity was compared between subject groups using voxelwise and fiber tractography analysis. Voxelwise and tractography analyses revealed that adolescents with HCU had reduced fractional anisotropy, increased radial diffusivity, and increased trace in the homologous areas known to be involved in ongoing development during late adolescence, particularly in the fronto-temporal connection via arcuate fasciculus. Our results support the hypothesis that heavy cannabis use during adolescence may affect the trajectory of normal brain maturation. Due to concurrent alcohol consumption in five HCU subjects, conclusions from this study should be considered preliminary, as the DTI findings reported here may be reflective of the combination of alcohol and marijuana use. Further research in larger samples, longitudinal in nature, and controlling for alcohol consumption is needed to better understand the pathophysiology of the effect of cannabis on the developing brain.

Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke

PubMed Central

Liu, Zhongwu; Chopp, Michael

2015-01-01

Astrocytes are the most abundant cell type within the central nervous system. They play essential roles in maintaining normal brain function, as they are a critical structural and functional part of the tripartite synapses and the neurovascular unit, and communicate with neurons, oligodendrocytes and endothelial cells. After an ischemic stroke, astrocytes perform multiple functions both detrimental and beneficial, for neuronal survival during the acute phase. Aspects of the astrocytic inflammatory response to stroke may aggravate the ischemic lesion, but astrocytes also provide benefit for neuroprotection, by limiting lesion extension via anti-excitotoxicity effects and releasing neurotrophins. Similarly, during the late recovery phase after stroke, the glial scar may obstruct axonal regeneration and subsequently reduce the functional outcome; however, astrocytes also contribute to angiogenesis, neurogenesis, synaptogenesis, and axonal remodeling, and thereby promote neurological recovery. Thus, the pivotal involvement of astrocytes in normal brain function and responses to an ischemic lesion designates them as excellent therapeutic targets to improve functional outcome following stroke. In this review, we will focus on functions of astrocytes and astrocyte-mediated events during stroke and recovery. We will provide an overview of approaches on how to reduce the detrimental effects and amplify the beneficial effects of astrocytes on neuroprotection and on neurorestoration post stroke, which may lead to novel and clinically relevant therapies for stroke. PMID:26455456

After the bomb drops: A new look at radiation-induced multiple organ dysfunction syndrome (MODS)

PubMed Central

Williams, Jacqueline P.; McBride, William H.

2012-01-01

Purpose There is increasing concern that, since the Cold War era, there has been little progress regarding the availability of medical countermeasures in the event of either a radiological or nuclear incident. Fortunately, since much is known about the acute consequences that are likely to be experienced by an exposed population, the probability of survival from the immediate hematological crises after total body irradiation (TBI) has improved in recent years. Therefore focus has begun to shift towards later down-stream effects, seen in such organs as the gastrointestinal tract (GI), skin, and lung. However, the mechanisms underlying therapy-related normal tissue late effects, resulting from localised irradiation, have remained somewhat elusive and even less is known about the development of the delayed syndrome seen in the context of whole body exposures, when it is likely that systemic perturbations may alter tissue microenvironments and homeostasis. Conclusions The sequence of organ failures observed after near-lethal TBI doses are similar in many ways to that of multiple organ dysfunction syndrome (MODS), leading to multiple organ failure (MOF). In this review, we compare the mechanistic pathways that underlie both MODS and delayed normal tissue effects since these may impact on strategies to identify radiation countermeasures. PMID:21417595

Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy for Early Prostate Cancer: Results From the UK Medical Research Council RT01 Trial (ISRCTN47772397)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syndikus, Isabel; Morgan, Rachel C.; Sydes, Matthew R., E-mail: ms@ctu.mrc.ac.u

2010-07-01

Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. Methods and Materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Managementmore » (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade {>=}2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade {>=}2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade {>=}2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.« less

Knowledge of Memory Aging in Students, Caregivers, and Senior Service Providers

ERIC Educational Resources Information Center

Cherry, Katie E.; Allen, Priscilla D.; Boudreaux, Emily O.; Robichaux, Mary L.; Hawley, Karri S.

2009-01-01

The Knowledge of Memory Aging Questionnaire (KMAQ) (Cherry, Brigman, Hawley, & Reese, 2003) measures laypersons' knowledge of normal memory changes in late life and pathological deficits due to nonnormative factors such as adult dementia. In this study, we examined memory knowledge in community college and university students, caregivers, and…

Nutritional condition of Northern Yellowstone Elk

USGS Publications Warehouse

Cook, R.C.; Cook, J.G.; Mech, L.D.

2004-01-01

Ultrasonography and body condition scoring was used to estimate nutritional condition of northern Yellowstone elk in late winter. Probability of pregnancy was related to body fat, and lactating cows had 50% less fat than non-lactating cows. For mild to normal winters, most of the elk were in good condition.

Late Presentation of a Type III Axis Fracture with Spondyloptosis

PubMed Central

Jayakumar, Prakash; Choi, David; Casey, Adrian

2008-01-01

A 58-year-old man presented with an undiagnosed Effendi type III classification fracture and spondyloptosis of the axis with remarkably normal neurology. We discuss his surgery 4 years since the initial injury, and the presentation, features and management of fractures of the axis. PMID:18430325

General anesthesia suppresses normal heart rate variability in humans

NASA Astrophysics Data System (ADS)

Matchett, Gerald; Wood, Philip

2014-06-01

The human heart normally exhibits robust beat-to-beat heart rate variability (HRV). The loss of this variability is associated with pathology, including disease states such as congestive heart failure (CHF). The effect of general anesthesia on intrinsic HRV is unknown. In this prospective, observational study we enrolled 100 human subjects having elective major surgical procedures under general anesthesia. We recorded continuous heart rate data via continuous electrocardiogram before, during, and after anesthesia, and we assessed HRV of the R-R intervals. We assessed HRV using several common metrics including Detrended Fluctuation Analysis (DFA), Multifractal Analysis, and Multiscale Entropy Analysis. Each of these analyses was done in each of the four clinical phases for each study subject over the course of 24 h: Before anesthesia, during anesthesia, early recovery, and late recovery. On average, we observed a loss of variability on the aforementioned metrics that appeared to correspond to the state of general anesthesia. Following the conclusion of anesthesia, most study subjects appeared to regain their normal HRV, although this did not occur immediately. The resumption of normal HRV was especially delayed on DFA. Qualitatively, the reduction in HRV under anesthesia appears similar to the reduction in HRV observed in CHF. These observations will need to be validated in future studies, and the broader clinical implications of these observations, if any, are unknown.

Investigating the relationship between FMR1 allele length and cognitive ability in children: a subtle effect of the normal allele range on the normal ability range?

PubMed

Loat, C S; Craig, G; Plomin, R; Craig, I W

2006-09-01

The FMR1 gene contains a trinucleotide repeat tract which can expand from a normal size of around 30 repeats to over 200 repeats, causing mental retardation (Fragile X Syndrome). Evidence suggests that premutation males (55-200 repeats) are susceptible to a late-onset tremor/ataxia syndrome and females to premature ovarian failure, and that intermediate alleles ( approximately 41-55 repeats) and premutations may be in excess in samples with special educational needs. We explored the relationship between FMR1 allele length and cognitive ability in 621 low ability and control children assessed at 4 and 7 years, as well as 122 students with high IQ. The low and high ability and control samples showed no between-group differences in incidence of longer alleles. In males there was a significant negative correlation between allele length and non-verbal ability at 4 years (p = 0.048), academic achievement in maths (p = 0.003) and English (p = 0.011) at 7 years, and IQ in the high ability group (p = 0.018). There was a significant negative correlation between allele length and a standardised score for IQ and general cognitive ability at age 7 in the entire male sample (p = 0.002). This suggests that, within the normal spectrum of allele length, increased repeat numbers may have a limiting influence on cognitive performance.

Ageing Holocaust survivors in Australia.

PubMed

Paratz, Elizabeth D; Katz, Benny

2011-02-21

In recent years, a phenomenon of "late effects of the Holocaust" has emerged, with impacts on the psychological and physical health of ageing Holocaust survivors. As Holocaust survivors age, they may experience heightened anxiety around normal processes of ageing, worsened post-traumatic stress disorder with cognitive decline, and fear of the medical system. Holocaust survivors are at increased risk of osteoporosis, cardiometabolic disease due to hypothalamic-pituitary-adrenal axis dysfunction, cancer, and sequelae of Nazi medical experiments. From existing medical literature on this topic, practical principles of management are derived to create a framework for sensitive medical management of Holocaust survivors in Australia. The issues discussed are also relevant to the wider geriatric refugee or prisoner-of-war experience.

Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Othmane, K.B.; Speer, M.C.; Stauffer, J.

1995-09-01

Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive Limb Girdle muscular dystrophy (LGMD2C) characterized by late age of onset, proximal muscle weakness leading to disability, high creatine kinase values, normal intelligence and normal dystrophin in muscle biopsy. We have shown previously that three DLMD families from Tunisia are linked to chromosome 13q12. To further localize the LGMD2C gene, we have investigated seven additional families (119 individuals). Both genotyping and two-point linkage analysis were performed as described elsewhere. 7 refs., 1 fig., 1 tab.

Structural geology of western part of Lemhi Range, east-central Idaho

USGS Publications Warehouse

Tysdal, Russell G.

2002-01-01

The Poison Creek Anticline is a major fold that occupies a large part of the western part of the Lemhi Range. The fold is now broken by normal faults, but removal of displacement on the normal faults permitted reconstruction of the anticline. The fold formed during late Mesozoic compressional deformation in the hinterland of the Cordilleran thrust belt. It is in the hanging wall of the Poison Creek thrust fault, a major fault in east-central Idaho, that displaced Proterozoic strata over lower Paleozoic rocks.

Effects of early and late harvest on agronomic performance and stability of late blight resistant (R-gene free) potato genotypes

USDA-ARS?s Scientific Manuscript database

To assess the effectiveness of genotype resistance to potato late blight, foliar blight development, area under disease progress curves (AUDPC) and tuber blight were quantified. Late blight resistant potato genotypes (R-gene free) were assessed for yield performance and stability at early (90 days) ...

Apparent Transition in the Human Height Distribution Caused by Age-Dependent Variation during Puberty Period

NASA Astrophysics Data System (ADS)

Iwata, Takaki; Yamazaki, Yoshihiro; Kuninaka, Hiroto

2013-08-01

In this study, we examine the validity of the transition of the human height distribution from the log-normal distribution to the normal distribution during puberty, as suggested in an earlier study [Kuninaka et al.: J. Phys. Soc. Jpn. 78 (2009) 125001]. Our data analysis reveals that, in late puberty, the variation in height decreases as children grow. Thus, the classification of a height dataset by age at this stage leads us to analyze a mixture of distributions with larger means and smaller variations. This mixture distribution has a negative skewness and is consequently closer to the normal distribution than to the log-normal distribution. The opposite case occurs in early puberty and the mixture distribution is positively skewed, which resembles the log-normal distribution rather than the normal distribution. Thus, this scenario mimics the transition during puberty. Additionally, our scenario is realized through a numerical simulation based on a statistical model. The present study does not support the transition suggested by the earlier study.

[Continuous registration of micropotentials of the human heart. Initial experiences with a new high resolution ECG amplifier system].

PubMed

Hombach, V; Kebbel, U; Höpp, H W; Winter, U J; Braun, V; Deutsch, H; Hirche, H; Hilger, H H

1982-12-24

A new ECG-amplifier system for recording cardiac microvolt potentials from the body surface is described. The improvement in signal-to-noise ratio was achieved by using specially designed suction electrodes, which were isolated from each other; by applying parallel signal averaging from four electrode pairs via four low-noise amplifiers; and by conducting the registration in Faraday cage. in 14 normal subjects, 12 patients with coronary heart disease and one patient with surgically corrected ventricular septal defect and pulmonary stenosis, pre-P-potentials (possible sinus node activity), His bundle potentials and ventricular late potentials were recorded with differing degrees of success. Variations of the time intervals to the preceding QRS complex were observed within the S-T segment in six of nine patients with demonstrable ventricular late ventricular late potentials. The advantage of such continuously recording ECG system lies in the highly accurate registration of cardiac micropotentials, particularly with ventricular late potentials that are changing in time, whereas the signal-averaging technique does not provide such possibilities.

ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome.

PubMed

Cagdas, Deniz; Gur Cetinkaya, Pınar; Karaatmaca, Betül; Esenboga, Saliha; Tan, Cagman; Yılmaz, Togay; Gümüş, Ersin; Barış, Safa; Kuşkonmaz, Barış; Ozgur, Tuba Turul; Bali, Pawan; Santisteban, Ines; Orhan, Diclehan; Yüce, Aysel; Cetinkaya, Duygu; Boztug, Kaan; Hershfield, Michael; Sanal, Ozden; Tezcan, İlhan

2018-05-09

Adenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. The aim of this study was to evaluate the outcome of 13 ADA-deficient patients. We planned to evaluate their clinical and laboratory findings before and after enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (aHSCT), and hematopoietic stem cell gene therapy (HSCGT). Measurement of ADA enzyme activity and metabolites and sequencing of the ADA gene were performed in most of the patients with ADA deficiency. One of the patients with late-onset ADA deficiency was diagnosed by the help of primary immunodeficiency panel screening. Ten out of 13 patients were diagnosed as SCID, while 3 out of 13 were diagnosed as delayed-/late-onset ADA deficiency. Late-onset ADA deficiency patients had clinical and laboratory findings of combined immunodeficiency (CID). Eight patients with ADA-SCID were found to have higher levels of ADA metabolite (dAXP%) (62.1% (34.6-71.9)) than 3 patients with delayed-/late-onset ADA deficiency (6.9% (2.1-8.9). All but one patient with SCID had T-B-NK- phenotype, one had T-B-NK+ phenotype. Genetic defect was documented in 11 patients. Four out of 11 patients had compound heterozygous defects. Three out of 4 patients with compound heterozygous defects had delayed-onset/late-onset ADA deficiency. Seven out of 11 patients with SCID had homozygous defects. Five out of 7 had the same homozygous indel frameshift mutation (c.955-959delGAAGA) showing a founder effect. There were two novel splice site defects: one (IVS10+2T>C) was heterozygous in a patient with late-onset ADA deficiency, and the other was homozygous (IVS2delT+2) in a SCID patient. Other defects were missense defects. Nine out of 13 patients were put on pegylated ADA ERT. Four out of six patients were transplanted without using a conditioning regimen. HSCGT was performed to one of the patients. The genetic diagnosis of SCID is utmost important. There is a chance to give ERT before the definitive therapy if the patient with SCID/CID has ADA deficiency. Although ERT was insufficient to restore a normal immune function in ADA-SCID patients, it was useful to improve and stabilize the clinical status before curative therapy (aHSCT/HSCGT). Enzyme replacement therapy was successful in patients with late-/delayed-onset ADA deficiency who presented with the features of combined immunodeficiency. Gastrointestinal polyposis in a patient with late-onset ADA deficiency may be an association or a coincidental finding. Intermittent neurodevelopmental evaluation especially for hearing impairment should be performed in most of the ADA-deficient patients. This may alleviate the speech delay and cognitive abnormalities which may be observed in the follow-up.

Chemical Evidence for Evolution of galaxies

NASA Astrophysics Data System (ADS)

Dutil, Yvan

I have compiled the very best data published on abundance gradients. From this sample of 29 galaxies, some information can be gained on the mecanism of morphological evolution in disk galaxies. From this sample, I find that early-type galaxies show an identical trend in the behavior of extrapolated central abundance versus morphological type to that shown by late-type galaxies with strong bars, even in the absence of bar! On a a diagram showing extrapolated central abundance versus morphological type, two sequences appear: late-type barred galaxies and early-type galaxies (barred or not barred) fall on sequence 0.5 dex below that of normal late-type galaxies. This behavior is consistent with a scenario of morphological evolution of disk galaxies by formation and dissolution of a bar over a period of a few 10^^9 yr, where later type galaxies (Sd,Sc,Sbc, evolve into earlier-type disk galaxies trough transitory SBc and SBb phases.

Tandem duplication dup(X)(q13q22) in a male proband inherited from the mother showing mosaicism of X-inactivation.

PubMed

Steinbach, P; Horstmann, W; Scholz, W

1980-01-01

An aberrant X chromosome containing extra material in the long arm was observed in a psychomotoric retarded boy and his healthy, short-statured mother. The proband showed generalized muscular hypotony, growth retardation, and somatic anomalies including hypoplastic genitalia and cryptorchism. Chromosomal banding techniques suggested a tandem duplication of the segment Xq13 leads to Xq22. In the mother the vast majority of lymphocytes showed late replication of the aberrant X chromosome. Some of her cells, however, contained an apparently active aberrant X. Both the early- and late-replicating aberrant X exhibited late replication patterns very similar to those described for normal X chromosomes in lymphocytes. Asynchrony of DNA replication among the two segments Xq13 leads to Xq22 in the dup(X) was never observed. We consider that the clinical picture of the proband is caused by an excess of active X material.

Religiousness, spiritual seeking, and personality: findings from a longitudinal study.

PubMed

Wink, Paul; Ciciolla, Lucia; Dillon, Michele; Tracy, Allison

2007-10-01

The hypothesis that personality characteristics in adolescence can be used to predict religiousness and spiritual seeking in late adulthood was tested using a structural equation modeling framework to estimate cross-lagged and autoregressive effects in a two-wave panel design. The sample consisted of 209 men and women participants in the Berkeley Guidance and Oakland Growth studies. In late adulthood, religiousness was positively related to Conscientiousness and Agreeableness, and spiritual seeking was related to Openness to Experience. Longitudinal models indicated that Conscientiousness in adolescence significantly predicted religiousness in late adulthood above and beyond adolescent religiousness. Similarly, Openness in adolescence predicted spiritual seeking in late adulthood. The converse effect, adolescent religiousness to personality in late adulthood, was not significant in either model. Among women, adolescent Agreeableness predicted late-life religiousness and adolescent religiousness predicted late-life Agreeableness; both these effects were absent among men. Adolescent personality appears to shape late-life religiousness and spiritual seeking independent of early religious socialization.

Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis.

PubMed

Sleat, D E; Donnelly, R J; Lackland, H; Liu, C G; Sohar, I; Pullarkat, R K; Lobel, P

1997-09-19

Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease whose defective gene has remained elusive. A molecular basis for LINCL was determined with an approach applicable to other lysosomal storage diseases. When the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, a single protein was identified that is absent in LINCL. Sequence comparisons suggest that this protein is a pepstatin-insensitive lysosomal peptidase, and a corresponding enzymatic activity was deficient in LINCL autopsy specimens. Mutations in the gene encoding this protein were identified in LINCL patients but not in normal controls.

Rhythms can overcome temporal orienting deficit after right frontal damage.

PubMed

Triviño, Mónica; Arnedo, Marisa; Lupiáñez, Juan; Chirivella, Javier; Correa, Angel

2011-12-01

The main aim of this study was to test whether the use of rhythmic information to induce temporal expectations can overcome the deficit in controlled temporal preparation shown by patients with frontal damage (i.e. temporal orienting and foreperiod effects). Two tasks were administered to a group of 15 patients with a frontal brain lesion and a group of 15 matched control subjects: a Symbolic Cued Task where the predictive information regarding the time of target appearance was provided by a symbolic cue (short line-early vs. long line-late interval) and a Rhythm Cued Task where the predictive temporal information was provided by a rhythm (fast rhythm-early vs. slow rhythm-late interval). The results of the Symbolic Cued Task replicated both the temporal orienting deficit in right frontal patients and the absence of foreperiod effects in both right and left frontal patients, reported in our previous study (Triviño, Correa, Arnedo, & Lupiañez, 2010). However, in the Rhythm Cued Task, the right frontal group showed normal temporal orienting and foreperiod effects, while the left frontal group showed a significant deficit of both effects. These findings show that automatic temporal preparation, as induced by a rhythm, can help frontal patients to make effective use of implicit temporal information to respond at the optimum time. Our neuropsychological findings also provide a novel suggestion for a neural model, in which automatic temporal preparation is left-lateralized and controlled temporal preparation is right-lateralized in the frontal lobes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of a 6-days-a-week low protein diet regimen on depressive symptoms in young-old type 2 diabetic patients.

PubMed

Ciarambino, Tiziana; Ferrara, Nicoletta; Castellino, Pietro; Paolisso, Giuseppe; Coppola, Ludovico; Giordano, Mauro

2011-01-01

Late-life depression is one of the main health problems among elderly diabetic subjects. In addition, depression is a common psychopathological condition among renal failure patients and most of these patients follow a low protein diet regimen (LPD). However, the effects of LPD on depressive symptoms are unclear. In the present study, the effects of LPD regimen on depressive symptoms in elderly type 2 diabetic subjects with renal failure were investigated. Fifty-two young-old type 2 diabetic patients with renal failure were enrolled in the study. All participants after normal protein diet regimen providing 1.2g/kg per d were instructed to consume either a LPD providing 0.8 g/kg per d, 7 d a wk (LPD 7/7), or a LPD providing 0.8 g/kg per d 6 d a wk (LPD 6/7) randomly. Mean 15-item Geriatric Depression Scale (GDS-15) (2.0±0.6) and Beck Depression Inventory (BDI) (4.1±1.0), during normal protein diet regimen, significantly increased to (6.7±1.6) and (12.2±1.4), respectively, after LPD 7/7 (P<0.05 versus normal protein diet). However, after LPD 6/7, mean GDS-15 and BDI significantly decreased to (4.4±1.5) and (6.7±1.6), respectively (P<0.05 versus LPD 7/7). LPD 6/7 regimen significantly decreased depressive symptoms in young-old type 2 diabetic patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Impact of late radiation effects on cancer survivor children: an integrative review

PubMed Central

Coura, Cibeli Fernandes; Modesto, Patrícia Cláudia

2016-01-01

ABSTRACT We aimed to identify the late effects of radiation exposure in pediatric cancer survivors. An integrated literature review was performed in the databases MEDLINE and LILACS and SciELO. Included were articles in Portuguese and English, published over the past 10 years, using the following keywords: “neoplasias/neoplasms” AND “radioterapia/radiotherapy” AND “radiação/radiation”. After analysis, 14 articles - published in nine well-known journals - met the inclusion criteria. The publications were divided into two categories: “Late endocrine effects” and “Late non-endocrine effects”. Considering the increased survival rates in children who had cancer, the impact of late effects of exposure to radiation during radiological examinations for diagnosis and treatment was analyzed. Childhood cancer survivors were exposed to several late effects and should be early and regularly followed up, even when exposed to low radiation doses. PMID:26313432

Association of late-night carbohydrate intake with glucose tolerance among pregnant African American women.

