Sample records for growth delay compared

  1. Importance of cell damage causing growth delay for high pressure inactivation of Saccharomyces cerevisiae

    NASA Astrophysics Data System (ADS)

    Nanba, Masaru; Nomura, Kazuki; Nasuhara, Yusuke; Hayashi, Manabu; Kido, Miyuki; Hayashi, Mayumi; Iguchi, Akinori; Shigematsu, Toru; Hirayama, Masao; Ueno, Shigeaki; Fujii, Tomoyuki

    2013-06-01

    A high pressure (HP) tolerant (barotolerant) mutant a2568D8 and a variably barotolerant mutant a1210H12 were generated from Saccharomyces cerevisiae using ultra-violet mutagenesis. The two mutants, a barosensitive mutant a924E1 and the wild-type strain, were pressurized (225 MPa), and pressure inactivation behavior was analyzed. In the wild-type strain, a proportion of the growth-delayed cells were detected after exposure to HP. In a924E1, the proportion of growth-delayed cells significantly decreased compared with the wild-type. In a2568D8, the proportion of growth-delayed cells increased and the proportion of inactivated cells decreased compared with the wild-type. In a1210H12, the growth-delayed cells could not be detected within 120 s of exposure to HP. The proportion of growth-delayed cells, which incurred the damage, would affect the survival ratio by HP. These results suggested that cellular changes in barotolerance caused by mutations are remarkably affected by the ability to recover from cellular damage, which results in a growth delay.

  2. Could head circumference be used to screen for autism in young males with developmental delay?

    PubMed

    Gray, Kylie M; Taffe, John; Sweeney, Deborah J; Forster, Sheridan; Tonge, Bruce J

    2012-04-01

    Research has suggested an abnormal acceleration in head circumference growth in children with autism within the first 12 months of life. This study aimed to examine head circumference at birth and head circumference growth rates in young children with autism and developmental delay, and young children with developmental delay without autism. This study assessed head circumference at birth and rate of change in head circumference in young children with autism (n=86) and children with developmental delay without autism (n=40). For both groups of children, head circumference at birth and head circumference growth were compared with Centers for Disease Control normative data. No differences were found between the group of children with autism and developmental delay compared with the group with developmental delay only. However, when the sample was compared with a range of selected Centers for Disease Control normative medians, the children with autism were found to have significantly smaller head circumferences at birth and significantly larger head circumference at 18.5 months of age. These results are discussed in relation to the potential of accelerated head circumference growth as an early marker for autism. This study failed to find a difference in the head circumferences of children with autism and developmental delay and children with developmental delay only, thus suggesting that head circumference measurement has limited value as an early marker for autism. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  3. Gompertzian stochastic model with delay effect to cervical cancer growth

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

    Mazlan, Mazma Syahidatul Ayuni binti; Rosli, Norhayati binti; Bahar, Arifah

    2015-02-03

    In this paper, a Gompertzian stochastic model with time delay is introduced to describe the cervical cancer growth. The parameters values of the mathematical model are estimated via Levenberg-Marquardt optimization method of non-linear least squares. We apply Milstein scheme for solving the stochastic model numerically. The efficiency of mathematical model is measured by comparing the simulated result and the clinical data of cervical cancer growth. Low values of Mean-Square Error (MSE) of Gompertzian stochastic model with delay effect indicate good fits.

  4. [Characteristics of growth and development in children from families at social risk].

    PubMed

    Stojadinović, A

    2001-01-01

    Body height and weight are important indicators of children's health status. There are many evidences that children from disadvantaged families have lower height and weight than children of the same age from families without social risk. The aim of this study was to investigate characteristics of growth and development of children from economically disadvantaged families. The study was partly retrospective and partly prospective. The retrospective study included 509 children from disadvantaged families hospitalized at the Institute of Child and Adolescent Health Care in Novi Sad, during a five-year period. The prospective study included 90 children from disadvantaged families (experimental group) and 132 children from families without social risk (control group) hospitalized at the Institute during a six month period. Height/length, weight, head circumference, and psychomotor/intellectual development have been examined. In the retrospective study results were compared with theoretically expected values, whereas the prospective study results of experimental and control group were compared. In the retrospective study that included only children from disadvantaged families, 136 (26.7%) children had height/length, 173 (34%) had weight, and 86 (16.9%) children had head circumference below 10th percentile. Delay in psychomotor/intellectual development was established in 177 (34.8%) children. Children from families with social risk have significantly more often height/length, weight, head circumference and developmental delay than theoretically expected. In the prospective study 40 (44.4%) children from experimental group had height/length, 29 (32.2%) had weight, 20 (22.2%) children had head circumference below 10th percentile, and 17 (26.2%) had delay in psychomotor/intellectual development. Children from disadvantaged families (experimental group) significantly more often had delay in growth and development comparing with children from families without social risk (control group). Children from disadvantaged families significantly more often exhibit delay in growth and development, comparing with children of the same age from families without social risk. Therefore, pediatricians should consider social risk factors whenever treating children with growth or developmental delay.

  5. Incidence of delayed hair re-growth, pruritus, and urinary retention after epidural anaesthesia in dogs.

    PubMed

    Kalchofner Guerrero, K S; Guerrero, T G; Schweizer-Kölliker, M; Ringer, S K; Hässig, M; Bettschart-Wolfensberger, R

    2014-04-16

    Delayed hair re-growth, pruritus and urinary retention are known complications after epidural anaesthesia in dogs. The aim of this study was to prospectively evaluate the effect of epidurally administered drugs on the occurrence of these complications in dogs. Ninety dogs were included in this study. Eighty client-owned dogs undergoing surgery were randomly assigned to one of three epidural treatment groups: either morphine and bupivacaine (MB), bupivacaine (B), or saline solution 0.9% (S) was administered epidurally to these patients. Ten dogs were only clipped in the lumbosacral area (C). Follow-up started 4 weeks after clipping and was performed every 4-5 weeks in cases of delayed hair re-growth or pruritus. Hair re-growth in the lumbosacral area was observed and compared to hair re-growth in the surgical field and the fentanyl patch area. Cytological analysis and a trichogram were performed if hair re-growth was delayed after 6 months. Time interval to first urination postoperatively was recorded (n = 80). Hair re-growth was delayed in 11 dogs (12.2%; B: n = 7, S: n = 2, MB: n = 1, C: n = 1) with no differences between groups. Pruritus was evident in two dogs (2.2%; MB: n = 1, S: n = 1). After 6 months, hair had started to re-grow in all but one dog (B). After 10 months the coat of this dog had re-grown. Time to first urination did not differ between groups. No direct correlation between the particular drugs injected epidurally and delayed hair re-growth, pruritus and urinary retention could be shown. Dog owners should be informed that hair re-growth after epidural anaesthesia could be markedly delayed.

  6. Aloe vera oral administration accelerates acute radiation-delayed wound healing by stimulating transforming growth factor-β and fibroblast growth factor production.

    PubMed

    Atiba, Ayman; Nishimura, Mayumi; Kakinuma, Shizuko; Hiraoka, Takeshi; Goryo, Masanobu; Shimada, Yoshiya; Ueno, Hiroshi; Uzuka, Yuji

    2011-06-01

    Delayed wound healing is a significant clinical problem in patients who have had previous irradiation. This study investigated the effectiveness of Aloe vera (Av) on acute radiation-delayed wound healing. The effect of Av was studied in radiation-exposed rats compared with radiation-only and control rats. Skin wounds were excised on the back of rats after 3 days of local radiation. Wound size was measured on days 0, 3, 6, 9, and 12 after wounding. Wound tissues were examined histologically and the expressions of transforming growth factor β-1 (TGF-β-1) and basic fibroblast growth factor (bFGF) were examined by immunohistochemistry and reverse-transcription polymerase chain reaction. Wound contraction was accelerated significantly by Av on days 6 and 12 after wounding. Furthermore, the inflammatory cell infiltration, fibroblast proliferation, collagen deposition, angiogenesis, and the expression levels of TGF-β-1 and bFGF were significantly higher in the radiation plus Av group compared with the radiation-only group. These data showed the potential application of Av to improve the acute radiation-delayed wound healing by increasing TGF-β-1 and bFGF production. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Early life exposure to PCB126 results in delayed mortality and growth impairment in the zebrafish larvae.

    PubMed

    Di Paolo, Carolina; Groh, Ksenia J; Zennegg, Markus; Vermeirssen, Etiënne L M; Murk, Albertinka J; Eggen, Rik I L; Hollert, Henner; Werner, Inge; Schirmer, Kristin

    2015-12-01

    The occurrence of chronic or delayed toxicity resulting from the exposure to sublethal chemical concentrations is an increasing concern in environmental risk assessment. The Fish Embryo Toxicity (FET) test with zebrafish provides a reliable prediction of acute toxicity in adult fish, but it cannot yet be applied to predict the occurrence of chronic or delayed toxicity. Identification of sublethal FET endpoints that can assist in predicting the occurrence of chronic or delayed toxicity would be advantageous. The present study characterized the occurrence of delayed toxicity in zebrafish larvae following early exposure to PCB126, previously described to cause delayed effects in the common sole. The first aim was to investigate the occurrence and temporal profiles of delayed toxicity during zebrafish larval development and compare them to those previously described for sole to evaluate the suitability of zebrafish as a model fish species for delayed toxicity assessment. The second aim was to examine the correlation between the sublethal endpoints assessed during embryonal and early larval development and the delayed effects observed during later larval development. After exposure to PCB126 (3-3000ng/L) until 5 days post fertilization (dpf), larvae were reared in clean water until 14 or 28 dpf. Mortality and sublethal morphological and behavioural endpoints were recorded daily, and growth was assessed at 28 dpf. Early life exposure to PCB126 caused delayed mortality (300 ng/L and 3000 ng/L) as well as growth impairment and delayed development (100 ng/L) during the clean water period. Effects on swim bladder inflation and cartilaginous tissues within 5 dpf were the most promising for predicting delayed mortality and sublethal effects, such as decreased standard length, delayed metamorphosis, reduced inflation of swim bladder and column malformations. The EC50 value for swim bladder inflation at 5 dpf (169 ng/L) was similar to the LC50 value at 8 dpf (188 and 202 ng/L in two experiments). Interestingly, the patterns of delayed mortality and delayed effects on growth and development were similar between sole and zebrafish. This indicates the comparability of critical developmental stages across divergent fish species such as a cold water marine flatfish and a tropical freshwater cyprinid. Additionally, sublethal effects in early embryo-larval stages were found promising for predicting delayed lethal and sublethal effects of PCB126. Therefore, the proposed method with zebrafish is expected to provide valuable information on delayed mortality and delayed sublethal effects of chemicals and environmental samples that may be extrapolated to other species. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Effects of lisdexamfetamine dimesylate treatment for ADHD on growth.

    PubMed

    Faraone, Stephen V; Spencer, Thomas J; Kollins, Scott H; Glatt, Stephen J

    2010-01-01

    To complete an exploratory uncontrolled study of the effects of lisdexamfetamine dimesylate (LDX) on growth of children treated for attention-deficit/hyperactivity disorder (ADHD). Height, weight, and body mass index (BMI) from 281 children ages 6 to 13 years from longitudinal assessments up to 15 months were compared to norms from the Centers for Disease Control. At study entry, children were taller and heavier than average. Growth delays were largest for weight and BMI, and there was a 13 percentile point decrease in height. Children continued to grow in terms of height while treated with LDX; we found no increase in raw weight or BMI during the study period. LDX treatment was significantly associated with diminished gains in height, weight, and BMI compared to levels that would be expected based on age-appropriate standards from the Centers for Disease Control. Growth delays were greatest for the heaviest and tallest children, for those who had not previously received stimulant therapy, and for those with a greater cumulative exposure to LDX. More work is needed to determine effects on ultimate adult height. Consistent with prior studies of stimulants, treatment with LDX leads to statistically significant reductions in expected height, weight, and BMI. Growth of patients with ADHD treated with LDX should be closely monitored and corrective action taken should growth delays be observed.

  9. Decreased head circumference velocity as related to developmental deficit in infancy.

    PubMed

    Tal, Galit; Cohen, Ayala; Habib, Sonia; Tirosh, Emanuel

    2012-11-01

    We evaluated the significance of head circumference growth velocity as related to developmental deficits during infancy. Head circumferences, lengths, and developmental diagnoses were retrieved in a standard manner at ≥ 2 time points from 437 infants with developmental deficits, and 3909 normally developing infants. Infants' ages ranged from 1-24 months, with final diagnoses ascertained at age 24 months. Increased velocity during the first 2 months in typical infants was evident in the study group during the period 2-4 months. A differential head circumference growth velocity was observed, and infants diagnosed with motor delay presented decreased velocity between ages 2-4 months, compared with infants receiving other nonmotor developmental diagnoses. These differences remained after controlling for birth weight and length. No significant sex effect was evident. Infants with developmental deficits demonstrate delayed acceleration of head circumference velocity, compared with typical infants in the first 2 months. Infants with motor delay manifest decreased velocity, compared with infants presenting other developmental deficits. These differences may be related to delayed white matter maturation. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Effects of Growth Hormone and Nutritional Therapy in Boys with Constitutional Growth Delay: A Randomized Controlled Trial

    PubMed Central

    Han, Joan C.; Damaso, Ligeia; Welch, Susan; Balagopal, Prabhakaran; Hossain, Jobayer; Mauras, Nelly

    2010-01-01

    Objective To examine whether supplemental nutrition augments the anabolic actions of growth hormone (GH) in boys with constitutional delay of growth and maturation (CDGM). Study design We conducted a randomized, controlled trial at an outpatient clinical research center. Subjects were 20 prepubertal boys (age 9.3±1.3y) with CDGM (height-SDS -2.0±0.5, bone age delay 1.8±0.8y, BMI-SDS -1.2±1.0, peak stimulated GH 15.7±7.7ng/mL), who were randomized (N=10/group) to 6 months observation or daily nutritional supplementation, followed by additional daily GH therapy in all for another 12 months. T-tests and repeated measures ANOVAs compared energy intake, total energy expenditure (TEE), growth, hormones and nutrition markers. Results Energy intake was increased at 6 months within the Nutrition (p=0.04) but not the Observation group, and TEE was not statistically different within either group at 6 months. Addition of 6 months GH resulted in higher energy intake and TEE in the GH/Nutrition group at 12 months (p<0.01), but not in the GH group vs. baseline. Height, weight, lean body mass, hormones and nutrition markers increased comparably in both groups throughout 18 months. Conclusions Boys with CDGM utilize energy at an accelerated rate, an imbalance not overcome with added nutrition. GH therapy increases growth comparably with or without added nutrition in these patients. PMID:20961566

  11. Skeletal muscle characterization of Japanese quail line selectively bred for lower body weight as an avian model of delayed muscle growth with hypoplasia.

    PubMed

    Choi, Young Min; Suh, Yeunsu; Shin, Sangsu; Lee, Kichoon

    2014-01-01

    This study was designed to extensively characterize the skeletal muscle development in the low weight (LW) quail selected from random bred control (RBC) Japanese quail in order to provide a new avian model of impaired and delayed growth in physically normal animals. The LW line had smaller embryo and body weights than the RBC line in all age groups (P<0.05). During 3 to 42 d post-hatch, the LW line exhibited approximately 60% smaller weight of pectoralis major muscle (PM), mainly resulting from lower fiber numbers compared to the RBC line (P<0.05). During early post-hatch period when myotubes are still actively forming, the LW line showed impaired PM growth with prolonged expression of Pax7 and lower expression levels of MyoD, Myf-5, and myogenin (P<0.05), likely leading to impairment of myogenic differentiation and consequently, reduced muscle fiber formation. Additionally, the LW line had delayed transition of neonatal to adult myosin heavy chain isoform, suggesting delayed muscle maturation. This is further supported by the finding that the LW line continued to grow unlike the RBC line; difference in the percentages of PMW to body weights between both quail lines diminished with increasing age from 42 to 75 d post-hatch. This delayed muscle growth in the LW line is accompanied by higher levels of myogenin expression at 42 d (P<0.05), higher percentage of centered nuclei at 42 d (P<0.01), and greater rate of increase in fiber size between 42 and 75 d post-hatch (P<0.001) compared to the RBC line. Analysis of physiological, morphological, and developmental parameters during muscle development of the LW quail line provided a well-characterized avian model for future identification of the responsible genes and for studying mechanisms of hypoplasia and delayed muscle growth.

  12. Intensity coding in electric hearing: effects of electrode configurations and stimulation waveforms.

    PubMed

    Chua, Tiffany Elise H; Bachman, Mark; Zeng, Fan-Gang

    2011-01-01

    Current cochlear implants typically stimulate the auditory nerve with biphasic pulses and monopolar electrode configurations. Tripolar stimulation can increase spatial selectivity and potentially improve place pitch related perception but requires higher current levels to elicit the same loudness as monopolar stimulation. The present study combined delayed pseudomonophonasic pulses, which produce lower thresholds, with tripolar stimulation in an attempt to solve the power-performance tradeoff problem. The present study systematically measured thresholds, dynamic range, loudness growth, and intensity discrimination using either biphasic or delayed pseudomonophonasic pulses under both monopolar and tripolar stimulation. Participants were five Clarion cochlear implant users. For each subject, data from apical, middle, and basal electrode positions were collected when possible. Compared with biphasic pulses, delayed pseudomonophonasic pulses increased the dynamic range by lowering thresholds while maintaining comparable maximum allowable levels under both electrode configurations. However, delayed pseudomonophonasic pulses did not change the shape of loudness growth function and actually increased intensity discrimination limens, especially at lower current levels. The present results indicate that delayed pseudomonophonasic pulses coupled with tripolar stimulation cannot provide significant power savings nor can it increase the functional dynamic range. Whether this combined stimulation could improve functional spectral resolution remains to be seen.

  13. Assessment of sella turcica area and skeletal maturation patterns of children with unilateral cleft lip and palate.

    PubMed

    Cesur, E; Altug, A T; Toygar-Memikoglu, U; Gumru-Celikel, D; Tagrikulu, B; Erbay, E

    2018-05-01

    The aim of this case-control study was to assess sella turcica area and skeletal maturity in children with unilateral cleft lip and palate (UCLP) and compare with those of non-cleft children. A total of 85 UCLP patients aged 7.5-17.08 years (Group 1: age 7-11 years, Group 2: age 11-14 years and Group 3: age 14-18 years) were compared with 85 control subjects without clefts who were divided into similar age groups. Hand-wrist radiographs and cervical vertebra maturation stages (CVMS) were used to evaluate growth. Lateral cephalograms were traced, and reference points of sella were determined. Sella turcica area was measured using a digital planimeter. Comparison of overall growth on hand-wrist radiographs revealed no significant difference between cleft and non-cleft subjects. However, according to the chronological age groups, Group 1-UCLP showed statistically significant delay in skeletal maturation when compared with the age-matched control subjects (P = .05). This difference was due to the delay among male subjects (P = .05). As for CVMS, more significant maturation delay was observed in Group 1-UCLP (P = .001) and was attributable to both male and female subjects (P = .05). Comparison of sella turcica area showed no significant difference between UCLP patients and controls. Although children with CLP showed significant delay in growth when they are younger compared with the non-cleft children, sella turcica area measurements were similar for individuals in both groups. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Growth of human colon cancer cells in nude mice is delayed by ketogenic diet with or without omega-3 fatty acids and medium-chain triglycerides.

    PubMed

    Hao, Guang-Wei; Chen, Yu-Sheng; He, De-Ming; Wang, Hai-Yu; Wu, Guo-Hao; Zhang, Bo

    2015-01-01

    Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis.

  15. Effects of interstitial heating on the RIF-1 tumor using an Nd:YAG laser with multiple fibers.

    PubMed

    Tobin, K M; Waldow, S M

    1996-01-01

    Hyperthermia was induced in tumor-bearing C3H mice using a Nd:YAG laser emitting near-infrared radiation at 1,064 nm. The efficacy of multiple implanted fiberoptics in the control of the RIF-1 tumor was investigated. RIF-1 tumors in the right hind leg were heated interstitially at 42, 44, or 46 degrees C for 30 or 60 minutes. Two, three, or four 400-microns quartz fibers terminating in a 1.0-cm cylindrical diffusor were inserted into each tumor, as were five microthermocouples to monitor temperature during treatment. Laser Doppler Flow (LDF) was also recorded pre- and post-treatment to determine changes in red blood cell flux in overlying skin (42, 44, or 46 degrees C) and the center of the tumor (46 degrees C). These experiments indicated that interstitial heating at 42, 44, and 46 degrees C resulted in tumor growth delay, although long-term control of tumors was not achieved. Treatment using four fibers resulted in the greatest tumor growth delay at 42 and 44 degrees C, increasing tumor doubling time by 50% or greater compared to control tumors; tumor growth delay following 46 degrees C treatments was seven times greater than that in control tumors. Significant changes (decreases) in LDF (P < .05) were seen in four treatment groups, using two fibers at 42 degrees C for 30 minutes, four fibers at 44 and 46 degrees C for 60 minutes on the overlying skin, and 46 degrees C for 60 minutes in the center of the tumor. Initial data indicate that interstitial heating with multiple fibers increases tumor growth delay compared to previous single fiber treatments, with tumor growth delay increasing with increasing treatment temperature; however, long-term tumor control was not achieved under the conditions investigated. Follow-up studies will explore the use of higher temperatures and/or longer treatment times in order to optimize tumor response.

  16. Delayed soil thawing affects root and shoot functioning and growth in Scots pine.

    PubMed

    Repo, Tapani; Lehto, Tarja; Finér, Leena

    2008-10-01

    In boreal regions, soil can remain frozen after the start of the growing season. We compared relationships between root characteristics and water relations in Scots pine (Pinus sylvestris L.) saplings subjected to soil frost treatments before and during the first week of the growing period in a controlled environment experiment. Delayed soil thawing delayed the onset of sap flow or totally blocked it if soil thawing lagged the start of the growing period by 7 days. This effect was reflected in the electrical impedance of needles and trunks and in the relative electrolyte leakage of needles. Prolonged soil frost reduced or completely inhibited root growth. In unfrozen soil, limited trunk sap flow was observed despite unfavorable aboveground growing conditions (low temperature, low irradiance, short photoperiod). Following the earliest soil thaw, sap flow varied during the growing season, depending on light and temperature conditions, phenological stage of the plant and the amount of live needles in the canopy. The results suggest that delayed soil thawing can reduce tree growth, and if prolonged, it can be lethal.

  17. Ogura-CMS in Chinese cabbage (Brassica rapa ssp. pekinensis) causes delayed expression of many nuclear genes.

    PubMed

    Dong, Xiangshu; Kim, Wan Kyu; Lim, Yong-Pyo; Kim, Yeon-Ki; Hur, Yoonkang

    2013-02-01

    We investigated the mechanism regulating cytoplasmic male sterility (CMS) in Brassica rapa ssp. pekinensis using floral bud transcriptome analyses of Ogura-CMS Chinese cabbage and its maintainer line in B. rapa 300-K oligomeric probe (Br300K) microarrays. Ogura-CMS Chinese cabbage produced few and infertile pollen grains on indehiscent anthers. Compared to the maintainer line, CMS plants had shorter filaments and plant growth, and delayed flowering and pollen development. In microarray analysis, 4646 genes showed different expression, depending on floral bud size, between Ogura-CMS and its maintainer line. We found 108 and 62 genes specifically expressed in Ogura-CMS and its maintainer line, respectively. Ogura-CMS line-specific genes included stress-related, redox-related, and B. rapa novel genes. In the maintainer line, genes related to pollen coat and germination were specifically expressed in floral buds longer than 3mm, suggesting insufficient expression of these genes in Ogura-CMS is directly related to dysfunctional pollen. In addition, many nuclear genes associated with auxin response, ATP synthesis, pollen development and stress response had delayed expression in Ogura-CMS plants compared to the maintainer line, which is consistent with the delay in growth and development of Ogura-CMS plants. Delayed expression may reduce pollen grain production and/or cause sterility, implying that mitochondrial, retrograde signaling delays nuclear gene expression. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Functional brain development in growth-restricted and constitutionally small fetuses: a fetal magnetoencephalography case-control study.

    PubMed

    Morin, E C; Schleger, F; Preissl, H; Braendle, J; Eswaran, H; Abele, H; Brucker, S; Kiefer-Schmidt, I

    2015-08-01

    Fetal magnetoencephalography records fetal brain activity non-invasively. Delayed brain responses were reported for fetuses weighing below the tenth percentile. To investigate whether this delay indicates delayed brain maturation resulting from placental insufficiency, this study distinguished two groups of fetuses below the tenth percentile: growth-restricted fetuses with abnormal umbilical artery Doppler velocity (IUGR) and constitutionally small-for-gestational-age fetuses with normal umbilical artery Doppler findings (SGA) were compared with fetuses of adequate weight for gestational age (AGA), matched for age and behavioural state. A case-control study of matched pairs. Fetal magnetoencephalography-Center at the University Hospital of Tuebingen. Fourteen IUGR fetuses and 23 SGA fetuses were matched for gestational age and fetal behavioural state with 37 healthy, normal-sized fetuses. A 156-channel fetal magentoencephalography system was used to record fetal brain activity. Light flashes as visual stimulation were applied to the fetus. The Student's t-test for paired groups was performed. Latency of fetal visual evoked magnetic responses (VER). The IUGR fetuses showed delayed VERs compared with controls (IUGR, 233.1 ms; controls, 184.6 ms; P = 0.032). SGA fetuses had similar evoked response latencies compared with controls (SGA, 216.1 ms; controls, 219.9 ms; P = 0.828). Behavioural states were similarly distributed. Visual evoked responses are delayed in IUGR fetuses, but not in SGA. Fetal behavioural state as an influencing factor of brain response latency was accounted for in the comparison. This reinforces that delayed brain maturation is the result of placental insufficiency. © 2015 Royal College of Obstetricians and Gynaecologists.

  19. The attitudes of family physicians toward a child with delayed growth and development.

    PubMed

    Aker, Servet; Şahin, Mustafa Kürşat; Kınalı, Ömer; Şimşek Karadağ, Elif; Korkmaz, Tuğba

    2017-09-01

    Aim The purpose of this study was to assess the attitude of family physicians toward a child with delayed growth and development. Primary healthcare professionals play a key role in monitoring growth and development, the best indicator of the child's health status. If delayed growth and development can be detected early, then it is usually possible to restore functioning. This descriptive study was performed in Samsun, Turkey, in May and June 2015. In total, 325 family physicians were included. The study consisted of two parts. In the first session of the research, the story of an 18-month-old child with delayed growth and development was presented using visual materials. An interview between the child's mother and a member of primary healthcare staff was then enacted by two of the authors using role-playing. Subsequently, participants were given the opportunity to ask the mother and member of primary healthcare staff questions about the case. During the sessions, two observers observed the participants, took notes and compared these after the presentation. In the second part of the study, the participants were asked to complete a questionnaire consisting of three open-ended questions. Findings When asking questions of the mother, family physicians generally used accusatory and judgmental language. One of the questions most commonly put to the mother was 'Do you think you are a good mother?' Family physicians were keen to provide instruction for the patient and relatives. Family physicians to a large extent thought that the problem of a child with delayed growth and development can be resolved through education. Family physicians' manner of establishing relations with the patient and relatives is inappropriate. We therefore think that they should receive on-going in-service training on the subject.

  20. Patterns of physical growth and dental development in Jordanian children and adolescents with thalassemia major.

    PubMed

    Hattab, Faiez N

    2013-03-01

    Dental development and physical growth are of particular interest in pediatric dentistry and orthodontics. This study evaluated these variables in patients with thalassemia major (TM). Physical growth was assessed in 54 patients (31 males and 23 females) aged 5.5 to 18.3 years and dental development was analyzed using panoramic radiographs from 39 of the 54 patients. The Demirjian system was used to characterize dental development of the seven left mandibular permanent teeth. Chronologic age (CA) and dental age (DA) were compared using the paired t-test, and the correlation between CA and extent of delay in dental development (DA minus CA) was assessed using Pearson's correlation coefficients. Growth retardation (< 10th percentile for height and weight) was present in 75.9% of TM patients. Height less than the third percentile was noted in 41.9% (13/31) of males and 34.8% (8/23) of females. Mean (SD) body mass index was 16.5 ± 2.2 kg/m(2). The extent of growth retardation increased with advancing age. Patient radiographs revealed a delay in dental development in 31 of 39 (79.5%) of participants (mean delay, 1.12 years in males and 0.81 years in females; range, 0.1 to 2.7 years). The mean difference between CA and DA was 0.97 years (P < 0.001). CA was significant correlated with extent of dental developmental delay (r = 0.64, P < 0.01). The results show that, among children and adolescents with TM, the proportions of those who had short stature, were underweight, and had a low growth rate increased with age. In addition, participants had significant delays in dental development.

  1. Intensity coding in electric hearing: Effects of electrode configurations and stimulation waveforms

    PubMed Central

    Chua, Tiffany Elise H.; Bachman, Mark; Zeng, Fan-Gang

    2011-01-01

    Objectives Current cochlear implants typically stimulate the auditory nerve with biphasic pulses and monopolar electrode configurations. Tripolar stimulation can increase spatial selectivity and potentially improve place pitch related perception, but requires higher current levels to elicit the same loudness as monopolar stimulation. The present study combined delayed pseudomonophonasic pulses, which produce lower thresholds, with tripolar stimulation in an attempt to solve the power-performance tradeoff problem. Design The present study systematically measured thresholds, dynamic range, loudness growth, and intensity discrimination using either biphasic or delayed pseudomonophonasic pulses under both monopolar and tripolar stimulation. Participants were 5 Clarion cochlear implant users. For each subject, data from apical, middle and basal electrode positions were collected when possible. Results Compared with biphasic pulses, delayed pseudomonophonasic pulses increased the dynamic range by lowering thresholds while maintaining comparable maximum allowable levels under both electrode configurations. However, delayed pseudomonophonasic pulses did not change the shape of loudness growth function and actually increased intensity discrimination limens, especially at lower current levels. Conclusions The present results indicate that delayed pseudomonophonasic pulses coupled with tripolar stimulation cannot provide significant power savings, nor can it increase the functional dynamic range. Whether this combined stimulation could improve functional spectral resolution remains to be seen. PMID:21610498

  2. Effects of Ion Irradiation on Seedlings Growth Monitored by Ultraweak Delayed Luminescence

    PubMed Central

    Abe, Tomoko; Cirrone, Giuseppe A. P.; Cuttone, Giacomo; Gulino, Marisa; Musumeci, Francesco; Romano, Francesco; Ryuto, Hiromichi; Scordino, Agata

    2016-01-01

    The optical technique based on the measurement of delayed luminescence emitted from the biological samples has demonstrated its ability to provide valid and predictive information on the functional status of various biological systems. We want to extend this technique to study the effect of ionizing radiation on biological systems. In particular we are interested in the action of ion beams, used for therapeutic purposes or to increase the biological diversity. In general, the assessment of the damage that radiation produces both in the target objects and in the surrounding tissues, requires considerable time because is based on biochemical analysis or on the examination of the evolution of the irradiated systems. The delayed luminescence technique could help to simplify this investigation. We have so started our studies performing irradiations of some relatively simple vegetable models. In this paper we report results obtained from mung bean (Vigna radiata) seeds submitted to a 12C ion beam at the energy of 62 MeV/nucleon. The dry seeds were irradiated at doses from 50 to 7000 Gy. The photoinduced delayed luminescence of each seed before and after ion irradiation was measured. The growth of seedlings after irradiation was compared with that of untreated seeds. A growth reduction on increasing the dose was registered. The results show strong correlations between the ion irradiation dose, seeds growth and delayed luminescence intensity. In particular, the delayed luminescence intensity is correlated by a logistic function to the seedlings elongation and, after performing a suitable measurement campaign based on blind tests, it could become a tool able to predict the growth of seeds after ion irradiation. Moreover these results demonstrate that measurements of delayed luminescence could be used as a fast and non-invasive technique to check the effects of ion beams on relatively simple biological systems. PMID:27936220

  3. Can the observed association between serum perfluoroalkyl substances and delayed menarche be explained on the basis of puberty-related changes in physiology and pharmacokinetics?

    PubMed

    Wu, Huali; Yoon, Miyoung; Verner, Marc-André; Xue, Jianping; Luo, Man; Andersen, Melvin E; Longnecker, Matthew P; Clewell, Harvey J

    2015-09-01

    An association between serum levels of two perfluoroalkyl substances (PFAS) and delayed age at menarche was reported in a cross-sectional study of adolescents. Because perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have half-lives of years, growth dilution and the development of a new route of excretion (menstruation) could account for some or all of the reported association. To assess how much of the epidemiologic association between PFAS and delayed menarche can be explained by the correlation of growth and maturation with PFAS body burden. We developed a Monte Carlo (MC) physiologically-based pharmacokinetic (PBPK) model of PFAS to simulate plasma PFAS levels in a hypothetical female population aged 2 to 20years old. Realistic distributions of physiological parameters as well as timing of growth spurts and menarche were incorporated in the model. The association between PFAS level and delayed menarche in the simulated data was compared with the reported association. The prevalence of menarche, distributions of age-dependent physiological parameters, and quartiles of serum PFAS concentrations in the simulated subjects were comparable to those reported in the epidemiologic study. The delay of menarche in days per natural log increase in PFAS concentrations in the simulated data were about one third as large as the observed values. The reported relationship between PFAS and age at menarche appears to be at least partly explained by pharmacokinetics rather than a toxic effect of these substances. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Optimization of combination therapy of arsenic trioxide and fractionated radiotherapy for malignant glioma

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

    Ning Shoucheng; Knox, Susan J.

    2006-06-01

    Purpose: The primary objective was to optimize the combined treatment regimen using arsenic trioxide (ATO) and fractionated radiotherapy for the treatment of malignant glioma. Methods and Materials: Nude mice with human glioma xenograft tumors were treated with fractionated local tumor radiation of 250 cGy/fraction/day and 5 mg/kg ATO for 5-10 days. Results: Time course experiments demonstrated that maximal tumor growth delay occurred when ATO was administered between 0 and 4 h after radiation. The combination treatment of ATO and radiation synergistically inhibited tumor growth and produced a tumor growth delay time of 13.2 days, compared with 1.4 days and 6.5more » days for ATO and radiation alone (p < 0.01), respectively. The use of concurrent therapy of radiation and ATO initially, followed by ATO as maintenance therapy, was superior to the use of preloading with ATO before combined therapy and produced a tumor growth delay time of 22.7 days as compared with 11.7 days for the ATO preloading regimen (p < 0.01). The maintenance dose of ATO after concurrent therapy was effective and important for continued inhibition of tumor growth. Conclusions: The combined use of fractionated radiation and ATO is effective for the treatment of glioma xenograft tumors. ATO was most effective when administered 0-4 h after radiation without pretreatment with ATO. These results have important implications for the optimization of treatment regimen using ATO and fractionated radiotherapy for the treatment of brain tumors.« less

  5. Decreased growth rate of P. falciparum blood stage parasitemia with age in a holoendemic population.

    PubMed

    Pinkevych, Mykola; Petravic, Janka; Chelimo, Kiprotich; Vulule, John; Kazura, James W; Moormann, Ann M; Davenport, Miles P

    2014-04-01

    In malaria holoendemic settings, decreased parasitemia and clinical disease is associated with age and cumulative exposure. The relative contribution of acquired immunity against various stages of the parasite life cycle is not well understood. In particular, it is not known whether changes in infection dynamics can be best explained by decreasing rates of infection, or by decreased growth rates of parasites in blood. Here, we analyze the dynamics of Plasmodium falciparum infection after treatment in a cohort of 197 healthy study participants of different ages. We use both polymerase chain reaction (PCR) and microscopy detection of parasitemia in order to understand parasite growth rates and infection rates over time. The more sensitive PCR assay detects parasites earlier than microscopy, and demonstrates a higher overall prevalence of infection than microscopy alone. The delay between PCR and microscopy detection is significantly longer in adults compared with children, consistent with slower parasite growth with age. We estimated the parasite multiplication rate from delay to PCR and microscopy detections of parasitemia. We find that both the delay between PCR and microscopy infection as well as the differing reinfection dynamics in different age groups are best explained by a slowing of parasite growth with age.

  6. Small head size and delayed body weight growth in wild Japanese monkey fetuses after the Fukushima Daiichi nuclear disaster.

    PubMed

    Hayama, Shin-Ichi; Tsuchiya, Moe; Ochiai, Kazuhiko; Nakiri, Sachie; Nakanishi, Setsuko; Ishii, Naomi; Kato, Takuya; Tanaka, Aki; Konno, Fumiharu; Kawamoto, Yoshi; Omi, Toshinori

    2017-06-14

    To evaluate the biological effect of the Fukushima Daiichi nuclear disaster, relative differences in the growth of wild Japanese monkeys (Macaca fuscata) were measured before and after the disaster of 2011 in Fukushima City, which is approximately 70 km from the nuclear power plant, by performing external measurements on fetuses collected from 2008 to 2016. Comparing the relative growth of 31 fetuses conceived prior to the disaster and 31 fetuses conceived after the disaster in terms of body weight and head size (product of the occipital frontal diameter and biparietal diameter) to crown-rump length ratio revealed that body weight growth rate and proportional head size were significantly lower in fetuses conceived after the disaster. No significant difference was observed in nutritional indicators for the fetuses' mothers. Accordingly, radiation exposure could be one factor contributed to the observed growth delay in this study.

  7. Time-delay-induced dynamical behaviors for an ecological vegetation growth system driven by cross-correlated multiplicative and additive noises.

    PubMed

    Wang, Kang-Kang; Ye, Hui; Wang, Ya-Jun; Li, Sheng-Hong

    2018-05-14

    In this paper, the modified potential function, the stationary probability distribution function (SPDF), the mean growth time and the mean degeneration time for a vegetation growth system with time delay are investigated, where the vegetation system is assumed to be disturbed by cross-correlated multiplicative and additive noises. The results reveal some fact that the multiplicative and additive noises can both reduce the stability and speed up the decline of the vegetation system, while the strength of the noise correlation and time delay can both enhance the stability of the vegetation and slow down the depression process of the ecological system. On the other hand, with regard to the impacts of noises and time delay on the mean development and degeneration processes of the ecological system, it is discovered that 1) in the development process of the vegetation population, the increase of the noise correlation strength and time delay will restrain the regime shift from the barren state to the boom one, while the increase of the additive noise can lead to the fast regime shift from the barren state to the boom one. 2) Conversely, in the depression process of the ecological system, the increase of the strength of the correlation noise and time delay will prevent the regime shift from the boom state to the barren one. Comparatively, the increase of the additive and multiplicative noises can accelerate the regime shift from the boom state to the barren state.

  8. Economics of replacing young-growth ponderosa pine stands . . . a case study

    Treesearch

    Dennis E. Teeguarden

    1968-01-01

    Compares the expected capital value growth of five ponderosa pine stands (70 to 80 years old) on the Challenge Experimental Forest, Yuba County, Calif., with the cost of delaying harvest (defined as sum of stock-holding and land-holding costs). Suggests that replacement of all five stands would be financially desirable under constant stumpage prices. Recommends...

  9. CO2 induced seawater acidification impacts sea urchin larval development I: elevated metabolic rates decrease scope for growth and induce developmental delay.

    PubMed

    Stumpp, M; Wren, J; Melzner, F; Thorndyke, M C; Dupont, S T

    2011-11-01

    Anthropogenic CO(2) emissions are acidifying the world's oceans. A growing body of evidence is showing that ocean acidification impacts growth and developmental rates of marine invertebrates. Here we test the impact of elevated seawater pCO(2) (129 Pa, 1271 μatm) on early development, larval metabolic and feeding rates in a marine model organism, the sea urchin Strongylocentrotus purpuratus. Growth and development was assessed by measuring total body length, body rod length, postoral rod length and posterolateral rod length. Comparing these parameters between treatments suggests that larvae suffer from a developmental delay (by ca. 8%) rather than from the previously postulated reductions in size at comparable developmental stages. Further, we found maximum increases in respiration rates of +100% under elevated pCO(2), while body length corrected feeding rates did not differ between larvae from both treatments. Calculating scope for growth illustrates that larvae raised under high pCO(2) spent an average of 39 to 45% of the available energy for somatic growth, while control larvae could allocate between 78 and 80% of the available energy into growth processes. Our results highlight the importance of defining a standard frame of reference when comparing a given parameter between treatments, as observed differences can be easily due to comparison of different larval ages with their specific set of biological characters. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Intraspecific priority effects modify compensatory responses to changes in hatching phenology in an amphibian.

    PubMed

    Murillo-Rincón, Andrea P; Kolter, Nora A; Laurila, Anssi; Orizaola, Germán

    2017-01-01

    In seasonal environments, modifications in the phenology of life-history events can alter the strength of time constraints experienced by organisms. Offspring can compensate for a change in timing of hatching by modifying their growth and development trajectories. However, intra- and interspecific interactions may affect these compensatory responses, in particular if differences in phenology between cohorts lead to significant priority effects (i.e. the competitive advantage that early-hatching individuals have over late-hatching ones). Here, we conducted a factorial experiment to determine whether intraspecific priority effects can alter compensatory phenotypic responses to hatching delay in a synchronic breeder by rearing moor frog (Rana arvalis) tadpoles in different combinations of phenological delay and food abundance. Tadpoles compensated for the hatching delay by speeding up their development, but only when reared in groups of individuals with identical hatching phenology. In mixed phenology groups, strong competitive effects by non-delayed tadpoles prevented the compensatory responses and delayed larvae metamorphosed later than in single phenology treatments. Non-delayed individuals gained advantage from developing with delayed larvae by increasing their developmental and growth rates as compared to single phenology groups. Food shortage prolonged larval period and reduced mass at metamorphosis in all treatments, but it did not prevent compensatory developmental responses in larvae reared in single phenology groups. This study demonstrates that strong intraspecific priority effects can constrain the compensatory growth and developmental responses to phenological change, and that priority effects can be an important factor explaining the maintenance of synchronic life histories (i.e. explosive breeding) in seasonal environments. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

  11. Time delay and noise explaining the behaviour of the cell growth in fermentation process

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

    Ayuobi, Tawfiqullah; Rosli, Norhayati; Bahar, Arifah

    2015-02-03

    This paper proposes to investigate the interplay between time delay and external noise in explaining the behaviour of the microbial growth in batch fermentation process. Time delay and noise are modelled jointly via stochastic delay differential equations (SDDEs). The typical behaviour of cell concentration in batch fermentation process under this model is investigated. Milstein scheme is applied for solving this model numerically. Simulation results illustrate the effects of time delay and external noise in explaining the lag and stationary phases, respectively for the cell growth of fermentation process.

  12. Time delay and noise explaining the behaviour of the cell growth in fermentation process

    NASA Astrophysics Data System (ADS)

    Ayuobi, Tawfiqullah; Rosli, Norhayati; Bahar, Arifah; Salleh, Madihah Md

    2015-02-01

    This paper proposes to investigate the interplay between time delay and external noise in explaining the behaviour of the microbial growth in batch fermentation process. Time delay and noise are modelled jointly via stochastic delay differential equations (SDDEs). The typical behaviour of cell concentration in batch fermentation process under this model is investigated. Milstein scheme is applied for solving this model numerically. Simulation results illustrate the effects of time delay and external noise in explaining the lag and stationary phases, respectively for the cell growth of fermentation process.

  13. Delays in maturation among adolescents with hemophilia and a history of inhibitors

    PubMed Central

    Lynn, Henry S.; Lail, Alice E.; Hoots, W. Keith; Berntorp, Erik; Gomperts, Edward D.

    2007-01-01

    Inhibitory antibodies to factors VIII or IX have the potential to affect a broad range of outcomes among people with hemophilia; however, their possible effect on growth and maturation has not been explored. We evaluated skeletal maturation (bone age), pubertal progression, serum testosterone levels, height velocity, and stature in the multicenter Hemophilia Growth and Development Study. A total of 333 children and adolescents (mean age, 12.4 years) were enrolled from 1989 to 1990 and followed for 7 years. Of these, 18% (n = 60) had a history of inhibitors. Bone age among HIV− adolescents with a history of inhibitors lagged 9 or more months behind those without inhibitors at every age from 12 to 15 years. Those with a history of inhibitors were older at every Tanner stage transition, attained a lower maximum growth velocity, and their serum testosterone levels were significantly lower compared with those without inhibitors. Delays were greater among HIV+ patients with a history of inhibitors compared with those without inhibitors; however, the differences were generally small and not statistically significant. The results of this investigation underscore the importance of monitoring the growth and maturation of children and adolescents with hemophilia, particularly those with inhibitors. PMID:17715388

  14. Spread of hatch and delayed feed access affect post hatch performance of female broiler chicks up to day 5.

    PubMed

    Wang, Y; Li, Y; Willems, E; Willemsen, H; Franssens, L; Koppenol, A; Guo, X; Tona, K; Decuypere, E; Buyse, J; Everaert, N

    2014-04-01

    It is not rare that newly hatched chicks remain without feed for about 24 to 48 h before they are placed on farms due to a series of logistic operations. Furthermore, the spread in hatching time can also mount up to 30 to 48 h for late v. early hatchers. In other words, the practice is a complex combination of spread of hatch and delayed feed access. The present study was aimed to investigate the combined effects of hatching time with a delay in feed access of 48 h, starting from their hatch-time (biological age). When chicks had access to feed immediately after hatch, late hatchers had a higher feed intake and relative growth rate up to day 5 compared with their early hatched counterparts. Feed deprivation during the first 48 h resulted in retarded early growth rate, which was further aggravated by an impaired feed intake after refeeding. In addition, the differential effects of hatching time on relative growth rate and feed intake observed in immediately fed chicks were eliminated by the 48 h feed delay. The yolk utilization after hatch was faster for the late hatchers up to biological day 2 regardless of the feeding treatments. Hatching muscle glycogen content was higher in the late hatchers compared with that of their early counterparts at hatch and at biological day 2 independent of feeding treatment. Moreover, the liver glycogen content of the late hatchers was also higher at hatch. For the immediately fed chicks, the proportional breast muscle weight of the late hatchers was higher at biological day 2 and 5. For the starved chicks, on the other hand, this effect was only observed after they had access to feed (biological day 5). The different plasma T3 levels at hatch may have contributed to the different post hatch performance. It is concluded that the spread of hatch influenced post hatch performance, especially appetite and growth at least until day 5. Moreover, the delay in feed access interacted with the hatching time and caused adverse effects on the post hatch performance.

  15. Decrease in hematopoietic stem cell domains as a delayed effect of x-irradiation

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

    Maloney, M.A.; Lamela, R.A.; Patt, H.M.

    Although the hematopoietic integrity of locally X-irradiated sites can be restored for a time even after fairly large doses, a secondary aplasia often occurs some months later. To gain further insight into this delayed effect within the framework of the stem cell regulatory domain hypothesis, we characterized the growth kinetics of spleen colony forming units (CFU-S) in WBB6FI-+/+ bone marrow transplanted into WBB6FI-W/WV mice in which one leg had been exposed to 10-30 Gy of X rays 4-5 months previously. Compared to unirradiated contralateral marrow, fewer CFU-S either reached the previously irradiated marrow or were seeded into sites that couldmore » support growth. The initial exponential growth of effectively seeded CFU-S was unchanged, but growth deceleration (inflection point) occurred at a lower level of CFU-S in marrow previously irradiated with 20-30 Gy. This change in the inflection point indicates a radiation dose-dependent decrease consistent with the decrease in bone marrow cellularity. The decrease in effective stem cell domains after 20 Gy was calculated to be about 35%. We interpret these results to reflect the highly localized nature of delayed radiation damage to the marrow microenvironment.« less

  16. A new method of applying a controlled soil water stress, and its effect on the growth of cotton and soybean seedlings at ambient and elevated carbon dioxide

    USDA-ARS?s Scientific Manuscript database

    While numerous studies have shown that elevated carbon dioxide can delay soil water depletion by causing partial stomatal closure, few studies have compared responses of plant growth to the same soil water deficits imposed at ambient and elevated carbon dioxide. We applied a vacuum to ceramic cups ...

  17. Lack of hepcidin ameliorates anemia and improves growth in an adenine-induced mouse model of chronic kidney disease

    PubMed Central

    Sureshbabu, Angara; Doty, Steve B.; Zhu, Yuan-Shan; Patino, Edwin; Cunningham-Rundles, Susanna; Choi, Mary E.; Boskey, Adele; Rivella, Stefano

    2016-01-01

    Growth delay is common in children with chronic kidney disease (CKD), often associated with poor quality of life. The role of anemia in uremic growth delay is poorly understood. Here we describe an induction of uremic growth retardation by a 0.2% adenine diet in wild-type (WT) and hepcidin gene (Hamp) knockout (KO) mice, compared with their respective littermates fed a regular diet. Experiments were started at weaning (3 wk). After 8 wk, blood was collected and mice were euthanized. Adenine-fed WT mice developed CKD (blood urea nitrogen 82.8 ± 11.6 mg/dl and creatinine 0.57 ± 0.07 mg/dl) and were 2.1 cm shorter compared with WT controls. WT adenine-fed mice were anemic and had low serum iron, elevated Hamp, and elevated IL6 and TNF-α. WT adenine-fed mice had advanced mineral bone disease (serum phosphorus 16.9 ± 3.1 mg/dl and FGF23 204.0 ± 115.0 ng/ml) with loss of cortical and trabecular bone volume seen on microcomputed tomography. Hamp disruption rescued the anemia phenotype resulting in improved growth rate in mice with CKD, thus providing direct experimental evidence of the relationship between Hamp pathway and growth impairment in CKD. Hamp disruption ameliorated CKD-induced growth hormone-insulin-like growth factor 1 axis derangements and growth plate alterations. Disruption of Hamp did not mitigate the development of uremia, inflammation, and mineral and bone disease in this model. Taken together, these results indicate that an adenine diet can be successfully used to study growth in mice with CKD. Hepcidin appears to be related to pathways of growth retardation in CKD suggesting that investigation of hepcidin-lowering therapies in juvenile CKD is warranted. PMID:27440777

  18. Elongator promotes germination and early post-germination growth.

    PubMed

    Woloszynska, Magdalena; Gagliardi, Olimpia; Vandenbussche, Filip; Van Lijsebettens, Mieke

    2018-01-02

    The Elongator complex interacts with RNA polymerase II and via histone acetylation and DNA demethylation facilitates epigenetically the transcription of genes involved in diverse processes in plants, including growth, development, and immune response. Recently, we have shown that the Elongator complex promotes hypocotyl elongation and photomorphogenesis in Arabidopsis thaliana by regulating the photomorphogenesis and growth-related gene network that converges on genes implicated in cell wall biogenesis and hormone signaling. Here, we report that germination in the elo mutant was delayed by 6 h in the dark when compared to the wild type in a time lapse and germination assay. A number of germination-correlated genes were down-regulated in the elo transcriptome, suggesting a transcriptional regulation by Elongator. We also show that the hypocotyl elongation defect observed in the elo mutants in darkness originates very early in the post-germination development and is independent from the germination delay.

  19. Effect of bevacizumab on angiogenesis and growth of canine osteosarcoma cells xenografted in athymic mice.

    PubMed

    Scharf, Valery F; Farese, James P; Coomer, Alastair R; Milner, Rowan J; Taylor, David P; Salute, Marc E; Chang, Myron N; Neal, Dan; Siemann, Dietmar W

    2013-05-01

    Objective-To investigate the effects of bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, on the angiogenesis and growth of canine osteosarcoma cells xenografted in mice. Animals-27 athymic nude mice. Procedures-To each mouse, highly metastasizing parent osteosarcoma cells of canine origin were injected into the left gastrocnemius muscle. Each mouse was then randomly allocated to 1 of 3 treatment groups: high-dose bevacizumab (4 mg/kg, IP), low-dose bevacizumab (2 mg/kg, IP), or control (no treatment). Tumor growth (the number of days required for the tumor to grow from 8 to 13 mm), vasculature, histomorphology, necrosis, and pulmonary metastasis were evaluated. Results-Mice in the high-dose bevacizumab group had significantly delayed tumor growth (mean ± SD, 13.4 ± 3.8 days; range, 9 to 21 days), compared with that for mice in the low-dose bevacizumab group (mean ± SD, 9.4 ± 1.5 days; range, 7 to 11 days) or control group (mean ± SD, 7. 2 ± 1.5 days; range, 4 to 9 days). Mice in the low-dose bevacizumab group also had significantly delayed tumor growth, compared with that for mice in the control group. Conclusions and Clinical Relevance-Results indicated that bevacizumab inhibited growth of canine osteosarcoma cells xenografted in mice, which suggested that vascular endothelial growth factor inhibitors may be clinically useful for the treatment of osteosarcoma in dogs. Impact for Human Medicine-Canine osteosarcoma is used as a research model for human osteosarcoma; therefore, bevacizumab may be clinically beneficial for the treatment of osteosarcoma in humans.

  20. Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology

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

    Flandin, Isabelle; Department of Radiotherapy/Oncology, Hospital Lyon Sud, Lyon; Hartmann, Olivier

    2006-04-01

    Purpose: To determine the contribution of total body irradiation (TBI) to late sequelae in children treated with high-dose chemotherapy and autologous bone marrow transplantation for Stage IV neuroblastoma. Patients and Methods: We compared two populations that were similar with regard to age, stage, pre-autologous bone marrow transplantation chemotherapy (CT) regimen, period of treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part of the megatherapy procedure (1982-1993), whereas the CT group (n 30) received conditioning without TBI (1985-1992). Analysis 12 years later focused on growth, weight and corpulence (body mass index) delay; hormonal deficiencies; liver,more » kidney, heart, ear, eye, and dental sequelae; school performance; and the incidence of secondary tumors. Results: Impact of TBI was most marked in relation to growth and weight delay, although the mean delay was not severe, probably because of treatment with growth hormones. Other consequences of TBI were thyroid insufficiency, cataracts, and a high incidence of secondary tumors. Hearing loss and dental agenesis were more prominent in the group treated with CT alone. No differences were observed in school performance. Conclusion: The most frequent side effects of TBI were cataracts, thyroid insufficiency, and growth delay, but more worrying is the risk of secondary tumors. Because of the young mean age of patients and the toxicity of TBI regimens without any survival advantage, regimens without TBI are preferable in the management of Stage IV neuroblastoma.« less

  1. Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. V. Bleomycin

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

    Twentyman, P.R.; Kallman, R.F.; Brown, J.M.

    1979-09-01

    Experiments have been carried out to determine the effect of different time intervals between the administration of x-radiation (1200 rad) and bleomycin (20 mg/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administered bymore » the intraperitoneal route either 24, 6, or 2 hr before radiation, immediately before the start of radiation, or 3, 6, or 24 hr after radiation. All irradiations were carried out in unanesthetized mice. For a single administration at this dose level, bleomycin alone did not produce a significant growth delay in any of the tumors. In the RIF-1 tumor, growth delays following combination treatments were equal to the addition of the single agent growth delays. In two experiments with EMT6, contrary results were obtained, one producing longer delays following combination treatments than predicted and the other producing shorter delays. This is apparently due to the variability in the growth delay after treatment with radiation alone for this tumor. For the KHT tumor, only small differences from the addition of single agent delays were seen.« less

  2. Intraperitoneal photodynamic therapy of the rat CC531 adenocarcinoma.

    PubMed Central

    Veenhuizen, R. B.; Marijnissen, J. P.; Kenemans, P.; Ruevekamp-Helmers, M. C.; 't Mannetje, L. W.; Helmerhorst, T. J.; Stewart, F. A.

    1996-01-01

    The goal of this study was to investigate the efficacy of photodynamic therapy (PDT) of a single tumour growing intraperitoneally. For this purpose the CC531 colon carcinoma, implanted in an intraperitoneal fat pad of Wag/RijA rats, was treated with intraperitoneal photodynamic therapy (IPPDT) using Photofrin as the photosensitiser. Two illumination techniques have been compared. An invasive illumination technique using Perspex blocks to illuminate 30 cm2 of the lower abdomen gave a significant delay in tumour growth with 25 J cm-2 applied 1 day after Photofrin. A minimally invasive illumination technique using a balloon catheter to illuminate 14 cm2 resulted in an equivalent growth delay with 75 J cm-2. The route of administration of the photosensitiser did not influence regrowth times of the tumour. Mitomycin C (MMC), a bioreductive agent, was used to exploit the known PDT-induced hypoxia. The combination of IPPDT with MMC resulted in an increased tumoricidal effect. In conclusion, IPPDT led to a significant growth delay for a single tumour implanted intraperitoneally and repetition of the PDT treatment was possible using a minimally invasive illumination technique. Repeated treatments resulted in increased tumour response. PMID:8645584

  3. Short- and long-term (final height) growth responses to growth hormone (GH) therapy in patients with Turner syndrome: correlation of growth response to stimulated GH levels, spontaneous GH secretion, and karyotype.

    PubMed

    Schmitt, K; Haeusler, G; Blümel, P; Plöchl, E; Frisch, H

    1997-01-01

    In 41 girls with Turner syndrome, the growth hormone (GH) peak values during stimulation tests and parameters of spontaneous nocturnal GH secretion were studied and compared with respect to different karyotypes, short-term growth response to GH therapy, and final height. 22.0% of the girls tested had a subnormal (peak < 11 ng/ml) and 9.7% a pathological (< 7 ng/ml) GH response. The spontaneous GH secretion showed a good correlation with the data of the provocation tests, providing no further information regarding GH capacity. Short-term growth response to GH treatment could not be predicted by any of the investigated parameters. Although patients with isochromosomes had frequent subnormal GH tests, their growth response to GH treatment after 1 year was comparable to that of girls with XO karyotype and mosaicism. In 18 patients who had reached final height, the height gain during treatment (calculated as final height minus projected adult height) was not different among patients with normal, subnormal, or pathological GH tests. In contrast, final height minus projected adult height in 4 girls with isochromosomes was 15.7 +/- 5.1 versus 7.6 +/- 3.3 cm in 14 patients with other karyotypes (p < 0.01). These girls had a more pronounced bone age delay (3.3 +/- 0.3 vs. 1.8 +/- 1.2 years) at the start of therapy and thus a better growth potential. We conclude that short- and long-term growth responses to GH treatment in Turner syndrome could not be predicted by GH testing. Patients with isochromosomes might represent a subpopulation which is more frequently GH deficient and shows a marked bone age delay.

  4. How long can fisheries management delay action in response to ecosystem and climate change?

    PubMed

    Brown, Christopher J; Fulton, Elizabeth A; Possingham, Hugh P; Richardson, Anthony J

    2012-01-01

    Sustainable management of fisheries is often compromised by management delaying implementation of regulations that reduce harvest, in order to maintain higher catches in the short-term. Decreases or increases in fish population growth rate driven by environmental change, including ecosystem and climate change, affect the harvest that can be taken sustainably. If not acted on rapidly, environmental change could result in unsustainable fishing or missed opportunity for higher catches. Using simulation models of harvested fish populations influenced by environmental change, we explore how long fisheries managers can afford to wait before changing harvest regulations in response to changes in population growth. If environmental change causes population declines, delays greater than five years increase the probability of population collapse. Species with fast and highly variable population growth rates are more susceptible to collapse under delays and should be a priority for revised management where delays occur. Generally, the long-term cost of delay, in terms of lost fishing opportunity, exceeds the short-term benefits of overfishing. Lowering harvest limits and monitoring for environmental change can alleviate the impact of delays; however, these measures may be more costly than reducing delays. We recommend that management systems that allow rapid responses to population growth changes be enacted for fisheries management to adapt to ecosystem and climate change.

  5. Growth retardation and reduced growth hormone secretion in cystic fibrosis. Clinical observations from three CF centers.

    PubMed

    Ciro, D'Orazio; Padoan, Rita; Blau, Hannah; Marostica, Anna; Fuoti, Maurizio; Volpi, Sonia; Pilotta, Alba; Meyerovitch, Joseph; Sher, Daniel; Assael, Baroukh M

    2013-03-01

    Growth delay in cystic fibrosis is frequent and is usually the result of several interacting causes. It most often derives from severe respiratory impairment and severe malabsorption. There are however patients whose clinical condition is not severe enough to be held accountable for this phenomenon. We aimed at describing patients who showed growth delay, who were not affected by severe pulmonary disease or malabsorption and who, when tested, showed a reduced GH secretion after stimulation with conventional agents. We noticed a disproportionately large prevalence of growth hormone (GH) release deficit (GHRD) in pediatric cystic fibrosis (CF) patients. We examined all patients under our care in the period 2006-11, who were older than 5 and younger than 16 years old. We focussed on those who fell below the 3rd height percentile, or whose growth during the previous 18 months faltered by >2SD, and who did not present clinical conditions that could reasonably explain their failure to thrive. These patients were subjected to standard GH provocative tests. Out of 285 who matched the age criterion, 33 patients also matched the height percentile criterion. While 15/33 suffered clinical conditions that could reasonably explain their failure to thrive, 18/33 underwent GH release provocative tests and 12/18 showed a release deficit. We conclude that impaired GH secretion is more frequent among CF patients compared to the prevalence of GH deficiency in the general population and that GH release impairment may be an independent cause of growth delay in CF. Our findings are in agreement with recent studies that have described low GH levels in CF piglets and in neonates with CF [1]. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  6. Microstructure development in Kolmogorov, Johnson-Mehl, and Avrami nucleation and growth kinetics

    NASA Astrophysics Data System (ADS)

    Pineda, Eloi; Crespo, Daniel

    1999-08-01

    A statistical model with the ability to evaluate the microstructure developed in nucleation and growth kinetics is built in the framework of the Kolmogorov, Johnson-Mehl, and Avrami theory. A populational approach is used to compute the observed grain-size distribution. The impingement process which delays grain growth is analyzed, and the effective growth rate of each population is estimated considering the previous grain history. The proposed model is integrated for a wide range of nucleation and growth protocols, including constant nucleation, pre-existing nuclei, and intermittent nucleation with interface or diffusion-controlled grain growth. The results are compared with Monte Carlo simulations, giving quantitative agreement even in cases where previous models fail.

  7. Uncertainty: A little bit not sure. Parental concern about child growth or development.

    PubMed

    Mulcahy, Helen; Savage, Eileen

    2016-09-01

    Delays in child growth or development are significant problems for children, their families and population health. Eliciting parental concerns as early as possible to promote child growth and development requires close collaborative working with parents. There is evidence that parents delay expressing concern and that health-care professionals are not always effective at eliciting and attending to parental concerns. The aim of this study was to understand the experiences of parents of preschool children who had expressed a child growth or development concern. An Interpretative Phenomenological Analysis (IPA) study design was used with a purposive sample of parents of 15 preschool children in Ireland. Data were collected by semi-structured interviews and analysed using IPA. One key superordinate theme - Uncertainty - 'a little bit not sure' captured how parents made sense of their concerns about their child's growth and development. In addition to watching, comparing and wondering, parents assessed whether their child could 'do other things' or if something in particular could have caused the growth or development problem. Parents, particularly mothers, grapple with uncertainty associated with unfamiliar cues in the complex and multifaceted nature of child growth and development in their efforts to make sense of what is happening with their child. © The Author(s) 2015.

  8. Constitutional growth delay pattern of growth in velo-cardio-facial syndrome: longitudinal follow up and final height of two cases.

    PubMed

    Turan, Serap; Ozdemir, Nihal; Güran, Tülay; Akalın, Figen; Akçay, Teoman; Ayabakan, Canan; Yılmaz, Yüksel; Bereket, Abdullah

    2008-01-01

    We report two patients with velo-cardio-facial syndrome (VCFS) who were admitted to our pediatric endocrinology clinic because of short stature and followed longitudinally until attainment of final height. Both patients followed a growth pattern consistent with constitutional delay of puberty with normal and near normal final height. Case 2 also had partial growth hormone (GH) deficiency and severe short stature (height SDS -3.4 SDS), but showed spontaneous catch-up and ended up with a final height of -2 SDS. These cases suggest that short stature in children with VCFS is due to a pattern of growth similar to that observed in constitutional delay of growth and puberty.

  9. Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing.

    PubMed

    Xu, M T; Sun, S; Zhang, L; Xu, F; Du, S L; Zhang, X D; Wang, D W

    2016-01-01

    Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2.

  10. Pubertal Height Velocity and Associations with Pre-pubertal and Adult Heights in Cystic Fibrosis

    PubMed Central

    Zhang, Zhumin; Lindstrom, Mary J.; Lai, HuiChuan J.

    2013-01-01

    Objectives To test the hypothesis that pubertal peak height velocity (PHV) in cystic fibrosis (CF) has improved and is influenced by pre-pubertal growth and genetic potential. Study design PHV from 1862 children born in 1984–87 and documented in the 1986–2008 US CF Foundation Registry was determined by statistical modeling and classified into normal, delayed (2-SD > average age), attenuated (magnitude < 5th percentile), or both (D&A). Genetic potential for height was estimated by parental stature. Results PHV averaged 8.4 cm/y at age 14.0 y in boys and 7.0 cm/y at age 12.1 y in girls, ~6 mo delay and ~15% reduction compared with healthy children. PHV was normal in 60%, delayed in 9%, attenuated in 21% and D&A in 5%. Patients with delayed PHV reached similar adult height percentile (boys: 34th, girls: 46th) to those with normal PHV (boys: 33rd, girls: 34th); both were significantly taller than the attenuated (boys: 11th, girls: 19th) and D&A PHV subgroups (boys: 8th, girls: 14th). Pancreatic sufficient patients had taller pre-pubertal and adult heights but similar PHV compared with pancreatic insufficient or meconium ileus patients. Adjusting for genetic potential reduced adult height percentiles more in boys (25th to 16th) than girls (28th to 24th). Height at age 7 y, PHV age and magnitude, and parental stature significantly predicted adult height. Conclusions Pubertal PHV has improved in children with CF born after mid 1980s compared with older cohorts but remains below normal. Suboptimal pre-pubertal and pubertal growth led to adult height below genetic potential in CF. PMID:23535012

  11. Risk Factors and Relationship Between Intestinal Parasites and the Growth Retardation and Psychomotor Development Delays of Children in Şanlıurfa, Turkey.

    PubMed

    Yentur Doni, Nebiye; Yildiz Zeyrek, Fadile; Simsek, Zeynep; Gurses, Gulcan; Sahin, İbrahim

    2015-12-01

    The objective of this study was to determine the risk factors for and relationship among parasitic infections, growth retardation, and psychomotor developmental delays in children aged 6 years and below. This case-control study was performed in Şanlıurfa in southeastern Turkey between October and December 2007. Data were collected using a structured questionnaire, anthropometry, Ankara Development Screening Inventory, and laboratory analysis of stool specimens. The most common parasite was Giardia intestinalis (42.53%) followed by Enterobius vermicularis (27.58%), Ascaris lumbricoides (18.39%), Hymenolepis nana (5.75%), Trichuris trichiura (3.45%), Escherichia coli (1.15%), and Blastocystis spp. (1.15%). Fifty-eight percent of all children were infected with intestinal parasites; 55.2% had only one parasite, whereas 44.8% had multiple parasites. The children infected with G. intestinalis and other intestinal parasites had significantly higher levels of growth retardation and psychomotor development delay than non-infected children. Children with parasitic infections had growth delay up to 2.9 times, general development delay up to 1.9 times, language-cognitive development delay up to 2.2 times, and fine motor development delay up to 2.9 times higher than children without any parasitic infections. However, no significant relationship among intestinal parasites, gross motor development, social-self skills, and development delay was identified. The education level of parents, poor economic situation, number of households, not washing hands, playing with soil, family history of parasitic infection were the significant risk factors for intestinal parasites. Our study indicates that the presence of either malnutrition or intestinal parasites may put a child in a high-risk group for developmental delays and growth retardation. Therefore, public health interventions can embrace nationwide deworming in children.

  12. Construction Cost Growth for New Department of Energy Nuclear Facilities

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

    Kubic, Jr., William L.

    Cost growth and construction delays are problems that plague many large construction projects including the construction of new Department of Energy (DOE) nuclear facilities. A study was conducted to evaluate cost growth of large DOE construction projects. The purpose of the study was to compile relevant data, consider the possible causes of cost growth, and recommend measures that could be used to avoid extreme cost growth in the future. Both large DOE and non-DOE construction projects were considered in this study. With the exception of Chemical and Metallurgical Research Building Replacement Project (CMRR) and the Mixed Oxide Fuel Fabrication Facilitymore » (MFFF), cost growth for DOE Nuclear facilities is comparable to the growth experienced in other mega construction projects. The largest increase in estimated cost was found to occur between early cost estimates and establishing the project baseline during detailed design. Once the project baseline was established, cost growth for DOE nuclear facilities was modest compared to non-DOE mega projects.« less

  13. Duration of lack of money for basic needs and growth delay in the Quebec Longitudinal Study of Child Development birth cohort.

    PubMed

    Ehounoux, N Z; Zunzunegui, M-V; Séguin, L; Nikiema, B; Gauvin, L

    2009-01-01

    To examine the relationship between duration of lack of money for basic needs and growth delay in a birth cohort. Mothers of children (n = 1929) from the Quebec Longitudinal Study of Child Development (QLSCD) participating when the children were ages 2(1/2) and 4 years were interviewed at home and data were extracted from birth records. Children's height at 4 years old was transformed into an age- and sex-adjusted z-score. A z-score under the 10th percentile of the Centers for Disease Control and Prevention population growth curve was equated with growth delay. Lack of money for basic needs (paying for rent, electricity and/or heating, clothing, medications or other needs) when the children were ages 2(1/2) and 4 years was reported by the mother. Only 2.5% of children experienced two episodes of lack of money for basic needs. Logistic regression analyses showed that, after adjusting for confounding variables, the probability of growth delay at 4 years among children whose families experienced two episodes of lack of money was higher than for their peers who had not lacked money (OR 3.43; 95% CI 1.54 to 7.66). Experiencing lack of money only at 2(1/2) years showed higher but not significant odds of growth delay at 4 years (OR 1.51; 95% CI 0.84 to 2.72), whereas the likelihood of growth delay was similar for children who experienced lack of money only at 4 years and for their counterparts who never lacked money (OR 0.74; 95% CI 0.26 to 2.11). In an industrialised country toddlers whose families experienced persistent lack of money for basic needs are more likely to have growth delay even after controlling for neonatal conditions and their mothers' characteristics.

  14. ROLES OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF-A) IN MEDIATION OF DIOXIN (TCDD)-INDUCED DELAYS IN DEVELOPMENT OF THE MOUSE MAMMARY GLAND

    EPA Science Inventory

    Roles of Epidermal Growth Factor (EGF) and Transforming Growth Factor-alpha (TGF-a) in Mediation of Dioxin (TCDD)-Induced Delays in Development of the Mouse Mammary Gland.
    Suzanne E. Fenton, Barbara Abbott, Lamont Bryant, and Angela Buckalew. U.S. EPA, NHEERL, Reproductive Tox...

  15. Effect of V-Nd co-doping on phase transformation and grain growth process of TiO2

    NASA Astrophysics Data System (ADS)

    Khatun, Nasima; Amin, Ruhul; Anita, Sen, Somaditya

    2018-05-01

    The pure and V-Nd co-doped TiO2 samples are prepared by the modified sol-gel process. The phase formation is confirmed by XRD spectrum. Phase transformation is delayed in V-Nd co-doped TiO2 (TVN) samples compared to pure TiO2. The particle size is comparatively small in TVN samples at both the temperature 450 °C and 900 °C. Hence the effect of Nd doping is dominated over V doping in both phase transformation and grain growth process of TiO2.

  16. Catalyst–substrate interaction and growth delay in vapor–liquid–solid nanowire growth

    NASA Astrophysics Data System (ADS)

    Kolíbal, Miroslav; Pejchal, Tomáš; Musálek, Tomáš; Šikola, Tomáš

    2018-05-01

    Understanding of the initial stage of nanowire growth on a bulk substrate is crucial for the rational design of nanowire building blocks in future electronic and optoelectronic devices. Here, we provide in situ scanning electron microscopy and Auger microscopy analysis of the initial stage of Au-catalyzed Ge nanowire growth on different substrates. Real-time microscopy imaging and elementally resolved spectroscopy clearly show that the catalyst dissolves the underlying substrate if held above a certain temperature. If the substrate dissolution is blocked (or in the case of heteroepitaxy) the catalyst needs to be filled with nanowire material from the external supply, which significantly increases the initial growth delay. The experiments presented here reveal the important role of the substrate in metal-catalyzed nanowire growth and pave the way for different growth delay mitigation strategies.