PubMed

Chandler-Laney, Paula C; Schneider, Camille R; Gower, Barbara A; Granger, Wesley M; Mancuso, Melissa S; Biggio, Joseph R

2016-10-01

Obesity and late-night food consumption are associated with impaired glucose tolerance. Late-night carbohydrate consumption may be particularly detrimental during late pregnancy because insulin sensitivity declines as pregnancy progresses. Further, women who were obese (Ob) prior to pregnancy have lower insulin sensitivity than do women of normal weight (NW). The aim of this study is to test the hypothesis that night-time carbohydrate consumption is associated with poorer glucose tolerance in late pregnancy and that this association would be exacerbated among Ob women. Forty non-diabetic African American women were recruited based upon early pregnancy body mass index (NW, <25 kg m(-2) ; Ob, ≥30 kg m(-2) ). Third trimester free-living dietary intake was assessed by food diary, and indices of glucose tolerance and insulin action were assessed during a 75-g oral glucose tolerance test. Women in the Ob group reported greater average 24-h energy intake (3055 kcal vs. 2415 kcal, P < 0.05). Across the whole cohort, night-time, but not day-time, carbohydrate intake was positively associated with glucose concentrations after the glucose load and inversely associated with early phase insulin secretion (P < 0.05). Multiple linear regression modelling within each weight group showed that the associations among late-night carbohydrate intake, glucose concentrations and insulin secretion were present only in the Ob group. This is the first study to report an association of night-time carbohydrate intake specifically on glucose tolerance and insulin action during pregnancy. If replicated, these results suggest that late-night carbohydrate intake may be a potential target for intervention to improve metabolic health of Ob women in late pregnancy. © 2015 John Wiley & Sons Ltd.

Updating the Evidence on the Association between Serum Cholesterol and Risk of Late-Life Dementia: Review and Meta-Analysis.

PubMed

Anstey, Kaarin J; Ashby-Mitchell, Kimberly; Peters, Ruth

2017-01-01

Cohort studies have reported that midlife high total serum cholesterol (TC) is associated with increased risk of Alzheimer's disease (AD) in late-life but findings have been based on few studies and previous reviews have been limited by a lack of compatible data. We synthesized all high quality data from cohort studies reporting on the association between total serum cholesterol measured and late-life cognitive outcomes including Alzheimer's disease (AD), vascular dementia (VaD), any dementia, mild cognitive impairment (MCI), and cognitive decline. The literature was searched up to October 2016 using a registered protocol. Thirty-four articles meeting study criteria were identified. Seventeen studies published from 1996 to 2014, including 23,338 participants were included in meta-analyses. Relative risk of developing AD for adults with high TC in midlife was 2.14 (95% CI 1.33-3.44) compared with normal cholesterol. Individual studies that could not be pooled also reported high TC in midlife increased the risk of MCI and cognitive decline in late-life. High TC in late-life was not associated with MCI, AD, VaD, any dementia, or cognitive decline. Late-life measured HDL cholesterol and triglycerides were not associated with increased risk of VaD, and HDL was not associated with risk of MCI, AD, or any dementia. There were insufficient data to examine other cholesterol sub-fractions, sex differences, or APOE interactions. Significant gaps in the literature regarding TC and late-life dementia remain. Evidence suggests that high midlife TC increases risk of late-life AD, and may correlate with the onset of AD pathology.

Impact of occult renal impairment on early and late outcomes following coronary artery bypass grafting

PubMed Central

Marui, Akira; Okabayashi, Hitoshi; Komiya, Tatsuhiko; Tanaka, Shiro; Furukawa, Yutaka; Kita, Toru; Kimura, Takeshi; Sakata, Ryuzo

2013-01-01

OBJECTIVES High serum creatinine is considered an independent risk factor for poor outcomes following coronary artery bypass grafting (CABG). However, the impact of occult renal impairment (ORI), defined as an impaired glomerular filtration rate (GFR) with a normal serum creatinine (SCr) level, remains unclear. Thus, we sought to investigate the impact of ORI on outcomes after CABG. METHODS Among patients undergoing their first percutaneous coronary intervention (PCI) or CABG enrolled in the CREDO-Kyoto Registry (a registry of first-time PCI and CABG patients in Japan), 1842 patients with normal SCr levels undergoing CABG were enrolled in the study. Patients were divided into two groups based on preoperative estimated GFR calculated by the Cockcroft–Gault equation: 1339 patients with estimated GFR of ≥60 ml/min/1.73 m2 (normal group) and 503 with estimated GFR of <60 ml/min/1.73 m2 (ORI group). RESULTS Preoperative estimated GFR differed between the groups (51.3 ± 6.6 vs 85.8 ± 23.0 ml/min/1.73 m2, P < 0.01). ORI was associated with high in-hospital mortality (3.2 vs 1.0%, P < 0.01) and need for dialysis (2.0 vs 0.2%, P < 0.01). In terms of long-term outcomes, ORI was associated with high mortality compared with the normal (hazard ratio [95% confidence interval]: 1.72 [1.16–2.54], P < 0.01) and high incidence of composite cardiovascular events (death, stroke or myocardial infarction: 1.53 [1.16–2.02], P < 0.01). CONCLUSIONS ORI was an independent risk factor for early and late death as well as cardiovascular events in patients undergoing CABG with normal SCr levels. A more accurate evaluation of renal function through a combination of SCr and estimated GFR is needed in patients with normal SCr levels. PMID:23793709

Impact of occult renal impairment on early and late outcomes following coronary artery bypass grafting.

PubMed

Marui, Akira; Okabayashi, Hitoshi; Komiya, Tatsuhiko; Tanaka, Shiro; Furukawa, Yutaka; Kita, Toru; Kimura, Takeshi; Sakata, Ryuzo

2013-10-01

High serum creatinine is considered an independent risk factor for poor outcomes following coronary artery bypass grafting (CABG). However, the impact of occult renal impairment (ORI), defined as an impaired glomerular filtration rate (GFR) with a normal serum creatinine (SCr) level, remains unclear. Thus, we sought to investigate the impact of ORI on outcomes after CABG. Among patients undergoing their first percutaneous coronary intervention (PCI) or CABG enrolled in the CREDO-Kyoto Registry (a registry of first-time PCI and CABG patients in Japan), 1842 patients with normal SCr levels undergoing CABG were enrolled in the study. Patients were divided into two groups based on preoperative estimated GFR calculated by the Cockcroft-Gault equation: 1339 patients with estimated GFR of ≥ 60 ml/min/1.73 m(2) (normal group) and 503 with estimated GFR of <60 ml/min/1.73 m(2) (ORI group). Preoperative estimated GFR differed between the groups (51.3 ± 6.6 vs 85.8 ± 23.0 ml/min/1.73 m(2), P < 0.01). ORI was associated with high in-hospital mortality (3.2 vs 1.0%, P < 0.01) and need for dialysis (2.0 vs 0.2%, P < 0.01). In terms of long-term outcomes, ORI was associated with high mortality compared with the normal (hazard ratio [95% confidence interval]: 1.72 [1.16-2.54], P < 0.01) and high incidence of composite cardiovascular events (death, stroke or myocardial infarction: 1.53 [1.16-2.02], P < 0.01). ORI was an independent risk factor for early and late death as well as cardiovascular events in patients undergoing CABG with normal SCr levels. A more accurate evaluation of renal function through a combination of SCr and estimated GFR is needed in patients with normal SCr levels.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Słonina, Dorota, E-mail: z5slonin@cyfronet.pl; Biesaga, Beata; Janecka, Anna

Purpose: In our previous study, using the micronucleus assay, a low-dose hyper-radiosensitivity (HRS)-like phenomenon was observed for normal fibroblasts of 2 of the 40 cancer patients investigated. In this article we report, for the first time, the survival response of primary fibroblasts from 25 of these patients to low-dose irradiation and answer the question regarding the effect of G2-phase enrichment on HRS elicitation. Methods and Materials: The clonogenic survival of asynchronous as well as G2-phase enriched fibroblast populations was measured. Separation of G2-phase cells and precise cell counting was performed using a fluorescence-activated cell sorter. Sorted and plated cells weremore » irradiated with single doses (0.1-4 Gy) of 6-MV x-rays. For each patient, at least 4 independent experiments were performed, and the induced-repair model was fitted over the whole data set to confirm the presence of HRS effect. Results: The HRS response was demonstrated for the asynchronous and G2-phase enriched cell populations of 4 patients. For the rest of patients, HRS was not defined in either of the 2 fibroblast populations. Thus, G2-phase enrichment had no effect on HRS elicitation. Conclusions: The fact that low-dose hyper-radiosensitivity is not a common effect in normal human fibroblasts implies that HRS may be of little consequence in late-responding connective tissues with regard to radiation fibrosis.« less

Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer's disease?

PubMed

Teipel, Stefan; Grothe, Michel J

2016-03-01

Posterior cingulate cortex (PCC) hypometabolism as measured by FDG PET is an indicator of Alzheimer's disease (AD) in prodromal stages, such as in mild cognitive impairment (MCI), and has been found to be closely associated with hippocampus atrophy in AD dementia. We studied the effects of local and remote atrophy and of local amyloid load on the PCC metabolic signal in patients with different preclinical and clinical stages of AD. We determined the volume of the hippocampus and PCC grey matter based on volumetric MRI scans, PCC amyloid load based on AV45 PET, and PCC metabolism based on FDG PET in 667 subjects participating in the Alzheimer's Disease Neuroimaging Initiative spanning the range from cognitively normal ageing through prodromal AD to AD dementia. In cognitively normal individuals and those with early MCI, PCC hypometabolism was exclusively associated with hippocampus atrophy, whereas in subjects with late MCI it was associated with both local and remote effects of atrophy as well as local amyloid load. In subjects with AD dementia, PCC hypometabolism was exclusively related to local atrophy. Our findings suggest that the effects of remote pathology on PCC hypometabolism decrease and the effects of local pathology increase from preclinical to clinical stages of AD, consistent with a progressive disconnection of the PCC from downstream cortical and subcortical brain regions.

On- and off-response ERGs elicited by sawtooth stimuli in normal subjects and glaucoma patients.

PubMed

Pangeni, Gobinda; Lämmer, Robert; Tornow, Ralf P; Horn, Folkert K; Kremers, Jan

2012-06-01

The aim of this study is to measure the on- and off-responses and their response asymmetries elicited by sawtooth stimuli in normal subjects and glaucoma patients. Furthermore, the correlation between the ERGs and other functional and structural parameters are investigated. Full-field stimuli were produced using a Ganzfeld bowl with Light Emitting Diodes (LEDs) as light sources. On- and off-response ERGs were recorded from 17 healthy subjects, 12 pre-perimetric and 15 perimetric glaucoma patients using 4-Hz luminance rapid-on and rapid-off sawtooth stimuli (white light; mean luminance 55 cd/m(2)) at 100% contrast. The on- and off-responses were added to study response asymmetries. In addition, flash ERGs were elicited by red stimuli (200 cd/m(2)) on a blue background (10 cd/m(2)). The mean deviations (MD) of the visual field defects were obtained by standard automated perimetry. The retinal nerve fibre layer thickness (RNFLT) was measured with Spectral Domain Optical Coherence Tomography (SOCT). We studied the correlation between ERG response amplitudes, visual field mean deviation (MDs) and RNFLT values. The on-responses showed an initial negative (N-on) followed by a positive (P-on), a late positive (LP-on) and a late negative responses (LN-on). The off-responses showed an initial positive (P-off) a late positive (LP-off) and a late negative response (LN-off). The addition of on- and off-responses revealed an initial positive (P-add) and a late negative response (LN-add). The on-response components (N-on, P-on and LN-on) in the glaucoma patients were relatively similar to those of the control subjects. However, the LP-on was significantly elevated (p = 0.03) in perimetric patients. The LP-off was significantly elevated (p < 0.001), and the amplitude of LN-off was significantly reduced in perimetric patients (p = 0.02). The LN-add amplitude was significantly reduced (p < 0.001) and delayed (p = 0.03) in perimetric patients. The amplitudes of the LN-off and LN-add ERG components were significantly correlated with the PhNR in the flash ERG (LN-off: p = 0.01; LN-add: p < 0.001) and with RNFLT (LN-off: p = 0.006; LN-add: p = 0.001). On- and off-response ERGs and their response asymmetries, elicited by sawtooth stimuli, are altered in the glaucoma patients. The late components are affected. Changes in the late negative components are correlated with structural and other functional changes.

Toward an understanding of late life suicidal behavior: the role of lifespan developmental theory.

PubMed

Fiske, Amy; O'Riley, Alisa A

2016-01-01

Suicidal behavior in late life differs in important ways from suicidal behavior that occurs earlier in the lifespan, suggesting the possibility of developmental differences in the etiology of suicidal behavior. This paper examines late life suicidal behavior within the context of lifespan developmental theory. This paper presents a conceptual framework for using lifespan developmental theory to better understand late life suicidal behavior. We argue that the motivational theory of lifespan development, which focuses on control, is particularly relevant to late life suicide. This theory posits that opportunities to exert control over important aspects of one's life diminish in late life as a result of declines in physical functioning and other factors, and that successful aging is associated with adaptive regulation of this developmental change. Although continued striving to meet goals is normative throughout the lifespan, most individuals also increase the use of compensatory strategies in old age or when faced with a decline in functioning. We propose that individuals who do not adapt to developmental changes by altering their strategies for exerting control will be at risk for suicidal behavior in late life. This paper reviews evidence that supports the importance of control with respect to suicidal outcomes in older adults, as well as findings regarding specific types of control strategies that may be related to suicide risk in older adults with health-related limitations. Although suicidal behavior is not a normal part of aging, the application of lifespan developmental theory may be useful in understanding and potentially preventing suicide among older adults.

Hygromycin B hypersensitive (hhy) mutants implicate an intact trans-Golgi and late endosome interface in efficient Tor1 vacuolar localization and TORC1 function.

PubMed

Ejzykowicz, Daniele E; Locken, Kristopher M; Ruiz, Fiona J; Manandhar, Surya P; Olson, Daniel K; Gharakhanian, Editte

2017-06-01

Saccharomyces cerevisiae vacuoles are functionally analogous to mammalian lysosomes. Both also serve as physical platforms for Tor Complex 1 (TORC1) signal transduction, the master regulator of cellular growth and proliferation. Hygromycin B is a eukaryotic translation inhibitor. We recently reported on hygromycin B hypersensitive (hhy) mutants that fail to grow at subtranslation inhibitory concentrations of the drug and exhibit vacuolar defects (Banuelos et al. in Curr Genet 56:121-137, 2010). Here, we show that hhy phenotype is not due to increased sensitivity to translation inhibition and establish a super HHY (s-HHY) subgroup of genes comprised of ARF1, CHC1, DRS2, SAC1, VPS1, VPS34, VPS45, VPS52, and VPS54 that function exclusively or inclusively at trans-Golgi and late endosome interface. Live cell imaging of s-hhy mutants revealed that hygromycin B treatment disrupts vacuolar morphology and the localization of late endosome marker Pep12, but not that of late endosome-independent vacuolar SNARE Vam3. This, along with normal post-late endosome trafficking of the vital dye FM4-64, establishes that severe hypersensitivity to hygromycin B correlates specifically with compromised trans-Golgi and late endosome interface. We also show that Tor1p vacuolar localization and TORC1 anabolic functions, including growth promotion and phosphorylation of its direct substrate Sch9, are compromised in s-hhy mutants. Thus, an intact trans-Golgi and late endosome interface is a requisite for efficient Tor1 vacuolar localization and TORC1 function.

Middle Micoene sandstone reservoirs of the Penal/Barrackpore field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dyer, B.L.

1991-03-01

The Penal/Barrackpore field was discovered in 1938 and is located in the southern subbasin of onshore Trinidad. The accumulation is one of a series of northeast-southwest trending en echelon middle Miocene anticlinal structures that was later accentuated by late Pliocene transpressional folding. Relative movement of the South American and Caribbean plates climaxed in the middle Miocene compressive tectonic event and produced an imbricate pattern of southward-facing basement-involved thrusts. Further compressive interaction between the plates in the late Pliocene produced a transpressive tectonic episode forming northwest-southeast oriented transcurrent faults, tear faults, basement thrust faults, lystric normal faults, and detached simple foldsmore » with infrequent diapiric cores. The middle Miocene Herrera and Karamat turbiditic sandstones are the primary reservoir rock in the subsurface anticline of the Penal/Barrackpore field. These turbidites were sourced from the north and deposited within the marls and clays of the Cipero Formation. Miocene and Pliocene deltaics and turbidites succeed the Cipero Formation vertically, lapping into preexisting Miocene highs. The late Pliocene transpression also coincides with the onset of oil migration along faults, diapirs, and unconformities from the Cretaceous Naparima Hill source. The Lengua Formation and the upper Forest clays are considered effective seals. Hydrocarbon trapping is structurally and stratigraphically controlled, with structure being the dominant trapping mechanism. Ultimate recoverable reserves for the field are estimated at 127.9 MMBo and 628.8 bcf. The field is presently owned and operated by the Trinidad and Tobago Oil Company Limited (TRINTOC).« less

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.

PubMed

Tharavichtikul, Ekkasit; Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-06-01

To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale.

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University

PubMed Central

Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-01-01

Purpose To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Materials and Methods Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Results Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). Conclusion The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale. PMID:25061573

Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Yong-Gang; Qi, Shu-Nan; Wang, Shu-Lian

Purpose: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). Methods and Materials: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (D{sub mean}) to the parotid glands on xerostomia. Results: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating verymore » good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The D{sub mean} to the parotid glands had a linear correlation with late grade ≥2 xerostomia. Conclusions: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.« less

Effect of glucocorticosteroid treatment on ovalbumin-induced IgE-mediated immediate and late allergic response in guinea pig.

PubMed

Andersson, P; Brange, C; von Kogerer, B; Sonmark, B; Stahre, G

1988-01-01

The effect of glucocorticosteroid (GCS) treatment on ovalbumine-induced IgE-mediated immediate and late allergic response was studied in sensitized guinea pigs. The results show that the GCS budesonide (BUD) inhibits the allergen-induced IgE-mediated immediate and late bronchial obstruction. The effect on the early reaction is correlated to the inhibition of leukotrienes and histamine release. The importance of mediator release inhibition for the antianaphylactic effect of GCS is discussed. In examining the effect on the late reaction, it was found that BUD had to be present during the early reaction but did not inhibit the early reaction. Furthermore, the effect on the late reaction was correlated to the inhibition of vascular leakage but not to the infiltration of inflammatory cells as examined in bronchoalveolar lavage. The results indicate that some triggering factors important for the development of the late reaction are released during the early reaction. Inhibition of the release of that factor or the activation of inflammatory cells by that factor might be the mechanism behind the antiinflammatory activities of GCS.

Radiation Therapy Did Not Induce Long-Term Changes in Rectal Mucosa: Results From the Randomized Scandinavian Prostate Cancer Group 7 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slagsvold, Jens Erik, E-mail: Jens.Erik.Slagsvold@stolav.no; Viset, Trond; Wibe, Arne

Purpose: To investigate long-term changes in the rectal mucosa after curative external beam radiation therapy in the treatment of prostate cancer. Methods and Materials: In the Scandinavian Prostate Cancer Group 7 trial, 880 men with locally advanced prostate cancer were randomized to hormonal therapy alone versus hormonal therapy plus radiation therapy to 70 Gy. A subcohort from this trial being randomized at our center (n=178) was invited to a study on late anorectal side effects during 2003-2005, approximately 5 years after treatment, including measuring health-reported quality of life and physician-assessed toxicity score by the Late Effects Normal Tissue Task Force/Subjective, Objective, Management, Analyticmore » (LENT/SOMA) and European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group score. Sixty-seven patients had a rectal mucosa biopsy. Sixty-four biopsies were included in the final analysis, of which 33 patients were randomized to hormonal treatment and 31 to hormonal treatment plus radiation therapy. The presence of fibrosis, number of capillaries, and lymphocyte infiltration was then evaluated by light microscopy. Results: The group receiving radiation therapy had significantly higher LENT/SOMA and function/bother scale scores than the group that only received hormonal treatment, but there was no significant difference in the presence of fibrosis, ectasia, number of capillaries in the lamina propria, or lymphocyte infiltration between the groups. Conclusion: Radiation therapy to 70 Gy to the prostate does not induce long-term microscopic mucosal changes in the rectum 5 years after treatment. This is in contrast to the general assumption that structural changes, including fibrosis, seen after radiation therapy include the mucosa. We speculate that the main late effects of radiation therapy on the structure of the rectum are located in the deeper layers of the rectal wall than the mucosa.« less

Mitral valve coaptation and its relationship to late diastolic flow: A color Doppler and vector flow map echocardiographic study in normal subjects.

PubMed

Sherrid, Mark V; Kushner, Josef; Yang, Georgiana; Ro, Richard

2017-04-01

Three competing theories about the mechanism of mitral coaptation in normal subjects were evaluated by color Doppler and vector flow mapping (VFM): (1) beginning of ventricular (LV) ejection, (2) "breaking of the jet" of diastolic LV inflow, and (3) returning diastolic vortices impacting the leaflets on their LV surfaces. We analyzed 80 color Doppler frames and 320 VFM measurements. In all 20 normal subjects, coaptation occurred before LV ejection, 78±16 ms before onset. On color Doppler frames the larger anterior, and smaller posterior vortices circle back and, in all cases, strike the ventricular surfaces of the leaflets. On the first closing-begins frame, for the first time, vortex velocity normal to the ventricular surface of the anterior leaflet (AML) is greater than that in the mitral orifice, and the angle of attack of LV vortical flow onto the AML is twice as high as the angle of flow onto the valve in orifice. Thus, at the moment coaptation begins, vortical flow strikes the mitral leaflet with higher velocity, and higher angle of attack than orifice flow, and thus with greater force. According to the "breaking of the jet" theory, one would expect to see de novo LV flow perpendicular to the leaflets beginning after transmitral flow terminates. Instead, the returning continuous LV vortical flow that impacts the valve builds continuously after the P-wave. Late diastolic vortices strike the ventricular surfaces of the mitral leaflets and contribute to valve coaptation, permitted by concomitant decline in transmitral flow. © 2017, Wiley Periodicals, Inc.