  17. Catalyst-substrate interaction and growth delay in vapor-liquid-solid nanowire growth.

    PubMed

    Kolíbal, Miroslav; Pejchal, Tomáš; Musálek, Tomáš; Šikola, Tomáš

    2018-05-18

    Understanding of the initial stage of nanowire growth on a bulk substrate is crucial for the rational design of nanowire building blocks in future electronic and optoelectronic devices. Here, we provide in situ scanning electron microscopy and Auger microscopy analysis of the initial stage of Au-catalyzed Ge nanowire growth on different substrates. Real-time microscopy imaging and elementally resolved spectroscopy clearly show that the catalyst dissolves the underlying substrate if held above a certain temperature. If the substrate dissolution is blocked (or in the case of heteroepitaxy) the catalyst needs to be filled with nanowire material from the external supply, which significantly increases the initial growth delay. The experiments presented here reveal the important role of the substrate in metal-catalyzed nanowire growth and pave the way for different growth delay mitigation strategies.

  18. Constitutional Growth Delay Pattern of Growth in Velo−Cardio−Facial Syndrome: Longitudinal follow up and final height of two cases

    PubMed Central

    Özdemir, Nihal; Güran, Tülay; Akalın, Figen; Akçay, Teoman; Ayabakan, Canan; Yılmaz, Yüksel; Bereket, Abdullah

    2008-01-01

    We report two patients with velo−cardio−facial syndrome (VCFS) who were admitted to our pediatric endocrinology clinic because of short stature and followed longitudinally until attainment of final height. Both patients followed a growth pattern consistent with constitutional delay of puberty with normal and near normal final height. Case 2 also had partial growth hormone (GH) deficiency and severe short stature (height SDS −3.4 SDS), but showed spontaneous catch−up and ended up with a final height of −2 SDS. These cases suggest that short stature in children with VCFS is due to a pattern of growth similar to that observed in constitutional delay of growth and puberty. Conflict of interest:None declared. PMID:21318064

  19. Irradiation combined with SU5416: Microvascular changes and growth delay in a human xenograft glioblastoma tumor line

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

    Schuuring, Janneke; Department of Neurology, Groene Hart Hospital, Gouda; Bussink, Johan

    Purpose: The combination of irradiation and the antiangiogenic compound SU5416 was tested and compared with irradiation alone in a human glioblastoma tumor line xenografted in nude mice. The aim of this study was to monitor microenvironmental changes and growth delay. Methods and materials: A human glioblastoma xenograft tumor line was implanted in nude mice. Irradiations consisted of 10 Gy or 20 Gy with and without SU5416. Several microenvironmental parameters (tumor cell hypoxia, tumor blood perfusion, vascular volume, and microvascular density) were analyzed after imunohistochemical staining. Tumor growth delay was monitored for up to 200 days after treatment. Results: SU5416, whenmore » combined with irradiation, has an additive effect over treatment with irradiation alone. Analysis of the tumor microenvironment showed a decreased vascular density during treatment with SU5416. In tumors regrowing after reaching only a partial remission, vascular characteristics normalized shortly after cessation of SU5416. However, in tumors regrowing after reaching a complete remission, permanent microenvironmental changes and an increase of tumor necrosis with a subsequent slower tumor regrowth was found. Conclusions: Permanent vascular changes were seen after combined treatment resulting in complete remission. Antiangiogenic treatment with SU5416 when combined with irradiation has an additive effect over treatment with irradiation or antiangiogenic treatment alone.« less

  20. Modelling and measurement of crack closure and crack growth following overloads and underloads

    NASA Technical Reports Server (NTRS)

    Dexter, R. J.; Hudak, S. J.; Davidson, D. L.

    1989-01-01

    Ignoring crack growth retardation following overloads can result in overly conservative life predictions in structures subjected to variable amplitude fatigue loading. Crack closure is believed to contribute to the crack growth retardation, although the specific closure mechanism is dabatable. The delay period and corresponding crack growth rate transients following overload and overload/underload cycles were systematically measured as a function of load ratio and overload magnitude. These responses are correlated in terms of the local 'driving force' for crack growth, i.e. the effective stress intensity factor range. Experimental results are compared with the predictions of a Dugdale-type (1960) crack closure model, and improvements in the model are suggested.

  1. Effects of Phytoplankton Growth Phase on Delayed Settling Behavior of Marine Snow Aggregates at Sharp Density Transitions

    NASA Astrophysics Data System (ADS)

    Proctor, K. W.; Montgomery, Q. W.; Prairie, J. C.

    2016-02-01

    Marine snow aggregates play a fundamental role in the marine carbon cycle. Since marine snow aggregates are larger and thus sink faster than individual phytoplankton, aggregates often dominate carbon flux. Previous studies have shown that marine snow aggregates will significantly decrease their settling velocity when passing through sharp density transitions within the ocean, a phenomenon defined as delayed settling. Given the importance of aggregate settling to carbon export, these small-scale changes in aggregate settling dynamics may have significant impacts on the efficiency of the biological pump. However, there is still a lack of knowledge about how different physical properties of aggregates can affect this delayed settling. In this study, we investigated the effect of phytoplankton growth phase on delayed settling behavior. Using phytoplankton cultures stopped at four different growth phases, we formed marine snow aggregates in the laboratory in rotating cylindrical tanks. We then observed individual aggregates as they settled through a stratified tank. We will present data which illustrates that aggregates experience greatly reduced settling rates when passing through sharp density gradients and that the growth phase of the phytoplankton used to form these aggregates has a significant effect on this delayed settling behavior. A thorough understanding of the impact of phytoplankton growth phase on the delayed settling behavior of marine snow will offer insight into the way phytoplankton growth phase may influence the efficiency of the biological pump, carbon flux, and the carbon cycle as a whole.

  2. Response to Growth Hormone Treatment in a Patient with Insulin-Like Growth Factor 1 Receptor Deletion

    PubMed Central

    Mahmoud, Ranim; Naidu, Ajanta; Risheg, Hiba; Kimonis, Virginia

    2017-01-01

    We report a six-year-old boy who presented with short stature, microcephaly, dysmorphic features, and developmental delay and who was identified with a terminal deletion of 15q26.2q26.3 containing the insulin-like growth factor receptor (IGF1R) gene in addition to a terminal duplication of the 4q35.1q35.2 region. We compare our case with other reports of deletions and mutations affecting the IGF1R gene associated with pre-and postnatal growth restriction. We report the dramatic response to growth hormone therapy in this patient which highlights the importance of identifying patients with IGF1R deletion and treating them early. PMID:28720553

  3. Response to Growth Hormone Treatment in a Patient with Insulin-Like Growth Factor 1 Receptor Deletion.

    PubMed

    Mahmoud, Ranim; Naidu, Ajanta; Risheg, Hiba; Kimonis, Virginia

    2017-12-15

    We report a six-year-old boy who presented with short stature, microcephaly, dysmorphic features, and developmental delay and who was identified with a terminal deletion of 15q26.2q26.3 containing the insulin-like growth factor receptor (IGF1R) gene in addition to a terminal duplication of the 4q35.1q35.2 region. We compare our case with other reports of deletions and mutations affecting the IGF1R gene associated with pre-and postnatal growth restriction. We report the dramatic response to growth hormone therapy in this patient which highlights the importance of identifying patients with IGF1R deletion and treating them early.

  4. Polyploidization delay in rat hepatocytes under liver growth inhibition by hypokinesia

    NASA Technical Reports Server (NTRS)

    Faktor, V. M.; Malyutin, V. F.; Li, S. Y.; Brodskiy, V. Y.

    1981-01-01

    A study of young rats, weighing 55 to 59 g, after being for 10 days in conditions of limited mobility, shows a retardation of body growth as well as that of liver growth. The decrease in the rate of growth is accompanied by a reduction of cell proliferation and by delay polyploidization of hepatocytes in the liver of experimental rats. The materials, methods, and results of research are discussed.

  5. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    PubMed Central

    Otto, Christoph; Kaemmerer, Ulrike; Illert, Bertram; Muehling, Bettina; Pfetzer, Nadja; Wittig, Rainer; Voelker, Hans Ullrich; Thiede, Arnulf; Coy, Johannes F

    2008-01-01

    Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further studies are needed to address the impact of this diet on other tumour-relevant functions such as invasive growth and metastasis. PMID:18447912

  6. Constitutional Delay Influences the Auxological Response to Growth Hormone Treatment in Children with Short Stature and Growth Hormone Sufficiency

    PubMed Central

    Gunn, Katherine C.; Cutfield, Wayne S.; Hofman, Paul L.; Jefferies, Craig A.; Albert, Benjamin B.; Gunn, Alistair J.

    2014-01-01

    In a retrospective, population based cohort study, we examined whether constitutional delay was associated with the growth response to growth hormone (GH) in children with short stature and normal GH responses. 70 patients were treated with 21 GH iu/m2/week from 1975 to 2013 throughout New Zealand. Demographic and auxological data were prospectively collected and standard deviation scores (SDS) were calculated for height (HtSDS), yearly growth velocity (GV-SDS), body mass index (BMI-SDS) and predicted adult height (PAH-SDS) at time of the last available bone age. In the first year, GH was associated with marked increase in HtSDS (+0.46 (0.19, 0.76), p < 0.001) and GV-SDS (from −1.9 (−3.6, −0.7) to +2.7 (0.45, 4.2), p < 0.001). The increase in HtSDS but not in GV-SDS was greatest with younger patients and greater bone age delay, with no effect of sex, BMI-SDS or baseline HtSDS. PAH-SDS increased with treatment (+0.94 (0.18, 1.5)); increased PAH-SDS was associated with less bone age delay and greater initial increase in HtSDS. This study shows that greater bone age delay was associated with greater initial improvement in height but less improvement in predicted adult heights, suggesting that children with very delayed bone ages may show accelerated maturation during GH treatment. PMID:25317732

  7. Constitutional delay influences the auxological response to growth hormone treatment in children with short stature and growth hormone sufficiency.

    PubMed

    Gunn, Katherine C; Cutfield, Wayne S; Hofman, Paul L; Jefferies, Craig A; Albert, Benjamin B; Gunn, Alistair J

    2014-08-14

    In a retrospective, population based cohort study, we examined whether constitutional delay was associated with the growth response to growth hormone (GH) in children with short stature and normal GH responses. 70 patients were treated with 21 GH iu/m2/week from 1975 to 2013 throughout New Zealand. Demographic and auxological data were prospectively collected and standard deviation scores (SDS) were calculated for height (HtSDS), yearly growth velocity (GV-SDS), body mass index (BMI-SDS) and predicted adult height (PAH-SDS) at time of the last available bone age. In the first year, GH was associated with marked increase in HtSDS (+0.46 (0.19, 0.76), p < 0.001) and GV-SDS (from -1.9 (-3.6, -0.7) to +2.7 (0.45, 4.2), p < 0.001). The increase in HtSDS but not in GV-SDS was greatest with younger patients and greater bone age delay, with no effect of sex, BMI-SDS or baseline HtSDS. PAH-SDS increased with treatment (+0.94 (0.18, 1.5)); increased PAH-SDS was associated with less bone age delay and greater initial increase in HtSDS. This study shows that greater bone age delay was associated with greater initial improvement in height but less improvement in predicted adult heights, suggesting that children with very delayed bone ages may show accelerated maturation during GH treatment.

  8. CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays.

    PubMed

    Windpassinger, Christian; Piard, Juliette; Bonnard, Carine; Alfadhel, Majid; Lim, Shuhui; Bisteau, Xavier; Blouin, Stéphane; Ali, Nur'Ain B; Ng, Alvin Yu Jin; Lu, Hao; Tohari, Sumanty; Talib, S Zakiah A; van Hul, Noémi; Caldez, Matias J; Van Maldergem, Lionel; Yigit, Gökhan; Kayserili, Hülya; Youssef, Sameh A; Coppola, Vincenzo; de Bruin, Alain; Tessarollo, Lino; Choi, Hyungwon; Rupp, Verena; Roetzer, Katharina; Roschger, Paul; Klaushofer, Klaus; Altmüller, Janine; Roy, Sudipto; Venkatesh, Byrappa; Ganger, Rudolf; Grill, Franz; Ben Chehida, Farid; Wollnik, Bernd; Altunoglu, Umut; Al Kaissi, Ali; Reversade, Bruno; Kaldis, Philipp

    2017-09-07

    In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice. Homozygous Cdk10-knockout mice died postnatally with severe growth retardation, skeletal defects, and kidney and lung abnormalities, symptoms that partly resemble the disease's effect in humans. Fibroblasts derived from affected individuals and Cdk10-knockout mouse embryonic fibroblasts (MEFs) proliferated normally; however, Cdk10-knockout MEFs developed longer cilia. Comparative transcriptomic analysis of mutant and wild-type mouse organs revealed lipid metabolic changes consistent with growth impairment and altered ciliogenesis in the absence of CDK10. Our results document the CDK10 loss-of-function phenotype and point to a function for CDK10 in transducing signals received at the primary cilia to sustain embryonic and postnatal development. Copyright © 2017 American Society of Human Genetics. All rights reserved.

  9. Brain-region–specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism

    PubMed Central

    2014-01-01

    Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon’s horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits. PMID:24612906

  10. Active surveillance for small renal masses diagnosed in elderly or comorbid patients: looking for the best treatment strategy.

    PubMed

    Brunocilla, E; Borghesi, M; Schiavina, R; Palmieri, F; Pernetti, R; Monti, C; Martorana, G

    2014-01-01

    Aim of this study is to provide our results after long-term active surveillance (AS) protocol for small renal masses (SRMs), and to report the outcomes of patients who remained in AS compared to those who underwent delayed surgical intervention. We retrospectively reviewed our database of 58 patients diagnosed with 60 contrast enhancing SRMs suspicious for renal cell carcinoma (RCC). All patients had clinical and radiological follow-up every 6 months. We evaluated the differences between patients who remained on AS and those who underwent surgical delayed intervention. The mean age was 75 years, the mean follow-up was 88.5 months. The median initial tumor size at presentation was 2.6cm, and the median estimated tumor volume was 8.7cm(3). The median linear growth rate of the cohort was 0.7cm/year, and the median volumetric growth rate was 8.8 cm(3)/year. Death for metastatic disease occurred in 2 patients (3.4%). No correlation was found between initial tumor size and size growth rate. The mean linear and volumetric growth rates of the group of patients who underwent surgery was higher than in those who remained on surveillance (1.9 vs. 0.4cm/year and 16.1 vs. 4.6 cm(3)/year, respectively; P<.001). Most of SRMs demonstrate to have an indolent course and low metastatic potential. Malignant disease could have faster linear and volumetric growth rates, thus suggesting the need for a delayed surgical intervention. In properly selected patients with low life-expectancy, AS could be a reasonable option in the management of SRMs. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  11. Fibrin glue inhibits migration of ocular surface epithelial cells

    PubMed Central

    Yeung, A M; Faraj, L A; McIntosh, O D; Dhillon, V K; Dua, H S

    2016-01-01

    Purpose Fibrin glue has been used successfully in numerous ophthalmic surgical procedures. Recently, fibrin glue has been used in limbal stem cell transplantation to reduce both operative time and to negate the need for sutures. The aim of this study was to determine the effects of fibrin glue on epithelial cell migration in vitro. Methods Corneoscleral rims were split to retain the epithelial layer, Bowman's layer, and anterior stroma. Rims were cut into eight equal-sized pieces and were placed directly on culture plates or affixed with fibrin glue. Rims were maintained in culture for 25 days and epithelial cell growth was monitored. Cells were photographed to measure area or growth and immunofluorescence staining of explants for fibrin was performed. Results Explants that were glued demonstrated significantly delayed epithelial cell growth and migration as compared with explants without glue. By day 16, all fibrin glue had dissolved and coincided with onset of cell growth from glued explants. Cell growth commenced between days 3 and 4 for control explants without glue and around days 14–16 for explants with fibrin glue. Conclusions Fibrin glue delays epithelial cell migration by acting as a physical barrier and can potentially interfere with explant-derived limbal epithelial cell migration on to the corneal surface. We propose that glue should be used to attach the conjunctival frill of the limbal explant but care should be taken to ensure that the glue does not wrap around the explant if used to secure the explant as well. Strategic use of glue, to attach the recessed conjunctiva, can be advantageous in delaying conjunctival cell migration and reducing the need for sequential sector conjunctival epitheliectomy. PMID:27367746

  12. Identifying ingredients that delay outgrowth of Listeria monocytogenes in natural, organic, and clean-label ready-to-eat meat and poultry products.

    PubMed

    McDonnell, Lindsey M; Glass, Kathleen A; Sindelar, Jeffrey J

    2013-08-01

    The objective of this study was to identify ingredients that inhibit Listeria monocytogenes in natural, organic, or clean-label ready-to-eat meat and poultry products. Fourteen ingredients were screened in uncured (no-nitrate-or-nitrite-added), traditional-cured (156 ppm of purified sodium nitrite), cultured (alternative cured, natural nitrate source, and Staphylococcus carnosus), or preconverted (alternative cured, natural nitrite source) turkey slurries. Slurries were cooked, cooled, inoculated to yield 3 log CFU/ml L. monocytogenes, stored at 4°C, and tested weekly for 4 weeks. Three antimicrobial ingredients, 1.5 % vinegar-lemon-cherry powder blend, 2.5 % buffered vinegar, and 3.0 % cultured sugar-vinegar blend, were incorporated into alternative-cured ham and uncured roast beef and deli-style turkey breast. Controls included all three meat products without antimicrobial ingredients and a traditional-cured ham with 2.8 % sodium lactate-diacetate. Cooked, sliced products were inoculated with 3 log CFU/g L. monocytogenes, vacuum packed, and stored at 4 or 7°C, for up to 12 weeks. For control products without antimicrobial agents stored at 4°C, a 2-log L. monocytogenes increase was observed at 2 weeks for ham and turkey and at 4 weeks for roast beef. Growth (>1-log increase) in the sodium lactate-diacetate was delayed until week 6. Compared with the control, the addition of either vinegar-lemon-cherry powder blend or buffered vinegar delayed L. monocytogenes growth for an additional 2 weeks, while the addition of cultured sugar-vinegar blend delayed growth for an additional 4 weeks for both ham and turkey. The greatest L. monocytogenes delay was observed in roast beef containing any of the three antimicrobial ingredients, with no growth detected through 12 weeks at 4°C for all the treatments. As expected, L. monocytogenes grew substantially faster in products stored at 7°C than at 4°C. These data suggest that antimicrobial ingredients from a natural source can enhance the safety of ready-to-eat meat and poultry products, but their efficacy is improved in products containing nitrite and with lower moisture and pH.

  13. In vivo combination of misonidazole and the chemotherapeutic agent CCNU.

    PubMed Central

    Siemann, D. W.

    1981-01-01

    The response of intramuscularly growing KHT sarcomas to the chemotherapeutic agent (1-(2-cloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) alone or simultaneously with the chemical radio-sensitizer misonidazole (MISO) was assessed using either a tumour growth-delay assay or an in vivo-in vitro tumour-excision assay. Median tumour growth delay following the combination of 20 mg/kg CCNU and either 0.5 or 1.0 mg/g MISO was 19.5 and 21.5 days, compared to 10 days for this CCNU dose alone. A similar degree of enhanced tumour response by MISO (factor of approximately 2 in tumour growth delay) was seen in RIF-1 tumours treated with 20 mg/kg CCNU plus 1.0 mg/g MISO. Clonogenic cell-survival studies with KHT sarcomas demonstrated that MISO at doses of 0.25, 0.5 or 1.0 mg/g given simultaneously with a range of CCNU doses produced dose-modifying factors (DMFs) of 1.9, 2.1 and 2.4 respectively. Normal tissue toxicity assessed by an LD50/7 assay led to DMFs of 1.2 and 1.4 for CCNU doses combined with 0.5 and 1.0 mg/g MISO. Thus in this animal tumour model the combination of CCNU and MISO appears to lead to a potential gain by a factor of approximately 1.7. PMID:7225287

  14. [Content of fluoride and magnesium in permanent teeth of children and adolescents with constitutional delay of growth and development].

    PubMed

    Bandura, Marzena; Opalko, Krystyna

    2005-01-01

    The objective of this study was to determine the content of fluorides and magnesium in permanent teeth of children and adolescents with constitutional delay of growth and development (CDGD) and to correlate the findings with susceptibility to caries. Our study group consisting of 20 patients with CDGD, aged 11 to 20 years, was compared with an age-matched control group of 20 normal subjects. Dentition status was assessed according to the average DMFs score. Acid biopsy of enamel on the labial surface of incisors was done to measure the content of calcium, magnesium, and fluorides. CDGD patients demonstrated a higher average DFs value and less permanent teeth than their normal counterparts. Microanalyses of enamel showed that the depth of the acid biopsy was similar in all subjects. The content of fluorides and magnesium in enamel was lower in patients with CDGD.

  15. Randomised control trial showed that delayed cord clamping and milking resulted in no significant differences in iron stores and physical growth parameters at one year of age.

    PubMed

    Agarwal, Shivam; Jaiswal, Vijay; Singh, Dharamveer; Jaiswal, Prateek; Garg, Amit; Upadhyay, Amit

    2016-11-01

    Placental redistribution has been shown to improve haematological outcomes in the immediate neonatal period and early infancy. This study compared the effects of delayed cord clamping (DCC) and umbilical cord milking (UCM) on haematological and growth parameters at 12 months of age. This was a follow-up study of a randomised control trial, conducted in a tertiary care paediatric centre from August 2013 to August 2014. We studied 200 apparently healthy Indian infants randomised at birth to receive DCC for 60-90 seconds or UCM. The outcome measures were iron status and physical growth parameters at 12 months. Of the 200 babies, 161 completed the follow-up and baseline characteristics were comparable in both groups. The mean haemoglobin in the DCC group (102.2 (17.2) g/L and serum ferritin 16.44 (2.77) μg/L) showed no significant differences to the UCM group (98.6 (17.1) g/L and 18.2 (2.8) μg/L) at one year. In addition, there were no significant differences in weight, height and mid-upper arm circumference in the two groups. Term-born Indian infants who had DCC at 60-90 seconds or UCM showed no significant differences in ferritin and haemoglobin levels and growth parameters at 12 months of age. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  16. A comparative study of ethylene growth response kinetics in eudicots and monocots reveals a role for gibberellin in growth inhibition and recovery.

    PubMed

    Kim, Joonyup; Wilson, Rebecca L; Case, J Brett; Binder, Brad M

    2012-11-01

    Time-lapse imaging of dark-grown Arabidopsis (Arabidopsis thaliana) hypocotyls has revealed new aspects about ethylene signaling. This study expands upon these results by examining ethylene growth response kinetics of seedlings of several plant species. Although the response kinetics varied between the eudicots studied, all had prolonged growth inhibition for as long as ethylene was present. In contrast, with continued application of ethylene, white millet (Panicum miliaceum) seedlings had a rapid and transient growth inhibition response, rice (Oryza sativa 'Nipponbare') seedlings had a slow onset of growth stimulation, and barley (Hordeum vulgare) had a transient growth inhibition response followed, after a delay, by a prolonged inhibition response. Growth stimulation in rice correlated with a decrease in the levels of rice ETHYLENE INSENSTIVE3-LIKE2 (OsEIL2) and an increase in rice F-BOX DOMAIN AND LRR CONTAINING PROTEIN7 transcripts. The gibberellin (GA) biosynthesis inhibitor paclobutrazol caused millet seedlings to have a prolonged growth inhibition response when ethylene was applied. A transient ethylene growth inhibition response has previously been reported for Arabidopsis ethylene insensitive3-1 (ein3-1) eil1-1 double mutants. Paclobutrazol caused these mutants to have a prolonged response to ethylene, whereas constitutive GA signaling in this background eliminated ethylene responses. Sensitivity to paclobutrazol inversely correlated with the levels of EIN3 in Arabidopsis. Wild-type Arabidopsis seedlings treated with paclobutrazol and mutants deficient in GA levels or signaling had a delayed growth recovery after ethylene removal. It is interesting to note that ethylene caused alterations in gene expression that are predicted to increase GA levels in the ein3-1 eil1-1 seedlings. These results indicate that ethylene affects GA levels leading to modulation of ethylene growth inhibition kinetics.

  17. Urban sprawl and delayed ambulance arrival in the U.S.

    PubMed

    Trowbridge, Matthew J; Gurka, Matthew J; O'Connor, Robert E

    2009-11-01

    Minimizing emergency medical service (EMS) response time is a central objective of prehospital care, yet the potential influence of built environment features such as urban sprawl on EMS system performance is often not considered. This study measures the association between urban sprawl and EMS response time to test the hypothesis that features of sprawling development increase the probability of delayed ambulance arrival. In 2008, EMS response times for 43,424 motor-vehicle crashes were obtained from the Fatal Analysis Reporting System, a national census of crashes involving > or =1 fatality. Sprawl at each crash location was measured using a continuous county-level index previously developed by Ewing et al. The association between sprawl and the probability of a delayed ambulance arrival (> or =8 minutes) was then measured using generalized linear mixed modeling to account for correlation among crashes from the same county. Urban sprawl is significantly associated with increased EMS response time and a higher probability of delayed ambulance arrival (p=0.03). This probability increases quadratically as the severity of sprawl increases while controlling for nighttime crash occurrence, road conditions, and presence of construction. For example, in sprawling counties (e.g., Fayette County GA), the probability of a delayed ambulance arrival for daytime crashes in dry conditions without construction was 69% (95% CI=66%, 72%) compared with 31% (95% CI=28%, 35%) in counties with prominent smart-growth characteristics (e.g., Delaware County PA). Urban sprawl is significantly associated with increased EMS response time and a higher probability of delayed ambulance arrival following motor-vehicle crashes in the U.S. The results of this study suggest that promotion of community design and development that follows smart-growth principles and regulates urban sprawl may improve EMS performance and reliability.

  18. Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. III. Cis-diamminedichloroplatinum

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

    Twentyman, P.R.; Kallman, R.F.; Brown, J.M.

    1979-08-01

    Experiments have been carried out to determine the effect of different time intervals between the administration of x-irradiation (1200 rad) and cis-diamminedichloroplatinum (cis-DDP) (7 mg/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administeredmore » by the intraperitoneal route either 24, 6, or 2 h before radiation, immediately before the start of radiation, or 3, 6, or 24 h after radiation. All irradiations were carried out in unanesthetized mice. The growth delays due to the drug alone were 2, 10, and 2 days for the EMT6, RIF-1, and KHT tumors, respectively. In the RIF-1 and KHT tumors, the combined modality groups tend to show longer growth delays than predicted by the addition of the growth delays for the single agents. For the EMT6 tumor, however, the trend is in the opposite direction. There is no particular timing between irradiation and drug administration which appears to produce consistently longer or shorter growth delays from system to system.« less

  19. Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. IV. Actinomycin-d

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

    Twentyman, P.R.; Kallman, R.F.; Brown, J.M.

    1979-09-01

    Experiments have been carried out to determine the effect of different intervals between the administration of x-radiation (1200 rad) and actinomycin-D (200 ..mu..g/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle, and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2 x (for KHT) or 4 x (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administeredmore » intraperitoneally either 24, 6, or 2 hr before radiation, immediately before the start of radiation, or 3, 6, or 24 hr after radiation. All irradiations were carried out in unanesthetized mice. For a single administration at this dose level (close to the maximum tolerated dose) actinomycin-D did not produce a significant delay in the growth of any of the tumors. For the RIF-1 and KHT tumors, the growth delays produced by drug/radiation combinations generally were not significantly greater than that produced by irradiation alone. For the EMT6 tumor, great variability in the growth delays of combined modality groups seen, with mean growth delays significantly longer than predicted by the radiation alone data. No consistent dependence on timing between irradiation and drug administration was seen.« less

  20. A cross-sectional study of growth, nutritional status and body proportions in children and adolescents at a medical center specializing in the treatment of cystic fibrosis in Poland.

    PubMed

    Sands, Dorota; Umławska, Wioleta; Zielińska, Anna

    2015-03-16

    Malnutrition, delayed growth and delayed puberty are commonly seen in children with cystic fibrosis. The aim of this study was to evaluate growth, nutritional status and body proportions in children and adolescents suffering from cystic fibrosis. The evaluation was based on 19 somatic measurements and indices calculated from these measurements. Somatic development was evaluated in relation to several factors connected to the clinical picture or the course of the disease. Anthropometric data were extracted from the medical histories of 41 boys and 48 girls diagnosed and treated at the Institute of Mother and Child in Warsaw (Poland). Mean values for somatic parameters and body build indices for the children suffering from CF were compared to those for the reference group. The results revealed that growth in these children was significantly delayed in comparison to that seen in the healthy population (Z-score = -0.56, p < 0.001). Nutritional status was also adversely affected (Z-score = -0.85, p < 0.001). The children suffered more from a deficit in muscularity than in adiposity (Z-score = -0.75 and Z-score = -0.34, p < 0.01, respectively). This was especially true for boys. The children had infantile body proportions and defects in trunk and chest structure. The factors that most affected somatic development were infection by Pseudomonas aeruginosa and the time at which the disease was diagnosed. Chronic infection by P. aeruginosa and type of CFTR mutation were the factors that most affected pulmonary function parameters.

  1. Relations of Growth in Effortful Control to Family Income, Cumulative Risk, and Adjustment in Preschool-age Children

    PubMed Central

    Lengua, Liliana J.; Moran, Lyndsey; Zalewski, Maureen; Ruberry, Erika; Kiff, Cara; Thompson, Stephanie

    2014-01-01

    The study examined growth in effortful control (executive control, delay ability) in relation to income, cumulative risk (aggregate of demographic and psychosocial risk factors), and adjustment in 306 preschool-age children (50% girls, 50% boys) from families representing a range of income (29% at- or near-poverty; 28% lower-income; 25% middle-income; 18% upper-income), with 4 assessments starting at 36–40 mos. Income was directly related to levels of executive control and delay ability. Cumulative risk accounted for the effects of income on delay ability but not executive control. Higher initial executive control and slope of executive control and delay ability predicted academic readiness, whereas levels, but not growth, of executive control and delay ability predicted social competence and adjustment problems. Low income is a marker for lower effortful control, which demonstrates additive or mediating effects in the relation of income to children’s preschool adjustment. PMID:25253079

  2. Growth velocity in constitutional delay of growth and development.

    PubMed

    Butenandt, Otfrid; Kunze, Detlef

    2010-01-01

    Growth velocity was determined in 121 boys and 58 girls with constitutional delay of growth and development (CDGD) of familial origin. No data were included from patients suffering from growth hormone insufficiency (i.e. neurosecretory dysfunction for growth hormone) or any disease. From 479 values obtained in boys and 230 values obtained in girls the 25th, 50th and 75th percentiles were calculated. The mean growth velocity in children and adolescents with CDGD before the beginning of puberty was lower than the mean growth velocity of other European (British, German or Swiss) standards. Specific data of growth velocity should be used in patients with CDGD since population-based data may underestimate the normal growth velocity of these patients.

  3. Severe intrauterine growth retardation with increased mitomycin C sensitivity: a further chromosome breakage syndrome.

    PubMed Central

    Woods, C G; Leversha, M; Rogers, J G

    1995-01-01

    We report an infant with pre- and postnatal microcephaly and growth retardation, a distinctive face, and developmental delay. The initial diagnosis was of Seckel syndrome. He became pancytopenic at 16 months and died soon after. His bone marrow was of normal cellularity but had a small lymphocyte infiltration. Increased spontaneous chromosome breakage was seen in blood and fibroblasts. Mitomycin C induced chromosome damage was increased and comparable to that seen in Fanconi anaemia. Reports of similar patients are reviewed. This entity of severe intrauterine growth retardation and increased mitomycin C sensitivity is hypothesised to be a distinct chromosome breakage syndrome. Images PMID:7643362

  4. A variant microcephalic osteodysplastic slender-bone disorder with growth hormone deficiency and a pigmentary retinopathy.

    PubMed

    Maclean, K; Ambler, G; Flaherty, M; Kozlowski, K; Adès, L C

    2002-10-01

    We present the case of a 3-year-old boy with post-natal growth failure, microcephaly, developmental delay, facial dysmorphism, an evolving pigmentary retinopathy, pituitary hypoplasia, micropenis, and growth hormone (GH) deficiency. He has a microcephalic osteodysplastic slender-bone disorder with disharmonic delayed osseous maturation, most closely resembling patients with microcephalic osteodysplastic primordial dwarfism type II (MOPD II). Intrauterine growth retardation, a universal finding in the MOPD II, was absent in our patient.

  5. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

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

    Deng, Yu; Cao, Hong; Cu, Fenglong

    Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotinemore » exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes.« less

  6. Mechanics of the Delayed Fracture of Viscoelastic Bodies with Cracks: Theory and Experiment (Review)

    NASA Astrophysics Data System (ADS)

    Kaminsky, A. A.

    2014-09-01

    Theoretical and experimental studies on the deformation and delayed fracture of viscoelastic bodies due to slow subcritical crack growth are reviewed. The focus of this review is on studies of subcritical growth of cracks with well-developed fracture process zones, the conditions that lead to their critical development, and all stages of slow crack growth from initiation to the onset of catastrophic growth. Models, criteria, and methods used to study the delayed fracture of viscoelastic bodies with through and internal cracks are analyzed. Experimental studies of the fracture process zones in polymers using physical and mechanical methods as well as theoretical studies of these zones using fracture mesomechanics models that take into account the structural and rheological features of polymers are reviewed. Particular attention is given to crack growth in anisotropic media, the effect of the aging of viscoelastic materials on their delayed fracture, safe external loads that do not cause cracks to propagate, the mechanism of multiple-flaw fracture of viscoelastic bodies with several cracks and, especially, processes causing cracks to coalesce into a main crack, which may result in a break of the body. Methods and results of solving two- and three-dimensional problems of the mechanics of delayed fracture of aging and non-aging viscoelastic bodies with cracks under constant and variable external loads, wedging, and biaxial loads are given

  7. Delayed flood recession in central Yangtze floodplains can cause significant food shortages for wintering geese: results of inundation experiment.

    PubMed

    Guan, Lei; Wen, Li; Feng, Duoduo; Zhang, Hong; Lei, Guangchun

    2014-12-01

    Carex meadows are critical habitat for wintering geese in the floodplains of the middle and lower reaches of Yangtze River, China. These meadows follow a growth cycle closely tied to the seasonal hydrological fluctuation: as water levels recede in the fall, exposed mudflats provide habitat for Carex spp. growth. The seasonal growth of Carex overlaps the arrival of wintering geese and provides an important food source for the migrants. Recent alterations to the Yangtze's hydrology, however, have disrupted the synchronous relationship between water levels, Carex growth and wintering geese at Dongting Lake. In October 2012, we carried out an outdoor mesocosm experiment to investigate potential impacts of delayed water recession on the germination and growth of Carex heterolepis, the dominant Carex species at Dongting Lake, to understand how changes in hydrology might impact wintering goose habitat. Results showed that the delayed flood recession exerted significant impact on the first growth cycle of Carex growth. Prolonged inundation significantly lowered the intrinsic growth rate (P = 0.03) and maximum growth rates (P = 0.02). It also took significantly longer time to reach the peak growth rate (P = 0.04 and 0.05 for number of shoot and biomass, respectively). As a result, biomass accumulation was reduced by 45, 62 and 90 % for 10-day, 20-day and 30-day inundation treatments, respectively. These results indicate a severe risk of food shortage for wintering geese when water recession delayed. This potential risk should be taken into consideration when operating any hydrological control structures that alter the flood regimes in Dongting Lake.

  8. Testosterone treatment and arginine-induced growth hormone stimulation in male delayed puberty: effects on serum calcium, phosphate and vitamin D metabolites.

    PubMed

    Hyldstrup, L; Christiansen, C; Nielsen, M D; Transbøl, I

    1984-06-01

    Hormonal changes after arginine-induced growth hormone stimulation and subsequent testosterone treatment were examined in 5 patients classified as having male delayed puberty. All the patients responded well to growth hormone stimulation and a significant negative correlation was found between the delay in height age and the maximal growth hormone response, r = 0.80, P less than 0.05. The testosterone treatment did not alter this pattern. Changes in PTH, 25OHD, 24.25(OH)2D, and 1.25(OH)2D were examined at 24 h after the infusion. The results showed significant reductions in PTH (P less than 0.05) and 24.25 (OH)2D (P less than 0.05) and a possible increase in 1.25(OH)2D, whereas 25OHD remained unchanged. These results may support the conception of growth hormone as a common denominator of growth and bone metabolism.

  9. Divergent effects of new cyclooxygenase inhibitors on gastric ulcer healing: Shifting the angiogenic balance

    PubMed Central

    Ma, Li; del Soldato, Piero; Wallace, John L.

    2002-01-01

    Delayed gastric ulcer healing is a well recognized problem associated with the use of cyclooxygenase (COX) inhibitors. In contrast, NO-releasing COX inhibitors do not interfere with ulcer healing. These divergent effects may in part be due to differences in their effects on platelets, which are known to influence ulcer healing. Therefore, we compared the effects of a nonselective COX inhibitor (flurbiprofen), a nitric oxide-releasing COX inhibitor (HCT-1026), and a selective COX-2 inhibitor (celecoxib) on gastric ulcer healing, angiogenesis, and platelet/serum levels of vascular endothelial growth factor (VEGF) and endostatin. Gastric ulcers were induced in rats by serosal application of acetic acid. Daily treatment with the test drugs was started 3 days later and continued for 1 week. Celecoxib and flurbiprofen impaired angiogenesis and delayed ulcer healing, as well as increasing serum endostatin levels relative to those of VEGF. HCT-1026 did not delay ulcer healing nor impair angiogenesis, and also did not change the ratio of serum endostatin to VEGF. Incubation of human umbilical vein endothelial cells with serum from celecoxib- or flurbiprofen-treated rats resulted in suppressed proliferation and increased apoptosis, effects that were reversed by an antiendostatin antibody. These results demonstrate a previously unrecognized mechanism through which nonsteroidal antiinflammatory drugs can delay ulcer healing, namely, through altering the balance of anti- and proangiogenic factors in the serum. The absence of a delaying effect of HCT-1026 on ulcer healing may be related to the maintenance of a more favorable balance in serum levels of pro- and antiangiogenic growth factors. PMID:12232050

  10. Role of Diet Modulation and AMPK in Ovarian Cancer Progression and Outcome

    DTIC Science & Technology

    2014-10-01

    preventive agent in not only preventing or delaying ovarian cancer growth but also cancers. It can be the ‘ aspirin ’ for cancers...preventive agent in not only preventing or delaying ovarian cancer growth but also cancers. It can be the ‘ aspirin ’ for cancers

  11. Comparing plant and fungal gravitropism using imitational models based on reiterative computation

    NASA Astrophysics Data System (ADS)

    Moore, David; Stočkus, Alvidas

    Mathematical models which imitate plant gravitropic responses were used to compare plant and fungal gravitropism with kinetic data from the agarics Coprinus cinereus and Flammulina velutipes. Similarities were: bending depends on differential growth; growth of the organ is most intensive just behind the apex; gravitropisms exhibit a substantial time delay. Differences were: the agaric stem apex always returns to the vertical (some plant organs show stable plagiogravitropic growth); curvature compensation occurred in C. cinereus; C. cinereus stems rarely overshot or oscillated around the vertical although data for F. velutipes showed a single overshoot and oscillation. The work focused attention on the need for data on detection-level thresholds, angle-response and acceleration-response relationships in fungi, and the need for detailed observations of gravitropism kinetics in a larger number and wider range of fungi.

  12. Stability and Hopf bifurcation for a regulated logistic growth model with discrete and distributed delays

    NASA Astrophysics Data System (ADS)

    Fang, Shengle; Jiang, Minghui

    2009-12-01

    In this paper, we investigate the stability and Hopf bifurcation of a new regulated logistic growth with discrete and distributed delays. By choosing the discrete delay τ as a bifurcation parameter, we prove that the system is locally asymptotically stable in a range of the delay and Hopf bifurcation occurs as τ crosses a critical value. Furthermore, explicit algorithm for determining the direction of the Hopf bifurcation and the stability of the bifurcating periodic solutions is derived by normal form theorem and center manifold argument. Finally, an illustrative example is also given to support the theoretical results.

  13. In vitro 3D regeneration-like growth of human patient brain tissue.

    PubMed

    Tang-Schomer, M D; Wu, W B; Kaplan, D L; Bookland, M J

    2018-05-01

    In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 μm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models. Copyright © 2018 John Wiley & Sons, Ltd.

  14. Growth and development of children with congenital heart disease.

    PubMed

    Chen, Chi-Wen; Li, Chung-Yi; Wang, Jou-Kou

    2004-08-01

    Children with congenital heart disease (CHD) commonly experience delayed growth. Because growth and development are closely related, both should be considered when a child's progress is examined. This paper reports a study to evaluate and compare the growth and development of preschool children with CHD to those of normal preschool children. The heights and weights of 42 preschool children with CHD and 116 normal preschool children were compared with standard growth curves. Differences in development of personal and social skills, fine motor skills and adaptability, language, and gross motor skills were evaluated. Developmental skills were assessed using the Denver Developmental Screening Test II. A significant difference was found in both body height (P < 0.05) and weight (P < 0.05) between the two groups. More preschoolers with congenital hear disease were below the 50th percentile in height (P < 0.05) and weight (P < 0.001). Preschoolers with CHD had more suspicious interpretations than non-CHD preschoolers, specifically in the language (P < 0.01) and gross motor sections (P < 0.001). Nevertheless, there were two items in the personal-social section and one in the language section on which the children with heart disease passed in the range of 55.6-63.2%. Problems were encountered with the Denver II test because of differences in language, culture and childrearing methods between Taiwanese and Western societies. These cultural differences must be considered when the test is used to assess development. Learning about the growth and developmental differences between children with CHD and normal children may help parents of the former to detect problems associated with delayed growth and development earlier. These children and their families should have the opportunity to participate in a long-term, follow-up programme that provides information and encourages developmental progress. The results could serve as a reference for those in both clinical and community workers who provide nursing care to children with CHD.

  15. Enhanced insulin sensitivity in prepubertal children with constitutional delay of growth and development.

    PubMed

    Wilson, Dyanne A; Hofman, Paul L; Miles, Harriet L; Sato, Tim A; Billett, Nathalie E; Robinson, Elizabeth M; Cutfield, Wayne S

    2010-02-01

    To test the hypothesis that prepubertal children with presumed constitutional delay of growth and development (CDGD) have enhanced insulin sensitivity and, therefore, insulin sensitivity is associated with later onset of puberty. Twenty-one prepubertal children with presumed CDGD and 23 prepubertal control children, underwent a frequently sampled intravenous glucose tolerance test to evaluate insulin sensitivity and other markers of insulin, glucose, and growth regulation. Children in the CDGD group were shorter and leaner than control subjects. Children with presumed CDGD were 40% more insulin sensitive (17.0 x 10(-4) min(-1)/[mU/L] versus 12.1 x 10(-4) min(-1)/[mU/L]; P = .0006) and had reduced acute insulin response, thus maintaining euglycemia (216 mU/L versus 330 mU/L; P = .02) compared with control subjects. In addition, the CDGD group had lower serum insulin-like growth factor binding protein 3 levels (3333 ng/mL versus 3775 ng/mL; P = .0004) and a trend toward lower serum insulin-like growth factor-II levels (794 ng/mL versus 911 ng/mL; P = .06). Prepubertal children with presumed CDGD have enhanced insulin sensitivity, supporting the hypothesis that insulin sensitivity is associated with timing of puberty. It may signify long-term biological advantages with lower risk of metabolic syndrome and malignancy. Copyright 2010 Mosby, Inc. All rights reserved.

  16. Effects of growth hormone over-expression on reproduction in the common carp Cyprinus carpio L.

    PubMed

    Cao, Mengxi; Chen, Ji; Peng, Wei; Wang, Yaping; Liao, Lanjie; Li, Yongming; Trudeau, Vance L; Zhu, Zuoyan; Hu, Wei

    2014-01-01

    To study the complex interaction between growth and reproduction we have established lines of transgenic common carp (Cyprinus carpio) carrying a grass carp (Ctenopharyngodon idellus) growth hormone (GH) transgene. The GH-transgenic fish showed delayed gonadal development compared with non-transgenic common carp. To gain a better understanding of the phenomenon, we studied body growth, gonad development, changes of reproduction related genes and hormones of GH-transgenic common carp for 2years. Over-expression of GH elevated peripheral gh transcription, serum GH levels, and inhibited endogenous GH expression in the pituitary. Hormone analyses indicated that GH-transgenic common carp had reduced pituitary and serum level of luteinizing hormone (LH). Among the tested genes, pituitary lhβ was inhibited in GH-transgenic fish. Further analyses in vitro showed that GH inhibited lhβ expression. Localization of ghr with LH indicates the possibility of direct regulation of GH on gonadotrophs. We also found that GH-transgenic common carp had reduced pituitary sensitivity to stimulation by co-treatments with a salmon gonadotropin-releasing hormone (GnRH) agonist and a dopamine antagonist. Together these results suggest that the main cause of delayed reproductive development in GH transgenic common carp is reduced LH production and release. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Delayed frost growth on jumping-drop superhydrophobic surfaces.

    PubMed

    Boreyko, Jonathan B; Collier, C Patrick

    2013-02-26

    Self-propelled jumping drops are continuously removed from a condensing superhydrophobic surface to enable a micrometric steady-state drop size. Here, we report that subcooled condensate on a chilled superhydrophobic surface are able to repeatedly jump off the surface before heterogeneous ice nucleation occurs. Frost still forms on the superhydrophobic surface due to ice nucleation at neighboring edge defects, which eventually spreads over the entire surface via an interdrop frost wave. The growth of this interdrop frost front is shown to be up to 3 times slower on the superhydrophobic surface compared to a control hydrophobic surface, due to the jumping-drop effect dynamically minimizing the average drop size and surface coverage of the condensate. A simple scaling model is developed to relate the success and speed of interdrop ice bridging to the drop size distribution. While other reports of condensation frosting on superhydrophobic surfaces have focused exclusively on liquid-solid ice nucleation for isolated drops, these findings reveal that the growth of frost is an interdrop phenomenon that is strongly coupled to the wettability and drop size distribution of the surface. A jumping-drop superhydrophobic condenser minimized frost formation relative to a conventional dropwise condenser in two respects: preventing heterogeneous ice nucleation by continuously removing subcooled condensate, and delaying frost growth by limiting the success of interdrop ice bridge formation.

  18. How Important Is Private Higher Education in Europe? A Regional Analysis in Global Context

    ERIC Educational Resources Information Center

    Levy, Daniel C.

    2012-01-01

    The importance of private higher education (PHE) is increasingly clear globally. But does Europe fit the global generalisation? This question can be assessed with reference to two major considerations: the size of PHE and the degree of private-public difference. The growth of PHE in Europe has been delayed and limited compared to that in most of…

  19. A cross-sectional study of growth, nutritional status and body proportions in children and adolescents at a medical center specializing in the treatment of cystic fibrosis in Poland

    PubMed Central

    Sands, Dorota; Zielińska, Anna

    2015-01-01

    Introduction Malnutrition, delayed growth and delayed puberty are commonly seen in children with cystic fibrosis. The aim of this study was to evaluate growth, nutritional status and body proportions in children and adolescents suffering from cystic fibrosis. Material and methods The evaluation was based on 19 somatic measurements and indices calculated from these measurements. Somatic development was evaluated in relation to several factors connected to the clinical picture or the course of the disease. Anthropometric data were extracted from the medical histories of 41 boys and 48 girls diagnosed and treated at the Institute of Mother and Child in Warsaw (Poland). Mean values for somatic parameters and body build indices for the children suffering from CF were compared to those for the reference group. Results The results revealed that growth in these children was significantly delayed in comparison to that seen in the healthy population (Z-score = –0.56, p < 0.001). Nutritional status was also adversely affected (Z-score = –0.85, p < 0.001). The children suffered more from a deficit in muscularity than in adiposity (Z-score = –0.75 and Z-score = –0.34, p < 0.01, respectively). This was especially true for boys. The children had infantile body proportions and defects in trunk and chest structure. Conclusions The factors that most affected somatic development were infection by Pseudomonas aeruginosa and the time at which the disease was diagnosed. Chronic infection by P. aeruginosa and type of CFTR mutation were the factors that most affected pulmonary function parameters. PMID:25861303

  20. Androgen therapy for delayed male puberty.

    PubMed

    Ambler, Geoffrey R

    2009-06-01

    Delayed puberty in men is a commonly presenting problem to paediatricians and an understanding of the available evidence on cause, treatments and outcomes is important to guide practice. Understanding of the regulation of the onset of puberty is gradually unfolding, although the genetic factors that dictate the timing of puberty in individuals and families remain poorly elucidated. Mutations and polymorphisms in candidate genes are being actively studied and it is likely that there is significant overlap between traditional diagnostic categories. Also, environmental endocrine disruptors may interact with the genetic regulation of puberty. Delayed puberty may not always be a benign condition, with increased risks of failing to achieve target height, adverse psychological and educational consequences, delayed sexual and psychosocial integration into society and effects on skeletal proportions and bone mass reported. Appropriate evaluation and follow-up is needed to guide clinical practice, particularly to distinguish constitutional delay in growth and puberty from that associated with other medical disease or permanent disorders. In milder cases of delayed puberty, treatment is often not required; however, considerable evidence exists for the efficacy and safety of short courses of low-dose testosterone therapy for appropriately selected individuals. This treatment is associated with high levels of patient satisfaction. There is not yet sufficient evidence for the routine use of other therapies (e.g. growth hormone, aromatase inhibitors) for constitutional delay in growth and puberty and better characterization of cause may lead to more targeted individual therapy.

  1. Mechanism of growth delay induced in Escherichia coli by near ultraviolet radiation.

    PubMed Central

    Ramabhadran, T V; Jagger, J

    1976-01-01

    Continuously growing cultures of E. coli B/r were irradiated with a fluence of broad-band near-ultraviolet radiation (315-405 nm) sufficient to cause extensive growth delay and complete cessation of net RNA synthesis. Chloramphenicol treatment was found to stimulate resumption of RNA synthesis, similar to that observed with chloramphenicol treatment after amino-acid starvation. E. coli strains in which amino-acid starvation does not result in cessation of RNA synthesis ("relaxed" or rel- strains) show no cessation of growth and only a slight effect on the rate of growth or of RNA synthesis. These findings show that such near-UV fluences do not inactivate the RNA synthetic machinery but affect the regulation of RNA synthesis, in a manner similat to that produced by amino-acid starvation. Such regulation is believed to be mediated through alterations in concentration of guanosine tetraphosphate (ppGpp), and our estimations of ppGpp after near-UV irradiation are consistent with such an interpretation. These data, combined with earlier published data, strongly suggest that the mechanism of near-UV-induced growth delay in E. coli involves partial inactivation of certain tRNA species, which is interpreted by the cell in a manner similar to that of amino-acid starvation, causing a rise in ppGpp levels, a shut-off of net RNA synthesis, and the induction of a growth delay. Images PMID:1108019

  2. Puberty is delayed in male mice with dextran sodium sulfate colitis out of proportion to changes in food intake, body weight, and serum levels of leptin.

    PubMed

    Deboer, Mark D; Li, Yongli

    2011-01-01

    In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the prepuce from the glans penis as a marker of pubertal progression. Compared with free-feeding control mice, DSS and FR mice had significantly lower weight on d 7-10 of treatment. DSS mice had later puberty than control and FR mice. DSS mice also had smaller testes, lower FSH levels, increased systemic cytokines, and increased colonic inflammation by histology. Leptin levels were similar between DSS and FR mice, whereas both had decreases in leptin compared with controls. We conclude that DSS colitis causes delayed puberty in sexually immature male mice beyond what is seen among FR mice of similar weight, food intake, and leptin levels. These experiments provide support for the hypothesis that pubertal delay in colitis is influenced by factors beyond poor weight gain alone.

  3. Effects of nisin on growth of bacteria attached to meat.

    PubMed Central

    Chung, K T; Dickson, J S; Crouse, J D

    1989-01-01

    Nisin had an inhibitory effect on gram-positive bacteria (Listeria monocytogenes, Staphylococcus aureus, and Streptococcus lactis) but did not have an inhibitory effect on gram-negative bacteria (Serratia marcescens, Salmonella typhimurium, and Pseudomonas aeruginosa) attached to meat. Nisin delayed bacterial growth on meats which were artificially inoculated with L. monocytogenes or Staphylococcus aureus for at least 1 day at room temperature. If the incubation temperature was 5 degrees C, growth of L. monocytogenes was delayed for more than 2 weeks, and growth of Staphylococcus aureus did not occur. We also found that the extractable activity of nisin decreased rapidly when the meats were incubated at ambient temperatures and that this decrease was inversely related to the observed inhibitory effect. These findings disclosed that nisin delays the growth of some gram-positive bacteria attached to meat. However, nisin alone may not be sufficient to prevent meat spoilage because of the presence of gram-negative and other nisin-resistant gram-positive bacteria. PMID:2764559

  4. Exploratory research into pathogen surface interactions.

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

    Sinclair, Michael B.; Lane, Todd W.; Jones, Howland D. T.

    2006-02-01

    In this short-duration project the research team was able to achieve growth of both drinking water biofilms and monospecific biofilms of Legionella pneurnophila. Preliminary comparative proteomic analyses were carried out on planktonic and biofilm-associated Legionella. After delay for completion of permitting and review by the director of the National Institutes for Allergy and Infectious Disease, the Utah 112 strain of Francisella novicida was obtained and preliminary culture and comparative proteomic analyses were carried out. Comprehensive literature searches and data mining were carried out on all research topics.

  5. Subcutaneous fat accumulation in early infancy is more strongly associated with motor development and delay than muscle growth.

    PubMed

    Kanazawa, H; Kawai, M; Niwa, F; Hasegawa, T; Iwanaga, K; Ohata, K; Tamaki, A; Heike, T

    2014-06-01

    Physical growth in neurologically healthy preterm infants affects motor development. This study investigated the separate relationships between muscle and fat in infancy and later motor development and physical growth. Muscle thickness and subcutaneous fat thickness of the anterior thigh were measured using ultrasound images obtained from neurologically healthy preterm infants at birth, 3, 6, 12 and 18 months' corrected age. We also obtained the Pediatric Evaluation of Disability Inventory and Alberta Infant Motor Scale scores at 18 months' corrected age to assess motor ability and motor delay. Thirty preterm infants completed the study protocol. There was a significant positive correlation between motor ability and increments in subcutaneous fat thickness during the first 3 and 6 months' corrected age (r = 0.48 and 0.40, p < 0.05, respectively), but not between motor ability and muscle thickness growth in any of the periods. A secondary, logistic regression analysis showed that increments in subcutaneous fat thickness during the first 3 months were a protective factor for motor delay. Subcutaneous fat accumulation in early infancy is more strongly associated with motor development and delay than muscle growth. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  6. Differentiation of Dictyostelium discoideum vegetative cells into spores during earth orbit in space

    NASA Astrophysics Data System (ADS)

    Takahashi, A.; Ohnishi, K.; Takahashi, S.; Masukawa, M.; Sekikawa, K.; Amano, T.; Nakano, T.; Nagaoka, S.; Ohnishi, T.

    2001-01-01

    We reported previously that emerged amoebae of Dictyosterium ( D.) discoideum grew, aggregated and differentiated to fruiting bodies with normal morphology in space. Here, we investigated the effects of space radiation and/or microgravity on the number, viability, kinetics of germination, growth rate and mutation frequency of spores formed in space in a radiation-sensitive strain, γs13, and the parental strain, NC4. In γs13, there were hardly spores in the fruiting bodies formed in space. In NC4, we found a decrease in the number of spores, a delay in germination of the spores and delayed start of cell growth of the spores formed in space when compared to the ground control. However, the mutation frequency of the NC4 spores formed in space was similar to that of the ground control. We conclude that the depression of spore formation might be induced by microgravity and/or space radiation through the depression of some stage(s) of DNA repair during cell differentiation in the slime mold.

  7. Absence of ERK5/MAPK7 delays tumorigenesis in Atm-/- mice.

    PubMed

    Granados-Jaén, Alba; Angulo-Ibáñez, Maria; Rovira-Clavé, Xavier; Gamez, Celina Paola Vasquez; Soriano, Francesc X; Reina, Manuel; Espel, Enric

    2016-11-15

    Ataxia-telangiectasia mutated (ATM) is a cell cycle checkpoint kinase that upon activation by DNA damage leads to cell cycle arrest and DNA repair or apoptosis. The absence of Atm or the occurrence of loss-of-function mutations in Atm predisposes to tumorigenesis. MAPK7 has been implicated in numerous types of cancer with pro-survival and pro-growth roles in tumor cells, but its functional relation with tumor suppressors is not clear. In this study, we show that absence of MAPK7 delays death due to spontaneous tumor development in Atm-/- mice. Compared with Atm-/- thymocytes, Mapk7-/-Atm-/- thymocytes exhibited an improved response to DNA damage (increased phosphorylation of H2AX) and a restored apoptotic response after treatment of mice with ionizing radiation. These findings define an antagonistic function of ATM and MAPK7 in the thymocyte response to DNA damage, and suggest that the lack of MAPK7 inhibits thymic lymphoma growth in Atm-/- mice by partially restoring the DNA damage response in thymocytes.

  8. BMP-2/PLGA delayed-release microspheres composite graft, selection of bone particulate diameters, and prevention of aseptic inflammation for bone tissue engineering.

    PubMed

    Ji, Ye; Xu, Gong Ping; Zhang, Zhi Peng; Xia, Jing Jun; Yan, Jing Long; Pan, Shang Ha

    2010-03-01

    Autogenous bone grafts are widely used in the repair of bone defects. Growth factors such as bone morphogenetic protein 2 (BMP-2) can induce bone regeneration and enhance bone growth. The combination of an autogenous bone graft and BMP-2 may provide a better osteogenic effect than either treatment alone, but BMP-2 is easily inactivated in body fluid. The objective of this study was to develop a technique that can better preserve the in vivo activity of BMP-2 incorporated in bone grafts. In this study, we first prepared BMP-2/poly(lactic-co-glycolic acid) (PLGA) delayed-release microspheres, and then combined collagen, the delayed-release microspheres, and rat autologous bone particulates to form four groups of composite grafts with different combinations: collagen in group A; collagen combined with bone particulates in group B; collagen combined with BMP-2/PLGA delayed-release microspheres in group C; and collagen combined with both bone particulates and BMP-2/PLGA delayed-release microspheres in group D. The four groups of composite grafts were implanted into the gluteus maximus pockets in rats. The ectopic osteogenesis and ALP level in group D (experimental group) were compared with those in groups A, B, and C (control groups) to study whether it had higher osteogenic capability. Results showed that the composite graft design increased the utility of BMP-2 and reduced the required dose of BMP-2 and volume of autologous bone. The selection of bone particulate diameter had an impact on the osteogenetic potential of bone grafts. Collagen prevented the occurrence of aseptic inflammation and improved the osteoinductivity of BMP-2. These results showed that this composite graft design is effective and feasible for use in bone repair.

  9. Sustained endocrine profiles of a girl with WAGR syndrome.

    PubMed

    Takada, Yui; Sakai, Yasunari; Matsushita, Yuki; Ohkubo, Kazuhiro; Koga, Yuhki; Akamine, Satoshi; Torio, Michiko; Ishizaki, Yoshito; Sanefuji, Masafumi; Torisu, Hiroyuki; Shaw, Chad A; Kagami, Masayo; Hara, Toshiro; Ohga, Shouichi

    2017-10-23

    Wilms tumor, aniridia, genitourinary anomalies and mental retardation (WAGR) syndrome is a rare genetic disorder caused by heterozygous deletions of WT1 and PAX6 at chromosome 11p13. Deletion of BDNF is known eto be associated with hyperphagia and obesity in both humans and animal models; however, neuroendocrine and epigenetic profiles of individuals with WAGR syndrome remain to be determined. We report a 5-year-old girl with the typical phenotype of WAGR syndrome. She showed profound delays in physical growth, motor and cognitive development without signs of obesity. Array comparative genome hybridization (CGH) revealed that she carried a 14.4 Mb deletion at 11p14.3p12, encompassing the WT1, PAX6 and BDNF genes. She experienced recurrent hypoglycemic episodes at 5 years of age. Insulin tolerance and hormonal loading tests showed normal hypothalamic responses to the hypoglycemic condition and other stimulations. Methylation analysis for freshly prepared DNA from peripheral lymphocytes using the pyro-sequencing-based system showed normal patterns of methylation at known imprinting control regions. Children with WAGR syndrome may manifest profound delay in postnatal growth through unknown mechanisms. Epigenetic factors and growth-associated genes in WAGR syndrome remain to be characterized.

  10. A diffusion-based approach to stochastic individual growth and energy budget, with consequences to life-history optimization and population dynamics.

    PubMed

    Filin, I

    2009-06-01

    Using diffusion processes, I model stochastic individual growth, given exogenous hazards and starvation risk. By maximizing survival to final size, optimal life histories (e.g. switching size for habitat/dietary shift) are determined by two ratios: mean growth rate over growth variance (diffusion coefficient) and mortality rate over mean growth rate; all are size dependent. For example, switching size decreases with either ratio, if both are positive. I provide examples and compare with previous work on risk-sensitive foraging and the energy-predation trade-off. I then decompose individual size into reversibly and irreversibly growing components, e.g. reserves and structure. I provide a general expression for optimal structural growth, when reserves grow stochastically. I conclude that increased growth variance of reserves delays structural growth (raises threshold size for its commencement) but may eventually lead to larger structures. The effect depends on whether the structural trait is related to foraging or defence. Implications for population dynamics are discussed.

  11. Growth hormone deficiency: an unusual presentation of floating harbor syndrome.

    PubMed

    Galli-Tsinopoulou, Assimina; Kyrgios, Ioannis; Emmanouilidou, Eleftheria; Maggana, Ioanna; Kotanidou, Eleni; Kokka, Paraskevi; Stylianou, Charilaos

    2011-01-01

    Floating-Harbor Syndrome (FHS) is a very rare condition of unknown etiology characterized by short stature, delayed bone age, characteristic facial features, delayed language skills and usually normal motor development. This syndrome has only once been associated with growth hormone deficiency and precocious puberty in the same patient. We describe a 5 4/12 year-old girl with the typical features of FHS in whom growth hormone deficiency was diagnosed and two years later central precocious puberty was noted. The patient showed a good response to human recombinant growth hormone as well as gonadotropin releasing hormone analogue treatment.

  12. Cold exposure inhibits hypothalamic Kiss-1 gene expression, serum leptin concentration, and delays reproductive development in male Brandt's vole ( Lasiopodomys brandtii)

    NASA Astrophysics Data System (ADS)

    Zhang, Qiang; Lin, Yi; Zhang, Xue-Ying; Wang, De-Hua

    2015-06-01

    Cold commonly affects growth and reproductive development in small mammals. Here, we test the hypothesis that low ambient temperature will affect growth and puberty onset, associated with altered hypothalamic Kiss-1 gene expression and serum leptin concentration in wild rodents. Male Brandt's voles ( Lasiopodomys brandtii) were exposed to cold (4 ± 1 °C) and warm (23 ± 1 °C) conditions from the birth and sacrificed on different developmental stages (day 26, day 40, day 60, and day 90, respectively). Brandt's voles increased the thermogenic capacity of brown adipose tissue, mobilized body fat, decreased serum leptin levels, and delayed the reproductive development especially on day 40 in the cold condition. They increased food intake to compensate for the high energy demands in the cold. The hypothalamic Kiss-1 gene expression on day 26 was decreased, associated with lower wet testis mass and testis testosterone concentration on day 40, in the cold-exposed voles compared to that in the warm. Serum leptin was positively correlated with body fat, testis mass, and testosterone concentration. These data suggested that cold exposure inhibited hypothalamic Kiss-1 gene expression during the early stage of development, decreased serum leptin concentration, and delayed reproductive development in male Brandt's voles.

  13. Watch Me Move: A Program For Parents of Young Children With Gross-Motor Delays.

    PubMed

    Natrasony, Candice; Teitelbaum, Debra

    2016-11-01

    Watch Me Move (WMM) is a 6-week parent education program for caregivers of children with gross-motor delays. The aims are to improve parent-child interaction in a gross-motor context, increase parents' knowledge of behavioral cues and gross-motor development, and decrease perceived parental stress. Forty mothers of children, 6 months to 3 years of age, with a gross-motor delay participated in a randomized control trial comparing parents who received the WMM program plus standard of care physiotherapy (n = 24) with parents whose children received standard of care physiotherapy (n = 16). Mothers who received the WMM program had significantly higher change scores on two subscales of the Nursing Child Assessment Teaching Scale (NCATS; i.e., cognitive growth fostering, and responsiveness to caregiver) and on the Parent Knowledge Questionnaire assessing knowledge of behavioral cues and gross-motor development. There were no significant group differences on the other four NCATS subscales (i.e., sensitivity to cues, response to child's distress, social emotional growth fostering, and clarity of cues) or the Parenting Stress Index. The addition of WMM to traditional physiotherapy improved aspects of mothers' ability to interact with their children and their knowledge of behavioral cues and gross-motor development.

  14. A Comparative Study of Ethylene Growth Response Kinetics in Eudicots and Monocots Reveals a Role for Gibberellin in Growth Inhibition and Recovery1[W][OA

    PubMed Central

    Kim, Joonyup; Wilson, Rebecca L.; Case, J. Brett; Binder, Brad M.

    2012-01-01

    Time-lapse imaging of dark-grown Arabidopsis (Arabidopsis thaliana) hypocotyls has revealed new aspects about ethylene signaling. This study expands upon these results by examining ethylene growth response kinetics of seedlings of several plant species. Although the response kinetics varied between the eudicots studied, all had prolonged growth inhibition for as long as ethylene was present. In contrast, with continued application of ethylene, white millet (Panicum miliaceum) seedlings had a rapid and transient growth inhibition response, rice (Oryza sativa ‘Nipponbare’) seedlings had a slow onset of growth stimulation, and barley (Hordeum vulgare) had a transient growth inhibition response followed, after a delay, by a prolonged inhibition response. Growth stimulation in rice correlated with a decrease in the levels of rice ETHYLENE INSENSTIVE3-LIKE2 (OsEIL2) and an increase in rice F-BOX DOMAIN AND LRR CONTAINING PROTEIN7 transcripts. The gibberellin (GA) biosynthesis inhibitor paclobutrazol caused millet seedlings to have a prolonged growth inhibition response when ethylene was applied. A transient ethylene growth inhibition response has previously been reported for Arabidopsis ethylene insensitive3-1 (ein3-1) eil1-1 double mutants. Paclobutrazol caused these mutants to have a prolonged response to ethylene, whereas constitutive GA signaling in this background eliminated ethylene responses. Sensitivity to paclobutrazol inversely correlated with the levels of EIN3 in Arabidopsis. Wild-type Arabidopsis seedlings treated with paclobutrazol and mutants deficient in GA levels or signaling had a delayed growth recovery after ethylene removal. It is interesting to note that ethylene caused alterations in gene expression that are predicted to increase GA levels in the ein3-1 eil1-1 seedlings. These results indicate that ethylene affects GA levels leading to modulation of ethylene growth inhibition kinetics. PMID:22977279

  15. Influence of chick hatch time and access to feed on broiler muscle development.

    PubMed

    Powell, D J; Velleman, S G; Cowieson, A J; Singh, M; Muir, W I

    2016-06-01

    The effect of hatch time and the timing of access to feed on growth rate and breast muscle development was assessed in Ross 308 broiler chickens. Chicks were removed from the incubator upon hatching, and classified as early (EH), midterm (MH), or late (LH) hatchers, based on the duration of their incubation. Feed and water were available either immediately at hatch, or 24 h after the conclusion of the hatch period. Hatchling body weight was uniform regardless of hatch time. Subsequently, bodyweight was increased in EH compared to LH birds following immediate access to feed, until 7 d in female, and 14 d in male birds. Relative breast weight was increased until 28 d in birds with immediate access to feed, and also EH and MH birds regardless of access to feed. Pectoralis major muscle morphology and expression of the myogenic regulatory factors myogenic determination factor 1 (MYOD1) and myogenin, and the proteoglycans syndecan-4, glypican-1, and decorin were measured. Myogenin and glypican-1 stimulate satellite cell (SC) differentiation. Glypican-1 expression was unaffected by treatment. A late increase in myogenin expression was observed in MH birds with delayed access to feed, and all LH birds. Syndecan-4 and MYOD1, expressed in proliferating SC, and decorin, which stimulates satellite cell proliferation and differentiation, were variably upregulated in the first wk posthatch in the same birds. These data suggest SC were activated and proliferating, but had reduced differentiation in later hatching and feed deprived birds. Conversely, EH birds with immediate access to feed had maximal myofiber width at 7 d, while fiber width was increased in birds with immediate access to feed compared to those with delayed access to feed through 40 d of age. These results demonstrate that delaying chick access to feed for 24 h upon removal from the incubator will impair muscle growth. Additionally, hatch time influences muscle development, with accelerated muscle growth in EH and MH, compared to LH birds, irrespective of access to feed. © 2016 Poultry Science Association Inc.

  16. Effects of moment of hatch and feed access on chicken development.

    PubMed

    Lamot, D M; van de Linde, I B; Molenaar, R; van der Pol, C W; Wijtten, P J A; Kemp, B; van den Brand, H

    2014-10-01

    The current study evaluated effects of hatch moment and immediate feed and water access within a 24-h hatch window on chicken growth and development. Five hundred four male chickens obtained from a 49-wk-old Ross 308 breeder flock were assigned to 72 cages based on hatching moment (early, midterm, or late; selected during periods of 475 to 481, 483 to 487, and 489 to 493 h after onset of incubation). At the end of each hatching period, chickens were moved to the grow-out facility and one-half of the chickens received feed and water ad libitum immediately. Remaining chickens received feed and water from 504 h after onset of incubation (d 0). Body weight gain and feed intake for each cage were recorded at d 0, 1, 4, 7, 11, and 18. Chickens were sampled at d 4 and 18 for organ and carcass development. Early hatchers had lower BW at placement compared with midterm and late hatchers but compensated for this afterward, resulting in a higher BW at d 4 (112.8, 107.1, and 103.3 g, respectively). From d 0 to 18, early hatchers tended to have higher BW gain than both other groups. Relative breast meat yield at d 18, expressed as percentage of carcass weight, was higher for early (30.4%) than midterm (28.5%) and late hatchers (27.8%). Up to d 7, direct feed access resulted in higher BW gain (6.1%) and feed intake (4.2%) compared with delayed feed access. No effect of moment of feed access on feed efficiency or organ weights was found. Direct feed access resulted in a higher weight:length ratio of the jejunum (12.5%) and ileum (7.5%) at d 4 compared with delayed feed access. These results suggest that early hatchers have a different developmental and growth pattern than midterm or late hatchers within a 24-h hatch window. A mild delay in feed access after hatch affects growth and development during the first week after hatch. ©2014 Poultry Science Association Inc.