Metaiodobenzylguanidine (/sup 131/I) scintigraphy detects impaired myocardial sympathetic neuronal transport function of canine mechanical-overload heart failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabinovitch, M.A.; Rose, C.P.; Rouleau, J.L.

1987-12-01

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine (/sup 131/I) to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine (/sup 131/I) and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4more » hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine (/sup 131/I) scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine (/sup 123/I) scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.« less

Interdecadal variations of East Asian summer monsoon northward propagation and influences on summer precipitation over East China

NASA Astrophysics Data System (ADS)

Jiang, Z.; Yang, S.; He, J.; Li, J.; Liang, J.

2008-08-01

The interdecadal variation of northward propagation of the East Asian Summer Monsoon (EASM) and summer precipitation in East China have been investigated using daily surface rainfall from a dense rain gauge network in China for 1957 2001, National Center for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) reanalysis, European Center for Medium-Range Weather Forecast (ECMWF) reanalysis, and Global Mean Sea Level Pressure Dataset (GMSLP2) from Climatic Research Unit (CRU). Results in general show a consistent agreement on the interdecadal variability of EASM northward propagations. However, it appears that the interdecadal variation is stronger in NCEP than in ECMWF and CRU datasets. A newly defined normalized precipitation index (NPI), a 5-day running mean rainfall normalized with its standard deviation, clearly depicts the characteristics of summer rainbelt activities in East China in terms of jumps and durations during its northward propagations. The EASM northward propagation shows a prominent interdecadal variation. EASM before late 1970s had a rapid northward advance and a northern edge beyond its normal position. As a result, more summer rainfall occurred for the North China rainy season, Huaihe-River Mei-Yu, and South China Mei-Yu. In contrast, EASM after late 1970s had a slow northward movement and a northern edge located south of its normal position. Less summer precipitation occurred in East China except in Yangtze River basin. The EASM northernmost position (ENP), northernmost intensity (ENI), and EASM have a complex and good relationship at interdecadal timescales. They have significant influences on interdecadal variation of the large-scale precipitation anomalies in East China.

Altered procollagen gene expression in mid-gestational mouse excisional wounds.

PubMed

Goldberg, Stephanie R; Quirk, Gerald L; Sykes, Virginia W; Kordula, Tomasz; Lanning, David A

2007-11-01

Many pathologic conditions are characterized by excessive tissue contraction and scar formation. Previously, we developed a murine model of excisional wound healing in which mid-gestational wounds heal scarlessly compared with late-gestational wounds. We theorized that variations in procollagen gene expression may contribute to the scarless and rapid closure. Time-dated pregnant FVB strain mice underwent laparotomy and hysterotomy on embryonic days 15 (E15) and 18 (E18). Full-thickness, excisional wounds (3 mm) were made on each of 4 fetuses per doe and then harvested at 32, 48, or 72 h. Control tissue consisted of age-matched normal fetal skin. Procollagen types 1alpha1, 1alpha2, and 3 gene expressions were measured by real-time polymerase chain reaction and normalized to glyceraldehyde-3-phosphate dehydrogenase. Trichrome staining was also performed. Procollagen 1alpha1 expression was decreased in E15 wounds at 32 h compared with their normal skin groups. Procollagen types 1alpha2 and 3 expressions were both increased in the E15 groups compared with the E18 groups at 48 h. At 72 h, the E15 wounds had a collagen density similar to the surrounding normal skin while E18 wounds exhibited increased collagen deposition in a disorganized pattern. This study demonstrates that the pattern of gene expression for types 1 and 3 collagen varies between mid- and late-gestational mouse excisional wounds. These alterations in procollagen expression may contribute to a pattern of collagen deposition in the mid-gestational fetuses that is more favorable for scarless healing with less type 1 and more type 3 collagen.

Evidence that congenital hydrocephalus is a precursor to idiopathic normal pressure hydrocephalus in only a subset of patients

PubMed Central

Wilson, Robin K; Williams, Michael A

2007-01-01

Objective To identify the proportion of patients in a large idiopathic normal pressure hydrocephalus (INPH) cohort with large head circumference (HC) who presumably have congenital hydrocephalus that has not become clinically apparent until late in life. Methods HC was measured in 158 patients diagnosed with communicating INPH and assigned to HC centile range adjusted for height and sex. The proportion of patients with INPH and HC above the 97th, 90th or 50th centiles was compared with the proportion expected in a normal population. Results The proportion of patients with HC >90th centile was significantly larger than would be expected in a normal distribution (19.6% vs 10%, p = 0.0001), as was the proportion of patients with HC >97th centile (8.9% vs 3%, p = 0.0001). The relative association between INPH and HC >97th centile was nearly tripled (relative association 2.95; CI 1.36 to 6.41), but the relative association between INPH and HC >50th centile was not significantly higher than predicted (relative association 1.13; CI 0.95 to 1.34). Conclusion A significantly larger proportion of elderly adults with INPH have a HC greater than the 90th or 97th centile than predicted by population norms, supporting the concept that compensated congenital hydrocephalus that does not become symptomatic until late in life is one aetiology of INPH, but is not responsible for all INPH. The mechanism that leads to the development of INPH in most patients remains elusive. PMID:17202229

Latent iron deficiency at birth influences auditory neural maturation in late preterm and term infants.

PubMed

Choudhury, Vivek; Amin, Sanjiv B; Agarwal, Asha; Srivastava, L M; Soni, Arun; Saluja, Satish

2015-11-01

In utero latent iron deficiency has been associated with abnormal neurodevelopmental outcomes during childhood. Its concomitant effect on auditory neural maturation has not been well studied in late preterm and term infants. The objective was to determine whether in utero iron status is associated with auditory neural maturation in late preterm and term infants. This prospective cohort study was performed at Sir Ganga Ram Hospital, New Delhi, India. Infants with a gestational age ≥34 wk were eligible unless they met the exclusion criteria: craniofacial anomalies, chromosomal disorders, hemolytic disease, multiple gestation, third-trimester maternal infection, chorioamnionitis, toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex virus infections (TORCH), Apgar score <5 at 5 min, sepsis, cord blood not collected, or auditory evaluation unable to be performed. Sixty consecutive infants with risk factors for iron deficiency, such as small for gestational age and maternal diabetes, and 30 without risk factors for iron deficiency were enrolled. Absolute wave latencies and interpeak latencies, evaluated by auditory brainstem response within 48 h after birth, were measured and compared between infants with latent iron deficiency (serum ferritin ≤75 ng/mL) and infants with normal iron status (serum ferritin >75 ng/mL) at birth. Twenty-three infants had latent iron deficiency. Infants with latent iron deficiency had significantly prolonged wave V latencies (7.10 ± 0.68 compared with 6.60 ± 0.66), III-V interpeak latencies (2.37 ± 0.64 compared with 2.07 ± 0.33), and I-V interpeak latencies (5.10 ± 0.57 compared with 4.72 ± 0.56) compared with infants with normal iron status (P < 0.05). This difference remained significant on regression analyses after control for confounders. No difference was noted between latencies I and III and interpeak latencies I-III. Latent iron deficiency is associated with abnormal auditory neural maturation in infants at ≥34 wk gestational age. This trial was registered at clinicaltrials.gov as NCT02503397. © 2015 American Society for Nutrition.

Pre-gravid physical activity and reduced risk of glucose intolerance in pregnancy: the role of insulin sensitivity.

PubMed

Retnakaran, Ravi; Qi, Ying; Sermer, Mathew; Connelly, Philip W; Zinman, Bernard; Hanley, Anthony J G

2009-04-01

Pre-gravid physical activity has been associated with a reduced risk of gestational diabetes mellitus (GDM), although neither the types of exercise nor the physiologic mechanisms underlying this protective effect have been well-studied. Thus, we sought to study the relationships between types of pre-gravid physical activity and metabolic parameters in pregnancy, including glucose tolerance, insulin sensitivity and beta-cell function. A total of 851 women underwent a glucose challenge test (GCT) and a 3-h oral glucose tolerance test (OGTT) in late pregnancy, yielding four glucose tolerance groups: (i) GDM; (ii) gestational impaired glucose tolerance (GIGT); (iii) abnormal GCT with normal glucose tolerance on OGTT (abnormal GCT NGT); and (iv) normal GCT with NGT on OGTT (normal GCT NGT). Pre-gravid physical activity was assessed using the Baecke questionnaire, which measures (i) total physical activity and (ii) its three component domains: work, nonsport leisure-time, and vigorous/sports activity. Glucose tolerance status improved across increasing quartiles of pre-gravid total physical activity (P = 0.0244). Whereas neither work nor nonsport leisure-time activity differed between glucose tolerance groups, pre-gravid vigorous/sports activity was significantly higher in women with normal GCT NGT compared to women with (i) abnormal GCT NGT (P = 0.0018) (ii) GIGT (P = 0.0025), and (iii) GDM (P = 0.0044). In particular, vigorous/sports activity correlated with insulin sensitivity (measured by IS(OGTT)) (r = 0.21, P < 0.0001). Furthermore, on multiple linear regression analysis, pre-gravid vigorous/sports activity emerged as a significant independent predictor of IS(OGTT) in pregnancy (t = 4.97, P < 0.0001). Pre-gravid vigorous/sports activity is associated with a reduced risk of glucose intolerance in pregnancy, an effect likely mediated by enhanced insulin sensitivity.

Electrophysiological Correlates of Impaired Reading in Dyslexic Pre-Adolescent Children

ERIC Educational Resources Information Center

Araujo, Susana; Bramao, Ines; Faisca, Luis; Petersson, Karl Magnus; Reis, Alexandra

2012-01-01

In this study, event related potentials (ERPs) were used to investigate the extent to which dyslexics (aged 9-13 years) differ from normally reading controls in early ERPs, which reflect prelexical orthographic processing, and in late ERPs, which reflect implicit phonological processing. The participants performed an implicit reading task, which…

When Autism Strikes: Families Cope with Childhood Disintegrative Disorder.

ERIC Educational Resources Information Center

Catalano, Robert A.

This book examines childhood disintegrative disorder, which is seen to be a disorder apart from autism although it has sometimes been called "late onset autism". The condition is characterized by sudden onset and severe developmental regression between 3 and 5 years of age after previously normal development. The long-term outcome is…

Mallard hatching from an egg cracked by freezing

USGS Publications Warehouse

Greenwood, R.J.

1969-01-01

The eggs of early-nesting waterfowl in North Dakota are frequently exposed to subfreezing temperatures. Mallards (Anas platyrhynchos) and Pintail (Anas acuta), normally the first ducks to arrive in the spring, begin limited early nesting in min-April. Nighttime temperatures during this period frequently drop below freezing, and late spring blizzards are not unusual.

Are "All" Teenagers Emotionally Illiterate? Charting a Neuroscientific Storying of Normative Deficit

ERIC Educational Resources Information Center

Payne, Monica A.

2012-01-01

Defining "emotional illiteracy" is a task located within the broader context of expert (and subsequently public) assumptions regarding the normally expectable competencies of the age group concerned. In the late 1990s a series of neuroscientific studies reporting adolescents' limited ability to recognize emotional states from facial expressions…

Quaternary marine terraces as indicators of neotectonic activity of the Ierapetra normal fault SE Crete (Greece)

NASA Astrophysics Data System (ADS)

Gaki-Papanastassiou, K.; Karymbalis, E.; Papanastassiou, D.; Maroukian, H.

2009-03-01

Along the southern coast of the island of Crete, a series of east-west oriented Late Pleistocene marine terraces exist, demonstrating the significant coastal uplift of this area. Five uplifted terraces were mapped in detail and correlated with Middle-Late Pleistocene sea-level stands following the global sea-level fluctuations. These terraces are deformed by the vertical movements of the NNE-SSW trending and dipping west Ierapetra normal fault. The elevation of the inner edges of the terraces was estimated at several sites by using aerial photographs and detailed topographic maps and diagrams, supported by extensive field observations. In this way detailed geomorphological maps were constructed utilizing GIS technology. All these allowed us to obtain rates of 0.3 mm/yr for the regional component of uplift and 0.1 mm/yr for the vertical slip movements of the Ierapetra fault. Based on the obtained rates and the existence of coastal archaeological Roman ruins it is concluded that Ierapetra fault should have been reactivated sometime after the Roman period.

Mrc1 Marks Early-Firing Origins and Coordinates Timing and Efficiency of Initiation in Fission Yeast ▿ †

PubMed Central

Hayano, Motoshi; Kanoh, Yutaka; Matsumoto, Seiji; Masai, Hisao

2011-01-01

How early- and late-firing origins are selected on eukaryotic chromosomes is largely unknown. Here, we show that Mrc1, a conserved factor required for stabilization of stalled replication forks, selectively binds to the early-firing origins in a manner independent of Cdc45 and Hsk1 kinase in the fission yeast Schizosaccharomyces pombe. In mrc1Δ cells (and in swi1Δ cells to some extent), efficiency of firing is stimulated, and its timing is advanced selectively at those origins that are normally bound by Mrc1. In contrast, the late or inefficient origins which are not bound by Mrc1 are not activated in mrc1Δ cells. The enhanced firing and precocious Cdc45 loading at Mrc1-bound early-firing origins are not observed in a checkpoint mutant of mrc1, suggesting that non-checkpoint function is involved in maintaining the normal program of early-firing origins. We propose that prefiring binding of Mrc1 is an important marker of early-firing origins which are precociously activated by the absence of this protein. PMID:21518960

Interferon-induced Sus scrofa Mx1 blocks endocytic traffic of incoming influenza A virus particles.

PubMed

Palm, Mélanie; Garigliany, Mutien-Marie; Cornet, François; Desmecht, Daniel

2010-01-01

The interferon-induced Mx proteins of vertebrates are dynamin-like GTPases, some isoforms of which can additionally inhibit the life cycle of certain RNA viruses. Here we show that the porcine Mx1 protein (poMx1) inhibits replication of influenza A virus and we attempt to identify the step at which the viral life cycle is blocked. In infected cells expressing poMx1, the level of transcripts encoding the viral nucleoprotein is significantly lower than normal, even when secondary transcription is prevented by exposure to cycloheximide. This reveals that a pretranscriptional block participates to the anti-influenza activity. Binding and internalization of incoming virus particles are normal in the presence of poMx1 but centripetal traffic to the late endosomes is interrupted. Surprisingly but decisively, poMx1 significantly alters binding of early endosome autoantigen 1 to early endosomes and/or early endosome size and spatial distribution. This is compatible with impairment of traffic of the endocytic vesicles to the late endosomes. INRA, EDP Sciences, 2010.

Attenuation of Activity in an Endogenous Analgesia Circuit by Ongoing Pain in the Rat

PubMed Central

Ferrari, Luiz F.; Gear, Robert W.; Levine, Jon D.

2010-01-01

Analgesic efficacy varies depending on the pain syndrome being treated. One reason for this may be a differential effect of individual pain syndromes on the function of endogenous pain control circuits at which these drugs act to produce analgesia. To test this hypothesis we examined the effects of diverse (i.e., ongoing inflammatory, neuropathic, or chronic widespread) pain syndromes on analgesia induced by activation of an opioid-mediated noxious stimulus-induced endogenous pain control circuit. This circuit was activated by subdermal capsaicin injection at a site remote from the site of nociceptive testing. Analgesia was not affected by carrageenan-induced inflammatory pain nor the early-phase of oxaliplatin neuropathy (a complication of cancer chemotherapy). However, the duration of analgesia was markedly shorter in the late-phase of oxaliplatin neuropathy and in alcoholic neuropathy. A model of fibromyalgia syndrome produced by chronic unpredictable stress and proinflammatory cytokines also shortened analgesia duration, but so did the same stress alone. Therefore, since chronic pain can activate neuroendocrine stress axes, we tested whether they are involved in the attenuation of analgesic duration induced by these pain syndromes. Rats in which the sympathoadrenal axis was ablated by adrenal medullectomy showed normal duration pain-induced analgesia in groups with either late-phase oxaliplatin neuropathy, alcoholic neuropathy, or exposure to sound stress. These results support the suggestion that pain syndromes can modulate activity in endogenous pain control circuits, and this effect is sympathoadrenal dependent. PMID:20943910

The Role of “Leakage” of Tubular Fluid in Anuria Due to Mercury Poisoning*

PubMed Central

Bank, Norman; Mutz, Bertrand F.; Aynedjian, Hagop S.

1967-01-01

The role of “leakage” of tubular fluid in anuria produced by mercury poisoning was studied in rats by micropuncture techniques. After an initial brisk diuresis, almost all animals were completely anuric 24 hours after HgCl2 injection. Lissamine green injected intravenously in the early stage of anuria appeared in the beginning of the proximal tubule, but the color became progressively lighter as the dye traversed the proximal convolutions. The dye was barely visible in the terminal segments of the proximal tubule; it did not appear at all in the distal tubules. These observations suggest that the proximal epithelium had become abnormally permeable to Lissamine green. Tubular fluid to plasma inulin (TF/PIn) ratios and inulin clearance were measured in individual nephrons at three sites: early proximal tubule, late proximal tubule, and distal tubule. It was found that TF/PIn ratios were abnormally low in the late proximal and distal tubules. Inulin clearance was normal at the beginning of the proximal tubule but fell by more than 60% by the late proximal convolutions. Thus, the proximal tubule had also become permeable to inulin. We conclude from these observations that anuria in mercury poisoning can occur in the presence of a normal glomerular filtration rate. The absence of urine flow appears to be due to complete absorption of the filtrate through an excessively permeable tubular epithelium. The driving force affecting this fluid absorption is probably the colloid oncotic pressure of the peritubular capillary blood. Images PMID:6025476

Kynurenine pathway changes in late-life depression.

PubMed

Wu, Yujie; Zhong, Xiaomei; Mai, Naikeng; Wen, Yuguan; Shang, Dewei; Hu, Lijun; Chen, Ben; Zhang, Min; Ning, Yuping

2018-08-01

Kynurenine pathway (KP) activation is associated with several neuropsychiatric diseases, including major depression disorder (MDD). Although several investigations have been conducted on MDD, these have seldom shed light on KP changes in late-life depression (LLD). We aimed to investigate whether tryptophan (TRP) metabolism and kynurenine (KYN) metabolism are imbalanced in LLD patients and to explore the differences in KP characteristics between early onset depression (EOD) and late onset depression (LOD) patients. We investigated 170 LLD patients (EOD 90, LOD 80) and 135 normal controls. Serum concentrations of TRP, KYN and kynurenic acid (KYNA) were detected by the liquid chromatography-tandem mass spectrometry method. Depressive symptoms were assessed by the 17-item Hamilton Depression Scale (HAMD-17). LLD patients exhibited lower levels of TRP, KYN, KYNA and KYNA/KYN ratio and a higher level of KYN/TRY ratio than normal controls. The decrease in TRP and the increase in KYN/TRP ratio were found in LOD patients. A low TRP level without increased KYN/TRP ratio was found in EOD patients. The "Depression" factor, which was extracted from HAMD-17 by the principal component factor analysis, was correlated with the TRP level and KYNA/KYN ratio in the EOD group, but no such correlation was found in the LOD group. KP changes were observed in LLD patients; LOD patients showed profound shifts in TRP metabolism, while EOD patients showed low TRP level and a shift in KYN metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

Recurrent somnolence in a 17-month-old infant: late-onset ornithine transcarbamylase (OTC) deficiency due to the novel hemizygous mutation c.535C > T (p.Leu179Phe).

PubMed

Fantur, Michaela; Karall, Daniela; Scholl-Buergi, Sabine; Häberle, Johannes; Rauchenzauner, Markus; Fruehwirth, Martin

2013-01-01

Herein, we describe a case of a now 28-month-old boy who presented at the age of 17 months with four episodes of recurrent vomiting and somnolence during a period of four months with increasing severity. A comprehensive clinical and metabolic evaluation revealed normal blood pH and blood glucose, normal cerebral computed tomography and electroencephalogram but an elevated plasma ammonia concentration, which raised the suspicion of a urea cycle disorder. The combination of elevated urinary orotic acid and plasma glutamine with normal citrulline suggested the diagnosis of ornithine transcarbamylase (OTC) deficiency, which was confirmed by molecular genetic testing revealing the novel hemizygous mutation c.535C > T (p.Leu179Phe) of the OTC gene. After restitution of anabolism by administration of parenteral glucose, substitution of citrulline and detoxification of ammonia with sodium benzoate, the patient recovered rapidly and is in a stable metabolic and neurological state since then. This case underlines that the diagnosis of a urea cycle defect should be considered in the differential diagnosis of recurrent idiopathic vomiting in combination with unexplained neurological symptoms also beyond the neonatal period due to the possibility of mild or atypical late-onset presentation (e.g. OTC deficiency in hemizygous males). Copyright © 2012 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Late Effects of Treatment for Childhood Cancer (PDQ®)—Health Professional Version

Cancer.gov

Late effects of cancer treatment can cause serious, disabling, and life-threatening chronic health conditions that adversely affect the health of aging childhood cancer survivors. Learn about subsequent neoplasms and the cardiovascular, cognitive, psychosocial, digestive, endocrine, immune, musculoskeletal, reproductive, and urinary late effects of pediatric cancer treatment in this expert-reviewed summary.

Late-successional forests and northern spotted owls: how effective is the Northwest Forest Plan?

Treesearch

Miles Hemstrom; Martin G. Raphael

2000-01-01

This paper describes the late-successional and old-growth forest and the northern spotted owl effectiveness monitoring plans for the Northwest Forest Plan. The effectiveness monitoring plan for late-successional and old-growth forests will track changes in forest spatial distribution, and within-stand structure and composition, and it will predict future trends.