  17. Early-onset scoliosis: current treatment.

    PubMed

    Cunin, V

    2015-02-01

    Early-onset scoliosis, which appears before the age of 10, can be due to congenital vertebral anomalies, neuromuscular diseases, scoliosis-associated syndromes, or idiopathic causes. It can have serious consequences for lung development and significantly reduce the life expectancy compared to adolescent scoliosis. Extended posterior fusion must be avoided to prevent the crankshaft phenomenon, uneven growth of the trunk and especially restrictive lung disease. Conservative (non-surgical) treatment is used first. If this fails, fusionless surgery can be performed to delay the final fusion procedure until the patient is older. The gold standard delaying surgical treatment is the implantation of growing rods as described by Moe and colleagues in the mid-1980s. These rods, which are lengthened during short surgical procedures at regular intervals, curb the scoliosis progression until the patient reaches an age where fusion can be performed. Knowledge of this technique and its complications has led to several mechanical improvements being made, namely use of rods that can be distracted magnetically on an outpatient basis, without the need for anesthesia. Devices based on the same principle have been designed that preferentially attach to the ribs to specifically address chest wall and spine dysplasia. The second category of surgical devices consists of rods used to guide spinal growth that do not require repeated surgical procedures. The third type of fusionless surgical treatment involves slowing the growth of the scoliosis convexity to help reduce the Cobb angle. The indications are constantly changing. Improvements in surgical techniques and greater surgeon experience may help to reduce the number of complications and make this lengthy treatment acceptable to patients and their family. Long-term effects of surgery on the Cobb angle have not been compared to those involving conservative "delaying" treatments. Because the latter has fewer complications associated with it than surgery, it should be the first-line treatment for most cases of early-onset scoliosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Effect of Compliant Walls on Secondary Instabilities in Boundary-Layer Transition

    NASA Technical Reports Server (NTRS)

    Joslin, Ronald D.; Morris, Philip J.

    1991-01-01

    For aerodynamic and hydrodynamic vehicles, it is highly desirable to reduce drag and noise levels. A reduction in drag leads to fuel savings. In particular for submersible vehicles, a decrease in noise levels inhibits detection. A suggested means to obtain these reduction goals is by delaying the transition from laminar to turbulent flow in external boundary layers. For hydrodynamic applications, a passive device which shows promise for transition delays is the compliant coating. In previous studies with a simple mechanical model representing the compliant wall, coatings were found that provided transition delays as predicted from the semi-empirical e(sup n) method. Those studies were concerned with the linear stage of transition where the instability of concern is referred to as the primary instability. For the flat-plate boundary layer, the Tollmien-Schlichting (TS) wave is the primary instability. In one of those studies, it was shown that three-dimensional (3-D) primary instabilities, or oblique waves, could dominate transition over the coatings considered. From the primary instability, the stretching and tilting of vorticity in the shear flow leads to a secondary instability mechanism. This has been theoretical described by Herbert based on Floquet theory. In the present study, Herbert's theory is used to predict the development of secondary instabilities over isotropic and non-isotropic compliant walls. Since oblique waves may be dominant over compliant walls, a secondary theory extention is made to allow for these 3-D primary instabilities. The effect of variations in primary amplitude, spanwise wavenumber, and Reynolds number on the secondary instabilities are examined. As in the rigid wall case, over compliant walls the subharmonic mode of secondary instability dominates for low-amplitude primary disturbances. Both isotropic and non-isotropic compliant walls lead to reduced secondary growth rates compared to the rigid wall results. For high frequencies, the non-isotropic wall suppresses the amplification of the secondary instabilities, while instabilities over the isotropic wall may grow with an explosive rate similar to the rigid wall results. For the more important lower frequencies, both isotropic and non-isotropic compliant walls suppress the amplification of secondary instabilities compared to the rigid wall results. The twofold major discovery and demonstration of the present investigation are: (1) the use of passive devices, such as compliant walls, can lead to significant reductions in the secondary instability growth rates and amplification; (2) suppressing the primary growth rates and subsequent amplification enable delays in the growth of the explosive secondary instability mechanism.

  19. Delayed growth in two German shepherd dog littermates with normal serum concentrations of growth hormone, thyroxine, and cortisol.

    PubMed

    Randolph, J F; Miller, C L; Cummings, J F; Lothrop, C D

    1990-01-01

    Four German Shepherd Dogs from a litter of 10 were evaluated because of postnatal onset of proportionate growth stunting that clinically resembled well-documented hypopituitary dwarfism in that breed. Although 2 pups had histologic evidence of hypopituitarism, the remaining 2 pups had normal serum growth hormone concentration and adrenocorticotropin secretory capability, and normal adrenal function test and thyroid function study results. Furthermore, the initially stunted German Shepherd Dogs grew at a steady rate until at 1 year, body weight and shoulder height approximated normal measurements. Seemingly, delayed growth in these pups may represent one end of a clinical spectrum associated with hypopituitarism in German Shepherd Dogs.

  20. Earlier growing seasons and changes in migration timing influence carbon uptake and plant production in Arctic coastal wetlands

    NASA Astrophysics Data System (ADS)

    Leffler, A. J.; Beard, K. H.; Kelsey, K.; Choi, R. T.; Welker, J. M.

    2015-12-01

    The wetlands of the Yukon-Kuskokwim Delta in western Alaska are important breeding areas for geese and are experiencing rapid climate change, specifically earlier onset of the growing season. Consequently, geese arrive 'later' in the growing season than in the past, potentially setting up a phenological mismatch with consequences for their nutrition, plant growth, and C and N processes in the ecosystem. We examined the interactive effects between the start of the growing season and Black Brant arrival time on these processes in a manipulative experiment. Advancing the growing season had a modest influence on CO2 exchange and plant growth. An early growing season shifted the rate of net ecosystem exchange (NEE) by 1-1.5 µmol m-2 s-1 toward a carbon (C) source. This change was driven by an increase in the rate of ecosystem respiration (ER). The advanced growing season nearly doubled the rate of leaf elongation in the early summer and this difference persisted as taller vegetation later in the year; belowground biomass was not affected. Timing of grazing had greater influence on CO2 exchange and plant growth. Grazing early in the season shifted the system to a carbon source by ca. 2 μmol m-2 s-1 while delaying grazing enhanced the carbon sink by 1 μmol m-2 s-1. Here, the influence was not through ER, but through reducing and enhancing standing leaf area, respectively. Early grazing also reduced season-long root production by over 50% while delayed grazing enhanced root production by 30%. Although delaying grazing enhanced C uptake and promoted plant growth in this ecosystem, leaf tissue in delayed-grazing plots had C:N of 16.7 compared to 14.2 in the typical-grazing plots, potentially reducing the digestibility of goose forage and slowing rates of decomposition. Biotic forcing in arctic tundra can thus be major drivers of ecosystem function and need to be considered as tundra system respond to changing conditions.

  1. [Effects of the extract from bergamot and boxthorn on the delay of skin aging and hair growth in mice].

    PubMed

    Shao, Lin-xiang

    2003-08-01

    To study the effects of the extract from bergamot and boxthorn on the skin and the hair growth in mice. The skin on the back of mice was shaved topically and smeared with bergamot and boxthorn extract for 42 days. Then the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) and collagen in the mice were measured. The growth of hair was also observed. Compared with control group, the extract from bergamot and boxthorn obviously increased the activity of superoxide dismutase (P < 0.05) and the content of collagen (P < 0.001), and decreased the content of malondialdehyde (P < 0.05) in the skin of mice. It also significantly promoted the growth of hair (P < 0.001). The extract from bergamot and boxthorn plays an active role in skin and the promotion of hair growth.

  2. Impact of prenatal hypoxia on fetal bone growth and osteoporosis in ovariectomized offspring rats.

    PubMed

    Yang, Yuxian; Fan, Xiaorong; Tao, Jianying; Xu, Ting; Zhang, Yingying; Zhang, Wenna; Li, Lingjun; Li, Xiang; Ding, Hongmei; Sun, Miao; Gao, Qinqin; Xu, Zhice

    2018-03-07

    Prenatal hypoxia causes intrauterine growth retardation. It is unclear whether/how hypoxia affects the bone in fetal and offspring life. This study showed that prenatal hypoxia retarded fetal skeletal growth in rats, inhibited extracellular matrix (ECM) synthesis and down-regulated of insulin-like growth factor 1 (IGF1) signaling in fetal growth plate chondrocytes in vivo and in vitro. In addition, ovariectomized (OVX) was used for study of postmenopausal osteoporosis. Compared with the control, OVX offspring in prenatal hypoxic group showed an enhanced osteoporosis in the femurs, associated with reduced proteoglycan and IGF1 signaling. The results indicated prenatal hypoxia not only delayed fetal skeletal growth, but also increased OVX-induced osteoporosis in the elder offspring probably through down-regulated IGF1 signaling and inhibition of ECM synthesis, providing important information of prenatal hypoxia on functional and molecular bone growth and metabolism in fetal and offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Delayed growth

    MedlinePlus

    Growth - slow (child 0 - 5 years); Weight gain - slow (child 0 - 5 years); Slow rate of growth; Retarded growth and development; ... A child should have regular, well-baby check-ups with a health care provider. These checkups are usually scheduled ...

  4. Understanding the dimensions of socioeconomic status that influence toddlers' health: unique impact of lack of money for basic needs in Quebec's birth cohort

    PubMed Central

    Seguin, L.; Xu, Q.; Gauvin, L.; Zunzunegui, M.; Potvin, L.; Frohlich, K.

    2005-01-01

    Study objectives: To examine the unique impact of financial difficulties as measured by a lack of money for basic needs on the occurrence of health problems between the ages of 17 and 29 months, controlling for mother's level of education and neonatal health problems. Design and participants: Analyses were performed on the 29 month data of the Quebec longitudinal study of child development. This longitudinal study followed up a birth cohort annually. Interviews were conducted in the home with the mother in 98.8% of cases. This information was supplemented with data from birth records. At 29 months, the response rate was 94.2% of the initial sample (n = 1946). The main outcome measures were mothers' report of acute health problems, asthma episodes, and hospitalisation as well as growth delay and a composite index of health problems (acute problems, asthma attack, growth delay). Main results: Children raised in a family experiencing a serious lack of money for basic needs during the preceding year were more likely to be reported by their mothers as presenting acute health problems, a growth delay, two or more health problems, and to have been hospitalised for the first time within the past few months as compared with babies living in a family not experiencing a lack of money for basic needs regardless of the mother's level of education and of neonatal health problems. Conclusion: Financial difficulties as measured by a lack of money for basic needs have a significant and unique impact on toddlers' health. PMID:15598725

  5. Childhood cognitive development after fetal growth restriction.

    PubMed

    Llurba, E; Baschat, A A; Turan, O M; Harding, J; McCowan, L M

    2013-04-01

    To examine the relationship between prenatal umbilical artery (UA) and internal carotid artery (ICA) Doppler findings and cognitive development at 3 and 6 years in low-birth-weight children. This was a study of 209 low-birth-weight (< 10(th) centile) children born after 28 gestational weeks with UA resistance index (RI) measured within 2 weeks before delivery. Children with normal UA- and ICA-RI were defined as small-for-gestational age (SGA) and those with abnormal UA or ICA Doppler findings as having fetal growth restriction (FGR). Cognitive ability at 3 and 6 years' corrected age was assessed using the fourth edition of the Stanford-Binet Intelligence Scale (SBIS) and compared between SGA and FGR groups. An SBIS score < 85 was considered to indicate delayed development. The median gestational age at diagnosis of abnormal fetal growth was 36.6 (range, 28-41) weeks. There were 87 (41.6%) children classified as having FGR and 122 (58.4%) as SGA. The mean global SBIS score at 3 years was 109.4 (SD, 22.8) and at 6 years it was 110.5 (SD, 13.9). Overall, 22 (10.5%) children had delayed development at 3 years. Total SBIS scores and individual domain scores did not differ between FGR and SGA groups at 3 or 6 years and similar proportions in each group had delayed development. Abnormal prenatal UA and ICA Doppler findings are not associated with lower developmental scores in low-birth-weight children delivered in the third trimester of pregnancy. Copyright © 2013 ISUOG. Published by John Wiley & Sons, Ltd.

  6. Understanding the dimensions of socioeconomic status that influence toddlers' health: unique impact of lack of money for basic needs in Quebec's birth cohort.

    PubMed

    Séguin, Louise; Xu, Qian; Gauvin, Lise; Zunzunegui, Maria-Victoria; Potvin, Louise; Frohlich, Katherine L

    2005-01-01

    To examine the unique impact of financial difficulties as measured by a lack of money for basic needs on the occurrence of health problems between the ages of 17 and 29 months, controlling for mother's level of education and neonatal health problems. Analyses were performed on the 29 month data of the Quebec longitudinal study of child development. This longitudinal study followed up a birth cohort annually. Interviews were conducted in the home with the mother in 98.8% of cases. This information was supplemented with data from birth records. At 29 months, the response rate was 94.2% of the initial sample (n = 1946). The main outcome measures were mothers' report of acute health problems, asthma episodes, and hospitalisation as well as growth delay and a composite index of health problems (acute problems, asthma attack, growth delay). Children raised in a family experiencing a serious lack of money for basic needs during the preceding year were more likely to be reported by their mothers as presenting acute health problems, a growth delay, two or more health problems, and to have been hospitalised for the first time within the past few months as compared with babies living in a family not experiencing a lack of money for basic needs regardless of the mother's level of education and of neonatal health problems. Financial difficulties as measured by a lack of money for basic needs have a significant and unique impact on toddlers' health.

  7. Structural and functional development of small intestine in intrauterine growth retarded porcine offspring born to gilts fed diets with differing protein ratios throughout pregnancy.

    PubMed

    Mickiewicz, M; Zabielski, R; Grenier, B; Le Normand, L; Savary, G; Holst, J J; Oswald, I P; Metges, C C; Guilloteau, P

    2012-06-01

    Protein level in the maternal diet plays a crucial role in fetal programming during pregnancy. Low or high protein level increases the risk of intrauterine growth retardation (IUGR). The aim of this study was to investigate the structural and functional development of the small intestine in piglets from sows fed a control (C, 12.1% protein), a high protein (HP, 30% protein), or a low protein (LP, 6.5% protein) diet during pregnancy. Newborns were classified as IUGR (birth weight ≤1.18 kg) and non-IUGR (birth weight >1.18 kg). The piglets were euthanized on postnatal day (PD)1, PD28 and PD188. The LP diet in non-IUGR neonates resulted in decreased body weight on PD1. The LP and HP diets resulted in both decreased body weight and delayed catch-up growth in the IUGR piglets. The HP and LP-diets increased the length of villi on PD1 in non-IUGRs but not in IUGRs. At birth, the expressions of Ki67 and active caspase 3 in mid-jejunum epithelium of HP and LP non-IUGR neonates were significantly lower as compared to C non-IUGRs whilst in IUGRs the respective expressions were as high as in C non-IUGRs. The postnatal dynamics of brush border enzyme activities and vacuolated enterocytes disappearance showed significant drop in enterocyte maturation in IUGR as compared to non-IUGR neonates. In conclusion, both HP and LP diets led to retarded development of non-IUGR piglets. In IUGR piglets both HP and LP diets resulted in delayed catch-up growth, without adaptive changes in brush border digestive enzymes.

  8. RNAi silenced Dd-grp94 (Dictyostelium discoideum glucose-regulated protein 94 kDa) cell lines in Dictyostelium exhibit marked reduction in growth rate and delay in development.

    PubMed

    Baviskar, Sandhya N; Shields, Malcolm S

    2010-01-01

    Glucose-regulated 94 kDa protein (Grp94) is a resident of the endoplasmic reticulum (ER) of multicellular eukaryotes. It is a constitutively expressed protein that is overexpressed in certain abnormal conditions of the cell such as depletion of glucose and calcium, and low oxygen and pH. The protein is also implicated in diseased conditions like cancer and Alzheimer's disease. In this study, the consequences of downregulation of Grp94 were investigated at both unicellular and multicellular stages of Dictyostelium discoideum. Previous studies have shown the expression of Dd-Grp94 (Dictyostelium discoideum glucose-regulated 94 kDa protein) in wild-type cells varies during development, and overexpression of Dd-Grp94 leads to abnormal cell shape and inhibition of development (i.e., formation of fruiting bodies). Grp94 is a known calcium binding protein and an efficient calcium buffer. Therefore, in the present study we hypothesized that downregulation of Dd-Grp94 protein would affect Dictyostelium cell structure, growth, and development. We found that Dd-grp94 RNAi recombinants exhibited reduced growth rate, cell size, and a subtle change in cell motility compared to the parental cells. The recombinants also exhibited a delay in development and small fruiting bodies. These results establish that Dd-grp94 plays a crucial role in determining normal cell structure, growth and differentiation.

  9. Turner syndrome in Albania and the efficacy of its treatment with growth hormone.

    PubMed

    Hoxha, Petrit; Babameto-Laku, Anila; Vyshka, Gentian; Gjoka, Klodiana; Minxuri, Dorina; Myrtaj, Elira; Çakërri, Luljeta

    2015-11-01

    The aim of this study was the evaluation of Turner syndrome inside the Albanian population, its clinical, cytological and genetic characteristics, the accompanying pathologies, and the efficacy of the treatment with the growth hormone. We performed a retrospective analysis of 59 patients suffering from this syndrome (aging from 5 to 23 years old). The diagnosis of female patients suffering from Turner syndrome is delayed, with a mean age at the moment of diagnosis of 13.74 years (5-23 years). The main reason for seeking medical advice was the growth retardation or a delayed puberty. Available data for 52 patients showed that the most frequent accompanying pathologies were the following: thyroid autoimmune disorders (59%), cardiovascular anomalies (43%), renal pathologies (41%), hearing impairment (4.3%) and hypertension (3.3%). Follow-up for the growth rate was possible for 52 patients out of the total of 59 patients. Twenty-five of the female patients suffering Turner syndrome and forming part of our study sample were treated with growth hormone for a period averaging 3 years and 4 months. A variety of reasons was identified as responsible for the missed treatment in 27 patients. We saw an enhanced growth (in terms of body height) within the treated subgroup, when compared with the untreated subgroup (27 patients), especially during the first 3 years of the follow-up. No side effects of this treatment were reported. Both groups of patients initiated as well a sexual hormone therapy (estrogens and progesterone) for inducing puberty at the age of 12 years. Further work is needed for an early diagnosis of this syndrome, the prompt treatment with growth hormone and the monitoring of accompanying disorders. This will ensure a better quality of life and an improvement of the longevity of patients suffering from the Turner syndrome.

  10. Sleep Problems and Early Developmental Delay: Implications for Early Intervention Programs

    ERIC Educational Resources Information Center

    Bonuck, Karen; Grant, Roy

    2012-01-01

    Sleep disorders negatively impact behavior, cognition, and growth--the same areas targeted by early intervention. Conversely, developmental delays and disabilities may themselves precipitate sleep disorders. Young children with developmental delays experience sleep disorders at a higher rate than do typically developing children; the most common…

  11. Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

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

    Kiran, Shashi; Oddi, Vineesha; Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com

    2015-02-01

    Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose ofmore » doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT7 attenuated p38/JNK activation and also p53 response. • Overall, SIRT7 promoted cellular survival in conditions of genomic stress.« less

  12. Maturation delay for the predators can enhance stable coexistence for a class of prey-predator models.

    PubMed

    Banerjee, Malay; Takeuchi, Yasuhiro

    2017-01-07

    Maturation time delay for the predators is introduced in prey-predator models to implicitly model the stage-structure of predators. Most of the prey-predator models with maturation delay are known to exhibit destabilization of coexistence steady-state. Discrete time delay induced destabilization is a common finding, however, this is due to the introduction of time delay with lack of ecological justification. The main objective of the present work is to show the stabilizing role of maturation delay for a class of delayed prey-predator model. To be specific, we consider prey-predator models with strong and weak Allee effects in prey growth and Michaelis-Menten type functional response. We provide ecological justification for the introduction of maturation delay parameter in predator's growth equation. We obtain the conditions for stable and oscillatory coexistence of prey and their specialist predator in case of strong as well as weak Allee effect for non-delayed and delayed models. Apart from the analytical results for the models under consideration, we perform extensive numerical simulations to construct the relevant bifurcation diagrams. Our analytical and supportive numerical findings reveal that delay is not always a destabilizing factor rather the stable coexistence in the presence of time delay depends upon the formulation of the delayed model. The biological implications of the current investigation are provided in the conclusion section. We also explain the validity of obtained results for other types of prey-predator models with a specialist predator. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Virulence of Pseudomonas syringae pv. tomato DC3000 Is Influenced by the Catabolite Repression Control Protein Crc.

    PubMed

    Chakravarthy, Suma; Butcher, Bronwyn G; Liu, Yingyu; D'Amico, Katherine; Coster, Matthew; Filiatrault, Melanie J

    2017-04-01

    Pseudomonas syringae infects diverse plant species and is widely used as a model system in the study of effector function and the molecular basis of plant diseases. Although the relationship between bacterial metabolism, nutrient acquisition, and virulence has attracted increasing attention in bacterial pathology, it is largely unexplored in P. syringae. The Crc (catabolite repression control) protein is a putative RNA-binding protein that regulates carbon metabolism as well as a number of other factors in the pseudomonads. Here, we show that deletion of crc increased bacterial swarming motility and biofilm formation. The crc mutant showed reduced growth and symptoms in Arabidopsis and tomato when compared with the wild-type strain. We have evidence that the crc mutant shows delayed hypersensitive response (HR) when infiltrated into Nicotiana benthamiana and tobacco. Interestingly, the crc mutant was more susceptible to hydrogen peroxide, suggesting that, in planta, the mutant may be sensitive to reactive oxygen species generated during pathogen-associated molecular pattern-triggered immunity (PTI). Indeed, HR was further delayed when PTI-induced tissues were challenged with the crc mutant. The crc mutant did not elicit an altered PTI response in plants compared with the wild-type strain. We conclude that Crc plays an important role in growth and survival during infection.

  14. Sphere-derived tumor cells exhibit impaired metastasis by a host-mediated quiescent phenotype

    PubMed Central

    Bleau, Anne-Marie; Zandueta, Carolina; Redrado, Miriam; Martínez-Canarias, Susana; Larzábal, Leyre; Montuenga, Luis M.

    2015-01-01

    The spread of lung cancer cells to distant sites represents a common event associated with poor prognosis. A fraction of tumor cells named cancer stem cells (CSCs) have the ability to overcome therapeutic stress and remain quiescent. However, whether these CSCs have also the capacity to initiate and sustain metastasis remains unclear. Here, we used tumor sphere cultures (TSC) isolated from mouse and human lung cancer models to enrich for CSCs, and assessed their metastatic potential as compared to non-CSCs. As expected, TSC overexpressed a variety of stem cell markers and displayed chemoresistance. The CSC phenotype of TSC was confirmed by their higher growth ability in soft agar and tumorigenic potential in vivo, despite their reduced in vitro cell growth kinetics. Surprisingly, the appearance of spontaneous lung metastases was strongly delayed in mice injected with TSC as compared to non-TSC cells. Similarly, this finding was confirmed in several other models of metastasis, an effect associated with a retarded colonization activity. Interestingly, such delay correlated with a quiescent phenotype whose underlined mechanisms included an increase in p27 protein and lower phospho-ERK1/2 levels. Thus, these data suggest that cells enriched for CSC properties display an impaired metastatic activity, a finding with potential clinical implications. PMID:26318423

  15. Hypopituitarism in children with cerebral palsy.

    PubMed

    Uday, Suma; Shaw, Nick; Krone, Ruth; Kirk, Jeremy

    2017-06-01

    Poor growth and delayed puberty in children with cerebral palsy is frequently felt to be related to malnutrition. Although growth hormone deficiency is commonly described in these children, multiple pituitary hormone deficiency (MPHD) has not been previously reported. We present a series of four children with cerebral palsy who were born before 29 weeks gestation who were referred to the regional endocrinology service, three for delayed puberty and one for short stature, in whom investigations identified MPHD. All patients had a height well below -2 standard deviation score (2nd centile) at presentation and three who had MRI scans had an ectopic posterior pituitary gland. We therefore recommend that the possibility of MPHD should be considered in all children with cerebral palsy and poor growth or delayed puberty. Early diagnosis and treatment is essential to maximise growth and prevent associated morbidity and mortality. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. Change or Durability? The Contribution of Metaconceptual Awareness in Preservice Early Childhood Teachers' Learning of Science Concepts

    NASA Astrophysics Data System (ADS)

    Saçkes, Mesut; Trundle, Kathy Cabe

    2017-06-01

    This longitudinal study examined the role of metaconceptual awareness in the change and the durability of preservice teachers' conceptual understandings over the course of several months. Sixteen preservice early childhood teachers participated in the study. Semi-structured interviews were conducted to reveal the participants' conceptual understandings of lunar phases (pre, post, and delayed-post) and level of metaconceptual awareness (delayed-post only). Based on the change and stability in participants' conceptual understandings from pre to post and from post to delayed-post interviews, participants' conceptual understandings were assigned into three groups that described the profile of their long-term conceptual understandings: " decay or stability", " continuous growth", and " growth and stability". The results indicated that participants in the " continuous growth" and " growth and stability" groups had significantly higher metaconceptual awareness scores than participants in the " decay or stability" group. The results provided evidence that metaconceptual awareness plays a more decisive role in the restructuring of conceptual understandings than the durability of conceptual understandings.

  17. Pathogenesis of growth failure and partial reversal with gene therapy in murine and canine Glycogen Storage Disease type Ia.

    PubMed

    Brooks, Elizabeth Drake; Little, Dianne; Arumugam, Ramamani; Sun, Baodong; Curtis, Sarah; Demaster, Amanda; Maranzano, Michael; Jackson, Mark W; Kishnani, Priya; Freemark, Michael S; Koeberl, Dwight D

    2013-06-01

    Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (-/-) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH. Expression of hepatic GH receptor and IGF 1 mRNAs and hepatic STAT5 (phospho Y694) protein levels are reduced prior to and after GH administration, indicating GH resistance. However, restoration of G6Pase expression in the liver by treatment with adeno-associated virus 8 pseudotyped vector expressing G6Pase (AAV2/8-G6Pase) corrected body weight, but failed to normalize plasma IGF 1 in G6pase (-/-) mice. Untreated G6pase (-/-) mice also demonstrated severe delay of growth plate ossification at 12 days of age; those treated with AAV2/8-G6Pase at 14 days of age demonstrated skeletal dysplasia and limb shortening when analyzed radiographically at 6 months of age, in spite of apparent metabolic correction. Moreover, gene therapy with AAV2/9-G6Pase only partially corrected growth in GSD-Ia affected dogs as detected by weight and bone measurements and serum IGF 1 concentrations were persistently low in treated dogs. We also found that heterozygous GSD-Ia carrier dogs had decreased serum IGF 1, adult body weights and bone dimensions compared to wild-type littermates. In sum, these findings suggest that growth failure in GSD-Ia results, at least in part, from hepatic GH resistance. In addition, gene therapy improved growth in addition to promoting long-term survival in dogs and mice with GSD-Ia. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Pathogenesis of growth failure and partial reversal with gene therapy in murine and canine Glycogen Storage Disease type Ia

    PubMed Central

    Brooks, Elizabeth Drake; Little, Dianne; Arumugam, Ramamani; Sun, Baodong; Curtis, Sarah; DeMaster, Amanda; Maranzano, Michael; Jackson, Mark W.; Kishnani, Priya; Freemark, Michael S.; Koeberl, Dwight D.

    2013-01-01

    Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (−/−) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH. Expression of hepatic GH receptor and IGF 1 mRNAs and hepatic STAT5 (phospho Y694) protein levels are reduced prior to and after GH administration, indicating GH resistance. However, restoration of G6Pase expression in the liver by treatment with adeno-associated virus 8 pseudotyped vector expressing G6Pase (AAV2/8-G6Pase) corrected body weight, but failed to normalize plasma IGF 1 in G6pase (−/−) mice. Untreated G6pase (−/−) mice also demonstrated severe delay of growth plate ossification at 12 days of age; those treated with AAV2/8-G6Pase at 14 days of age demonstrated skeletal dysplasia and limb shortening when analyzed radiographically at 6 months of age, in spite of apparent metabolic correction. Moreover, gene therapy with AAV2/9-G6Pase only partially corrected growth in GSD-Ia affected dogs as detected by weight and bone measurements and serum IGF 1 concentrations were persistently low in treated dogs. We also found that heterozygous GSD-Ia carrier dogs had decreased serum IGF 1, adult body weights and bone dimensions compared to wild-type littermates. In sum, these findings suggest that growth failure in GSD-Ia results, at least in part, from hepatic GH resistance. In addition, gene therapy improved growth in addition to promoting long-term survival in dogs and mice with GSD-Ia. PMID:23623482

  19. Enzyme replacement therapy for mucopolysaccharidosis VI: Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase

    PubMed Central

    Decker, Celeste; Yu, Zi-Fan; Giugliani, Roberto; Schwartz, Ida Vanessa D.; Guffon, Nathalie; Teles, Elisa Leão; Miranda, M. Clara Sá; Wraith, J. Edmond; Beck, Michael; Arash, Laila; Scarpa, Maurizio; Ketteridge, David; Hopwood, John J.; Plecko, Barbara; Steiner, Robert; Whitley, Chester B.; Kaplan, Paige; Swiedler, Stuart J.; Conrad, Susan; Harmatz, Paul

    2010-01-01

    Background and Methods Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling. Results Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16 years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96 weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60%) completed puberty. Conclusion Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation. PMID:20634905

  20. Removal of the local geomagnetic field affects reproductive growth in Arabidopsis.

    PubMed

    Xu, Chunxiao; Wei, Shufeng; Lu, Yan; Zhang, Yuxia; Chen, Chuanfang; Song, Tao

    2013-09-01

    The influence of the geomagnetic field-removed environment on Arabidopsis growth was investigated by cultivation of the plants in a near-null magnetic field and local geomagnetic field (45 µT) for the whole growth period under laboratory conditions. The biomass accumulation of plants in the near-null magnetic field was significantly suppressed at the time when plants were switching from vegetative growth to reproductive growth compared with that of plants grown in the local geomagnetic field, which was caused by a delay in the flowering of plants in the near-null magnetic field. At the early or later growth stage, no significant difference was shown in the biomass accumulation between the plants in the near-null magnetic field and local geomagnetic field. The average number of siliques and the production of seeds per plant in the near-null magnetic field was significantly lower by about 22% and 19%, respectively, than those of control plants. These resulted in a significant reduction of about 20% in the harvest index of plants in the near-null magnetic field compared with that of the controls. These results suggest that the removal of the local geomagnetic field negatively affects the reproductive growth of Arabidopsis, which thus affects the yield and harvest index. Copyright © 2013 Wiley Periodicals, Inc.

  1. Effects of delayed metamorphosis on larval survival, metamorphosis, and juvenile performance of four closely related species of tropical sea urchins (genus Echinometra).

    PubMed

    Rahman, M Aminur; Yusoff, Fatimah Md; Arshad, A; Uehara, Tsuyoshi

    2014-01-01

    We report here, the effects of extended competency on larval survival, metamorphosis, and postlarval juvenile growth of four closely related species of tropical sea urchins, Echinometra sp. A (Ea), E. mathaei (Em), Echinometra sp. C (Ec), and E. oblonga (Eo). Planktotrophic larvae of all four species fed on cultured phytoplankton (Chaetoceros gracilis) attained metamorphic competence within 22-24 days after fertilization. Competent larvae were forced to delay metamorphosis for up to 5 months by preventing them from settling in culture bottles with continuous stirring on a set of 10 rpm rotating rollers and larval survival per monthly intervals was recorded. Larval survival was highest at 24 days, when competence was attained (0 delayed period), and there were no significant differences among the four species. Larvae that had experienced a prolonged delay had reduced survival rate, metamorphosis success, and juvenile survival, but among older larvae, Em had the highest success followed by Ea, Eo, and Ec. Juveniles from larvae of all four species that metamorphosed soon after becoming competent tended to have higher growth rates (test diameter and length of spines) than juveniles from larvae that metamorphosed after a prolonged period of competence with progressively slower growth the longer the prolonged period. Despite the adverse effects of delaying metamorphosis on growth parameters, competent larvae of all four species were able to survive up to 5 months and after metamorphosis grew into 1-month-old juveniles in lab condition. Overall, delayed larvae of Em showed significantly higher larval survival, metamorphosis, and juvenile survival than Ea and Eo, while Ec showed the lowest values in these performances. Em has the most widespread distribution of these species ranging from Africa to Hawaii, while Ec probably has the most restricted distribution. Consequently, differences in distribution may be related to differences in the ability to delay metamorphosis.

  2. Effects of Delayed Metamorphosis on Larval Survival, Metamorphosis, and Juvenile Performance of Four Closely Related Species of Tropical Sea Urchins (Genus Echinometra)

    PubMed Central

    Rahman, M. Aminur; Yusoff, Fatimah Md.; Arshad, A.; Uehara, Tsuyoshi

    2014-01-01

    We report here, the effects of extended competency on larval survival, metamorphosis, and postlarval juvenile growth of four closely related species of tropical sea urchins, Echinometra sp. A (Ea), E. mathaei (Em), Echinometra sp. C (Ec), and E. oblonga (Eo). Planktotrophic larvae of all four species fed on cultured phytoplankton (Chaetoceros gracilis) attained metamorphic competence within 22–24 days after fertilization. Competent larvae were forced to delay metamorphosis for up to 5 months by preventing them from settling in culture bottles with continuous stirring on a set of 10 rpm rotating rollers and larval survival per monthly intervals was recorded. Larval survival was highest at 24 days, when competence was attained (0 delayed period), and there were no significant differences among the four species. Larvae that had experienced a prolonged delay had reduced survival rate, metamorphosis success, and juvenile survival, but among older larvae, Em had the highest success followed by Ea, Eo, and Ec. Juveniles from larvae of all four species that metamorphosed soon after becoming competent tended to have higher growth rates (test diameter and length of spines) than juveniles from larvae that metamorphosed after a prolonged period of competence with progressively slower growth the longer the prolonged period. Despite the adverse effects of delaying metamorphosis on growth parameters, competent larvae of all four species were able to survive up to 5 months and after metamorphosis grew into 1-month-old juveniles in lab condition. Overall, delayed larvae of Em showed significantly higher larval survival, metamorphosis, and juvenile survival than Ea and Eo, while Ec showed the lowest values in these performances. Em has the most widespread distribution of these species ranging from Africa to Hawaii, while Ec probably has the most restricted distribution. Consequently, differences in distribution may be related to differences in the ability to delay metamorphosis. PMID:24624048

  3. Profitless delays for extinction in nonautonomous Lotka-Volterra system

    NASA Astrophysics Data System (ADS)

    Liu, Shengqiang; Chen, Lansun

    2001-12-01

    We study the delayed periodic n-species Lotka-Voterra systems where the growth rate of each species is not always positive. The sufficient conditions for the extinction that are independent of the delays are obtained. Some known results are improved and generalized. Our results suggest that under some conditions, the introduction and the variance of the time delays can be both harmless and profitless. Discussion about the effect of time delays on the extinction of the system is also advanced.

  4. Effects of additional food in a delayed predator-prey model.

    PubMed

    Sahoo, Banshidhar; Poria, Swarup

    2015-03-01

    We examine the effects of supplying additional food to predator in a gestation delay induced predator-prey system with habitat complexity. Additional food works in favor of predator growth in our model. Presence of additional food reduces the predatory attack rate to prey in the model. Supplying additional food we can control predator population. Taking time delay as bifurcation parameter the stability of the coexisting equilibrium point is analyzed. Hopf bifurcation analysis is done with respect to time delay in presence of additional food. The direction of Hopf bifurcations and the stability of bifurcated periodic solutions are determined by applying the normal form theory and the center manifold theorem. The qualitative dynamical behavior of the model is simulated using experimental parameter values. It is observed that fluctuations of the population size can be controlled either by supplying additional food suitably or by increasing the degree of habitat complexity. It is pointed out that Hopf bifurcation occurs in the system when the delay crosses some critical value. This critical value of delay strongly depends on quality and quantity of supplied additional food. Therefore, the variation of predator population significantly effects the dynamics of the model. Model results are compared with experimental results and biological implications of the analytical findings are discussed in the conclusion section. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Enhancing dendritic cell immunotherapy for melanoma using a simple mathematical model.

    PubMed

    Castillo-Montiel, E; Chimal-Eguía, J C; Tello, J Ignacio; Piñon-Zaráte, G; Herrera-Enríquez, M; Castell-Rodríguez, A E

    2015-06-09

    The immunotherapy using dendritic cells (DCs) against different varieties of cancer is an approach that has been previously explored which induces a specific immune response. This work presents a mathematical model of DCs immunotherapy for melanoma in mice based on work by Experimental Immunotherapy Laboratory of the Medicine Faculty in the Universidad Autonoma de Mexico (UNAM). The model is a five delay differential equation (DDEs) which represents a simplified view of the immunotherapy mechanisms. The mathematical model takes into account the interactions between tumor cells, dendritic cells, naive cytotoxic T lymphocytes cells (inactivated cytotoxic cells), effector cells (cytotoxic T activated cytotoxic cells) and transforming growth factor β cytokine (T G F-β). The model is validated comparing the computer simulation results with biological trial results of the immunotherapy developed by the research group of UNAM. The results of the growth of tumor cells obtained by the control immunotherapy simulation show a similar amount of tumor cell population than the biological data of the control immunotherapy. Moreover, comparing the increase of tumor cells obtained from the immunotherapy simulation and the biological data of the immunotherapy applied by the UNAM researchers obtained errors of approximately 10 %. This allowed us to use the model as a framework to test hypothetical treatments. The numerical simulations suggest that by using more doses of DCs and changing the infusion time, the tumor growth decays compared with the current immunotherapy. In addition, a local sensitivity analysis is performed; the results show that the delay in time " τ", the maximal growth rate of tumor "r" and the maximal efficiency of tumor cytotoxic cells rate "aT" are the most sensitive model parameters. By using this mathematical model it is possible to simulate the growth of the tumor cells with or without immunotherapy using the infusion protocol of the UNAM researchers, to obtain a good approximation of the biological trials data. It is worth mentioning that by manipulating the different parameters of the model the effectiveness of the immunotherapy may increase. This last suggests that different protocols could be implemented by the Immunotherapy Laboratory of UNAM in order to improve their results.

  6. Postnatal hyperoxia or DEHP exposure leads to growth restriction and delayed lung development in newborn rats.

    PubMed

    Liang, Zhong-Jie; Wu, Qiu-Ping; Chen, Bei-Tao; Lin, Zhen-Lang; Lin, Jing; Chen, Shang-Qin

    2018-02-01

    Di-(2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in many medical devices. We previously showed that maternal DEHP exposure led to restricted growth and delayed lung maturation in newborn rats. As oxygen toxicity continues to be a major risk factor for bronchopulmonary dysplasia, the aim of this study was to examine the effect of hyperoxia, DEHP or DEHP combined with hyperoxia on the growth and lung maturation of newborn rats. Newborn rats received DEHP injection, hyperoxia exposure or DEHP injection combined with hyperoxia exposure for one week or two weeks. A control group received an equal volume of vehicle and was maintained in room air. Hyperoxia and hyperoxia + DEHP exposure for one week led to growth failure in newborn rats. Pups in the hyperoxia group showed catch-up growth after being maintained in room air for an additional 7 days but this was not the case with the latter group, which continued to receive DEHP. Hyperoxia and DEHP both delayed lung development, as evidenced by decreased radial alveolar count. Quantitative RT-PCR showed that hyperoxia decreased the transcripts of VEGF, VEGFR-2 and eNOS on days 7 and 14, and DEHP exposure alone also led to decreased expression of VEGF gene in 14-day-old rat pups. Postnatal hyperoxia and/or DEHP exposure lead to growth restriction and delayed lung alveolar development. The VEGF gene expression was altered and may be involved as one of the possible molecular mechanisms. Copyright © 2017. Published by Elsevier B.V.

  7. Kangaroo mother care may help oral growth and development in premature infants.

    PubMed

    Zhang, Feng; Liu, Shoutao

    2012-08-01

    Premature infants have a shorter prenatal development period and are prone to many serious medical problems during neonatal period. This may impact the development of oral tissues, as manifested by enamel hypoplasia, palatal distortion, malocclusion, or delay in tooth eruption and maturation. Kangaroo mother care (KMC) is a standardized and protocol-based care system for premature infants, based on skin-to-skin contact between the infant and their mother. Kangaroo mother care has been demonstrated to greatly improve the nurturing of premature infants and comparatively reduce the risk factors of oral defects. We hypothesize that KMC also facilitates oral growth and development in premature infants.

  8. Cow dung extract: a medium for the growth of pseudomonads enhancing their efficiency as biofertilizer and biocontrol agent in rice.

    PubMed

    Srivastava, Rashmi; Aragno, Michel; Sharma, A K

    2010-09-01

    Some pseudomands are being utilized as biofertilizers and biopesticides because of their role in plant growth promotion and plant protection against root parasites, respectively. Two strains of Pseudomonas, P. jessenii LHRE62 and P. synxantha HHRE81, recovered from wheat rhizosphere, have shown their potential in field bioinoculation tests under rice-wheat and pulse-wheat rotation systems. Normally, pseudomonads are cultivated on synthetic media-like King's B and used for inoculation on seeds/soil drench with talcum or charcoal as carrier material. Cow dung is being used for different purposes from the ancient time and has a significant role in crop growth because of the content in humic compounds and fertilizing bioelements available in it. Here, cow dung extract was tested as a growth medium for strains LHRE62 and HHRE81, in comparison with growth in King's B medium. The log phase was delayed by 2 h as compared to growth in King's B medium. The bacterial growth yield, lower in plain cow dung extract as compared to King's B medium, was improved upon addition of different carbon substrates. Growth of rice var. Pant Dhan 4 in pot cultures was increased using liquid formulation of cow dung extract and bacteria as foliar spray, compared to their respective controls. Biocontrol efficacy of the bioagents was assessed by challenging rice crop with Rhizoctonia solani, a sheath blight pathogen. The growth promotion and biocontrol efficiencies were more pronounced in the case of mixed inocula of strains LHRE62 and HHRE81.

  9. Schedule Matters: Understanding the Relationship between Schedule Delays and Costs on Overruns

    NASA Technical Reports Server (NTRS)

    Majerowicz, Walt; Shinn, Stephen A.

    2016-01-01

    This paper examines the relationship between schedule delays and cost overruns on complex projects. It is generally accepted by many project practitioners that cost overruns are directly related to schedule delays. But what does "directly related to" actually mean? Some reasons or root causes for schedule delays and associated cost overruns are obvious, if only in hindsight. For example, unrealistic estimates, supply chain difficulties, insufficient schedule margin, technical problems, scope changes, or the occurrence of risk events can negatively impact schedule performance. Other factors driving schedule delays and cost overruns may be less obvious and more difficult to quantify. Examples of these less obvious factors include project complexity, flawed estimating assumptions, over-optimism, political factors, "black swan" events, or even poor leadership and communication. Indeed, is it even possible the schedule itself could be a source of delay and subsequent cost overrun? Through literature review, surveys of project practitioners, and the authors' own experience on NASA programs and projects, the authors will categorize and examine the various factors affecting the relationship between project schedule delays and cost growth. The authors will also propose some ideas for organizations to consider to help create an awareness of the factors which could cause or influence schedule delays and associated cost growth on complex projects.

  10. Effects of delayed mating on the reproductive biology of the vine mealybug, Planococcus ficus (Hemiptera: Pseudococcidae).

    PubMed

    Lentini, A; Mura, A; Muscas, E; Nuvoli, M T; Cocco, A

    2018-04-01

    The effect of increasing mating delay on the reproductive performance and population growth rates of the vine mealybug, Planococcus ficus (Signoret) (Hemiptera: Pseudococcidae), was investigated under laboratory conditions. Virgin females were mated at 1, 3, 5, 7, 14, 21 and 28 days after emergence and reproductive and life table parameters were estimated. The pre-oviposition period (number of days between mating and the onset of oviposition) significantly decreased in females mated within 7 days, whereas females mated at older ages showed equivalent pre-oviposition periods (7 days, as shorter delays in mating did not reduce the population growth rates.

  11. Effects of fluoride on development and growth of Rana chensinensis embryos and larvae.

    PubMed

    Chai, Lihong; Dong, Suiming; Zhao, Hongfeng; Deng, Hongzhang; Wang, Hongyuan

    2016-04-01

    The present study examined the adverse effects of fluoride exposure on embryos and larvae of Rana chensinensis. Survival, morphological abnormalities, growth and development, time to metamorphosis and size at metamorphic climax of R. chensinensis were examined. Our results showed that embryos malformation occurred in all fluoride treatments. Morphological abnormalities of embryos are characterized by axial flexures, the extrusion of fin axis, edema, and ruffled dorsal and ventral fin. Additionally, 4.1mg F(-)/L and above could significantly inhibit embryos growth and development. On day 15, total length and weight of tadpole were significantly lower in 19.6 and 42.4 mg F(-)/L treatments compared to control. However, significant reductions in total length and weight were observed only at 42.4 mg F(-)/L on day 30. Moreover, significant metamorphic delay and decrease in the size at metamorphic climax were found in larvae exposed to 42.4 mg F(-)/L. Taken together, embryos of R. chensinensis are more vulnerable to fluoride exposure than their tadpoles. Our results suggested that the presence of high concentrations fluoride might increase mortality risk and a reduction in juvenile recruitment in the field by increasing embryos malformation, delaying metamorphosis and decreasing size at metamorphosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Nucleostemin Delays Cellular Senescence and Negatively Regulates TRF1 Protein Stability▿ †

    PubMed Central

    Zhu, Qubo; Yasumoto, Hiroaki; Tsai, Robert Y. L.

    2006-01-01

    Nucleostemin (NS) encodes a nucleolar GTP-binding protein highly enriched in the stem cells and cancer cells. To determine its biological activity in vivo, we generated NS loss- and gain-of-function mouse models. The embryogenesis of homozygous NS-null (NS−/−) mice was aborted before the blastula stage. Although the growth and fertility of heterozygous NS-null (NS+/−) mice appeared normal, NS+/− mouse embryonic fibroblasts (MEFs) had fewer NS proteins, a lower population growth rate, and higher percentages of senescent cells from passage 5 (P5) to P7 than their wild-type littermates. Conversely, transgenic overexpression of NS could rescue the NS−/− embryo in a dose-dependent manner, increase the population growth rate, and reduce the senescent percentage of MEFs. Cell cycle analyses revealed increased pre-G1 percentages in the late-passage NS+/− MEF cultures compared to the wild-type cultures. We demonstrated that NS could interact with telomeric repeat-binding factor 1 (TRF1) and enhance the degradation but not the ubiquitination of the TRF1 protein, which negatively regulates telomere length and is essential for early embryogenesis. This work demonstrates the roles of NS in establishing early embryogenesis and delaying cellular senescence of MEFs and reveals a mechanism of a NS-regulated degradation of TRF1. PMID:17000763

  13. Coexisting diseases modifying each other’s presentation - lack of growth failure in Turner syndrome due to the associated pituitary gigantism.

    PubMed

    Dragović, Tamara; Đuran, Zorana; Jelić, Svetlana; Marinković, Dejan; Kiković, Saša; Kuzmić-Janković, Snežana; Hajduković, Zoran

    2016-10-01

    Turner syndrome presents with one of the most frequent chromosomal aberrations in female, typically presented with growth retardation, ovarian insufficiency, facial dysmorphism, and numerous other somatic stigmata. Gigantism is an extremely rare condition resulting from an excessive growth hormone (GH) secretion that occurs during childhood before the fusion of epiphyseal growth plates. The major clinical feature of gigantism is growth acceleration, although these patients also suffer from hypogonadism and soft tissue hypertrophy. We presented a girl with mosaic Turner syndrome, delayed puberty and normal linear growth for the sex and age, due to the simultaneous GH hypersecretion by pituitary tumor. In the presented case all the typical phenotypic stigmata related to Turner syndrome were missing. Due to excessive pituitary GH secretion during the period while the epiphyseal growth plates of the long bones are still open, characteristic stagnation in longitudinal growth has not been demonstrated. The patient presented with delayed puberty and primary amenorrhea along with a sudden appearance of clinical signs of hypersomatotropinism, which were the reasons for seeking medical help at the age of 16. Physical examination of children presenting with delayed puberty but without growth arrest must include an overall hormonal and genetic testing even in the cases when typical clinical presentations of genetic disorder are absent. To the best of our knowledge, this is the first reported case of simultaneous presence of Turner syndrome and gigantism in the literature.

  14. The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides effective tumor control in human lung cancer cells.

    PubMed

    Hirakawa, Hirokazu; Fujisawa, Hiroshi; Masaoka, Aya; Noguchi, Miho; Hirayama, Ryoichi; Takahashi, Momoko; Fujimori, Akira; Okayasu, Ryuichi

    2015-03-01

    Hsp90 inhibitors have become well-studied antitumor agents for their selective property against tumors versus normal cells. The combined treatment of Hsp90 inhibitor and conventional photon radiation also showed more effective tumor growth delay than radiation alone. However, little is known regarding the combined treatment of Hsp90 inhibitor and heavy-ion irradiation. In this study, SQ5 human lung tumor cells were used in vitro for clonogenic cell survival and in vivo for tumor growth delay measurement using a mouse xenograft model after 17-allylamino-17-demethoxygeldanamycin (17AAG) pretreatment and carbon ion irradiation. Repair of DNA double strand breaks (DSBs) was also assessed along with expressions of DSB repair-related proteins. Cell cycle analysis after the combined treatment was also performed. The combined treatment of 17AAG and carbon ions revealed a promising treatment option in both in vitro and in vivo studies. One likely cause of this effectiveness was shown to be the inhibition of homologous recombination repair by 17AAG. The more intensified G2 cell cycle delay was also associated with the combined treatment when compared with carbon ion treatment alone. Our findings indicate that the combination of Hsp90 inhibition and heavy-ion irradiation provides a new effective therapeutic alternative for treatment of solid tumors. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  15. Inhibitory effects of omega-3 fatty acids on injury-induced epidermal growth factor receptor transactivation contribute to delayed wound healing

    PubMed Central

    Turk, Harmony F.; Monk, Jennifer M.; Fan, Yang-Yi; Callaway, Evelyn S.; Weeks, Brad

    2013-01-01

    Epidermal growth factor receptor (EGFR)-mediated signaling is required for optimal intestinal wound healing. Since n-3 polyunsaturated fatty acids (PUFA), specifically docosahexaenoic acid (DHA), alter EGFR signaling and suppress downstream activation of key signaling pathways, we hypothesized that DHA would be detrimental to the process of intestinal wound healing. Using a mouse immortalized colonocyte model, DHA uniquely reduced EGFR ligand-induced receptor activation, whereas DHA and its metabolic precursor eicosapentaenoic acid (EPA) reduced wound-induced EGFR transactivation compared with control (no fatty acid or linoleic acid). Under wounding conditions, the suppression of EGFR activation was associated with a reduction in downstream activation of cytoskeletal remodeling proteins (PLCγ1, Rac1, and Cdc42). Subsequently, DHA and EPA reduced cell migration in response to wounding. Mice were fed a corn oil-, DHA-, or EPA-enriched diet prior to intestinal wounding (2.5% dextran sodium sulfate for 5 days followed by termination after 0, 3, or 6 days of recovery). Mortality was increased in EPA-fed mice and colonic histological injury scores were increased in EPA- and DHA-fed mice compared with corn oil-fed (control) mice. Although kinetics of colonic EGFR activation and downstream signaling (PLCγ1, Rac1, and Cdc42) were delayed by both n-3 PUFA, colonic repair was increased in EPA- relative to DHA-fed mice. These results indicate that, during the early response to intestinal wounding, DHA and EPA uniquely delay the activation of key wound-healing processes in the colon. This effect is mediated, at least in part, via suppression of EGFR-mediated signaling and downstream cytoskeletal remodeling. PMID:23426968

  16. Delayed Adrenarche may be an Additional Feature of Immunoglobulin Super Family Member 1 Deficiency Syndrome.

    PubMed

    Van Hulle, Severine; Craen, Margarita; Callewaert, Bert; Joustra, Sjoerd; Oostdijk, Wilma; Losekoot, Monique; Wit, Jan Maarten; Turgeon, Marc Olivier; Bernard, Daniel J; De Schepper, Jean

    2016-03-05

    Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency.

  17. Delayed Adrenarche may be an Additional Feature of Immunoglobulin Super Family Member 1 Deficiency Syndrome

    PubMed Central

    Hulle, Severine Van; Craen, Margarita; Callewaert, Bert; Joustra, Sjoerd; Oostdijk, Wilma; Losekoot, Monique; Wit, Jan Maarten; Turgeon, Marc Olivier; Bernard, Daniel J.; Schepper, Jean De

    2016-01-01

    Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency. PMID:26757742

  18. Absence of ERK5/MAPK7 delays tumorigenesis in Atm−/− mice

    PubMed Central

    Rovira-Clavé, Xavier; Gamez, Celina Paola Vasquez; Soriano, Francesc X.; Reina, Manuel; Espel, Enric

    2016-01-01

    Ataxia-telangiectasia mutated (ATM) is a cell cycle checkpoint kinase that upon activation by DNA damage leads to cell cycle arrest and DNA repair or apoptosis. The absence of Atm or the occurrence of loss-of-function mutations in Atm predisposes to tumorigenesis. MAPK7 has been implicated in numerous types of cancer with pro-survival and pro-growth roles in tumor cells, but its functional relation with tumor suppressors is not clear. In this study, we show that absence of MAPK7 delays death due to spontaneous tumor development in Atm−/− mice. Compared with Atm−/− thymocytes, Mapk7−/−Atm−/− thymocytes exhibited an improved response to DNA damage (increased phosphorylation of H2AX) and a restored apoptotic response after treatment of mice with ionizing radiation. These findings define an antagonistic function of ATM and MAPK7 in the thymocyte response to DNA damage, and suggest that the lack of MAPK7 inhibits thymic lymphoma growth in Atm−/− mice by partially restoring the DNA damage response in thymocytes. PMID:27793024

  19. Eradication failure of newly acquired Pseudomonas aeruginosa isolates in cystic fibrosis.

    PubMed

    Cohen-Cymberknoh, Malena; Gilead, Noa; Gartner, Silvia; Rovira, Sandra; Blau, Hannah; Mussaffi, Huda; Rivlin, Joseph; Gur, Michal; Shteinberg, Michal; Bentur, Lea; Livnat, Galit; Aviram, Micha; Picard, Elie; Tenenbaum, Ariel; Armoni, Shoshana; Breuer, Oded; Shoseyov, David; Kerem, Eitan

    2016-11-01

    Eradication of Pseudomonas aeruginosa (PA) is critical in cystic fibrosis (CF) patients. To determine eradication success rate of newly acquired PA and to identify characteristics associated with eradication failure. In an observational study, data from patients with newly acquired PA infection from 2007 to 2013 were collected. Clinical variables were compared in patients with and without successful eradication for ≥1year. Of 183 patients out of 740 (25%) from 7 CF Centers that had newly acquired PA, eradication succeeded in 72%. Patients with the highest risk of failure had multi-resistant PA, fewer sputum cultures taken, were older, and were diagnosed at a later age. The risk of eradication failure increased by 1.3% with each year of delayed CF diagnosis; successful eradication increased by 17% with each additional sputum culture taken. Delayed detection of PA infection leading to delayed treatment and growth of multi-resistant organisms is associated with eradication failure. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  20. Single and multiple stressor effect of road deicers and Cu on Atlantic salmon (Salmo salar) alevins from hatching till swim-up.

    PubMed

    Mahrosh, Urma; Rosseland, Bjørn Olav; Salbu, Brit; Teien, Hans-Christian

    2018-04-01

    Road salts are frequently used for deicing of roads in the Nordic countries. During snow-melt, the road run-off containing high concentrations of road salt and various metals such as Cu remobilized from sand, silt and dust may negatively influence organisms in downstream receiving water bodies. The present work focuses on the impact of road salt (NaCl) and Cu, separately and in mixtures on Atlantic salmon alevins from hatching till swim-up. The results showed that high road salt concentrations could induce a series of negative effects in alevins such as reduced growth, deformities, delayed swim-up and mortality. For alevins exposed to all tested road salt concentrations (100-1000mg/L), mortality was significantly higher compared to control. In exposure to Cu solutions (5-20μgCu/L), no effects on growth, morphology, swim-up or mortality of alevins compared to control were observed. In mixture solutions (road salt and Cu), ultrafiltration of the exposure water demonstrated that only 20%-40% of Cu was present as positively charged low molecular mass (LMM) Cu species assumed to be bioavailable. When exposed to road salt and Cu mixtures, negative effects in alevins such as reduced growth, deformities, delayed swim-up and mortality were observed. The overall results indicated that the road salt application could seriously affect sensitive life stages of Atlantic salmon, and application of road salt should be avoided during the late winter-early spring period. Copyright © 2017. Published by Elsevier B.V.

  1. Targeting the HER family with Pan-HER effectively overcomes resistance to cetuximab

    PubMed Central

    Iida, Mari; Bahrar, Harsh; Brand, Toni M; Pearson, Hannah E; Coan, John P; Orbuch, Rachel A; Flanigan, Bailey G; Swick, Adam D; Prabakaran, Prashanth; Lantto, Johan; Horak, Ivan D.; Kragh, Michael; Salgia, Ravi; Kimple, Randy J; Wheeler, Deric L

    2016-01-01

    Cetuximab, an antibody against the Epidermal Growth Factor Receptor (EGFR) has shown efficacy in treating head and neck squamous cell carcinoma (HNSCC), metastatic colorectal cancer and non-small cell lung cancer (NSCLC). Despite the clinical success of cetuximab, many patients do not respond to cetuximab. Furthermore, virtually all patients who do initially respond become refractory, highlighting both intrinsic and acquired resistance to cetuximab as significant clinical problems. To understand mechanistically how cancerous cells acquire resistance, we previously developed models of acquired resistance using the H226 NSCLC and UM-SCC1 HNSCC cell lines. Cetuximab-resistant clones showed a robust upregulation and dependency on the HER family receptors EGFR, HER2 and HER3. Here, we examined Pan-HER, a mixture of six antibodies targeting these receptors on cetuximab-resistant clones. In cells exhibiting acquired or intrinsic resistance to cetuximab, Pan-HER treatment decreased all three receptors’ protein levels and down-stream activation of AKT and MAPK. This correlated with decreased cell proliferation in cetuximab-resistant clones. To determine whether Pan-HER had a therapeutic benefit in vivo, we established de novo cetuximab-resistant mouse xenografts and treated resistant tumors with Pan-HER. This regimen resulted in a superior growth delay of cetuximab-resistant xenografts compared to mice continued on cetuximab. Furthermore, intrinsically cetuximab-resistant HNSCC patient-derived xenograft tumors treated with Pan-HER exhibited significant growth delay compared to vehicle/cetuximab controls. These results suggest that targeting HER family receptors simultaneously with Pan-HER is a promising treatment strategy for tumors displaying intrinsic or acquired resistance to cetuximab. PMID:27422810

  2. Scaling-up vaccine production: implementation aspects of a biomass growth observer and controller.

    PubMed

    Soons, Zita I T A; van den IJssel, Jan; van der Pol, Leo A; van Straten, Gerrit; van Boxtel, Anton J B

    2009-04-01

    This study considers two aspects of the implementation of a biomass growth observer and specific growth rate controller in scale-up from small- to pilot-scale bioreactors towards a feasible bulk production process for whole-cell vaccine against whooping cough. The first is the calculation of the oxygen uptake rate, the starting point for online monitoring and control of biomass growth, taking into account the dynamics in the gas-phase. Mixing effects and delays are caused by amongst others the headspace and tubing to the analyzer. These gas phase dynamics are modelled using knowledge of the system in order to reconstruct oxygen consumption. The second aspect is to evaluate performance of the monitoring and control system with the required modifications of the oxygen consumption calculation on pilot-scale. In pilot-scale fed-batch cultivation good monitoring and control performance is obtained enabling a doubled concentration of bulk vaccine compared to standard batch production.

  3. [Hepatomegaly due to glycogen storage disease and type 1 diabetes mellitus].

    PubMed

    Flotats Bastardas, M; Miserachs Barba, M; Ricart Cumeras, A; Clemente León, M; Gussinyer Canadell, M; Yeste Fernández, D; Albisu Aparicio, María A; Carrascosa Lezcano, A

    2007-08-01

    Patients with type 1 diabetes and poor metabolic control can develop hepatomegaly due to intrahepatic glycogen deposition. If these patients also have elevated liver enzymes, dyslipidemia, cushingoid features and delayed growth or sexual maturation, Mauriac syndrome can be diagnosed. This disorder is common and reversible with optimization of insulin therapy. We report three adolescents with type 1 diabetes and a long-standing history of poor glycemic control, who developed hepatomegaly, elevated liver enzymes and dyslipidemia with preserved liver function. One of these patients also had delayed growth and another had hypogonadotropic hypogonadism. Liver ultrasound showed changes suggestive of glycogenosis. In all three patients, optimization of insulin therapy achieved good glycemic control and reversed the manifestations within 2 weeks. The etiology of Mauriac syndrome is controversial since both prolonged hyperglycemia and hyperinsulinization produce glycogen accumulation in the liver. Hypercortisolism (due to ketosis or hypoglycemia) contributes to glycogen storage and also causes growth and sexual maturation delay.

  4. Collective Ion Acceleration.

    DTIC Science & Technology

    1980-01-01

    be of limiting current in larger tubes where the beamwidth is significance when bunching is important. More immediately small compared to its radius...arrangement the probe signal was directly calibrat- a) 04.04 ed in terms of the azimuthal magnetic field immediately in- 101 10, 101 10, ,e 1o side the...surface damping is increased, we find that the onset of the instability is delayed . In the absence of dissi- pation the signal growth usually occurs for

  5. Neonatal blood cultures: effect of delayed entry into the blood culture machine and bacterial concentration on the time to positive growth in a simulated model.

    PubMed

    Jardine, Luke Anthony; Sturgess, Barbara Ruth; Inglis, Garry Donald Trevor; Davies, Mark William

    2009-04-01

    To determine if: time from blood culture inoculation to positive growth (total time to positive) and time from blood culture machine entry to positive growth (machine time to positive) is altered by delayed entry into the automated blood culture machine, and if the total time to positive differs by the concentration of organisms inoculated into blood culture bottles. Staphylococcus epidermidis, Escherichia coli and group B beta-haemolytic streptococci were chosen as clinically significant representative organisms. Two concentrations (> or =10 colony-forming units per millilitre and <1 colony-forming units per millilitre) were inoculated into PEDS BacT/Alert blood culture bottles and randomly allocated to one of three delayed automated blood culture machine entry times (30 min/8.5 h/15.5 h). For all organisms at all concentrations, except the Staphylococcus epidermidis, the machine time to positive was significantly decreased by delayed entry. For all organisms at all concentrations, the mean total time to positive significantly increased with increasing delayed entry into the blood culture machine. Higher concentrations of group B beta-haemolytic streptococci and Escherichia coli grew significantly faster than lower concentrations. Bacterial growth in inoculated bottles, stored at room temperature, continues although at a slower rate than in those blood culture bottles immediately entered into the machine. If a blood culture specimen has been stored at room temperature for greater than 15.5 h, the currently allowed safety margin of 36 h (before declaring a result negative) may be insufficient.

  6. Theory-of-mind development in oral deaf children with cochlear implants or conventional hearing aids.

    PubMed

    Peterson, Candida C

    2004-09-01

    In the context of the established finding that theory-of-mind (ToM) growth is seriously delayed in late-signing deaf children, and some evidence of equivalent delays in those learning speech with conventional hearing aids, this study's novel contribution was to explore ToM development in deaf children with cochlear implants. Implants can substantially boost auditory acuity and rates of language growth. Despite the implant, there are often problems socialising with hearing peers and some language difficulties, lending special theoretical interest to the present comparative design. A total of 52 children aged 4 to 12 years took a battery of false belief tests of ToM. There were 26 oral deaf children, half with implants and half with hearing aids, evenly divided between oral-only versus sign-plus-oral schools. Comparison groups of age-matched high-functioning children with autism and younger hearing children were also included. No significant ToM differences emerged between deaf children with implants and those with hearing aids, nor between those in oral-only versus sign-plus-oral schools. Nor did the deaf children perform any better on the ToM tasks than their age peers with autism. Hearing preschoolers scored significantly higher than all other groups. For the deaf and the autistic children, as well as the preschoolers, rate of language development and verbal maturity significantly predicted variability in ToM, over and above chronological age. The finding that deaf children with cochlear implants are as delayed in ToM development as children with autism and their deaf peers with hearing aids or late sign language highlights the likely significance of peer interaction and early fluent communication with peers and family, whether in sign or in speech, in order to optimally facilitate the growth of social cognition and language.

  7. Maternal depressive symptoms are negatively associated with child growth and development: Evidence from rural India.

    PubMed

    Nguyen, Phuong Hong; Friedman, Jed; Kak, Mohini; Menon, Purnima; Alderman, Harold

    2018-05-17

    Maternal depression has been suggested as a risk factor for both poor child growth and development in many low- and middle-income countries, but the validity of many studies is hindered by small sample sizes, varying cut-offs used in depression diagnostics, and incomplete control of confounding factors. This study examines the association between maternal depressive symptoms (MDSs) and child physical growth and cognitive development in Madhya Pradesh, India, where poverty, malnutrition, and poor mental health coexist. Data were from a baseline household survey (n = 2,934) of a randomized controlled trial assessing an early childhood development programme. Multivariate linear and logistic regression analyses were conducted, adjusting for socio-economic factors to avoid confounding the association of mental health and child outcomes. MDS (measured using the Center for Epidemiologic Studies Short Depression Scale) was categorized as low, medium, and high in 47%, 42%, and 10% of mothers, respectively. The prevalence of child developmental delay ranged from 16% to 27% for various development domains. Compared with children of mothers with low MDS, those of high MDS mothers had lower height-for-age, weight-for-age, and weight-for-height z-scores (0.22, 0.21, and 0.15, respectively), a higher rate of stunting and underweight (~1.5 times), and higher rate of developmental delay (partial adjusted odds ratio ranged from 1.3-1.8 for different development domains and fully adjusted odds ratio = 1.4 for fine motor). Our results-that MDS is significantly associated with both child undernutrition and development delay-add to the call for practical interventions to address maternal depression to simultaneously address multiple outcomes for both women and children. © 2018 The Authors. Maternal & Child Nutrition Published by John Wiley & Sons, Ltd.

  8. Delayed cerebral development in twins with congenital hyperthyroidism.

    PubMed

    Kopelman, A E

    1983-09-01

    Twins had congenital hyperthyroidism and delayed cerebral development manifested as ventriculomegaly, increased space in the interhemispheric fissure, and an exaggerated gyral pattern on cranial computed tomographic scans. At 3 1/2 years of age, both children had delayed development. Fetal and neonatal hyperthyroidism may interfere with normal brain growth and maturation with both neuranatomic and developmental sequelae.

  9. Global and Regional Differences in Brain Anatomy of Young Children Born Small for Gestational Age

    PubMed Central

    De Bie, Henrica M. A.; Oostrom, Kim J.; Boersma, Maria; Veltman, Dick J.; Barkhof, Frederik

    2011-01-01

    In children who are born small for gestational age (SGA), an adverse intrauterine environment has led to underdevelopment of both the body and the brain. The delay in body growth is (partially) restored during the first two years in a majority of these children. In addition to a negative influence on these physical parameters, decreased levels of intelligence and cognitive impairments have been described in children born SGA. In this study, we used magnetic resonance imaging to examine brain anatomy in 4- to 7-year-old SGA children with and without complete bodily catch-up growth and compared them to healthy children born appropriate for gestational age. Our findings demonstrate that these children strongly differ on brain organisation when compared with healthy controls relating to both global and regional anatomical differences. Children born SGA displayed reduced cerebral and cerebellar grey and white matter volumes, smaller volumes of subcortical structures and reduced cortical surface area. Regional differences in prefrontal cortical thickness suggest a different development of the cerebral cortex. SGA children with bodily catch-up growth constitute an intermediate between those children without catch-up growth and healthy controls. Therefore, bodily catch-up growth in children born SGA does not implicate full catch-up growth of the brain. PMID:21931650

  10. What Are the Symptoms of Puberty, Precocious Puberty, and Delayed Puberty?

    MedlinePlus

    ... puberty include: Growth of pubic and other body hair Growth spurt Breast development Onset of menstruation (after puberty ... of pubic hair, other body hair, and facial hair Enlargement of testicles and penis Muscle growth Growth spurt Acne Deepening of the voice Precocious ...

  11. Fetal Tissue Procurement for Karyotype Analysis: Clinician or Pathologist - Which is Better?

    PubMed

    Conant, Joanna L; Tang, Mary E; Waters, Brenda L

    2016-01-01

    Chromosomal abnormalities are detected in up to 13% of stillbirths and over 20% of those with developmental anomalies. These estimates may be low since up to 50% of samples fail to achieve a result due to microbial overgrowth or nonviability. Tissue for cytogenetics can be procured at bedside by the clinician or by the pathologist in the laboratory. With clinical collection, tissue is placed into culture media immediately, increasing chances of growth. However, collection competes for attention with other activities, which may result in microbial overgrowth or selection of maternal rather than fetal tissue. Laboratory procurement occurs in a controlled environment using sterile technique, but delay in collection may decrease viability. Our goal was to determine which collection method yields better results. We reviewed cases from 2007-2013 that had two samples submitted for cytogenetics, one from the clinician and one from the pathologist. Specimen source, delivery, collection, and culture setup times, harvest date, cell growth, microbial overgrowth, maternal contamination and final result were obtained from medical records and cytogenetic culture sheets. There was no difference in growth rate, maternal cell contamination, or reporting time between clinician- and pathologist-procured samples despite delay in collection time for laboratory samples. Clinical samples had more microbial overgrowth. Compared to samples collected at bedside, samples collected in the laboratory had a lower rate of microbial contamination with similar growth and maternal cell contamination rates, despite prolonged time to collection. Collecting samples both at bedside and in the laboratory is unnecessary.

  12. Hormones and Human and Nonhuman Primate Growth.

    PubMed

    Bernstein, Robin Miriam

    2017-01-01

    The aim of this paper was to review information pertaining to the hormonal regulation of nonhuman primate growth, with specific focus on the growth hormone (GH)-insulin-like growth factor (IGF) axis and adrenal androgens. Hormones of the GH-IGF axis are consistently associated with measures of growth - linear, weight, or both - during the growth period; in adulthood, concentrations of IGF-I, IGF-binding protein-3, and GH-binding protein are not associated with any measures of size. Comparing patterns of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) may be especially relevant for understanding whether the childhood stage of growth and development is unique to humans and perhaps other apes. Genetic, hormonal, and morphological data on adrenarche in other nonhuman primate species suggest that this endocrine transition is delayed in humans, chimpanzees, and possibly gorillas, while present very early in postnatal life in macaques. This suggests that although perhaps permitted by an extension of the pre-adolescent growth period, childhood builds upon existing developmental substrates rather than having been inserted de novo into an ancestral growth trajectory. Hormones can provide insight regarding the evolution of the human growth trajectory. © 2017 S. Karger AG, Basel.

  13. Growth and development of very low birth weight infants aged 18-24 months at Queen Sirikit National Institute of Child Health.

    PubMed

    Sangtawesin, Varaporn; Singarj, Yupayao; Kanjanapattanakul, Wiboon

    2011-08-01

    The number of very low birth weight (VLBW) births is increasing worldwide. Despite better care in recent years, they have a high incidence of delayed growth and development. There are no previous studies regarding the growth and development of these infants at Queen Sirikit National Institute of Child Health (QSNICH). To study growth and developmental outcome of VLBW infants, aged 18-24 months who were discharged from QSNICH. VLBW infants who were discharged from QSNICH during the year 2007 were recruited in the study. Patients with chromosomal abnormalities, major congenital anomalies, definite congenital infections and positive maternal anti-HIV tests were excluded. At the corrected age of 18-24 months, the parents were called upon to bring their infants for complete physical examination and developmental evaluation on 2 occasions, two months apart. There were 111 cases of VLBW infants who were discharged from QSNICH during the year 2007. Fifty-four patients were eligible for the present study. Thirty cases (55.56%) were contacted for the first examination. During this examination, there were 3 cases (10%) with low head circumference, 1 case (3.33%) with poor weight gain, 5 cases (16.67%) with visual defect, 1 case (3.33%) with moderately severe hearing loss, 1 case (3.33%) with cerebral palsy and 7 cases (23.33%) with delayed development. Twenty-one cases could be recalled for a second evaluation. Two of the 5 cases had delayed language development. There were no cases with hydrocephalous, blindness or profound hearing loss. VLBW infants at QSNICH had much better survival during recent years. Most of these survivors had normal growth and development. Those with delayed growth and development need aggressive intervention and long-term follow-up for enhancement of quality of their lives.