COGNITION AS A THERAPEUTIC TARGET IN LATE-LIFE DEPRESSION: POTENTIAL FOR NICOTINIC THERAPEUTICS

PubMed Central

Zurkovsky, Lilia; Taylor, Warren D.; Newhouse, Paul A.

2013-01-01

Depression is associated with impairments to cognition and brain function at any age, but such impairments in the elderly are particularly problematic because of the additional burden of normal cognitive aging and in some cases, structural brain pathology. Individuals with late-life depression exhibit impairments in cognition and brain structural integrity, alongside mood dysfunction. Antidepressant treatment improves symptoms in some but not all patients, and those who benefit may not return to the cognitive and functional level of nondepressed elderly. Thus, for comprehensive treatment of late-life depression, it may be necessary to address both the affective and cognitive deficits. In this review, we propose a model for the treatment of late-life depression in which nicotinic stimulation is used to improve cognitive performance and improve the efficacy of an antidepressant treatment of the syndrome of late-life depression. The cholinergic system is well-established as important to cognition. Although muscarinic stimulation may exacerbate depressive symptoms, nicotinic stimulation may improve cognition and neural functioning without a detriment to mood. While some studies of nicotinic subtype specific receptor agonists have shown promise in improving cognitive performance, less is known regarding how nicotinic receptor stimulation affects cognition in depressed elderly patients. Late-life depression thus represents a new therapeutic target for the development of nicotinic agonist drugs and parallel treatment of cognitive dysfunction along with medical and psychological approaches to treating mood dysfunction may be necessary to ensure full resolution of depressive illness in aging. PMID:23933385

Early versus late GD-DTPA MRI enhancement in experimental glioblastomas.

PubMed

Farace, Paolo; Tambalo, Stefano; Fiorini, Silvia; Merigo, Flavia; Daducci, Alessandro; Nicolato, Elena; Conti, Giamaica; Degrassi, Anna; Sbarbati, Andrea; Marzola, Pasquina

2011-03-01

To compare early versus late enhancement in two glioblastoma models characterized by different infiltrative/edematous patterns. Three weeks after inoculation into nude mice of U87MG and U251 cells, T1-weighted images were acquired early (10.5 min), intermediate (21 min) and late (30.5 min) after a bolus injection of Gd-DTPA at 300 μ mol/kg dosage. EARLY(TH) and LATE(TH) were the corresponding volumes with an enhancement higher than a threshold TH, defined by the mean (μ) and standard deviation (σ) on a contralateral healthy area. ADD(TH) was the enhancing volume found in LATE(TH) but not in EARLY(TH). T2 imaging of both tumors was performed, and T2 mapping of U251. In all tumors, LATE(TH) was significantly higher than EARLY(TH) for TH ranging from μ+σ to μ+5σ. The ADD(TH) /EARLY(TH) ratio was not significantly different when U251 and U87MG tumors were compared. In the U87MG tumors, some enhancement was observed outside the regularly demarcated T2-hyperintense area. In the U251 tumors, irregularly T2 demarcated, a large portion of ADD(μ+3σ) had normal T2 values. At histology, U251 showed a higher infiltrative pattern than U87MG. In these models, the increase over time in the enhancing volume did not depend on the different infiltrative/edematous patterns and was not closely related with edema. Copyright © 2011 Wiley-Liss, Inc.

A Stimulus-Locked Vector Autoregressive Model for Slow Event-Related fMRI Designs

PubMed Central

Siegle, Greg

2009-01-01

Summary Neuroscientists have become increasingly interested in exploring dynamic relationships among brain regions. Such a relationship, when directed from one region toward another, is denoted by “effective connectivity.” An fMRI experimental paradigm which is well-suited for examination of effective connectivity is the slow event-related design. This design presents stimuli at sufficient temporal spacing for determining within-trial trajectories of BOLD activation, allowing for the analysis of stimulus-locked temporal covariation of brain responses in multiple regions. This may be especially important for emotional stimuli processing, which can evolve over the course of several seconds, if not longer. However, while several methods have been devised for determining fMRI effective connectivity, few are adapted to event-related designs, which include non-stationary BOLD responses and multiple levels of nesting. We propose a model tailored for exploring effective connectivity of multiple brain regions in event-related fMRI designs - a semi-parametric adaptation of vector autoregressive (VAR) models, termed “stimulus-locked VAR” (SloVAR). Connectivity coefficients vary as a function of time relative to stimulus onset, are regularized via basis expansions, and vary randomly across subjects. SloVAR obtains flexible, data-driven estimates of effective connectivity and hence is useful for building connectivity models when prior information on dynamic regional relationships is sparse. Indices derived from the coefficient estimates can also be used to relate effective connectivity estimates to behavioral or clinical measures. We demonstrate the SloVAR model on a sample of clinically depressed and normal controls, showing that early but not late cortico-amygdala connectivity appears crucial to emotional control and early but not late cortico-cortico connectivity predicts depression severity in the depressed group, relationships that would have been missed in a more traditional VAR analysis. PMID:19236927

Characteristics and Mechanisms of Zonal Oscillation of Western Pacific Subtropical High in Summer

NASA Astrophysics Data System (ADS)

Guan, W.; Ren, X.; Hu, H.

2017-12-01

The zonal oscillation of the western Pacific subtropical high (WPSH) influences the weather and climate over East Asia significantly. This study investigates the features and mechanisms of the zonal oscillation of the WPSH during summer on subseasonal time scales. The zonal oscillation index of the WPSH is defined by normalized subseasonal geopotential height anomaly at 500hPa averaged over the WPSH's western edge (110° - 140°E, 10° - 30°N). The index shows a predominant oscillation with a period of 10-40 days. Large positive index indicates a strong anticyclonic anomaly over East Asia and its coastal region south of 30°N at both 850hPa and 500hPa. The WPSH stretches more westward accompanied by warmer SST anomalies beneath the western edge of the WPSH. Meanwhile, above-normal precipitation is seen over the Yangtze-Huaihe river basin and below-normal precipitation over the south of the Yangtze River. Negative index suggests a more eastward position of WPSH. The anomalies in circulation and SST for negative index are almost the mirror image of those for the positive index. In early summer, the zonal shift of the WPSH is affected by both the East Asia/Pacific (EAP) teleconnection pattern and the Silk road pattern (SRP). The positive (negative) phase of the EAP pattern is characterized by a low-level anticyclonic (cyclonic) anomaly over the subtropical western Pacific, indicating the western extension (eastward retreat) of the WPSH. Comparing with the EAP pattern, the SRP forms an upper-level anticyclonic (cyclonic) anomaly in mid-latitudes of East Asia, and then leads to the westward (eastward) movement of the WPSH. In late summer, the zonal shift of the WPSH is mainly affected by the EAP pattern, because the EAP pattern in late summer is stronger than that in early summer. The zonal shift of the WPSH is also influenced by the subseasonal air-sea interaction locally. During the early stage of WPSH's westward stretch, the local SST anomaly in late summer is colder than that in early summer. This forms a more favorable condition for the increasing of local anticyclonic anomaly. Thus, the anticyclonic anomaly in late summer is stronger than that in early summer.

Late Paleogene rifting along the Malay Peninsula thickened crust

NASA Astrophysics Data System (ADS)

Sautter, Benjamin; Pubellier, Manuel; Jousselin, Pierre; Dattilo, Paolo; Kerdraon, Yannick; Choong, Chee Meng; Menier, David

2017-07-01

Sedimentary basins often develop above internal zones of former orogenic belts. We hereafter consider the Malay Peninsula (Western Sunda) as a crustal high separating two regions of stretched continental crust; the Andaman/Malacca basins in the western side and the Thai/Malay basins in the east. Several stages of rifting have been documented thanks to extensive geophysical exploration. However, little is known on the correlation between offshore rifted basins and the onshore continental core. In this paper, we explore through mapping and seismic data, how these structures reactivate pre-existing Mesozoic basement heterogeneities. The continental core appears to be relatively undeformed after the Triassic Indosinian orogeny. The thick crustal mega-horst is bounded by complex shear zones (Ranong, Klong Marui and Main Range Batholith Fault Zones) initiated during the Late Cretaceous/Early Paleogene during a thick-skin transpressional deformation and later reactivated in the Late Paleogene. The extension is localized on the sides of this crustal backbone along a strip where earlier Late Cretaceous deformation is well expressed. To the west, the continental shelf is underlain by three major crustal steps which correspond to wide crustal-scale tilted blocks bounded by deep rooted counter regional normal faults (Mergui Basin). To the east, some pronounced rift systems are also present, with large tilted blocks (Western Thai, Songkhla and Chumphon basins) which may reflect large crustal boudins. In the central domain, the extension is limited to isolated narrow N-S half grabens developed on a thick continental crust, controlled by shallow rooted normal faults, which develop often at the contact between granitoids and the host-rocks. The outer limits of the areas affected by the crustal boudinage mark the boundary towards the large and deeper Andaman basin in the west and the Malay and Pattani basins in the east. At a regional scale, the rifted basins resemble N-S en-echelon structures along large NW-SE shear bands. The rifting is accommodated by large low angle normal faults (LANF) running along crustal morphostructures such as broad folds and Mesozoic batholiths. The deep Andaman, Malay and Pattani basins seem to sit on weaker crust inherited from Gondwana-derived continental blocks (Burma, Sibumasu, and Indochina). The set of narrow elongated basins in the core of the Region (Khien Sa, Krabi, and Malacca basins) suffered from a relatively lesser extension.

The nature of the late B-type stars HD 67044 and HD 42035

NASA Astrophysics Data System (ADS)

Monier, R.; Gebran, M.; Royer, F.

2016-04-01

While monitoring a sample of apparently slowly rotating superficially normal bright late B and early A stars in the northern hemisphere, we have discovered that HD 67044 and HD 42035, hitherto classified as normal late B-type stars, are actually respectively a new chemically peculiar star and a new spectroscopic binary containing a very slow rotator HD 42035 S with ultra-sharp lines (v_{{e}}sin i= 3.7 km s^{-1}) and a fast rotator HD 42035 B with broad lines. The lines of Ti ii, Cr ii, Mn ii, Sr ii, Y ii, Zr ii and Ba ii are conspicuous features in the high resolution SOPHIE spectrum (R=75000) of HD 67044. The Hg ii line at 3983.93 Å is also present as a weak feature. The composite spectrum of HD 42035 is characterised by very sharp lines formed in HD 42035 S superimposed onto the shallow and broad lines of HD 42035 B. These very sharp lines are mostly due to light elements from C to Ni, the only heavy species definitely present are strontium and barium. Selected lines of 21 chemical elements from He up to Hg have been synthesized using model atmospheres computed with ATLAS9 and the spectrum synthesis code SYNSPEC48 including hyperfine structure of various isotopes when relevant. These synthetic spectra have been adjusted to high resolution high signal-to-noise spectra of HD 67044 and HD 42035 S in order to derive abundances of these key elements. HD 67044 is found to have distinct enhancements of Ti, Cr, Mn, Sr, Y, Zr, Ba and Hg and underabundances in He, C, O, Ca and Sc which shows that this star is not a superficially normal late B-type star, but actually is a new CP star most likely of the HgMn type. HD 42035 S has provisional underabundances of the light elements from C to Ti and overabundances of heavier elements (except for Fe and Sr which are also underabundant) up to barium. These values are lower limits to the actual abundances as we cannot currently place properly the continuum of HD 42035 S. More accurate fundamental parameters and abundances for HD 42035 S and HD 42035 B will be derived if we manage to disentangle their spectra. They will help clarify the status of the two components in this interesting new spectroscopic binary.

Paleomagnetism of the Cretaceous Galula Formation and implications for vertebrate evolution

NASA Astrophysics Data System (ADS)

Widlansky, Sarah J.; Clyde, William C.; O'Connor, Patrick M.; Roberts, Eric M.; Stevens, Nancy J.

2018-03-01

This study uses magnetostratigraphy to help constrain the age of the paleontologically important Galula Formation (Rukwa Rift Basin, southwestern Tanzania). The formation preserves a Cretaceous vertebrate fauna, including saurischian dinosaurs, a putative gondwanatherian mammal, and notosuchian crocodyliforms. With better dating, the Galula Formation and its fossils help fill a temporal gap in our understanding of vertebrate evolution in continental Africa, enabling better evaluation of competing paleobiogeographic hypotheses concerning faunal exchange throughout Gondwana during the Cretaceous. Paleomagnetic samples for this study were collected from the Namba (higher in section) and Mtuka (lower in section) members of the Galula Formation and underwent stepwise thermal demagnetization. All samples displayed a strong normal magnetic polarity overprint, and maximum unblocking temperatures at approximately 690 °C. Three short reversed intervals were identified in the Namba Member, whereas the Mtuka Member lacked any clear reversals. Given the relatively limited existing age constraints, one interpretation correlates the Namba Member to Chron C32. An alternative correlation assigns reversals in the Namba Member to recently proposed short reversals near the end of the Cretaceous Normal Superchron (Chron C34), a time that is traditionally interpreted as having stable normal polarity. The lack of reversals in the Mtuka Member supports deposition within Chron C34. These data suggest that the Namba Member is no older than Late Cretaceous (Cenomanian-Campanian), with the Mtuka Member less well constrained to the middle Cretaceous (Aptian-Cenomanian). The paleomagnetic results are supported by the application of fold and reversal tests for paleomagnetic stability, and paleomagnetic poles for the Namba (246.4°/77.9°, α95 5.9°) and Mtuka (217.1°/72.2°, α95 11.1°) members closely matching the apparent polar wander path for Africa during the Late Cretaceous. These results confidently indicate a Late Creteceous age assignment for the Namba Member of the Galula Formation, a unit that has yielded key crocodyliform (e.g., Pakasuchus; Rukwasuchus) and dinosaur (e.g., Rukwatitan; Shingopana) fossils from eastern Africa.

The Bear River Fault Zone, Wyoming and Utah: Complex Ruptures on a Young Normal Fault

NASA Astrophysics Data System (ADS)

Schwartz, D. P.; Hecker, S.; Haproff, P.; Beukelman, G.; Erickson, B.

2012-12-01

The Bear River fault zone (BRFZ), a set of normal fault scarps located in the Rocky Mountains at the eastern margin of Basin and Range extension, is a rare example of a nascent surface-rupturing fault. Paleoseismic investigations (West, 1994; this study) indicate that the entire neotectonic history of the BRFZ may consist of two large surface-faulting events in the late Holocene. We have estimated a maximum per-event vertical displacement of 6-6.5 m at the south end of the fault where it abuts the north flank of the east-west-trending Uinta Mountains. However, large hanging-wall depressions resulting from back rotation, which front scarps that locally exceed 15 m in height, are prevalent along the main trace, obscuring the net displacement and its along-strike distribution. The modest length (~35 km) of the BRFZ indicates ruptures with a large displacement-to-length ratio, which implies earthquakes with a high static stress drop. The BRFZ is one of several immature (low cumulative displacement) normal faults in the Rocky Mountain region that appear to produce high-stress drop earthquakes. West (1992) interpreted the BRFZ as an extensionally reactivated ramp of the late Cretaceous-early Tertiary Hogsback thrust. LiDAR data on the southern section of the fault and Google Earth imagery show that these young ruptures are more extensive than currently mapped, with newly identified large (>10m) antithetic scarps and footwall graben. The scarps of the BRFZ extend across a 2.5-5.0 km-wide zone, making this the widest and most complex Holocene surface rupture in the Intermountain West. The broad distribution of Late Holocene scarps is consistent with reactivation of shallow bedrock structures but the overall geometry of the BRFZ at depth and its extent into the seismogenic zone are uncertain.

Guidelines for screening and management of late and long-term consequences of myeloma and its treatment.

PubMed

Snowden, John A; Greenfield, Diana M; Bird, Jennifer M; Boland, Elaine; Bowcock, Stella; Fisher, Abigail; Low, Eric; Morris, Monica; Yong, Kwee; Pratt, Guy

2017-03-01

A growing population of long-term survivors of myeloma is now accumulating the 'late effects' not only of myeloma itself, but also of several lines of treatment given throughout the course of the disease. It is thus important to recognise the cumulative burden of the disease and treatment-related toxicity in both the stable and active phases of myeloma, some of which is unlikely to be detected by routine monitoring. We summarise here the evidence for the key late effects in long-term survivors of myeloma, including physical and psychosocial consequences (in Parts 1 and 2 respectively), and recommend the use of late-effects screening protocols in detection and intervention. The early recognition of late effects and effective management strategies should lead to an improvement in the management of myeloma patients, although evidence in this area is currently limited and further research is warranted. © 2017 John Wiley & Sons Ltd.

The Effect of Dose-Volume Parameters and Interfraction Interval on Cosmetic Outcome and Toxicity After 3-Dimensional Conformal Accelerated Partial Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leonard, Kara Lynne, E-mail: karalynne.kerr@gmail.com; Hepel, Jaroslaw T.; Department of Radiation Oncology, Rhode Island Hospital, Warren Alpert School of Medicine of Brown University, Providence, Rhode Island

2013-03-01

Purpose: To evaluate dose-volume parameters and the interfraction interval (IFI) as they relate to cosmetic outcome and normal tissue effects of 3-dimensional conformal radiation therapy (3D-CRT) for accelerated partial breast irradiation (APBI). Methods and Materials: Eighty patients were treated by the use of 3D-CRT to deliver APBI at our institutions from 2003-2010 in strict accordance with the specified dose-volume constraints outlined in the National Surgical Adjuvant Breast and Bowel Project B39/Radiation Therapy Oncology Group 0413 (NSABP-B39/RTOG 0413) protocol. The prescribed dose was 38.5 Gy in 10 fractions delivered twice daily. Patients underwent follow-up with assessment for recurrence, late toxicity, andmore » overall cosmetic outcome. Tests for association between toxicity endpoints and dosimetric parameters were performed with the chi-square test. Univariate logistic regression was used to evaluate the association of interfraction interval (IFI) with these outcomes. Results: At a median follow-up time of 32 months, grade 2-4 and grade 3-4 subcutaneous fibrosis occurred in 31% and 7.5% of patients, respectively. Subcutaneous fibrosis improved in 5 patients (6%) with extended follow-up. Fat necrosis developed in 11% of women, and cosmetic outcome was fair/poor in 19%. The relative volume of breast tissue receiving 5%, 20%, 50%, 80%, and 100% (V5-V100) of the prescribed dose was associated with risk of subcutaneous fibrosis, and the volume receiving 50%, 80%, and 100% (V50-V100) was associated with fair/poor cosmesis. The mean IFI was 6.9 hours, and the minimum IFI was 6.2 hours. The mean and minimum IFI values were not significantly associated with late toxicity. Conclusions: The incidence of moderate to severe late toxicity, particularly subcutaneous fibrosis and fat necrosis and resulting fair/poor cosmesis, remains high with continued follow-up. These toxicity endpoints are associated with several dose-volume parameters. Minimum and mean IFI values were not associated with late toxicity.« less

Pulmonary Outcomes in Survivors of Childhood Cancer

PubMed Central

Hudson, Melissa M.; Stokes, Dennis C.; Krasin, Matthew J.; Spunt, Sheri L.; Ness, Kirsten K.

2011-01-01

Background: The purpose of this article is to summarize the literature that documents the long-term impact of cancer treatment modalities on pulmonary function among survivors of cancer and to identify potential areas for further research. Methods: Systematic reviews of clinical trials, observational studies, case series, and review articles were conducted. Articles were limited to the studies that discussed pulmonary toxicity or late effects among pediatric cancer survivors and to follow-up investigations that were conducted a minimum of 2 years after completion of cancer-related treatment or 1 year after hematopoietic stem cell transplant. Results: Sixty publications (51 clinical studies/reports and nine reviews) published from January 1970 to June 2010 in PubMed met the inclusion criteria. Data showed an association between radiotherapy, alkylating agents, bleomycin, hematopoietic stem cell transplant, and thoracic surgery and pulmonary toxicity, as well as possible interactions among these modalities. Conclusions: Pulmonary toxicity is a common long-term complication of exposure to certain anticancer therapies in childhood and can vary from subclinical to life threatening. Pulmonary function and associated loss of optimal exercise capacity may have adverse effects on long-term quality of life in survivors. Lung function diminishes as a function of normal aging, and the effects of early lung injury from cancer therapy may compound these changes. The information presented in this review is designed to provide a stimulus to promote both observational and interventional research that expands our knowledge and aids in the design of interventions to prevent or ameliorate pulmonary late effects among survivors of childhood cancer. PMID:21415131

Emotional withdrawal, CT abnormalities and drug response in late life depression.

PubMed

Altamura, A Carlo; Bassetti, Roberta; Santini, Annalisa; Frisoni, G B; Mundo, Emanuela

2004-03-01

In this study, the authors investigated if CNS degenerative abnormalities could correlate with depressive symptoms in elderly patients, if the presence of mild/moderate cognitive impairment could be related to the response to treatment and the role of peculiar clinical features in influencing the response to treatment. Fifty-three patients (60-75 years) diagnosed as affected by late onset (after 60 years) Major Depressive Episodes according to DSM-IV criteria were studied. Brain vascular and degenerative markers were assessed by computed tomography (CT) through measurements of a lateralized version of the bifrontal index and a rating scale addressing subcortical disease. The presence of mild/moderate cognitive impairment [(24-28 total score at the Mini-Mental State Examination (MMSE)], and of specific symptoms were assessed at baseline and evaluated with respect to the antidepressant response. Patients with CT abnormalities showed higher baseline scores on Hamilton Rating Scale for Depression (HAM-D) items "late insomnia" (t=-2.674, P=.002), "somatic symptoms" (t=-3.355 P=.002), and Brief Psychiatric Rating Scale (BPRS) item "emotional withdrawal" (t=-3.355, P=.002). No significant correlation was found between the vascular index and baseline clinical symptoms, while the HAM-D "depressed mood" item was negatively correlated to the right frontal index (R=-0.692, P=.006). Patients with CT abnormalities showed a lower reduction of HAM-D total scores than patients with normal CT (time effect: F=29.277, P<.0001; group effect: F=5.154, P<.03), while a significant reduction of symptoms in time (time effect: F=33.33, P<.0001) but no differences between groups were found on Hamilton Rating Scale for Anxiety (HAM-A). Both patients with and without mild cognitive impairment improved on the HAM-D (time effect: F=19.668, P<.0001), BPRS (time effect: F=18.345, P<.0001), and HAM-A (time effect: F=17.959, P<.0001) total scores. Patients with emotional withdrawal showed lower improvement on BPRS total scores (time effect: F=26.946, P<.0001; group effect: F=5.121, P<.03). The results from this study showed that patients with baseline emotional withdrawal and CT abnormalities have poorer outcome. Further investigations on larger samples are needed to confirm these findings.