  14. Carbidopa abrogates L-dopa decarboxylase coactivation of the androgen receptor and delays prostate tumor progression.

    PubMed

    Wafa, Latif A; Cheng, Helen; Plaa, Nathan; Ghaidi, Fariba; Fukumoto, Takahiro; Fazli, Ladan; Gleave, Martin E; Cox, Michael E; Rennie, Paul S

    2012-06-15

    The androgen receptor (AR) plays a central role in prostate cancer progression to the castration-resistant (CR) lethal state. L-Dopa decarboxylase (DDC) is an AR coactivator that increases in expression with disease progression and is coexpressed with the receptor in prostate adenocarcinoma cells, where it may enhance AR activity. Here, we hypothesize that the DDC enzymatic inhibitor, carbidopa, can suppress DDC-coactivation of AR and retard prostate tumor growth. Treating LNCaP prostate cancer cells with carbidopa in transcriptional assays suppressed the enhanced AR transactivation seen with DDC overexpression and decreased prostate-specific antigen (PSA) mRNA levels. Carbidopa dose-dependently inhibited cell growth and decreased survival in LNCaP cell proliferation and apoptosis assays. The inhibitory effect of carbidopa on DDC-coactivation of AR and cell growth/survival was also observed in PC3 prostate cancer cells (stably expressing AR). In vivo studies demonstrated that serum PSA velocity and tumor growth rates elevated ∼2-fold in LNCaP xenografts, inducibly overexpressing DDC, were reverted to control levels with carbidopa administration. In castrated mice, treating LNCaP tumors, expressing endogenous DDC, with carbidopa delayed progression to the CR state from 6 to 10 weeks, while serum PSA and tumor growth decreased 4.3-fold and 5.4-fold, respectively. Our study is a first time demonstration that carbidopa can abrogate DDC-coactivation of AR in prostate cancer cells and tumors, decrease serum PSA, reduce tumor growth and delay CR progression. Since carbidopa is clinically approved, it may be readily used as a novel therapeutic strategy to suppress aberrant AR activity and delay prostate cancer progression. Copyright © 2011 UICC.

  15. Positive parenting mitigates the effects of poor self-regulation on body mass index trajectories from ages 4-15 years.

    PubMed

    Connell, Lauren E; Francis, Lori A

    2014-08-01

    This study sought to determine whether parenting style moderates the effects of delay of gratification on body mass index (BMI) trajectories from ages 4-15 years. Longitudinal data were analyzed for 778 children drawn from the Study of Early Child Care and Youth Development. Parenting style (i.e., authoritative, authoritarian, permissive, and neglectful) was created from measures of mothers' sensitivity and expectations for self-control when children were age 4 years. Self-regulation was also measured at 4 years using a well-known delay of gratification protocol. BMI was calculated from measured height and weight at each time point. Mixed modeling was used to test the interaction of parenting styles and ability to delay gratification on BMI trajectories from 4-15 years. There was a significant interaction effect of parenting and ability to delay on BMI growth from 4-15 years for boys. Boys who had authoritarian mothers and failed to delay gratification had a significantly steeper rate of growth in BMI from childhood through adolescence than children in any other parenting by delay group. Authoritative and permissive parenting styles were protective against more rapid BMI gains for boys who could not delay gratification. Ability to delay gratification was protective against BMI gains for boys who had parents with authoritarian or neglectful parenting styles.

  16. Positive parenting mitigates the effects of poor self-regulation on BMI trajectories from age 4 to 15 years

    PubMed Central

    Connell, Lauren E.; Francis, Lori A.

    2014-01-01

    Objective This study sought to determine whether parenting style moderated the effects of delay of gratification on BMI trajectories from age 4 to 15 years. Methods Longitudinal data were analyzed on 778 children drawn from the Study of Early Child Care and Youth Development. Parenting style (authoritative, authoritarian, permissive, neglectful) was created from measures of mothers’ sensitivity and expectations for self-control when children were age 4 years. Self-regulation was also measured at 4 years using a well-known delay of gratification protocol. BMI was calculated from measured height and weight at each time point. Mixed modeling was used to test the interaction of parenting styles and ability to delay gratification on BMI trajectories from 4 to 15 years. Results There was a significant interaction effect of parenting and ability to delay on BMI growth from 4 to 15 years for boys. Boys who had authoritarian mothers and failed to delay gratification had a significantly steeper rate of growth in BMI from childhood through adolescence than children in any other parenting x delay group. Conclusions Authoritative and permissive parenting styles were protective against more rapid BMI gains for boys who could not delay gratification. Ability to delay gratification was protective against BMI gains for boys who had parents with authoritarian or neglectful parenting styles. PMID:23977874

  17. Epidemiology of acromegaly in Ecuador.

    PubMed

    López Gavilanez, Enrique; Guerrero Franco, Kempis; Solórzano Zambrano, Narcisa; Navarro Chávez, Manuel; López Estrella, Camilo; Vaca Burbano, Luis; Marriott Díaz, Eduardo

    2016-01-01

    To assess the epidemiology of acromegaly in the city of Guayaquil, Ecuador, and to compare our results to those reported in the literature. An analysis was made of retrospective and prospective data from all patients with acromegaly attending endocrinology clinics at the 4 main hospitals of the public health network of Guayaquil from January 2000 to December 2014. Age at diagnosis, estimated delay in diagnosis, imaging studies of pituitary gland, basal growth hormone (GH) level, GH after an oral glucose tolerance test (OGTT-GH), and serum levels of insulin-like growth factor 1 (IGF-1) were recorded. Incidence and prevalence of the disease were estimated using information from the 2010 census of population and housing. Forty-eight cases were recorded in the study period in 17 males (35.4%) and 31 females (64.5%); M/F ratio=1.8:1. Mean age at diagnosis was 47.3±16.8 years (range 18-86). Delay in diagnosis was 7.3±6.3 years (range 1-30). Mean age at diagnosis was 47.9±18.2 years in males and 46.3±15.8 years in females. Delay in diagnosis was 10.2±7.9 and 5.7±3.9 years in males and females, respectively. Prevalence of acromegaly is 18.7 cases per million inhabitants, and incidence of acromegaly 1.3 cases per million people per year. Acromegaly predominates in females, and is diagnosed in the fourth decade with a delay of approximately 8 years, usually even longer in males. Incidence and prevalence are lower than reported in international series. The disease is underdiagnosed and underreported in Ecuador. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Prediction of subacute infarct size in acute middle cerebral artery stroke: comparison of perfusion-weighted imaging and apparent diffusion coefficient maps.

    PubMed

    Drier, Aurélie; Tourdias, Thomas; Attal, Yohan; Sibon, Igor; Mutlu, Gurkan; Lehéricy, Stéphane; Samson, Yves; Chiras, Jacques; Dormont, Didier; Orgogozo, Jean-Marc; Dousset, Vincent; Rosso, Charlotte

    2012-11-01

    To compare perfusion-weighted (PW) imaging and apparent diffusion coefficient (ADC) maps in prediction of infarct size and growth in patients with acute middle cerebral artery infarct. This study was approved by the local institutional review board. Written informed consent was obtained from all 80 patients. Subsequent infarct volume and growth on follow-up magnetic resonance (MR) images obtained within 6 days were compared with the predictions based on PW images by using a time-to-peak threshold greater than 4 seconds and ADC maps obtained less than 12 hours after middle cerebral artery infarct. ADC- and PW imaging-predicted infarct growth areas and infarct volumes were correlated with subsequent infarct growth and follow-up diffusion-weighted (DW) imaging volumes. The impact of MR imaging time delay on the correlation coefficient between the predicted and subsequent infarct volumes and individual predictions of infarct growth by using receiver operating characteristic curves were assessed. The infarct volume measurements were highly reproducible (concordance correlation coefficient [CCC] of 0.965 and 95% confidence interval [CI]: 0.949, 0.976 for acute DW imaging; CCC of 0.995 and 95% CI: 0.993, 0.997 for subacute DW imaging). The subsequent infarct volume correlated (P<.0001) with ADC- (ρ=0.853) and PW imaging- (ρ=0.669) predicted volumes. The correlation was higher for ADC-predicted volume than for PW imaging-predicted volume (P<.005), but not when the analysis was restricted to patients without recanalization (P=.07). The infarct growth correlated (P<.0001) with PW imaging-DW imaging mismatch (ρ=0.470) and ADC-DW imaging mismatch (ρ=0.438), without significant differences between both methods (P=.71). The correlations were similar among time delays with ADC-predicted volumes but decreased with PW imaging-based volumes beyond the therapeutic window. Accuracies of ADC- and PW imaging-based predictions of infarct growth in an individual prediction were similar (area under the receiver operating characteristic curve [AUC] of 0.698 and 95% CI: 0.585, 0.796 vs AUC of 0.749 and 95% CI: 0.640, 0.839; P=.48). The ADC-based method was as accurate as the PW imaging-based method for evaluating infarct growth and size in the subacute phase. © RSNA, 2012

  19. Chloromethyl chlorosulfate as a voltage delay inhibitor in lithium cells

    DOEpatents

    Delnick, F.M.

    1993-04-13

    Chloromethyl chlorosulfate (CMCS) is used as a passive film growth inhibitor in electrochemical cells to minimize voltage delay and low-voltage discharge. Film growth on lithium anodes is significantly diminished when CMCS is added to SOCl[sub 2] and SO[sub 2]Cl[sub 2] electrolytes of lithium batteries. The CMCS also has the effect of extending the shelf-life of Li/SOCl[sub 2] and Li/SO[sub 2]Cl[sub 2] batteries.

  20. Chloromethyl chlorosulfate as a voltage delay inhibitor in lithium cells

    DOEpatents

    Delnick, Frank M.

    1993-01-01

    Chloromethyl chlorosulfate (CMCS) is used as a passive film growth inhibitor in electrochemical cells to minimize voltage delay and low-voltage discharge. Film growth on lithium anodes is significantly diminished when CMCS is added to SOCl.sub.2 and SO.sub.2 Cl.sub.2 electrolytes of lithium batteries. The CMCS also has the effect of extending the shelf-life of Li/SOCl.sub.2 and Li/SO.sub.2 Cl.sub.2 batteries.

  1. The Development of Coordinated Communication in Infants at Heightened Risk for Autism Spectrum Disorder

    PubMed Central

    Parladé, Meaghan V.; Iverson, Jana M.

    2015-01-01

    This study evaluated the extent to which developmental change in coordination of social communication in early infancy differentiates children eventually diagnosed with ASD from those not likely to develop the disorder. A prospective longitudinal design was used to compare 9 infants at heightened risk for ASD (HR) later diagnosed with ASD, to 13 HR infants with language delay, 28 HR infants with no diagnosis, and 30 low risk infants. Hierarchical Linear Modeling (HLM) analyses revealed that ASD infants exhibited significantly slower growth in coordinations overall and in gestures coordinated with vocalizations, even relative to HR infants with language delay. Disruption in the development of gesture-vocalization coordinations may result in negative cascading effects that negatively impact later social and linguistic development. PMID:25689930

  2. Sotos Syndrome. Clinical Exchange.

    ERIC Educational Resources Information Center

    Shuey, Elaine M.; Jamison, Kristen

    1996-01-01

    Sotos syndrome is characterized by high birth length, rapid bone growth, distinctive facial features, and possible verbal and motor delays. It is more common in males than females. Developmental deficits, specific learning problems, and speech/language delays may also occur. (DB)

  3. Influence of distributed delays on the dynamics of a generalized immune system cancerous cells interactions model

    NASA Astrophysics Data System (ADS)

    Piotrowska, M. J.; Bodnar, M.

    2018-01-01

    We present a generalisation of the mathematical models describing the interactions between the immune system and tumour cells which takes into account distributed time delays. For the analytical study we do not assume any particular form of the stimulus function describing the immune system reaction to presence of tumour cells but we only postulate its general properties. We analyse basic mathematical properties of the considered model such as existence and uniqueness of the solutions. Next, we discuss the existence of the stationary solutions and analytically investigate their stability depending on the forms of considered probability densities that is: Erlang, triangular and uniform probability densities separated or not from zero. Particular instability results are obtained for a general type of probability densities. Our results are compared with those for the model with discrete delays know from the literature. In addition, for each considered type of probability density, the model is fitted to the experimental data for the mice B-cell lymphoma showing mean square errors at the same comparable level. For estimated sets of parameters we discuss possibility of stabilisation of the tumour dormant steady state. Instability of this steady state results in uncontrolled tumour growth. In order to perform numerical simulation, following the idea of linear chain trick, we derive numerical procedures that allow us to solve systems with considered probability densities using standard algorithm for ordinary differential equations or differential equations with discrete delays.

  4. Auditory processing deficits in growth restricted fetuses affect later language development.

    PubMed

    Kisilevsky, Barbara S; Davies, Gregory A L

    2007-01-01

    An increased risk for language deficits in infants born growth restricted has been reported in follow-up studies for more than 20 years, suggesting a relation between fetal auditory system development and later language learning. Work with animal models indicate that there are at least two ways in which growth restriction could affect the development of auditory perception in human fetuses: a delay in myelination or conduction and an increase in sensorineural threshold. Systematic study of auditory function in growth restricted human fetuses has not been reported. However, results of studies employing low-risk fetuses delivering as healthy full-term infants demonstrate that, by late gestation, the fetus can hear, sound properties modulate behavior, and sensory information is available from both inside (e.g., maternal vascular) and outside (e.g., noise, voices, music) of the maternal body. These data provide substantive evidence that the auditory system is functioning and that environmental sounds are available for shaping neural networks and laying the foundation for language acquisition before birth. We hypothesize that fetal growth restriction affects auditory system development, resulting in atypical auditory information processing in growth restricted fetuses compared to healthy, appropriately-grown-for-gestational-age fetuses. Speech perception that lays the foundation for later language competence will differ in growth restricted compared to normally grown fetuses and be associated with later language abilities.

  5. Direct in situ observation of ZnO nucleation and growth via transmission X-ray microscopy

    NASA Astrophysics Data System (ADS)

    Tay, S. E. R.; Goode, A. E.; Nelson Weker, J.; Cruickshank, A. A.; Heutz, S.; Porter, A. E.; Ryan, M. P.; Toney, M. F.

    2016-01-01

    The nucleation and growth of a nanostructure controls its size and morphology, and ultimately its functional properties. Hence it is crucial to investigate growth mechanisms under relevant growth conditions at the nanometer length scale. Here we image the nucleation and growth of electrodeposited ZnO nanostructures in situ, using a transmission X-ray microscope and specially designed electrochemical cell. We show that this imaging technique leads to new insights into the nucleation and growth mechanisms in electrodeposited ZnO including direct, in situ observations of instantaneous versus delayed nucleation.The nucleation and growth of a nanostructure controls its size and morphology, and ultimately its functional properties. Hence it is crucial to investigate growth mechanisms under relevant growth conditions at the nanometer length scale. Here we image the nucleation and growth of electrodeposited ZnO nanostructures in situ, using a transmission X-ray microscope and specially designed electrochemical cell. We show that this imaging technique leads to new insights into the nucleation and growth mechanisms in electrodeposited ZnO including direct, in situ observations of instantaneous versus delayed nucleation. Electronic supplementary information (ESI) available: Methods and videos of nanoparticle growth. See DOI: 10.1039/c5nr07019h

  6. Human milk for the premature infant

    PubMed Central

    Underwood, Mark A.

    2012-01-01

    Synopsis Premature infants are a heterogeneous group with widely differing needs for nutrition and immune protection with risk of growth failure, developmental delays, necrotizing enterocolitis, and late-onset sepsis increasing with decreasing gestational age and birth weight. Human milk from women delivering prematurely has more protein and higher levels of many bioactive molecules compared to milk from women delivering at term. Human milk must be fortified for small premature infants to achieve adequate growth. Mother’s own milk improves growth and neurodevelopment and decreases the risk of necrotizing enterocolitis and late-onset sepsis and should therefore be the primary enteral diet of premature infants. Donor milk is a valuable resource for premature infants whose mothers are unable to provide an adequate supply of milk, but presents significant challenges including the need for pasteurization, nutritional and biochemical deficiencies and a limited supply. PMID:23178065

  7. A model of economic growth with physical and human capital: The role of time delays.

    PubMed

    Gori, Luca; Guerrini, Luca; Sodini, Mauro

    2016-09-01

    This article aims at analysing a two-sector economic growth model with discrete delays. The focus is on the dynamic properties of the emerging system. In particular, this study concentrates on the stability properties of the stationary solution, characterised by analytical results and geometrical techniques (stability crossing curves), and the conditions under which oscillatory dynamics emerge (through Hopf bifurcations). In addition, this article proposes some numerical simulations to illustrate the behaviour of the system when the stationary equilibrium is unstable.

  8. The Effect of Nb Micro-alloying on the Bainitic Phase Transformation Under Strip Casting Conditions

    NASA Astrophysics Data System (ADS)

    Stanford, N.; Dorin, T.; Hodgson, P. D.

    2018-04-01

    The effect of Nb concentration on the transformation from austenite to bainitic ferrite has been examined under simulated strip casting conditions. Nb concentration was found to delay the nucleation of bainite, but accelerated its growth. It is suggested that the delay in nucleation increases the driving force for transformation, which results in an increase in the growth rate of the bainite. The bainite/austenite interfaces are proposed to move too quickly to suffer appreciable solute drag.

  9. Forecasting the timing of peak mandibular growth in males by using skeletal age.

    PubMed

    Hunter, W Stuart; Baumrind, Sheldon; Popovich, Frank; Jorgensen, Gertrud

    2007-03-01

    It is generally believed that the orthodontic treatment of a patient with a Class II malocclusion and a small mandible is enhanced by good growth at puberty, so that the timing of peak mandibular growth at puberty becomes of interest. To test the belief that skeletal age, whether early, average, or late, can be used to predict the timing of maximum growth of the mandible, whether early, average, or late, the predictive relationship between skeletal age and peak mandibular growth velocity (PMdV) at puberty was evaluated in 94 boys by using their longitudinal records from 4 to 18 years of age. Skeletal age was determined for each subject at ages 9 through 14 by using the method of Greulich and Pyle. At age 9, the Greulich and Pyle measurements predicted that 30 of the 94 subjects would have delayed PMdV equal to or exceeding 1 SD (of the mean age for PMdV), and 10 would have advanced PMdV equal to or exceeding 1 SD. When the actual age of PMdV was determined retrospectively from plots of annual mandibular growth increments, it was found that only 4 of the 30 in the delayed group had actually experienced delays in PMdV, and only 2 of the 10 in the advanced group had experienced accelerated PMdV. Skeletal age is not a reliable predictor of the timing of PMdV.

  10. Gigantism and comparative life-history parameters of tyrannosaurid dinosaurs.

    PubMed

    Erickson, Gregory M; Makovicky, Peter J; Currie, Philip J; Norell, Mark A; Yerby, Scott A; Brochu, Christopher A

    2004-08-12

    How evolutionary changes in body size are brought about by variance in developmental timing and/or growth rates (also known as heterochrony) is a topic of considerable interest in evolutionary biology. In particular, extreme size change leading to gigantism occurred within the dinosaurs on multiple occasions. Whether this change was brought about by accelerated growth, delayed maturity or a combination of both processes is unknown. A better understanding of relationships between non-avian dinosaur groups and the newfound capacity to reconstruct their growth curves make it possible to address these questions quantitatively. Here we study growth patterns within the Tyrannosauridae, the best known group of large carnivorous dinosaurs, and determine the developmental means by which Tyrannosaurus rex, weighing 5,000 kg and more, grew to be one of the most enormous terrestrial carnivorous animals ever. T. rex had a maximal growth rate of 2.1 kg d(-1), reached skeletal maturity in two decades and lived for up to 28 years. T. rex's great stature was primarily attained by accelerating growth rates beyond that of its closest relatives.

  11. Causes and consequences of complex population dynamics in an annual plant, Cardamine pensylvanica

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

    Crone, E.E.

    1995-11-08

    The relative importance of density-dependent and density-independent factors in determining the population dynamics of plants has been widely debated with little resolution. In this thesis, the author explores the effects of density-dependent population regulation on population dynamics in Cardamine pensylvanica, an annual plant. In the first chapter, she shows that experimental populations of C. pensylvanica cycled from high to low density in controlled constant-environment conditions. These cycles could not be explained by external environmental changes or simple models of direct density dependence (N{sub t+1} = f[N{sub t}]), but they could be explained by delayed density dependence (N{sub t+1} = f[N{submore » t}, N{sub t+1}]). In the second chapter, she shows that the difference in the stability properties of population growth models with and without delayed density dependence is due to the presence of Hopf as well as slip bifurcations from stable to chaotic population dynamics. She also measures delayed density dependence due to effects of parental density on offspring quality in C. pensylvanica and shows that this is large enough to be the cause of the population dynamics observed in C. pensylvanica. In the third chapter, the author extends her analyses of density-dependent population growth models to include interactions between competing species. In the final chapter, she compares the effects of fixed spatial environmental variation and variation in population size on the evolutionary response of C. pensylvanica populations.« less

  12. The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo.

    PubMed

    Susanto, Johana M; Colvin, Emily K; Pinese, Mark; Chang, David K; Pajic, Marina; Mawson, Amanda; Caldon, C Elizabeth; Musgrove, Elizabeth A; Henshall, Susan M; Sutherland, Robert L; Biankin, Andrew V; Scarlett, Christopher J

    2015-05-01

    Despite incremental advances in the diagnosis and treatment for pancreatic cancer (PC), the 5‑year survival rate remains <5%. Novel therapies to increase survival and quality of life for PC patients are desperately needed. Epigenetic thera-peutic agents such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have demonstrated therapeutic benefits in human cancer. We assessed the efficacy of these epigenetic therapeutic agents as potential therapies for PC using in vitro and in vivo models. Treatment with HDACi [suberoylanilide hydroxamic acid (SAHA)] and DNMTi [5‑AZA‑2' deoxycytidine (5‑AZA‑dc)] decreased cell proliferation in MiaPaCa2 cells, and SAHA treatment, with or without 5‑AZA‑dc, resulted in higher cell death and lower DNA synthesis compared to 5‑AZA‑dc alone and controls (DMSO). Further, combination treatment with SAHA and 5‑AZA‑dc significantly increased expression of p21WAF1, leading to G1 arrest. Treatment with epigenetic agents delayed tumour growth in vivo, but did not decrease growth of established pancreatic tumours. In conclusion, these data demonstrate a potential role for epigenetic modifier drugs for the management of PC, specifically in the chemoprevention of PC, in combination with other chemotherapeutic agents.

  13. Diversity of Pubertal Development in Cartilage-Hair Hypoplasia; Two Illustrative Cases.

    PubMed

    Holopainen, Elina; Vakkilainen, Svetlana; Mäkitie, Outi

    2018-08-01

    Cartilage-hair hypoplasia (CHH) is a rare chondrodysplasia, including disproportionate short stature, hypoplastic hair, immunodeficiency, and increased risk of malignancies. Absent pubertal growth spurt and absent pubic hair complicate monitoring of pubertal development in these patients. Two CHH patients with delayed puberty and excessive growth failure are described. One of the girls had hypogonadotropic hypogonadism whereas the other had hyponormogonadotropic hypogonadism with no spontaneous pubertal development and slow response to estrogen therapy, both requiring permanent replacement therapy. Careful follow-up of pubertal development in individuals with CHH and other growth-restricting bone diseases is needed. In delayed pubertal development timely hormone therapy is essential to ensure maximal growth and well developed secondary sex characteristics. Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  14. Effect of Rocket (Eruca sativa) Extract on MRSA Growth and Proteome: Metabolic Adjustments in Plant-Based Media

    PubMed Central

    Doulgeraki, Agapi I.; Efthimiou, Georgios; Paramithiotis, Spiros; Pappas, Katherine M.; Typas, Milton A.; Nychas, George-John

    2017-01-01

    The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in food has provoked a great concern about the presence of MRSA in associated foodstuff. Although MRSA is often detected in various retailed meat products, it seems that food handlers are more strongly associated with this type of food contamination. Thus, it can be easily postulated that any food could be contaminated with this pathogen in an industrial environment or in household and cause food poisoning. To this direction, the effect of rocket (Eruca sativa) extract on MRSA growth and proteome was examined in the present study. This goal was achieved with the comparative study of the MRSA strain COL proteome, cultivated in rocket extract versus the standard Luria-Bertani growth medium. The obtained results showed that MRSA was able to grow in rocket extract. In addition, proteome analysis using 2-DE method showed that MRSA strain COL is taking advantage of the sugar-, lipid-, and vitamin-rich substrate in the liquid rocket extract, although its growth was delayed in rocket extract compared to Luria–Bertani medium. This work could initiate further research about bacterial metabolism in plant-based media and defense mechanisms against plant-derived antibacterials. PMID:28529502

  15. Effect of Rocket (Eruca sativa) Extract on MRSA Growth and Proteome: Metabolic Adjustments in Plant-Based Media.

    PubMed

    Doulgeraki, Agapi I; Efthimiou, Georgios; Paramithiotis, Spiros; Pappas, Katherine M; Typas, Milton A; Nychas, George-John

    2017-01-01

    The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in food has provoked a great concern about the presence of MRSA in associated foodstuff. Although MRSA is often detected in various retailed meat products, it seems that food handlers are more strongly associated with this type of food contamination. Thus, it can be easily postulated that any food could be contaminated with this pathogen in an industrial environment or in household and cause food poisoning. To this direction, the effect of rocket (Eruca sativa ) extract on MRSA growth and proteome was examined in the present study. This goal was achieved with the comparative study of the MRSA strain COL proteome, cultivated in rocket extract versus the standard Luria-Bertani growth medium. The obtained results showed that MRSA was able to grow in rocket extract. In addition, proteome analysis using 2-DE method showed that MRSA strain COL is taking advantage of the sugar-, lipid-, and vitamin-rich substrate in the liquid rocket extract, although its growth was delayed in rocket extract compared to Luria-Bertani medium. This work could initiate further research about bacterial metabolism in plant-based media and defense mechanisms against plant-derived antibacterials.

  16. Stimulant medication effects on growth and bone age in children with attention-deficit/hyperactivity disorder: a prospective cohort study.

    PubMed

    Poulton, Alison S; Bui, Quoc; Melzer, Elaine; Evans, Richard

    2016-03-01

    Stimulant medication is known to cause transient weight loss and slowing down of growth, but whether it delays physical maturation is unclear. We studied growth and bone age over the first 3 years of treatment in children with attention-deficit/hyperactivity disorder (patients) compared with healthy siblings (controls). Bone age was estimated blindly by two independent radiologists using Tanner and Whitehouse version 3. Dexamphetamine or methylphenidate was titrated and continued when clinically indicated. Forty out of 73 patients, together with 22 controls, completed the study. There were no significant growth differences between the two groups at baseline. Despite slower growth on treatment [5.1 cm/year, 95% confidence interval (CI): 4.7-5.5, vs. 6.3 cm/year, 95% CI: 5.7-6.8, P=0.002; and 2.7 kg/year, 95% CI: 2.1-3.3, vs. 4.4 kg/year, 95% CI: 3.5-5.3, P=0.005], the patients showed no significant maturational delay (RUS score: 49 U/year, 95% CI: 44-55, vs. 55 U/year, 95% CI: 47-63, P=0.27). A subgroup of patients underwent serial biochemistry and dual-energy X-ray absorptiometry, recording a significant reduction in fat (5.61±3.56-4.22±3.09 kg, P<0.001) and leptin (3.88±2.87-2.57±1.94 ng/ml, P=0.017). The pattern of change in height z-score over time was modified by the dose of medication (P for interaction=0.024). We found no medication effect on the rate of maturation, which was instead predicted by baseline leptin (P=0.035 controlling for age and sex).

  17. Impact of dyeing industry effluent on germination and growth of pea (Pisum sativum).

    PubMed

    Malaviya, Piyush; Hali, Rajesh; Sharma, Neeru

    2012-11-01

    Dye industry effluent was analyzed for physico-chemical characteristics and its impact on germination and growth behaviour of Pea (Pisum sativum). The 100% effluent showed high pH (10.3) and TDS (1088 mg l(-1)). The germination parameters included percent germination, delay index, speed of germination, peak value and germination period while growth parameters comprised of root and shoot length, root and shootweight, root-shoot ratio and number of stipules. The study showed the maximum values of positive germination parameters viz. speed of germination (7.85), peak value (3.28), germination index (123.87) and all growth parameters at 20% effluent concentration while the values of negative germination parameters viz. delay index (-0.14) and percent inhibition (-8.34) were found to be minimum at 20% effluent concentration. The study demonstrated that at lower concentrations the dyeing industry effluent caused a positive impact on germination and growth of Pisum sativum.

  18. Amino-terminal propeptide of C-type natriuretic peptide and linear growth in children: effects of puberty, testosterone, and growth hormone.

    PubMed

    Olney, Robert C; Prickett, Timothy C R; Yandle, Timothy G; Espiner, Eric A; Han, Joan C; Mauras, Nelly

    2007-11-01

    C-type natriuretic peptide (CNP), a paracrine factor of the growth plate, plays a key role in stimulating bone growth. The amino-terminal propeptide of CNP (NTproCNP) is produced in equimolar amounts with CNP and is measurable in plasma, providing a potential biomarker for growth plate activity and, hence, linear growth. We explored the effects of puberty, testosterone, and GH treatment on NTproCNP levels in normal and short-statured children. This was a retrospective analysis of samples obtained during previous studies. The study was conducted at a pediatric clinical research center. Children with short stature due to GH deficiency, idiopathic short stature (ISS), or constitutional delay of growth and maturation (CDGM) were studied (n = 37). A cohort of normal-statured adolescent boys was also studied (n = 23). Children with GH deficiency and ISS were studied before and during testosterone and/or GH treatment. Boys with CDGM and healthy controls were studied once. The main outcomes were NTproCNP levels before and during growth-promoting therapy and during pubertal growth. Children with short stature due to GH deficiency, ISS, or CDGM had comparable baseline levels of NTproCNP, and levels increased markedly in response to GH or testosterone treatment. In boys with CDGM, levels were comparable with height-matched controls but were less than those from age-matched controls. In healthy boys, NTproCNP appears to peak with the pubertal growth spurt. NTproCNP levels increase during growth-promoting therapy and are increased during puberty in boys. This novel biomarker of growth may have clinical utility in the evaluation of children with short stature and for monitoring growth-promoting therapy.

  19. Hide, Keep Quiet, and Keep Low: Properties That Make Aspergillus fumigatus a Successful Lung Pathogen

    PubMed Central

    Escobar, Natalia; Ordonez, Soledad R.; Wösten, Han A. B.; Haas, Pieter-Jan A.; de Cock, Hans; Haagsman, Henk P.

    2016-01-01

    Representatives of the genus Aspergillus are opportunistic fungal pathogens. Their conidia can reach the alveoli by inhalation and can give rise to infections in immunocompromised individuals. Aspergillus fumigatus is the causal agent of invasive aspergillosis in nearly 90% of the cases. It is not yet well-established what makes this fungus more pathogenic than other aspergilli such as A. niger. Here, we show that A. fumigatus and A. niger conidia adhere with similar efficiency to lung epithelial A549 cells but A. fumigatus conidia internalized 17% more efficiently. Conidia of both aspergilli were taken up in phagolysosomes 8 h after the challenge. These organelles only acidified in the case of A. niger, which is probably due to the type of melanin coating of the conidia. Viability of both types of conidia was not affected after uptake in the phagolysosomes. Germination of A. fumigatus and A. niger conidia in the presence of epithelial cells was delayed when compared to conidia in the medium. However, germination of A. niger conidia was still higher than that of A. fumigatus 10 h after exposure to A549 cells. Remarkably, A. fumigatus hyphae grew mainly parallel to the epithelium, while growth direction of A. niger hyphae was predominantly perpendicular to the plane of the cells. Neutrophils reduced germination and hyphal growth of A. niger, but not of A fumigatus, in presence of epithelial cells. Taken together, efficient internalization, delayed germination, and hyphal growth parallel to the epithelium gives a new insight into what could be the causes for the success of A. fumigatus compared to A. niger as an opportunistic pathogen in the lung. PMID:27092115

  20. Pulsed Versus Conventional Radiation Therapy in Combination With Temozolomide in a Murine Orthotopic Model of Glioblastoma Multiforme

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

    Lee, David Y.; Chunta, John L.; Park, Sean S.

    Purpose: To evaluate the efficacy of pulsed low-dose radiation therapy (PLRT) combined with temozolomide (TMZ) as a novel treatment approach for radioresistant glioblastoma multiforme (GBM) in a murine model. Methods and Materials: Orthotopic U87MG hGBM tumors were established in Nu-Foxn1{sup nu} mice and imaged weekly using a small-animal micropositron emission tomography (PET)/computed tomography (CT) system. Tumor volume was determined from contrast-enhanced microCT images and tumor metabolic activity (SUVmax) from the F18-FDG microPET scan. Tumors were irradiated 7 to 10 days after implantation with a total dose of 14 Gy in 7 consecutive days. The daily treatment was given as amore » single continuous 2-Gy dose (RT) or 10 pulses of 0.2 Gy using an interpulse interval of 3 minutes (PLRT). TMZ (10 mg/kg) was given daily by oral gavage 1 hour before RT. Tumor vascularity and normal brain damage were assessed by immunohistochemistry. Results: Radiation therapy with TMZ resulted in a significant 3- to 4-week tumor growth delay compared with controls, with PLRT+TMZ the most effective. PLRT+TMZ resulted in a larger decline in SUVmax than RT+TMZ. Significant differences in survival were evident. Treatment after PLRT+TMZ was associated with increased vascularization compared with RT+TMZ. Significantly fewer degenerating neurons were seen in normal brain after PLRT+TMZ compared with RT+TMZ. Conclusions: PLRT+TMZ produced superior tumor growth delay and less normal brain damage when compared with RT+TMZ. The differential effect of PLRT on vascularization may confirm new treatment avenues for GBM.« less

  1. Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. II. Cyclophosphamide

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

    Twentyman, P.R.; Kallman, R.F.; Brown, J.M.

    1979-09-01

    Experiments have been carried out to determine the effect of different time intervals between the administration of x-radiation (1200 rad) and cyclophosphamide (100 mg/kg) on the growth delay produced in 3 mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administered intraperitoneallymore » either 24, 6, or 2 hr before radiation, immediately before the start of radiation, or 3, 6, or 24 hr after radiation. All irradiations were carried out in unanesthetized mice. For the RIF-1, EMT6, and KHT tumors, the growth delays due to the drug alone were 11, 4.5, and 12 days, respectively. In the RIF-1 system, the growth delays following combination treatment tended to be longer than predicted by the addition of the single agent delays. For the KHT tumor, the opposite trend was seen, whereas in EMT6, there was no significant trend in either direction. No consistent dependence upon the timing between irradiation and drug administration was seen from system to system.« less

  2. Clopidogrel inhibits angiogenesis of gastric ulcer healing via downregulation of vascular endothelial growth factor receptor 2.

    PubMed

    Luo, Jiing-Chyuan; Peng, Yen-Ling; Chen, Tseng-Shing; Huo, Teh-Ia; Hou, Ming-Chih; Huang, Hui-Chun; Lin, Han-Chieh; Lee, Fa-Yauh

    2016-09-01

    Although clopidogrel does not cause gastric mucosal injury, it does not prevent peptic ulcer recurrence in high-risk patients. We explored whether clopidogrel delays gastric ulcer healing via inhibiting angiogenesis and to elucidate the possible mechanisms. Gastric ulcers were induced in Sprague Dawley rats, and ulcer healing and angiogenesis of ulcer margin were compared between clopidogrel-treated rats and controls. The expressions of the proangiogenic growth factors and their receptors including basic fibroblast growth factor (bFGF), bFGF receptor (FGFR), vascular endothelial growth factor (VEGF), VEGFR1, VEGFR2, platelet-derived growth factor (PDGF)A, PDGFB, PDGFR A, PDGFR B, and phosphorylated form of mitogenic activated protein kinase pathways over the ulcer margin were compared via western blot and reverse transcription polymerase chain reaction. In vitro, human umbilical vein endothelial cells (HUVECs) were used to elucidate how clopidogrel inhibited growth factors-stimulated HUVEC proliferation. The ulcer sizes were significantly larger and the angiogenesis of ulcer margin was significantly diminished in the clopidogrel (2 and 10 mg/kg/d) treated groups. Ulcer induction markedly increased the expression of phosphorylated form of extracellular signal-regulated kinase (pERK), FGFR2, VEGF, VEGFR2, and PDGFRA when compared with those of normal mucosa. Clopidogrel treatment significantly decreased pERK, FGFR2, VEGF, VEGFR2, and PDGFRA expression at the ulcer margin when compared with those of the respective control group. In vitro, clopidogrel (10(-6)M) inhibited VEGF-stimulated (20 ng/mL) HUVEC proliferation, at least, via downregulation of VEGFR2 and pERK. Clopidogrel inhibits the angiogenesis of gastric ulcer healing at least partially by the inhibition of the VEGF-VEGFR2-ERK signal transduction pathway. Copyright © 2015. Published by Elsevier B.V.

  3. Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth

    PubMed Central

    Dauchy, Robert T; Hoffman, Aaron E; Wren-Dail, Melissa A; Hanifin, John P; Warfield, Benjamin; Brainard, George C; Xiang, Shulin; Yuan, Lin; Hill, Steven M; Belancio, Victoria P; Dauchy, Erin M; Smith, Kara; Blask, David E

    2015-01-01

    Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts. Compared with male nude rats housed in clear cages under a 12:12-h light:dark cycle, rats in blue-tinted cages (with increased transmittance of 462–484 nm and decreased red light greater than 640 nm) evinced over 6-fold higher peak plasma melatonin levels at middark phase (time, 2400), whereas midlight-phase levels (1200) were low (less than 3 pg/mL) in both groups. Circadian rhythms of arterial plasma levels of linoleic acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were disrupted in rats in blue cages as compared with the corresponding entrained rhythms in clear-caged rats. After implantation with tissue-isolated PC3 human prostate cancer xenografts, tumor latency-to-onset of growth and growth rates were markedly delayed, and tumor cAMP levels, uptake–metabolism of linoleic acid, aerobic glycolysis (Warburg effect), and growth signaling activities were reduced in rats in blue compared with clear cages. These data show that the amplification of nighttime melatonin levels by exposing nude rats to blue light during the daytime significantly reduces human prostate cancer metabolic, signaling, and proliferative activities. PMID:26678364

  4. Daytime Blue Light Enhances the Nighttime Circadian Melatonin Inhibition of Human Prostate Cancer Growth.

    PubMed

    Dauchy, Robert T; Hoffman, Aaron E; Wren-Dail, Melissa A; Hanifin, John P; Warfield, Benjamin; Brainard, George C; Xiang, Shulin; Yuan, Lin; Hill, Steven M; Belancio, Victoria P; Dauchy, Erin M; Smith, Kara; Blask, David E

    2015-12-01

    Light controls pineal melatonin production and temporally coordinates circadian rhythms of metabolism and physiology in normal and neoplastic tissues. We previously showed that peak circulating nocturnal melatonin levels were 7-fold higher after daytime spectral transmittance of white light through blue-tinted (compared with clear) rodent cages. Here, we tested the hypothesis that daytime blue-light amplification of nocturnal melatonin enhances the inhibition of metabolism, signaling activity, and growth of prostate cancer xenografts. Compared with male nude rats housed in clear cages under a 12:12-h light:dark cycle, rats in blue-tinted cages (with increased transmittance of 462-484 nm and decreased red light greater than 640 nm) evinced over 6-fold higher peak plasma melatonin levels at middark phase (time, 2400), whereas midlight-phase levels (1200) were low (less than 3 pg/mL) in both groups. Circadian rhythms of arterial plasma levels of linoleic acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were disrupted in rats in blue cages as compared with the corresponding entrained rhythms in clear-caged rats. After implantation with tissue-isolated PC3 human prostate cancer xenografts, tumor latency-to-onset of growth and growth rates were markedly delayed, and tumor cAMP levels, uptake-metabolism of linoleic acid, aerobic glycolysis (Warburg effect), and growth signaling activities were reduced in rats in blue compared with clear cages. These data show that the amplification of nighttime melatonin levels by exposing nude rats to blue light during the daytime significantly reduces human prostate cancer metabolic, signaling, and proliferative activities.

  5. Impact of long-term erythrocytapheresis on growth and peak height velocity of children with sickle cell disease.

    PubMed

    Bavle, Abhishek; Raj, Ashok; Kong, Maiying; Bertolone, Salvatore

    2014-11-01

    Children with sickle cell disease (SCD) lag in weight and height and have a delayed growth spurt compared to normal children. We studied the effect of long-term erythrocytapheresis (LTE) on the growth of children with SCD and the age at which they attained peak height velocity. A retrospective chart review was performed recording weight, height, and body mass index (BMI) measurements of 36 patients with SCD who received LTE every 3-5 weeks for an average duration of 5 years. The z-scores for weight, height, and BMI of these patients were compared with that of patients with SCD from the Cooperative Study of Sickle Cell Disease (CSSCD) and a sub-set of 64 controls matched for age, sex, and initial growth parameter z-scores at the start of LTE. The z-scores for all parameters improved significantly for our patients on LTE compared to match controls from CSSCD and the entire pediatric CSSCD cohort (P-value: <0.01). Peak height velocity was achieved 2 months earlier for females (P-value: 0.94) and 11 months earlier for males (P-value: 0.02), who started LTE before 14 years of age, compared to matched CSSCD controls. The study subjects who had not been on regular simple transfusions prior to starting LTE had a mean serum ferritin of 681 ng/ml after LTE for an average duration of 63 months. LTE improves the growth of children with SCD without the risk of iron overload. © 2014 Wiley Periodicals, Inc.

  6. Effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumours. VI. BCNU

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

    Lelieveld, P.; Twentyman, P.R.; Kallman, R.F.

    1979-09-01

    Experiments have been carried out to determine the effect of different time intervals between the administration of x-irradiation (1200 rad) and BCNU (15 mg/kg) on the growth delay produced in three mouse tumors. The tumors used were the EMT6 tumor in BALB/c mice and the KHT and RIF-1 sarcomas in C3H mice. All tumors were grown intramuscularly in the gastrocnemius muscle and treatment was carried out at a mean tumor weight of 450 mg. Time to reach 2X (for KHT) or 4X (for EMT6 and RIF-1) treatment volume was used as the endpoint of response. The drug was administered bymore » the intraperitoneal route either 24, 6, or 2 hr before radiation. All irradiations were carried out in unanesthetized mice. The growth delays due to the drug alone were 2,6, and 11 days for the RIF-1, EMT6, and KHT tumors, respectively. No consistent general pattern emerged from the results of combination treatments. For the RIF-1 tumor, the growth delays following combination treatments were generally less than predicted by the simple addition of the growth delays for the single modalities. For EMT6 this was true when BCNU was administered immediately before x-rays, but not for other timings. In the KHT tumor an unexpectedly high incidence of long-term tumor controls was seen in the group which received BCNU at 2 hr before x-rays. In addition to the single dose studies (above), fractionated regimens in which radiation and BCNU were combined in several different ways were tested with the RIF-1 tumor. None of the combination schedules tested showed a greater-than-additive effect.« less

  7. Refinement of the 12q14 microdeletion syndrome: primordial dwarfism and developmental delay with or without osteopoikilosis

    PubMed Central

    Mari, Francesca; Hermanns, Pia; Giovannucci-Uzielli, Maria L; Galluzzi, Fiorella; Scott, Daryl; Lee, Brendan; Renieri, Alessandra; Unger, Sheila; Zabel, Bernhard; Superti-Furga, Andrea

    2009-01-01

    In their studies on the molecular basis of osteopoikilosis, Menten et al have identified three individuals with microdeletions on chromosome 12q14.4, which removed several genes including LEMD3, the osteopoikilosis gene. In addition to osteopoikilosis, affected individuals had growth retardation and developmental delay. We now report a smaller 12q14.4 microdeletion in a boy with severe pre and postnatal growth failure, and mild developmental delay; the patient was small at birth and presented with poor feeding and failure to thrive during the first 2 years of life, similar to the phenotype of primordial dwarfism or severe Silver-Russell syndrome (SRS). The 12q14 deletion did not include LEMD3, and no signs of osteopoikilosis were observed on skeletal radiographs. Among the deleted genes, HMGA2 is of particular interest in relationship to the aberrant somatic growth in our patient, as HMGA2 variants have been linked to stature variations in the general population and loss of function of Hmga2 in the mouse results in the pygmy phenotype that combines pre and postnatal growth failure, with resistance to the adipogenic effect of overfeeding. Sequencing of the remaining HMGA2 allele in our patient showed a normal sequence, suggesting that HMGA2 haploinsufficiency may be sufficient to produce the aberrant growth phenotype. We conclude that the 12q14.4 microdeletion syndrome can occur with or without deletion of LEMD3 gene; in LEMD3-intact cases, the phenotype includes primordial short stature and failure to thrive with moderate developmental delay, but osteopoikilosis is absent. Such cases will likely be diagnosed as Silver-Russell-like or as primordial dwarfism. PMID:19277063

  8. Obesity and growth during childhood and puberty.

    PubMed

    Marcovecchio, M Loredana; Chiarelli, Francesco

    2013-01-01

    Growth during childhood and adolescence occurs at different rates and is influenced by the interaction between genetic and environmental factors. Nutritional status plays an important role in regulating growth, and excess body weight early in life can influence growth patterns. Childhood obesity is a growing and alarming problem, associated with several short-term and long-term metabolic and cardiovascular complications. In addition, there is evidence suggesting that excess adiposity during childhood influences growth patterns and pubertal development. Several studies have shown that during prepubertal years obese children have higher height velocity and accelerated bone age compared to lean subjects. However, this prepubertal advantage in growth tends to gradually decrease during puberty, when obese children show a reduced growth spurt compared with lean subjects. Growth hormone (GH) secretion in obese children is reduced, therefore suggesting that increased growth is GH independent. Factors which have been implicated in the accelerated growth in obese children include increased leptin and insulin levels, adrenal androgens, insulin-like growth factor (IGF)-1, IGF-binding protein-1 and GH-binding proteins. Excess body weight during childhood can also influence pubertal development, through an effect on timing of pubertal onset and levels of pubertal hormonal levels. There is clear evidence indicating that obesity leads to early appearance of pubertal signs in girls. In addition, obese girls are also at increased risk of hyperandrogenism. In boys, excess adiposity has been associated with advanced puberty in some studies, whereas others have reported a delay in pubertal onset. The existing evidence on the association between childhood and adolescence obesity underlines a further reason for fighting the epidemics of childhood obesity; that is preventing abnormal growth and pubertal patterns. Copyright © 2013 S. Karger AG, Basel.

  9. Mitigating delay and non-payment in the Malaysian construction industry

    NASA Astrophysics Data System (ADS)

    Mohamad, N.; Suman, A. S.; Harun, H.; Hashim, H.

    2018-02-01

    Construction industry is one of the industries that have contributed towards the rapid growth of development and economics in Malaysia. However, the industry is inundated with delay and non-payment issues between the two parties in contract that is the clients and contractors Even though there are contractual and administrative provisions in the standard forms of contract in Malaysia regarding payments, delay and non-payment issues still occur between them. The aim of the study is to develop measures to mitigate delay and non-payment issues between contractors and clients in the Malaysian construction industry. Questionnaire survey was conducted with clients and contractors in Klang Valley. Results from data analysis identified significant measures to mitigate delay and non-payment issues between contractors and clients which include contractors should submit their progress work invoicing with adequate documents; contractors should follow up constantly with client regarding payment; proper understanding of requirements with regards to payment; mutual discussion of problems with client to address problems in a timely manner and proper use of payment provisions in the standard form of contract. This study is significant to contractors and clients and to other construction players in order to reduce and minimise delay and non-payment issues for the growth of economy in the Malaysian construction industry.

  10. Delayed extubation to nasal continuous positive airway pressure in the immature baboon model of bronchopulmonary dysplasia: lung clinical and pathological findings.

    PubMed

    Thomson, Merran A; Yoder, Bradley A; Winter, Vicki T; Giavedoni, Luis; Chang, Ling Yi; Coalson, Jacqueline J

    2006-11-01

    Using the 125-day baboon model of bronchopulmonary dysplasia treated with prenatal steroid and exogenous surfactant, we hypothesized that a delay of extubation from low tidal volume positive pressure ventilation to nasal continuous positive airway pressure at 5 days (delayed nasal continuous positive airway pressure group) would not induce more lung injury when compared with baboons aggressively weaned to nasal continuous positive airway pressure at 24 hours (early nasal continuous positive airway pressure group), because both received positive pressure ventilation. After delivery by cesarean section at 125 days (term: 185 days), infants received 2 doses of Curosurf (Chiesi Farmaceutica S.p.A., Parma, Italy) and daily caffeine citrate. The delay in extubation to 5 days resulted in baboons in the delayed nasal continuous positive airway pressure group having a lower arterial to alveolar oxygen ratio, high PaCO2, and worse respiratory function. The animals in the delayed nasal continuous positive airway pressure group exhibited a poor respiratory drive that contributed to more reintubations and time on mechanical ventilation. A few animals in both groups developed necrotizing enterocolitis and/or sepsis, but infectious pneumonias were not documented. Cellular bronchiolitis and peribronchiolar alveolar wall thickening were more frequently seen in the delayed nasal continuous positive airway pressure group. Bronchoalveolar lavage levels of interleukin-6, interleukin-8, monocyte chemotactic protein-1, macrophage inflammatory protein-1 alpha, and growth-regulated oncogene-alpha were significantly increased in the delayed nasal continuous positive airway pressure group. Standard and digital morphometric analyses showed no significant differences in internal surface area and nodal measurements between the groups. Platelet endothelial cell adhesion molecule vascular staining was not significantly different between the 2 nasal continuous positive airway pressure groups. Volutrauma and/or low-grade colonization of airways secondary to increased reintubations and ventilation times are speculated to play causative roles in the delayed nasal continuous positive airway pressure group findings.

  11. Brief communication: a proposed method for the assessment of pubertal stage in human skeletal remains using cervical vertebrae maturation.

    PubMed

    Shapland, Fiona; Lewis, Mary E

    2014-01-01

    The assessment of age-at-death in non-adult skeletal remains is under constant review. However, in many past societies an individual's physical maturation may have been more important in social terms than their exact age, particularly during the period of adolescence. In a recent article (Shapland and Lewis: Am J Phys Anthropol 151 (2013) 302-310) highlighted a set of dental and skeletal indicators that may be useful in mapping the progress of the pubertal growth spurt. This article presents a further skeletal indicator of adolescent development commonly used by modern clinicians: cervical vertebrae maturation (CVM). This method is applied to a collection of 594 adolescents from the medieval cemetery of St. Mary Spital, London. Analysis reveals a potential delay in ages of attainment of the later CVM stages compared with modern adolescents, presumably reflecting negative environmental conditions for growth and development. The data gathered on CVM is compared to other skeletal indicators of pubertal maturity and long bone growth from this site to ascertain the usefulness of this method on archaeological collections. Copyright © 2013 Wiley Periodicals, Inc.

  12. NF-E2 Overexpression Delays Erythroid Maturation and Increases Erythrocyte Production

    PubMed Central

    Mutschler, Manuel; Magin, Angela S.; Buerge, Martina; Roelz, Roland; Schanne, Daniel H.; Will, Britta; Pilz, Ingo H.; Migliaccio, Anna Rita; Pahl, Heike L.

    2009-01-01

    Summary The transcription factor Nuclear Factor-Erythroid 2 (NF-E2) is overexpressed in the vast majority of patients with polycythaemia vera (PV). In murine models, NF-E2 overexpression increases proliferation and promotes cellular viability in the absence of erythropoietin (EPO). EPO-independent growth is a hallmark of PV. We therefore hypothesized that NF-E2 overexpression contributes to erythrocytosis, the pathognomonic feature of PV. Consequently, we investigated the effect of NF-E2 overexpression in healthy CD34+ cells. NF-E2 overexpression led to a delay in erythroid maturation, manifested by a belated appearance of glycophorin A-positive erythroid precursors. Maturation delay was similarly observed in primary PV patient erythroid cultures compared to healthy controls. Protracted maturation led to a significant increase in the accumulated number of erythroid cells both in PV cultures and in CD34+ cells overexpressing NF-E2. Similarly, NF-E2 overexpression altered erythroid colony formation, leading to an increase in BFU-E formation. These data indicate that NF-E2 overexpression delays the early phase of erythroid maturation, resulting in an expansion of erythroid progenitors, thereby increasing the number of erythrocytes derived from one CD34+ cell. These data propose a role for NF-E2 in mediating the erythrocytosis of PV. PMID:19466964

  13. Delayed cutaneous wound healing in aged rats compared to younger ones.

    PubMed

    Soybir, Onur C; Gürdal, Sibel Ö; Oran, Ebru Ş; Tülübaş, Feti; Yüksel, Meral; Akyıldız, Ayşenur İ; Bilir, Ayhan; Soybir, Gürsel R

    2012-10-01

    Delayed wound healing in elderly males is a complex process in which the factors responsible are not fully understood. This study investigated the hormonal, oxidative and angiogenic factors affecting wound healing in aged rats. Two groups consisting of eight healthy male Wistar Albino rats [young (30 ± 7 days) and aged (360 ± 30 days)], and a cutaneous incision wound healing model were used. Scar tissue samples from wounds on the 7th, 14th and 21st days of healing were evaluated for hydroxyproline and vascular endothelial growth factor content. Macrophage, lymphocyte, fibroblast and polymorphonuclear cell infiltration; collagen formation and vascularization were assessed by light and electron microscopy. The free oxygen radical content of the wounds was measured by a chemiluminescence method. Blood sample analysis showed that the hydroxyproline and total testosterone levels were significantly higher, and the oxygen radical content was significantly lower in young rats. Histopathological, immunohistochemical and ultrastructural evaluations revealed higher amounts of fibroblasts and collagen fibers, and more vascularization in young rats. These results are indicative of the delayed wound healing in aged rats. A combination of multiple factors including hormonal regulation, free oxygen radicals and impaired angiogenesis appears to be the cause of delayed cutaneous healing. © 2011 The Authors. International Wound Journal © 2011 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

  14. Grain growth in U–7Mo alloy: A combined first-principles and phase field study

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

    Mei, Zhi-Gang; Liang, Linyun; Kim, Yeon Soo

    2016-05-01

    Grain size is an important factor in controlling the swelling behavior in irradiated U-Mo dispersion fuels. Increasing the grain size in UeMo fuel particles by heat treatment is believed to delay the fuel swelling at high fission density. In this work, a multiscale simulation approach combining first-principles calculation and phase field modeling is used to investigate the grain growth behavior in U-7Mo alloy. The density functional theory based first-principles calculations were used to predict the material properties of U-7Mo alloy. The obtained grain boundary energies were then adopted as an input parameter for mesoscale phase field simulations. The effects ofmore » annealing temperature, annealing time and initial grain structures of fuel particles on the grain growth in U-7Mo alloy were examined. The predicted grain growth rate compares well with the empirical correlation derived from experiments. (C) 2016 Elsevier B.V. All rights reserved.« less

  15. Delayed animal aging through the recovery of stem cell senescence by platelet rich plasma.

    PubMed

    Liu, Hen-Yu; Huang, Chiung-Fang; Lin, Tzu-Chieh; Tsai, Ching-Yu; Tina Chen, Szu-Yu; Liu, Alice; Chen, Wei-Hong; Wei, Hong-Jian; Wang, Ming-Fu; Williams, David F; Deng, Win-Ping

    2014-12-01

    Aging is related to loss of functional stem cell accompanying loss of tissue and organ regeneration potentials. Previously, we demonstrated that the life span of ovariectomy-senescence accelerated mice (OVX-SAMP8) was significantly prolonged and similar to that of the congenic senescence-resistant strain of mice after platelet rich plasma (PRP)/embryonic fibroblast transplantation. The aim of this study is to investigate the potential of PRP for recovering cellular potential from senescence and then delaying animal aging. We first examined whether stem cells would be senescent in aged mice compared to young mice. Primary adipose derived stem cells (ADSCs) and bone marrow derived stem cells (BMSCs) were harvested from young and aged mice, and found that cell senescence was strongly correlated to animal aging. Subsequently, we demonstrated that PRP could recover cell potential from senescence, such as promote cell growth (cell proliferation and colony formation), increase osteogenesis, decrease adipogenesis, restore cell senescence related markers and resist the oxidative stress in stem cells from aged mice. The results also showed that PRP treatment in aged mice could delay mice aging as indicated by survival, body weight and aging phenotypes (behavior and gross morphology) in term of recovering the cellular potential of their stem cells compared to the results on aged control mice. In conclusion these findings showed that PRP has potential to delay aging through the recovery of stem cell senescence and could be used as an alternative medicine for tissue regeneration and future rejuvenation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Kisspeptin regulates ovarian steroidogenesis during delayed embryonic development in the fruit bat, Cynopterus sphinx.

    PubMed

    Anuradha; Krishna, Amitabh

    2017-11-01

    Cynopterus sphinx, a fruit bat, undergoes delayed embryonic development during the winter months, a period that corresponds to low levels of progesterone and estradiol synthesis by the ovary. Kisspeptins (KPs) are a group of neuropeptide hormones that act via G-protein coupled receptor 54 (GPR54) to stimulate hypothalamic secretion of Gonadotropin-releasing hormone, thereby regulating ovarian steroidogenesis, folliculogenesis, and ovulation. GPR54 is also expressed in the ovary, suggesting a direct role for KPs in ovarian steroidogenesis. The aim of present study was to determine if a low serum level of KP is responsible for reduced progesterone and estradiol levels during the period of delayed embryonic development in C. sphinx. Indeed, low serum KP abundance corresponded to reduced expression of GPR54 in ovarian luteal cells during the period of delayed development compared to normal development. In vitro and in vivo treatment with KP increased GPR54 abundance, via Extracellular signal regulated kinase and its downstream mediators, leading to increased progesterone synthesis in the ovary during delayed embryonic development. KP treatment also increased cholesterol uptake and elevated expression of Luteinizing hormone receptor and Steroid acute regulatory protein in the ovary, suggesting that elevation in circulating KP during delayed embryonic development may reactivate luteal activity. KPs may also enhance cell survival (BCL-2, reduced Caspase 3 activity) and angiogenesis (Vascular endothelium growth factor) during this period. The findings of this study thus demonstrate a regulatory role for KPs in the maintenance of luteal steroidogenesis during pregnancy in C. sphinx. © 2017 Wiley Periodicals, Inc.

  17. Effects of shading on plant growth, flower quality and photosynthetic capacity of Rosa hybrida

    NASA Astrophysics Data System (ADS)

    Hou, Wei; Luo, Ya; Wang, Xiaorong; Chen, Qing; Sun, Bo; Wang, Yan; Liu, Zejing; Tang, Haoru; Zhang, Yong

    2018-04-01

    With the acceleration of the urbanization process, numbers of garden plants are grown in shaded environment. Rose (Rosa hybrida) is one of the most important ornamental plants used in urban green spaces. In the present study, effects of shading on plant growth, flower quality and photosynthetic capacity of R. hybrida were investigated. The results showed that shade not only delayed the initial flowering date, but also prolonged the flowering time. The physiological indices, including flower fresh weight, total anthocyanins and flavonoids contents, were lower in plants grown with shade compared with those grown in sun exposure. Overall, R. hybrida seemed to be a shade adapted plant which could be successfully grown in urban green spaces or understory with slight shade.

  18. Phenotypic indications of FtsZ inhibition in hok/sok-induced bacterial growth changes and stress response.

    PubMed

    Chukwudi, Chinwe Uzoma; Good, Liam

    2018-01-01

    The hok/sok locus has been shown to enhance the growth of bacteria in adverse growth conditions such as high temperature, low starting-culture densities and antibiotic treatment. This is in addition to their well-established plasmid-stabilization effect via post-segregational killing of plasmid-free daughter cells. It delays the onset of growth by prolonging the lag phase of bacterial culture, and increases the rate of exponential growth when growth eventually begins. This enables the cells adapt to the prevailing growth conditions and enhance their survival in stressful conditions. These effects functionally complement defective SOS response mechanism, and appear analogous to the growth effects of FtsZ in the SOS pathway. In this study, the role of FtsZ in the hok/sok-induced changes in bacterial growth and cell division was investigated. Morphologic studies of early growth-phase cultures and cells growing under temperature stress showed elongated cells typical of FtsZ inhibition/deficiency. Both ftsZ silencing and over-expression produced comparable growth effects in control cells, and altered the growth changes observed otherwise in the hok/sok + cells. These changes were diminished in SOS-deficient strain containing mutant FtsZ. The involvement of FtsZ in the hok/sok-induced growth changes may be exploited as drug target in host bacteria, which often propagate antibiotic resistance elements. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Antitumor activity of ZD6126, a novel vascular-targeting agent, is enhanced when combined with ZD1839, an epidermal growth factor receptor tyrosine kinase inhibitor, and potentiates the effects of radiation in a human non-small cell lung cancer xenograft model.

    PubMed

    Raben, David; Bianco, Cataldo; Damiano, Vincenzo; Bianco, Roberto; Melisi, Davide; Mignogna, Chiara; D'Armiento, Francesco Paolo; Cionini, Luca; Bianco, A Raffaele; Tortora, Giampaolo; Ciardiello, Fortunato; Bunn, Paul

    2004-08-01

    Targeting the tumor vasculature may offer an alternative or complementary therapeutic approach to targeting growth factor signaling in lung cancer. The aim of these studies was to evaluate the antitumor effects in vivo of the combination of ZD6126, a tumor-selective vascular-targeting agent; ZD1839 (gefitinib, Iressa), an epidermal growth factor receptor tyrosine kinase inhibitor; and ionizing radiation in the treatment of non-small cell lung cancer xenograft model. Athymic nude mice with established flank A549 human non-small cell lung cancer xenograft model xenografts were treated with fractionated radiation therapy, ZD6126, ZD1839, or combinations of each treatment. ZD6126 (150 mg/kg) was given i.p. the day after each course of radiation. Animals treated with ZD1839 received 100 mg/kg per dose per animal, 5 or 7 days/wk for 2 weeks. Immunohistochemistry was done to evaluate the effects on tumor growth using an anti-Ki67 monoclonal antibody. Effects on tumor-induced vascularization were quantified using an anti-factor VIII-related antigen monoclonal antibody. ZD6126 attenuated the growth of human A549 flank xenografts compared with untreated animals. Marked antitumor effects were observed when animals were treated with a combination of ZD6126 and fractionated radiation therapy with protracted tumor regression. ZD6126 + ZD1839 resulted in a greater tumor growth delay than either agent alone. Similar additive effects were seen with ZD1839 + fractionated radiation. Finally, the addition of ZD6126 to ZD1839 and radiation therapy seemed to further improve tumor growth control, with a significant tumor growth delay compared with animals treated with single agent or with double combinations. Immunohistochemistry showed that ZD1839 induced a marked reduction in A549 tumor cell proliferation. Both ZD1839 and ZD6126 treatment substantially reduced tumor-induced angiogenesis. ZD6126 caused marked vessel destruction through loss of endothelial cells and thrombosis, substantially increasing the level of necrosis seen when combined with radiation therapy. The combination of radiation therapy, ZD6126, and ZD1839 induced the greatest effects on tumor growth and angiogenesis. This first report shows that a selective vascular-targeting agent (ZD6126) + an anti-epidermal growth factor receptor agent (ZD1839) and radiation have additive in vivo effects in a human cancer model. Targeting the tumor vasculature offers an excellent strategy to enhance radiation cytotoxicity. Polytargeted therapy with agents that interfere with both growth factor and angiogenic signaling warrants further investigation.

  20. Abnormal skeletal growth patterns in adolescent idiopathic scoliosis--a longitudinal study until skeletal maturity.

    PubMed

    Yim, Annie P Y; Yeung, Hiu-Yan; Hung, Vivian W Y; Lee, Kwong-Man; Lam, Tsz-Ping; Ng, Bobby K W; Qiu, Yong; Cheng, Jack C Y

    2012-08-15

    A cross-sectional and prospective longitudinal study on the anthropometric parameters and growth pattern of girls with adolescent idiopathic scoliosis (AIS). To investigate the growth pattern of girls with AIS with different severities, using cross-sectional and prospective longitudinal data set in comparison with age-matched healthy controls. AIS occurs in children during their pubertal growth spurt. Although there is no clear consensus on the difference in body height between girls with AIS and healthy controls, it is generally thought that the development and curve progression in girls with AIS is closely associated with their growth rate. There is no concrete prospective longitudinal study to document clearly the growth pattern and growth rate of subjects with AIS . A total of 611 girls with AIS and 296 healthy age-matched controls were included in the study and among them, 194 girls with AIS and 116 healthy controls were followed up until skeletal maturity. The girls with AIS were grouped into moderate (AIS20) and severe curve (AIS40) groups on the basis of maximum curve magnitude at skeletal maturity. Clinical data and detailed anthropometric parameters were recorded. In the cross-sectional analysis, the groups of subjects were compared within different age groups (from the age of 12-16 yr). In the longitudinal study, linear mixed modeling with respect to age or years since menarche was employed to formulate the growth trajectory of different anthropometric parameters. In the cross-sectional analysis, the girls with AIS were generally taller, with longer arm span and lower body mass index than the healthy controls. The girls with AIS40 were found to be significantly shorter in height (P = 0.006) and arm span (P = 0.025) at the age of 12 years but caught up and overtook the control group at the age of 14 to 16 years. In the longitudinal study, the average growth rate of arm span in girls with AIS40 was significantly higher than that in girls with AIS20 (> 30%) (P = 0.004) and controls (> 70%) (P = 0.0004). The age of menarche of girls with AIS40 was significantly delayed by 5.9 months and 3.8 months when compared with the control group and girls with AIS20, respectively (P < 0.05). The growth patterns of girls with AIS with confirmed curve severities were significantly different from healthy age-matched controls. Girls with severe AIS had delayed menarche with faster skeletal growth rate during the age of 12 to 16 years. Monitoring the rate of change of arm span of girls with AIS could be an important additional clinical parameter in helping predict curve severity in girls with AIS.

  1. Growth form-dependent response to physical disturbance and thermal stress in Acropora corals

    NASA Astrophysics Data System (ADS)

    Muko, S.; Arakaki, S.; Nagao, M.; Sakai, Kazuhiko

    2013-03-01

    To predict the community structure in response to changing environmental conditions, it is necessary to know the species-specific reaction and relative impact strength of each disturbance. We investigated the coral communities in two sites, an exposed and a protected site, at Iriomote Island, Japan, from 2005 to 2008. During the study period, a cyclone and thermal stress were observed. All Acropora colonies, classified into four morphologies (arborescent, tabular, corymbose, and digitate), were identified and tracked through time to calculate the annual mortality and growth rate. The mortality of all Acropora colonies in the protected site was lower than that in the exposed site during the period without disturbances. Extremely higher mortality due to bleaching was observed in tabular and corymbose Acropora, compared to other growth forms, at the protected sites after thermal stress. In contrast, physical disturbance by a tropical cyclone induced the highest mortality in arborescent and digitate corals at the exposed site. Moreover, arborescent corals exhibited a remarkable decline 1 year after the tropical cyclone at the exposed site. The growth of colonies that survived coral bleaching did not decrease in the following year compared to previous year for all growth forms, but the growth of arborescent and tabular remnant corals at the exposed site declined severely after the tropical cyclone compared to previous year. The delayed mortality and lowered growth rate after the tropical cyclone were probably due to the damage caused by the tropical cyclone. These results indicate that the cyclone had a greater impact on fragile corals than expected. This study provides useful information for the evaluation of Acropora coral response to progressing global warming conditions, which are predicted to increase in frequency and intensity in the near future.

  2. Modelling the effect of water activity reduction by sodium chloride or glycerol on conidial germination and radial growth of filamentous fungi encountered in dairy foods.

    PubMed

    Nguyen Van Long, Nicolas; Rigalma, Karim; Coroller, Louis; Dadure, Robin; Debaets, Stella; Mounier, Jérôme; Vasseur, Valérie

    2017-12-01

    Water activity (a w ) is one of the most influential abiotic factors affecting fungal development in foods. The effects of a w reduction on conidial germination and radial growth are generally studied by supplementing culture medium with the non-ionic solute glycerol despite food a w can also depend on the concentration of ionic solutes such as sodium chloride (NaCl). The present study aimed at modelling and comparing the effects of a w , either modified using NaCl or glycerol, on radial growth and/or conidial germination parameters for five fungal species occurring in the dairy environment. The estimated cardinal values were then used for growth prediction and compared to growth kinetics observed on commercial fresh cheese. Overall, as compared to glycerol, NaCl significantly increased the fungistatic effect resulting from a w reduction by extending latency and/or reducing radial growth rates of Paecilomyces niveus, Penicillium brevicompactum, Penicillium expansum and Penicillium roqueforti but not of Mucor lanceolatus. Besides, NaCl significantly reduced a w range for conidial germination and delayed median germination time of P. expansum but not of P. roqueforti. Despite these observations, cardinal a w values obtained on glycerol-medium yielded similar predictions of radial growth and germination time in commercial fresh cheese as those obtained with NaCl. Thus, it indicates that, for the studied species and a w range used for model validation, the use of NaCl instead of glycerol as a a w depressor had only limited impact for fungal behavior prediction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Neural activation during delay discounting is associated with 6-month change in risky sexual behavior in adolescents.

    PubMed

    Gardiner, Casey K; Karoly, Hollis C; Thayer, Rachel E; Gillman, Arielle S; Sabbineni, Amithrupa; Bryan, Angela D

    2018-04-19

    Identifying cognitive and neural mechanisms of decision making in adolescence can enhance understanding of, and interventions to reduce, risky health behaviors in adolescence. Delay discounting, or the propensity to discount the magnitude of temporally distal rewards, has been associated with diverse health risk behaviors, including risky sex. This cognitive process involves recruitment of reward and cognitive control brain regions, which develop on different trajectories in adolescence and are also implicated in real-world risky decision making. However, no extant research has examined how neural activation during delay discounting is associated with adolescents' risky sexual behavior. To determine whether a relationship exists between adolescents' risky sexual behavior and neural activation during delay discounting. Adolescent participants completed a delay discounting paradigm during functional magnetic resonance imaging (fMRI) scanning, and they reported risky sexual behavior at baseline, 3-, 6-, 9-, and 12-month follow-up time points. Latent growth curve models were employed to determine relationships between brain activation during delay discounting and change in risky sexual behavior over time. Greater activation in brain regions associated with reward and cognitive control (caudate, putamen, nucleus accumbens, anterior cingulate, insula, orbitofrontal cortex, inferior frontal gyrus, dorsolateral prefrontal cortex) during delay discounting was associated with lower mean levels of risky sexual behavior but greater growth over the period from baseline to 6 months. Neural activation during delay discounting is cross-sectionally and prospectively associated with risky sexual behavior in adolescence, highlighting a neural basis of risky decision-making as well as opportunities for early identification and intervention.

  4. Constrained growth flips the direction of optimal phenological responses among annual plants.

    PubMed

    Lindh, Magnus; Johansson, Jacob; Bolmgren, Kjell; Lundström, Niklas L P; Brännström, Åke; Jonzén, Niclas

    2016-03-01

    Phenological changes among plants due to climate change are well documented, but often hard to interpret. In order to assess the adaptive value of observed changes, we study how annual plants with and without growth constraints should optimize their flowering time when productivity and season length changes. We consider growth constraints that depend on the plant's vegetative mass: self-shading, costs for nonphotosynthetic structural tissue and sibling competition. We derive the optimal flowering time from a dynamic energy allocation model using optimal control theory. We prove that an immediate switch (bang-bang control) from vegetative to reproductive growth is optimal with constrained growth and constant mortality. Increasing mean productivity, while keeping season length constant and growth unconstrained, delayed the optimal flowering time. When growth was constrained and productivity was relatively high, the optimal flowering time advanced instead. When the growth season was extended equally at both ends, the optimal flowering time was advanced under constrained growth and delayed under unconstrained growth. Our results suggests that growth constraints are key factors to consider when interpreting phenological flowering responses. It can help to explain phenological patterns along productivity gradients, and links empirical observations made on calendar scales with life-history theory. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  5. Effects of growth hormone treatment on growth in children with juvenile idiopathic arthritis.

    PubMed

    Simon, D; Bechtold, S

    2009-11-01

    Several therapeutic trials have been conducted over the past decade to evaluate the role of exogenous growth hormone (GH) as a means of correcting the growth deficiency seen in children with juvenile idiopathic arthritis (JIA). Early studies showed the benefit of GH treatment with respect to final height in patients with JIA. Of 13 patients receiving GH, 84% (11 patients) achieved a final height within their target range compared with only 22% (4 of 18 patients) of untreated patients. There are, however, factors that may limit the statural gains achieved with GH therapy including severe inflammation, severe statural deficiency at GH therapy initiation, long disease duration and delayed puberty. Data on the efficacy of GH replacement therapy in children with JIA and factors that influence the statural growth response will be reviewed. Results from therapeutic trials show that treatment with GH can decrease the statural deficit that occurs during the active phase of JIA, producing an adult height that is close to the genetically determined target height. Copyright 2009 S. Karger AG, Basel.

  6. Effects of high-energy shock waves combined with biological response modifiers or Adriamycin on a human kidney cancer xenograft.

    PubMed

    Oosterhof, G O; Smiths, G A; deRuyter, J E; Schalken, J A; Debruyne, F M

    1990-01-01

    We have studied the effect of high-energy shock waves (HESW) alone or in combination with biological response modifiers (BRMs) or Adriamycin on the growth of the NU-1 human kidney cancer xenograft. When HESW are administered repeatedly (four sessions of 800 shock waves on days 0, 2, 4 and 6) a prolonged delay in tumor growth was found compared with that following a single administration. This effect was temporary, and several days after stopping the HESW administration the tumor regained its original growth potential (same doubling time). Tumor growth was suppressed for a longer period by the combination of 4 sessions of HESW and a single administration of Adriamycin, 5 mg/kg. Combination of HESW treatment with interferon alpha (5.0 ng/g body weight, three times/week) and tumor necrosis factor alpha (500 ng/g body weight, 5 days/week) s.c. around the tumor resulted in a complete cessation of tumor growth. While Adriamycin had an additive effect on HESW treatment, the combination with BRMs was highly synergistic.

  7. The use of autologous concentrated growth factors to promote syndesmosis fusion in the Agility total ankle replacement. A preliminary study.

    PubMed

    Coetzee, J Chris; Pomeroy, Gregory C; Watts, J David; Barrow, Craig

    2005-10-01

    The Agility (DePuy, Warsaw, Indiana) total ankle replacement has been in use since 1984. One of the most common complications continues to be delayed union or nonunions of the distal tibiofibular syndesmosis. In the reported studies on the Agility ankle the delayed union and nonunion rate can be as high as 38%. Since 1999, 114 Agility total ankle replacements were done at two centers in the United States without the use of autologous concentrated growth factors. Since July of 2001, 66 Agility ankles were implanted with Symphony (DePuy, Warsaw, Indiana) augmented bone grafting. The standard operative technique was followed in all the patients. Prospective data was collected on all patients. The standard ankle radiographs were taken preoperatively and postoperative at 8 weeks, 12 weeks, 16 weeks, 6 months, and yearly. CT scans were obtained at 6 months if fusion at the syndesmosis was questionable. The Graphpad Instat software (Graphpad Software Inc., San Diego, CA) was used for statistical analysis. The two-tailed unpaired t-test was used, and the value <0.05 was considered significant. There was no statistical difference in the demographic data for the two groups. In 114 ankle replacements without autologous concentrated growth factors 70 fused at 8 weeks (61%), 14 fused at 12 weeks (12%), 13 fused at 6 months (12%). There were 17 nonunions (15%); delayed unions (3 to 6 months) and nonunions, therefore, equaled 27%. The syndesmosis fused in 50 of the 66 ankle replacements (76%) that had autologous concentrated growth fractures at 8 weeks (76%); 12 fused at 3 months (18%), 2 fused at 6 months (3%), 2 had nonunions (3%). Delayed unions (3 to 6 months) and nonunions equaled 6%. There was a statistically significant improvement in the 8- and 12-week fusion rates, and a statistically significant reduction in delayed unions and nonunions. Autologous concentrated growth factors appear to make a significant positive difference in the syndesmosis union rate in total ankle replacements.

  8. Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

    PubMed Central

    Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

    2013-01-01

    Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Results Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (Ito), the rapidly activated omponent of delayed rectifier potassium current (IKr), the slowly activated component of delayed rectifier potassium current (IKs), and the L-type calcium current (ICaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Conclusions Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca2+ current are likely the underlying mechanism of action. PMID:23610573

  9. Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction.

    PubMed

    Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

    2013-03-01

    To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (I to), the rapidly activated omponent of delayed rectifier potassium current (I Kr), the slowly activated component of delayed rectifier potassium current (I Ks), and the L-type calcium current (I CaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca(2+) current are likely the underlying mechanism of action.

  10. Somatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity

    PubMed Central

    Sun, Liou Y.; Longo, Valter

    2013-01-01

    Growth hormone (GH) is a key determinant of postnatal growth and plays an important role in the control of metabolism and body composition. Surprisingly, deficiency in GH signaling delays aging and remarkably extends longevity in laboratory mice. In GH-deficient and GH-resistant animals, the “healthspan” is also extended with delays in cognitive decline and in the onset of age-related disease. The role of hormones homologous to insulin-like growth factor (IGF, an important mediator of GH actions) in the control of aging and lifespan is evolutionarily conserved from worms to mammals with some homologies extending to unicellular yeast. The combination of reduced GH, IGF-I, and insulin signaling likely contributes to extended longevity in GH or GH receptor-deficient organisms. Diminutive body size and reduced fecundity of GH-deficient and GH-resistant mice can be viewed as trade-offs for extended longevity. Mechanisms responsible for delayed aging of GH-related mutants include enhanced stress resistance and xenobiotic metabolism, reduced inflammation, improved insulin signaling, and various metabolic adjustments. Pathological excess of GH reduces life expectancy in men as well as in mice, and GH resistance or deficiency provides protection from major age-related diseases, including diabetes and cancer, in both species. However, there is yet no evidence of increased longevity in GH-resistant or GH-deficient humans, possibly due to non-age-related deaths. Results obtained in GH-related mutant mice provide striking examples of mutations of a single gene delaying aging, reducing age-related disease, and extending lifespan in a mammal and providing novel experimental systems for the study of mechanisms of aging. PMID:23589828

  11. Response inhibition difficulties in preterm children aged 9-12 years: Relations with emotion and behavior.

    PubMed

    Réveillon, Morgane; Borradori Tolsa, Cristina; Monnier, Maryline; Hüppi, Petra S; Barisnikov, Koviljka

    2016-01-01

    Previous studies with children have demonstrated inhibition difficulties associated with prematurity, but the question of potentially catching up with a delay in inhibition processes before adolescence still remains. Moreover, preterm adolescents are more at risk than their term-born peers for presenting behavioral problems such as emotional difficulties and attention deficit/hyperactivity disorder. In addition to examining response inhibition, this study addressed, for the first time, the impact of an emotional context on response inhibition abilities and its relation to behavioral problems in late school-aged preterm children. Fifty-eight preterm children aged 9-12 years were compared with 61 controls on two versions of a stop-signal task, the Delay Frustration Task, and the Strengths and Difficulties Questionnaire. Results showed general difficulties in inhibiting a response, rather than a specific impact of emotional context in preterm children. Compared with controls, these children exhibited more and longer button presses in a delay situation, as well as faster go reaction times associated with lower probability of inhibition in the stop-signal tasks. These difficulties reflected impulsivity and were associated with higher hyperactivity/inattention and conduct problems. Additionally, intrauterine growth restriction was found to be an additional perinatal risk factor for hyperactivity/inattention symptoms. These findings suggest that remaining inhibition difficulties in the preterm population at preadolescence could reveal increasing behavioral issues.

  12. Cognitive Function in Individuals with Atypical Pubertal Development.

    ERIC Educational Resources Information Center

    Rovet, Joanne F.; And Others

    A study of 55 growth-disturbed children, aged 8-17, was conducted to assess how rate of physical maturation and pubertal development influences cognitive and neuropsychological functioning. The sample included 27 boys with short stature and delayed pubertal development (SSB), 15 girls with delayed puberty (DPG), and 13 girls with precocious…

  13. Kidney transplantation fails to provide adequate growth in children with chronic kidney disease born small for gestational age.

    PubMed

    Franke, Doris; Steffens, Rena; Thomas, Lena; Pavičić, Leo; Ahlenstiel, Thurid; Pape, Lars; Gellermann, Jutta; Müller, Dominik; Querfeld, Uwe; Haffner, Dieter; Živičnjak, Miroslav

    2017-03-01

    Children with chronic kidney disease are frequently born small for gestational age (SGA) and prone to disproportionately short stature. It is unclear how SGA affects growth after kidney transplantation (KTx). Linear growth (height, sitting height, and leg length) was prospectively investigated in a cohort of 322 pediatric KTx recipients, with a mean follow-up of 4.9 years. Sitting height index (ratio of sitting height to total body height) was used to assess body proportions. Predictors of growth outcome in KTx patients with (n = 94) and without (n = 228) an SGA history were evaluated by the use of linear mixed-effects models. Mean z-scores for all linear body dimensions were lower in SGA compared with non-SGA patients (p < 0.001). SGA patients presented with higher target height deficit and degree of body disproportion (p < 0.001). The latter was mainly due to reduced leg growth during childhood. Pubertal trunk growth was diminished in SGA patients, and the pubertal growth spurt of legs was delayed in both groups, resulting in further impairment of adult height, which was more frequently reduced in SGA than in non-SGA patients (50 % vs 18 %, p < 0.001). Use of growth hormone treatment in the pre-transplant period, preemptive KTx, transplant function, and control of metabolic acidosis were the only potentially modifiable correlates of post-transplant growth in SGA groups. By contrast, living related KTx, steroid exposure, and degree of anemia proved to be correlates in non-SGA only. In children born SGA, growth outcome after KTx is significantly more impaired and affected by different clinical parameters compared with non-SGA patients.

  14. Antitumor activity of cryptophycins: effect of infusion time and combination studies.

    PubMed

    Menon, K; Alvarez, E; Forler, P; Phares, V; Amsrud, T; Shih, C; Al-Awar, R; Teicher, B A

    2000-01-01

    Cryptophycins are a family of antitubulin antitumor agents. A synthetic cryptophycin derivative (LY355703, CRYPTO 52) is in early clinical evaluation. The effect of infusion time on the antitumor activity of four cryptophycins was assessed in rats bearing the 13762 mammary carcinoma and combination treatment regimens were assessed in nude mice bearing human tumor xenografts. The cryptophycins were prepared in 2% PEG300/8% cremophor/90% normal saline and delivered by jugular vein catheter on days 7, 9 and 11 post tumor implant to 13762 tumor-bearing rats. The cryptophycins prepared in the same formulation were administered by intravenous bolus injection on an alternate day schedule for five doses to human tumor xenograft bearing nude mice. An infusion time of 2 h in the rats increased the tumor growth delay produced by CRYPTO 52 and CRYPTO 55, while increasing the infusion time to 6 h continued to increase the tumor growth delay for CRYPTO 292 and CRYPTO 296. Administering CRYPTO 292 at a higher dose two times was more effective than administering it at a lower dose three times. The tumor growth delays produced by the cryptophycins in the rat 13762 mammary carcinoma were greater than those with cisplatin, doxorubicin, 5-fluorouracil and 5 x 3 Gray and comparable with cyclophosphamide and gemcitabine. Combination studies were carried out in human tumor xenografts including the MX-1 breast carcinoma, the Calu-6 non-small cell lung carcinoma, the H82 small cell lung carcinoma and the SW-2 small cell lung carcinoma. CRYPTO 52 and CRYPTO 55 combined with doxorubicin, paclitaxel and 5-fluorouracil to form highly effective regimens against the human MX-1 breast carcinoma. CRYPTO 52 and CRYPTO 55 were also highly effective against the three lung carcinoma xenografts when combined with the antitumor platinum complexes, cisplatin, carboplatin or oxaliplatin. Cryptophycins represent a promising new class of antitumor agents that may be optimally administered by intravenous infusion and in combination with doxorubicin, paclitaxel and 5-fluorouracil.

  15. Effects of masker frequency and duration in forward masking: further evidence for the influence of peripheral nonlinearity.

    PubMed

    Oxenham, A J; Plack, C J

    2000-12-01

    Forward masking has often been thought of in terms of neural adaptation, with nonlinearities in the growth and decay of forward masking being accounted for by the nonlinearities inherent in adaptation. In contrast, this study presents further evidence for the hypothesis that forward masking can be described as a linear process, once peripheral, mechanical nonlinearities are taken into account. The first experiment compares the growth of masking for on- and off-frequency maskers. Signal thresholds were measured as a function of masker level for three masker-signal intervals of 0, 10, and 30 ms. The brief 4-kHz sinusoidal signal was masked by a 200-ms sinusoidal forward masker which had a frequency of either 2.4 kHz (off-frequency) or 4 kHz (on-frequency). As in previous studies, for the on-frequency condition, the slope of the function relating signal threshold to masker level became shallower as the delay between the masker and signal was increased. In contrast, the slopes for the off-frequency condition were independent of masker-signal delay and had a value of around unity, indicating linear growth of masking for all masker-signal delays. In the second experiment, a broadband Gaussian noise forward masker was used to mask a brief 6-kHz sinusoidal signal. The spectrum level of the masker was either 0 or 40 dB (re: 20 microPa). The gap between the masker and signal was either 0 or 20 ms. Signal thresholds were measured for masker durations from 5 to 200 ms. The effect of masker duration was found to depend more on signal level than on gap duration or masker level. Overall, the results support the idea that forward masking can be modeled as a linear process, preceded by a static nonlinearity resembling that found on the basilar membrane.

  16. On the delay factors of the private construction projects in Medan city

    NASA Astrophysics Data System (ADS)

    Perwira Mulia Tarigan, A.; Subroto

    2018-03-01

    The delay in construction projects undertaken by contractors is impeding the economic growth of a region. Medan city which is one of the big cities in Indonesia is suffering from it. This study aims to identify the dominant factors causing delays in construction projects conducted by private contractors. The interview method with questionnaires is used to involve 20 contractors, 10 consultants, and 10 owner representatives in the study. From the 45 identified factors causing delays, the highest ranking is the change of work demand by the project owners with 71.84% importance index.

  17. Fitted Fourier-pseudospectral methods for solving a delayed reaction-diffusion partial differential equation in biology

    NASA Astrophysics Data System (ADS)

    Adam, A. M. A.; Bashier, E. B. M.; Hashim, M. H. A.; Patidar, K. C.

    2017-07-01

    In this work, we design and analyze a fitted numerical method to solve a reaction-diffusion model with time delay, namely, a delayed version of a population model which is an extension of the logistic growth (LG) equation for a food-limited population proposed by Smith [F.E. Smith, Population dynamics in Daphnia magna and a new model for population growth, Ecology 44 (1963) 651-663]. Seeing that the analytical solution (in closed form) is hard to obtain, we seek for a robust numerical method. The method consists of a Fourier-pseudospectral semi-discretization in space and a fitted operator implicit-explicit scheme in temporal direction. The proposed method is analyzed for convergence and we found that it is unconditionally stable. Illustrative numerical results will be presented at the conference.

  18. De morseir syndrome presenting as ambiguous genitalia.

    PubMed

    Thukral, Anubhav; Chitra, S; Chakraborty, Partho P; Roy, Ajitesh; Goswami, Soumik; Bhattacharjee, Rana; Dutta, Deep; Maisnam, Indira; Ghosh, Sujoy; Mukherjee, Satinath; Chowdhury, Subhankar

    2012-12-01

    A 10-year-old boy presented with genital ambiguity, poor linear growth, and delayed milestones. The aim and to highlight that although rare but congenital, hypogonadotropic hypogonadism may rarely present as ambiguity. The patient was found to have bilateral cryptorchidism with proximal penile hypospadias, microphallus with a proportionate dwarfism with mildly delayed bone age, and karyotype 46XY. Euthyroid with normal steroid axis, growth hormone insufficient as suggested by auxology, low IGF1, and poor response to clonidine stimulation. MRI brain shows hypoplastic corpus callosum, hypoplastic anterior pituitary, and ectopic posterior pituitary bright spot. The patient underwent laparoscopic removal of right intrabdominal testis and orchidoplexy was performed on the left one. Testicular biopsy revealed no malignancy and growth hormone replacement was initiated. The patient awaits definitive repair of hypospadias. As a provisional diagnosis of combined growth hormone and gonadotropin deficiency, most probable diagnosis is septo-optic dysplasia or de moseir syndrome leading to genital ambiguity.

  19. Cloud condensation nuclei droplet growth kinetics of ultrafine particles during anthropogenic nucleation events

    NASA Astrophysics Data System (ADS)

    Shantz, N. C.; Pierce, J. R.; Chang, R. Y.-W.; Vlasenko, A.; Riipinen, I.; Sjostedt, S.; Slowik, J. G.; Wiebe, A.; Liggio, J.; Abbatt, J. P. D.; Leaitch, W. R.

    2012-02-01

    Evolution of the cloud condensation nucleus (CCN) activity of 36 ± 4 nm diameter anthropogenic aerosol particles at a water supersaturation of 1.0 ± 0.1% is examined for particle nucleation and growth. During the early stages of one event, relatively few of the anthropogenic particles at 36 nm were CCN active and their growth rates by water condensation were delayed relative to ammonium sulphate particles. As the event progressed, the particle size distribution evolved to larger sizes and the relative numbers of particles at 36 nm that were CCN active increased until all the 36 nm particles were activating at the end of the event. Based on the chemistry of larger particles and the results from an aerosol chemical microphysics box model, the increase in CCN activity of the particles was most likely the result of the condensation of sulphate in this case. Despite the increased CCN activity, a delay was observed in the initial growth of these particles into cloud droplets, which persisted even when the aerosol was most CCN active later in the afternoon. Simulations show that the delay in water uptake is explained by a reduction of the mass accommodation coefficient assuming that the composition of the 36 nm particles is the same as the measured composition of the 60-100 nm particles.

  20. The effects of the framing of time on delay discounting.

    PubMed

    DeHart, William Brady; Odum, Amy L

    2015-01-01

    We examined the effects of the framing of time on delay discounting. Delay discounting is the process by which delayed outcomes are devalued as a function of time. Time in a titrating delay discounting task is often framed in calendar units (e.g., as 1 week, 1 month, etc.). When time is framed as a specific date, delayed outcomes are discounted less compared to the calendar format. Other forms of framing time; however, have not been explored. All participants completed a titrating calendar unit delay-discounting task for money. Participants were also assigned to one of two delay discounting tasks: time as dates (e.g., June 1st, 2015) or time in units of days (e.g., 5000 days), using the same delay distribution as the calendar delay-discounting task. Time framed as dates resulted in less discounting compared to the calendar method, whereas time framed as days resulted in greater discounting compared to the calendar method. The hyperboloid model fit best compared to the hyperbola and exponential models. How time is framed may alter how participants attend to the delays as well as how the delayed outcome is valued. Altering how time is framed may serve to improve adherence to goals with delayed outcomes. © Society for the Experimental Analysis of Behavior.

  1. Effect of Multiple Delays in an Eco-Epidemiological Model with Strong Allee Effect

    NASA Astrophysics Data System (ADS)

    Ghosh, Kakali; Biswas, Santanu; Samanta, Sudip; Tiwari, Pankaj Kumar; Alshomrani, Ali Saleh; Chattopadhyay, Joydev

    In the present article, we make an attempt to investigate the effect of two time delays, logistic delay and gestation delay, on an eco-epidemiological model. In the proposed model, strong Allee effect is considered in the growth term of the prey population. We incorporate two time lags and inspect elementary mathematical characteristic of the proposed model such as boundedness, uniform persistence, stability and Hopf-bifurcation for all possible combinations of both delays at the interior equilibrium point of the system. We observe that increase in gestation delay leads to chaotic solutions through the limit cycle. We also observe that the Allee effect play a major role in controlling the chaos. We execute several numerical simulations to illustrate the proposed mathematical model and our analytical findings.

  2. Influence of postmortem time on the outcome of blood cultures among cadaveric tissue donors.

    PubMed

    Saegeman, V; Verhaegen, J; Lismont, D; Verduyckt, B; De Rijdt, T; Ectors, N

    2009-02-01

    Tissue banks provide tissues of human cadaver donors for transplantation. The maximal time limit for tissue retrieval has been set at 24 h postmortem. This study aimed at evaluating the evidence for this limit from a microbiological point of view. The delay of growth in postmortem blood cultures, the identification of the species isolated and clinical/environmental factors were investigated among 100 potential tissue donors. No significant difference was found in the rate of donors with grown blood cultures within (25/65=38%) compared with after (24/65=37%) 24 h of death. Coagulase-negative staphylococci and gastro-intestinal microorganisms were isolated within and after 24 h of death. Two factors--antimicrobial therapy and "delay before body cooling"--were significantly inversely related with donors' blood culture results. From a microbiological point of view, there is no evidence for avoiding tissue retrieval among donors after 24 h of death.

  3. A method of operation scheduling based on video transcoding for cluster equipment

    NASA Astrophysics Data System (ADS)

    Zhou, Haojie; Yan, Chun

    2018-04-01

    Because of the cluster technology in real-time video transcoding device, the application of facing the massive growth in the number of video assignments and resolution and bit rate of diversity, task scheduling algorithm, and analyze the current mainstream of cluster for real-time video transcoding equipment characteristics of the cluster, combination with the characteristics of the cluster equipment task delay scheduling algorithm is proposed. This algorithm enables the cluster to get better performance in the generation of the job queue and the lower part of the job queue when receiving the operation instruction. In the end, a small real-time video transcode cluster is constructed to analyze the calculation ability, running time, resource occupation and other aspects of various algorithms in operation scheduling. The experimental results show that compared with traditional clustering task scheduling algorithm, task delay scheduling algorithm has more flexible and efficient characteristics.

  4. [Delayed testing for the diagnosis of fungi in the urines. Evaluation of the BD Vacutainer C&S tubes for the storage of urine samples at room temperature].

    PubMed

    Baixench, M T; Al-Sheikh, M; Paugam, A

    2005-01-01

    The study included 37 urine samples which have been artificially infected with low levels (10(3) CFU/mL) of various fungi strains. We compared the effects of sample storage, up to 48 hours, at room temperature, in a urine evacuated tube containing specific additives with storage at + 4 degrees C, for the same length of time, in a urine evacuated tube without any additives. There have been no differences of results (speed of growth and colony size) between the 2 modes of storage. However, the experience has shown that samples needed a careful mixing before seeding to avoid underdetection of the strains. Based on the study results, the BD Vacutainer C&S tubes are suitable for delayed testing for the diagnosis of urine fungal infection.

  5. Blocking VEGF signaling delays development of replacement teeth in zebrafish.

    PubMed

    Crucke, J; Huysseune, A

    2015-01-01

    The dentition in zebrafish is extremely and richly vascularized, but the function of the vasculature, in view of the continuous replacement of the teeth, remains elusive. Through application of SU5416, a vascular endothelial growth factor receptor inhibitor, we studied the role of the blood vessels in the dentition of the zebrafish. We were unable to show an effect on the development of first-generation teeth as well as first tooth replacement. However, in juvenile fish, a delay was observed in the developmental state of the replacement tooth compared with what was expected based on the maturation state of the functional tooth. Furthermore, we observed a difference between treated and nontreated fish in the distance between blood vessels and developing replacement teeth. In conclusion, our results provide support for a nutritive, rather than an inductive, function of the vasculature in the process of tooth development and replacement. © International & American Associations for Dental Research 2014.

  6. Growth and maturity status of elite British junior tennis players.

    PubMed

    Myburgh, Gillian K; Cumming, Sean P; Coelho E Silva, Manuel; Cooke, Karl; Malina, Robert M

    2016-10-01

    Growth and maturation impact the selection, development and progression of youth athletes. Individual differences in the growth and maturity may afford a performance advantage, clouding coaches and practitioners' perceptions regarding current ability and future potential. This may result in the exclusion of talented, yet less physically gifted athletes. Participants were 91 male (n = 47) and female (n = 44) elite British Junior tennis players, 8-17 years of age (12.5 ± 1.9 years). Height and body mass were measured and compared to growth charts; hand-wrist radiographs were taken. Skeletal age (SA) was estimated with the Fels method and contrasted to chronological age (CA). Mean height and body mass of individual players ranged between the 50th and 90th centiles for age and sex. Females were advanced in SA relative to CA (0.3-0.89 years.) from 8 years. Males were average to delayed in maturation from 8 to 12 years, but advanced in SA from 14 to 16 years (0.75-1.23 years). Individual differences in growth and maturation appear to contribute towards the selection of elite junior tennis players, with a bias towards males and females who are advanced in maturation and comparatively tall and heavy for their age. This has important implications for talent identification and development.

  7. A novel multi-drug metronomic chemotherapy significantly delays tumor growth in mice.

    PubMed

    Tagliamonte, Maria; Petrizzo, Annacarmen; Napolitano, Maria; Luciano, Antonio; Rea, Domenica; Barbieri, Antonio; Arra, Claudio; Maiolino, Piera; Tornesello, Marialina; Ciliberto, Gennaro; Buonaguro, Franco M; Buonaguro, Luigi

    2016-02-24

    The tumor immunosuppressive microenvironment represents a major obstacle to an effective tumor-specific cellular immune response. In the present study, the counterbalance effect of a novel metronomic chemotherapy protocol on such an immunosuppressive microenvironment was evaluated in a mouse model upon sub-cutaneous ectopic implantation of B16 melanoma cells. The chemotherapy consisted of a novel multi-drug cocktail including taxanes and alkylating agents, administered in a daily metronomic fashion. The newly designed strategy was shown to be safe, well tolerated and significantly efficacious. Treated animals showed a remarkable delay in tumor growth and prolonged survival as compared to control group. Such an effect was directly correlated with CD4(+) T cell reduction and CD8(+) T cell increase. Furthermore, a significant reduction in the percentage of both CD25(+)FoxP3(+) and CD25(+)CD127(low) regulatory T cell population was found both in the spleens and in the tumor lesions. Finally, the metronomic chemotherapy induced an intrinsic CD8(+) T cell response specific to B16 naturally expressed Trp2 TAA. The novel multi-drug daily metronomic chemotherapy evaluated in the present study was very effective in counterbalancing the immunosuppressive tumor microenvironment. Consequently, the intrinsic anti-tumor T cell immunity could exert its function, targeting specific TAA and significantly containing tumor growth. Overall, the results show that this represents a promising adjuvant approach to significantly enhance efficacy of intrinsic or vaccine-elicited tumor-specific cellular immunity.

  8. Enhanced cytostatic activity of the sesquiterpene lactone eupatoriopicrin by glutathione depletion.

    PubMed Central

    Woerdenbag, H. J.; Lemstra, W.; Malingré, T. M.; Konings, A. W.

    1989-01-01

    Eupatoriopicrin (EUP), a sesquiterpene lactone from Eupatorium cannabinum L., possesses cytostatic activity. This was demonstrated for FIO 26 cells in vitro with the aid of a clonogenic assay and in vivo by tumour growth delay in FIO 26 and Lewis lung tumour-bearing mice. In vitro the IC50 for 1 h exposure to EUP was 1.5 microgram ml-1 (4.1 nmol ml-1). This concentration depleted about 25% of its cellular GSH concentration. Pretreatment of FIO 26 cells with BSO, resulting in greater than 99%. GSH depletion, enhanced the cytotoxic effect of EUP. The dose-enhancement factor at the level of 10% cell survival was 2.3. Growth inhibition of the Lewis lung carcinoma and the FIO 26 fibrosarcoma, solidly growing in C57Bl mice, was found after i.v. injection of 20 or 40 mg kg-1 EUP, at a tumour volume of about 500 microliters. Pretreatment with BSO at a dose of 4 mmol kg-1 i.p., 6 h before EUP administration, resulted in a significantly stronger growth delay of both tumours compared with EUP only. At the time of EUP treatment, cellular GSH in the tumours was reduced by BSO treatment to about 60%. It is concluded that EUP possesses antitumour activity in vivo and that chemosensitisation of EUP may be accomplished by pretreatment with BSO, indicating that endogenous GSH protects against the cytostatic action of EUP. PMID:2757925

  9. Scaling induced performance challenges/limitations of on-chip metal interconnects and comparisons with optical interconnects

    NASA Astrophysics Data System (ADS)

    Kapur, Pawan

    The miniaturization paradigm for silicon integrated circuits has resulted in a tremendous cost and performance advantage. Aggressive shrinking of devices provides faster transistors and a greater functionality for circuit design. However, scaling induced smaller wire cross-sections coupled with longer lengths owing to larger chip areas, result in a steady deterioration of interconnects. This degradation in interconnect trends threatens to slow down the rapid growth along Moore's law. This work predicts that the situation is worse than anticipated. It shows that in the light of technology and reliability constraints, scaling induced increase in electron surface scattering, fractional cross section area occupied by the highly resistive barrier, and realistic interconnect operation temperature will lead to a significant rise in effective resistivity of modern copper based interconnects. We start by discussing various technology factors affecting copper resistivity. We, next, develop simulation tools to model these effects. Using these tools, we quantify the increase in realistic copper resistivity as a function of future technology nodes, under various technology assumptions. Subsequently, we evaluate the impact of these technology effects on delay and power dissipation of global signaling interconnects. Modern long on-chip wires use repeaters, which dramatically improves their delay and bandwidth. We quantify the repeated wire delays and power dissipation using realistic resistance trends at future nodes. With the motivation of reducing power, we formalize a methodology, which trades power with delay very efficiently for repeated wires. Using this method, we find that although the repeater power comes down, the total power dissipation due to wires is still found to be very large at future nodes. Finally, we explore optical interconnects as a possible substitute, for specific interconnect applications. We model an optical receiver and waveguides. Using this we assess future optical system performance. Finally, we compare the delay and power of future metal interconnects with that of optical interconnects for global signaling application. We also compare the power dissipation of the two approaches for an upper level clock distribution application. We find that for long on-chip communication links, optical interconnects have lower latencies than future metal interconnects at comparable levels of power dissipation.

  10. Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy.

    PubMed

    Wang, Yabo; Wang, Xingyu; Le Bitoux, Marie-Aude; Wagnieres, Georges; Vandenbergh, Hubert; Gonzalez, Michel; Ris, Hans-Beat; Perentes, Jean Y; Krueger, Thorsten

    2015-04-01

    The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response. Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group). Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls. Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics. © 2015 Wiley Periodicals, Inc.

  11. Floating-Harbor syndrome: description of a further patient, review of the literature, and suggestion of autosomal dominant inheritance.

    PubMed

    Lacombe, D; Patton, M A; Elleau, C; Battin, J

    1995-08-01

    The Floating-Harbor syndrome is a growth retardation syndrome with delayed bone age, speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips. We present an additional patient and review 16 cases from the literature. The possible phenotype in the patient's mother suggests a dominant mode of inheritance for the syndrome. The Floating Harbor syndrome is a growth deficiency syndrome characterized by proportionate short stature, characteristic face and delayed speech development. Inheritance is possibly autosomal dominant.

  12. Prolonged survival of dendritic cell-vaccinated melanoma patients correlates with tumor-specific delayed type IV hypersensitivity response and reduction of tumor growth factor beta-expressing T cells.

    PubMed

    López, Mercedes N; Pereda, Cristian; Segal, Gabriela; Muñoz, Leonel; Aguilera, Raquel; González, Fermín E; Escobar, Alejandro; Ginesta, Alexandra; Reyes, Diego; González, Rodrigo; Mendoza-Naranjo, Ariadna; Larrondo, Milton; Compán, Alvaro; Ferrada, Carlos; Salazar-Onfray, Flavio

    2009-02-20

    The aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines. Forty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records. The overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) beta+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P < .0001). Our findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFbeta+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.

  13. DNA-dependent protein kinase is a molecular target for the development of noncytotoxic radiation-sensitizing drugs.

    PubMed

    Shinohara, Eric T; Geng, Ling; Tan, Jiahui; Chen, Heidi; Shir, Yu; Edwards, Eric; Halbrook, James; Kesicki, Edward A; Kashishian, Adam; Hallahan, Dennis E

    2005-06-15

    DNA-dependent protein kinase (DNA-PK)-defective severe combined immunodeficient (SCID) mice have a greater sensitivity to ionizing radiation compared with wild-type mice due to deficient repair of DNA double-strand break. SCID cells were therefore studied to determine whether radiosensitization by the specific inhibitor of DNA-PK, IC87361, is eliminated in the absence of functional DNA-PK. IC87361 enhanced radiation sensitivity in wild-type C57BL6 endothelial cells but not in SCID cells. The tumor vascular window model was used to assess IC87361-induced radiosensitization of SCID and wild-type tumor microvasculature. Vascular density was 5% in irradiated SCID host compared with 50% in C57BL6 mice (P < 0.05). IC87361 induced radiosensitization of tumor microvasculature in wild-type mice that resembled the radiosensitive phenotype of tumor vessels in SCID mice. Radiosensitization by IC87361 was eliminated in SCID tumor vasculature, which lack functional DNA-PK. Irradiated LLC and B16F0 tumors implanted into SCID mice showed greater tumor growth delay compared with tumors implanted into either wild-type C57BL6 or nude mice. Furthermore, LLC tumors treated with radiation and IC87361 showed tumor growth delay that was significantly greater than tumors treated with radiation alone (P < 0.01 for 3 Gy alone versus 3 Gy + IC87361). DNA-PK inhibitors induced no cytotoxicity and no toxicity in mouse normal tissues. Mouse models deficient in enzyme activity are useful to assess the specificity of novel kinase inhibitors. DNA-PK is an important target for the development of novel radiation-sensitizing drugs that have little intrinsic cytotoxicity.

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

    Meyer, Kurt; Krueger, Sarah A.; Kane, Jonathan L.

    Purpose: To assess the efficacy of 3-week schedules of low-dose pulsed radiation treatment (PRT) and standard radiation therapy (SRT), with concurrent cisplatin (CDDP) in a head and neck squamous cell carcinoma xenograft model. Methods and Materials: Subcutaneous UT-SCC-14 tumors were established in athymic NIH III HO female mice. A total of 30 Gy was administered as 2 Gy/d, 5 d/wk for 3 weeks, either by PRT (10 × 0.2 Gy/d, with a 3-minute break between each 0.2-Gy dose) or SRT (2 Gy/d, uninterrupted delivery) in combination with concurrent 2 mg/kg CDDP 3 times per week in the final 2 weeks of radiation therapy. Treatment-induced growth delays were defined from twice-weeklymore » tumor volume measurements. Tumor hypoxia was assessed by {sup 18}F-fluoromisonidazole positron emission tomography imaging, and calculated maximum standardized uptake values compared with tumor histology. Tumor vessel density and hypoxia were measured by quantitative immunohistochemistry. Normal tissues effects were evaluated in gut and skin. Results: Untreated tumors grew to 1000 mm{sup 3} in 25.4 days (±1.2), compared with delays of 62.3 days (±3.5) for SRT + CDDP and 80.2 days (±5.0) for PRT + CDDP. Time to reach 2× pretreatment volume ranged from 8.2 days (±1.8) for untreated tumors to 67.1 days (±4.7) after PRT + CDDP. Significant differences in tumor growth delay were observed for SRT versus SRT + CDDP (P=.04), PRT versus PRT + CDDP (P=.035), and SRT + CDDP versus PRT + CDDP (P=.033), and for survival between PRT versus PRT + CDDP (P=.017) and SRT + CDDP versus PRT + CDDP (P=.008). Differences in tumor hypoxia were evident by {sup 18}F-fluoromisonidazole positron emission tomography imaging between SRT and PRT (P=.025), although not with concurrent CDDP. Tumor vessel density differed between SRT + CDDP and PRT + CDDP (P=.011). No differences in normal tissue parameters were seen. Conclusions: Concurrent CDDP was more effective in combination PRT than SRT at restricting tumor growth. Significant differences in tumor vascular density were evident between PRT and SRT, suggesting a preservation of vascular network with PRT.« less

  15. Long-Term Neurodevelopmental Outcome of Neonates with Hypernatremic Dehydration.

    PubMed

    Boskabadi, Hassan; Akhondian, Javad; Afarideh, Maliheh; Maamouri, Gholamali; Bagheri, Sepideh; Parizadeh, Seyyed Mostafa; Mobarhan, Majid Ghayour; Mohammadi, Shabnam; Frens, Gordon A A

    2017-04-01

    Neonatal hypernatremic dehydration (NHD) is a dangerous condition that can lead to severe weight loss, renal impairment, and central nervous system complications. We aimed to evaluate the consequences of NHD in infants in their second year of life. This was a prospective case-control study in Ghaem hospital, Mashhad, Iran. Sixty-five healthy breastfed neonates (serum sodium concentration <150 mmol/L) and 65 hypernatremic (serum sodium concentration ≥150 mmol/L) neonates were followed up from 2008 to 2011. Maternal and neonatal factors were compared between the two groups together with their growth parameters, and developmental milestones (using Denver II developmental assessment scores) were assessed and compared in ages 6, 12, 18, and 24 months, respectively. The weight of infants at 6 months of age was significantly different between the two groups (7,264 ± 1,089 g vs. 7,596 ± 957 g, p = 0.009). Twenty-five percent of infants in the group who had developed NHD had a delay in development at 6 months of age, with corresponding values of 21% at 12 months, 19% at 18 months, and 12% at 24 months of age. Developmental delay was ∼0.3% for the control group at similar ages. The severity of hypernatremia was strongly correlated with poor developmental outcome at 6 months (p = 0.001). Serum sodium concentration of neonates was 153-195 mg/dL in the NHD group. Median peak serum sodium was 158 ± 16 in case group and 141 ± 9 in control group. Serious complications were cerebral edema (five cases), hemorrhage (five cases), and kidney stones (six cases). Hypernatremic dehydration has an adverse effect on child development especially in the first year of life, their prevalence decreases with advanced age. Growth problems are also present during their first year of life. The major signs and symptoms of infants with poor prognosis on admission were poor feeding (8 infants, 61.5%), seizure (3 infants, 23.1%), hyperthermia (1 infant, 7.7%), and lethargy (1 infant, 7.7%). NHD affects growth parameters and developmental milestones of children. Occasionally the child's weight gain was normalized by the end of first year of life; although developmental delay continued, its severity was reduced, with age.

  16. Periodic and chaotic oscillations in a tumor and immune system interaction model with three delays

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

    Bi, Ping; Center for Partial Differential Equations, East China Normal University, 500 Dongchuan Rd., Shanghai 200241; Ruan, Shigui, E-mail: ruan@math.miami.edu

    2014-06-15

    In this paper, a tumor and immune system interaction model consisted of two differential equations with three time delays is considered in which the delays describe the proliferation of tumor cells, the process of effector cells growth stimulated by tumor cells, and the differentiation of immune effector cells, respectively. Conditions for the asymptotic stability of equilibria and existence of Hopf bifurcations are obtained by analyzing the roots of a second degree exponential polynomial characteristic equation with delay dependent coefficients. It is shown that the positive equilibrium is asymptotically stable if all three delays are less than their corresponding critical valuesmore » and Hopf bifurcations occur if any one of these delays passes through its critical value. Numerical simulations are carried out to illustrate the rich dynamical behavior of the model with different delay values including the existence of regular and irregular long periodic oscillations.« less

  17. Retarded head growth and neurocognitive development in infants of mothers with a history of eating disorders: longitudinal cohort study.

    PubMed

    Koubaa, S; Hällström, T; Hagenäs, L; Hirschberg, A L

    2013-10-01

    To characterise early growth and neurocognitive development in children of mothers with a history of eating disorders (ED). A longitudinal cohort study. Child-care centres in Stockholm, Sweden. Children born to mothers with previous ED (n = 47) (24 anorexia nervosa, 20 bulimia nervosa, 3 unspecified ED), and controls (n = 65). Mean values and standard deviation scores of weight and height from birth to 5 years of age and head circumference up to 18 months of age were compared between groups. Neurocognitive development was studied at the age of 5 years by the validated parent questionnaire Five to Fifteen. Head growth and neurocognitive development. We previously reported that mothers with a history of ED conceived infants with lower birthweight and head circumference than controls. At 3 months of age, body mass index (BMI) was no longer reduced but mean head circumferences of the children born to mothers with ED were smaller throughout the observation period. Similarly, the longitudinal results of the standard deviation scores of head circumference showed a significant overall group effect with lower levels in both subgroups of ED (anorexia nervosa and bulimia nervosa). The children of the ED mothers also had significantly higher Five to Fifteen scores than controls, reflecting difficulties in language skills. Head circumference at birth correlated with language skills in the children of mothers with ED. Children of mothers with previous ED demonstrated an early catch-up in BMI, but the average head circumference continued to be delayed until at least 18 months of age. The reduced head growth was related to delayed neurocognitive development. © 2013 RCOG.

  18. Plasmin-clipped beta(2)-glycoprotein-I inhibits endothelial cell growth by down-regulating cyclin A, B and D1 and up-regulating p21 and p27.

    PubMed

    Beecken, Wolf-Dietrich C; Ringel, Eva Maria; Babica, Jan; Oppermann, Elsie; Jonas, Dietger; Blaheta, Roman A

    2010-10-28

    beta(2)-Glycoprotein-I (beta(2)gpI), an abundant plasma glycoprotein, functions as a regulator of thrombosis. Previously, we demonstrated that plasmin-clipped beta(2)gpI (cbeta(2)gpI) exerts an anti-angiogenic effect on human umbilical vein endothelial cells (HUVEC). The present study was focused on the molecular background responsible for this phenomenon. cbeta(2)gpI strongly reduced HUVEC growth and proliferation as evidenced by the MTT and BrdU assay and delayed cell cycle progression arresting HUVEC in the S-and G2/M-phase. Western blot analysis indicated that cbeta(2)gpI inhibited cyclin A, B and D1, and enhanced p21 and p27 expression. Activity of p38 was down-regulated independently from the cbeta(2)gpI incubation time. Phosphorylation of ERK1/2 was not changed early (30 and 60 min) but became enhanced later (90 min, 4h). JNK activity was reduced rapidly after cbeta(2)gpI treatment but compared to controls, increased thereafter. Annexin II blockade prevented growth inhibition and cell cycle delay evoked by cbeta(2)gpI. We assume that cbeta(2)gpI's effects on HUVEC growth is mediated via cyclin A, B and D1 suppression, up-regulation of p21 and p27 and coupled to modifications of the mitogen-activated protein (MAP) kinase signalling pathway. cbeta(2)gpI may represent a potential endogenous angiogenesis-targeted compound, opening the possibility of a novel tool to treat cancer. 2010 Elsevier Ireland Ltd. All rights reserved.

  19. An assessment of clinical pathways and missed opportunities for the diagnosis of nodular melanoma versus superficial spreading melanoma.

    PubMed

    Cicchiello, Mark; Lin, Matthew J; Pan, Yan; McLean, Catriona; Kelly, John W

    2016-05-01

    Missed opportunities in the diagnosis of nodular melanoma (NM) carry high prognostic penalties due to the rapid rate of NM growth. To date, an assessment of the pathways to diagnosis of NM versus superficial spreading melanoma (SSM) specifically comparing numbers of opportunities missed to undertake biopsy has not been performed. A retrospective questionnaire of 120 patients (60 NM patients, age and sex matched to 60 SSM patients) from the Victorian Melanoma Service (VMS) database was undertaken to assess pathways to diagnosis. The numbers of opportunities missed to undertake a biopsy and doctor behaviour at such encounters were recorded. Diagnostic delay (overall, patient's and doctor's delay) in terms of time was assessed. Significant differences in opportunities missed to make a diagnosis of NM compared to SSM were found. In all, 43% of NM were biopsied at a first encounter compared to 70% of SSM. All SSM were diagnosed within three reviews. Overall, 33% of NM required at least three and up six reviews until biopsy. Patients with NM were more likely than those with SSM to be reassured that their lesions were benign. No significant differences in terms of time delay to diagnosis between NM and SSM were found. NM contributes disproportionately to melanoma mortality in Australia. Addressing earlier diagnosis of NM with renewed focus may make the biggest impact on the overall mortality of melanoma. The message that a period of observation is not appropriate for patients re-presenting with lesions of concern must be more effectively communicated. © 2015 The Australasian College of Dermatologists.

  20. The Role of Convection and Growth Competition in Phase Selection in Microgravity: Controlled Convection in the Containerless Processing of Steel Alloys

    NASA Technical Reports Server (NTRS)

    Matson, D. M.; Loser, W.; Rogers, J. R.; Flemings, M. C.

    2001-01-01

    Containerless processing using electromagnetic levitation (EML) is a powerful technique in the investigation of reactive molten metal systems. On ground, the power required to overcome the weight of the sample is sufficient to cause significant heating and induce substantial melt convection. In microgravity, the heating and positioning fields may be decoupled and the field strength may be varied to achieve the desired level of convection within the limits set by the geometry of the levitation coil and the sample size. From high-speed digital images of the double recalescence behavior of Fe-Cr-Ni alloys in ground-based testing and in reduced-gravity aboard the NASA KC-135 parabolic aircraft, we have shown that phase selection can be predicted based on a growth competition model. An important parameter in this model is the delay time between primary nucleation and subsequent nucleation of the stable solid within the liquid/metastable solid array. This delay time is a strong function of composition and a weak function of the undercooling of the melt below the metastable liquidus. From the results obtained during the first Microgravity Sciences Laboratory (MSL-1) mission, we also know that convection may significantly influence the delay time, especially at low undercoolings. Currently, it is unclear what mechanism controls the formation of a heterogeneous site that allows nucleation of the austenitic phase on the pre-existing ferrite skeleton. By examining the behavior of the delay time under different convective conditions, we hypothesize that we can differentiate between several of these mechanisms to gain an understanding of how to control microstructural. evolution. We will anchor these predictions by examining samples quenched at different times following primary recalescence in microgravity. A second important parameter in the growth competition model is the identification of the growth rate of the stable phase into the semi-solid array that formed during primary recalescence. Current dendritic growth theory is inadequate in predicting solidification behavior under these conditions as metallographic analyses show that stable phase growth proceeds along the interface between the metastable solid and residual liquid. Since growth velocity is independent of the initial undercooling relative to the metastable liquidus, we hypothesize that purely thermal effects can be separated from other important growth model parameters by careful selection of the liquid composition in a ternary system.

  1. Performance of South African children on the Communication and Symbolic Behavior Scales-Developmental Profile (CSBS DP).

    PubMed

    Chambers, Nola; Stronach, Sheri T; Wetherby, Amy M

    2016-05-01

    Substantial development in social communication skills occurs in the first two years of life. Growth should be evident in sharing emotion and eye gaze; rate of communication, communicating for a variety of functions; using gestures, sounds and words; understanding language, and using functional and pretend actions with objects in play. A delay in these early social communication skills may be the first sign of a developmental delay in young children in nearly all categories of disabilities-including specific language impairment, autism spectrum disorder, HIV/AIDS, lack of environmental stimulation or institutionalization, and global developmental delays-and early detection of these delays is critical for enrolment in appropriate early intervention services. No standardized tests of early social communication skills exist for very young children in South Africa (SA). An existing evaluation tool that has the potential to be culturally fair for children from cultural backgrounds different to the standardization group is the Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS DP). This study aimed to document the performance of a group of English-speaking SA children ranging in age from 12 to 24 months on the CSBS DP and to compare this performance with the original standardization sample. Sixty-seven English-speaking SA children from a range of cultural and linguistic backgrounds were assessed on the CSBS DP Behaviour Sample. Group scores were compared with the original standardization sample using inferential statistics. The results provide preliminary support for the suitability and validity of the face-to-face Behaviour Sample as a measure of early social communication skills in this sample of English-speaking SA children from a range of cultural groups between 12 and 24 months of age. While further research in the SA population is needed, these findings are a first step towards validating a culturally appropriate measure for early detection of social communication delays in a sample of SA toddlers. © 2015 Royal College of Speech and Language Therapists.

  2. Personality-Targeted Interventions Delay the Growth of Adolescent Drinking and Binge Drinking

    ERIC Educational Resources Information Center

    Conrod, Patricia J.; Castellanos, Natalie; Mackie, Clare

    2008-01-01

    Background: Personality factors are implicated in the vulnerability to adolescent alcohol misuse. This study examined whether providing personality-targeted interventions in early adolescence can delay drinking and binge drinking in high-risk youth. Methods: A randomised control trial was carried out with 368 adolescents recruited from years 9 and…

  3. Trajectories of Developmental Functioning among Children of Adolescent Mothers: Factors Associated with Risk for Delay

    ERIC Educational Resources Information Center

    Jahromi, Laudan B.; Umaña-Taylor, Adriana J.; Updegraff, Kimberly A.; Zeiders, Katharine H.

    2016-01-01

    Children of adolescent mothers are at risk for developmental delays. Less is known about the heterogeneity in these children's developmental trajectories, and factors associated with different patterns of development. This longitudinal study used latent class growth analysis (LCGA) to identify distinct trajectories in children of Mexican-origin…

  4. The case for delaying planting of bottomland oaks: an example involving Nuttall oaks

    Treesearch

    David C. Mercker; David S. Buckley; John P. Conn

    2013-01-01

    A prominent difficulty during bottomland hardwood afforestation in the southeastern United States is that sites are often flooded during the preferred months of planting (January - March), which results in delayed planting (April - June) and reduced survival. We monitored growth and survival of Nuttall oak (Quercus texana Buckley) seedlings planted...

  5. The Association of Increased Total Glycosylated Hemoglobin Levels with Delayed Age at Menarche in Young Women with Type 1 Diabetes

    PubMed Central

    Danielson, Kirstie K.; Palta, Mari; Allen, Catherine; D’Alessio, Donn J.

    2005-01-01

    Context: Delayed menarche is associated with subsequent reproductive and skeletal complications. Previous research has found delayed growth and pubertal maturation with type 1 diabetes and with poor glycemic control. The effect of diabetes management on menarche is important to clarify because tighter control might prevent these complications. Objective: To investigate age at menarche in young women with type 1 diabetes, and examine the effect of diabetes management (e.g. total glycosylated hemoglobin (GHb) level, number of blood glucose checks, insulin therapy intensity, insulin dose) on age at menarche in those diagnosed before menarche. Design: The Wisconsin Diabetes Registry Project is a follow-up study of a type 1 diabetes population-based incident cohort initially enrolled 1987 – 1992. Setting: Twenty-eight counties in south-central Wisconsin. Patients or Other Participants: Recruited through referrals, self-report, and hospital/clinic ascertainment. Individuals with newly diagnosed type 1 diabetes, <30 years old, were invited to participate. Of 288 young women enrolled, 188 reported menarche by 2002; 105 were diagnosed before menarche. Interventions: Not applicable. Main Outcome Measure: Age at menarche. Results: Mean age at menarche was 12.78 years, compared to 12.54 years in the United States (p = 0.01). Ages at menarche and diagnosis were not associated. For those diagnosed before menarche, age at menarche was delayed 1.3 months with each one percent increase in mean total GHb level in the three years prior to menarche. Conclusions: Age at menarche was moderately delayed in young women with type 1 diabetes. Delayed menarche could potentially be minimized with improved GHb levels. PMID:16204372

  6. Effect of thiacloprid on early life stages of common carp (Cyprinus carpio).

    PubMed

    Velisek, Josef; Stara, Alzbeta

    2018-03-01

    Toxicity of the neonicotinoid pesticide thiacloprid to embryos and larvae of common carp Cyprinus carpio was assessed under laboratory conditions. Carp embryos and larvae were exposed to thiacloprid at four concentrations: 4.5 (environmental concentration), 45, 225, and 450 μg/L for 35 days and compared to a non-treated control group. The effects on lipid peroxidation, antioxidant enzyme levels (superoxide dismutase, glutathione reductase, catalase, glutathione S-transferase, and reduced glutathione), mortality, growth, development, and histopathogenesis were assessed. Thiacloprid at tested concentrations were not associated with negative effects on hatching, behaviour, embryo viability, or Fulton's condition factor. Carp exposed to 45 μg/L thiacloprid showed lower weight and length compared to controls. Thiacloprid at 225 and 450 μg/L delayed development and led to lower weight and length of carp. Significantly lower superoxide dismutase and glutathione reductase activity was observed at all tested concentrations of thiacloprid compared with the control group. Chronic thiacloprid exposure of early-life stages of carp affected ontogeny and growth rate, and inhibited antioxidant capacity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. A model for thin layer formation by delayed particle settling at sharp density gradients

    NASA Astrophysics Data System (ADS)

    Prairie, Jennifer C.; White, Brian L.

    2017-02-01

    Thin layers - regions where plankton or particles accumulate vertically on scales of a few meters or less - are common in coastal waters, and have important implications for both trophic dynamics and carbon cycling. These features can form by a variety of biological and physical mechanisms, including localized growth, shear-thinning, and directed swimming. An additional mechanism may result in the formation of thin layers of marine aggregates, which have been shown to decrease their settling velocity when passing through sharp density gradients, a behavior termed delayed settling. Here, we apply a simple vertical advection-diffusion model to predict the properties of aggregate thin layers formed by this process. We assume a constant vertical flux of particles from the surface, which is parameterized by observations from laboratory experiments with marine aggregates. The formation, maintenance, and shape of the layers are described in relation to non-dimensional numbers that depend on environmental conditions and particle settling properties. In particular, model results demonstrate layer intensity and sharpness both increase with higher Péclet number (Pe), that is, under conditions with weaker mixing relative to layer formation. Similarly, more intense and sharper layers are found when the delayed settling behavior of aggregates is characterized by a lower velocity minimum. The model also predicts layers that are vertically asymmetric and highly "peaky" when compared with a Gaussian distribution, features often seen in thin layers in natural environments. Lastly, by comparing model predictions with observations of thin layers in the field, we are able to gain some insight into the applicability of delayed settling as a thin layer formation mechanism in different environmental conditions.

  8. The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature

    PubMed Central

    Abbas, Elham; Cox, Devin M.; Smith, Teri; Butler, Merlin G.

    2016-01-01

    We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams–Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation. PMID:27617154

  9. The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature.

    PubMed

    Abbas, Elham; Cox, Devin M; Smith, Teri; Butler, Merlin G

    2016-09-01

    We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams-Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation.

  10. Growth and development of children aged 1-5 years in low-intensity armed conflict areas in Southern Thailand: a community-based survey.

    PubMed

    Jeharsae, Rohani; Sangthong, Rassamee; Wichaidit, Wit; Chongsuvivatwong, Virasakdi

    2013-04-04

    A low-intensity armed conflict has been occurring for nearly a decade in southernmost region of Thailand. However, its impact on child health has not yet been investigated. This study aimed to estimate the prevalence of delayed child growth and development in the affected areas and to determine the association between the violence and health among children aged 1-5 years. A total of 498 children aged 1-5 years were recruited. Intensity of conflict for each sub-district was calculated as the 6-year average number of incidents per 100,000 population per year and classified into quartiles. Growth indices were weight-for-age, height-for-age, and weight-for-height, while development was measured by the Denver Development Screening Test II (Thai version). Food insecurity, child-rearing practice, health service accessibility, household sanitation, and depression among the caregivers were assessed using screening scales and questionnaires. Contextual information such as average income and numbers of violent events in each sub-district was obtained from external sources. Growth retardation was highly prevalent in the area as reported by rates of underweight, stunting, and wasting at 19.3%, 27.6% and 7.4%, respectively. The prevalence of developmental delay was also substantially high (37.1%). Multi-level analysis found no evidence of association between insurgency and health outcomes. However, children in areas with higher intensity of violence had a lower risk of delay in personal-social development (OR = 0.4; 95% CI = 0.2 - 0.9; p-value = 0.05). Unlike war refugees and internally-displaced persons in camp-like settings, the relationship between level of armed conflict and growth and developmental delay among children aged 1-5 years could not be demonstrated in the community setting of this study where food supply had been minimally perturbed.

  11. Ultrasound image-guided therapy enhances antitumor effect of cisplatin.

    PubMed

    Sasaki, Noboru; Kudo, Nobuki; Nakamura, Kensuke; Lim, Sue Yee; Murakami, Masahiro; Kumara, W R Bandula; Tamura, Yu; Ohta, Hiroshi; Yamasaki, Masahiro; Takiguchi, Mitsuyoshi

    2014-01-01

    The aim of this study was to clarify whether ultrasound image-guided cisplatin delivery with an intratumor microbubble injection enhances the antitumor effect in a xenograft mouse model. Canine thyroid adenocarcinoma cells were used for all experiments. Before in vivo experiments, the cisplatin and microbubble concentration and ultrasound exposure time were optimized in vitro. For in vivo experiments, cells were implanted into the back of nude mice. Observed by a diagnostic ultrasound machine, a mixture of cisplatin and ultrasound contrast agent, Sonazoid, microbubbles was injected directly into tumors. The amount of injected cisplatin and microbubbles was 1 μg/tumor and 1.2 × 10(7) microbubbles/tumor, respectively, with a total injected volume of 20 μl. Using the same diagnostic machine, tumors were exposed to ultrasound for 15 s. The treatment was repeated four times. The combination of cisplatin, microbubbles, and ultrasound significantly delayed tumor growth as compared with no treatment (after 18 days, 157 ± 55 vs. 398 ± 49 mm(3), P = 0.049). Neither cisplatin alone nor the combination of cisplatin and ultrasound delayed tumor growth. The treatment did not decrease the body weight of mice. Ultrasound image-guided anticancer drug delivery may enhance the antitumor effects of drugs without obvious side effects.

  12. 2q37 Deletion syndrome confirmed by high-resolution cytogenetic analysis

    PubMed Central

    Cho, Eun-Kyung; Kim, Jinsup; Yang, Aram; Jin, Dong-Kyu

    2017-01-01

    Chromosome 2q37 deletion syndrome is a rare chromosomal disorder characterized by mild to moderate developmental delay, brachydactyly of the third to fifth digits or toes, short stature, obesity, hypotonia, a characteristic facial appearance, and autism spectrum disorder. Here, we report on a patient with 2q37 deletion presenting with dilated cardiomyopathy (DCMP). Congenital heart malformations have been noted in up to 20% of patients with 2q37 deletions. However, DCMP has not been reported in 2q37 deletion patients previously. The patient exhibited the characteristic facial appearance (a flat nasal bridge, deep-set eyes, arched eyebrows, and a thin upper lip), developmental delay, mild mental retardation, peripheral nerve palsy, and Albright hereditary osteodystrophy (AHO)-like phenotypes (short stature and brachydactyly). Conventional chromosomal analysis results were normal; however, microarray-based comparative genomic hybridization revealed terminal deletion at 2q37.1q37.3. In addition, the patient was confirmed to have partial growth hormone (GH) deficiency and had shown a significant increase in growth rate after substitutive GH therapy. Chromosome 2q37 deletion syndrome should be considered in the differential diagnosis of patients presenting with AHO features, especially in the presence of facial dysmorphism. When patients are suspected of having a 2q37 deletion, high-resolution cytogenetic analysis is recommended. PMID:28690993

  13. A partial differential equation model and its reduction to an ordinary differential equation model for prostate tumor growth under intermittent hormone therapy.

    PubMed

    Tao, Youshan; Guo, Qian; Aihara, Kazuyuki

    2014-10-01

    Hormonal therapy with androgen suppression is a common treatment for advanced prostate tumors. The emergence of androgen-independent cells, however, leads to a tumor relapse under a condition of long-term androgen deprivation. Clinical trials suggest that intermittent androgen suppression (IAS) with alternating on- and off-treatment periods can delay the relapse when compared with continuous androgen suppression (CAS). In this paper, we propose a mathematical model for prostate tumor growth under IAS therapy. The model elucidates initial hormone sensitivity, an eventual relapse of a tumor under CAS therapy, and a delay of a relapse under IAS therapy, which are due to the coexistence of androgen-dependent cells, androgen-independent cells resulting from reversible changes by adaptation, and androgen-independent cells resulting from irreversible changes by genetic mutations. The model is formulated as a free boundary problem of partial differential equations that describe the evolution of populations of the abovementioned three types of cells during on-treatment periods and off-treatment periods. Moreover, the model can be transformed into a piecewise linear ordinary differential equation model by introducing three new volume variables, and the study of the resulting model may help to devise optimal IAS schedules.

  14. Warmer winters modulate life history and energy storage but do not affect sensitivity to a widespread pesticide in an aquatic insect.

    PubMed

    Arambourou, Hélène; Stoks, Robby

    2015-10-01

    Despite the increased attention for the effects of pesticides under global warming no studies tested how winter warming affects subsequent sensitivity to pesticides. Winter warming is expected to cause delayed negative effects when it increases metabolic rates and thereby depletes energy reserves. Using a common-garden experiment, we investigated the combined effect of a 4 °C increase in winter temperature and subsequent exposure to chlorpyrifos in the aquatic larvae of replicated low- and high-latitude European populations of the damselfly Ischnura elegans. The warmer winter (8 °C) resulted in a higher winter survival and higher growth rates compared to the cold winter (4 °C) commonly experienced by European high-latitude populations. Low-latitude populations were better at coping with the warmer winter, indicating thermal adaptation to the local winter temperatures. Subsequent chlorpyrifos exposure at 20 °C induced strong negative effects on survival, growth rate, lipid content and acetylcholinesterase activity while phenoloxidase activity increased. These pesticide effects were not affected by winter warming. Our results suggest that for species where winter warming has positive effects on life history, no delayed effects on the sensitivity to subsequent pesticide exposure should be expected. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Plasma growth hormone (GH), insulin and amino acid responses to arginine with or without aspartic acid in pigs. Effect of the dose.

    PubMed

    Cochard, A; Guilhermet, R; Bonneau, M

    1998-01-01

    The aim of the present study was to examine, for the first time in pigs, the dose-dependent effect of arginine (ARG) on growth hormone (GH) and insulin release and the effect of the combined ARG and aspartic acid (ASP) treatment on GH and insulin release. ARG (0.5 or 1 g/kg body weight) with or without an equimolar supplement of ASP (0.38 or 0.76 g/kg, respectively) was administered in piglets via the duodenum. ARG increased plasma arginine, ornithine, urea, proline and branched chain amino acid concentrations. ASP increased specifically plasma aspartic acid, glutamic acid, alanine and citrulline concentrations. Plasma insulin increased with no apparent difference between treatments. Maximum GH level and the area under the GH curve (AUC) were increased in a dose-dependent manner in response to ARG treatment. GH response to the combined ARG and ASP treatment (ARGASP) was delayed compared to ARG alone and was not dose-dependent. AUC for GH after ARGASP treatments were intermediate between those observed after the two ARG doses. Our data suggest that high ASP doses transiently inhibit and delay ARG-induced GH release in pigs and that an equimolar supplement of ASP stimulates or inhibits ARG-induced GH release depending on the dose used.

  16. Developmental Delays in Executive Function from 3 to 5 Years of Age Predict Kindergarten Academic Readiness.

    PubMed

    Willoughby, Michael T; Magnus, Brooke; Vernon-Feagans, Lynne; Blair, Clancy B

    Substantial evidence has established that individual differences in executive function (EF) in early childhood are uniquely predictive of children's academic readiness at school entry. The current study tested whether growth trajectories of EF across the early childhood period could be used to identify a subset of children who were at pronounced risk for academic impairment in kindergarten. Using data that were collected at the age 3, 4, and 5 home assessments in the Family Life Project ( N = 1,120), growth mixture models were used to identify 9% of children who exhibited impaired EF performance (i.e., persistently low levels of EF that did not show expected improvements across time). Compared to children who exhibited typical trajectories of EF, the delayed group exhibited substantial impairments in multiple indicators of academic readiness in kindergarten (Cohen's ds = 0.9-2.7; odds ratios = 9.8-23.8). Although reduced in magnitude following control for a range of socioeconomic and cognitive (general intelligence screener, receptive vocabulary) covariates, moderate-sized group differences remained (Cohen's ds = 0.2-2.4; odds ratios = 3.9-5.4). Results are discussed with respect to the use of repeated measures of EF as a method of early identification, as well as the resulting translational implications of doing so.

  17. Home-based smoking prevention program Smoke-free Kids on smoking-related cognitions: Secondary outcomes from a cluster randomized controlled trial.

    PubMed

    Hiemstra, Marieke; Engels, Rutger C M E; van Schayck, Onno C P; Otten, Roy

    2016-01-01

    The home-based smoking prevention programme 'Smoke-free Kids' did not have an effect on primary outcome smoking initiation. A possible explanation may be that the programme has a delayed effect. The aim of this study was to evaluate the effects on the development of important precursors of smoking: smoking-related cognitions. We used a cluster randomised controlled trial in 9- to 11-year-old children and their mothers. The intervention condition received five activity modules, including a communication sheet for mothers, by mail at four-week intervals. The control condition received a fact-based programme. Secondary outcomes were attitudes, self-efficacy and social norms. Latent growth curves analyses were used to calculate the development of cognitions over time. Subsequently, path modelling was used to estimate the programme effects on the initial level and growth of each cognition. Analyses were performed on 1398 never-smoking children at baseline. Results showed that for children in the intervention condition, perceived maternal norms increased less strongly as compared to the control condition (β = -.10, p = .03). No effects were found for the other cognitions. Based on the limited effects, we do not assume that the programme will have a delayed effect on smoking behaviour later during adolescence.

  18. An epidemiological study of urban and rural children in Pakistan: examining the relationship between delayed psychomotor development, low birth weight and postnatal growth failure.

    PubMed

    Avan, Bilal I; Raza, Syed A; Kirkwood, Betty R

    2015-03-01

    Low birth weight is known to be associated with postnatal growth failure. It is not yet established that both conditions are determinants of psychomotor development. The study investigated whether or not low birth weight leads to delayed psychomotor development of a child, and whether it can be mitigated by adequate postnatal growth. A cross-sectional study was conducted in 2002 in 15 rural and 11 urban communities of Sindh province, Pakistan. Assessment of 1234 children less than 3 years of age included Bayley's Scale of Infant Development II, socioeconomic questionnaire and anthropometry; WHO standards were used to calculate z-scores of height-for-age, weight-for-height and weight-for-age. The underlying study hypotheses were tested through multiple regression modelling. Out of 1219 children, 283 (23.2%) had delayed psychomotor development and 639 (52.4%) were undernourished according to the composite index of anthropometric failure. Strong negative associations with the psychomotor development index were detected between stunting and being underweight, with a larger magnitude of effect for stunting (p<0.001). The strong relationship persisted even when the analysis was restricted to non-malnourished children. The psychomotor index increased by 2.07 points with every unit increase in height-for-age z-score. The relationship between low birth weight and psychomotor development appears to be mediated largely by postnatal growth and nutritional status. This association suggests that among undernourished children there is significant likelihood of a group that is developmentally delayed. It is important to emphasize developmental needs in programmes that target underprivileged children. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Contrasting growth phenology of native and invasive forest shrubs mediated by genome size.

    PubMed

    Fridley, Jason D; Craddock, Alaä

    2015-08-01

    Examination of the significance of genome size to plant invasions has been largely restricted to its association with growth rate. We investigated the novel hypothesis that genome size is related to forest invasions through its association with growth phenology, as a result of the ability of large-genome species to grow more effectively through cell expansion at cool temperatures. We monitored the spring leaf phenology of 54 species of eastern USA deciduous forests, including native and invasive shrubs of six common genera. We used new measurements of genome size to evaluate its association with spring budbreak, cell size, summer leaf production rate, and photosynthetic capacity. In a phylogenetic hierarchical model that differentiated native and invasive species as a function of summer growth rate and spring budbreak timing, species with smaller genomes exhibited both faster growth and delayed budbreak compared with those with larger nuclear DNA content. Growth rate, but not budbreak timing, was associated with whether a species was native or invasive. Our results support genome size as a broad indicator of the growth behavior of woody species. Surprisingly, invaders of deciduous forests show the same small-genome tendencies of invaders of more open habitats, supporting genome size as a robust indicator of invasiveness. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  20. Growth promoting potential of fresh and stored Moringa oleifera leaf extracts in improving seedling vigor, growth and productivity of wheat crop.

    PubMed

    Khan, Shahbaz; Basra, Shahzad Maqsood Ahmed; Afzal, Irfan; Nawaz, Muhammad; Rehman, Hafeez Ur

    2017-12-01

    Wheat is staple food of region, as it contributes 60% of daily caloric intake, but its delayed sowing reduces yield due to short life span. Moringa leaf extract (MLE) is considered to improve growth and development of field crops. Study comprised of two experiments. First experiment, freshly extracted MLE and in combination with growth-promoting substances were stored at two temperature regimes. Chemical analysis, after 1, 2, and 3 months' storage period, showed that phenolics and ascorbic acid concentrations decreased with increasing storage period. Fresh extracts improved speed and spread of emergence and seedling vigor. Effectiveness of MLE in terms of phenolics and ascorbate concentrations was highest up to 1 month which decreased with prolonged storage. Growth enhancing potential of MLE also reduced with increasing storage duration. Under field conditions, the bio-efficacy of these fresh and stored MLE was compared when applied as foliar spray at tillering and booting stages of wheat. Foliar applied fresh MLE was the most effective in improving growth parameters. Fresh MLE enhanced biochemical and yield attributes in late sown wheat. This growth-promoting potential of MLE decreased with storage time. Application of fresh MLE helped to achieve higher economic yield.

  1. Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer.

    PubMed

    Xiao, Jie; Xu, Xiaobo; Li, Xiao; Li, Yanli; Liu, Guobing; Tan, Hui; Shen, Hua; Shi, Hongcheng; Cheng, Dengfeng

    2016-09-30

    The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC), we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188 ReO₄ - or 188 Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188 Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188 Re-bevacizumab (11.1 MBq/mice) group were not reduced but growth was delayed compared with other groups. Thus, 188 Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.

  2. Impact of Sodium Tungstate and Tungsten Alloys on the Growth of Selected Microorganisms with Environmental Significance

    DTIC Science & Technology

    2010-07-30

    TUNGSTEN ALLOYS ON THE GROWTH OF SELECTED MICROORGANISMS WITH ENVIROMENTAL SIGNIFICANCE 5a. Contract Number: 5b. Grant Number: 5c. Program Element...lower tolerances. Interestingly, bacteria cultivated from the environment displayed only minor delays and reduction in growth relative to pure...settings where nutrients may be limited. 15. SUBJECT TERMS Tungsten, sodium tungstate, microbial growth , environmental microbiology, bacteria , Shewanella

  3. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

    PubMed Central

    Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

    2015-01-01

    Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  4. Usefulness of magnetic resonance findings of the hypothalamic-pituitary region in the management of short children with growth hormone deficiency: evidence from a longitudinal study.

    PubMed

    Kalina, Maria A; Kalina-Faska, Barbara; Gruszczyńska, Katarzyna; Baron, Jan; Małecka-Tendera, Ewa

    2012-01-01

    The purpose of this study is to assess the relationship between magnetic resonance images (MRI) of the hypothalamic-pituitary (H-P) region and response to recombinant human growth hormone (rhGH) treatment in short children with growth hormone deficiency, basing on changes of auxologic parameters, as well as to answer the question if MRI may serve for selecting and monitoring the rhGH responders. The study group comprised 85 children treated with rhGH, aged 7.3-18.7 years, followed for the mean period of 3.2 years (range, 2.1-9.5 years). Auxologic parameters (height deficit hSDS, deviation from the mid-parental height hSDS-mpSDS, bone delay index bone age/chronological age ratio (BA/CA)) were assessed before, during and at the end of rhGH treatment; growth velocity was calculated before and during rhGH therapy. Parameters were correlated with the MRI of the H-P region. Structural anomalies of the H-P region were found in 22 (25.9%) children: empty sella syndrome (ESS) in 12 (14.1%) patients, ectopic posterior pituitary (EPP) in ten (11.8%). Patients' height deficit and their deviation from parental height before rhGH therapy was significantly greater in the EPP group (median hSDS = -3.8; hSDS-mpSDS = -2.5), bone age delay was the greatest in the ESS group (median BA/CA = 0.69), after therapy - in the EPP group (median BA/CA = 0.82). Growth velocity improved in the first year of the rhGH therapy in all groups; however, the most significant acceleration was observed in the EPP group (median delta hSDS = 0.9), then stabilised and was comparable in all groups. MRI may be helpful in predicting response to the rhGH treatment, providing midline abnormalities are taken into account.