Roles of the Drosophila LRRK2 homolog in Rab7-dependent lysosomal positioning.

PubMed

Dodson, Mark W; Zhang, Ting; Jiang, Changan; Chen, Shengdi; Guo, Ming

2012-03-15

LRRK2 (PARK8) is the most common genetic determinant of Parkinson's disease (PD), with dominant mutations in LRRK2 causing inherited PD and sequence variation at the LRRK2 locus associated with increased risk for sporadic PD. Although LRRK2 has been implicated in diverse cellular processes encompassing almost all cellular compartments, the precise functions of LRRK2 remain unclear. Here, we show that the Drosophila homolog of LRRK2 (Lrrk) localizes to the membranes of late endosomes and lysosomes, physically interacts with the crucial mediator of late endosomal transport Rab7 and negatively regulates rab7-dependent perinuclear localization of lysosomes. We also show that a mutant form of lrrk analogous to the pathogenic LRRK2(G2019S) allele behaves oppositely to wild-type lrrk in that it promotes rather than inhibits rab7-dependent perinuclear lysosome clustering, with these effects of mutant lrrk on lysosome position requiring both microtubules and dynein. These data suggest that LRRK2 normally functions in Rab7-dependent lysosomal positioning, and that this function is disrupted by the most common PD-causing LRRK2 mutation, linking endolysosomal dysfunction to the pathogenesis of LRRK2-mediated PD.

Soft-sediment deformation structures interpreted as seismites in the uppermost Aptian to lowermost Albian transgressive deposits of the Chihuahua basin (Mexico)

USGS Publications Warehouse

Blanc, E.J.-P.; Blanc-Aletru, M. -C.; Mojon, P.-O.

1998-01-01

Several levels of soft-sediment deformation structures (s.-s.d.s.) cut by synsedimentary normal faults have been observed in the transition beds between the "Las Vigas" and "La Virgen" formations (Cretaceous) in the northeastern part of the Chihuahua basin in Mexico. These structures consisted of four kinds of motifs (floating breccias, flame-like structures, large pillow structures, and wavy structures). They are restricted to five "stratigraphie" levels (Z1-Z5) and surrounded by undeformed beds in fluvio-lacustrine and tidal deposits and can be traced over a distance of several hundred meters. This deformation is interpreted to have resulted from the combined effects of liquidization and shear stress in soft-sediments due to local earthquakes in the area which could have been generated during the rifting stage of the Chihuahua basin. New constraints placed on the age of the "Las Vigas" Formation (bracketed by Late Aptian charophytes at the bottom and colomiellids of late Aptian to earliest Albian age at the top) suggest that this synrift tectonism lasted at least until the end of the Aptian. ?? Springer-Verlag 1998.

Roles of the Drosophila LRRK2 homolog in Rab7-dependent lysosomal positioning

PubMed Central

Dodson, Mark W.; Zhang, Ting; Jiang, Changan; Chen, Shengdi; Guo, Ming

2012-01-01

LRRK2 (PARK8) is the most common genetic determinant of Parkinson's disease (PD), with dominant mutations in LRRK2 causing inherited PD and sequence variation at the LRRK2 locus associated with increased risk for sporadic PD. Although LRRK2 has been implicated in diverse cellular processes encompassing almost all cellular compartments, the precise functions of LRRK2 remain unclear. Here, we show that the Drosophila homolog of LRRK2 (Lrrk) localizes to the membranes of late endosomes and lysosomes, physically interacts with the crucial mediator of late endosomal transport Rab7 and negatively regulates rab7-dependent perinuclear localization of lysosomes. We also show that a mutant form of lrrk analogous to the pathogenic LRRK2G2019S allele behaves oppositely to wild-type lrrk in that it promotes rather than inhibits rab7-dependent perinuclear lysosome clustering, with these effects of mutant lrrk on lysosome position requiring both microtubules and dynein. These data suggest that LRRK2 normally functions in Rab7-dependent lysosomal positioning, and that this function is disrupted by the most common PD-causing LRRK2 mutation, linking endolysosomal dysfunction to the pathogenesis of LRRK2-mediated PD. PMID:22171073

Mitotic effects of monochromatic ultraviolet radiation at 225, 265, and 280 nm on eleven stages of the cell cycle of the grasshopper neuroblast in culture. II. Changes in progression rate and cell sequence between the stage irradiated and nuclear membrane breakdown

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carlson, J.G.

1976-10-01

Portions of embryos of the grasshopper, Chortophaga viridifasciata (DeGeer), were cultured in hanging drops under quartz cover slips. Immediately after exposure to 225, 265, or 280 nm radiation, microscope observations at 38/sup 0/C were begun. The morphologically identified stage and the time after treatment of selected neuroblasts were recorded at short-time intervals until prometaphase was reached. Mitotic retardation induced by irradiation of prereplication stages (metaphase, anaphase, or early telophase) or S phase (middle or late telophase, interphase, or very early prophase) is greatest in postreplication stages (early, middle, and late prophase) and absent or minimal in stages morphologically identified asmore » parts of S phase. Ultraviolet irradiation superimposes on the normal diversity of progression rates an additional variation factor, so that cells do not necessarily reach prometaphase in the order of their sequence at the time of treatment. This suggests the need for caution in ascribing particular radiosensitivities to substages of limited duration on the basis of the order in which they attain a subsequent stage.« less

Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood.

PubMed

Taskinen, M; Saarinen-Pihkala, U M; Hovi, L; Lipsanen-Nyman, M

2000-09-16

This follow-up study aimed to assess the frequency of late effects on glucose and lipid metabolism after bone-marrow transplantation in childhood. 23 long-term survivors (median age 20 years) were studied 3-18 years after bone-marrow transplantation and compared with 23 healthy controls matched for age and sex and with 13 patients in remission from leukaemia. 12 (52%) of the 23 bone-marrow transplantation patients had insulin resistance, including impaired glucose tolerance in six and type 2 diabetes in four. The core signs of the metabolic syndrome (hyperinsulinaemia and hypertriglyceridaemia combined), were found in nine (39%) of the bone-marrow transplantation patients compared with one (8%) of the 13 leukaemia patients and none of the healthy controls (p=0.0015). The frequency of insulin resistance increased with the time since bone-marrow transplantation. Abdominal obesity, but not overweight, was common among the patients with insulin resistance. Long-term survivors of bone-marrow transplantation are at substantial risk of insulin resistance, impaired glucose tolerance, and type 2 diabetes even at normal weight and young age. They also develop typical signs of the metabolic syndrome. We advocate measurement of serum lipids, fasting blood glucose, and serum insulin for the follow-up of all patients who undergo transplants in childhood, to be continued regularly and possibly life-long.

Small molecule inhibitors of Late SV40 Factor (LSF) abrogate hepatocellular carcinoma (HCC): Evaluation using an endogenous HCC model.

PubMed

Rajasekaran, Devaraja; Siddiq, Ayesha; Willoughby, Jennifer L S; Biagi, Jessica M; Christadore, Lisa M; Yunes, Sarah A; Gredler, Rachel; Jariwala, Nidhi; Robertson, Chadia L; Akiel, Maaged A; Shen, Xue-Ning; Subler, Mark A; Windle, Jolene J; Schaus, Scott E; Fisher, Paul B; Hansen, Ulla; Sarkar, Devanand

2015-09-22

Hepatocellular carcinoma (HCC) is a lethal malignancy with high mortality and poor prognosis. Oncogenic transcription factor Late SV40 Factor (LSF) plays an important role in promoting HCC. A small molecule inhibitor of LSF, Factor Quinolinone Inhibitor 1 (FQI1), significantly inhibited human HCC xenografts in nude mice without harming normal cells. Here we evaluated the efficacy of FQI1 and another inhibitor, FQI2, in inhibiting endogenous hepatocarcinogenesis. HCC was induced in a transgenic mouse with hepatocyte-specific overexpression of c-myc (Alb/c-myc) by injecting N-nitrosodiethylamine (DEN) followed by FQI1 or FQI2 treatment after tumor development. LSF inhibitors markedly decreased tumor burden in Alb/c-myc mice with a corresponding decrease in proliferation and angiogenesis. Interestingly, in vitro treatment of human HCC cells with LSF inhibitors resulted in mitotic arrest with an accompanying increase in CyclinB1. Inhibition of CyclinB1 induction by Cycloheximide or CDK1 activity by Roscovitine significantly prevented FQI-induced mitotic arrest. A significant induction of apoptosis was also observed upon treatment with FQI. These effects of LSF inhibition, mitotic arrest and induction of apoptosis by FQI1s provide multiple avenues by which these inhibitors eliminate HCC cells. LSF inhibitors might be highly potent and effective therapeutics for HCC either alone or in combination with currently existing therapies.

[Disorders of endocrine function after brain tumor therapy in childhood].

PubMed

Marx, M; Langer, T; Beck, J D; Dörr, H G

1999-07-01

Advances in the therapy of malignant brain tumors in children have led to a significant improvement in survival rates over the last few decades. As a result, the recognition and treatment of late effects have become more important. In addition to secondary tumors and deficiencies in cognitive and intellectual skills, the resulting endocrine disturbances play an important role. Own data and literature review. Deviations from the normal growth hormone secretion are usually recognized first and are most common, and have already been observed after conventional whole brain irradiation with 18 Gy. With some delay, other hypothalamo-pituitary deficiencies may occur, including panhypopituitarism. Puberty may come too early or too late or may not appear at all. Girls in particular, frequently experience an early and rapid pubertal development after brain tumor therapy, which may lead to further reduction in height due to an accelerated bone maturation. Functional disturbances of the thyroid and adrenal glands due to hypothalamic or pituitary deficiency are less common, and usually seen only after a radiation dose of over 40 Gy. Survivors of childhood brain tumors must be considered as long-term survivors, in whom the first therapy-induced long-term side effects appear almost immediately after the end of therapy. Maximum quality of life for the individual patient can only be achieved by long-term care and close cooperation of specialists in the different medical disciplines involved.

Differential roles of osteopontin/Eta-1 in early and late lpr disease

PubMed Central

Weber, G F; Cantor, H

2001-01-01

The cytokine osteopontin (Eta-1) leads to macrophage-dependent polyclonal B-cell activation and is induced early in autoimmune prone mice with the lpr mutation, suggesting a significant pathogenic role for this molecule. Indeed, C57BL/6-Faslpr/lpr mice crossed with osteopontin−/– mice display delayed onset of polyclonal B-cell activation, as judged by serum immunoglobulin levels. In contrast, they are subject to normal onset, but late exacerbation of lymphoproliferation and evidence of kidney disease. These observations define two stages of Faslpr/lpr disease with respect to osteopontin-dependent pathogenesis that should be taken into account in the design of therapeutic approaches to the clinical disease. PMID:11737079

Heat transfer and fluid mechanics measurements in transitional boundary layer flows

NASA Technical Reports Server (NTRS)

Wang, T.; Simon, T. W.; Buddhavarapu, J.

1985-01-01

Experimental results are presented to document hydrodynamic and thermal development of flat-plate boundary layers undergoing natural transition. Local heat transfer coefficients, skin friction coefficients and profiles of velocity, temperature and Reynolds normal and shear stresses are presented. A case with no transition and transitional cases with 0.68% and 2.0% free-stream disturbance intensities were investigated. The locations of transition are consistent with earlier data. A late-laminar state with significant levels of turbulence is documented. In late-transitional and early-turbulent flows, turbulent Prandtl number and conduction layer thickness values exceed, and the Reynolds analogy factor is less than, values previously measured in fully turbulent flows.

Integrated Planning for Telepresence with Time Delays

NASA Technical Reports Server (NTRS)

Johnston, Mark D.; Rabe, Kenneth J.

2006-01-01

Integrated planning and execution of teleoperations in space with time delays is shown. The topics include: 1) The Problem; 2) Future Robot Surgery? 3) Approach Overview; 4) Robonaut; 5) Normal Planning and Execution; 6) Planner Context; 7) Implementation; 8) Use of JSHOP2; 9) Monitoring and Testing GUI; 10) Normal sequence: first the supervisor acts; 11) then the robot; 12) Robot might be late; 13) Supervisor can work ahead; 14) Deviations from Plan; 15) Robot State Change Example; 16) Accomplished goals skipped in replan; 17) Planning continuity; 18) Supervisor Deviation From Plan; 19) Intentional Deviation; and 20) Infeasible states.

Seawater Phosphorites of the Seamount, Southwestern Pacific

NASA Astrophysics Data System (ADS)

Yoo, C.; Moon, J.; Kim, J.; Kim, K.; Lee, K.

2002-12-01

Phosphatized carbonate rocks associated with ferromanganese crusts (Fe-Mn crust) were investigated for better understanding of diagenetic evolution of the seamount (one of the Margellan Seamount Trail), southwestern Pacific. Three stages of phosphatization are inferred on the basis of paragenetic relation with Fe-Mn crusts, which are divided into four layers by their textures; 1) layer 1, massive, columnar growth structures with some porosity, 2) layer 2, porous, digitate growth structures with brown Fe-oxide filling, 3) layer 3, digitate and ovoidal growth structures with carbonate sediments filling, 4) layer 4, massive, parallel to undulatory laminated textures. Early phosphatization (phosphorite I) occurred before the formation of the oldest layer 4 crust. Foraminiferal-nannofossil limestones and shallow-water bioclastic limestones, encrusted by layer 4 crusts, are replaced by phosphorite I. Strontium isotope ratios (0.70743 to 0.70766) indicate that this phosphorite is formed at Late Cretaceous (85.2 to 73.5 Ma). Oxygen isotope values (-0.6 to 0.1% PDB) and shale-normalized REE pattern suggest that phosphorite I was formed in normal seawater. Phosphorite I appears as subhedral to euhedral, prismatic hexagonal crystallites approximately less than 5 æm in length. The second phosphorite (phosphorite II) is formed during the cessation of layer 4 crusts. Foraminiferal-nannofossil limestones filling the fractures developed within layer 4 crust are phosphatized during this episode. Age of phospatization II is defined as Late Eocene to Early Oligocene (36.5 to 31.6 Ma) from strontium isotope ratios (0.70777 to 0.70793). Oxygen isotope values (-2.9 to 2.9% PDB) and shale-normalized REE pattern of phosphorite II also suggest normal seawater origin. Phosphorite II replaced carbonate grain appears as anhedral, submicron-sized crystallites, whereas euhedral, prismatic hexagonal crystallites are filling the open space. Global climatic transition from a nonglacial to glacial period during Late Eocene to Early Oligocene intensified oceanic circulation and upwelling in deep-sea environment. Under this circumstance, phosphorite II may have been formed by redistribution of dissolved phosphous, accumulated in deep-sea during stable condition, to shallow environment. The last phosphatization (phosphorite III) occurred during or after the formation of layer 3 crust. Foraminiferal-nannofossil limestones filling the porosity and interstices within digitate layer 3 crust are phosphatized during this stage. Strontium isotope ratios (0.70827 to 0.70882) suggest that phosphorite III is formed from Oligocene/Miocene boundary to Middle Miocene (23.6 to 13.1 Ma). Shale-normalized REE pattern indicates this phosphorite was formed in normal seawater. Exclusively low oxygen isotope values (-10.7 to -2.4% PDB) suggest phosphorous ions responsible to phosphorite III probably provided during diagenesis of surrounding layer 3 crust.

Late-life depression in the primary care setting: Challenges, collaborative care, and prevention

PubMed Central

Hall, Charles A.; Reynolds, Charles F.

2014-01-01

Late-life depression is highly prevalent worldwide. In addition to being a debilitating illness, it is a risk factor for excess morbidity and mortality. Older adults with depression are at risk for dementia, coronary heart disease, stroke, cancer and suicide. Individuals with late-life depression often have significant medical comorbidity and, poor treatment adherence. Furthermore, psychosocial considerations such as gender, ethnicity, stigma and bereavement are necessary to understand the full context of late-life depression. The fact that most older adults seek treatment for depression in primary care settings led to the development of collaborative care interventions for depression. These interventions have consistently demonstrated clinically meaningful effectiveness in the treatment of late-life depression. We describe three pivotal studies detailing the management of depression in primary care settings in both high and low-income countries. Beyond effectively treating depression, collaborative care models address additional challenges associated with late-life depression. Although depression treatment interventions are effective compared to usual care, they exhibit relatively low remission rates and small to medium effect sizes. Several studies have demonstrated that depression prevention is possible and most effective in at-risk older adults. Given the relatively modest effects of treatment in averting years lived with disability, preventing late-life depression at the primary care level should be highly prioritized as a matter of health policy. PMID:24996484

Effect of N(G)-nitro-L-arginine methyl ester on intestinal permeability following intestinal ischemia-reperfusion injury in a rat model.

PubMed

Luo, C C; Chen, H M; Chiu, C H; Lin, J N; Chen, J C

2001-07-01

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase in intestinal permeability in rats following IRI. Sprague-Dawley rats weighing 200-300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early N(G)-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI. Copyright 2001 S. Karger AG, Basel

Validation of color Doppler ultrasonography for evaluating the uterine blood flow and perfusion during late normal pregnancy and uterine torsion in buffaloes.

PubMed

Hussein, Hassan A

2013-04-15

The aim of this study was to verify the efficacy of color Doppler ultrasonography for diagnosis of degree and duration of uterine torsion in buffaloes. In Assiut province/Upper Egypt, 65 buffaloes (37 with uterine torsion, 28 with normal late pregnancy) were examined clinically and using Doppler ultrasonography. The Doppler indices including resistance index (RI), pulsatility index (PI), time-averaged maximum velocity (TAMV), and blood flow volume (BFV) in the arteries ipsilateral to the uterine torsion (IPUT) and in arteries contralateral to the uterine torsion (COUT) were recorded. Methods of correction were documented along with dam and calf survival. Torsion was recorded postcervically with vaginal involvement in 35/37 (94.6%) of the cases. The degrees of uterine torsion were light and high in 9/37 (24.3%) and 28/37 (75.7%) of the cases, respectively (P = 0.001). Right uterine torsion was present in 36/37 (97.3%) of the cases (P = 0.0001). Pulsatility index, RI, TAMV, and BFV in IPUT and COUT did not differ significantly (P > 0.05) in normal late pregnancy. The PI and RI in IPUT were significantly higher (P < 0.01) than in COUT, and the TAMV and BFV in IPUT were less (P < 0.001) than that in COUT in uterine torsion. The PI and RI of torsion cases in IPUT were higher (P < 0.001) than that in normal pregnancy. Time-averaged maximum velocity and BFV in torsion cases were lower (P < 0.01) than that of normal pregnancy in IPUT. There was approximately 50% of RI and PI higher than in light degree uterine torsion in IPUT (P < 0.001). Consequently, TAMV and BFV were greatly lower (P < 0.0001) than that in light degree in IPUT. Pulsatility index and RI were positively correlated (r = 0.856; P < 0.001) with the duration and degree of the uterine torsion, and TAMV and BFV were negatively correlated (r = -0.763; P < 0.001). In all cases of uterine torsion the uterine flow velocity waveform showed high systolic flow and absence of early diastolic flow and poor uterine and placentomal blood perfusion. In conclusion, depicting blood flow within the middle uterine artery using color Doppler sonography could be helpful in correct diagnosis of duration and degree of uterine torsion and concurrently predicting the viability of the fetus and dam. Copyright © 2013 Elsevier Inc. All rights reserved.

Split Nitrogen Application Improves Wheat Baking Quality by Influencing Protein Composition Rather Than Concentration.

PubMed

Xue, Cheng; Auf'm Erley, Gunda Schulte; Rossmann, Anne; Schuster, Ramona; Koehler, Peter; Mühling, Karl-Hermann

2016-01-01

The use of late nitrogen (N) fertilization (N application at late growth stages of wheat, e.g., booting, heading or anthesis) to improve baking quality of wheat has been questioned. Although it increases protein concentration, the beneficial effect on baking quality (bread loaf volume) needs to be clearly understood. Two pot experiments were conducted aiming to evaluate whether late N is effective under controlled conditions and if these effects result from increased N rate or N splitting. Late N fertilizers were applied either as additional N or split from the basal N at late boot stage or heading in the form of nitrate-N or urea. Results showed that late N fertilization improved loaf volume of wheat flour by increasing grain protein concentration and altering its composition. Increasing N rate mainly enhanced grain protein quantitatively. However, N splitting changed grain protein composition by enhancing the percentages of gliadins and glutenins as well as certain high molecular weight glutenin subunits (HMW-GS), which led to an improved baking quality of wheat flour. The late N effects were greater when applied as nitrate-N than urea. The proportions of glutenin and x-type HMW-GS were more important than the overall protein concentration in determining baking quality. N splitting is more effective in improving wheat quality than the increase in the N rate by late N, which offers the potential to cut down N fertilization rates in wheat production systems.