  5. Slower CCN growth kinetics of anthropogenic aerosol compared to biogenic aerosol observed at a rural site

    NASA Astrophysics Data System (ADS)

    Shantz, N. C.; Chang, R. Y.-W.; Slowik, J. G.; Vlasenko, A.; Abbatt, J. P. D.; Leaitch, W. R.

    2010-01-01

    Growth rates of water droplets were measured with a static diffusion cloud condensation chamber in May-June 2007 at a rural field site in Southern Ontario, Canada, 70 km north of Toronto. The observations include periods when the winds were from the south and the site was impacted by anthropogenic air from the U.S. and Southern Ontario as well as during a 5-day period of northerly wind flow when the aerosol was dominated by biogenic sources. The growth of droplets on anthropogenic size-selected particles centred at 0.1 μm diameter and composed of approximately 40% organic and 60% ammonium sulphate (AS) by mass, was delayed by on the order of 1 s compared to a pure AS aerosol. Simulations of the growth rate on monodisperse particles indicate that a lowering of the water mass accommodation coefficient from αc=1 to an average of αc=0.04 is needed (assuming an insoluble organic with hygroscopicity parameter, κorg, of zero). Simulations of the initial growth rate on polydisperse anthropogenic particles agree best with observations for αc=0.07. In contrast, the growth rate of droplets on size-selected aerosol of biogenic character, consisting of >80% organic, was similar to that of pure AS. Simulations of the predominantly biogenic polydisperse aerosol show agreement between the observations and simulations when κorg=0.2 (with upper and lower limits of 0.5 and 0.07, respectively) and αc=1. Inhibition of water uptake by the anthropogenic organic applied to an adiabatic cloud parcel model in the form of a constant low αc increases the number of droplets in a cloud compared to pure AS. If the αc is assumed to increase with increasing liquid water on the droplets, then the number of droplets decreases which could diminish the indirect climate forcing effect. The slightly lower κorg in the biogenic case decreases the number of droplets in a cloud compared to pure AS.

  6. A Novel Double Subculture Method and Its Theory for the Enumeration of Injured Cells in Stressed Microbial Population.

    PubMed

    Tsuchido, Tetsuaki

    2017-01-01

     A novel double subculture method, termed DiVSaL (Differential Viabilities between Solid and Liquid media) method, for the enumeration of injured cell population of a microorganism, which occurs after some sublethal to lethal treatment, was proposed. In this method injured cells were enumerated as the differential value between viabilities determined with two different techniques, the conventional plate counting using a solid agar medium and the growth delay analysis using a liquid medium. In the former technique, the viable cell number is obtained as colony forming unit (CFU) formed on an agar medium where sublethally injured cells are as much rescued as possible. In the latter technique, on the other hand," the integrated viability" defined by Takano and Tsuchido (1982) is introduced and is calculated from the growth delay of a stressed population, referred to unstressed one. For the growth delay analysis, in this paper, not only the original theoretical model, where the specific growth rate (and therefore the defined G 10 value) does not change after the exposure to a stress treatment, but also a novel modified theory, where the parameter changes, is proposed. On the theoretical background, this DiVSaL method as a double subculture method can be used to enumerate the injured cells without selection by addition of some inhibitor or by nutritional shortage.

  7. Delay-induced rebounds in CO2 emissions and critical time-scales to meet global warming targets

    NASA Astrophysics Data System (ADS)

    Manoli, Gabriele; Katul, Gabriel G.; Marani, Marco

    2016-12-01

    While climate science debates are focused on the attainment of peak anthropogenic CO2 emissions and policy tools to reduce peak temperatures, the human-energy-climate system can hold "rebound" surprises beyond this peak. Following the second industrial revolution, global per capita CO2 emissions (cc) experienced a punctuated growth of about 100% every 60 years, mainly attributable to technological development and its global spread. A model of the human-energy-climate system capable of reproducing past punctuated dynamics shows that rebounds in global CO2 emissions emerge due to delays intrinsic to the diffusion of innovations. Such intrinsic delays in the adoption and spread of low-carbon emitting technologies, together with projected population growth, upset the warming target set by the Paris Agreement. To avoid rebounds and their negative climate effects, model calculations show that the diffusion of climate-friendly technologies must occur with lags one-order of magnitude shorter (i.e., ˜6 years) than the characteristic timescale of past punctuated growth in cc. Radically new strategies to globally implement the technological advances at unprecedented rates are needed if the current emission goals are to be achieved.

  8. Facet-selective nucleation and conformal epitaxy of Ge shells on Si nanowires

    DOE PAGES

    Nguyen, Binh -Minh; Swartzentruber, Brian; Ro, Yun Goo; ...

    2015-10-08

    Knowledge of nanoscale heteroepitaxy is continually evolving as advances in material synthesis reveal new mechanisms that have not been theoretically predicted and are different than what is known about planar structures. In addition to a wide range of potential applications, core/shell nanowire structures offer a useful template to investigate heteroepitaxy at the atomistic scale. We show that the growth of a Ge shell on a Si core can be tuned from the theoretically predicted island growth mode to a conformal, crystalline, and smooth shell by careful adjustment of growth parameters in a narrow growth window that has not been exploredmore » before. In the latter growth mode, Ge adatoms preferentially nucleate islands on the {113} facets of the Si core, which outgrow over the {220} facets. Islands on the low-energy {111} facets appear to have a nucleation delay compared to the {113} islands; however, they eventually coalesce to form a crystalline conformal shell. As a result, synthesis of epitaxial and conformal Si/Ge/Si core/multishell structures enables us to fabricate unique cylindrical ring nanowire field-effect transistors, which we demonstrate to have steeper on/off characteristics than conventional core/shell nanowire transistors.« less

  9. BCG vaccination of full-term infants with chronic intrauterine malnutrition: influence of immunization age on development of post-vaccination, delayed tuberculin hypersensitivity.

    PubMed Central

    Mussi-Pinhata, M. M.; Goncalves, A. L.; Foss, N. T.

    1993-01-01

    To determine the effect of intrauterine growth retardation (IUGR) on the response to BCG vaccination, we evaluated the specific delayed tuberculin hypersensitivity of 57 full-term infants with symmetric IUGR (SGA or small for gestational age) and 52 full-term infants with normal intrauterine growth (AGA or appropriate for gestational age). The infants were evaluated using post-vaccination skin tests to tuberculin purified protein derivative (PPD) and tuberculin lymphocyte transformation tests. Using a positive response to the skin test as an indicator of delayed hypersensitivity, we found that the rate of response to BCG in the SGA and AGA groups was similar. A total of 65% of infants with IUGR responded to BCG vaccination. The response rate among SGA infants who were vaccinated at 5 days of age, about 26 days of age (weight > or = 2500 g), 3 months of age, and 6 months of age was 68%, 47%, 69%, and 88%, respectively. The overall response rate for infants with no IUGR was 71%; the rate response to BCG vaccination among this group was 52% (those vaccinated at 5 days of age), 90% (3 months of age), and 80% (6 months of age). Our data suggest that the immunogenicity of BCG vaccine is similar in term infants who have normal or abnormal intrauterine growth and the presence of IUGR should not be a reason for delaying BCG vaccination. PMID:8440036

  10. Growth and development in internationally adopted children: extent and timing of recovery after early adversity.

    PubMed

    Palacios, Jesús; Román, Maite; Camacho, Carlos

    2011-03-01

    Following initial adversity, internationally adopted children arrive with significant growth and developmental delays. Post-placement recovery has been widely documented, but little has been known about its extent and timing several years after placement and in children with diverse pre-adoptive experiences. A total of 289 children adopted from six countries into Spanish families were studied. Growth and psychological development were considered on arrival and after an average of over 3 years. Growth and developmental initial delays affected a substantial percentage of the children. Post-adoption recovery seemed quicker and more complete in weight and height than in head circumference and psychological development. Initial and later values were correlated, but growth-development relation on arrival subsequently lost significance. Most of the catch-up happened in the first three post-adoption years. Adoption offers an impressive opportunity for recovery after previous adversity, although continuity between past and present persists. The improvement is more marked in some areas than in others and more substantial in the first post-adoption years. © 2010 Blackwell Publishing Ltd.

  11. MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat.

    PubMed

    Casas, Rafael; Muthusamy, Siva; Wakim, Paul G; Sinharay, Sanhita; Lentz, Margaret R; Reid, William C; Hammoud, Dima A

    2018-01-01

    HIV infection is known to be associated with brain volume loss, even in optimally treated patients. In this study, we assessed whether dynamic brain volume changes over time are predictive of neurobehavorial performance in the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients. Cross-sectional brain MRI imaging was first performed comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI and neurobehavioral testing of another group of Tg and WT rats was then performed from 5 to 23 weeks of age. Whole brain and subregional image segmentation was used to assess the rate of brain growth over time. We used repeated-measures mixed models to assess differences in brain volumes and to establish how predictive the volume differences are of specific neurobehavioral deficits. Cross-sectional imaging showed smaller whole brain volumes in Tg compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain volumes were smaller than age-matched WT rats at all time points, starting as early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks of age was greater than that of the whole brain. Striatal volume in combination with genotype was the most predictive of rota-rod scores and in combination with genotype and age was the most predictive of total exploratory activity scores in the Tg rats. The disproportionately delayed striatal growth compared to whole brain between 5 and 9 weeks of age and the role of striatal volume in predicting neurobehavioral deficits suggest an important role of the dopaminergic system in HIV associated neuropathology. This might explain problems with motor coordination and executive decisions in this animal model. Smaller brain and subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy testing in this model should thus target this early stage of development, before brain damage becomes irreversible.

  12. Elevated phthalates' exposure in children with constitutional delay of growth and puberty.

    PubMed

    Xie, Changming; Zhao, Yan; Gao, Lianlian; Chen, Jiao; Cai, Depei; Zhang, Yunhui

    2015-05-15

    Phthalates have been proven to be antiandrogenic, which may interfere with the timing of puberty. Children with Constitutional Delay of Growth and Puberty (CDGP) typically display short stature and pubertal delay. This study investigated whether phthalate's exposure was associated with CDGP, and evaluated the potential mediator role of testosterone. In this case-control study, a total of 167 boys, including 57 boys with CDGP (cases) and 110 controls were enrolled. We measured six major phthalate metabolites in urine samples using high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). The serum testosterone level was determined by radioimmunoassay. Children in the CDGP group were determined to have significantly elevated urinary phthalates concentration compared with control subjects (total phthalates median: case, 107.00 ng/ml; control, 62.22 ng/ml, p = 0.001). After adjustment for BMI and other confounding factors: mono-n-butyl phthalate (MBP), monoethyl phthalate (MEP) and total phthalate concentrations were significantly negatively associated with serum testosterone level (MBP: β = -45.7, p = 0.017; MEP: β = -31.6, p = 0.022; total phthalates: β = -24.6, p = 0.011); MBP, MEP, mono (2-ethylhexyl) phthalate (MEHP) and total phthalates were significantly associated with CDGP (odds ratio: MBP: 8.30, p = 0.002; MEP: 5.43, p = 0.002; MEHP: 3.83, p = 0.017; total phthalates: 9.09, p = 0.001). Serum testosterone level acted as a mediator of the association between phthalates' exposure and CDGP (p = 0.002) (proportion mediated: 34.4%). In this case-control study, elevated phthalates' level was detected in children with CDGP in Shanghai, China and phthalate level was associated with CDGP, which appeared to be mediated by circulating testosterone level. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Variation in chemical composition and allelopathic potential of mixoploid Trigonella foenum-graecum L. with developmental stages.

    PubMed

    Omezzine, Faten; Bouaziz, Mohamed; Simmonds, Monique S J; Haouala, Rabiaa

    2014-04-01

    This study was conducted to evaluate the influence of developmental stages (vegetative, flowering and fruiting) of mixoploid fenugreek aerial parts on their chemical composition and allelopathic potential, assessed on lettuce germination and seedling growth. Aqueous and organic extracts significantly delayed germination, reduced its rate and affected seedling growth. Ethyl acetate and methanol extracts of aerial parts harvested at vegetative stage were the most toxic for lettuce germination and seedling growth, respectively. LC-MS/MS analysis of T. foenum-graecum aerial parts methanolic extract showed nine different flavonol glycosides (quercetin and kaempferol glucosides). Chemical composition of aerial parts differed with the developmental stage; indeed, at the vegetative and fruiting stages, analysis revealed the presence of 9 compounds as compared to only 6 compounds at the flowering stage. Thus, it is necessary to follow the qualitative changes of allelochemicals production at different developmental stages to identify the most productive one. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Effects of a novel poly (AA-co-AAm)/AlZnFe₂O₄/potassium humate superabsorbent hydrogel nanocomposite on water retention of sandy loam soil and wheat seedling growth.

    PubMed

    Shahid, Shaukat Ali; Qidwai, Ansar Ahmad; Anwar, Farooq; Ullah, Inam; Rashid, Umer

    2012-10-25

    A novel poly(acrylic acid-co-acrylamide)AlZnFe₂O₄/potassium humate( )superabsorbent hydrogel nanocomposite (PHNC) was synthesized and its physical properties characterized using SEM, Energy Dispersive X-ray (EDX) and FTIR spectroscopic techniques. Air dried sandy loam soil was amended with 0.1 to 0.4 w/w% of PHNC to evaluate its soil moisture retention attributes. Effect of PHNC amendment on pH, electrical conductivity (EC), porosity, bulk density and hydraulic conductivity of sandy loam soil was also studied. The soil amendment with 0.1 to 0.4 w/w% of PHNC remarkably enhanced the moisture retention at field capacity as compared to the un-amended soils. Seed germination and seedling growth of wheat (Triticum aestivum L.) was considerably increased and a delay by 6-9 days in wilting of seedlings was observed in the soil amended with PHNC, resulting in improved wheat plant establishment and growth.

  15. Activity of Icacinol from Icacina trichantha on Seedling Growth of Oryza sativa and Arabidopsis thaliana.

    PubMed

    Zhao, Ming; Guo, Brian; Onakpa, Michael M; Wong, Tiffany; Wakasa, Kyo; Che, Chun-Tao; Warpeha, Katherine

    2017-12-22

    Broadleaf weeds are very costly for crop growers. Additional herbicidal compounds need to be obtained, especially from natural sources. Extracts of Icacina trichantha were evaluated for responses in germinating seeds and seedlings of rice (Oryza sativa) and Arabidopsis (Arabidopsis thaliana). An ethyl acetate fraction of I. trichantha tuber and a diterpenoid constituent, icacinol (1), were found to have impacts on germination and growth of seedlings. The seed germination inhibitory activity on rice was minimal, but significant on Arabidopsis. While rice indicated some growth delay in leaf expansion in the presence of 1, the effects appeared temporary; chlorophyll and anthocyanins were not significantly altered compared to DMSO controls. Rice seedlings attained biomass similar to DMSO controls, and rice grains per panicle were not significantly different from the DMSO controls. On the other hand, Arabidopsis exhibited damage to leaf expansion, reduced chlorophyll, and increased anthocyanins in aerial portions of the seedlings. Icacinol (1) may be a suitable chemical agent to investigate further for the treatment of eudicot weeds.

  16. Reduction of Weather-Related Terminal Area Delays in the Free-Flight Era

    NASA Technical Reports Server (NTRS)

    Johnson, Sally C.; Chin, David K.; Rovinsky, Robert B.; Kostiuk, Peter F.; Lee, David A.; Hemm, Robert V.; Wingrove, Earl R., III

    1996-01-01

    While much of the emphasis of the free-flight movement has been concentrated on reducing en-route delays, airport capacity is a major bottleneck in the current airspace system, particularly during bad weather. According to the Air Transport Association (ATA) Air Carrier Delay Reports, ground delays (gate-hold, taxi-in, and taxi-out) comprise 75 percent of total delays. It is likely that the projected steady growth in traffic will only exacerbate these losses. Preliminary analyses show that implementation of the terminal area technologies and procedures under development in NASA s Terminal Area Productivity program can potentially save the airlines at least $350M annually in weather-related delays by the year 2005 at Boston Logan and Detroit airports alone. This paper briefly describes the Terminal Area Productivity program, outlines the costhenefit analyses that are being conducted in support of the program, and presents some preliminary analysis results.

  17. Early stages of zeolite growth

    NASA Astrophysics Data System (ADS)

    Kumar, Sandeep

    Zeolites are crystalline nonporous aluminosilicates with important applications in separation, purification, and adsorption of liquid and gaseous molecules. However, an ability to tailor the zeolite microstructure, such as particle size/shape and pore-size, to make it benign for specific application requires control over nucleation and particle growth processes. But, the nucleation and crystallization mechanisms of zeolites are not fully understood. In this context, the synthesis of an all-silica zeolite with MFI-type framework has been studied extensively as a model system. Throughout chapters 2, 4 and 5, MFI growth process has been investigated by small-angle x-ray scattering (SAXS) and transmission electron microscopy (TEM). Of fundamental importance is the role of nanoparticles (~5 nm), which are present in the precursor sol, in MFI nucleation and crystallization. Formation of amorphous aggregates and their internal restructuring are concluded as essential steps in MFI nucleation. Early stage zeolite particles have disordered and less crystalline regions within, which indicates the role of structurally distributed population of nanoparticles in growth. Faceting occurs after the depletion of nanoparticles. The chapter 6 presents growth studies in silica sols prepared by using a dimer of tertaprpylammonium (TPA) and reports that MFI nucleation and crystallization are delayed with a more pronounced delay in crystal growth.

  18. Malaria infection and feather growth rate predict reproductive success in house martins.

    PubMed

    Marzal, Alfonso; Reviriego, Maribel; Hermosell, Ignacio G; Balbontín, Javier; Bensch, Staffan; Relinque, Carmen; Rodríguez, Laura; Garcia-Longoria, Luz; de Lope, Florentino

    2013-04-01

    Carry-over effects take place when events occurring in one season influence individual performance in a subsequent season. Blood parasites (e.g. Plasmodium and Haemoproteus) have strong negative effects on the body condition of their hosts and could slow the rate of feather growth on the wintering grounds. In turn, these winter moult costs could reduce reproductive success in the following breeding season. In house martins Delichon urbica captured and studied at a breeding site in Europe, we used ptilochronology to measure growth rate of tail feathers moulted on the winter range in Africa, and assessed infection status of blood parasites transmitted on the wintering grounds. We found a negative association between haemosporidian parasite infection status and inferred growth rate of tail feathers. A low feather growth rate and blood parasite infections were related to a delay in laying date in their European breeding quarters. In addition, clutch size and the number of fledglings were negatively related to a delayed laying date and blood parasite infection. These results stress the importance of blood parasites and feather growth rate as potentially mechanisms driving carry-over effects to explain fitness differences in wild populations of migratory birds.

  19. Effect of growth hormone deficiency on brain MRI findings among children with growth restrictions.

    PubMed

    Naderi, Fariba; Eslami, Samira Rajabi; Mirak, Sohrab Afshari; Khak, Mohammad; Amiri, Jalaladin; Beyrami, Bahram; Shekarchi, Babak; Poureisa, Masoud

    2015-01-01

    Growth hormone deficiency (GHD) is a major problem among children with short stature. In this study, the role of brain magnetic resonance imaging (MRI) in defining the underlying defects among short children with GHD is evaluated. In a cross-sectional study, data of 158 children were evaluated. Growth hormone (GH) levels were measured using stimulating tests and brain MRI with gadolinium contrast was applied, as well. Some 25.3% of patients had GHD with a mean age of 8.01±3.40 years. MRI results showed 35 as normal, four with pituitary hypoplasia, and one with microadenoma. The MRI results were significantly associated with GH levels and presence of other endocrine disorders. There was a significant association between prenatal disorders and patients' bone age delay. In patients with severe GHD and patients with multiple pituitary hormone deficiencies, MRI is more likely to be abnormal, and bone age is much delayed in patients with history of prenatal disorders.

  20. Global gene expression profiling related to temperature-sensitive growth abnormalities in interspecific crosses between tetraploid wheat and Aegilops tauschii

    PubMed Central

    Sakaguchi, Kouhei; Ohno, Ryoko; Yoshida, Kentaro

    2017-01-01

    Triploid wheat hybrids between tetraploid wheat and Aegilops tauschii sometimes show abnormal growth phenotypes, and the growth abnormalities inhibit generation of wheat synthetic hexaploids. In type II necrosis, one of the growth abnormalities, necrotic cell death accompanied by marked growth repression occurs only under low temperature conditions. At normal temperature, the type II necrosis lines show grass-clump dwarfism with no necrotic symptoms, excess tillers, severe dwarfism and delayed flowering. Here, we report comparative expression analyses to elucidate the molecular mechanisms of the temperature-dependent phenotypic plasticity in the triploid wheat hybrids. We compared gene and small RNA expression profiles in crown tissues to characterize the temperature-dependent phenotypic plasticity. No up-regulation of defense-related genes was observed under the normal temperature, and down-regulation of wheat APETALA1-like MADS-box genes, considered to act as flowering promoters, was found in the grass-clump dwarf lines. Some microRNAs, including miR156, were up-regulated, whereas the levels of transcripts of the miR156 target genes SPLs, known to inhibit tiller and branch number, were reduced in crown tissues of the grass-clump dwarf lines at the normal temperature. Unusual expression of the miR156/SPLs module could explain the grass-clump dwarf phenotype. Dramatic alteration of gene expression profiles, including miRNA levels, in crown tissues is associated with the temperature-dependent phenotypic plasticity in type II necrosis/grass-clump dwarf wheat hybrids. PMID:28463975

  1. A putative APSES transcription factor is necessary for normal growth and development of Aspergillus nidulans.

    PubMed

    Lee, Ji-Yeon; Kim, Lee-Han; Kim, Ha-Eun; Park, Jae-Sin; Han, Kap-Hoon; Han, Dong-Min

    2013-12-01

    The nsdD gene encoding a GATA type transcription factor positively controls sexual development in Aspergillus nidulans. According to microarray data, 20 genes that were upregulated by deleting nsdD during various life cycle stages were randomly selected and deleted for functional analysis. None of the mutants showed apparent changes in growth or development compared with those of the wild-type except the AN3154 gene that encodes a putative APSES transcription factor and is an ortholog of Saccharomyces cerevisiae swi4. Deleting AN3154 resulted in retarded growth and development, and the gene was named rgdA (retared growth and development). The rgdA deletion mutant developed a reduced number of conidia even under favorable conditions for asexual development. The retarded growth and development was partially suppressed by the veA1 mutation. The conidial heads of the mutant aborted, showing reduced and irregular shaped phialides. Fruiting body development was delayed compared with that in the wild-type. The mutant did not respond to various nutritional or environmental factors that affected the development patterns. The rgdA gene was expressed at low levels throughout the life cycle and was not significantly affected by several regulators of sexual and asexual development such as nsdD, veA, stuA, or brlA. However, the rgdA gene affected brlA and abaA expression, which function as key regulators of asexual sporulation, suggesting that rgdA functions upstream of those genes.

  2. Cervical vertebral maturation of children with orofacial clefts.

    PubMed

    Sun, Ling; Li, Wei Ran

    2012-11-01

    To evaluate the skeletal maturation of male children with orofacial clefts using the cervical vertebral maturation (CVM) method. Case-control study. The School of Stomatology, Peking University. Subjects were 443 boys with cleft lip and/or cleft palate (CL/P) aged 8 to 16 years who were compared with 1772 boys without clefts in an age-matched control group. The 8- to 10-year-old boys of both groups were in CS1. Most of the 11- to 14-year-old boys without CL/P were in CS3 and CS4, though it was not so obvious in boys with CL/P. Most 15- to 16-year-old boys without CL/P were in CS5 and CS6, while there were a lot of boys with CL/P who were still in cervical stages before CS5. Clefts had a significant effect on growth, and boys without CL/P were 1.737 times more likely to have achieved higher cervical stages. From Mann-Whitney test of every age phase, the difference existed in each year of the age range of 11 to 16 years, except from 12 to 13 years (p  =  .100). In these age phases, the cervical stages of boys with CL/P were lower than those for boys without CL/P. By the age of 14, children with CL/P had a 4.679 times higher risk of delayed CS3, and the 95% confidence interval for the odds ratio was 2.129 to 10.286. Boys with CL/P are at a higher risk of delayed growth period and retarded pubertal growth peak.

  3. Orientation-specific responses to sustained uniaxial stretching in focal adhesion growth and turnover

    PubMed Central

    Chen, Yun; Pasapera, Ana M.; Koretsky, Alan P.; Waterman, Clare M.

    2013-01-01

    Cells are mechanosensitive to extracellular matrix (ECM) deformation, which can be caused by muscle contraction or changes in hydrostatic pressure. Focal adhesions (FAs) mediate the linkage between the cell and the ECM and initiate mechanically stimulated signaling events. We developed a stretching apparatus in which cells grown on fibronectin-coated elastic substrates can be stretched and imaged live to study how FAs dynamically respond to ECM deformation. Human bone osteosarcoma epithelial cell line U2OS was transfected with GFP-paxillin as an FA marker and subjected to sustained uniaxial stretching. Two responses at different timescales were observed: rapid FA growth within seconds after stretching, and delayed FA disassembly and loss of cell polarity that occurred over tens of minutes. Rapid FA growth occurred in all cells; however, delayed responses to stretch occurred in an orientation-specific manner, specifically in cells with their long axes perpendicular to the stretching direction, but not in cells with their long axes parallel to stretch. Pharmacological treatments demonstrated that FA kinase (FAK) promotes but Src inhibits rapid FA growth, whereas FAK, Src, and calpain 2 all contribute to delayed FA disassembly and loss of polarity in cells perpendicular to stretching. Immunostaining for phospho-FAK after stretching revealed that FAK activation was maximal at 5 s after stretching, specifically in FAs oriented perpendicular to stretch. We hypothesize that orientation-specific activation of strain/stress-sensitive proteins in FAs upstream to FAK and Src promote orientation-specific responses in FA growth and disassembly that mediate polarity rearrangement in response to sustained stretch. PMID:23754369

  4. An analysis of dental development in Pleistocene Homo using skeletal growth and chronological age.

    PubMed

    Šešelj, Maja

    2017-07-01

    This study takes a new approach to interpreting dental development in Pleistocene Homo in comparison with recent modern humans. As rates of dental development and skeletal growth are correlated given age in modern humans, using age and skeletal growth in tandem yields more accurate dental development estimates. Here, I apply these models to fossil Homo to obtain more individualized predictions and interpretations of their dental development relative to recent modern humans. Proportional odds logistic regression models based on three recent modern human samples (N = 181) were used to predict permanent mandibular tooth development scores in five Pleistocene subadults: Homo erectus/ergaster, Neanderthals, and anatomically modern humans (AMHs). Explanatory variables include a skeletal growth indicator (i.e., diaphyseal femoral length), and chronological age. AMHs Lagar Velho 1 and Qafzeh 10 share delayed incisor development, but exhibit considerable idiosyncratic variation within and across tooth types, relative to each other and to the reference samples. Neanderthals Dederiyeh 1 and Le Moustier 1 exhibit delayed incisor coupled with advanced molar development, but differences are reduced when femoral diaphysis length is considered. Dental development in KNM-WT 15,000 Homo erectus/ergaster, while advanced for his age, almost exactly matches the predictions once femoral length is included in the models. This study provides a new interpretation of dental development in KNM-WT 15000 as primarily reflecting his faster rates of skeletal growth. While the two AMH specimens exhibit considerable individual variation, the Neanderthals exhibit delayed incisor development early and advanced molar development later in ontogeny. © 2017 Wiley Periodicals, Inc.

  5. Nutrition and growth: assessing the impact of regional nutritional intake on childhood development and metacarpal parameters.

    PubMed

    Moro, Christian; Covino, Jessica

    2018-03-01

    Measuring skeletal development throughout juvenile growth can provide a greater understanding into the health, hormonal function and genetics of children. The metacarpals have been of interest for their potential to provide insights into healthy juvenile skeletal development. This study investigated the growth patterns of developing females from isolated communities who had varied diets. Anthropometrical measurements and hand-wrist X-rays were taken of 353 juvenile females from three populations: Pari Coastal Village and Bundi Highlands Village, Papua New Guinea (PNG); and Brisbane, Australia between 1968 to 1983. Radiographs were digitized, and the length and width of the second and third metacarpals compared to each subject's height and weight. As subject heights increased, metacarpal length and width increased. However, stature and second metacarpal length indicated the strongest correlation ( P <0.01), compared to third metacarpal length ( P <0.01) or width. From 11 to 13 years of age, Brisbane subjects were significantly heavier and taller in comparison to subjects from PNG, and coastal females were heavier and taller than the highland females. A prominent difference between the two PNG populations was the regional intake of protein in their diets. The second metacarpal presents particularly accurate measurements when determining the height or development of a child. Nutritional intake appears to have a major influence normal childhood growth, with a potential for protein deficiency to strongly inhibit growth. Any delayed growth is particularly evident in the child's stature, as well as in the development of the metacarpal long bones of the hand.

  6. Integration and scaling of UV-B radiation effects on plants: from molecular interactions to whole plant responses.

    PubMed

    Suchar, Vasile Alexandru; Robberecht, Ronald

    2016-07-01

    A process based model integrating the effects of UV-B radiation to molecular level processes and their consequences to whole plant growth and development was developed from key parameters in the published literature. Model simulations showed that UV-B radiation induced changes in plant metabolic and/or photosynthesis rates can result in plant growth inhibitions. The costs of effective epidermal UV-B radiation absorptive compounds did not result in any significant changes in plant growth, but any associated metabolic costs effectively reduced the potential plant biomass. The model showed significant interactions between UV-B radiation effects and temperature and any factor leading to inhibition of photosynthetic production or plant growth during the midday, but the effects were not cumulative for all factors. Vegetative growth were significantly delayed in species that do not exhibit reproductive cycles during a growing season, but vegetative growth and reproductive yield in species completing their life cycle in one growing season did not appear to be delayed more than 2-5 days, probably within the natural variability of the life cycles for many species. This is the first model to integrate the effects of increased UV-B radiation through molecular level processes and their consequences to whole plant growth and development.

  7. Hormonal control of aging in rodents: The somatotropic axis

    PubMed Central

    Brown-Borg, Holly M.

    2015-01-01

    There is a growing body of literature focusing on the somatotropic axis and regulation of aging and longevity. Many of these reports derive data from multiple endocrine mutants, those that exhibit both elevated growth hormone (GH) and insulin-like growth factor I (IGF-1) or deficiencies in one or both of these hormones. In general, both spontaneous and genetically engineered GH and IGF-1 deficiencies have lead to small body size, delayed development of sexual maturation and age-related pathology, and life span extension. In contrast, characteristics of high circulating GH included larger body sizes, early puberty and reproductive senescence, increased cancer incidence and reduced life span when compared to wild-type animals with normal plasma hormone concentrations. This information, along with that found in multiple other species, implicates this anabolic pathway as the major regulator of longevity in animals. PMID:18674587

  8. Skin fibroblasts from individuals hemizygous for the familial adenopolyposis susceptibility gene show delayed crisis in vitro

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

    Chen, S.; Kazim, D.; Kraveka, J.

    Normal human fibroblast cells have not been reported to escape crisis--that is they die after about 24 doublings in culture. The authors have been studying the growth properties of skin fibroblast cells from persons in families with familial adenopolyposis of the colon (FAP). An individual hemizygous at the FAP locus will develop hyperplasia of the colonic epithelium followed by colonic polyps, both at an early age. Polyps themselves still retain a single functional FAP allele. A mutation or deletion in this allele in a polyp is hypothesized to lead to further loss of growth control; thus, a tumor is formed.more » They found that the in vitro life-span of skin fibroblast cells from FAP individuals and from some asymptomatic children were markedly extended when compared with normal individuals.« less

  9. Theory-of-Mind Development in Oral Deaf Children with Cochlear Implants or Conventional Hearing Aids

    ERIC Educational Resources Information Center

    Peterson, Candida C.

    2004-01-01

    Background: In the context of the established finding that theory-of-mind (ToM) growth is seriously delayed in late-signing deaf children, and some evidence of equivalent delays in those learning speech with conventional hearing aids, this study's novel contribution was to explore ToM development in deaf children with cochlear implants. Implants…

  10. Growth dominates choice in network percolation

    NASA Astrophysics Data System (ADS)

    Vijayaraghavan, Vikram S.; Noël, Pierre-André; Waagen, Alex; D'Souza, Raissa M.

    2013-09-01

    The onset of large-scale connectivity in a network (i.e., percolation) often has a major impact on the function of the system. Traditionally, graph percolation is analyzed by adding edges to a fixed set of initially isolated nodes. Several years ago, it was shown that adding nodes as well as edges to the graph can yield an infinite order transition, which is much smoother than the traditional second-order transition. More recently, it was shown that adding edges via a competitive process to a fixed set of initially isolated nodes can lead to a delayed, extremely abrupt percolation transition with a significant jump in large but finite systems. Here we analyze a process that combines both node arrival and edge competition. If started from a small collection of seed nodes, we show that the impact of node arrival dominates: although we can significantly delay percolation, the transition is of infinite order. Thus, node arrival can mitigate the trade-off between delay and abruptness that is characteristic of explosive percolation transitions. This realization may inspire new design rules where network growth can temper the effects of delay, creating opportunities for network intervention and control.

  11. Length distributions of nanowires: Effects of surface diffusion versus nucleation delay

    NASA Astrophysics Data System (ADS)

    Dubrovskii, Vladimir G.

    2017-04-01

    It is often thought that the ensembles of semiconductor nanowires are uniform in length due to the initial organization of the growth seeds such as lithographically defined droplets or holes in the substrate. However, several recent works have already demonstrated that most nanowire length distributions are broader than Poissonian. Herein, we consider theoretically the length distributions of non-interacting nanowires that grow by the material collection from the entire length of their sidewalls and with a delay of nucleation of the very first nanowire monolayer. The obtained analytic length distribution is controlled by two parameters that describe the strength of surface diffusion and the nanowire nucleation rate. We show how the distribution changes from the symmetrical Polya shape without the nucleation delay to a much broader and asymmetrical one for longer delays. In the continuum limit (for tall enough nanowires), the length distribution is given by a power law times an incomplete gamma-function. We discuss interesting scaling properties of this solution and give a recipe for analyzing and tailoring the experimental length histograms of nanowires which should work for a wide range of material systems and growth conditions.

  12. Cellular expansion and gene expression in the developing grape (Vitis vinifera L.).

    PubMed

    Schlosser, J; Olsson, N; Weis, M; Reid, K; Peng, F; Lund, S; Bowen, P

    2008-01-01

    Expression profiles of genes involved in cell wall metabolism and water transport were compared with changes in grape (Vitis vinifera L.) berry growth, basic chemical composition, and the shape, size, and wall thickness of cells within tissues of the berry pericarp. Expression of cell wall-modifying and aquaporin genes in berry pericarp tissues generally followed a bimodal expression profile with high levels of expression coinciding with the two periods of rapid berry growth, stages I and III, and low levels of expression corresponding to the slow-growth period, stage II. Cellular expansion was observed throughout all tissues during stage I, and only mesocarp cellular expansion was observed during stage III. Expansion of only exocarp cells was evident during transition between stages II and III. Cell wall-modifying and aquaporin gene expression profiles followed similar trends in exocarp and mesocarp tissues throughout berry development, with the exception of the up-regulation of pectin methylesterase, pectate lyase, two aquaporin genes (AQ1 and AQ2), and two expansin genes (EXP3 and EXPL) during stage II, which was delayed in the exocarp tissue compared with mesocarp tissue. Exocarp endo-(1-->3)-beta-glucanase and expansin-like gene expression was concurrent with increases in epidermal and hypodermal cell wall thickness. These results indicate a potential role of the grape berry skin in modulating grape berry growth.

  13. A matrix metalloproteinase inhibitor enhances anti-cytotoxic T lymphocyte antigen-4 antibody immunotherapy in breast cancer by reprogramming the tumor microenvironment

    PubMed Central

    LI, MINGYUE; XING, SHUGANG; ZHANG, HAIYING; SHANG, SIQI; LI, XIANGXIANG; REN, BO; LI, GAIYUN; CHANG, XIAONA; LI, YILEI; LI, WEI

    2016-01-01

    Anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) treatment is effective for the treatment of primary tumors, but not sufficient for the treatment of metastatic tumors, likely owing to the effects of the tumor microenvironment. In this study, we aimed to determine the therapeutic effects of combined treatment with a matrix metalloproteinase (MMP) inhibitor (MMPI) and anti-CTLA-4 antibody in a breast cancer model in mice. Interestingly, combined treatment with MMPI and anti-CTLA-4 antibody delayed tumor growth and reduced lung and liver metastases compared with anti-CTLA-4 alone or vehicle treatment. The functions of the liver and kidney in mice in the different groups did not differ significantly compared with that in normal mice. The CD8+/CD4+ ratio in T cells in the spleen and tumor were increased after monotherapy or combined anti-CTLA-4 antibody plus MMPI therapy compared with that in vehicle-treated mice. Anti-CTLA-4 antibody plus MMPI therapy reduced the percentage of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) and decreased the Treg/Th17 cell ratio in the spleen compared with those in the vehicle-treated group. Additionally, anti-CTLA-4 antibody plus MMPI therapy reduced the percentages of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and Th17 cells in tumors compared with that in the vehicle-treated group. Moreover, combined treatment with MMPI and anti-CTLA-4 antibody reduced the microvessel density (MVD) in tumors compared with that in vehicle or MMPI-treated mice. There was a negative correlation between MVD and the CD8+ T cell percentage, CD4+ T cell percentage, and CD8+/CD4+ T cell ratio, but a positive correlation with Tregs, Th17 cells, Treg/Th17 cell ratio, and MDSCs. Thus, these data demonstrated that addition of MMPI enhanced the effects of anti-CTLA-4 antibody treatment in a mouse model of breast cancer by delaying tumor growth and reducing metastases. PMID:26752000

  14. Early Generalized Overgrowth in Boys With Autism

    PubMed Central

    Chawarska, Katarzyna; Campbell, Daniel; Chen, Lisha; Shic, Frederick; Klin, Ami; Chang, Joseph

    2016-01-01

    Context Multiple studies have reported an overgrowth in head circumference (HC) in the first year of life in autism. However, it is unclear whether this phenomenon is independent of overall body growth and whether it is associated with specific social or cognitive features. Objectives To examine the trajectory of early HC growth in autism compared with control groups; to assess whether HC growth in autism is independent of height and weight growth during infancy; and to examine HC growth from birth to 24 months in relationship to social, verbal, cognitive, and adaptive functioning levels. Design Retrospective study. Setting A specialized university-based clinic. Participants Boys diagnosed as having autistic disorder (n=64), pervasive developmental disorder–not otherwise specified (n=34), global developmental delay (n=13), and other developmental problems (n=18) and typically developing boys (n=55). Main Outcome Measures Age-related changes in HC, height, and weight between birth and age 24 months; measures of social, verbal, and cognitive functioning at age 2 years. Results Compared with typically developing controls, boys with autism were significantly longer by age 4.8 months, had a larger HC by age 9.5 months, and weighed more by age 11.4 months (P=.05 for all). None of the other clinical groups showed a similar overgrowth pattern. Boys with autism who were in the top 10% of overall physical size in infancy exhibited greater severity of social deficits (P=.009) and lower adaptive functioning (P=.03). Conclusions Boys with autism experienced accelerated HC growth in the first year of life. However, this phenomenon reflected a generalized process affecting other morphologic features, including height and weight. The study highlights the importance of studying factors that influence not only neuronal development but also skeletal growth in autism. PMID:21969460

  15. Effect of in ovo feeding of dextrin-iodinated casein in broilers: II. Hatch window and growth performance.

    PubMed

    Abousaad, S; Lassiter, K; Piekarski, A; Chary, P; Striplin, K; Christensen, K; Bielke, L R; Hargis, B M; Dridi, S; Bottje, W G

    2017-05-01

    Studies were conducted using a commercial InovojectTM system to determine effects of in ovo feeding of dextrin and iodinated casein (IC) on hatch and posthatch growth in broilers. At ∼18.5 d embryonic development, eggs were treated with 0, 240, or 480 μg IC/mL in saline (Cont, IC240, and IC480) or dextrin (Dext, DextIC240 and DextIC480). The Dext solution consisted of 18% maltodextrin and 10% potato starch dextrin; saline was the vehicle used by the company for in ovo vaccination. The volume for all in ovo treatments was 50 μL/injection. Eggs in Experiment 1 were transferred to a commercial hatcher unit whereas eggs in Experiments 2 and 3 were transferred to a research hatcher unit to assess effects of treatments on timing of hatch. At hatch, chicks were randomly selected and placed in floor pens and grown to 6 wk. In Experiment 1, there were no differences in hatch weights, but broilers provided Dext IC240 in ovo were heavier (P < 0.05) at 6 wk compared to other treatments with the exception of the Dext IC240 group. In Experiment 2, hatch weights were heavier (P < 0.05) in chicks receiving IC240 and DexIC480 treatments compared to Controls. At 6 wk, broilers in all treatments were heavier (P < 0.05) than Cont with the exception of IC480. In Experiment 3, hatch was stimulated by IC240 (in saline), but was delayed by Dext IC240. Serum analysis of β-hydroxybutyrate (μM/mL), as an indicator of ketone accumulation from fat metabolism of chicks held in chick boxes for 24 h posthatch (to simulate delay in placement after hatch), indicated that chicks in the IC240 group (that hatched earlier) had higher blood ketones compared to chicks that received Dext or DextIC240 in ovo (that hatched later). We conclude dextrin and iodinated casein (240 μg/mL) provided in ovo (∼18.5 d of embryonic development) has the potential to improve chick quality and posthatch body weight by delaying or narrowing hatch window. © 2016 Poultry Science Association Inc.

  16. Identification of three signaling molecules required for calcineurin-dependent monopolar growth induced by the DNA replication checkpoint in fission yeast.

    PubMed

    Kume, Kazunori; Hashimoto, Tomoyo; Suzuki, Masashi; Mizunuma, Masaki; Toda, Takashi; Hirata, Dai

    2017-09-30

    Cell polarity is coordinately regulated with the cell cycle. Growth polarity of the fission yeast Schizosaccharomyces pombe transits from monopolar to bipolar during G2 phase, termed NETO (new end take off). Upon perturbation of DNA replication, the checkpoint kinase Cds1/CHK2 induces NETO delay through activation of Ca 2+ /calmodulin-dependent protein phosphatase calcineurin (CN). CN in turn regulates its downstream targets including the microtubule (MT) plus-end tracking CLIP170 homologue Tip1 and the Casein kinase 1γ Cki3. However, whether and which Ca 2+ signaling molecules are involved in the NETO delay remains elusive. Here we show that 3 genes (trp1322, vcx1 and SPAC6c3.06c encoding TRP channel, antiporter and P-type ATPase, respectively) play vital roles in the NETO delay. Upon perturbation of DNA replication, these 3 genes are required for not only the NETO delay but also for the maintenance of cell viability. Trp1322 and Vcx1 act downstream of Cds1 and upstream of CN for the NETO delay, whereas SPAC6c3.06c acts downstream of CN. Consistently, Trp1322 and Vcx1, but not SPAC6c3.06c, are essential for activation of CN. Interestingly, we have found that elevated extracellular Ca 2+ per se induces a NETO delay, which depends on CN and its downstream target genes. These findings imply that Ca 2+ -CN signaling plays a central role in cell polarity control by checkpoint activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Acute exposure to tris (2-butoxyethyl) phosphate (TBOEP) affects growth and development of embryo-larval zebrafish.

    PubMed

    Liu, Yiran; Wu, Ding; Xu, Qinglong; Yu, Liqin; Liu, Chunsheng; Wang, Jianghua

    2017-10-01

    Tris (2-butoxyethyl) phosphate (TBOEP), is used as a flame retardant worldwide. It is an additive in materials and can be easily discharged into the surrounding environment. There is evidence linking TBOEP exposure to abnormal development and growth in zebrafish embryos/larvae. Here, using zebrafish embryo as a model, we investigated toxicological effects on developing zebrafish (Danio rerio) caused by TBOEP at concentrations of 0, 20, 200, 1000, 2000μg/L starting from 2h post-fertilization (hpf). Our findings revealed that TBOEP exposure caused developmental toxicity, such as malformation, growth delay and decreased heart rate in zebrafish larvae. Correlation analysis indicated that inhibition of growth was possibly due to down-regulation of expression of genes related to the growth hormone/insulin-like growth factor (GH/IGF) axis. Furthermore, exposure to TBOEP significantly increased thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in whole larvae. In addition, changed expression of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis was observed, indicating that perturbation of HPT axis might be responsible for the developmental damage and growth delay induced by TBOEP. The present study provides a new set of evidence that exposure of embryo-larval zebrafish to TBOEP can cause perturbation of GH/IGF axis and HPT axis, which could result in developmental impairment and growth inhibition. Copyright © 2017. Published by Elsevier B.V.

  18. Fetal growth from mid- to late pregnancy is associated with infant development: the Generation R Study.

    PubMed

    Henrichs, Jens; Schenk, Jacqueline J; Barendregt, Charlotte S; Schmidt, Henk G; Steegers, Eric Ap; Hofman, Albert; Jaddoe, Vincent W V; Moll, Henriette A; Verhulst, Frank C; Tiemeier, Henning

    2010-07-01

    The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10-17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71-0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73-0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49-0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy. Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes.

  19. Early Compared With Delayed Physician Rounds on Patient Satisfaction of Postpartum Women: A Randomized Controlled Trial.

    PubMed

    Roberts, Robyn P; Blackwell, Sean C; Brown, Kelly M; Pedroza, Claudia; Sibai, Baha M; Tyson, Jon E

    2016-08-01

    To investigate whether delayed timing of physician rounds improves patient satisfaction for postpartum women. Women were randomized to early (5-7 AM) or delayed (8-10 AM) physician rounding. Women with stillbirth, high-risk pregnancy, or complications precluding delayed rounding were excluded. At discharge, women completed a modified Hospital Consumer Assessment of Healthcare Providers and Systems survey. The primary outcome was rating of the hospital. Secondary outcomes included patient assessment of patient-physician communication, various hospital experiences, and timing of maternal and neonatal discharge. We estimated that 74 women were needed to detect a 20% difference in rating of the hospital (0-10 score) between groups (assumption P=.05, power 90%). Given limited information on primary outcome, an a priori plan was in place to conduct the study for 2 months. One hundred fifty-two women were randomized (n=76 early rounding; n=76 delayed rounding). More women had a cesarean delivery in the early compared with the delayed rounding group (47.4% compared with 22.4%). Median rating of the hospital was higher in the delayed as compared with the early rounding group (9.0 [7.0-9.0] compared with 7.0 [6.0-8.0]; P<.01). Median scores regarding physician communication and perception of hospital experiences were higher in the delayed compared with the early group (8.0 [7.0-9.0] compared with 6.0 [5.0-7.0]; P<.001). Adjustment for delivery mode did not alter results (P<.01). No differences in timing of maternal (P=.47) or neonatal hospital discharge (P=.35) were observed. Postpartum women receiving delayed physician rounding were more satisfied with their hospital experience and patient-physician communication without prolonging maternal or neonatal discharge. ClinicalTrials.gov, https://clinicaltrials.gov, NCT02432573.

  20. Short stature in genetic syndromes: Selected issues.

    PubMed

    Łaczmańska, Izabela; Kuliczkowska-Płaksej, Justyna; Stembalska, Agnieszka

    2018-03-14

    Short stature, which is defined as height below 2 standard deviations of the mean height for the age and sex, is one of the most frequent reasons for medical consultations in children. Short stature may occur due to a constitutional delay in growth, familial short stature or chronic diseases, including many genetic syndromes, metabolic and endocrine disorders. In this article the authors provide a mini-review of the most frequent genetic syndromes associated with short stature that should be taken into account in the differential diagnosis process. Syndromes caused by chromosomal aberrations and gene mutations were divided into 2 main groups: syndromes that are associated with intrauterine growth retardation (IUGR) and those in which IUGR does not occur in the natural history of the patient. The authors described the most important anomalies in each syndrome. Metabolic diseases and skeletal dysplasias were omitted, as they are major separate groups of diseases involving growth delay.

  1. Cushing disease in a toddler: not all obese children are just fat.

    PubMed

    Moriarty, Megan; Hoe, Francis

    2009-08-01

    Cushing disease is exceedingly rare in children, especially in those under the age of 2 years. This case report describes an 18-month-old female child who presented with morbid obesity, decreased linear growth, and reversal of developmental milestones. Her diagnosis was delayed; however, she was successfully treated by surgical excision of the microadenoma. This was followed by resolution of signs and symptoms of Cushing syndrome. Although the patient's hypertension resolved, linear growth improved and development began to progress, she is still developmentally delayed and now has hypopituitarism. Review of this case, as well as a handful of other cases of infantile Cushing disease in the literature, suggests that features such as hypertension and slowed linear growth, which are rare in nutritional causes of obesity in infants, can help identify this rare, but life-threatening, illness among an increasing number of overweight infants.

  2. A rare presentation of craniopharyngioma: delayed puberty

    PubMed Central

    İnci, Mehmet Fatih; Özkan, Fuat; Bozkurt, Selim; Demir, Caner Feyzi

    2012-01-01

    Craniopharyngiomas are the most frequently encountered suprasellar tumours in children. Owing to the slow growth rate of these tumours, they are often quite large before becoming symptomatic. They are more common among children and older adults (55–74 years). Depending upon the direction of growth and tumour size, craniopharyngiomas can affect the hypothalamus, pituitary stalk, optic nerves and chiasm and carotid arteries. Compression of these neural and vascular structures frequently precipitates endocrine disorders, visual loss and an increased intracranial pressure. Hypopituitarism leading to a delayed puberty is a rare presentation of craniopharyngioma. The diagnosis of craniopharyngioma is usually made with the classic radiological imaging features based on CT and MRI. PMID:23195827

  3. A unique case of growth hormone and human chorionic gonadotropin treatment in a 45,X male with Y: autosome translocation and literature review.

    PubMed

    Mareri, Arianna; Iezzi, MariaLaura; Salvatore, Alessia; Ligas, Claudio; D'Alessandro, Elvira

    2016-07-01

    Maleness associated with a 45,X karyotype is a rare condition in childhood. It is usually diagnosed in adult age because of infertility. We report a unique case of an unbalanced translocation t(Y;21) in a 14-year-old boy with 45,X karyotype referred because of short stature, thin habitus and puberty delay. Hormone analysis showed low serum levels of basal testosterone, insulin-like growth factor (IGF-I) and gonadotrophins. Diagnosis of GH deficiency and puberty delay were made. He was treated with human chorionic gonadotropin (hCG) and GH therapy, respectively, for 6 and 24 months.

  4. BLACK SPOT INFESTATION IN JUVENILE COHO SALMON AND THE INFLUENCE OF OREGON COASTAL STREAM SUMMER TEMPERATURES

    EPA Science Inventory

    Freshwater survival and growth of juvenile salmon are affected by many factors, including high summer temperatures and other stressors such as parasitism. Delayed or suppressed growth related to stress can influence subsequent survival of juvenile salmonids in freshwater and mar...

  5. The effects of zinc status on early growth in infants with sickle cell disease

    USDA-ARS?s Scientific Manuscript database

    Growth failure, maturational delay, and alterations in body composition occur in older children and adults with Sickle Cell Disease (SCD). Poor nutritional status, specifically zinc deficiency, has been widely implicated, although infants with SCD have not been studied. We determined zinc status in ...

  6. Alagille syndrome with deletion 20p12.2-p12.3 and hypoplastic left heart.

    PubMed

    Robert, Marie Leema P; Lopez, Tony; Crolla, John; Huang, Shuwen; Owen, Carol; Burvill-Holmes, Lisa; Stumper, Oliver; Turnpenny, Peter D

    2007-10-01

    We report a male patient born at 37-weeks gestation, weighing 1.885 kg (<0.4th centile). Shortly after birth, he was diagnosed with hypoplastic left heart syndrome for which he underwent a Norwood procedure. Subsequently, he developed problems with failure to thrive and developmental delay. At the age of 4 years his delay in growth and development led to further investigations, which revealed a small de-novo interstitial deletion of chromosome 20p12.2. JAGGED1 haploinsufficiency was confirmed by fluorescence in situ hybridization. Array-comparative genomic hybridization analysis confirmed and quantified an approximate 5.4 Mb interstitial deletion involving the chromosomal region 20p12.2-p12.3. This precise interstitial deletion has not been previously reported. Further clinical evaluation revealed posterior embryotoxon and butterfly vertebrae. He has normal liver function tests, facial features consistent with Alagille syndrome, and mild learning difficulties. To our knowledge this is the first report of Alagille syndrome associated with hypoplastic left heart syndrome.

  7. The Cyclic Nucleotide-Gated Channel CNGC14 Regulates Root Gravitropism in Arabidopsis thaliana.

    PubMed

    Shih, Han-Wei; DePew, Cody L; Miller, Nathan D; Monshausen, Gabriele B

    2015-12-07

    In plant roots, auxin inhibits cell expansion, and an increase in cellular auxin levels on the lower flanks of gravistimulated roots suppresses growth and thereby causes downward bending. These fundamental features of root growth responses to auxin were first described over 80 years ago, but our understanding of the underlying molecular mechanisms has remained scant. Here, we report that CYCLIC NUCLEOTIDE-GATED CHANNEL 14 (CNGC14) is essential for the earliest phase of auxin-induced ion signaling and growth inhibition in Arabidopsis roots. Using a fluorescence-imaging-based genetic screen, we found that cngc14 mutants exhibit a complete loss of rapid Ca(2+) and pH signaling in response to auxin treatment. Similarly impaired ion signaling was observed upon gravistimulation. We further developed a kinematic analysis approach to study dynamic root growth responses to auxin at high spatiotemporal resolution. These analyses revealed that auxin-induced growth inhibition and gravitropic bending are significantly delayed in cngc14 compared to wild-type roots, where auxin suppresses cell expansion within 1 min of treatment. Finally, we demonstrate that auxin-induced cytosolic Ca(2+) changes are required for rapid growth inhibition. Our results support a direct role for CNGC14-dependent Ca(2+) signaling in regulating the early posttranscriptional phase of auxin growth responses in Arabidopsis roots. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Mild Wolf-Hirschhorn phenotype and partial GH deficiency in a patient with a 4p terminal deletion.

    PubMed

    Titomanlio, L; Romano, A; Conti, A; Genesio, R; Salerno, M; De Brasi, D; Nitsch, L; Del Giudice, E

    2004-06-01

    Wolf-Hirschhorn syndrome (WHS) is caused by a variably-sized deletion of chromosome 4 involving band 4p16 whose typical craniofacial features are "Greek warrior helmet appearance" of the nose, microcephaly, and prominent glabella. Almost all patients show mental retardation and pre- and post-natal growth delay. Patient was born at term, after a pregnancy characterized by intra-uterine growth retardation (IUGR). Delivery was uneventful. Developmental delay was evident since the first months of life. At 2 years, he developed generalized tonic-clonic seizures. Because of short stature, low growth velocity and delayed bone age, at 4 years he underwent growth hormone (GH) evaluation. Peak GH after two provocative tests revealed a partial GH deficiency. Clinical observation at 7 years disclosed a distinctive facial appearance, with microcephaly, prominent eyes, and beaked nose. Brain MRI showed left temporal mesial sclerosis. GTG banded karyotype was normal. Because of mental retardation, subtelomeric fluorescence in situ hybridization (FISH) analysis was performed, disclosing a relatively large deletion involving 4p16.2 --> pter (about 4.5 Mb), in the proband, not present in the parents. The smallest deletion detected in a WHS patient thus far includes two candidate genes, WHSC1 and WHSC2. Interestingly, that patient did not show shortness of stature, and that could be due to the haploinsufficiency of other genes localized in the flanking regions. Contribution of GH alterations and possible GH therapy should be further considered in WHS patients. Copyright 2004 Wiley-Liss, Inc.

  9. Dietary supplementation of L-glutamine and L-glutamate in broiler chicks subjected to delayed placement.

    PubMed

    Zulkifli, I; Shakeri, M; Soleimani, A F

    2016-12-01

    This study was conducted to investigate the effect of dietary glutamine (Gln) + glutamic acid (Glu) supplementation on growth performance and physiological stress response in broiler chickens subjected to 24 h delay in placement. Equal number of day-old broiler chicks were assigned to either immediate placement or with 24 h delay in placement with no access to feed and water. Chicks from each placement group were fed either standard starter diet (control) or standard starter diet +1% AminoGut (AG; mixture of 10% Gln and 10% Glu) from 1 to 21 d. Blood and duodenal samples were collected at 21 d for analysis of serum levels of ceruloplasmin (CER), ovotransferin (OVT) and α-1 acid glycoprotein (AGP), duodenal heat shock protein (HSP) 70 expression, and villi length and crypt depth. Results showed that delayed placement for 24 h was detrimental to weight gain during the starter phase (1 to 21 d) but not thereafter. AG supplementation was not able to eliminate that reduction in weight gain and feed intake during the starter stage. However, the observed enhancement in villi length and crypt depth at d 21 resulted in improvement of FCR and weight gain during the finisher stage (22 to 42 d) and consequently the overall period (1 to 42 d). Broiler chickens supplemented with AG also showed lower mortality rate, and higher AGP, OVT, CER, and HSP 70 expression compared to their control counterparts. Based on AGP, OVT, CER, and HSP 70 expression, there is no indication that delayed placement was physiologically stressful to the broiler chickens at 21 d of age. © 2016 Poultry Science Association Inc.

  10. MSW Variable Time-Delay Techniques.

    DTIC Science & Technology

    1982-07-01

    21 I, 5. RITAXIAL GEOWTH O COG FILKS G0 film growth by lpe was Investigated as a possible nouagnetic, dielectric spacer sediun between two YG fls...using two yttrium iron garnet films sandwiching simple single finger transducers. Difficulties In exciting the symetric forward volume mode are explained...direction. Measurements of time delay versus frequency are presented for epitaxially grown Yttrium Iron Garnet (YIG) films . Finally, transducer coupling

  11. Source-sink regulation of cotyledonary reserve mobilization during cashew (Anacardium occidentale) seedling establishment under NaCl salinity.

    PubMed

    Voigt, Eduardo Luiz; Almeida, Tânia Dias; Chagas, Roberta Magalhães; Ponte, Luiz Ferreira Aguiar; Viégas, Ricardo Almeida; Silveira, Joaquim Albenísio Gomes

    2009-01-01

    Seedling establishment is a critical process to crop productivity, especially under saline conditions. This work was carried out to investigate the hypothesis that reserve mobilization is coordinated with salt-induced inhibition of seedling growth due to changes in source-sink relations. To test this hypothesis, cashew nuts (Anacardium occidentale) were sown in vermiculite irrigated daily with distilled water (control) or 50mM NaCl and they were evaluated at discrete developmental stages from the seed germination until the whole seedling establishment. The salt treatment coordinately delayed the seedling growth and the cotyledonary reserve mobilization. However, these effects were more pronounced at late seedling establishment than in earlier stages. The storage protein mobilization was affected by salt stress before the lipid and starch breakdown. The globulin fraction represented the most important storage proteins of cashew cotyledons, and its mobilization was markedly delayed by NaCl along the seedling establishment. Free amino acids were mostly retained in the cotyledons of salt-treated seedlings when the mobilization of storage proteins, lipids and starch was strongly delayed. Proline was not considerably accumulated in the cotyledons of cashew seedlings as a response to NaCl salinity. According to these results it is noteworthy that the salt-induced inhibition of seedling growth is narrowly coordinated with the delay of reserve mobilization and the accumulation of hydrolysis products in cotyledons. Also, it was evidenced that free amino acids, especially those related to nitrogen transport, are potential signals involved in the regulation of storage protein hydrolysis during cashew seedling establishment under NaCl salinity.

  12. Chronic unilateral ureteral obstruction in the neonatal mouse delays maturation of both kidneys and leads to late formation of atubular glomeruli

    PubMed Central

    Forbes, Michael S.; Thornhill, Barbara A.; Galarreta, Carolina I.; Minor, Jordan J.; Gordon, Katherine A.

    2013-01-01

    Unilateral ureteral obstruction (UUO) in the adult mouse is the most widely used model of progressive renal disease: the proximal tubule is the nephron segment most severely affected and atubular glomeruli are formed after only 7 days of UUO. To determine the proximal nephron response to UUO in the maturing kidney, neonatal mice were examined 7 to 28 days following complete UUO under general anesthesia. Proximal tubular mass and maturation were determined by staining with Lotus tetragolonobus lectin. Superoxide was localized by nitroblue tetrazolium and collagen by Sirius red. Cell proliferation, cell death, PAX-2, megalin, α-smooth muscle actin (α-SMA), renin, and fibronectin were identified by immunohistochemistry. During the first 14 days of ipsilateral UUO, despite oxidative stress (4-hydroxynonenal staining), glomerulotubular continuity was maintained and mitochondrial superoxide production persisted. However, from 14 to 28 days, papillary growth was impaired and proximal tubules collapsed with increased apoptosis, autophagy, mitochondrial loss, and formation of atubular glomeruli. Fibronectin, α-SMA, and collagen increased in the obstructed kidney. Oxidative stress was present also in the contralateral kidney: renin was decreased, glomerulotubular maturation and papillary growth were delayed, followed by increased cortical and medullary growth. We conclude that neonatal UUO initially delays renal maturation and results in oxidative stress in both kidneys. In contrast to the adult, proximal tubular injury in the neonatal obstructed kidney is delayed at 14 days, followed only later by the formation of atubular glomeruli. Antioxidant therapies directed at proximal tubular mitochondria during early renal maturation may slow progression of congenital obstructive nephropathy. PMID:24107422

  13. ZRBA1, a Mixed EGFR/DNA Targeting Molecule, Potentiates Radiation Response Through Delayed DNA Damage Repair Process in a Triple Negative Breast Cancer Model

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

    Heravi, Mitra; Department of Radiation Oncology, McGill University, Montreal; Segal Cancer Center, Jewish General Hospital, Montreal

    2015-06-01

    Purpose: ZRBA1 is a combi-molecule designed to induce DNA alkylating lesions and to block epidermal growth factor receptor (EGFR) TK domain. Inasmuch as ZRBA1 downregulates the EGFR TK-mediated antisurvival signaling and induces DNA damage, we postulated that it might be a radiosensitizer. The aim of this study was to further investigate the potentiating effect of ZRBA1 in combination with radiation and to elucidate the possible mechanisms of interaction between these 2 treatment modalities. Methods and Materials: The triple negative human breast MDA-MB-468 cancer cell line and mouse mammary cancer 4T1 cell line were used in this study. Clonogenic assay, Westernmore » blot analysis, and DNA damage analysis were performed at multiple time points after treatment. To confirm our in vitro findings, in vivo tumor growth delay assay was performed. Results: Our results show that a combination of ZRBA1 and radiation increases the radiation sensitivity of both cell lines significantly with a dose enhancement factor of 1.56, induces significant numbers of DNA strand breaks, prolongs higher DNA damage up to 24 hours after treatment, and significantly increases tumor growth delay in a syngeneic mouse model. Conclusions: Our data suggest that the higher efficacy of this combination could be partially due to increased DNA damage and delayed DNA repair process and to the inhibition of EGFR. The encouraging results of this combination demonstrated a significant improvement in treatment efficiency and therefore could be applicable in early clinical trial settings.« less

  14. Extraocular motoneurons of the adult rat show higher levels of vascular endothelial growth factor and its receptor Flk-1 than other cranial motoneurons.

    PubMed

    Silva-Hucha, Silvia; Hernández, Rosendo G; Benítez-Temiño, Beatriz; Pastor, Ángel M; de la Cruz, Rosa R; Morcuende, Sara

    2017-01-01

    Recent studies show a relationship between the deficit of vascular endothelial growth factor (VEGF) and motoneuronal degeneration, such as that occurring in amyotrophic lateral sclerosis (ALS). VEGF delivery protects motoneurons from cell death and delayed neurodegeneration in animal models of ALS. Strikingly, extraocular motoneurons show lesser vulnerability to neurodegeneration in ALS compared to other cranial or spinal motoneurons. Therefore, the present study investigates possible differences in VEGF and its main receptor VEGFR-2 or Flk-1 between extraocular and non-extraocular brainstem motoneurons. We performed immunohistochemistry and Western blot to determine the presence of VEGF and Flk-1 in rat motoneurons located in the three extraocular motor nuclei (abducens, trochlear and oculomotor) and to compare it to that observed in two other brainstem nuclei (hypoglossal and facial) that are vulnerable to degeneration. Extraocular motoneurons presented higher amounts of VEGF and its receptor Flk-1 than other brainstem motoneurons, and thus these molecules could be participating in their higher resistance to neurodegeneration. In conclusion, we hypothesize that differences in VEGF availability and signaling could be a contributing factor to the different susceptibility of extraocular motoneurons, when compared with other motoneurons, in neurodegenerative diseases.

  15. Effects of depleted uranium on survival, growth, and metamorphosis in the african clawed frog (Xenopus laevis)

    USGS Publications Warehouse

    Mitchell, S.E.; Caldwell, C.A.; Gonzales, G.; Gould, W.R.; Arimoto, R.

    2005-01-01

    Embryos (stage 8-47, Nieuwkoop and Faber) of the African clawed frog (Xenopus laevis) were subjected to water-borne depleted uranium (DU) concentrations that ranged from 4.8 to 77.7 mg/Lusing an acute 96-h frog embryo teratogenesis assay-Xenopus (FETAX). In a chronic 64-d assay, X. laevis (from embryo through metamorphosis; stages 8-66) were subjected to concentrations of DU that ranged from 6.2 to 54.3 mg/L Our results indicate DU is a non teratogenic metal. No effects on mortality, malformations, or growth were observed in the 96-h FETAX with concentrations of DU that ranged from 4.8 to 77.7 mg/L From stage 8 to stage 47, X. laevis tadpoles do not actively feed and the gills are not well developed. Thus, uptake of DU was reduced despite exposure to elevated concentrations. The 64-d assay resulted in no concentration response for either mortality or malformations; however, a delay in metamorphosis was observed in tadpoles subjected to elevated DU concentrations (from 13.1 to 54.3 mg/L) compared to tadpoles in both the well-water control and reference. The delay in metamorphosis was likely due to increasing body burden of DU that ranged from 0.98 to 2.82 mg/kg. Copyright?? Taylor & Francis Inc.

  16. Maternal low-protein diet-induced delayed reflex ontogeny is attenuated by moderate physical training during gestation in rats.

    PubMed

    Falcão-Tebas, Filippe; Bento-Santos, Adriano; Fidalgo, Marco Antônio; de Almeida, Marcelus Brito; dos Santos, José Antônio; Lopes de Souza, Sandra; Manhães-de-Castro, Raul; Leandro, Carol Góis

    2012-02-01

    We evaluated the effects of moderate- to low-intensity physical training during gestation on reflex ontogeny in neonate rats whose mothers were undernourished. Virgin female Wistar rats were divided into four groups as follows: untrained (NT, n 7); trained (T, n 7); untrained with a low-protein diet (NT+LP, n 7); trained with a low-protein diet (T+LP, n 4). Trained rats were subjected to a protocol of moderate physical training on a treadmill over a period of 4 weeks (5 d/week and 60 min/d, at 65 % of VO₂max). After confirming the pregnancy, the intensity and duration of the exercise were reduced. Low-protein groups were provided with an 8 % casein diet, and controls were provided with a 17 % casein diet. Their respective offspring were evaluated (during the 10th-17th days of postnatal life) in terms of physical feature maturation, somatic growth and reflex ontogeny. Pups born to mothers provided with the low-protein diet during gestation and lactation showed delayed physical feature and reflex maturation and a deficit in somatic growth when compared with controls. However, most of these deficiencies were attenuated in pups of undernourished mothers undergoing training. In conclusion, physical training during gestation attenuates the effects of perinatal undernutrition on some patterns of maturation in the central nervous system during development.

  17. Developmental Delays in Executive Function from 3 to 5 Years of Age Predict Kindergarten Academic Readiness

    PubMed Central

    Willoughby, Michael T.; Magnus, Brooke; Vernon-Feagans, Lynne; Blair, Clancy B.

    2017-01-01

    Substantial evidence has established that individual differences in executive function (EF) in early childhood are uniquely predictive of children’s academic readiness at school entry. The current study tested whether growth trajectories of EF across the early childhood period could be used to identify a subset of children who were at pronounced risk for academic impairment in kindergarten. Using data that were collected at the age 3, 4, and 5 home assessments in the Family Life Project (N = 1,120), growth mixture models were used to identify 9% of children who exhibited impaired EF performance (i.e., persistently low levels of EF that did not show expected improvements across time). Compared to children who exhibited typical trajectories of EF, the delayed group exhibited substantial impairments in multiple indicators of academic readiness in kindergarten (Cohen’s ds = 0.9–2.7; odds ratios = 9.8–23.8). Although reduced in magnitude following control for a range of socioeconomic and cognitive (general intelligence screener, receptive vocabulary) covariates, moderate-sized group differences remained (Cohen’s ds = 0.2–2.4; odds ratios = 3.9–5.4). Results are discussed with respect to the use of repeated measures of EF as a method of early identification, as well as the resulting translational implications of doing so. PMID:26755570

  18. A novel whole exon deletion in WWOX gene causes early epilepsy, intellectual disability and optic atrophy.

    PubMed

    Ben-Salem, Salma; Al-Shamsi, Aisha M; John, Anne; Ali, Bassam R; Al-Gazali, Lihadh

    2015-05-01

    Recent studies have implicated the WW domain-containing oxidoreductase encoding gene (WWOX) in a severe form of autosomal recessive neurological disorder. This condition showed an overlapping spectrum of clinical features including spinocerebellar ataxia associated with generalized seizures and delayed psychomotor development to growth retardation, spasticity, and microcephaly. We evaluated a child from a consanguineous Emirati family that presented at birth with growth retardation, microcephaly, epileptic seizures, and later developed spasticity and delayed psychomotor development. Screening for deletions and duplications using whole-chromosomal microarray analysis identified a novel homozygous microdeletion encompassing exon 5 of the WWOX gene. Analysis of parental DNA indicated that this deletion was inherited from both parents and lies within a large region of homozygosity. Sanger sequencing of the cDNA showed that the deletion resulted in exon 5 skipping leading to a frame-shift and creating a premature stop codon at amino acid position 212. Quantification of mRNA revealed striking low level of WWOX expression in the child and moderate level of expression in the mother compared to a healthy control. To the best of our knowledge, this is the first homozygous germline structural variation in WWOX gene resulting in truncated transcripts that were presumably subject to NMD pathway. Our findings extend the clinical and genetic spectrum of WWOX mutations and support a crucial role of this gene in neurological development.

  19. Growth curve for Propionibacterium acnes.

    PubMed

    Hall, G S; Pratt-Rippin, K; Meisler, D M; Washington, J A; Roussel, T J; Miller, D

    1994-06-01

    We established growth curves for Propionibacterium acnes isolates recovered from eyes with chronic postoperative endophthalmitis. The growth curve plotted the average of the duplicate bacterial concentration against time. The generation time for P. acnes calculated from the growth curves was approximately 5.1 hours. The growth of P. acnes is slower than other anaerobic bacteria. This may account for its delayed appearance in culture of ocular specimens. It may also explain treatment failure if the concentration of an antibiotic injected into the vitreous does not remain at an effective level during the critical replicative phase of the organism.

  20. Tumour volume response, initial cell kill and cellular repopulation in B16 melanoma treated with cyclophosphamide and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

    PubMed Central

    Stephens, T. C.; Peacock, J. H.

    1977-01-01

    The relationship between tumour volume response and cell kill in B16 melanoma following treatment in vivo with cyclophosphamide (CY) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was investigated. Tumour volume response, expressed as growth delay, was estimated from measurements of tumour dimensions. Depression of in vitro colony-forming ability of cells from treated tumours was used as the measure of tumour cell kill. The relationship between these parameters was clearly different for the two agents studied. CY produced more growth delay (7.5 days) per decade of tumour cell kill than CCNU (2 to 3.5 days). The possibility that this was due to a technical artefact was rejected in favour of an alternative explanation that different rates of cellular repopulation in tumours treated with CY and CCNU might be responsible. Cellular repopulation was measured directly, by performing cell-survival assays at various times after treatment with doses of CY and CCNU which produced about 3 decades of cell kill. The rate of repopulation by clonogenic cells was much slower after treatment with CY than with CCNU, and this appears to account for the longer duration of the growth delay obtained with CY. PMID:921888

  1. Is early cord clamping, delayed cord clamping or cord milking best?

    PubMed

    Vatansever, Binay; Demirel, Gamze; Ciler Eren, Elif; Erel, Ozcan; Neselioglu, Salim; Karavar, Hande Nur; Gundogdu, Semra; Ulfer, Gozde; Bahadir, Selcen; Tastekin, Ayhan

    2018-04-01

    To compare the antioxidant status of three cord clamping procedures (early clamping, delayed clamping and milking) by analyzing the thiol-disulfide balance. This randomized controlled study enrolled 189 term infants who were divided into three groups according to the cord clamping procedure: early clamping, delayed clamping and milking. Blood samples were collected from the umbilical arteries immediately after clamping, and the thiol/disulfide homeostasis was analyzed. The native and total thiol levels were significantly (p < .05) lower in the early cord clamping group compared with the other two groups. The disulfide/total thiol ratio was significantly (p = .026) lower in the delayed cord clamping and milking groups compared with the early clamping groups. Early cord clamping causes the production of more disulfide bonds and lower thiol levels, indicating that oxidation reactions are increased in the early cord clamping procedure compared with the delayed cord clamping and milking procedures. The oxidant capacity is greater with early cord clamping than with delayed clamping or cord milking. Delayed cord clamping or milking are beneficial in neonatal care, and we suggest that they be performed routinely in all deliveries.

  2. Speech and language delay in two children: an unusual presentation of hyperthyroidism.

    PubMed

    Sohal, Aman P S; Dasarathi, Madhuri; Lodh, Rajib; Cheetham, Tim; Devlin, Anita M

    2013-01-01

    Hyperthyroidism is rare in pre-school children. Untreated, it can have a profound effect on normal growth and development, particularly in the first 2 years of life. Although neurological manifestations of dysthyroid states are well known, specific expressive speech and language disorder as a presentation of hyperthyroidism is rarely documented. Case reports of two children with hyperthyroidism presenting with speech and language delay. We report two pre-school children with hyperthyroidism, who presented with expressive speech and language delay, and demonstrated a significant improvement in their language skills following treatment with anti-thyroid medication. Hyperthyroidism must be considered in all children presenting with speech and language difficulties, particularly expressive speech delay. Prompt recognition and early treatment are likely to improve outcome.

  3. Symbolic Play and Novel Noun Learning in Deaf and Hearing Children: Longitudinal Effects of Access to Sound on Early Precursors of Language.

    PubMed

    Quittner, Alexandra L; Cejas, Ivette; Wang, Nae-Yuh; Niparko, John K; Barker, David H

    2016-01-01

    In the largest, longitudinal study of young, deaf children before and three years after cochlear implantation, we compared symbolic play and novel noun learning to age-matched hearing peers. Participants were 180 children from six cochlear implant centers and 96 hearing children. Symbolic play was measured during five minutes of videotaped, structured solitary play. Play was coded as "symbolic" if the child used substitution (e.g., a wooden block as a bed). Novel noun learning was measured in 10 trials using a novel object and a distractor. Cochlear implant vs. normal hearing children were delayed in their use of symbolic play, however, those implanted before vs. after age two performed significantly better. Children with cochlear implants were also delayed in novel noun learning (median delay 1.54 years), with minimal evidence of catch-up growth. Quality of parent-child interactions was positively related to performance on the novel noun learning, but not symbolic play task. Early implantation was beneficial for both achievement of symbolic play and novel noun learning. Further, maternal sensitivity and linguistic stimulation by parents positively affected noun learning skills, although children with cochlear implants still lagged in comparison to hearing peers.

  4. Symbolic Play and Novel Noun Learning in Deaf and Hearing Children: Longitudinal Effects of Access to Sound on Early Precursors of Language

    PubMed Central

    Quittner, Alexandra L.; Cejas, Ivette; Wang, Nae-Yuh; Niparko, John K.; Barker, David H.

    2016-01-01

    In the largest, longitudinal study of young, deaf children before and three years after cochlear implantation, we compared symbolic play and novel noun learning to age-matched hearing peers. Participants were 180 children from six cochlear implant centers and 96 hearing children. Symbolic play was measured during five minutes of videotaped, structured solitary play. Play was coded as "symbolic" if the child used substitution (e.g., a wooden block as a bed). Novel noun learning was measured in 10 trials using a novel object and a distractor. Cochlear implant vs. normal hearing children were delayed in their use of symbolic play, however, those implanted before vs. after age two performed significantly better. Children with cochlear implants were also delayed in novel noun learning (median delay 1.54 years), with minimal evidence of catch-up growth. Quality of parent-child interactions was positively related to performance on the novel noun learning, but not symbolic play task. Early implantation was beneficial for both achievement of symbolic play and novel noun learning. Further, maternal sensitivity and linguistic stimulation by parents positively affected noun learning skills, although children with cochlear implants still lagged in comparison to hearing peers. PMID:27228032

  5. Antifungal Activity of Phenyllactic Acid against Molds Isolated from Bakery Products

    PubMed Central

    Lavermicocca, Paola; Valerio, Francesca; Visconti, Angelo

    2003-01-01

    Phenyllactic acid (PLA) has recently been found in cultures of Lactobacillus plantarum that show antifungal activity in sourdough breads. The fungicidal activity of PLA and growth inhibition by PLA were evaluated by using a microdilution test and 23 fungal strains belonging to 14 species of Aspergillus, Penicillium, and Fusarium that were isolated from bakery products, flours, or cereals. Less than 7.5 mg of PLA ml−1 was required to obtain 90% growth inhibition for all strains, while fungicidal activity against 19 strains was shown by PLA at levels of ≤10 mg ml−1. Levels of growth inhibition of 50 to 92.4% were observed for all fungal strains after incubation for 3 days in the presence of 7.5 mg of PLA ml−1 in buffered medium at pH 4, which is a condition more similar to those in real food systems. Under these experimental conditions PLA caused an unpredictable delaying effect that was more than 2 days long for 12 strains, including some mycotoxigenic strains of Penicillium verrucosum and Penicillium citrinum and a strain of Penicillium roqueforti (the most widespread contaminant of bakery products); a growth delay of about 2 days was observed for seven other strains. The effect of pH on the inhibitory activity of PLA and the combined effects of the major organic acids produced by lactic acid bacteria isolated from sourdough bread (PLA, lactic acid, and acetic acid) were also investigated. The ability of PLA to act as a fungicide and delay the growth of a variety of fungal contaminants provides new perspectives for possibly using this natural antimicrobial compound to control fungal contaminants and extend the shelf lives of foods and/or feedstuffs. PMID:12514051

  6. Brain injury and altered brain growth in preterm infants: predictors and prognosis.

    PubMed

    Kidokoro, Hiroyuki; Anderson, Peter J; Doyle, Lex W; Woodward, Lianne J; Neil, Jeffrey J; Inder, Terrie E

    2014-08-01

    To define the nature and frequency of brain injury and brain growth impairment in very preterm (VPT) infants by using MRI at term-equivalent age and to relate these findings to perinatal risk factors and 2-year neurodevelopmental outcomes. MRI scans at term-equivalent age from 3 VPT cohorts (n = 325) were reviewed. The severity of brain injury, including periventricular leukomalacia and intraventricular and cerebellar hemorrhage, was graded. Brain growth was assessed by using measures of biparietal width (BPW) and interhemispheric distance. Neurodevelopmental outcome at age 2 years was assessed across all cohorts (n = 297) by using the Bayley Scales of Infant Development, Second Edition (BSID-II) or Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and evaluation for cerebral palsy. Of 325 infants, 107 (33%) had some grade of brain injury and 33 (10%) had severe injury. Severe brain injury was more common in infants with lower Apgar scores, necrotizing enterocolitis, inotropic support, and patent ductus arteriosus. Severe brain injury was associated with delayed cognitive and motor development and cerebral palsy. Decreased BPW was related to lower gestational age, inotropic support, patent ductus arteriosus, necrotizing enterocolitis, prolonged parenteral nutrition, and oxygen at 36 weeks and was associated with delayed cognitive development. In contrast, increased interhemispheric distance was related to male gender, dexamethasone use, and severe brain injury. It was also associated with reduced cognitive development, independent of BPW. At term-equivalent age, VPT infants showed both brain injury and impaired brain growth on MRI. Severe brain injury and impaired brain growth patterns were independently associated with perinatal risk factors and delayed cognitive development. Copyright © 2014 by the American Academy of Pediatrics.

  7. Power-law Growth and Punctuated Equilibrium Dynamics in Water Resources Systems

    NASA Astrophysics Data System (ADS)

    Parolari, A.; Katul, G. G.; Porporato, A. M.

    2015-12-01

    The global rise in population-driven water scarcity and recent appreciation of strong dynamic coupling between human and natural systems has called for new approaches to predict the future sustainability of regional and global water resources systems. The dynamics of coupled human-water systems are driven by a complex set of social, environmental, and technological factors. Present projections of water resources systems range from a finite carrying capacity regulated by accessible freshwater, or `peak renewable water,' to punctuated evolution with new supplied and improved efficiency gained from technological and social innovation. However, these projections have yet to be quantified from observations or in a comprehensive theoretical framework. Using data on global water withdrawals and storage capacity of regional water supply systems, non-trivial dynamics are identified in water resources systems development over time, including power-law growth and punctuated equilibria. Two models are introduced to explain this behavior: (1) a delay differential equation and (2) a power-law with log-periodic oscillations, both of which rely on past conditions (or system memory) to describe the present rate of growth in the system. In addition, extension of the first model demonstrates how system delays and punctuated equilibria can emerge from coupling between human population growth and associated resource demands. Lastly, anecdotal evidence is used to demonstrate the likelihood of power-law growth in global water use from the agricultural revolution 3000 BC to the present. In a practical sense, the presence of these patterns in models with delayed oscillations suggests that current decision-making related to water resources development results from the historical accumulation of resource use decisions, technological and social changes, and their consequences.

  8. Total and Conceptual Vocabulary in Spanish–English Bilinguals From 22 to 30 Months: Implications for Assessment

    PubMed Central

    Core, Cynthia; Hoff, Erika; Rumiche, Rosario; Señor, Melissa

    2015-01-01

    Purpose Vocabulary assessment holds promise as a way to identify young bilingual children at risk for language delay. This study compares 2 measures of vocabulary in a group of young Spanish–English bilingual children to a single-language measure used with monolingual children. Method Total vocabulary and conceptual vocabulary were used to measure mean vocabulary size and growth in 47 Spanish–English bilingually developing children from 22 to 30 months of age based on results from the MacArthur–Bates Communicative Development Inventory (CDI; Fenson et al., 1993) and the Inventario del Desarrollo de Habilidades Comunicativas (Jackson-Maldonado et al., 2003). Bilingual children’s scores of total vocabulary and conceptual vocabulary were compared with CDI scores for a control group of 56 monolingual children. Results The total vocabulary measure resulted in mean vocabulary scores and average rate of growth similar to monolingual growth, whereas conceptual vocabulary scores were significantly smaller and grew at a slower rate than total vocabulary scores. Total vocabulary identified the same proportion of bilingual children below the 25th percentile on monolingual norms as the CDI did for monolingual children. Conclusion These results support the use of total vocabulary as a means of assessing early language development in young bilingual Spanish–English speaking children. PMID:24023382

  9. Total and conceptual vocabulary in Spanish-English bilinguals from 22 to 30 months: implications for assessment.

    PubMed

    Core, Cynthia; Hoff, Erika; Rumiche, Rosario; Señor, Melissa

    2013-10-01

    Vocabulary assessment holds promise as a way to identify young bilingual children at risk for language delay. This study compares 2 measures of vocabulary in a group of young Spanish-English bilingual children to a single-language measure used with monolingual children. Total vocabulary and conceptual vocabulary were used to measure mean vocabulary size and growth in 47 Spanish-English bilingually developing children from 22 to 30 months of age based on results from the MacArthur-Bates Communicative Development Inventory (CDI; Fenson et al., 1993) and the Inventario del Desarrollo de Habilidades Comunicativas ( Jackson-Maldonado et al., 2003). Bilingual children's scores of total vocabulary and conceptual vocabulary were compared with CDI scores for a control group of 56 monolingual children. The total vocabulary measure resulted in mean vocabulary scores and average rate of growth similar to monolingual growth, whereas conceptual vocabulary scores were significantly smaller and grew at a slower rate than total vocabulary scores. Total vocabulary identified the same proportion of bilingual children below the 25th percentile on monolingual norms as the CDI did for monolingual children. These results support the use of total vocabulary as a means of assessing early language development in young bilingual Spanish-English speaking children.

  10. Delayed puberty caused by hyperthyroidism in ram lambs is not a result of suppression in body growth.

    PubMed

    Chandrasekhar, Y; D'Occhio, M J; Setchell, B P

    1986-03-01

    Over a period of 8 weeks ram lambs (16 weeks old) were made hyperthyroidal (serum thyroxine approximately equal to 150 ng/ml, compared with control approximately equal to 48 ng/ml) by daily subcutaneous injections of thyroxine or maintained at a constant body weight by restriction of the feed intake. Hyperthyroidal and restricted-intake lambs remained at a constant body weight during the period of treatment whilst control rams gained body weight. Testicular growth was normal in restricted-intake lambs but was suppressed in hyperthyroidal animals. Hyperthyroidism, but not feed restriction, was also associated with decrease in LH pulse frequency (1.3 +/- 0.3/12 h compared with controls 4.8 +/- 0.9/12 h. Hyperthyroidal lambs showed normal LH responses to exogenous LHRH. After cessation of treatment testicular growth continued to be suppressed for up to 16 weeks in previously hyperthyroidic rams; thereafter testes began to increase in size but at 30 weeks after treatment were still smaller than those of control rams. It is concluded that elevated thyroxine concentrations directly influence sexual maturation in ram lambs through actions at hypothalamic and/or higher brain centres which control LH secretion. Transient hyperthyroidism during sexual maturation may cause permanent impairment of sexual development.

  11. Application of the Prunus spp. Cyanide Seed Defense System onto Wheat: Reduced Insect Feeding and Field Growth Tests.

    PubMed

    Mora, Carlos A; Halter, Jonas G; Adler, Cornel; Hund, Andreas; Anders, Heidrun; Yu, Kang; Stark, Wendelin J

    2016-05-11

    Many crops are ill-protected against insect pests during storage. To protect cereal grains from herbivores during storage, pesticides are often applied. While pesticides have an undoubtable functionality, increasing concerns are arising about their application. In the present study, we investigated a bioinspired cyanogenic grain coating with amygdalin as cyanogenic precursor mimicking the feeding-triggered release of hydrogen cyanide (HCN) found for example in bitter almonds. The multilayer coating consisted of biodegradable polylactic acid with individual layers containing amygdalin or β-glucosidase which is capable of degrading amygdalin to HCN. This reaction occurred only when the layers were ruptured, e.g., by a herbivore attack. Upon feeding coated cyanogenic wheat grains to Tenebrio molitor (mealworm beetle), Rhizopertha dominica (lesser grain borer), and Plodia interpunctella (Indianmeal moth), their reproduction as well as consumption rate were significantly reduced, whereas germination ability increased compared to noncoated grains. In field experiments, we observed an initial growth delay compared to uncoated grains which became negligible at later growth stages. The here shown strategy to artificially apply a naturally occurring defense mechanisms could be expanded to other crops than wheat and has the potential to replace certain pesticides with the benefit of complete biodegradability and increased safety during storage.

  12. INTERACTIONS BETWEEN SOIL TEMPERATURE AND PLANT GROWTH STAGE ON NITROGEN UPTAKE AND AMINO ACID CONTENT OF APPLE NURSERY STOCK DURING EARLY SPRING GROWTH

    EPA Science Inventory

    In the spring, nitrogen (N) uptake by apple roots is known to be delayed about three weeks after bud break. We used one-year-old 'Fuji' (Malus domestica Borkh) on M26 bare-root apple trees to determine whether timing of N uptake in the spring is dependant solely on the growth st...

  13. Assessment of the Changes in 9L and C6 Glioma pO2 by EPR Oximetry as a Prognostic Indicator of Differential Response to Radiotherapy

    PubMed Central

    Hou, Huagang; Mupparaju, Sriram P.; Lariviere, Jean P.; Hodge, Sassan; Gui, Jiang; Swartz, Harold M.; Khan, Nadeem

    2013-01-01

    Tumor hypoxia impedes the outcome of radiotherapy. As the extent of hypoxia in solid tumors varies during the course of radiotherapy, methods that can provide repeated assessment of tumor pO2 such as EPR oximetry may enhance the efficacy of radiotherapy by scheduling irradiations when the tumors are oxygenated. The repeated measurements of tumor pO2 may also identify responders, and thereby facilitate the design of better treatment plans for nonresponding tumors. We have investigated the temporal changes in the ectopic 9L and C6 glioma pO2 irradiated with single radiation doses less than 10 Gy by EPR oximetry. The 9L and C6 tumors were hypoxic with pO2 of approximately 5–9 mmHg. The pO2 of C6 tumors increased significantly with irradiation of 4.8–9.3 Gy. However, no change in the 9L tumor pO2 was observed. The irradiation of the oxygenated C6 tumors with a second dose of 4.8 Gy resulted in a significant delay in growth compared to hypoxic and 2 Gy × 5 treatment groups. The C6 tumors with an increase in pO2 of greater than 50% from the baseline of irradiation with 4.8 Gy (responders) had a significant tumor growth delay compared to nonresponders. These results indicate that the ectopic 9L and C6 tumors responded differently to radiotherapy. We propose that the repeated measurement of the oxygen levels in the tumors during radiotherapy can be used to identify responders and to design tumor oxygen guided treatment plans to improve the outcome. PMID:23391148

  14. Phenology Shifts at Start vs. End of Growing Season in Temperate Vegetation Over the Northern Hemisphere for the Period 1982-2008

    NASA Technical Reports Server (NTRS)

    Jeong, Su-Jong; Ho, Chang-Hoi; Gim, Hyeon-Ju; Brown, Molley E.

    2011-01-01

    Changes in vegetative growing seasons are dominant indicators of the dynamic response of ecosystems to climate change. Therefore, knowledge of growing seasons over the past decades is essential to predict ecosystem changes. In this study, the long-term changes in the growing seasons of temperate vegetation over the Northern Hemisphere were examined by analyzing satellite-measured normalized difference vegetation index and reanalysis temperature during 1982 2008. Results showed that the length of the growing season (LOS) increased over the analysis period; however, the role of changes at the start of the growing season (SOS) and at the end of the growing season (EOS) differed depending on the time period. On a hemispheric scale, SOS advanced by 5.2 days in the early period (1982-1999) but advanced by only 0.2 days in the later period (2000-2008). EOS was delayed by 4.3 days in the early period, and it was further delayed by another 2.3 days in the later period. The difference between SOS and EOS in the later period was due to less warming during the preseason (January-April) before SOS compared with the magnitude of warming in the preseason (June September) before EOS. At a regional scale, delayed EOS in later periods was shown. In North America, EOS was delayed by 8.1 days in the early period and delayed by another 1.3 days in the later period. In Europe, the delayed EOS by 8.2 days was more significant than the advanced SOS by 3.2 days in the later period. However, in East Asia, the overall increase in LOS during the early period was weakened in the later period. Admitting regional heterogeneity, changes in hemispheric features suggest that the longer-lasting vegetation growth in recent decades can be attributed to extended leaf senescence in autumn rather than earlier spring leaf-out. Keywords: climate change, growing season, NDVI (normalized difference vegetation index), Northern Hemisphere, phenology,

  15. The effect of an overload on the rate of fatigue crack propagation under plane stress conditions

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

    Bao, H.; McEvily, A.J.

    1995-07-01

    It has been shown that the retardation in the rate of fatigue crack growth following an overload is largely the result of surface-related, plane-stress deformation. In the present article, in order to isolate the plane-stress behavior, the effect of an overload on the subsequent rate of fatigue crack growth of 0.3-mm-thick specimens of 9Cr-1Mo steel has been investigated and compared to results obtained using 6.35-mm-thick specimens. It was found that for the 0.3-mm thickness, as with thicker specimens, two opening load levels were associated with the overload process. The upper opening load is associated with plane-stress deformation in the overloadmore » plastic zone, and this opening process is more clearly observed with thin as compared to thicker specimens. Based upon the determined level of the upper opening load, a semiempirical analysis is developed for calculating the number of delay cycles due to an overload as a function of thickness.« less

  16. A Biogeotechnical engineering approach to Combat Desertification

    NASA Astrophysics Data System (ADS)

    Chang, I.; Im, J.; Cho, G. C.; Lee, S. J.

    2016-12-01

    The acceleration of global warming is not only inducing rising sea levels and abnormal climate problems, but also geotechnical hazards such as desertification. Recently, 30% of Earth's dry land has been affected by desertification, and approximately 850 million people are suffering due to famine, poverty, and hygiene problems induced by desertification. Global warming and unsustainable land development are known to be major triggers promoting desertification. Numerous global agencies and companies are thus contributing to anti-desertification movements. However, tree planting alone is not an ideal solution given that it takes approximately 2 3 years for stabilization. It is thus imperative to develop innovative technology that can promote vegetation growth and improve soil erosion resistance. In this study, a unique soil treatment and anti-desertification method is developed using microbial biopolymers. Biopolymers can effectively strengthen soil and improve durability. In particular, anionic-hydrophilic biopolymers delay water evaporation, thereby retaining a higher soil moisture condition compared to non-treated soil. Results of this study show that microbial biopolymer treatment is highly effective in improving both vegetation growth (3 times faster) and soil erosion resistance (less than 2%), compared to untreated earth surfaces.

  17. The Diagnostic Yield of Array Comparative Genomic Hybridization Is High Regardless of Severity of Intellectual Disability/Developmental Delay in Children.

    PubMed

    D'Arrigo, Stefano; Gavazzi, Francesco; Alfei, Enrico; Zuffardi, Orsetta; Montomoli, Cristina; Corso, Barbara; Buzzi, Erika; Sciacca, Francesca L; Bulgheroni, Sara; Riva, Daria; Pantaleoni, Chiara

    2016-05-01

    Microarray-based comparative genomic hybridization is a method of molecular analysis that identifies chromosomal anomalies (or copy number variants) that correlate with clinical phenotypes. The aim of the present study was to apply a clinical score previously designated by de Vries to 329 patients with intellectual disability/developmental disorder (intellectual disability/developmental delay) referred to our tertiary center and to see whether the clinical factors are associated with a positive outcome of aCGH analyses. Another goal was to test the association between a positive microarray-based comparative genomic hybridization result and the severity of intellectual disability/developmental delay. Microarray-based comparative genomic hybridization identified structural chromosomal alterations responsible for the intellectual disability/developmental delay phenotype in 16% of our sample. Our study showed that causative copy number variants are frequently found even in cases of mild intellectual disability (30.77%). We want to emphasize the need to conduct microarray-based comparative genomic hybridization on all individuals with intellectual disability/developmental delay, regardless of the severity, because the degree of intellectual disability/developmental delay does not predict the diagnostic yield of microarray-based comparative genomic hybridization. © The Author(s) 2015.

  18. Use of Fenbendazole-Containing Therapeutic Diets for Mice in Experimental Cancer Therapy Studies

    PubMed Central

    Duan, Qiwen; Liu, Yanfeng; Booth, Carmen J; Rockwell, Sara

    2012-01-01

    Pinworm infection (oxyuriasis) is a common problem in rodent colonies. Facility-wide prophylactic treatment of all mice with a diet containing therapeutic levels of fenbendazole for several weeks is often used to control pinworm outbreaks. We examined the effect of feeding a therapeutic diet containing 150 ppm fenbendazole on the growth of EMT6 mouse mammary tumors implanted into BALB/c Rw mice. Mice were randomized to receive either a fenbendazole-containing or control diet for 1 wk before tumor cells were injected intradermally in the flanks and throughout tumor growth. Tumor growth was monitored by serial measurements of tumor diameters from the time tumors became palpable until they reached 1000 mm3. The medicated diet did not alter tumor growth, invasion, or metastasis. When tumors reached volumes of approximately 100 mm3, some were irradiated locally with 10 Gy of X-rays. Irradiation significantly delayed tumor growth; fenbendazole did not alter the radiation-induced growth delay. However, cell culture studies showed that fenbendazole concentrations not far above those expected in the tissues of mice on this diet altered the growth of the tumor cells in culture. Recent data from other laboratories also have demonstrated effects of fenbendazole that could complicate experiments. Care should therefore be exercised in deciding whether chow containing fenbendazole should be administered to mouse colonies being used in cancer research. PMID:22776123

  19. Use of fenbendazole-containing therapeutic diets for mice in experimental cancer therapy studies.

    PubMed

    Duan, Qiwen; Liu, Yanfeng; Booth, Carmen J; Rockwell, Sara

    2012-03-01

    Pinworm infection (oxyuriasis) is a common problem in rodent colonies. Facility-wide prophylactic treatment of all mice with a diet containing therapeutic levels of fenbendazole for several weeks is often used to control pinworm outbreaks. We examined the effect of feeding a therapeutic diet containing 150 ppm fenbendazole on the growth of EMT6 mouse mammary tumors implanted into BALB/c Rw mice. Mice were randomized to receive either a fenbendazole-containing or control diet for 1 wk before tumor cells were injected intradermally in the flanks and throughout tumor growth. Tumor growth was monitored by serial measurements of tumor diameters from the time tumors became palpable until they reached 1000 mm3. The medicated diet did not alter tumor growth, invasion, or metastasis. When tumors reached volumes of approximately 100 mm3, some were irradiated locally with 10 Gy of X-rays. Irradiation significantly delayed tumor growth; fenbendazole did not alter the radiation-induced growth delay. However, cell culture studies showed that fenbendazole concentrations not far above those expected in the tissues of mice on this diet altered the growth of the tumor cells in culture. Recent data from other laboratories also have demonstrated effects of fenbendazole that could complicate experiments. Care should therefore be exercised in deciding whether chow containing fenbendazole should be administered to mouse colonies being used in cancer research.

  20. Action Mechanism of Chamaecyparis obtusa Oil on Hair Growth

    PubMed Central

    Park, Young-Ok; Kim, Su-Eun; Kim, Young-Chul

    2013-01-01

    This study was carried out to examine the action mechanism of Chamaecyparis obtusa oil (CO) on hair growth in C57BL/6 mice. For alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (γ-GT) activities in the skin tissue, at week 4, the 3% minoxidil (MXD) and 3% CO treatment groups showed an ALP activity that was significantly higher by 85% (p < 0.001) and 48% (p < 0.05) and an γ-GT activity that was significantly higher by 294% (p < 0.01) and 254% (p < 0.05) respectively, as compared to the saline (SA) treatment group. For insulin-like growth factor-1 (IGF-1) mRNA expression in the skin tissue, at week 4, the MXD and CO groups showed a significantly higher expression by 204% (p < 0.05) and 426% (p < 0.01) respectively, as compared to the SA group. At week 4, vascular endothelial growth factor (VEGF) expression in the MXD and CO groups showed a significantly higher expression by 74% and 96% (p < 0.05) respectively, however, epidermal growth factor (EGF) expression in the MXD and CO groups showed a significantly lower expression by 66% and 61% (p < 0.05) respectively, as compared to the SA group. Stem cell factor (SCF) expression in the MXD and CO groups was observed by immunohistochemistry as significant in a part of the bulge around the hair follicle and in a part of the basal layer of the epidermis. Taking all the results together, on the basis of effects on ALP and γ-GT activity, and the expression of IGF-1, VEGF and SCF, which are related to the promotion of hair growth, it can be concluded that CO induced a proliferation and division of hair follicle cells and maintained the anagen phase. Because EGF expression was decreased significantly, CO could delay the transition to the catagen phase. PMID:24578794

  1. Consequences of Feeder Delays for the Success of A380 Operations

    NASA Technical Reports Server (NTRS)

    Ruehle, Jens; Goetsch, Bjoern; Koch, Benjamin

    2006-01-01

    Due to existing slot and infrastructure constraints at international hub-and-spoke airports, an increase in feeder traffic seems only possible if larger feeder aircraft are used. Using a case study of Lufthansa German Airlines at Frankfurt International Airport, three possible A380 routes (Beijing, Tokyo-Narita, Los Angeles) were examined to assess the extent to which delays of feeder traffic may impact the economic performance of very large aircraft. On the basis of today s delays and anticipated traffic growth in the future, we found that between 9.5% and 13.5% of connecting passengers are unable to transfer to their respective intercontinental flights. In addition, the results demonstrate that a further increase in delays can be detrimental to the profitable operation of very large aircraft, as demonstrated by two out of three simulated routes. We suggest options for airlines operating very large aircraft to counteract the negative impacts of feeder delays.

  2. Steady states and outbreaks of two-phase nonlinear age-structured model of population dynamics with discrete time delay.

    PubMed

    Akimenko, Vitalii; Anguelov, Roumen

    2017-12-01

    In this paper we study the nonlinear age-structured model of a polycyclic two-phase population dynamics including delayed effect of population density growth on the mortality. Both phases are modelled as a system of initial boundary values problem for semi-linear transport equation with delay and initial problem for nonlinear delay ODE. The obtained system is studied both theoretically and numerically. Three different regimes of population dynamics for asymptotically stable states of autonomous systems are obtained in numerical experiments for the different initial values of population density. The quasi-periodical travelling wave solutions are studied numerically for the autonomous system with the different values of time delays and for the system with oscillating death rate and birth modulus. In both cases it is observed three types of travelling wave solutions: harmonic oscillations, pulse sequence and single pulse.

  3. Chilling and chipping influence plant growth and reproduction of star-of-Bethlehem (Ornithogalum umbellatum)

    USDA-ARS?s Scientific Manuscript database

    Greenhouse studies were conducted on two southern Illinois star-of-Bethlehem biotypes to determine the influence of chilling and bulb chipping on plant growth and reproduction. Chilling was not required for leaf emergence of dormant bulbs, but an increase to 10 weeks of chilling proportionally delay...

  4. Lactoferrin and lysozyme to reduce environmental enteric dysfunction and stunting in Malawian children: Study protocol for a randomized controlled trial

    USDA-ARS?s Scientific Manuscript database

    Chronic childhood malnutrition, as manifested by stunted linear growth, remains a persistent barrier to optimal child growth and societal development. Environmental enteric dysfunction (EED) is a significant underlying factor in the causal pathway to stunting, delayed cognitive development, and ulti...

  5. Typology of nonlinear activity waves in a layered neural continuum.

    PubMed

    Koch, Paul; Leisman, Gerry

    2006-04-01

    Neural tissue, a medium containing electro-chemical energy, can amplify small increments in cellular activity. The growing disturbance, measured as the fraction of active cells, manifests as propagating waves. In a layered geometry with a time delay in synaptic signals between the layers, the delay is instrumental in determining the amplified wavelengths. The growth of the waves is limited by the finite number of neural cells in a given region of the continuum. As wave growth saturates, the resulting activity patterns in space and time show a variety of forms, ranging from regular monochromatic waves to highly irregular mixtures of different spatial frequencies. The type of wave configuration is determined by a number of parameters, including alertness and synaptic conditioning as well as delay. For all cases studied, using numerical solution of the nonlinear Wilson-Cowan (1973) equations, there is an interval in delay in which the wave mixing occurs. As delay increases through this interval, during a series of consecutive waves propagating through a continuum region, the activity within that region changes from a single-frequency to a multiple-frequency pattern and back again. The diverse spatio-temporal patterns give a more concrete form to several metaphors advanced over the years to attempt an explanation of cognitive phenomena: Activity waves embody the "holographic memory" (Pribram, 1991); wave mixing provides a plausible cause of the competition called "neural Darwinism" (Edelman, 1988); finally the consecutive generation of growing neural waves can explain the discontinuousness of "psychological time" (Stroud, 1955).

  6. Delayed bet-hedging resilience strategies under environmental fluctuations

    NASA Astrophysics Data System (ADS)

    Ogura, Masaki; Wakaiki, Masashi; Rubin, Harvey; Preciado, Victor M.

    2017-05-01

    Many biological populations, such as bacterial colonies, have developed through evolution a protection mechanism, called bet hedging, to increase their probability of survival under stressful environmental fluctuation. In this context, the concept of preadaptation refers to a common type of bet-hedging protection strategy in which a relatively small number of individuals in a population stochastically switch their phenotypes to a dormant metabolic state in which they increase their probability of survival against potential environmental shocks. Hence, if an environmental shock took place at some point in time, preadapted organisms would be better adapted to survive and proliferate once the shock is over. In many biological populations, the mechanisms of preadaptation and proliferation present delays whose influence in the fitness of the population are not well understood. In this paper, we propose a rigorous mathematical framework to analyze the role of delays in both preadaptation and proliferation mechanisms in the survival of biological populations, with an emphasis on bacterial colonies. Our theoretical framework allows us to analytically quantify the average growth rate of a bet-hedging bacterial colony with stochastically delayed reactions with arbitrary precision. We verify the accuracy of the proposed method by numerical simulations and conclude that the growth rate of a bet-hedging population shows a nontrivial dependency on their preadaptation and proliferation delays. Contrary to the current belief, our results show that faster reactions do not, in general, increase the overall fitness of a biological population.

  7. A de novo KMT2D mutation in a girl with Kabuki syndrome associated with endocrine symptoms: a case report.

    PubMed

    Moon, Jung-Eun; Lee, Su-Jeong; Ko, Cheol Woo

    2018-06-18

    Kabuki syndrome is characterized by distinctive facial features and varying degrees of growth retardation. It leads to malformations in skeletal, urogenital and cardiac structures; moreover, endocrine conditions such as premature thelarche, precocious puberty, growth hormone deficiency, diabetes insipidus, thyroid dysfunction and obesity have been reported. Kabuki syndrome is caused by a heterozygous mutation in the KMT2D or KDM6A genes. An 11-year-old girl with the typical facial features of Kabuki syndrome visited our hospital due to her short stature. She was found to have the de novo heterozygous mutation of c.8200C > T, p(Arg2734*) in exon 32 of the KMT2D gene and was diagnosed with Kabuki syndrome. The patient also exhibited endocrine abnormalities such as a constitutional delay of puberty, transiently congenial hypothyroidism, obesity and growth hormone deficiency. This is a case of a mutation in the KMT2D gene in a girl with Kabuki syndrome who presented with endocrine symptoms (constitutional delay of puberty, hypothyroidism, obesity and growth hormone deficiency).

  8. New mouse tumor model system (RIF-1) for comparison of end-point studies

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

    Twentyman, P.R.; Brown, J.M.; Gray, J.W.

    1980-03-01

    A new tumor model system (RIF-1) was developed that is very suitable for studies in which clonogenic survival is compared with growth delay and control probability following various forms of treatment. The tumor was a radiation-induced sarcoma in the inbred female C3H/Km mouse. It had a low median tumor dose, had a satisfactory plating efficiency direct from in vivo to in vitro, was nonimmunogenic or minimally immunogenic, and metastasized only at a relatively advanced stage of growth. The cell line grew either as a monolayer on plastic dishes, as tumor spheroids in spinner culture, as lung nodules following injection ofmore » a single-cell suspension into the tall veins of syngeneic mice, or as a solid tumor. Both diploid and tetraploid clonogenic cells were found in monolayer cultures of the RIF-1 line.« less

  9. A carbon nanotube-polymer composite for T-cell therapy

    NASA Astrophysics Data System (ADS)

    Fadel, Tarek R.; Sharp, Fiona A.; Vudattu, Nalini; Ragheb, Ragy; Garyu, Justin; Kim, Dongin; Hong, Enping; Li, Nan; Haller, Gary L.; Pfefferle, Lisa D.; Justesen, Sune; Harold, Kevin C.; Fahmy, Tarek M.

    2014-08-01

    Clinical translation of cell therapies requires strategies that can manufacture cells efficiently and economically. One promising way to reproducibly expand T cells for cancer therapy is by attaching the stimuli for T cells onto artificial substrates with high surface area. Here, we show that a carbon nanotube-polymer composite can act as an artificial antigen-presenting cell to efficiently expand the number of T cells isolated from mice. We attach antigens onto bundled carbon nanotubes and combined this complex with polymer nanoparticles containing magnetite and the T-cell growth factor interleukin-2 (IL-2). The number of T cells obtained was comparable to clinical standards using a thousand-fold less soluble IL-2. T cells obtained from this expansion were able to delay tumour growth in a murine model for melanoma. Our results show that this composite is a useful platform for generating large numbers of cytotoxic T cells for cancer immunotherapy.

  10. Copper excess impairs mobilization of storage proteins in bean cotyledons.

    PubMed

    Karmous, Inès; El Ferjani, Ezzedine; Chaoui, Abdelilah

    2011-12-01

    Germination represents a limiting stage of plant life cycle. One of the underlying metabolic activities following imbibition of seed is the reserve mobilization. Seeds of bean (Phaseolus vulgaris L. var. soisson nain hatif) were germinated by soaking in distilled water or 200 μM CuCl(2). Storage proteins breakdown and amino acids freeing from reserve tissues were investigated. Compared to the control, Cu caused a reduction in germination rate, embryo growth, and in mobilization of cotyledonary biomass. The failure in albumin and globulin hydrolysis after the exposure to the pollutant was argued by (1) higher contents of remaining proteins than control ones, (2) persistence of some polypeptide bands resolved by polyacrylamide gel electrophoresis of albumin and globulin-rich fractions, and (3) decrease in the availability of amino acids. Nitrogen starvation in embryonic axis should be associated with the Cu-imposed delay in growth.

  11. Wigner time delay in photodetachment of Tm-and in photoionization of Yb: A comparative study

    NASA Astrophysics Data System (ADS)

    Saha, Soumyajit; Jose, Jobin; Deshmukh, Pranawa; Dolmatov, Valeriy; Kheifets, Anatoli; Manson, Steven

    2017-04-01

    Preliminary studies of Wigner time delay in photodetachment spectra of negative ions have been reported. Photodetachment time delay for some dipole channels of Tm- and of Cl- were calculated using relativistic random phase approximation (RRPA). Comparisons between photodetachment time delay of Cl- and photoionization time delay of Ar were made. We investigate the photodetachment time delay for all three relativistically split nd -> ɛ f channels of Tm- and for nd -> ɛ f channels of Yb (isoelectronic to Tm-) using RRPA. We study the effect of the shape resonance, brought about by the centrifugal barrier potential, on photodetachment time delay. A negative ion is a good laboratory for studying the effects of shape resonances on time delay since the phase is unaffected by the Coulomb component. Wigner time delay in photodetachment of Tm- and in photoionization of Yb: A comparative study.

  12. Requirement of alveolar bone formation for eruption of rat molars

    PubMed Central

    Wise, Gary E.; He, Hongzhi; Gutierrez, Dina L.; Ring, Sherry; Yao, Shaomian

    2011-01-01

    Tooth eruption is a localized event that requires a dental follicle (DF) to regulate the resorption of alveolar bone to form an eruption pathway. During the intra-osseous phase of eruption, the tooth moves through this pathway. The mechanism or motive force that propels the tooth through this pathway is controversial but many studies have shown that alveolar bone growth at the base of the crypt occurs during eruption. To determine if this bone growth (osteogenesis) was causal, experiments were designed in which the expression of an osteogenic gene in the DF, bone morphogenetic protein-6 (BMP6), was inhibited by injection of the 1st mandibular molar of the rat with an siRNA targeted against BMP6. The injection was followed by electroporation to promote uptake of the siRNA. In 45 first molars injected, eruption either was delayed or completely inhibited (7 molars). In the impacted molars, an eruption pathway formed but bone growth at the base of the crypt was greatly reduced as compared to the erupted first molar controls. These studies show that alveolar bone growth at the base of the crypt is required for tooth eruption and that BMP6 may be an essential gene for promoting this growth. PMID:21896048

  13. Overexpression of Adenylyl Cyclase Encoded by the Mycobacterium tuberculosis Rv2212 Gene Confers Improved Fitness, Accelerated Recovery from Dormancy and Enhanced Virulence in Mice.

    PubMed

    Shleeva, Margarita O; Kondratieva, Tatyana K; Demina, Galina R; Rubakova, Elvira I; Goncharenko, Anna V; Apt, Alexander S; Kaprelyants, Arseny S

    2017-01-01

    Earlier we demonstrated that the adenylyl cyclase (AC) encoded by the MSMEG_4279 gene plays a key role in the resuscitation and growth of dormant Mycobacterium smegmatis and that overexpression of this gene leads to an increase in intracellular cAMP concentration and prevents the transition of M. smegmatis from active growth to dormancy in an extended stationary phase accompanied by medium acidification. We surmised that the homologous Rv2212 gene of M. tuberculosis ( Mtb ), the main cAMP producer, plays similar physiological roles by supporting, under these conditions, the active state and reactivation of dormant bacteria. To test this hypothesis, we established Mtb strain overexpressing Rv2212 and compared its in vitro and in vivo growth characteristics with a control strain. In vitro , the AC-overexpressing pMind Rv2212 strain demonstrated faster growth in a liquid medium, prolonged capacity to form CFUs and a significant delay or even prevention of transition toward dormancy. AC-overexpressing cells exhibited easier recovery from dormancy. In vivo , AC-overexpressing bacteria demonstrated significantly higher growth rates (virulence) in the lungs and spleens of infected mice compared to the control strain, and, unlike the latter, killed mice in the TB-resistant strain before month 8 of infection. Even in the absence of selecting hygromycin B, all pMind Rv2212 CFUs retained the Rv2212 insert during in vivo growth, strongly suggesting that AC overexpression is beneficial for bacteria. Taken together, our results indicate that cAMP supports the maintenance of Mtb cells vitality under unfavorable conditions in vitro and their virulence in vivo .

  14. Distortion management in slow-light pulse delay.

    PubMed

    Stenner, Michael D; Neifeld, Mark A; Zhu, Zhaoming; Dawes, Andrew M C; Gauthier, Daniel J

    2005-12-12

    We describe a methodology to maximize slow-light pulse delay subject to a constraint on the allowable pulse distortion. We show that optimizing over a larger number of physical variables can increase the distortion-constrained delay. We demonstrate these concepts by comparing the optimum slow-light pulse delay achievable using a single Lorentzian gain line with that achievable using a pair of closely-spaced gain lines. We predict that distortion management using a gain doublet can provide approximately a factor of 2 increase in slow-light pulse delay as compared with the optimum single-line delay. Experimental results employing Brillouin gain in optical fiber confirm our theoretical predictions.

  15. Maternal and Neonatal Outcomes With Early Compared With Delayed Pushing Among Nulliparous Women.

    PubMed

    Yee, Lynn M; Sandoval, Grecio; Bailit, Jennifer; Reddy, Uma M; Wapner, Ronald J; Varner, Michael W; Caritis, Steve N; Prasad, Mona; Tita, Alan T N; Saade, George; Sorokin, Yoram; Rouse, Dwight J; Blackwell, Sean C; Tolosa, Jorge E

    2016-11-01

    To describe factors associated with delayed pushing and evaluate the relationship between delayed pushing and perinatal outcomes in nulliparous women with singleton term gestations. This was a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Assessment of Perinatal Excellence cohort of 115,502 women and their neonates born in 25 U.S. hospitals from 2008 to 2011. Nulliparous women with singleton, cephalic, nonanomalous term births who achieved 10-cm cervical dilation were included. Women in whom pushing was delayed by 60 minutes or greater (delayed group) were compared with those who initiated pushing within 30 minutes (early group). Multivariable regression analyses were used to assess the independent association of delayed pushing with mode of delivery, length of the second stage, and other maternal and perinatal outcomes (significance defined as P<.05). Of 21,034 women in the primary analysis sample, pushing was delayed in 18.4% (n=3,870). Women who were older, privately insured, or non-Hispanic white as well as those who had induction or augmentation of labor, diabetes, or epidural analgesia were more likely to have delayed pushing. Delayed pushing was more common when the second stage began during daytime hours or in hospitals with dedicated 24-hour obstetric anesthesia, although differences were small. After adjusting for differences in baseline and labor characteristics including center, women in the delayed group had longer mean durations of the second stage (191 compared with 84 minutes, P<.001) and of active pushing (86 compared with 76 minutes, P<.001). Delayed pushing was associated with greater rates of cesarean delivery (11.2% compared with 5.1%; adjusted odds ratio [OR] 1.86, 95% confidence interval [CI] 1.63-2.12), operative vaginal delivery (adjusted OR 1.26, 95% CI 1.14-1.40), postpartum hemorrhage (adjusted OR 1.43, 95% CI 1.05-1.95), and blood transfusion (adjusted OR 1.51, 95% CI 1.04-2.17). Delayed pushing was not associated with increased odds of adverse neonatal outcomes compared with early pushing. In this large birth cohort, delayed pushing was associated with longer second stage duration, increased odds of cesarean delivery, and increased odds of postpartum hemorrhage, but was not associated with neonatal morbidity.

  16. Decadal-scale ecosystem memory reveals interactive effects of drought and insect defoliation on boreal forest productivity

    NASA Astrophysics Data System (ADS)

    Itter, M.; D'Orangeville, L.; Dawson, A.; Kneeshaw, D.; Finley, A. O.

    2017-12-01

    Drought and insect defoliation have lasting impacts on the dynamics of the boreal forest. Impacts are expected to worsen under global climate change as hotter, drier conditions forecast for much of the boreal increase the frequency and severity of drought and defoliation events. Contemporary ecological theory predicts physiological feedbacks in tree responses to drought and defoliation amplify impacts potentially causing large-scale productivity losses and forest mortality. Quantifying the interactive impacts of drought and insect defoliation on regional forest health is difficult given delayed and persistent responses to disturbance events. We developed a Bayesian hierarchical model to estimate forest growth responses to interactions between drought and insect defoliation by species and size class. Delayed and persistent responses to past drought and defoliation were quantified using empirical memory functions allowing for improved detection of interactions. The model was applied to tree-ring data from stands in Western (Alberta) and Eastern (Québec) regions of the Canadian boreal forest with different species compositions, disturbance regimes, and regional climates. Western stands experience chronic water deficit and forest tent caterpillar (FTC) defoliation; Eastern stands experience irregular water deficit and spruce budworm (SBW) defoliation. Ecosystem memory to past water deficit peaked in the year previous to growth and decayed to zero within 5 (West) to 8 (East) years; memory to past defoliation ranged from 8 (West) to 12 (East) years. The drier regional climate and faster FTC defoliation dynamics (compared to SBW) likely contribute to shorter ecosystem memory in the West. Drought and defoliation had the largest negative impact on large-diameter, host tree growth. Surprisingly, a positive interaction was observed between drought and defoliation for large-diameter, non-host trees likely due to reduced stand-level competition for water. Results highlight the temporal persistence of drought and defoliation stress on boreal forest growth dynamics and provide an empirical estimate of their interactive effects with explicit uncertainty.

  17. Growth hormone distribution kinetics are markedly reduced in adults with growth hormone deficiency.

    PubMed

    Catalina, Pablo F; Páramo, Concepción; Andrade, Maria Amalia; Mallo, Federico

    2007-03-01

    Growth hormone (GH) circulating levels are highly dependent not only on GH secretion rate from the pituitary, but also on the hormone distribution in the compartments of the body and elimination phenomena. In adult GH-deficient patients these factors become critical nowadays, especially when recombinant human GH (rhGH) is available for replacement therapy. In the present study, we assess the influence of both distribution and elimination phenomena on GH pharmacokinetics in adult GH-deficient patients. We used a four-step methodology following a compartmental approach after an intravenous bolus of recombinant GH in adult GH-deficient patients. We found that GH kinetics are clearly explained by a bi-exponential, two-compartmental model in GH-deficient patients, similarly than in normal or diabetic subjects, as previously shown. We have also observed a marked delay in the whole GH elimination process in GH-deficient patients compared to normal adult subjects, as revealed by metabolic clearance ratio (MCR), elimination constant from central compartment (k(10)), and mean resident time in the body (MRT). Interestingly, such a delay appear to be caused by deep changes in the distribution phase (Mtt(1)- mean transit time-1; T(1/2alpha)- GH half-life at distribution phase), while the elimination phenomenon remains unaltered. Our results emphasize the relevance of distribution phenomena in GH pharmacokinetics, and indicates that studies avoiding data from the GH distribution phase, such as those carried out in steady-state conditions, or those using noncompartmental models, could easily miss relevant information. Our data should be taken into consideration when establishing the appropriate dosage for GH replacement treatments in GH-deficient patients, and calculations should include GH distribution kinetics.

  18. Validation and Comparison of the Therapeutic Efficacy of Boron Neutron Capture Therapy Mediated By Boron-Rich Liposomes in Multiple Murine Tumor Models

    DOE PAGES

    Maitz, Charles A.; Khan, Aslam A.; Kueffer, Peter J.; ...

    2017-08-01

    Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. We implanted mice with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH 3(CH 2) 15–7,8-C 2B 9H 11] in the lipid bilayer and encapsulated Na 3[1-(2`-B 10H 9)-2-NH 3B 10H 8] within the liposomal core. Mice were irradiated 30 hours after the second injection inmore » a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. In spite of relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.« less

  19. Validation and Comparison of the Therapeutic Efficacy of Boron Neutron Capture Therapy Mediated By Boron-Rich Liposomes in Multiple Murine Tumor Models

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

    Maitz, Charles A.; Khan, Aslam A.; Kueffer, Peter J.

    Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. We implanted mice with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH 3(CH 2) 15–7,8-C 2B 9H 11] in the lipid bilayer and encapsulated Na 3[1-(2`-B 10H 9)-2-NH 3B 10H 8] within the liposomal core. Mice were irradiated 30 hours after the second injection inmore » a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. In spite of relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.« less

  20. Ventricular septal defect

    MedlinePlus

    ... causing an irregular or slow heart rhythm) Delayed growth and development ( failure to thrive in infancy) Heart failure Infective endocarditis (bacterial infection of the heart) Pulmonary hypertension (high blood ...

  1. An optimized small animal tumour model for experimentation with low energy protons.

    PubMed

    Beyreuther, Elke; Brüchner, Kerstin; Krause, Mechthild; Schmidt, Margret; Szabo, Rita; Pawelke, Jörg

    2017-01-01

    The long-term aim of developing laser based particle acceleration towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short and ultra-intensive particle beam pulses. After comprehensive cell studies a mouse ear tumour model was established allowing for the penetration of low energy protons (~20 MeV) currently available at laser driven accelerators. The model was successfully applied for a first tumour growth delay study with laser driven electrons, whereby the need of improvements crop out. To optimise the mouse ear tumour model with respect to a stable, high take rate and a lower number of secondary tumours, Matrigel was introduced for tumour cell injection. Different concentrations of two human tumour cell lines (FaDu, LN229) and Matrigel were evaluated for stable tumour growth and fulfilling the allocation criteria for irradiation experiments. The originally applied cell injection with PBS was performed for comparison and to assess the long-term stability of the model. Finally, the optimum suspension of cells and Matrigel was applied to determine applicable dose ranges for tumour growth delay studies by 200 kV X-ray irradiation. Both human tumour models showed a high take rate and exponential tumour growth starting at a volume of ~10 mm3. As disclosed by immunofluorescence analysis these small tumours already interact with the surrounding tissue and activate endothelial cells to form vessels. The formation of delimited, solid tumours at irradiation size was shown by standard H&E staining and a realistic dose range for inducing tumour growth delay without permanent tumour control was obtained for both tumour entities. The already established mouse ear tumour model was successfully upgraded now providing stable tumour growth with high take rate for two tumour entities (HNSCC, glioblastoma) that are of interest for future irradiation experiments at experimental accelerators.

  2. Experimental drought and heat can delay phenological development and reduce foliar and shoot growth in semiarid trees

    DOE PAGES

    Adams, Henry D.; Collins, Adam D.; Briggs, Samuel P.; ...

    2015-09-22

    Higher temperatures associated with climate change are anticipated to trigger an earlier start to the growing season, which could increase the terrestrial C sink strength. Greater variability in the amount and timing of precipitation is also expected with higher temperatures, bringing increased drought stress to many ecosystems. We experimentally assessed the effects of higher temperature and drought on the foliar phenology and shoot growth of mature trees of two semiarid conifer species. We exposed field-grown trees to a ~45% reduction in precipitation with a rain-out structure (‘drought’), a ~4.8 °C temperature increase with open-top chambers (‘heat’), and a combination ofmore » both simultaneously (‘drought + heat’). Over the 2013 growing season, drought, heat, and drought + heat treatments reduced shoot and needle growth in piñon pine ( Pinus edulis) by ≥39%, while juniper ( Juniperus monosperma) had low growth and little response to these treatments. Needle emergence on primary axis branches of piñon pine was delayed in heat, drought, and drought + heat treatments by 19–57 days, while secondary axis branches were less likely to produce needles in the heat treatment, and produced no needles at all in the drought + heat treatment. Growth of shoots and needles, and the timing of needle emergence correlated inversely with xylem water tension and positively with nonstructural carbohydrate concentrations. Our findings demonstrate the potential for delayed phenological development and reduced growth with higher temperatures and drought in tree species that are vulnerable to drought and reveal potential mechanistic links to physiological stress responses. Furthermore, climate change projections of an earlier and longer growing season with higher temperatures, and consequent increases in terrestrial C sink strength, may be incorrect for regions where plants will face increased drought stress with climate change.« less

  3. Experimental drought and heat can delay phenological development and reduce foliar and shoot growth in semiarid trees.

    PubMed

    Adams, Henry D; Collins, Adam D; Briggs, Samuel P; Vennetier, Michel; Dickman, L Turin; Sevanto, Sanna A; Garcia-Forner, Núria; Powers, Heath H; McDowell, Nate G

    2015-11-01

    Higher temperatures associated with climate change are anticipated to trigger an earlier start to the growing season, which could increase the terrestrial C sink strength. Greater variability in the amount and timing of precipitation is also expected with higher temperatures, bringing increased drought stress to many ecosystems. We experimentally assessed the effects of higher temperature and drought on the foliar phenology and shoot growth of mature trees of two semiarid conifer species. We exposed field-grown trees to a ~45% reduction in precipitation with a rain-out structure ('drought'), a ~4.8 °C temperature increase with open-top chambers ('heat'), and a combination of both simultaneously ('drought + heat'). Over the 2013 growing season, drought, heat, and drought + heat treatments reduced shoot and needle growth in piñon pine (Pinus edulis) by ≥39%, while juniper (Juniperus monosperma) had low growth and little response to these treatments. Needle emergence on primary axis branches of piñon pine was delayed in heat, drought, and drought + heat treatments by 19-57 days, while secondary axis branches were less likely to produce needles in the heat treatment, and produced no needles at all in the drought + heat treatment. Growth of shoots and needles, and the timing of needle emergence correlated inversely with xylem water tension and positively with nonstructural carbohydrate concentrations. Our findings demonstrate the potential for delayed phenological development and reduced growth with higher temperatures and drought in tree species that are vulnerable to drought and reveal potential mechanistic links to physiological stress responses. Climate change projections of an earlier and longer growing season with higher temperatures, and consequent increases in terrestrial C sink strength, may be incorrect for regions where plants will face increased drought stress with climate change. © 2015 John Wiley & Sons Ltd.

  4. Experimental drought and heat can delay phenological development and reduce foliar and shoot growth in semiarid trees

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

    Adams, Henry D.; Collins, Adam D.; Briggs, Samuel P.

    Higher temperatures associated with climate change are anticipated to trigger an earlier start to the growing season, which could increase the terrestrial C sink strength. Greater variability in the amount and timing of precipitation is also expected with higher temperatures, bringing increased drought stress to many ecosystems. We experimentally assessed the effects of higher temperature and drought on the foliar phenology and shoot growth of mature trees of two semiarid conifer species. We exposed field-grown trees to a ~45% reduction in precipitation with a rain-out structure (‘drought’), a ~4.8 °C temperature increase with open-top chambers (‘heat’), and a combination ofmore » both simultaneously (‘drought + heat’). Over the 2013 growing season, drought, heat, and drought + heat treatments reduced shoot and needle growth in piñon pine ( Pinus edulis) by ≥39%, while juniper ( Juniperus monosperma) had low growth and little response to these treatments. Needle emergence on primary axis branches of piñon pine was delayed in heat, drought, and drought + heat treatments by 19–57 days, while secondary axis branches were less likely to produce needles in the heat treatment, and produced no needles at all in the drought + heat treatment. Growth of shoots and needles, and the timing of needle emergence correlated inversely with xylem water tension and positively with nonstructural carbohydrate concentrations. Our findings demonstrate the potential for delayed phenological development and reduced growth with higher temperatures and drought in tree species that are vulnerable to drought and reveal potential mechanistic links to physiological stress responses. Furthermore, climate change projections of an earlier and longer growing season with higher temperatures, and consequent increases in terrestrial C sink strength, may be incorrect for regions where plants will face increased drought stress with climate change.« less

  5. The effect of recombinant growth hormone on intestinal anastomotic wound healing in rats with obstructive jaundice.

    PubMed

    Cağlikülekçi, Mehmet; Ozçay, Necdet; Oruğ, Taner; Aydoğ, Gülden; Renda, Nurten; Atalay, Fuat

    2002-03-01

    Several clinical and experimental studies have shown that obstructive jaundice delays wound healing. Growth hormone may prevent delayed wound healing, since it has effects on the release of mediators in jaundice, as well as increasing the protein synthesis. Forty male Wistar rats were allocated to four groups: Group I (n=10): intestinal anastomosis to normal small bowel, Group II (n=10): intestinal anastomosis to normal small bowel followed by growth hormone therapy (2mg/kg/day, subcutaneously), Group III (n=10): intestinal anastomosis to obstructive jaundice rat's small bowel, Group IV (n=10): intestinal anastomosis to obstructive jaundice rat's small bowel followed by growth hormone therapy at the same dosage The animals were observed for seven days then killed. Intraabdominal adhesions, anastomotic complications and anastomotic bursting pressures were recorded and tissue samples from the anastomotic site were obtained to measure hydroxyproline levels and for histopathologic examination. Growth hormone had a beneficial effect on the healing of intestinal anastomosis in both jaundiced and non-jaundiced rats. This was demonstrated by clinical and mechanical parameters such as a significant increase in anastomotic bursting pressure, hydroxyproline content and histopathological scores. Growth hormone reverses the adverse effects of obstructive jaundice on small bowel anastomotic healing. It can be hypothesized that this effect is due to augmentation of insulin-like growth factors, protection of hepatocytes, enhancement of intestinal epithelization, and reversal of the resultant malnutritional state caused by growth hormone in obstructive jaundice.

  6. Genetically engineered flavonol enriched tomato fruit modulates chondrogenesis to increase bone length in growing animals.

    PubMed

    Choudhary, Dharmendra; Pandey, Ashutosh; Adhikary, Sulekha; Ahmad, Naseer; Bhatia, Chitra; Bhambhani, Sweta; Trivedi, Prabodh Kumar; Trivedi, Ritu

    2016-02-26

    Externally visible body and longitudinal bone growth is a result of proliferation of chondrocytes. In growth disorder, there is delay in the age associated increase in height. The present study evaluates the effect of extract from transgenic tomato fruit expressing AtMYB12 transcription factor on bone health including longitudinal growth. Constitutive expression of AtMYB12 in tomato led to a significantly enhanced biosynthesis of flavonoids in general and the flavonol biosynthesis in particular. Pre-pubertal ovary intact BALB/c mice received daily oral administration of vehicle and ethanolic extract of wild type (WT-TOM) and transgenic AtMYB12-tomato (MYB12-TOM) fruits for six weeks. Animal fed with MYB12-TOM showed no inflammation in hepatic tissues and normal sinusoidal Kupffer cell morphology. MYB12-TOM extract significantly increased tibial and femoral growth and subsequently improved the bone length as compared to vehicle and WT-TOM. Histomorphometry exhibited significantly wider distal femoral and proximal tibial growth plate, increased number and size of hypertrophic chondrocytes in MYB12-TOM which corroborated with micro-CT and expression of BMP-2 and COL-10, marker genes for hypertrophic cells. We conclude that metabolic reprogramming of tomato by AtMYB12 has the potential to improve longitudinal bone growth thus helping in achievement of greater peak bone mass during adolescence.

  7. Genetics Home Reference: SADDAN

    MedlinePlus

    ... CLOSE navigation Home Page Search Home Health ... delay and acanthosis nigricans) is a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities. All people with this ...

  8. Warm winter, thin ice?

    NASA Astrophysics Data System (ADS)

    Stroeve, Julienne C.; Schroder, David; Tsamados, Michel; Feltham, Daniel

    2018-05-01

    Winter 2016/2017 saw record warmth over the Arctic Ocean, leading to the least amount of freezing degree days north of 70° N since at least 1979. The impact of this warmth was evaluated using model simulations from the Los Alamos sea ice model (CICE) and CryoSat-2 thickness estimates from three different data providers. While CICE simulations show a broad region of anomalously thin ice in April 2017 relative to the 2011-2017 mean, analysis of three CryoSat-2 products show more limited regions with thin ice and do not always agree with each other, both in magnitude and direction of thickness anomalies. CICE is further used to diagnose feedback processes driving the observed anomalies, showing 11-13 cm reduced thermodynamic ice growth over the Arctic domain used in this study compared to the 2011-2017 mean, and dynamical contributions of +1 to +4 cm. Finally, CICE model simulations from 1985 to 2017 indicate the negative feedback relationship between ice growth and winter air temperatures may be starting to weaken, showing decreased winter ice growth since 2012, as winter air temperatures have increased and the freeze-up has been further delayed.

  9. Production of Bakers' Yeast in Cheese Whey Ultrafiltrate †

    PubMed Central

    Champagne, C. P.; Goulet, J.; Lachance, R. A.

    1990-01-01

    A process for the production of bakers' yeast in whey ultrafiltrate (WU) is described. Lactose in WU was converted to lactic acid and galactose by fermentation. Streptococcus thermophilus was selected for this purpose. Preculturing of S. thermophilus in skim milk considerably reduced its lag. Lactic fermentation in 2.3×-concentrated WU was delayed compared with that in unconcentrated whey, and fermentation could not be completed within 60 h. The growth rate of bakers' yeast in fermented WU differed among strains. The rate of galactose utilization was similar for all strains, but differences in lactic acid utilization occurred. Optimal pH ranges for galactose and lactic acid utilization were 5.5 to 6.0 and 5.0 to 5.5, respectively. The addition of 4 g of corn steep liquor per liter to fermented WU increased cell yields. Two sources of nitrogen were available for growth of Saccharomyces cerevisiae: amino acids (corn steep liquor) and ammonium (added during the lactic acid fermentation). Ammonium was mostly assimilated during growth on lactic acid. This process could permit the substitution of molasses by WU for the industrial production of bakers' yeast. PMID:16348117

  10. Laboratory Studies on Molting and Growth of the Shore Crab, Hemigrapsus sanguineus de Haan, Parasitized by a Rhizocephalan Barnacle.

    PubMed

    Takahashi, T; Matsuura, S

    1994-06-01

    Molting of shore crabs (Hemigrapsus sanguineus) parasitized by rhizocephalans (Sacculina senta) was observed in the laboratory, and the growth of the molted crabs was compared with that of unparasitized animals. Molting of the host was obstructed by the infestation, but was still possible. After the release of several broods of larvae, the externa (the external reproductive system of the parasite) detached from the host. Subsequent molting occurred within 40 days in about 80% of the animals, but in the remainder, it was delayed for at most 4 months. Soon after molting, a new externa protruded from the abdomen of every crab. Thus, the life-span of the externa and the molting of the host would seem to be closely connected. In the female, the molt frequency was reduced, but the molt increment of the parasitized crabs was not different from that in the unparasitized ones. In the male, however, both the molt frequency and the molt increment were reduced. Thus, the annual growth of parasitized males and females was about half that of unparasitized crabs.

  11. Vascular delay and administration of basic fibroblast growth factor augment latissimus dorsi muscle flap perfusion and function.

    PubMed

    Carroll, S M; Carroll, C M; Stremel, R W; Heilman, S J; Steffen, J M; Tobin, G R; Barker, J H

    2000-03-01

    Ischemia of the distal latissimus dorsi muscle flap occurs when the entire muscle is acutely elevated. Although this level of ischemia may not be critical if the muscle is to be used as a conventional muscle flap, the ischemia causes decreased distal muscle function if it is used for dynamic muscle flap transfer. This experiment was designed to determine whether or not the administration of exogenous basic fibroblast growth factor (bFGF), combined with a sublethal ischemic insult (i.e., vascular delay), would further augment muscle perfusion and function. Both latissimus dorsi muscles of nine canines were subjected to a bipedicle vascular delay procedure immediately followed by thoracodorsal intraarterial injection of 100 microg of bFGF on one side and by intraarterial injection of vehicle on the other. Ten days later, both latissimus dorsi muscles were raised as thoracodorsally based island flaps, with perfusion determined by laser-Doppler fluximetry. The muscles were wrapped around silicone chambers, simulating cardiomyoplasty, and stimulating electrodes were placed around each thoracodorsal nerve. The muscles were then subjected to an experimental protocol to determine muscle contractile function. At the end of the experiment, latissimus dorsi muscle biopsies were obtained for measurement of bFGF expression. The results demonstrated that the administration of 100 microg of bFGF immediately after the vascular delay procedure increases expression of native bFGF. In the distal and middle muscle segments, it also significantly increased muscle perfusion by approximately 20 percent and fatigue resistance by approximately 300 percent. The administration of growth factors may serve as an important adjuvant to surgical procedures using dynamic muscle flap transfers.

  12. Trajectories of Early Brain Volume Development in Fragile X and Autism RH: Trajectory of Brain Volume in Fragile X

    PubMed Central

    Hazlett, Heather Cody; Poe, Michele D.; Lightbody, Amy A.; Styner, Martin; MacFall, James R.; Reiss, Allan L.; Piven, Joseph

    2012-01-01

    Objective To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared to a comparison group (controls) and a group with idiopathic autism. Method The study included 53 boys between 18–42 months of age with FXS, 68 boys with idiopathic autism (ASD), and a comparison group of 50 typically-developing and developmentally-delayed controls. We examined structural brain volumes using magnetic resonance imaging (MRI) across two timepoints between ages 2–3 and 4–5 years and examined total brain volumes and regional (lobar) tissue volumes. Additionally, we studied a selected group of subcortical structures implicated in the behavioral features of FXS (e.g., basal ganglia, hippocampus, amygdala). Results Children with FXS had greater global brain volumes compared to controls, but were not different than children with idiopathic autism, and the rate of brain growth between ages 2 and 5 paralleled that seen in controls. In contrast to the children with idiopathic autism who had generalized cortical lobe enlargement, the children with FXS showed a specific enlargement in temporal lobe white matter, cerebellar gray matter, and caudate nucleus, but significantly smaller amygdala. Conclusions This structural longitudinal MRI study of preschoolers with FXS observed generalized brain overgrowth in FXS compared to controls, evident at age 2 and maintained across ages 4–5. We also find different patterns of brain growth that distinguishes boys with FXS from children with idiopathic autism. PMID:22917205

  13. Combined cetuximab and genistein treatment shows additive anti-cancer effect on oral squamous cell carcinoma.

    PubMed

    Park, Sung-Jin; Kim, Myung-Jin; Kim, Yu-Kyoung; Kim, Soung-Min; Park, Ju-Yong; Myoung, Hoon

    2010-06-01

    The purpose of this study was to evaluate the potency of EGFR pathway inhibition achieved by combining cetuximab, an anti-EGFR monoclonal antibody, and genistein, a tyrosine kinase inhibitor, which target extracellular and intracellular domains of the receptor, respectively, in oral squamous cell carcinoma (OSCC) in vitro and in vivo. Two OSCC cell lines, HSC3 and KB, were treated with cetuximab (C, 0-400mug/ml), genistein (G, 0-80muM), or a combination of both at a range of concentrations. Downstream protein expression of EGFR, p-EGFR, and p-Akt were evaluated by Western blot. Cell proliferation and apoptosis indices were calculated to assess anti-cancer effects in vitro. The in vivo effects of cetuximab and genistein on tumor cell growth were examined using an OSCC xenografted nude mouse model and immunohistochemical analyses of proliferation (PCNA) and microvessel density (CD31). Treatment of cells with dual anti-EGFR agents reduced the expressions of p-EGFR, and p-Akt in HSC3 cell line, but there was no significant difference in downregulation between cetuximab alone and in combination with genistein in KB cells. Both HSC3 and KB cells showed a dose-dependent decrease in cell proliferation significantly with single agent treatment and combination (p<0.05). In low concentration, combined cetuximab and genistein therapy resulted in additive growth inhibition and more apoptosis compared to that achieved with single-agent exposure in both cell lines. A combination of cetuximab and genistein significantly inhibited tumor growth and caused a substantial growth delay in in vivo models of both cell lines while each single-agent exposure caused no delay of tumor growth. Immunohistochemical staining with PCNA revealed that the group receiving combined cetuximab and genistein exhibited the lowest number of proliferating cells and microvessel density (p<0.05). Combined therapy with genistein and cetuximab can add the potency of EGFR signaling inhibition. Because not all OSCC cell types appear to respond uniformly, however, selective targeting of distinct molecular pathways is required for effective clinical response. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  14. Early Head Growth in Infants at Risk of Autism: A Baby Siblings Research Consortium Study

    PubMed Central

    Zwaigenbaum, Lonnie; Young, Gregory S.; Stone, Wendy L.; Dobkins, Karen; Ozonoff, Sally; Brian, Jessica; Bryson, Susan E.; Carver, Leslie J.; Hutman, Ted; Iverson, Jana M.; Landa, Rebecca J.; Messinger, Daniel

    2014-01-01

    Objective: While early brain overgrowth is frequently reported in autism spectrum disorder (ASD), the relationship between ASD and head circumference (HC) is less clear, with inconsistent findings from longitudinal studies that include community controls. Our aim was to examine whether head growth in the first 3 years differed between children with ASD from a high-risk (HR) sample of infant siblings of children with ASD (by definition, multiplex), HR siblings not diagnosed with ASD, and low-risk (LR) controls. Method: Participants included 442 HR and 253 LR infants from 12 sites of the international Baby Siblings Research Consortium. Longitudinal HC data were obtained prospectively, supplemented by growth records. Random effects non-linear growth models were used to compare HC in HR infants and LR infants. Additional comparisons were conducted with the HR group stratified by diagnostic status at age 3: ASD (n=77), developmental delay (DD; n=32), and typical development (TD; n=333). Nonlinear growth models were also developed for height to assess general overgrowth associated with ASD. Results: There was no overall difference in head circumference growth over the first 3 years between HR and LR infants, although secondary analyses suggested possible increased total growth in HR infants, reflected by the model asymptote. Analyses stratifying the HR group by 3-year outcomes did not detect differences in head growth or height between HR infants who developed ASD and those who did not, nor between infants with ASD and LR controls. Conclusion: Head growth was uninformative as an ASD risk marker within this HR cohort. PMID:25245349

  15. Catch-up Growth: Cellular and Molecular Mechanisms

    PubMed Central

    Finkielstain, GP; Lui, JC; Baron, J

    2012-01-01

    In mammals, after a period of growth inhibition, body growth often does not just return to a normal rate but actually exceeds the normal rate, resulting in catch-up growth. Recent evidence suggests that catch-up growth occurs because growth-inhibiting conditions delay progression of the physiological mechanisms that normally cause body growth to slow and cease with age. As a result, following the period of growth inhibition, tissues retain a greater proliferative capacity than normal, and therefore grow more rapidly than normal for age. There is evidence that this mechanism contributes both to catch-up growth in terms of body length, which involves proliferation in the growth plate, and to catch-up growth in terms of organ mass, which involves proliferation in multiple non-skeletal tissues. PMID:23428687

  16. Pure culture response of ectomycorrhizal fungi to imposed water stress

    Treesearch

    Mark D. Coleman; Caroline S. Bledsoe; William Lopushinsky

    1989-01-01

    The ability of ectomycorrhizal fungal isolates to tolerate imposed water stress in pure culture was examined in 55 isolates of 18 species. Water potential treatments, adjusted with polyethylene glycol, were applied to Petri dish units. These units allowed colony diameter measurements of fungi grown on liquid media. Delayed growth initiation and inhibition of growth...