Split Nitrogen Application Improves Wheat Baking Quality by Influencing Protein Composition Rather Than Concentration

PubMed Central

Xue, Cheng; auf’m Erley, Gunda Schulte; Rossmann, Anne; Schuster, Ramona; Koehler, Peter; Mühling, Karl-Hermann

2016-01-01

The use of late nitrogen (N) fertilization (N application at late growth stages of wheat, e.g., booting, heading or anthesis) to improve baking quality of wheat has been questioned. Although it increases protein concentration, the beneficial effect on baking quality (bread loaf volume) needs to be clearly understood. Two pot experiments were conducted aiming to evaluate whether late N is effective under controlled conditions and if these effects result from increased N rate or N splitting. Late N fertilizers were applied either as additional N or split from the basal N at late boot stage or heading in the form of nitrate-N or urea. Results showed that late N fertilization improved loaf volume of wheat flour by increasing grain protein concentration and altering its composition. Increasing N rate mainly enhanced grain protein quantitatively. However, N splitting changed grain protein composition by enhancing the percentages of gliadins and glutenins as well as certain high molecular weight glutenin subunits (HMW-GS), which led to an improved baking quality of wheat flour. The late N effects were greater when applied as nitrate-N than urea. The proportions of glutenin and x-type HMW-GS were more important than the overall protein concentration in determining baking quality. N splitting is more effective in improving wheat quality than the increase in the N rate by late N, which offers the potential to cut down N fertilization rates in wheat production systems. PMID:27313585

Alcohol Exposure During Late Adolescence Increases Drinking in Adult Wistar Rats, an Effect that is not Reduced by Finasteride

PubMed Central

Milivojevic, Verica; Covault, Jonathan

2013-01-01

Aims: We tested whether an exposure to alcohol in late adolescence, an age of rapid increase in neuroactive steroid precursors, would increase voluntary alcohol consumption in adult rats and whether this effect would be modulated by finasteride, an inhibitor of neuroactive steroid synthesis. Methods: In Experiment 1, we exposed male Wistar rats to 8% alcohol during the dark cycle for 1 week during late adolescence [postnatal days (PNDs) 51–58], and then measured voluntary alcohol consumption 1 month later in adulthood (PNDs 91–104). In Experiment 2, finasteride was administered during the forced alcohol exposure in late adolescence and, in Experiment 3, during voluntary alcohol consumption in adulthood. Plasma was collected at the end of each finasteride treatment to confirm the reduction of plasma neuroactive steroid levels. Results: We found that a daily 12-h exposure to alcohol for 7 days in late adolescence significantly increased voluntary alcohol consumption (4-fold) a month later during adulthood. Finasteride administration in late adolescence increased group alcohol intake in late adolescence but did not block the effect of adolescent alcohol exposure on increasing alcohol preference in adulthood. There was no effect of finasteride treatment in adulthood on alcohol preference. Conclusions: A daily 12-h exposure to alcohol for 7 days in late adolescence was sufficient to induce chronically increased alcohol preference in adulthood, indicating that this age may be sensitive to the effects of alcohol. PMID:22997410

Neural conduction abnormality in the brain stem and prevalence of the abnormality in late preterm infants with perinatal problems.

PubMed

Jiang, Ze Dong

2013-08-01

Neurodevelopment in late preterm infants has recently attracted considerable interest. The prevalence of brain stem conduction abnormality remains unknown. We examined maximum length sequence brain stem auditory evoked response in 163 infants, born at 33-36 weeks gestation, who had various perinatal problems. Compared with 49 normal term infants without problems, the late preterm infants showed a significant increase in III-V and I-V interpeak intervals at all 91-910/s clicks, particularly at 455 and 910/s (p < 0.01-0.001). The I-III interval was slightly increased, without statistically significant difference from the controls at any click rates. These results suggest that neural conduction along the, mainly more central or rostral part of, auditory brain stem is abnormal in late preterm infants with perinatal problems. Of the 163 late preterm infant, the number (and percentage rate) of infants with abnormal I-V interval at 91, 227, 455, and 910/s clicks was, respectively, 11 (6.5%), 17 (10.2%), 37 (22.3%), and 31 (18.7%). The number (and percentage rate) of infants with abnormal III-V interval at these rates was, respectively, 10 (6.0%), 17 (10.2%), 28 (16.9), and 36 (21.2%). Apparently, the abnormal rates were much higher at 455 and 910/s clicks than at lower rates 91 and 227/s. In total, 42 (25.8%) infants showed abnormal I-V and/or III-V intervals. Conduction in, mainly in the more central part, the brain stem is abnormal in late preterm infants with perinatal problems. The abnormality is more detectable at high- than at low-rate sensory stimulation. A quarter of late preterm infants with perinatal problems have brain stem conduction abnormality.

The Contributions of Chemistry and Transport to Low Arctic Ozone in March 2011 Derived from Aura MLS Observations

NASA Technical Reports Server (NTRS)

Strahan, S. E.; Douglass, A. R.; Newman, P. A.

2012-01-01

Stratospheric and total columns of Arctic O3 (63-90 N) in late March 2011 averaged 320 and 349 DU, respectively. These values are 74 DU lower than averages for the previous 6 years. We use Aura MLS O3 observations to quantify the roles of chemistry and transport and find there are two major reasons for low O3 in March 2011: heterogeneous chemical loss and a late final warming that delayed the resupply of O3 until April. Daily vortex-averaged partial columns in the lowermost stratosphere (p greater than 133 hPa) and middle stratosphere (p less than 29 hPa) are unaffected by local heterogeneous chemistry and show a near total lack of transport into the vortex between late January and late March, contributing to the observed low column. The lower stratospheric (LS) column (133-29 hPa) is affected by both heterogeneous chemistry and transport. Low interannual variability of Aura MLS 0 3 columns and temperature inside the Arctic vortex (2004-2011) shows that the transport contribution to vortex O3 in fall and early winter is nearly the same each year. The descent of MLS N2O vortex profiles in 2011 provides an estimate of O3 transported into the LS column during late winter. By quantifying the role of transport we determine that PSC-driven chemical loss causes 80 (plus or minus 10) DU of vortex-averaged O3 loss by late March 2011. Without heterogeneous chemical loss, March 2011 vortex O3 would have been 40 DU lower than normal due to the late final warming and resupply of O3 which did not occur until April.

Long-term health effects among testicular cancer survivors.

PubMed

Hashibe, Mia; Abdelaziz, Sarah; Al-Temimi, Mohammed; Fraser, Alison; Boucher, Kenneth M; Smith, Ken; Lee, Yuan-Chin Amy; Rowe, Kerry; Rowley, Braden; Daurelle, Micky; Holton, Avery E; VanDerslice, James; Richiardi, Lorenzo; Bishoff, Jay; Lowrance, Will; Stroup, Antoinette

2016-12-01

Testicular cancer is diagnosed at a young age and survival rates are high; thus, the long-term effects of cancer treatment need to be assessed. Our objectives are to estimate the incidence rates and determinants of late effects in testicular cancer survivors. We conducted a population-based cohort study of testicular cancer survivors, diagnosed 1991-2007, followed up for a median of 10 years. We identified 785 testicular cancer patients who survived ≥5 years and 3323 men free of cancer for the comparison group. Multivariate Cox regression analysis was used to compare the hazard ratio between the cases and the comparison group and for internal analysis among case patients. Testicular cancer survivors experienced a 24 % increase in risk of long-term health effects >5 years after diagnosis. The overall incidence rate of late effects among testicular cancer survivors was 66.3 per 1000 person years. Higher risks were observed among testicular cancer survivors for hypercholesterolemia, infertility, and orchitis. Chemotherapy and retroperitoneal lymph node dissection appeared to increase the risk of late effects. Being obese prior to cancer diagnosis appeared to be the strongest factor associated with late effects. Testicular cancer survivors were more likely to develop chronic health conditions when compared to cancer-free men. While the late effects risk was increased among testicular cancer survivors, the incidence rates of late effects after cancer diagnosis was fairly low.

From Personae to Persons: A Good Drama

ERIC Educational Resources Information Center

Geiger, Matthew W.

2016-01-01

There are two kinds of drama that is normally associated with high school: the "drama" that accompanies social life in late adolescence and the dramas that are performed in a school's auditorium or performing arts center. The drama about which the author writes about in this article is of a different sort altogether. It is, however, like…

Foucault, Governmentality, Neoliberalism and Adult Education--Perspective on the Normalization of Social Risks

ERIC Educational Resources Information Center

Kopecký, Martin

2011-01-01

The article deals with the relevance of the work of Foucault to critical analysis of the political concept of lifelong learning that currently dominates. This concept relates to the field of adult education and learning. The article makes reference to the relatively late incorporation of Foucault's work within andragogy. It shows the…

A Comparative Study on Social Media Addiction of High School and University Students

ERIC Educational Resources Information Center

Simsek, Ali; Elciyar, Kemal; Kizilhan, Taner

2017-01-01

For a long time the concept of addiction has been considered within the medical context of consuming certain materials excessively. Lately, it has been used to describe by psychologists some behavioral habits that are outside the normal life of the general population, such as gambling which affect a particular group of individuals. After the…

Stellar X-Ray Polarimetry

NASA Technical Reports Server (NTRS)

Swank, J.

2011-01-01

Most of the stellar end-state black holes, pulsars, and white dwarfs that are X-ray sources should have polarized X-ray fluxes. The degree will depend on the relative contributions of the unresolved structures. Fluxes from accretion disks and accretion disk corona may be polarized by scattering. Beams and jets may have contributions of polarized emission in strong magnetic fields. The Gravity and Extreme Magnetism Small Explorer (GEMS) will study the effects on polarization of strong gravity of black holes and strong magnetism of neutron stars. Some part of the flux from compact stars accreting from companion stars has been reflected from the companion, its wind, or accretion streams. Polarization of this component is a potential tool for studying the structure of the gas in these binary systems. Polarization due to scattering can also be present in X-ray emission from white dwarf binaries and binary normal stars such as RS CVn stars and colliding wind sources like Eta Car. Normal late type stars may have polarized flux from coronal flares. But X-ray polarization sensitivity is not at the level needed for single early type stars.

Conservative and surgical treatment of haemorrhoids.

PubMed

Altomare, Donato F; Giuratrabocchetta, Simona

2013-09-01

The management of haemorrhoids has evolved rapidly during the past few decades. Several new treatments have been proposed with the aim of reducing patients' postoperative pain, time to return to normal life, risk of early and late complications, and recurrence rate. Although conservative treatment based on dietary and lifestyle changes can help the majority of patients, and rubber band ligation and phlebotonic drugs can effectively treat grade I and II haemorrhoids, surgery is required for the most advanced stages. Milligan-Morgan haemorrhoidectomy is considered to be the gold-standard approach for grade IV haemorrhoids. An increasing number of minimally invasive treatment options, including mucopexy with or without mucosal resection and haemorrhoid artery ligation, have now been proposed for the management of grade III haemorrhoids. These approaches aim to correct the underlying pathophysiological mechanisms involved in the aetiology of haemorrhoids. An increased risk of recurrence is the price to pay for these minimally invasive and less painful treatments, but the sparing of the sensitive anoderm and a rapid return to normal life without pain are greatly appreciated by patients. An algorithm for the management of haemorrhoids using evidence-based medicine is also presented here.

Unusual neutral oligosaccharides in mature Sindbis virus glycoproteins are synthesized from truncated precursor oligosaccharides in Chinese hamster ovary cells.

PubMed

Davidson, S K; Hunt, L A

1983-03-01

We have previously demonstrated the presence of unusual small asparaginyl-oligosaccharides [(Man)3GlcNAc2-ASN] in the mature glycoproteins of Sindbis virus released from both wild-type and lectin-resistant Chinese hamster ovary cells, but the mechanism of synthesis of these structures was not determined. Gel filtration and endo-beta-N-acetylglucosaminidase analyses of Pronase-digested glycopeptides from [3H]mannose-labelled Sindbis virus released at different times after infection of a phytohaemagglutinin-resistant line of Chinese hamster ovary cells demonstrated that these small asparaginyl-oligosaccharides were present in similar relative amounts in virus released throughout the virus infection, rather than arising primarily at late times when cytopathic effects were maximal. Similar analyses of pulse-labelled, cell-associated viral glycopeptides suggested that these small oligosaccharides on mature virus glycoprotein resulted from the normal alpha 1,2-mannosidase processing of truncated precursor oligosaccharides (containing five rather than nine mannoses), rather than from aberrant processing or degradation of the full-size precursor oligosaccharides or normal intermediates.

Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia

PubMed Central

Paszkiewicz, Paulina J.; Fräßle, Simon P.; Srivastava, Shivani; Sommermeyer, Daniel; Hudecek, Michael; Sadelain, Michel; Liu, Lingfeng; Jensen, Michael C.; Riddell, Stanley R.; Busch, Dirk H.

2016-01-01

The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface. Here, we show that targeting EGFRt with the IgG1 monoclonal antibody cetuximab eliminates CD19 CAR T cells both early and late after adoptive transfer in mice, resulting in complete and permanent recovery of normal functional B cells, without tumor relapse. EGFRt can be incorporated into many clinical applications to regulate the survival of gene-engineered cells. These results support the concept that EGFRt represents a promising approach to improve safety of cell-based therapies. PMID:27760047

Fetal and post-natal lung defects reveal a novel and required role for Fgf8 in lung development

PubMed Central

Yu, Shibin; Poe, Bryan; Schwarz, Margaret; Elliot, Sarah; Albertine, Kurt H.; Fenton, Stephen; Garg, Vidu; Moon, Anne M.

2016-01-01

The fibroblast growth factor, FGF8, has been shown to be essential for vertebrate cardiovascular, craniofacial, brain and limb development. Here we report that Fgf8 function is required for normal progression through the late fetal stages of lung development that culminate in alveolar formation. Budding, lobation and branching morphogenesis are unaffected in early stage Fgf8 hypomorphic and conditional mutant lungs. Excess proliferation during fetal development disrupts distal airspace formation, mesenchymal and vascular remodeling, and Type I epithelial cell differentiation resulting in postnatal respiratory failure and death. Our findings reveal a previously unknown, critical role for Fgf8 function in fetal lung development and suggest that this factor may also contribute to postnatal alveologenesis. Given the high number of premature infants with alveolar dysgenesis and lung dysplasia, and the accumulating evidence that short-term benefits of available therapies may be outweighed by long term detrimental effects on postnatal alveologenesis, the therapeutic implications of identifying a factor or pathway that can be targeted to stimulate normal alveolar development are profound. PMID:20727874

Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia.

PubMed

Paszkiewicz, Paulina J; Fräßle, Simon P; Srivastava, Shivani; Sommermeyer, Daniel; Hudecek, Michael; Drexler, Ingo; Sadelain, Michel; Liu, Lingfeng; Jensen, Michael C; Riddell, Stanley R; Busch, Dirk H

2016-11-01

The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface. Here, we show that targeting EGFRt with the IgG1 monoclonal antibody cetuximab eliminates CD19 CAR T cells both early and late after adoptive transfer in mice, resulting in complete and permanent recovery of normal functional B cells, without tumor relapse. EGFRt can be incorporated into many clinical applications to regulate the survival of gene-engineered cells. These results support the concept that EGFRt represents a promising approach to improve safety of cell-based therapies.

Dissociation of Recombinant Prion Protein Fibrils into Short Protofilaments: Implications for the Endocytic Pathway and Involvement of the N-Terminal Domain

PubMed Central

Qi, Xu; Moore, Roger A.; McGuirl, Michele A.

2012-01-01

Fibril dissociation is necessary for efficient conversion of normal prion protein to its misfolded state and continued propagation into amyloid. Recent studies have revealed that conversion occurs along the endocytic pathway. To better understand the dissociation process, we have investigated the effect of low pH on the stability of recombinant prion fibrils. We show that under conditions that mimic the endocytic environment, amyloid fibrils made from full length prion protein dissociate both laterally and axially to form protofilaments. About 5% of the protofilaments are short enough to be considered soluble and contain ~100–300 monomers per structure; these also retain the biophysical characteristics of the filaments. We propose that protonation of His residues and charge repulsion in the N-terminal domain trigger fibril dissociation. Our data suggest that lysosomes and late endosomes are competent milieus for propagating the misfolded state not only by destabilizing the normal prion protein, but by accelerating fibril dissociation into smaller structures that may act as seeds. PMID:22591453

Biostratigraphic restudy documents Triassic/Jurassic section in Georges Bank COST G-2 well

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cousminer, H.L.; Steinkraus, W.E.; Hall, R.E.

1984-04-01

In 1977, the COST G-2 well as drilled in Georges Bank, 132 mi (212 km) east of Nantucket Island to a total depth of 21,874 ft (6667 m). Biostratigraphic studies of 363 sidewall and conventional cores and 695 cutting samples resulted in a detailed zonation from the Late Jurassic to the present. Restudy of the original samples, as well as new preparations from previously unstudied core material, resulted in revision of the zonation of the Late Jurassic and older section. On the basis of our study of pollen and spores, dinoflagellates, nannofossils, and foraminifers, we revised the age sequence asmore » follows: 5856 ft (1785 m) Late Jurassic (Thithonian); 6000 ft (1829 m) Kimmeridgian; 6420 ft (1957 m) Oxfordian; 6818 ft (2078 m) Callovian; 8200 ft (2499 m) Bathonian; 9677 ft (2950 m) Bajocian; 14567 ft (4440 m) Norian (Late Triassic). Norian dinoflagellate cysts and Tasmanites sp. indicate that intermittent normal marine sedimentation was taking place on Georges Bank as early as Norian time, although most of the Triassic section (+14,500 ft or 4420 m to T.D.) interpreted as having been deposited under evaporitic sabkha-like conditions. The Norian dinoflagellates (Noricysta, Heibergella, Hebecysta, Suessia, Dapcodinium, and Rhombodella) include species common to both Arctic Canada and the Tethyan region, indicating a possible Late Triassic marine connection.« less

Circular RNAs play an important role in late-stage gastric cancer: Circular RNA expression profiles and bioinformatics analyses.

PubMed

Fang, Yantian; Ma, Minzhe; Wang, Jiangli; Liu, Xiaowen; Wang, Yanong

2017-06-01

Gastric cancer is one of the most common tumors of the digestive system. Here, analysis of the expression profiles of circular RNAs in advanced gastric adenocarcinoma and adjacent normal mucosa tissues revealed differential expression of 306 circular RNAs, among which 273 were predicted to exert regulatory effects on target microRNAs. The downstream pathway networks of circular RNA-microRNA were mapped and the node genes were identified. In particular, we found that the expression of hsa_circ_0058246 was elevated in tumor specimens of patients with poor clinical outcomes. Our collective findings indicate that circular RNAs play a critical role in gastric cancer tumorigenesis. Data from this study provide a new perspective on the molecular pathways underlying metastasis and recurrence of gastric cancer and highlight potential therapeutic targets that may contribute to more effective diagnosis and treatment of the disease.

Rubber band ligation of haemorrhoids in the out-patient clinic.

PubMed Central

Kumar, N.; Paulvannan, S.; Billings, P. J.

2002-01-01

Rubber band ligation (RBL) is an effective treatment for symptomatic haemorrhoids but carries significant morbidity. We performed a prospective study of 98 consecutive patients treated by RBL in the out-patient clinic. Immediate, intermediate (within 2 weeks) and late (within 2 months) complications were recorded. Immediate complications occurred in 66 (67.3%) patients. Pain was the predominant symptom in 50 patients (51%). Fifteen (15.3%) patients had vasovagal attacks and 1 (1%) had bleeding. Twenty-five patients (25.5%) were unable to perform normal activities on the day of RBL. One patient needed hospital admission for control of pain. Seventy four (75.5%) patients would have RBL if they needed further treatment for haemorrhoids. Symptomatic cure was achieved in 71 patients (72.4%). RBL is an effective treatment but with significant complications. Patients should be adequately warned, especially of pain and vasovagal attacks. PMID:12092868

Far-infrared emission and star formation in spiral galaxies

NASA Technical Reports Server (NTRS)

Trinchieri, G.; Fabbiano, G.; Bandiera, R.

1989-01-01

The correlations between the emission in the far-IR, H-alpha, and blue in a sample of normal spiral galaxies are investigated. It is found that the luminosities in these three bands are all tightly correlated, although both the strength of the correlations and their functional dependencies are a function of the galaxies' morphological types. The best-fit power laws to these correlations are different for the comparison of different quantities and deviate significantly from linearity in some cases, implying the presence of additional emission mechanisms not related to the general increase of luminosity with galactic mass. Clear evidence is found of two independent effects in the incidence of warm far-IR emission in late-type spirals. One is a luminosity effect shown by the presence of excess far-IR relative to H-alpha or optical emission in the more luminous galaxies. The other is a dependence on widespread star-formation activity.

Preclinical diagnosis of Alzheimer’s disease: Prevention or prediction?

PubMed Central

Nitrini, Ricardo

2010-01-01

The diagnosis of Alzheimer’s disease (AD) for cases with dementia may be too late to allow effective treatment. Criteria for diagnosis of preclinical AD suggested by the Alzheimer’s Association include the use of molecular and structural biomarkers. Preclinical diagnosis will enable testing of new drugs and forms of treatment toward achieving successful preventive treatment. But what are the advantages for the individual? To know that someone who is cognitively normal is probably going to develop AD’s dementia when there is no effective preventive treatment is definitely not good news. A research method whereby volunteers are assigned to receive treatment or placebo without knowing whether they are in the control or at-risk arm of a trial would overcome this potential problem. If these new criteria are used wisely they may represent a relevant milestone in the search for a definitive treatment for AD. PMID:29213696

A novel technique to treat acquired Chiari I malformation after supratentorial shunting.

PubMed

Potgieser, Adriaan R E; Hoving, Eelco W

2016-09-01

The acquired Chiari I malformation with abnormal cranial vault thickening is a rare late complication of supratentorial shunting. It poses a difficult clinical problem, and there is debate about the optimal surgical strategy. Some authors advocate supratentorial skull enlarging procedures while others prefer a normal Chiari decompression consisting of a suboccipital craniectomy, with or without C1 laminectomy and dural patch grafting. We illustrate three cases of symptomatic acquired Chiari I malformation due to inward cranial vault thickening. We describe a new surgical approach that appears to be effective in these patients. This approach includes the standard Chiari decompression combined with posterior fossa augmentation by thinning the occipital planum. Internal volume re-expansion of the posterior fossa by thinning the occipital planum appears to be an effective novel surgical strategy in conjunction with the standard surgical therapy of Chiari decompression.

Effect of vitamin D treatments on plasma metabolism and immune parameters of healthy dairy cows.

PubMed

Yue, Yuan; Hymøller, Lone; Jensen, Søren Krogh; Lauridsen, Charlotte

2018-06-01

The objective of this study was to investigate the possible beneficial effect of vitamin D repletion on certain immune parameters of vitamin D insufficient dairy cows. Twenty dairy cows in late lactation were treated daily with vitamin D in five different ways: sunlight exposure (SUN), D 2 supplementation combined with sunlight exposure (D2SUN), D 2 supplementation (D2), D 3 supplementation (D3), and D 2 and D 3 supplementation combined (D2D3). The cows had very low vitamin D levels at d 0 because of the vitamin D deprivation before the study. After 1 month of vitamin D repletion, all cows had plasma 25(OH)D levels within the normal range. Total 25(OH)D concentration was significantly higher in SUN, D2SUN and D2D3 than D2 or D3 at the end of the study. However, milk yield, as well as protein and fat content of the milk, was not influenced by vitamin D treatments. There was no difference obtained in the measured immune parameters: Leucocyte populations, somatic cell count, immunoglobulin concentrations in plasma and milk, and antigen-stimulated cytokine productions did not change in response to vitamin D repletion or difference in vitamin D sources, and no relations to plasma 25(OH)D levels were identified. Despite the fact that plasma 25(OH)D increased from a very low level to normal range, the present study did not show any effect of vitamin D repletion on the tested immune parameters of healthy dairy cows. Therefore, in this study, it was concluded that repletion to physiologically normal plasma 25-hydroxyvitamin D levels of vitamin D-depleted healthy dairy cows had no influence on immune parameters.

Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System

PubMed Central

Steininger, Stefanie C.; Liu, Xinyang; Gietl, Anton; Wyss, Michael; Schreiner, Simon; Gruber, Esmeralda; Treyer, Valerie; Kälin, Andrea; Leh, Sandra; Buck, Alfred; Nitsch, Roger M.; Prüssmann, Klaas P.; Hock, Christoph; Unschuld, Paul G.

2014-01-01

Background: Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system. Methods: We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling. Results: Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. Conclusion: Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD. PMID:24672483

Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System.

PubMed

Steininger, Stefanie C; Liu, Xinyang; Gietl, Anton; Wyss, Michael; Schreiner, Simon; Gruber, Esmeralda; Treyer, Valerie; Kälin, Andrea; Leh, Sandra; Buck, Alfred; Nitsch, Roger M; Prüssmann, Klaas P; Hock, Christoph; Unschuld, Paul G

2014-01-01

Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system. We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling. Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD.

The Impact of Dealing with the Late Effects of National Socialist Terror on West German Psychiatric Care.

PubMed

Söhner, Felicitas; Baader, Gerhard

2018-06-01

Health damages and the late effects of NS trauma were largely ignored in German-speaking countries. This paper describes how dealing with the late effects of Nazi terror influenced post-war psychiatry in West Germany and thus the development of the psychiatric reform. As part of a greater overview study of the impulses and framework conditions of the reform-orientated development of post-war psychiatry in West Germany, this analysis is based on a thorough literary and documentary analysis. The sources show that publications by Helmut Paul and Herberg [81] as well as Baeyer et al. [12] can be considered as remarkable milestones. The awareness of psychological late effects of NS persecution was only reluctantly taken up by the scientific community. Nevertheless, this discussion was an essential component of the reform-orientated psychiatry in West Germany in the late 1960s to 1970s.

Episodic memory change in late adulthood: generalizability across samples and performance indices.

PubMed

Dixon, Roger A; Wahlin, Ake; Maitland, Scott B; Hultsch, David F; Hertzog, Christopher; Bäckman, Lars

2004-07-01

Younger adults recall more information from episodic memory tasks than do older adults. Because longitudinal studies are rare and often incompatible, the extent of actual late-life memory change is not well established. We assemble two different longitudinal samples of normal older adults, each of which is tested twice at a 3-year interval, using a large battery of episodic memory indicators. Together, two-wave data from both the Victoria Longitudinal Study in Canada (n = 400) and the Kungsholmen Project in Sweden (n = 168) cover a 40-year span of adulthood, ranging from 54 to 94 years of age. Principal memory tasks include categorizable word lists, story recall, and random word lists, as well as indicators of cognitive support. Overall, an examination of performance on sets of common and complementary episodic tasks reveals that, for both samples, actual 3-year changes are modest and that, when decline occurs, it is gradual. The exception-greater decline for more supported tasks-suggests that these may be especially sensitive to late-life changes.

[Expression of FAP and alpha-SMA during the incised wound healing in mice skin].

PubMed

Gao, Yang; Peng, Xue; Jin, Zhan-Fen; Fu, Zhi-Jun

2009-12-01

OBJECTIVE To investigate the time-dependent expression of fibroblast activation protein (FAP) and alpha-smooth muscle actin(alpha-SMA) during the incised wound healing of the skin in mice. The expression of FAP and alpha-SMA in incised wound of mice skin was detected by immunohistochemistry and Western blot. By immunohistochemistry, the expression of FAP and alpha-SMA in the normal skin and the skin 1 h after injury maintained at a very low level, but the positive cells expressing FAP and alpha-SMA started to elevate 6 h after injury and reached its peak on 5 d for FAP and on 3 d for alpha-SMA, then gradually decreased to the normal level on 14 d. The expression of FAP and alpha-SMA was observed throughout the wound healing stages 1 d after injuries by Western blot as well with a peak expression occurring on 5 d for FAP and on 3 d for alpha-SMA after injury. FAP may be a potentially useful marker for wound age determination and alpha-SMA may be used as an effective indicator for the mid- and late stage incised wound of mice skin. The combination use of FAP and alpha-SMA may be potentially effective indicators for wound age determination.

Heterogeneity of clonogenic cells in acute myeloblastic leukemia.

PubMed Central

Sabbath, K D; Ball, E D; Larcom, P; Davis, R B; Griffin, J D

1985-01-01

The expression of differentiation-associated surface antigens by the clonogenic leukemic cells from 20 patients with acute myeloblastic leukemia (AML) was studied with a panel of seven cytotoxic monoclonal antibodies (anti-Ia, -MY9, -PM-81, -AML-2-23, -Mol, -Mo2, and -MY3). The surface antigen phenotypes of the clonogenic cells were compared with the phenotypes of the whole leukemic cell population, and with the phenotypes of normal hematopoietic progenitor cells. In each case the clonogenic leukemic cells were found within a distinct subpopulation that was less "differentiated" than the total cell population. Clonogenic leukemic cells from different patients could be divided into three phenotype groups. In the first group (7 of 20 cases), the clonogenic cells expressed surface antigens characteristic of the normal multipotent colony-forming cell (Ia, MY9). These cases tended to have "undifferentiated" (FAB M1) morphology, and the total cell population generally lacked expression of "late" monocyte antigens such as MY3 and Mo2. A second group (seven cases) of clonogenic cells expressed surface antigens characteristic of an "early" (day 14) colony-forming unit granulocyte-monocyte (CFU-GM), and a third group (six cases) was characteristic of a "late" (day 7) CFU-GM. The cases in these latter two groups tended to have myelomonocytic (FAB M4) morphology and to express monocyte surface antigens. These results suggest that the clonogenic cells are a distinct subpopulation in all cases of AML, and may be derived from normal hematopoietic progenitor cells at multiple points in the differentiation pathway. The results further support the possibility that selected monoclonal antibodies have the potential to purge leukemic clonogenic cells from bone marrow in some AML patients without eliminating critical normal progenitor cells. PMID:3855866

Heterogeneity of clonogenic cells in acute myeloblastic leukemia.

PubMed

Sabbath, K D; Ball, E D; Larcom, P; Davis, R B; Griffin, J D

1985-02-01

The expression of differentiation-associated surface antigens by the clonogenic leukemic cells from 20 patients with acute myeloblastic leukemia (AML) was studied with a panel of seven cytotoxic monoclonal antibodies (anti-Ia, -MY9, -PM-81, -AML-2-23, -Mol, -Mo2, and -MY3). The surface antigen phenotypes of the clonogenic cells were compared with the phenotypes of the whole leukemic cell population, and with the phenotypes of normal hematopoietic progenitor cells. In each case the clonogenic leukemic cells were found within a distinct subpopulation that was less "differentiated" than the total cell population. Clonogenic leukemic cells from different patients could be divided into three phenotype groups. In the first group (7 of 20 cases), the clonogenic cells expressed surface antigens characteristic of the normal multipotent colony-forming cell (Ia, MY9). These cases tended to have "undifferentiated" (FAB M1) morphology, and the total cell population generally lacked expression of "late" monocyte antigens such as MY3 and Mo2. A second group (seven cases) of clonogenic cells expressed surface antigens characteristic of an "early" (day 14) colony-forming unit granulocyte-monocyte (CFU-GM), and a third group (six cases) was characteristic of a "late" (day 7) CFU-GM. The cases in these latter two groups tended to have myelomonocytic (FAB M4) morphology and to express monocyte surface antigens. These results suggest that the clonogenic cells are a distinct subpopulation in all cases of AML, and may be derived from normal hematopoietic progenitor cells at multiple points in the differentiation pathway. The results further support the possibility that selected monoclonal antibodies have the potential to purge leukemic clonogenic cells from bone marrow in some AML patients without eliminating critical normal progenitor cells.

Growth Failure in Children with Systemic Juvenile Idiopathic Arthritis and Prolonged Inflammation despite Treatment with Biologicals: Late Normalization of Height by Combined Hormonal Therapies.

PubMed

de Zegher, Francis; Reynaert, Nele; De Somer, Lien; Wouters, Carine; Roelants, Mathieu

2018-06-25

Biologicals targeting the interleukin (IL)-1β or IL-6 pathway are becoming prime choices for the treatment of children with systemic juvenile idiopathic arthritis (sJIA). Up to 1 in 3 sJIA children receiving such treatment continues to have inflammatory activity and to require supra-physiological glucocorticoid doses which may reduce growth velocity for years and may lead to an extremely short stature for age, if not for life. Currently, there is no long-term proposal to normalize the adult height of these children with sJIA. We present long-term (up to 10 years), proof-of-concept evidence that the adult stature and adipose body composition of short sJIA children can be normalized with a hormonal combination strategy: (i) pubertal onset is postponed with a gonadotropin-releasing hormone analog (triptorelin) until a minimum height is reached, or until prepubertal growth is exhausted, and (ii) height gain is promoted with growth hormone (≈50 μg/kg/day), once inflammation is under control and high glucocorticoid doses are no longer needed. The latter treatment takes advantage of the window of relative glucocorticoid deficiency, which is known to open after prolonged glucocorticoid administration, and to be uniquely favorable to height gain. A long-term combination of biological and hormonal treatments for short sJIA children can be guided by a simple concept that involves (i) postponement of pubertal development and (ii) growth-promoting therapy after the episodes of major inflammation and high-dose glucocorticoid treatment. Limited long-term experience in short sJIA children suggests that this strategy leads consistently - albeit late - to a normal adult stature. © 2018 S. Karger AG, Basel.

Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates

PubMed Central

Andrews, Rachel N.; Metheny-Barlow, Linda J.; Peiffer, Ann M.; Hanbury, David B.; Tooze, Janet A.; Bourland, J. Daniel; Hampson, Robert E.; Deadwyler, Samuel A.; Cline, J. Mark

2017-01-01

Andrews, R. N., Metheny-Barlow, L. J., Peiffer, A. M., Hanbury, D. B., Tooze, J. A., Bourland, J. D., Hampson, R. E., Deadwyler, S. A. and Cline, J. M. Cerebrovascular Remodeling and Neuroinflammation is a Late Effect of Radiation-Induced Brain Injury in Non-Human Primates. Radiat. Res. 187, 599–611 (2017). Fractionated whole-brain irradiation (fWBI) is a mainstay of treatment for patients with intracranial neoplasia; however late-delayed radiation-induced normal tissue injury remains a major adverse consequence of treatment, with deleterious effects on quality of life for affected patients. We hypothesize that cerebrovascular injury and remodeling after fWBI results in ischemic injury to dependent white matter, which contributes to the observed cognitive dysfunction. To evaluate molecular effectors of radiation-induced brain injury (RIBI), real-time quantitative polymerase chain reaction (RT-qPCR) was performed on the dorsolateral prefrontal cortex (DLPFC, Brodmann area 46), hippocampus and temporal white matter of 4 male Rhesus macaques (age 6–11 years), which had received 40 Gray (Gy) fWBI (8 fractions of 5 Gy each, twice per week), and 3 control comparators. All fWBI animals developed neurologic impairment; humane euthanasia was elected at a median of 6 months. Radiation-induced brain injury was confirmed histopathologically in all animals, characterized by white matter degeneration and necrosis, and multifocal cerebrovascular injury consisting of perivascular edema, abnormal angiogenesis and perivascular extracellular matrix deposition. Herein we demonstrate that RIBI is associated with white matter-specific up-regulation of hypoxia-associated lactate dehydrogenase A (LDHA) and that increased gene expression of fibronectin 1 (FN1), SERPINE1 and matrix metalloprotease 2 (MMP2) may contribute to cerebrovascular remodeling in late-delayed RIBI. Additionally, vascular stability and maturation associated tumor necrosis super family member 15 (TNFSF15) and vascular endothelial growth factor beta (VEGFB) mRNAs were increased within temporal white matter. We also demonstrate that radiation-induced brain injury is associated with decreases in white matter-specific expression of neurotransmitter receptors SYP, GRIN2A and GRIA4. We additionally provide evidence that macrophage/microglial mediated neuroinflammation may contribute to RIBI through increased gene expression of the macrophage chemoattractant CCL2 and macrophage/ microglia associated CD68. Global patterns in cerebral gene expression varied significantly between regions examined (P < 0.0001, Friedman’s test), with effects most prominent within cerebral white matter. PMID:28398880

POSTSURGICAL RECURRENT CUSHING DISEASE: CLINICAL BENEFIT OF EARLY INTERVENTION IN PATIENTS WITH NORMAL URINARY FREE CORTISOL.

PubMed

Carroll, Ty B; Javorsky, Bradley R; Findling, James W

2016-10-01

To assess the performance of biochemical markers in the detection of recurrent Cushing disease (CD), as well as the potential benefit of early intervention in recurrent CD patients with elevated late-night salivary cortisol (LNSC) and normal urinary free cortisol (UFC). The design was a single-center, retrospective chart review. Patients treated by the authors from 2008-2013 were included. Recurrence was defined by postsurgical remission of CD with subsequent abnormal LNSC, UFC, or dexamethasone suppression test (DST). We identified 15 patients with postsurgical recurrent CD after initial remission; all but one underwent testing with LNSC, DST, and UFC. Although 12 of 15 patients had normal UFC at time of recurrence, DST was abnormal in 11 of 15, and all 14 patients with LNSC results had ≥1 elevated measurement. Nine patients (7 with normal UFC) showed radiologic evidence of a pituitary tumor at time of recurrence. Among the 14 patients with available follow-up data, 12 have demonstrated significant improvement since receiving treatment. Five patients underwent repeat pituitary surgery and 4 achieved clinical and biochemical remission. Eight patients received mifepristone or cabergoline, and 6 showed clinical and/or biochemical improvement. Three patients (2 with prior mifepristone) underwent bilateral adrenalectomy and 2 demonstrated significant clinical improvements. LNSC is more sensitive than UFC or DST for detection of CD recurrence. Prompt intervention when LNSC is elevated, despite normal UFC, may yield significant clinical benefit for many patients with CD. Early treatment for patients with recurrent CD should be prospectively evaluated, utilizing LNSC elevation as an early biochemical marker. ACTH = adrenocorticotropic hormone CD = Cushing disease CS = Cushing syndrome CV = coefficient of variation DST = dexamethasone suppression test IPSS = inferior petrosal sinus sampling LNSC = late-night salivary cortisol QoL = quality of life TSS = transsphenoidal adenoma resection UFC = urinary free cortisol.

Tectonic Setting and Bimodal Magmatic Evolution of Eocene Volcanic Rocks of the Bijgerd-Kuh-e Kharchin area, Uromieh-Dokhtar Zone, Iran

NASA Astrophysics Data System (ADS)

Davarpanah, A.; Khalatbari-Jafari, M.; Babaie, H. A.; Krogstad, E. J.; Mobasher, K.; La Tour, T. E.; Deocampo, D. M.

2008-12-01

Geochemical composition and texture of the Middle and Late Eocene volcanic, volcaniclastic, and volcanic- sedimentary rocks in the Bijgerd-Kuh-e Kharchin area, northwest of Saveh, provide significant geochemical and geological clues for the tectonic and magmatic evolution of the Uromieh-Dokhtar volcanic-plutonic zone of Iran. The Middle Eocene volcanic rocks have an intermediate composition and include green tuff and tuffaceous sandstone with intercalated sandstone, sandy tuff, and shale. The shale has lenses of nummulite- bearing limestone with a Middle Eocene detrital age. The time between the Middle and Late Eocene volcanic activities in this area is marked by the presence of andesite and rhyolitic tuff. The Late Eocene succession is distinguished by the presence of four alternating levels (horizons) of intermediate lava and ignimbrite which we designate as Eig. The ignimbrites of the Eig sequence have a rhyolitic composition and include ignimbrite- breccia, ignimbrite-tuff, and ignimbrite-lava pairs. The volume of the felsic volcanic rocks in this sequence far exceeds that of the intermediate rocks, which makes it unlikely that they evolved through the magmatic differentiation of a basaltic magma. The presence of the nummulite-bearing limestone lenses, and sandstone and conglomerate interbeds between the ignimbrites, suggests a shallow marine environment for the pyroclastic deposition and probably the eruptions. The tuff and siltstone of the Est unit that sits above the first ignimbrite may represent deep water, Late Eocene deposit. Oligo-Miocene limestone of the Qom Formation unconformably overlies the uppermost Late Eocene ignimbrite. Washings from red marls give microfossils with Late Eocene age for the Eig sequence, which is synchronous with other paleontological evidence that puts the peak volcanic activity as Late Eocene in the Bijgerd-Kuh-e Kharchin area. Field and petrographic evidence for magma mixing/mingling is given by the presence of mafic- intermediate enclaves in the ignimbrite, hybrid breccias with felsic and mafic clasts, felsic pseudo-flames filled with intermediate lava, heterogeneity in the ignimbrite texture, and sieve texture and oscillatory zoning of plagioclase and opacitization of olivine in the intermediate lava. Geochemical analyses of the major and trace elements (including the REE) and rock texture and assemblages indicate the bimodal magmatic characteristics of the mafic-intermediate lavas and ignimbrites. The tuff and the breccia show a hybrid elemental distribution between those of rhyolite and basalt. The ignimbrites show more enriched compositions than those of the mafic and intermediate rocks on the chondrite-normalized trace element distribution diagram. The higher enrichment of the LREE in the ignimbrites may be due to a crustal contribution. The primitive mantle-normalized elemental distributions show a distinct depletion of Nb and Ti, which suggests a subduction-related volcanism during Eocene.

The effect of different atrioventricular delays on left atrium and left atrial appendage function in patients with DDD pacemaker.

PubMed

Kanadaşı, Mehmet; Caylı, Murat; Sahin, Durmuş Yıldıray; Sen, Ömer; Koç, Mevlüt; Usal, Ayhan; Batur, Mustafa Kemal; Demirtaş, Mustafa

2011-07-01

Although it has been known that optimization of atrioventricular delay (AVD) has favorable effect on the left ventricular functions in patients with DDD pacemaker, the effect of different AVDs on left atrium (LA) and left atrial appendage (LAA) functions has not been exactly evaluated. The aim of the present study was to assess the effect of different AVDs on LA and LAA functions in DDD pacemaker implanted patients with atrioventricular block. Forty-eight patients with DDD pacemaker were enrolled into the study. Patients were divided into two groups according to the echocardiographic diastolic function: Group I (normal diastolic function) and Group II (diastolic dysfunction). LAA emptying velocity on pulsed wave Doppler and LAA late systolic wave velocity by using tissue Doppler were recorded. Patients were paced for five successive continuous pacing periods of 10 minutes duration using five selective AVDs (80-250 ms). Significant effect on LA and LAA functions has not been observed by the setting of AVD in Group I. However, when the AVD was gradually shortened form 150 ms to 80 ms, LA and LAA functions gradually decreased in Group II patients. When AVD increased to 200 ms, LA and LAA functions were improved. Further increase in AVD resulted in decreased LA and LAA functions. Setting of AVD has not significant effect on the LA and LAA functions in patients with normal diastolic function, but moderate prolongation of AVD in physiological limits improved LA and LAA functions in DDD pacemaker implanted patients with diastolic dysfunction. © 2011, Wiley Periodicals, Inc.

Vitamin C uncouples the Warburg metabolic switch in KRAS mutant colon cancer.

PubMed

Aguilera, Oscar; Muñoz-Sagastibelza, María; Torrejón, Blanca; Borrero-Palacios, Aurea; Del Puerto-Nevado, Laura; Martínez-Useros, Javier; Rodriguez-Remirez, María; Zazo, Sandra; García, Estela; Fraga, Mario; Rojo, Federico; García-Foncillas, Jesús

2016-07-26

KRAS mutation is often present in many hard-to-treat tumors such as colon and pancreatic cancer and it is tightly linked to serious alterations in the normal cell metabolism and clinical resistance to chemotherapy.In 1931, the winner of the Nobel Prize in Medicine, Otto Warburg, stated that cancer was primarily caused by altered metabolism interfering with energy processing in the normal cell. Increased cell glycolytic rates even in the presence of oxygen is fully recognized as a hallmark in cancer and known as the Warburg effect.In the late 1970's, Linus Pauling and Ewan Cameron reported that vitamin C may have positive effects in cancer treatment, although deep mechanistic knowledge about this activity is still scarce.We describe a novel antitumoral mechanism of vitamin C in KRAS mutant colorectal cancer that involves the Warburg metabolic disruption through downregulation of key metabolic checkpoints in KRAS mutant cancer cells and tumors without killing human immortalized colonocytes.Vitamin C induces RAS detachment from the cell membrane inhibiting ERK 1/2 and PKM2 phosphorylation. As a consequence of this activity, strong downregulation of the glucose transporter (GLUT-1) and pyruvate kinase M2 (PKM2)-PTB dependent protein expression are observed causing a major blockage of the Warburg effect and therefore energetic stress.We propose a combination of conventional chemotherapy with metabolic strategies, including vitamin C and/or other molecules targeting pivotal key players involved in the Warburg effect which may constitute a new horizon in anti-cancer therapies.

The physiology and pathophysiology of rapamycin resistance

PubMed Central

Boylan, Joan M; Sanders, Jennifer A

2011-01-01

Rapamycin is an inhibitor of the mammalian Target of Rapamycin, mTOR, a nutrient-sensing signaling kinase and a key regulator of cell growth and proliferation. While rapamycin and related compounds have anti-tumor activity, a prevalent characteristic of cancer cells is resistance to their anti-proliferative effects. Our studies on nutrient regulation of fetal development showed that hepatocyte proliferation in the late gestation fetal rat is resistant to rapamycin. Extension of these studies to other tissues in the fetal and neonatal rat indicated that rapamycin resistance is a characteristic of normal cell proliferation in the growing organism. In hepatic cells, ribosomal biogenesis and cap-dependent protein translation were found to be relatively insensitive to the drug even though mTOR signaling was highly sensitive. Cell cycle progression was also resistant at the level of cyclin E-dependent kinase activity. Studies on the effect of rapamycin on gene expression in vitro and in vivo demonstrated that mTOR-mediated regulation of gene expression is independent of effects on cell proliferation and cannot be accounted for by functional regulation of identifiable transcription factors. Genes involved in cell metabolism were overrepresented among rapamycin-sensitive genes. We conclude that normal cellular proliferation in the context of a developing organism can be independent of mTOR signaling, that cyclin E-containing complexes are a critical locus for rapamycin sensitivity, and that mTOR functions as a modulator of metabolic gene expression in cells that are resistant to the anti-proliferative effects of the drug. PMID:21389767

Effects of menstrual cycle phase on cocaine self-administration in rhesus macaques.

PubMed

Cooper, Ziva D; Foltin, Richard W; Evans, Suzette M

2013-01-01

Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates. Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine's reinforcing effects than males, with estrous cycle stage as a key determinant of this effect. The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans. Dose-dependent intravenous cocaine self-administration (0.0125, 0.0250, and 0.0500 mg/kg/infusion) using a progressive-ratio schedule of reinforcement was determined across the menstrual cycle. The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone. Dependent variables including number of infusions self-administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase. Analysis of plasma hormone levels verified phase-dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase. Progressive ratio breakpoint, infusions self-administered, and cocaine intake did not consistently vary based on menstrual cycle phase. These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques. Copyright © 2012 Elsevier Inc. All rights reserved.

Magneto- and litho-stratigraphic records of the Oligocene-Early Miocene climatic changes from deep drilling in the Linxia Basin, Northeast Tibetan Plateau

NASA Astrophysics Data System (ADS)

Wu, Fuli; Fang, Xiaomin; Meng, Qingquan; Zhao, Yan; Tang, Fenjun; Zhang, Tao; Zhang, Weilin; Zan, Jinbo

2017-11-01

The East Asian monsoon is generally regarded to have initiated at the transition from the Late Oligocene to the Early Miocene. However, little is known about this process because of a lack of continuous strata across the boundary between the Late Oligocene and the Early Miocene in Asia. Based on previous drilling (core HZ-1) in the Miocene sediments in the southern Linxia Basin in NW China, we drilled a new 620 m core (HZ-2) into the Late Oligocene strata and obtained 206 m of continuous new core. The detailed paleomagnetism of the new core reveals eleven pairs of normal and reversed polarity zones that can be readily correlated with chrons 6Bn-9n of the geomagnetic polarity time scale (GPTS), define an age interval of 21.6-26.5 Ma and indicate continuity from the Late Oligocene to Early Miocene. The core is characterized by the remarkable occurrence of brownish-red paleosols of luvic cambisols (brown to luvic drab soils) above reddish-brown floodplain siltstones and mudstones, which suggest that the East Asian monsoon likely began by 26.5 Ma. In contrast to the siltstone and mudstone of the Late Oligocene strata, the Miocene strata begin with a thick fine sandstone bed, which marks sudden increases in erosion and loading that most likely reflect a response to tectonic uplift. The hematite content and redness index records of the core further demonstrate that the monsoonal climate in the Late Oligocene to Early Miocene in this area was mainly controlled by global temperature trends and events.

Alpine thermal events in the central Serbo-Macedonian Massif (southeastern Serbia)

NASA Astrophysics Data System (ADS)

Antić, Milorad D.; Kounov, Alexandre; Trivić, Branislav; Wetzel, Andreas; Peytcheva, Irena; von Quadt, Albrecht

2016-07-01

The Serbo-Macedonian Massif (SMM) represents a crystalline belt situated between the two diverging branches of the Eastern Mediterranean Alpine orogenic system, the northeast-vergent Carpatho-Balkanides and the southwest-vergent Dinarides and the Hellenides. We have applied fission-track analysis on apatites and zircons, coupled with structural field observations in order to reveal the low-temperature evolution of the SMM. Additionally, the age and geochemistry of the Palaeogene igneous rocks (i.e. Surdulica granodiorite and dacitic volcanic rocks) were determined by the LA-ICPMS U-Pb geochronology of zircons and geochemical analysis of main and trace elements in whole-rock samples. Three major cooling stages have been distinguished from the late Early Cretaceous to the Oligocene. The first stage represents rapid cooling through the partial annealing zones of zircon and apatite (300-60 °C) during the late Early to early Late Cretaceous (ca. 110-ca. 90 Ma). It is related to a post-orogenic extension following the regional nappe-stacking event in the Early Cretaceous. Middle to late Eocene (ca. 48-ca. 39 Ma) cooling is related to the formation of the Crnook-Osogovo-Lisets extensional dome and its exhumation along low-angle normal faults. The third event is related to regional cooling following the late Eocene magmatic pulse. During this pulse, the areas surrounding the Surdulica granodiorite (36 ± 1 Ma) and the slightly younger volcanic bodies (ca. 35 Ma) have reached temperatures higher than the apatite closure temperature (120 °C) but lower than ca. 250 °C. The geochemistry of the igneous samples reveals late- to post-orogenic tectonic setting during magma generation.

Functional challenges among late effects cancer survivors: a preliminary report on work engagement issues.

PubMed

Crist, Patricia

2013-01-01

While the cancer survivor rate is nearly 68% now, intervention regimens may leave residual conditions that impact engagement in work and various life tasks. Survivors are underemployed and report stigmatizing attitudes among co-workers. When late effects from cancer arise over 10 years later, the impact on individuals in the prime of their productive employment life is evident. Assisting these individuals begins with awareness of late effects in order to create work-related, adaptive strategies. Sixteen adult cancer survivors experiencing late effects completed the Occupational Self Assessment (Version 2.2) and the Quality of Life-Cancer Survivors (QOL-CS). Knowledge of functional problems secondary to recognized late effects medical conditions reported in the literature was utilized to sort items according to professional definitions of work, performance skills and performance patterns. Late effects survivors reported that cancer illness and treatment has negatively impacted their employment. Individual response to the impact of late effects is highly variant. "Getting things done" and physical energy limitations are most pronounced. Cancer survivors report lower competence in significant work-related skills and patterns. Quality of life associated with the aftereffects of fatigue, aches and pain, and sleep changes are the lowest. Responses range across the 16 survivors to both performance skills and performance patterns. Cancer survivorship has clearly interfered with employment. An interdisciplinary focus on meaningful engagement in life activities, particularly work is crucial to support survivors through advocacy, adaptation and positive change to focus on engaging the work talents and gifts for all cancer survivors.

Rosiglitazone delayed weight loss and anorexia while attenuating adipose depletion in mice with cancer cachexia.

PubMed

Asp, Michelle L; Tian, Min; Kliewer, Kara L; Belury, Martha A

2011-12-01

Cachexia is characterized by severe weight loss, including adipose and muscle wasting, and occurs in a large percentage of cancer patients. Insulin resistance contributes to dysregulated metabolism in cachexia and occurs prior to weight loss in mice with colon-26 tumor-induced cachexia. Therefore, we hypothesized that the insulin sensitizer, rosiglitazone, would attenuate the loss of adipose and muscle to result in improved outcomes for mice with late-stage cachexia. Male CD2F1 mice were inoculated with colon-26 adenocarcinoma cells or vehicle. Treatments included vehicle, rosiglitazone (10 mg/kg body weight/day) or rosiglitazone plus pair-feeding to food intake of vehicle-treated mice with tumors. Rosiglitazone delayed weight loss onset by 2 d over the 16 d duration of this aggressive tumor model. This finding was associated, in part, with increased food intake. In addition, adipose mass, adipocyte cross-sectional area and inflammation were improved with rosiglitazone. However, at the time of necropsy 16 d after tumor inoculation rosiglitazone had no effect on retention of muscle mass, strength or proteolysis in late-stage cachexia. We did not measure stamina or endurance in this study. In early-stage cachexia, rosiglitazone normalized PDK4 and PPAR-delta mRNA in quadriceps muscle and rescued the decrease in insulin-stimulated glucose disappearance in mice with tumors. Rosiglitazone may delay weight loss onset by decreasing tumor-induced markers of metabolic change in early-stage cachexia. These changes predict for modest improvement in adipose, but no improvement in muscle strength in late-stage cachexia.

Rosiglitazone delayed weight loss and anorexia while attenuating adipose depletion in mice with cancer cachexia

PubMed Central

Asp, Michelle L.; Tian, Min; Kliewer, Kara L.

2011-01-01

Cachexia is characterized by severe weight loss, including adipose and muscle wasting, and occurs in a large percentage of cancer patients. Insulin resistance contributes to dysregulated metabolism in cachexia and occurs prior to weight loss in mice with colon-26 tumor-induced cachexia. Therefore, we hypothesized that the insulin sensitizer, rosiglitazone, would attenuate the loss of adipose and muscle to result in improved outcomes for mice with late-stage cachexia. Male CD2F1 mice were inoculated with colon-26 adenocarcinoma cells or vehicle. Treatments included vehicle, rosiglitazone (10 mg/kg body weight/day) or rosiglitazone plus pair-feeding to food intake of vehicle-treated mice with tumors. Rosiglitazone delayed weight loss onset by 2 d over the 16 d duration of this aggressive tumor model. This finding was associated, in part, with increased food intake. In addition, adipose mass, adipocyte cross-sectional area and inflammation were improved with rosiglitazone. However, at the time of necropsy 16 d after tumor inoculation rosiglitazone had no effect on retention of muscle mass, strength or proteolysis in late-stage cachexia. We did not measure stamina or endurance in this study. In early-stage cachexia, rosiglitazone normalized PDK4 and PPAR-delta mRNA in quadriceps muscle and rescued the decrease in insulin-stimulated glucose disappearance in mice with tumors. Rosiglitazone may delay weight loss onset by decreasing tumor-induced markers of metabolic change in early-stage cachexia. These changes predict for modest improvement in adipose, but no improvement in muscle strength in late-stage cachexia. PMID:22104958

New Late Gene, dar, Involved in DNA Replication of Bacteriophage T4 I. Isolation, Characterization, and Genetic Location.

PubMed

Wu, J R; Yeh, Y C

1975-05-01

Suppressors of gene 59-defective mutants were isolated by screening spontaneous, temperature-sensitive (ts) revertants of the amber mutant, amC5, in gene 59. Six ts revertants were isolated. No gene 59-defective ts recombinant was obtained by crossing each ts revertant with the wild type, T4D. However, suppressors of gene 59-defective mutants were obtained from two of these ts revertants. These suppressor mutants are referred to as dar (DNA arrested restoration). dar mutants specifically restored the abnormalities, both in DNA synthesis and burst size, caused by gene 59-defective mutants to normal levels. It is unlikely that dar mutants are nonsense suppressors since theý failed to suppress amber mutations in 11 other genes investigated. The genetic expression of dar is controlled by gene 55; therefore, dar is a late gene. The genetic location of dar has been mapped between genes 24 and 25, a region contiguous to late genes. dar appears to be another nonessential gene of T4 since burst sizes of dar were almost identical to those of the wild type. Mutations in dar did not affect genetic recombination and repair of UV-damaged DNA, but caused a sensitivity to hydroxyurea in progeny formation. The effect of the dar mutation on host DNA degradation cannot account for its hydroxyurea sensitivity. dar mutant alleles were recessive to the wild-type allele as judged by restoration of arrested DNA synthesis. The possible mechanisms for the suppression of defects in gene 59 are discussed.

Germ cell differentiation and proliferation in the developing testis of the South American plains viscacha, Lagostomus maximus (Mammalia, Rodentia).

PubMed

Gonzalez, C R; Muscarsel Isla, M L; Fraunhoffer, N A; Leopardo, N P; Vitullo, A D

2012-08-01

Cell proliferation and cell death are essential processes in the physiology of the developing testis that strongly influence the normal adult spermatogenesis. We analysed in this study the morphometry, the expression of the proliferation cell nuclear antigen (PCNA), cell pluripotency marker OCT-4, germ cell marker VASA and apoptosis in the developing testes of Lagostomus maximus, a rodent in which female germ line develops through abolished apoptosis and unrestricted proliferation. Morphometry revealed an increment in the size of the seminiferous cords with increasing developmental age, arising from a significant increase of PCNA-positive germ cells and a stable proportion of PCNA-positive Sertoli cells. VASA showed a widespread cytoplasmic distribution in a great proportion of proliferating gonocytes that increased significantly at late development. In the somatic compartment, Leydig cells increased at mid-development, whereas peritubular cells showed a stable rate of proliferation. In contrast to other mammals, OCT-4 positive gonocytes increased throughout development reaching 90% of germ cells in late-developing testis, associated with a conspicuous increase in circulating FSH from mid- to late-gestation. TUNEL analysis was remarkable negative, and only a few positive cells were detected in the somatic compartment. These results show that the South American plains viscacha displays a distinctive pattern of testis development characterized by a sustained proliferation of germ cells throughout development, with no signs of apoptosis cell demise, in a peculiar endocrine in utero ambiance that seems to promote the increase of spermatogonial number as a primary direct effect of FSH.

Early and late menarche are associated with oligomenorrhea and predict metabolic syndrome 26 years later.

PubMed

Glueck, Charles J; Morrison, John A; Wang, Ping; Woo, Jessica G

2013-11-01

We determined whether simple, clinical information on late and early menarche could help identify adult women with metabolic syndrome (MetS) and oligomenorrhea. We carried out a 26-year prospective follow-up of 272 suburban schoolgirls from ages 5-22 to 30-46. Early menarche (≤10 years, 5.2% of girls) and late menarche (≥16 years, 6.7% of girls) were both associated with oligomenorrhea (≥42 days) in adulthood, 29% and 11%, vs. 5% for normal menarche (11-15 years), p=.004. Early menarche was characterized by high childhood BMI (LS mean±SE: 21.2 ±1.0 kg/m2) and by high childhood and adult MetS (15%, 36%). Girls with late menarche had the lowest childhood BMI (18.1±1.0), no childhood MetS, and the highest adult MetS (47%). Increasing age at menarche was associated with uniformly decreasing childhood BMI and MetS, but with a U-shaped pattern of BMI (p = .05), MetS (p=.008), and oligomenorrhea (p=.02) in adulthood. Change to MetS from median ages 13 to 38 was associated with early-late menarche (OR=3.11, 95% CI 1.37-7.07, p=.007). MetS in adulthood was associated with childhood MetS (OR=8.03, 95% CI 2.57-25.08, p=.0003) and with early-late menarche (OR =3.43, 95% CI 1.44-8.15, p=.005). Menarche age had a curvilinear ('U' shaped) relationship with MetS and oligomenorrhea in adulthood. Late menarche and early menarche are risk factors for adult oligomenorrhea, MetS, and cardiometabolic abnormalities. Girls with early (≤ age 10) and with late menarche (≥ 16) represent a group at high risk for adult cardiometabolic abnormalities and oligomenorrhea that is easily identifiable by physicians. © 2013.

Altered Structural and Functional Connectivity in Late Preterm Preadolescence: An Anatomic Seed-Based Study of Resting State Networks Related to the Posteromedial and Lateral Parietal Cortex.

PubMed

Degnan, Andrew J; Wisnowski, Jessica L; Choi, SoYoung; Ceschin, Rafael; Bhushan, Chitresh; Leahy, Richard M; Corby, Patricia; Schmithorst, Vincent J; Panigrahy, Ashok

2015-01-01

Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth. Thirty-eight preadolescents (ages 9-13; 19 born in the late preterm period (≥32 weeks gestational age) and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN (posterior cingulate cortex, precuneus) and lateral parietal DMN (superior marginal and angular gyri). Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups. Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing.

Perinatal Risks in “Late Motherhood” Defined Based On Parity and Preterm Birth Rate – an Analysis of the German Perinatal Survey (20th Communication)

PubMed Central

Schure, V.; Voigt, M.; Schild, R. L.; Hesse, V.; Carstensen, M.; Schneider, K. T. M.; Straube, S.

2012-01-01

Aim: “Late motherhood” is associated with greater perinatal risks but the term lacks precise definition. We present an approach to determine what “late motherhood” associated with “high risk” is, based on parity and preterm birth rate. Materials and Methods: Using data from the German Perinatal Survey of 1998–2000 we analysed preterm birth rates in women with zero, one, or two previous live births. We compared groups of “late” mothers (with high preterm birth rates) with “control” groups of younger women (with relatively low preterm birth rates). Data of 208 342 women were analysed. For women with zero (one; two) previous live births, the “control” group included women aged 22–26 (27–31; 29–33) years. Women in the “late motherhood” group were aged > 33 (> 35; > 38) years. Results: The “late motherhood” groups defined in this way were also at higher risk of adverse perinatal events other than preterm birth. For women with zero (one; two) previous live births, normal cephalic presentation occurred in 89 % (92.7 %; 93.3 %) in the “control” group, but only in 84.5 % (90 %; 90.4 %) in the “late motherhood” group. The mode of delivery was spontaneous or at most requiring manual help in 71.3 % (83.4 %; 85.8 %) in the “control” group, but only in 51.4 % (72.2 %; 76.4 %) in the “late motherhood” group. Five-minute APGAR scores were likewise worse for neonates of “late” mothers and the proportion with a birth weight ≤ 2499 g was greater. Conclusion: “Late motherhood” that is associated with greater perinatal risks can be defined based on parity and preterm birth rate. PMID:25253904

Expression of genes involved in carbohydrate-lipid metabolism in muscle and fat tissues in the initial stage of adult-age obesity in fed and fasted mice.

PubMed

Bazhan, Nadezhda M; Baklanov, Alexandr V; Piskunova, Julia V; Kazantseva, Antonina J; Makarova, Elena N

2017-10-01

C57Bl mice exhibit impaired glucose metabolism by the late adult age under standard living conditions. The aim of this study was to evaluate white adipose tissue (WAT), brown adipose tissue (BAT), and skeletal muscle expression of genes involved in carbohydrate-lipid metabolism at postpubertal stages preceding the late adult age in C57Bl mice. Muscle mRNA levels of uncoupling protein 3 ( Ucp3 ) and carnitine palmitoyltransferase 1 ( Cpt1 ) (indicators of FFA oxidation), WAT mRNA levels of hormone-sensitive lipase ( Lipe ) and lipoprotein lipase ( Lpl ) (indicators of lipolysis and lipogenesis), muscle and WAT mRNA levels of the type 4 glucose transporter Slc2a4 (indicators of insulin-dependent glucose uptake), and BAT mRNA levels of uncoupling protein 1 ( Ucp1 ) (indicator of thermogenesis) were measured in fed and 16 h-fasted mice in three age groups: 10-week-old (young), 15-week-old (early adult), and 30-week-old (late adult). Weight gain from young to early adult age was not accompanied by changes in WAT and BAT indexes and biochemical blood parameters. Weight gain from early to late adult age was accompanied by increased WAT and BAT indexes and decreased glucose tolerance. Muscle Ucp3 and Cpt1 mRNA levels and WAT Lipe and Slc2a4 mRNA levels increased from young to early adult age and then sharply decreased by the late adult age. Moreover, BAT Ucp1 mRNA level decreased in the late adult age. Fasting failed to increase muscle Cpt1 mRNA levels in late adult mice. These transcriptional changes could contribute to impaired glucose metabolism and the onset of obesity in late adult mice during normal development. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Length of home hospice care, family-perceived timing of referrals, perceived quality of care, and quality of death and dying in terminally ill cancer patients who died at home.

PubMed

Yamagishi, Akemi; Morita, Tatsuya; Kawagoe, Shohei; Shimizu, Megumi; Ozawa, Taketoshi; An, Emi; Kobayakawa, Makoto; Tsuneto, Satoru; Shima, Yasuo; Miyashita, Mitsunori

2015-02-01

This study aims to clarify the length of home hospice care, family-perceived timing of referrals, and their effects on the family-perceived quality of care and quality of death and dying of terminally ill cancer patients who died at home and identify the determinants of perceived late referrals. A multicenter questionnaire survey was conducted involving 1,052 family members of cancer patients who died at home supported by 15 home-based hospice services throughout Japan. A total of 693 responses were analyzed (effective response rate, 66 %). Patients received home-based hospice care for a median of 35.0 days, and 8.0 % received home hospice care for less than 1 week. While 1.5 % of the families reported the timing of referrals as early, 42 % reported the timing as late or too late. The families of patients with a length of care of less than 4 weeks were more likely to regard the timing of referrals as late or too late. The patients of family members who regarded the timing of referrals as late or too late had a significantly lower perceived quality of care (effect size, 0.18; P = 0.039) and lower quality of death and dying (effect size, 0.15, P = 0.063). Independent determinants of higher likelihoods of perceived late referrals included: frequent visits to emergency departments, patient being unprepared for worsening condition, and patient having concerns about relationship with new doctor. Discharge nurse availability was independently associated with lower likelihoods of perceived late referrals. A significant number of bereaved families regarded the timing of referrals to home hospices as late, and the perceived timing was associated with the family-perceived quality of care and quality of death and dying. Systematic strategies to overcome the barriers related to perceived late referrals are necessary.