  17. 76 FR 414 - Tier 1 Environmental Impact Statement for the Los Angeles to San Luis Obispo (LOSSAN North) Rail...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ... expected growth in population and resulting increases in intercity travel demand between Los Angeles and San Luis Obispo. As a result of this growth in travel demand, their travel delays from the growing... environmental analysis to help make corridor level decisions regarding the level of intercity passenger rail...

  18. Screening for Language Delay: Growth Trajectories of Language Ability in Low- and High-Performing Children

    ERIC Educational Resources Information Center

    Klem, Marianne; Hagtvet, Bente; Hulme, Charles; Gustafsson, Jan-Eric

    2016-01-01

    Purpose: This study investigated the stability and growth of preschool language skills and explores latent class analysis as an approach for identifying children at risk of language impairment. Method: The authors present data from a large-scale 2-year longitudinal study, in which 600 children were assessed with a language-screening tool…

  19. Effects of prolonged storage on survival and growth of outplanted bottomland oaks

    Treesearch

    David C. Mercker; David S. Buckley; John P. Conn

    2011-01-01

    A prominent difficulty during bottomland hardwood afforestation is that sites are often flooded during the preferred months of planting (January-March), which results in delayed planting (April-June) and reduced survival. We monitored growth and survival of oak seedlings planted in 11 different months (February through December) after varying periods of humidified cold...

  20. Unstable Resonator Mid-Infrared Laser Sources

    DTIC Science & Technology

    2016-02-26

    of individual materials depending on metal species and growth temperatures . Fig. 8 (a) Average power consumption and (b) delay of C2MOS and double...feedback lasers, chirped gratings, interferometric lithography, nanowire transistors, tunnel field- effect transistors, nanoscale epitaxial growth, nanowire...technical approaches. Approaches to wavelength tuning include thermal/operation temperature tuning [1], variable cavity length with cantilever/piezo

  1. Brown-Spot Needle Blight of Pines

    Treesearch

    W.R. Phelps; A.G. Kais; T.H. Nicholls

    1978-01-01

    Brown-spot needle blight, caused by Scirrhia acicola (Dearn.) Siggers, delays growth and causes mortality of longleaf pine (Pinus palustris Mill.). Brown spot reduces total annual growth of southern pines by more than 16 million cubic feet (0.453 million cubic meters) of timber. Damage is most severe on longleaf seedlings in the grass stage; i.e., those that have not...

  2. Comparison of developmental milestone attainment in early treated HIV-infected infants versus HIV-unexposed infants: a prospective cohort study.

    PubMed

    Benki-Nugent, Sarah; Wamalwa, Dalton; Langat, Agnes; Tapia, Kenneth; Adhiambo, Judith; Chebet, Daisy; Okinyi, Helen Moraa; John-Stewart, Grace

    2017-01-17

    Infant HIV infection is associated with delayed milestone attainment. The extent to which effective antiretroviral therapy (ART) prevents these delays is not well defined. Ages at attainment of milestones were compared between HIV-infected (initiated ART by age <5 months), and HIV-unexposed uninfected (HUU) infants. Kaplan Meier analyses were used to estimate and compare (log-rank tests) ages at milestones between groups. Adjusted analyses were performed using Cox proportional hazards models. Seventy-three HIV-infected on ART (median enrollment age 3.7 months) and 92 HUU infants (median enrollment age 1.6 months) were followed prospectively. HIV-infected infants on ART had delays in developmental milestone attainment compared to HUU: median age at attainment of sitting with support, sitting unsupported, walking with support, walking unsupported, monosyllabic speech and throwing toys were each delayed (all p-values <0.0005). Compared with HUU, the subset of HIV-infected infants with both virologic suppression and immune recovery at 6 months had delays for speech (delay: 2.0 months; P = 0.0002) and trend to later walking unsupported. Among HIV-infected infants with poor 6-month post-ART responses (lacking viral suppression and immune recovery) there were greater delays versus HUU for: walking unsupported (delay: 4.0 months; P = 0.0001) and speech (delay: 5.0 months; P < 0.0001). HIV infected infants with viral suppression on ART had better recovery of developmental milestones than those without suppression, however, deficits persisted compared to uninfected infants. Earlier ART may be required for optimized cognitive outcomes in perinatally HIV-infected infants. NCT00428116 ; January 22, 2007.

  3. The model of root graviresponse with retarded arguments

    NASA Astrophysics Data System (ADS)

    Kondrachuk, Alexander

    The graviperception mechanism (GPM) of the roots of higher plants localized in the cap region of a root and supposedly related to statoliths sedimentation produces the signals in response to the change of the root axis orientation relative to the gravity vector G. Meanwhile, the regions (Distal Elongation Zone -DEZ and Central Elongation Zone-CEZ), where the signals initiate the changes of the growth rates of the upper and lower flanks of the root, are located at the significant distances from the cap (thousands microns for some plants). It causes the time delays between the relocation of statoliths in statocytes and the change of the growth rates in elongation zones. It is suggested that the signal targeting the CEZ modulates the initially uniform lateral distribution of some specific substances (S) in the cap region. Then already nonhomogeneous lateral distribution of S is transferred to the CEZ to initiate the change of the growth rates of the opposite flanks. It results in the bending of the root in the line of G and thus in the change of the GPM signal in the cap region. In the present model the kinetics of a root apex bending (angle A) in response to the time (t)-dependent change of the G orientation is described by the integro-differential equation in A(t). The main peculiarity of this model is the presence of retarded (time-delayed) arguments t-TCEZ and t-TDEZ . In this case the solutions of this equation depend on the preceding kinetics of A(t) during the time delays TCEZ and TDEZ . It is suggested that the signals activating the CEZ and DEZ are of different nature. The work is focused on two problems concerning the modeling of the effects of time-delay(s) on the root bending. The first problem supposes the existence of one zone (CEZ) and one time-delay TCEZ . This equation was studied and solved using analytical and numerical methods. We analyzed the model as to whether it can be used to describe the kinetics of root graviresponse in the case of different orientations of the root apex relative to the G vector during the time interval equal to TCEZ (TCEZ > TDEZ ) that precedes the beginning of gravistimultion. Also we explored the conditions of the overshooting (the vertical) and non-overshooting regimes of gravistimulated root bending. Good correlation between the results of the modeling and known experimental data (Barlow et al, 1993, Stochkus, 1994, Mullen, 1998) was found. This allowed us to estimate and analyze the parameters of the model. The second problem supposed the existence of two zones of growth (CEZ and DEZ) and two corresponding time-delays. The effects of the second time-delay connected with the presence of the DEZ on the behavior of the model equation of the root graviresponse kinetics were analyzed and discussed.

  4. DISCRIMINATION ACQUISITION IN CHILDREN WITH DEVELOPMENTAL DISABILITIES UNDER IMMEDIATE AND DELAYED REINFORCEMENT

    PubMed Central

    Sy, Jolene R.; Vollmer, Timothy R.

    2012-01-01

    We evaluated the discrimination acquisition of individuals with developmental disabilities under immediate and delayed reinforcement. In Experiment 1, discrimination between two alternatives was examined when reinforcement was immediate or delayed by 20 s, 30 s, or 40 s. In Experiment 2, discrimination between 2 alternatives was compared across an immediate reinforcement condition and a delayed reinforcement condition in which subjects could respond during the delay. In Experiment 3, discrimination among 4 alternatives was compared across immediate and delayed reinforcement. In Experiment 4, discrimination between 2 alternatives was examined when reinforcement was immediate and 0-s or 30-s intertrial intervals (ITI) were programmed. For most subjects, discrimination acquisition occurred under immediate reinforcement. However, for some subjects, introducing delays slowed or prevented discrimination acquisition under some conditions. Results from Experiment 4 suggest that longer ITIs cannot account for the lack of discrimination under delayed reinforcement. PMID:23322925

  5. Influence of growth hormone therapy on selected dental and skeletal system parameters.

    PubMed

    Partyka, Małgorzata; Chałas, Renata; Dunin-Wilczyńska, Izabella; Drohomyretska, Myroslava; Klatka, Maria

    2018-03-14

    Growth hormone deficiency (GHD) is one of the main indications for growth hormone therapy. One characteristic of this disease is bone age delay in relation to the chronological age. Pituitary dysfunction negatively affects the growth and development of the jaws and teeth of the child. The secretion of endocrine glands regulates growth, development, and gender differentiation. It also controls the growth of bones and teeth, regulates metabolism of calcium and phosphate, proteins, lipids and carbohydrates. The primary role in the endocrine system is played by the pituitary gland which is responsible for the production of somatotropin [1]. Dysfunction of the pituitary gland has a negative effect on the growth and development of long bones in the body, and may have an adverse effect on the development of maxilla, mandible and dentition of a child. There is some information in the literature that dental age is delayed in short stature children; the replacement of deciduous teeth by permanent teeth is also delayed, and newly erupted permanent teeth often require orthodontic treatment. Applying hormonal therapy positively affects the process of replacement of dentition [2, 3, 4, 5, 6]. The aim of the study was to assess bone and dental age, as well as analyze the state of dentition in children diagnosed with GH deficiency treated with growth hormone, depending on the duration of treatment. The study material consisted of 110 children (27 males, 83 females), hospitalized for somatotropin hypopituitarism in the Department of Paediatric Endocrinology and Diabetology at the Medical University of Lublin, Poland. The mean birth age was 13 years (156 months) with a standard deviation of 2 years and 6 months (30 months). 47 children (43%) started treatment with the growth hormone (group starting treatment) and 63 children (57%) whose treatment was started 2-3 years previously (group in the course of treatment). The control group consisted of 41 generally healthy children (15males, 25 females) with ENT problems, such as hypoacusis and a condition after nasal injury, hospitalized in the Department of Paediatric Otolaryngology at the Medical University of Lublin, Poland. The mean age was 11 years and 5 months (137 months) with standard deviation of 2 years and 5 months (29 months). Informed consent was obtained from the parents. The study was approved by the Bioethical Committee at the Medical University of Lublin (Resolution No. KE-0254 /216 /2012).

  6. Heat shock protein 27 overexpression in CHO cells modulates apoptosis pathways and delays activation of caspases to improve recombinant monoclonal antibody titre in fed-batch bioreactors.

    PubMed

    Tan, Janice G L; Lee, Yih Yean; Wang, Tianhua; Yap, Miranda G S; Tan, Tin Wee; Ng, Say Kong

    2015-05-01

    CHO cells are major production hosts for recombinant biologics including the rapidly expanding recombinant monoclonal antibodies (mAbs). Heat shock protein 27 (HSP27) expression was observed to be down-regulated towards the late-exponential and stationary phase of CHO fed-batch bioreactor cultures, whereas HSP27 was found to be highly expressed in human pathological cells and reported to have anti-apoptotic functions. These phenotypes suggest that overexpression of HSP27 is a potential cell line engineering strategy for improving robustness of CHO cells. In this work, HSP27 was stably overexpressed in CHO cells producing recombinant mAb and the effects of HSP27 on cell growth, volumetric production titer and product quality were assessed. Concomitantly, HSP27 anti-apoptosis functions in CHO cells were investigated. Stably transfected clones cultured in fed-batch bioreactors displayed 2.2-fold higher peak viable cell density, delayed loss of culture viability by two days and 2.3-fold increase in mAb titer without affecting the N-glycosylation profile, as compared to clones stably transfected with the vector backbone. Co-immunoprecipitation studies revealed HSP27 interactions with Akt, pro-caspase 3 and Daxx and caspase activity profiling showed delayed increase in caspase 2, 3, 8 and 9 activities. These results suggest that HSP27 modulates apoptosis signaling pathways and delays caspase activities to improve performance of CHO fed-batch bioreactor cultures. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Women who are well informed about prenatal genetic screening delay emotional attachment to their fetus.

    PubMed

    Rowe, Heather; Fisher, Jane; Quinlivan, Julie

    2009-03-01

    Prenatal maternal serum screening allows assessment of risk of chromosomal abnormalities in the fetus and is increasingly being offered to all women regardless of age or prior risk. However ensuring informed choice to participate in screening is difficult and the psychological implications of making an informed decision are uncertain. The aim of this study was to compare the growth of maternal-fetal emotional attachment in groups of women whose decisions about participation in screening were informed or not informed. A prospective longitudinal design was used. English speaking women were recruited in antenatal clinics prior to the offer of second trimester maternal screening. Three self-report questionnaires completed over the course of pregnancy used validated measures of informed choice and maternal-fetal emotional attachment. Attachment scores throughout pregnancy in informed and not-informed groups were compared in repeated measures analysis. 134 completed the first assessment (recruitment 73%) and 68 (58%) provided compete data. The informed group had significantly lower attachment scores (p = 0.023) than the not-informed group prior to testing, but scores were similar (p = 0.482) after test results were known. The findings raise questions about the impact of delayed maternal-fetal attachment and appropriate interventions to facilitate informed choice to participate in screening.

  8. An actidione resistant Candida tropicalis from custard apple juice.

    PubMed

    Onkarayya, H; Suresh, E R; Ethiraj, S

    1981-01-01

    An actidione resistant yeast, Candida tropicalis, was isolated from fermenting custard apple juice. Though a slight inhibition of growth was observed on the first day with 5000 ppm of actidione, growth was equal to control after one week. Sorbic acid at 500 ppm and above inhibited the growth of this yeast while sodium benzoate and potassium metabisulphite were unable to suppress the growth even at 1000 ppm. Fermentation and assimilation of different carbon sources were delayed in the presence of 1000 ppm of actidione suggesting the disruption of protein synthesis by actidione.

  9. How should we investigate children with growth failure?

    PubMed

    Léger, Juliane

    2017-06-01

    The early diagnosis of short stature is essential for effective management and treatment. Investigations for children with growth failure are required to distinguish between idiopathic short stature due to physiological variants (familial short stature, and constitutional delays of growth and puberty, or both), primary causes of short stature, such as syndromic and/or genetic defects and skeletal dysplasia, and secondary growth deficits due to endocrine or other chronic disorders such as celiac disease, Crohn's disease, malnutrition, renal, anorexia nervosa or other chronic diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Associations of Infant Feeding and Timing of Weight Gain and Linear Growth during Early Life with Childhood Blood Pressure: Findings from a Prospective Population Based Cohort Study

    PubMed Central

    Vrijkotte, Tanja G. M.; van Eijsden, Manon; Gemke, Reinoud J. B. J.

    2016-01-01

    Objective Small birth size and rapid postnatal growth have been associated with higher future blood pressure. The timing of these effects, the relative importance of weight gain and linear growth and the role of infant feeding need to be clarified. Methods We assessed how blood pressure relates to birth weight, infant and childhood growth and infant feeding (duration of exclusive breastfeeding and timing of introduction of complementary feeding) in 2227 children aged 5 years from a prospective cohort study (Amsterdam Born Children and their Development). Postnatal growth was represented by statistically independent measures of relative weight gain (weight gain independent of height) and linear growth in four age periods during infancy (0–1 month; 1–3 months; 3–6 months; 6–12 months) and from 12 months to 5 years. Results Lower birth weight was associated with higher childhood diastolic blood pressure (-0.38 mm Hg.SD-1; P = 0.007). Faster relative weight gain and linear growth after 1 month were positively associated with systolic and diastolic blood pressure. Associations of linear growth with systolic blood pressure ranged from 0.47 to 1.49 mm Hg.SD-1; P<0.01 for all. Coefficients were similar for different periods of infancy and also for relative weight gain and linear growth. Compared to breastfeeding <1 month, breastfeeding >1 month was associated with lower blood pressure (e.g. >6 months -1.56 mm Hg systolic blood pressure; P<0.001). Compared to >6 months, introduction of complementary feeding <6 months was associated with higher blood pressure (e.g. 4–6 months 0.91 mm Hg systolic blood pressure; P = 0.004). Conclusions After the age of one month faster growth in either weight or height is associated with higher childhood blood pressure. It is unknown whether faster weight gain and linear growth carry the same risk for adult hypertension and cardiovascular morbidity. Longer breastfeeding and delayed introduction of complementary feeding may be associated with lower adult blood pressure. PMID:27832113

  11. Associations of Infant Feeding and Timing of Weight Gain and Linear Growth during Early Life with Childhood Blood Pressure: Findings from a Prospective Population Based Cohort Study.

    PubMed

    de Beer, Marieke; Vrijkotte, Tanja G M; Fall, Caroline H D; van Eijsden, Manon; Osmond, Clive; Gemke, Reinoud J B J

    2016-01-01

    Small birth size and rapid postnatal growth have been associated with higher future blood pressure. The timing of these effects, the relative importance of weight gain and linear growth and the role of infant feeding need to be clarified. We assessed how blood pressure relates to birth weight, infant and childhood growth and infant feeding (duration of exclusive breastfeeding and timing of introduction of complementary feeding) in 2227 children aged 5 years from a prospective cohort study (Amsterdam Born Children and their Development). Postnatal growth was represented by statistically independent measures of relative weight gain (weight gain independent of height) and linear growth in four age periods during infancy (0-1 month; 1-3 months; 3-6 months; 6-12 months) and from 12 months to 5 years. Lower birth weight was associated with higher childhood diastolic blood pressure (-0.38 mm Hg.SD-1; P = 0.007). Faster relative weight gain and linear growth after 1 month were positively associated with systolic and diastolic blood pressure. Associations of linear growth with systolic blood pressure ranged from 0.47 to 1.49 mm Hg.SD-1; P<0.01 for all. Coefficients were similar for different periods of infancy and also for relative weight gain and linear growth. Compared to breastfeeding <1 month, breastfeeding >1 month was associated with lower blood pressure (e.g. >6 months -1.56 mm Hg systolic blood pressure; P<0.001). Compared to >6 months, introduction of complementary feeding <6 months was associated with higher blood pressure (e.g. 4-6 months 0.91 mm Hg systolic blood pressure; P = 0.004). After the age of one month faster growth in either weight or height is associated with higher childhood blood pressure. It is unknown whether faster weight gain and linear growth carry the same risk for adult hypertension and cardiovascular morbidity. Longer breastfeeding and delayed introduction of complementary feeding may be associated with lower adult blood pressure.

  12. Walking delays anticipatory postural adjustments but not reaction times in a choice reaction task.

    PubMed

    Haridas, C; Gordon, I T; Misiaszek, J E

    2005-06-01

    During standing, anticipatory postural adjustments (APAs) and focal movements are delayed while performing a choice reaction task, compared with a simple reaction task. We hypothesized that APAs and focal movements of a choice reaction task would be similarly delayed during walking. Furthermore, reaction times are delayed during walking compared with standing. We further hypothesized that APAs and focal movements would be delayed during walking, compared with standing, for both simple and choice reaction tasks. Subjects either walked or stood on a treadmill while holding on to stable handles. They were asked to push or pull on the handles in response to a visual cue. Muscle activity was recorded from muscles of the leg (APA) and arm (RT). Our results were in agreement with previous work showing APA onset was delayed in the choice reaction task compared with the simple reaction task. In addition, the interval between the onset of APA and focal movement activity increased with choice reaction tasks. The task of walking did not delay the onset of focal movement for either the simple or choice reaction tasks. Walking did delay the onset of the APA, but only during choice reaction tasks. The results suggest the added demand of walking does not significantly modify the control of focal arm movements. However, additional attentional demands while walking may compromise anticipatory postural control.

  13. Indian and sonic hedgehogs regulate synchondrosis growth plate and cranial base development and function.

    PubMed

    Young, Blanche; Minugh-Purvis, Nancy; Shimo, Tsuyoshi; St-Jacques, Benoit; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi; Koyama, Eiki; Pacifici, Maurizio

    2006-11-01

    The synchondroses consist of mirror-image growth plates and are critical for cranial base elongation, but relatively little is known about their formation and regulation. Here we show that synchondrosis development is abnormal in Indian hedgehog-null mice. The Ihh(-/-) cranial bases displayed reduced growth and chondrocyte proliferation, but chondrocyte hypertrophy was widespread. Rather than forming a typical narrow zone, Ihh(-/-) hypertrophic chondrocytes occupied an elongated central portion of each growth plate and were flanked by immature collagen II-expressing chondrocytes facing perichondrial tissues. Endochondral ossification was delayed in much of the Ihh(-/-) cranial bases but, surprisingly, was unaffected most posteriorly. Searching for an explanation, we found that notochord remnants near incipient spheno-occipital synchondroses at E13.5 expressed Sonic hedgehog and local chondrocytes expressed Patched, suggesting that Shh had sustained chondrocyte maturation and occipital ossification. Equally unexpected, Ihh(-/-) growth plates stained poorly with Alcian blue and contained low aggrecan transcript levels. A comparable difference was seen in cultured wild-type versus Ihh(-/-) synchondrosis chondrocytes. Treatment with exogenous Ihh did not fully restore normal proteoglycan levels in mutant cultures, but a combination of Ihh and BMP-2 did. In summary, Ihh is required for multiple processes during synchondrosis and cranial base development, including growth plate zone organization, chondrocyte orientation, and proteoglycan production. The cranial base appears to be a skeletal structure in which growth and ossification patterns along its antero-posterior axis are orchestrated by both Ihh and Shh.

  14. Longitudinal analysis of head and somatic growth in fetuses with congenital heart defects.

    PubMed

    Turan, Sifa; Rosenbloom, Joshua I; Hussein, Mostafa; Berg, Christoph; Gembruch, Ulrich; Baschat, Ahmet A; Turan, Ozhan M

    2017-02-01

    Fetal head and somatic growth dynamics differs in fetuses with congenital heart defects (CHD). We longitudinally characterized fetal head and somatic growth in relation to the type of CHD. Four hundred eleven exams from isolated CHD were compared with 1,219 controls. Head and somatic growth was assessed using head circumference (HC), brain volume (BrV = 1/6 × π × (HC/π)3)/2), fetal cephalization index (FCI = BrV/[estimated fetal weight]), and growth percentile. Umbilical and middle cerebral artery Doppler indices were obtained. CHD were grouped as: (1) d-transposition of great arteries (n = 11); (2) left ventricular outflow tract obstruction with retrograde isthmic flow (n = 18); (3) left ventricular outflow tract obstruction with antegrade isthmic flow (n = 16); (4) pulmonary outflow tract obstructions (n = 22). The smallest head size was seen in group 1. Growth asymmetry was diagnosed in group 2. Brain sparing was seen in groups 2 and 4 (p < 0.0001). HC and BrV percentiles decreased with advancing gestational age (p < 0.001) in group 2, and a significant drop was observed around 28 weeks. d-Transposition of great arteries and left-sided CHD leading to isthmic blood flow reversal are associated with delayed head growth. Prenatal evaluation of central hemodynamics in CHD may be contributive for predicting neurodevelopmental risks in CHD and help directing prenatal interventions. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:96-104, 2017. © 2016 Wiley Periodicals, Inc.

  15. Prepubertal exposure to arsenic(III) suppresses circulating insulin-like growth factor-1 (IGF-1) delaying sexual maturation in female rats.

    PubMed

    Reilly, Michael P; Saca, James C; Hamilton, Alina; Solano, Rene F; Rivera, Jesse R; Whitehouse-Innis, Wendy; Parsons, Jason G; Dearth, Robert K

    2014-04-01

    Arsenic (As) is a prevalent environmental toxin readily accessible for human consumption and has been identified as an endocrine disruptor. However, it is not known what impact As has on female sexual maturation. Therefore, in the present study, we investigated the effects of prepubertal exposure on mammary gland development and pubertal onset in female rats. Results showed that prepubertal exposure to 10 mg/kg of arsenite (As(III)) delayed vaginal opening (VO) and prepubertal mammary gland maturation. We determined that As accumulates in the liver, disrupts hepatocyte function and suppresses serum levels of the puberty related hormone insulin-like growth factor 1 (IGF-1) in prepubertal animals. Overall, this is the first study to show that prepubertal exposure to As(III) acts peripherally to suppress circulating levels of IGF-1 resulting in delayed sexual maturation. Furthermore, this study identifies a critical window of increased susceptibility to As(III) that may have a lasting impact on female reproductive function. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Prevention of Tartrate Crystallization in Wine by Hydrocolloids: The Mechanism Studied by Dynamic Light Scattering.

    PubMed

    Lankhorst, Peter P; Voogt, Benjamin; Tuinier, Remco; Lefol, Blandine; Pellerin, Patrice; Virone, Cristiana

    2017-10-11

    Young wines are supersaturated in potassium bitartrate, which induces rather uncontrolled crystallization processes. Delayed crystallization may occur even after bottling of the young wines, which is undesirable because it gives rise to a visual defect in the wine. Colloids such as mannoproteins, metatartaric acid, and carboxymethylcellulose are available on the market and may be added to delay crystallization. It has been a matter of debate whether such hydrocolloids prevent nucleation, growth of crystals, or both. It was the objective of this investigation to study the crystallization event by a new approach using dynamic light scattering and to clarify the mode of action of these hydrocolloids. To achieve this, model solutions and standardized wines were enriched with potassium bitartrate (KHT) to trigger crystallization. In this way, it was possible to distinguish between the influence of the hydrocolloids on nucleation and on crystal growth. It was found that the hydrocolloids do not prevent KHT nucleation. Instead, these compounds delay or even arrest the outgrowth of the crystals to a macroscopic, visual size.

  17. Growth and development of children prenatally exposed to telbivudine administered for the treatment of chronic hepatitis B in their mothers.

    PubMed

    Zeng, Huihui; Cai, Haodong; Wang, Ying; Shen, Ying

    2015-04-01

    We studied the growth and development of children prenatally exposed to telbivudine used to treat chronic hepatitis B virus (HBV) infection in their mothers. Maternal abnormalities during pregnancy and delivery and infant congenital anomalies, physical development status, developmental quotient (DQ), HBV vertical transmission status, and HBV vaccination outcomes of 54 infants were evaluated (2010-2013). No fetal abnormalities were observed during pregnancy or delivery. Postpartum, three infants (5.56%) had abnormalities: ankyloglossia, cutaneous hemangioma, and vaginal canal leak. Height and weight were within the normal range at birth and at 6 weeks, but were higher than the reference at 12 months (p<0.05). Body mass index increased gradually with age (p<0.05). DQ scores were normal (84.81%, 229/270) in 37 children (68.52%), abnormal or suspicious for a developmental delay (15.19%, 41/270) in 17 children (31.48%), and indicated a developmental delay (4.07%, 11/270) in seven children (12.96%). There were no significant differences in developmental delay between children prenatally exposed to telbivudine and controls (p>0.05). HBV vertical transmission was successfully blocked in all infants. The effective HBV vaccination rate was 98.15% (53/54). The growth and development of children prenatally exposed to telbivudine was normal, indicating that telbivudine treatment during pregnancy is safe and effective. Copyright © 2015. Published by Elsevier Ltd.

  18. Delay of gratification by orangutans (Pongo pygmaeus) in the accumulation task.

    PubMed

    Parrish, Audrey E; Perdue, Bonnie M; Stromberg, Erin E; Bania, Amanda E; Evans, Theodore A; Beran, Michael J

    2014-05-01

    There is considerable evidence indicating that chimpanzees can delay gratification for extended time intervals, particularly in the accumulation task in which food items accumulate within a participant's reach until the participant begins to consume them. However, there is limited evidence that other ape species might also exhibit this capacity, despite there being a number of similar studies indicating that nonape species (e.g., monkeys and birds) can delay gratification, but not for nearly as long as chimpanzees. To help define the taxonomic distribution of delay of gratification behavior in the order Primates, we tested 6 orangutans in the current experiments and compared their performance with comparable data from a previous study with capuchin monkeys. We varied delay length and visibility of the items that were still available for accumulation to determine the impact of these factors on performance. Species differences on the accumulation task emerged when comparing the current data to data from a previous study. Orangutans outperformed capuchin monkeys, suggesting that ape species may generally show better delay of gratification and delay maintenance abilities than monkeys. However, more studies are necessary to rule out alternative hypotheses on the distribution of delay maintenance abilities across primate species. ©2014 APA, all rights reserved.

  19. Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model.

    PubMed

    Renner, Christof; Zemitzsch, Nadine; Fuchs, Beate; Geiger, Kathrin D; Hermes, Matthias; Hengstler, Jan; Gebhardt, Rolf; Meixensberger, Jürgen; Gaunitz, Frank

    2010-01-06

    It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu), were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 microl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p < 0.0003) than untreated animals, confirming that carnosine affects proliferation in vivo. As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.

  20. Delayed puberty in girls

    MedlinePlus

    ... the ovaries A tumor in the pituitary gland Turner syndrome , a genetic disorder ... child's growth: The MAGIC Foundation -- www.magicfoundation.org Turner Syndrome Society of the United States -- www.turnersyndrome.org

  1. Embryonic delay in growth and development related to confined placental trisomy 16 mosaicism, diagnosed by I-Space Virtual Reality.

    PubMed

    Verwoerd-Dikkeboom, Christine M; van Heesch, Peter N A C M; Koning, Anton H J; Galjaard, Robert-Jan H; Exalto, Niek; Steegers, Eric A P

    2008-11-01

    To demonstrate the use of a novel three-dimensional (3D) virtual reality (VR) system in the visualization of first trimester growth and development in a case of confined placental trisomy 16 mosaicism (CPM+16). Case report. Prospective study on first trimester growth using a 3D VR system. A 34-year-old gravida 1, para 0 was seen weekly in the first trimester for 3D ultrasound examinations. Chorionic villus sampling was performed because of an enlarged nuchal translucency (NT) measurement and low pregnancy-associated plasma protein-A levels, followed by amniocentesis. Amniocentesis revealed a CPM+16. On two-dimensional (2D) and 3D ultrasound no structural anomalies were found with normal fetal Dopplers. Growth remained below the 2.3 percentile. At 37 weeks, a female child of 2010 g (<2.5 percentile) was born. After birth, growth climbed to the 50th percentile in the first 2 months. The I-Space VR system provided information about phenotypes not obtainable by standard 2D ultrasound. In this case, the delay in growth and development could be observed very early in pregnancy. Since first trimester screening programs are still improving and becoming even more important, systems such as the I-Space open a new era for in vivo studies on the physiologic and pathologic processes involved in embryogenesis.

  2. Persistent G. lamblia impairs growth in a murine malnutrition model

    PubMed Central

    Bartelt, Luther A.; Roche, James; Kolling, Glynis; Bolick, David; Noronha, Francisco; Naylor, Caitlin; Hoffman, Paul; Warren, Cirle; Singer, Steven; Guerrant, Richard

    2013-01-01

    Giardia lamblia infections are nearly universal among children in low-income countries and are syndemic with the triumvirate of malnutrition, diarrhea, and developmental growth delays. Amidst the morass of early childhood enteropathogen exposures in these populations, G. lamblia–specific associations with persistent diarrhea, cognitive deficits, stunting, and nutrient deficiencies have demonstrated conflicting results, placing endemic pediatric giardiasis in a state of equipoise. Many infections in endemic settings appear to be asymptomatic/subclinical, further contributing to uncertainty regarding a causal link between G. lamblia infection and developmental delay. We used G. lamblia H3 cyst infection in a weaned mouse model of malnutrition to demonstrate that persistent giardiasis leads to epithelial cell apoptosis and crypt hyperplasia. Infection was associated with a Th2-biased inflammatory response and impaired growth. Malnutrition accentuated the severity of these growth decrements. Faltering malnourished mice exhibited impaired compensatory responses following infection and demonstrated an absence of crypt hyperplasia and subsequently blunted villus architecture. Concomitantly, severe malnutrition prevented increases in B220+ cells in the lamina propria as well as mucosal Il4 and Il5 mRNA in response to infection. These findings add insight into the potential role of G. lamblia as a “stunting” pathogen and suggest that, similarly, malnourished children may be at increased risk of G. lamblia–potentiated growth decrements. PMID:23728173

  3. Persistent G. lamblia impairs growth in a murine malnutrition model.

    PubMed

    Bartelt, Luther A; Roche, James; Kolling, Glynis; Bolick, David; Noronha, Francisco; Naylor, Caitlin; Hoffman, Paul; Warren, Cirle; Singer, Steven; Guerrant, Richard

    2013-06-01

    Giardia lamblia infections are nearly universal among children in low-income countries and are syndemic with the triumvirate of malnutrition, diarrhea, and developmental growth delays. Amidst the morass of early childhood enteropathogen exposures in these populations, G. lamblia–specific associations with persistent diarrhea, cognitive deficits, stunting, and nutrient deficiencies have demonstrated conflicting results, placing endemic pediatric giardiasis in a state of equipoise. Many infections in endemic settings appear to be asymptomatic/ subclinical, further contributing to uncertainty regarding a causal link between G. lamblia infection and developmental delay. We used G. lamblia H3 cyst infection in a weaned mouse model of malnutrition to demonstrate that persistent giardiasis leads to epithelial cell apoptosis and crypt hyperplasia. Infection was associated with a Th2-biased inflammatory response and impaired growth. Malnutrition accentuated the severity of these growth decrements. Faltering malnourished mice exhibited impaired compensatory responses following infection and demonstrated an absence of crypt hyperplasia and subsequently blunted villus architecture. Concomitantly, severe malnutrition prevented increases in B220+ cells in the lamina propria as well as mucosal Il4 and Il5 mRNA in response to infection. These findings add insight into the potential role of G. lamblia as a "stunting" pathogen and suggest that, similarly, malnourished children may be at increased risk of G. lamblia– potentiated growth decrements.

  4. Interact to Survive: Phyllobacterium brassicacearum Improves Arabidopsis Tolerance to Severe Water Deficit and Growth Recovery

    PubMed Central

    Bresson, Justine; Vasseur, François; Dauzat, Myriam; Labadie, Marc; Varoquaux, Fabrice; Touraine, Bruno; Vile, Denis

    2014-01-01

    Mutualistic bacteria can alter plant phenotypes and confer new abilities to plants. Some plant growth-promoting rhizobacteria (PGPR) are known to improve both plant growth and tolerance to multiple stresses, including drought, but reports on their effects on plant survival under severe water deficits are scarce. We investigated the effect of Phyllobacterium brassicacearum STM196 strain, a PGPR isolated from the rhizosphere of oilseed rape, on survival, growth and physiological responses of Arabidopsis thaliana to severe water deficits combining destructive and non-destructive high-throughput phenotyping. Soil inoculation with STM196 greatly increased the survival rate of A. thaliana under several scenarios of severe water deficit. Photosystem II efficiency, assessed at the whole-plant level by high-throughput fluorescence imaging (F v/F m), was related to the probability of survival and revealed that STM196 delayed plant mortality. Inoculated surviving plants tolerated more damages to the photosynthetic tissues through a delayed dehydration and a better tolerance to low water status. Importantly, STM196 allowed a better recovery of plant growth after rewatering and stressed plants reached a similar biomass at flowering than non-stressed plants. Our results highlight the importance of plant-bacteria interactions in plant responses to severe drought and provide a new avenue of investigations to improve drought tolerance in agriculture. PMID:25226036

  5. Relationship between cervical vertebral maturation and mandibular growth.

    PubMed

    Ball, Gina; Woodside, Donald; Tompson, Bryan; Hunter, W Stuart; Posluns, James

    2011-05-01

    The cervical vertebrae have been proposed as a method of determining biologic maturity. The purposes of this study were to establish a pattern of mandibular growth and to relate this pattern to the stages of cervical vertebral maturation. Cephalometric radiographs, taken annually from ages 9 to 18 years, were evaluated for 90 boys from the Burlington Growth Center, Toronto, Ontario, Canada. Mandibular lengths were measured from articulare to gnathion, and incremental growth was determined. Cervical vertebral maturation stages were assessed by using a 6-stage method. Advanced, average, and delayed maturation groups were established. The prepubertal mandibular growth minimum velocity occurred during cervical stages 1 through 4 (P = 0.7327). Peak mandibular growth velocity occurred most frequently during stage 4 in all 3 maturation groups, with a statistical difference in the average and delayed groups (P <0.0001) and the advanced group (P = 0.0143). The average number of years spent in stage 4 was 3.79 (P <0.0001). The average amount of mandibular growth occurring during stage 4 was 9.40 mm (P <0.0001). The average amount of growth in stages 5 and 6 combined was 7.09 mm. Progression from cervical stages 1 through 6 does not occur annually; time spent in each stage varies depending on the stage and the maturation group. Cervical vertebral maturation stages cannot accurately identify the mandibular prepubertal growth minimum and therefore cannot predict the onset of the peak in mandibular growth. The cervical vertebral maturation stages should be used with other methods of biologic maturity assessment when considering both dentofacial orthopedic treatment and orthognathic surgery. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  6. Radiologic manifestations in the musculoskeletal system of miscellaneous endocrine disorders.

    PubMed

    Chew, F S

    1991-01-01

    The manifestations of endocrine derangements in the musculoskeletal system in infancy and childhood are disturbances in growth and maturation and in adulthood are disturbances in maintenance and metabolism. Hypercortisolism during skeletal immaturity suppresses growth. In the adult, hypercortisolism leads to osteoporosis, osteonecrosis, and muscle wasting. Deficiency of growth hormone during skeletal development results in short stature. An excess of growth hormone in a skeletally immature individual results in gigantism, an excess in a skeletally mature individual results in acromegaly. Patients with gigantism have extreme height with normal body proportions. Musculoskeletal manifestations of acromegaly include soft-tissue thickening, vertebral body enlargement, characteristic hand and foot changes, and enthesal bony proliferation. Hyperthyroidism causes catabolism of protein and loss of connective tissue, which manifest as muscle wasting. Deficient levels of thyroid hormone cause defects in growth and development. Severe growth retardation from congenital hypothyroidism is rare because neonatal screening recognizes the disorder and leads to early treatment. The skeletal manifestation of hypergonadism in children is precocious growth and early skeletal maturation. Although the initial precocious growth spurt results in a tall child, early closure of the growth plates results in a short adult. Hypogonadism in the prepubertal child results in delayed adolescence and delayed skeletal maturation. Diabetes mellitus in childhood results in decreased growth, a phenomenon presumed to be secondary to nutritional abnormalities. Generalized osteoporosis and short stature are common. In the adult, generalized osteoporosis may accompany insulin-dependent diabetes mellitus if obesity is absent. Calcification of interdigital arteries of the foot is common in diabetics and uncommon in other conditions. Additional skeletal manifestations relate to complications of diabetes such as peripheral neuropathy and diabetic foot disease.

  7. Growth Coordination During Drosophila melanogaster Imaginal Disc Regeneration Is Mediated by Signaling Through the Relaxin Receptor Lgr3 in the Prothoracic Gland.

    PubMed

    Jaszczak, Jacob S; Wolpe, Jacob B; Bhandari, Rajan; Jaszczak, Rebecca G; Halme, Adrian

    2016-10-01

    Damage to Drosophila melanogaster imaginal discs activates a regeneration checkpoint that (1) extends larval development and (2) coordinates the regeneration of the damaged disc with the growth of undamaged discs. These two systemic responses to damage are both mediated by Dilp8, a member of the insulin/insulin-like growth factor/relaxin family of peptide hormones, which is released by regenerating imaginal discs. Growth coordination between regenerating and undamaged imaginal discs is dependent on Dilp8 activation of nitric oxide synthase (NOS) in the prothoracic gland (PG), which slows the growth of undamaged discs by limiting ecdysone synthesis. Here we demonstrate that the Drosophila relaxin receptor homolog Lgr3, a leucine-rich repeat-containing G-protein-coupled receptor, is required for Dilp8-dependent growth coordination and developmental delay during the regeneration checkpoint. Lgr3 regulates these responses to damage via distinct mechanisms in different tissues. Using tissue-specific RNA-interference disruption of Lgr3 expression, we show that Lgr3 functions in the PG upstream of NOS, and is necessary for NOS activation and growth coordination during the regeneration checkpoint. When Lgr3 is depleted from neurons, imaginal disc damage no longer produces either developmental delay or growth inhibition. To reconcile these discrete tissue requirements for Lgr3 during regenerative growth coordination, we demonstrate that Lgr3 activity in both the CNS and PG is necessary for NOS activation in the PG following damage. Together, these results identify new roles for a relaxin receptor in mediating damage signaling to regulate growth and developmental timing. Copyright © 2016 by the Genetics Society of America.

  8. THE EFFECT OF ADRENAL STEROIDS, CORTICOTROPIN, AND GROWTH HORMONE ON RESISTANCE TO EXPERIMENTAL INFECTIONS

    PubMed Central

    Kass, Edward H.; Lundgren, Marguerite M.; Finland, Maxwell

    1954-01-01

    Cortisone acetate, hydrocortisone, and hydrocortisone acetate depress the resistance of mice to pneumococcal and influenza viral infections, although hydrocortisone acetate is somewhat less effective than the free alcohol, when given subcutaneously. Pituitary adrenocorticotropin, even in highly purified form and in oil and beeswax, does not significantly alter the resistance of mice to these experimental infections, even when given in doses which may cause profound eosinopenia, lymphopenia, and weight loss, and which are at the limit of tolerance of the animals. Corticosterone depresses resistance to pneumococcal infections significantly, but fails to alter resistance to influenza viral infections. The findings suggest that murine adrenals may produce one of the known adrenal steroids such as corticosterone along with another steroid, or may produce a steroid other than cortisone, hydrocortisone, or corticosterone. When resistance is decreased by adrenal steroids, survival time is invariably shortened, and the effect of the steroid hormones is frequently demonstrable within the 1st day after infection with pneumococci, making it unlikely that the depression of resistance that is seen is primarily due to depression of antibody formation. A single dose of 5 mg. of cortisone may cause depression of resistance and may decrease the survival time for 3 to 6 days afterward. Growth hormone (somatotropic hormone) in highly purified form, and in the doses used, did not overcome the weight loss induced by cortisone, but the animals treated with growth hormone and cortisone regained their lost weight more rapidly than those receiving cortisone alone. Growth hormone alone caused a slight increase in the rate of gain in weight over controls. Growth hormone alone did not increase resistance to infection, and did not increase the survival time, in mice infected with either pneumococci or influenza virus. Growth hormone in various dosages failed to overcome the effect of cortisone in depressing resistance to these infections. Cortisone, hydrocortisone, corticosterone, and corticotropin did not alter significantly the titers of influenza virus attained in the murine lungs during the first 2 days after infection, but cortisone and hydrocortisone markedly delayed the rate at which virus titers declined during the subsequent 6 days. Corticosterone and corticotropin delayed the rate at which the titers declined but slightly, and growth hormone had no apparent effect, as compared with controls. Growth hormone did not overcome the effect of cortisone and hydrocortisone on viral titers. No detectable antibody was found as late as 6 days after infection, in controls or in hormone-treated animals. PMID:13118066

  9. In Vitro and in vivo Evaluation of Electrochemotherapy with trans-platinum Analogue trans-[PtCl2(3-Hmpy)2

    PubMed Central

    Cemazar, Maja; Sersa, Gregor; Scancar, Janez; Grabner, Sabina

    2017-01-01

    Abstract Background Cisplatin is used in cancer therapy, but its side effects and acquired resistance to cisplatin have led to the synthesis and evaluation of new platinum compounds. Recently, the synthesized platinum compound trans-[PtCl2(3-Hmpy)2] (3-Hmpy = 3-hydroxymethylpyridine) (compound 2) showed a considerable cytotoxic and antitumour effectiveness. To improve compound 2 cytotoxicity in vitro and antitumour effectiveness in vivo, electroporation was used as drug delivery approach to increase membrane permeability (electrochemotherapy). Materials and methods In vitro, survival of sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive) was determined using a clonogenic assay after treatment with compound 2 or cisplatin electrochemotherapy. In vivo, the antitumour effectiveness of electrochemotherapy with compound 2 or cisplatin was evaluated using a tumour growth delay assay. In addition, platinum in the serum, tumours and platinum bound to the DNA in the cells were performed using inductively coupled plasma mass spectrometry. Results In vitro, cell survival after treatment with compound 2 electrochemotherapy was significantly decreased in all tested sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive). However, this effect was less pronounced compared to cisplatin. Interestingly, the enhancement factor (5-fold) of compound 2 cytotoxicity was equal in cisplatin-sensitive TBLCl2 and cisplatin-resistant TBLCl2Pt cells. In vivo, the growth delay of subcutaneous tumours after treatment with compound 2 electrochemotherapy was lower compared to cisplatin. The highest antitumour effectiveness after cisplatin or compound 2 electrochemotherapy was obtained in TBLCl2 tumours, resulting in 67% and 11% of tumour cures, respectively. Compound 2 induced significantly smaller loss of animal body weight compared to cisplatin. Furthermore, platinum amounts in tumours after compound 2 or cisplatin electrochemotherapy were approximately 2-fold higher compared to the drug treatment only, and the same increase of platinum bound to DNA was observed. Conclusions The obtained results in vitro and in vivo suggest compound 2 as a potential antitumour agent in electrochemotherapy. PMID:28959166

  10. Introducing time delay in the evolution of new technology: the case study of nanotechnology

    NASA Astrophysics Data System (ADS)

    Georgalis, Evangelos E.; Aifantis, Elias C.

    2013-12-01

    Starting with Feynman's "There's Plenty of Room at the Bottom" prophetic lecture at Caltech in the 1960s, the term "nanotechnology" was first coined in the scientific literature in the 1980s. This was followed by the unprecedented growth in the corresponding scientific field in 2000 due to the financial incentive provided by President Clinton in the US, followed up by similar efforts in Europe, Japan, China and Russia. Today, nanotechnology has become a driving force for economic development, with applications in all fields of engineering, information technology, transport and energy, as well as biology and medicine. Thus, it is important to forecast its future growth and evolution on the basis of two different criteria: (1) the government and private capital invested in related activities, and (2) the number of scientific publications and popular articles dedicated to this field. This article aims to extract forecasts on the evolution of nanotechnology, using the standard logistic equation that result in familiar sigmoid curves, as well as to explore the effect of time delay on its evolution. Time delay is commonly known from previous biological and ecological models, in which time lag is either already known or can be experimentally measured. In contrast, in the case of a new technology, we must first define the method for determining time delay and then interpret its existence and role. Then we describe the implications that time delay may have on the stability of the sigmoidal behavior of nanotechnology evolution and on the related oscillations that may appear.

  11. Delayed changes in auditory status in cochlear implant users with preserved acoustic hearing.

    PubMed

    Scheperle, Rachel A; Tejani, Viral D; Omtvedt, Julia K; Brown, Carolyn J; Abbas, Paul J; Hansen, Marlan R; Gantz, Bruce J; Oleson, Jacob J; Ozanne, Marie V

    2017-07-01

    This retrospective review explores delayed-onset hearing loss in 85 individuals receiving cochlear implants designed to preserve acoustic hearing at the University of Iowa Hospitals and Clinics between 2001 and 2015. Repeated measures of unaided behavioral audiometric thresholds, electrode impedance, and electrically evoked compound action potential (ECAP) amplitude growth functions were used to characterize longitudinal changes in auditory status. Participants were grouped into two primary categories according to changes in unaided behavioral thresholds: (1) stable hearing or symmetrical hearing loss and (2) delayed loss of hearing in the implanted ear. Thirty-eight percent of this sample presented with delayed-onset hearing loss of various degrees and rates of change. Neither array type nor insertion approach (round window or cochleostomy) had a significant effect on prevalence. Electrode impedance increased abruptly for many individuals exhibiting precipitous hearing loss; the increase was often transient. The impedance increases were significantly larger than the impedance changes observed for individuals with stable or symmetrical hearing loss. Moreover, the impedance changes were associated with changes in behavioral thresholds for individuals with a precipitous drop in behavioral thresholds. These findings suggest a change in the electrode environment coincident with the change in auditory status. Changes in ECAP thresholds, growth function slopes, and suprathreshold amplitudes were not correlated with changes in behavioral thresholds, suggesting that neural responsiveness in the region excited by the implant is relatively stable. Further exploration into etiology of delayed-onset hearing loss post implantation is needed, with particular interest in mechanisms associated with changes in the intracochlear environment. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Clinical review: Distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests.

    PubMed

    Harrington, Jennifer; Palmert, Mark R

    2012-09-01

    Determining the etiology of delayed puberty during initial evaluation can be challenging. Specifically, clinicians often cannot distinguish constitutional delay of growth and puberty (CDGP) from isolated hypogonadotropic hypogonadism (IHH), with definitive diagnosis of IHH awaiting lack of spontaneous puberty by age 18 yr. However, the ability to make a timely, correct diagnosis has important clinical implications. The aim was to describe and evaluate the literature regarding the ability of diagnostic tests to distinguish CDGP from IHH. A PubMed search was performed using key words "puberty, delayed" and "hypogonadotropic hypogonadism," and citations within retrieved articles were reviewed to identify studies that assessed the utility of basal and stimulation tests in the diagnosis of delayed puberty. Emphasis was given to a test's ability to distinguish prepubertal adolescents with CDGP from those with IHH. Basal gonadotropin and GnRH stimulation tests have limited diagnostic specificity, with overlap in gonadotropin levels between adolescents with CDGP and IHH. Stimulation tests using more potent GnRH agonists and/or human chorionic gonadotropin may have better discriminatory value, but small study size, lack of replication of diagnostic thresholds, and prolonged protocols limit clinical application. A single inhibin B level in two recent studies demonstrated good differentiation between groups. Distinguishing IHH from CDGP is an important clinical issue. Basal inhibin B may offer a simple, discriminatory test if results from recent studies are replicated. However, current literature does not allow for recommendation of any diagnostic test for routine clinical use, making this an important area for future investigation.

  13. Etanercept Injection

    MedlinePlus

    ... own joints, causing pain, swelling, and loss of function) in adults, psoriatic arthritis (condition that causes joint ... its own joints, causing pain, swelling, loss of function, and delays in growth and development) in children ...

  14. Maternal synthesis of abscisic acid controls seed development and yield in Nicotiana plumbaginifolia.

    PubMed

    Frey, Anne; Godin, Béatrice; Bonnet, Magda; Sotta, Bruno; Marion-Poll, Annie

    2004-04-01

    The role of maternally derived abscisic acid (ABA) during seed development has been studied using ABA-deficient mutants of Nicotiana plumbaginifolia Viviani. ABA deficiency induced seed abortion, resulting in reduced seed yield, and delayed growth of the remaining embryos. Mutant grafting onto wild-type stocks and reciprocal crosses indicated that maternal ABA, synthesized in maternal vegetative tissues and translocated to the seed, promoted early seed development and growth. Moreover ABA deficiency delayed both seed coat pigmentation and capsule dehiscence. Mutant grafting did not restore these phenotypes, indicating that ABA synthesized in the seed coat and capsule envelope may have a positive effect on capsule and testa maturation. Together these results shed light on the positive role of maternal ABA during N. plumbaginifolia seed development.

  15. Asymmetric effects of cooler and warmer winters on beech phenology last beyond spring

    NASA Astrophysics Data System (ADS)

    Signarbieux, Constant; Toledano, Ester; Sangines, Paula; Fu, Yongshuo; Schlaepfer, Rodolphe; Buttler, Alexandre; Vitasse, Yann

    2017-04-01

    In temperate trees, the timing of plant growth onset and cessation affect biogeochemical cycles, water and energy balance. Currently, phenological studies largely focus on specific phenophases and on their responses to warming. How differently spring phenology responds to the warming and cooling, and affects the subsequent phases, has not been well investigated. Here, we exposed saplings of Fagus sylvatica L. to warmer and cooler climate during the winter 2013-2014 by conducting a reciprocal transplant experiment between two elevations (1340 vs. 371 m.a.s.l., ca. 6°C difference) in the Swiss Jura mountains. To test the legacy effects of earlier or later budburst on the budset timing, saplings were moved back to their original elevation shortly after the occurrence of budburst in spring 2014. One degree decrease of air temperature resulted in a delay of 10.9 days in budburst dates, whereas one degree of warming advanced the date by 8.8 days. Interestingly, we found an asymmetric effect of the warmer winter vs. cooler winter on the budset timing in autumn: saplings experiencing a cooler winter showed a delay of 31 days in their budset timing compared to the control, whereas saplings experiencing a warmer winter showed 10 days earlier budset. The dependency of spring over autumn phenophases might be partly explained by the building up of the non-structural carbohydrate storage and suggests that the potential delay in growth cessation due to global warming might be smaller than expected. We did not find a significant correlation in budburst dates between 2014 and 2015, indicating that the legacy effects of the different phenophases might be reset during each winter. Adapting phenological models to the whole annual phenological cycle, and considering the different response to cooling and warming, would improve predictions of tree phenology under future climate warming conditions.

  16. Palivizumab prophylaxis in infants with cystic fibrosis does not delay first isolation of Pseudomonas aeruginosa or Staphylococcus aureus.

    PubMed

    Buchs, Clélia; Dalphin, Marie-Laure; Sanchez, Stéphane; Perceval, Marie; Coutier, Laurianne; Mainguy, Catherine; Kassaï-Koupaï, Behrouz; Reix, Philippe

    2017-07-01

    Respiratory syncytial virus (RSV) infections may worsen cystic fibrosis (CF) lung disease and favor Pseudomonas aeruginosa (Pa) or Staphylococcus aureus (Sa) acquisition, which is of particular importance in the youngest patients. We aimed to determine the effectiveness of PVZ on microbiological outcomes in young children with CF. We conducted a retrospective case-control study to compare these outcomes in children who systematically received PVZ (PVZ+; n = 40) or not (PVZ-; n = 140). One case was matched with at least three same-gender controls born the same year and month. Median (range) age at first Pa isolation was not statistically different between PVZ- (12.3 [3.8-32.6] months) and PVZ+ (10.4 [1.2-33.0] months; p = 0.953) patients. A similar trend was found for Sa (PVZ+: 6.4 [2.0-59.0] months; PVZ-: 3.8 [0.1-74.1] months; p = 0.191). The proportion of Pa isolations by 3 years of age did not differ between groups (PVZ+ 40% vs. PVZ- 41.4%), but this proportion was higher for Sa in the PVZ+ group (97%) than in the PVZ- group (85%; p = 0.001). Healthcare consumption and growth outcomes did not significantly differ between groups. Systematic PVZ use did not delay key pathogen acquisition in young children with CF. What is known: • Palivizumab is the only available monoclonal antibody against respiratory syncytial virus infection. • Whether or not it is useful in infants with cystic fibrosis remains controversial. What is new: • Palivizumab does not delay key pathogens (Pseudomonas aeruginosa, Staphylococcus aureus) first isolation in young children with cystic fibrosis. • Palivizumab does not reduce healthcare consumption or improve growth during the first 3 years of life of young children with cystic fibrosis.

  17. Concurrent versus sequential sorafenib therapy in combination with radiation for hepatocellular carcinoma.

    PubMed

    Wild, Aaron T; Gandhi, Nishant; Chettiar, Sivarajan T; Aziz, Khaled; Gajula, Rajendra P; Williams, Russell D; Kumar, Rachit; Taparra, Kekoa; Zeng, Jing; Cades, Jessica A; Velarde, Esteban; Menon, Siddharth; Geschwind, Jean F; Cosgrove, David; Pawlik, Timothy M; Maitra, Anirban; Wong, John; Hales, Russell K; Torbenson, Michael S; Herman, Joseph M; Tran, Phuoc T

    2013-01-01

    Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design.

  18. Concurrent versus Sequential Sorafenib Therapy in Combination with Radiation for Hepatocellular Carcinoma

    PubMed Central

    Chettiar, Sivarajan T.; Aziz, Khaled; Gajula, Rajendra P.; Williams, Russell D.; Kumar, Rachit; Taparra, Kekoa; Zeng, Jing; Cades, Jessica A.; Velarde, Esteban; Menon, Siddharth; Geschwind, Jean F.; Cosgrove, David; Pawlik, Timothy M.; Maitra, Anirban; Wong, John; Hales, Russell K.; Torbenson, Michael S.; Herman, Joseph M.; Tran, Phuoc T.

    2013-01-01

    Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design. PMID:23762417

  19. In Vitro and In Vivo Enhancement of Chemoradiation Using the Oral PARP Inhibitor ABT-888 in Colorectal Cancer Cells

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

    Shelton, Joseph W., E-mail: jwshelt@emory.edu; Waxweiler, Timothy V.; Landry, Jerome

    2013-07-01

    Purpose: Poly(ADP-ribose) polymerase plays a critical role in the recognition and repair of DNA single-strand breaks and double-strand breaks (DSBs). ABT-888 is an orally available inhibitor of this enzyme. This study seeks to evaluate the use of ABT-888 combined with chemotherapy and radiation therapy (RT) in colorectal carcinoma models. Methods and Materials: RT clonogenic assays were performed on HCT116 and HT29 cells treated with 5-fluorouracil, irinotecan, or oxaliplatin with or without ABT. The surviving fraction at 2 Gy and dose-modifying factor at 10% survival were analyzed. Synergism was assessed by isobologram analysis for combination therapies. γH2AX and neutral comet assaysmore » were performed to assess the effect of therapy on DSB formation/repair. In vivo assessments were made by use of HCT116 cells in a xenograft mouse model. Tumor growth delay was measured at a volume of 500 mm{sup 3}. Results: Both lines were radiosensitized by ABT alone, and ABT further increased chemotherapy dose-modifying factors to the 1.6 to 1.8 range. All combinations were synergistic (combination indices <0.9). ABT treatment significantly increased DSB after RT (γH2AX, 69% vs 43%; P=.017) and delayed repair. We found tumor growth delays of 7.22 days for RT; 11.90 days for RT and ABT; 13.5 days for oxaliplatin, RT, and ABT; 14.17 days for 5-fluorouracil, RT, and ABT; and 23.81 days for irinotecan, RT, and ABT. Conclusion: ABT-888 radiosensitizes at similar or higher levels compared with classic chemotherapies and acts synergistically with these chemotherapies to enhance RT effects. In vivo confirmation of these results indicates a potential role for combining its use with existing chemoradiation regimens.« less

  20. The effects of density dependent resource limitation on size of wild reindeer.

    PubMed

    Skogland, Terje

    1983-11-01

    A density-dependent decrement in size for wild reindeer from 12 different Norwegian herds at 16 different densities was shown using lower jawbone-length as the criterion of size. This criterion was tested and found to adequately predict body size of both bucks and does. Lactation in does did not affect jaw length but significantly affected dressed weights.A decrement in the size of does as a result of gross density was found. This size decrement was further analysed in relation to the habitat densities in winter (R 2 =0.85) and in summer (R 2 =0.75) separately, in order to estimate the relative effects of each factor. For herds with adequate food in winter (no signs of overgrazing of lichens) density in relation to summer habitat and mires yielded the highest predictive power in a multiple regression. For herds with adequate summer pastures, densities per winter habitat and lichen volumes showed likewise a highly significant correlation. The inclusion of the lichen volume data in the regression increased its predictive power. The major effect of resource limitation was to delay the time of calving because a maternal carry-over effect allowed the calf a shorter period of growth to be completed during its first summer. Neonate size at birth was highly correlated with maternal size regardless of the mean calving date although the latter was significantly delayed for small-sized does in food resource-limited herds. Likewise the postnatal growth rate of all calves were not significantly different during 50 days postpartum regardless of maternal conditions in winter feeding. The summer growth rates of bucks ≧1 year did not vary significantly between herds. The age of maturity of food resource-limited does was delayed by one year and growth ceased after the initiation of reproduction. This shows that under conditions of limited resources the does with delayed births of calves allocated less energy to body growth simply because they had less time to replenish body reserves once they were freed of the energetic demands of lactation. The overriding effects of such limitation of food resources is thus to produce a time-lag for the completition of all the important life-history events, such as growth, maintenance and reproduction. From a theoretical point of view, i.e. according to the reproductive effort model their only option is to try to overcome this time limitation to reproductive success.

  1. Anti-aging Effect of Transplanted Amniotic Membrane Mesenchymal Stem Cells in a Premature Aging Model of Bmi-1 Deficiency

    PubMed Central

    Xie, Chunfeng; Jin, Jianliang; Lv, Xianhui; Tao, Jianguo; Wang, Rong; Miao, Dengshun

    2015-01-01

    To determine whether transplanted amniotic membrane mesenchymal stem cells (AMSCs) ameliorated the premature senescent phenotype of Bmi-1-deficient mice, postnatal 2-day-old Bmi-1−/− mice were injected intraperitoneally with the second-passage AMSCs from amniotic membranes of β-galactosidase (β-gal) transgenic mice or wild-type (WT) mice labeled with DiI. Three reinjections were given, once every seven days. Phenotypes of 5-week-old β-gal+ AMSC-transplanted or 6-week-old DiI+ AMSC-transplanted Bmi-1−/− mice were compared with vehicle-transplanted Bmi-1−/− and WT mice. Vehicle-transplanted Bmi-1−/− mice displayed growth retardation and premature aging with decreased cell proliferation and increased cell apoptosis; a decreased ratio and dysmaturity of lymphocytic series; premature osteoporosis with reduced osteogenesis and increased adipogenesis; redox imbalance and DNA damage in multiple organs. Transplanted AMSCs carried Bmi-1 migrated into multiple organs, proliferated and differentiated into multiple tissue cells, promoted growth and delayed senescence in Bmi-1−/− transplant recipients. The dysmaturity of lymphocytic series were ameliorated, premature osteoporosis were rescued by promoting osteogenesis and inhibiting adipogenesis, the oxidative stress and DNA damage in multiple organs were inhibited by the AMSC transplantation in Bmi-1−/− mice. These findings indicate that AMSC transplantation ameliorated the premature senescent phenotype of Bmi-1-deficient mice and could be a novel therapy to delay aging and prevent aging-associated degenerative diseases. PMID:26370922

  2. Microprocessor-controlled Nd:YAG laser for hyperthermia induction in the RIF-1 tumor.

    PubMed

    Waldow, S M; Russell, G E; Wallner, P E

    1992-01-01

    Near-infrared radiation from a Nd:YAG laser at 1,064 nm was used interstitially or superficially to induce hyperthermia in RIF-1 tumors in C3H male mice. A single 600-microns quartz fiber with a 0.5-cm cylindrical diffusor or a weakly diverging microlens at its distal end was used to deliver laser energy to tumors in the hind leg (mean volume = 100 mm3). Two thermocouples were inserted into each tumor. One thermocouple controlled a microprocessor-driven hyperthermia program (maximum output of 3.5 Watts) to maintain the desired temperature. Tumors were exposed to various temperature-time combinations (42-45 degrees C/30 min). Our initial results indicated that excellent temperature control to within 0.2 degrees C of the desired temperature at the feedback thermocouple was achievable during both superficial and interstitial heat treatments. Temperatures at the second thermocouple, however, were found to be lower by as much as 2.3 degrees C (using the cylindrical diffusor) or higher by up to 4.6 degrees C (using the microlens) when compared to the feedback thermocouple temperature. Several correlations were seen between total dose, tumor growth delay, percent skin necrosis, and temperature at the second thermocouple after several superficial and interstitial treatments. Statistically significant improvements in tumor growth delay (at 42 and 45 degrees C) and increased percent skin necrosis at all temperatures were observed after superficial versus interstitial treatment.

  3. Carbon economy of sour orange in response to different Glomus spp.

    PubMed

    Graham, J. H.; Drouillard, D. L.; Hodge, N. C.

    1996-01-01

    Vesicular-arbuscular mycorrhizal (M) fungal colonization, growth, and nonstructural carbohydrate status of sour orange (Citrus aurantium L.) seedlings were compared at low- and high-phosphorus (P) supply following inoculation with four Glomus isolates: G. intraradices (Gi, FL208), G. etunicatum (Ge, UT316), G. claroideum (Gc, SC186), and Glomus sp. (G329, FL906). Nonmycorrhizal (NM) seedlings served as controls. At low-P supply, increases in incidence of M colonization, vesicles and accumulation of fungal fatty acid 16:1omega(5)C in roots were most rapid for G329-inoculated seedlings, followed closely by Gi- and Gc-inoculated seedlings. Glomus etunicatum was a less aggressive colonizer and produced lower rates of fungal fatty acid accumulation in seedling roots than the other Glomus species. Nonmycorrhizal and Ge-inoculated seedlings had lower P status and growth rates than seedlings inoculated with Gi or G329. Glomus claroideum increased seedling P status, but growth rate was lower than for seedlings colonized by Gi or G329, suggesting higher belowground costs for Gc colonization. In P-sufficient roots colonized by Gi, Gc, or G329, starch and ketone sugar concentrations were lower than in P-deficient NM and Ge-inoculated plants. Under conditions of high-P supply where mycorrhizae provided no P benefit to the seedlings, colonization by Gc, Gi, and G329 was delayed and reduced compared to that at low-P supply; however, the relative colonization rates among Glomus spp. were similar. Colonization by Ge was not detected in roots until 64 days after inoculation. Compared to NM seedlings, growth rates of mycorrhizal seedlings were reduced by the three aggressive fungi but not by the less aggressive Ge. After 64 days, starch and ketone sugar concentrations were lower in fibrous roots colonized by Gc, Gi, and G329 than in NM roots, indicating greater utilization of nonstructural carbohydrates in roots colonized by the aggressive fungi. After 49 days, colonization by the aggressive fungi increased root biomass allocation which may have contributed to the lower growth rate of mycorrhizal seedlings compared to NM seedlings. Thus, Glomus spp. that were aggressive colonizers of roots at low-P supply were also aggressive colonizers at high-P supply, resulting in greater belowground C costs and growth depression compared with the less aggressive colonizer, Ge.

  4. Distributed delays in a hybrid model of tumor-immune system interplay.

    PubMed

    Caravagna, Giulio; Graudenzi, Alex; d'Onofrio, Alberto

    2013-02-01

    A tumor is kinetically characterized by the presence of multiple spatio-temporal scales in which its cells interplay with, for instance, endothelial cells or Immune system effectors, exchanging various chemical signals. By its nature, tumor growth is an ideal object of hybrid modeling where discrete stochastic processes model low-numbers entities, and mean-field equations model abundant chemical signals. Thus, we follow this approach to model tumor cells, effector cells and Interleukin-2, in order to capture the Immune surveillance effect. We here present a hybrid model with a generic delay kernel accounting that, due to many complex phenomena such as chemical transportation and cellular differentiation, the tumor-induced recruitment of effectors exhibits a lag period. This model is a Stochastic Hybrid Automata and its semantics is a Piecewise Deterministic Markov process where a two-dimensional stochastic process is interlinked to a multi-dimensional mean-field system. We instantiate the model with two well-known weak and strong delay kernels and perform simulations by using an algorithm to generate trajectories of this process. Via simulations and parametric sensitivity analysis techniques we (i) relate tumor mass growth with the two kernels, we (ii) measure the strength of the Immune surveillance in terms of probability distribution of the eradication times, and (iii) we prove, in the oscillatory regime, the existence of a stochastic bifurcation resulting in delay-induced tumor eradication.

  5. The 12q14 microdeletion syndrome: six new cases confirming the role of HMGA2 in growth

    PubMed Central

    Lynch, Sally Ann; Foulds, Nicola; Thuresson, Ann-Charlotte; Collins, Amanda L; Annerén, Göran; Hedberg, Bernt-Oves; Delaney, Carol A; Iremonger, James; Murray, Caroline M; Crolla, John A; Costigan, Colm; Lam, Wayne; Fitzpatrick, David R; Regan, Regina; Ennis, Sean; Sharkey, Freddie

    2011-01-01

    We report six patients with array deletions encompassing 12q14. Out of a total of 2538 array investigations carried out on children with developmental delay and dysmorphism in three diagnostic testing centres, six positive cases yielded a frequency of 1 in 423 for this deletion syndrome. The deleted region in each of the six cases overlaps significantly with previously reported cases with microdeletions of this region. The chromosomal range of the deletions extends from 12q13.3q15. In the current study, we report overlapping deletions of variable extent and size but primarily comprising chromosomal bands 12q13.3q14.1. Four of the six deletions were confirmed as de novo events. Two cases had deletions that included HMGA2, and both children had significant short stature. Neither case had osteopoikilosis despite both being deleted for LEMD3. Four cases had deletions that ended proximal to HMGA2 and all of these had much better growth. Five cases had congenital heart defects, including two with atrial septal defects, one each with pulmonary stenosis, sub-aortic stenosis and a patent ductus. Four cases had moderate delay, two had severe developmental delay and a further two had a diagnosis of autism. All six cases had significant speech delay with subtle facial dysmorphism. PMID:21267005

  6. Association between Prepregnancy Body Mass Index and Gestational Weight Gain with Size, Tempo, and Velocity of Infant Growth: Analysis of the Newborn Epigenetic Study Cohort.

    PubMed

    Fuemmeler, Bernard F; Wang, Lin; Iversen, Edwin S; Maguire, Rachel; Murphy, Susan K; Hoyo, Cathrine

    2016-06-01

    The first 1000 days of life is a critical period of infant growth that has been linked to future adult health. Understanding prenatal factors that contribute to variation in growth during this period could inform successful prevention strategies. Prenatal and maternal characteristics, including prepregnancy obesity and gestational weight gain were evaluated in relation to weight growth trajectories during the first 24 months of life using the SuperImposition by Translation and Rotation (SITAR) method, which provides estimates of infant size, timing to peak velocity, and growth velocity. The study sample included 704 mother-infant dyads from a multiethnic prebirth cohort from the Southeastern United States. The total number of weight measures was 8670 (median number per child = 14). Several prenatal and maternal characteristics were linked with infant growth parameters. The primary findings show that compared to women with a prepregnancy BMI between 18 and 24.9, women with a prepregnancy BMI ≥40 had infants that were 8% larger during the first 24 months, a delayed tempo of around 9 days, and a slower velocity. Mothers who had greater than adequate gestational weight gain had infants that were 5% larger even after controlling for prepregnancy BMI and several other covariates. The findings contribute new data on the associations between gestational weight gain and aspects of early growth using the SITAR method, and support a growing consensus in the literature that both prepregnancy BMI and gestational weight gain relate independently to risk for greater postnatal weight growth.

  7. Association between Prepregnancy Body Mass Index and Gestational Weight Gain with Size, Tempo, and Velocity of Infant Growth: Analysis of the Newborn Epigenetic Study Cohort

    PubMed Central

    Wang, Lin; Iversen, Edwin S.; Maguire, Rachel; Murphy, Susan K.; Hoyo, Cathrine

    2016-01-01

    Abstract Background: The first 1000 days of life is a critical period of infant growth that has been linked to future adult health. Understanding prenatal factors that contribute to variation in growth during this period could inform successful prevention strategies. Methods: Prenatal and maternal characteristics, including prepregnancy obesity and gestational weight gain were evaluated in relation to weight growth trajectories during the first 24 months of life using the SuperImposition by Translation and Rotation (SITAR) method, which provides estimates of infant size, timing to peak velocity, and growth velocity. The study sample included 704 mother-infant dyads from a multiethnic prebirth cohort from the Southeastern United States. The total number of weight measures was 8670 (median number per child = 14). Results: Several prenatal and maternal characteristics were linked with infant growth parameters. The primary findings show that compared to women with a prepregnancy BMI between 18 and 24.9, women with a prepregnancy BMI ≥40 had infants that were 8% larger during the first 24 months, a delayed tempo of around 9 days, and a slower velocity. Mothers who had greater than adequate gestational weight gain had infants that were 5% larger even after controlling for prepregnancy BMI and several other covariates. Conclusions: The findings contribute new data on the associations between gestational weight gain and aspects of early growth using the SITAR method, and support a growing consensus in the literature that both prepregnancy BMI and gestational weight gain relate independently to risk for greater postnatal weight growth. PMID:27135650

  8. Multilevel linear modelling of the response-contingent learning of young children with significant developmental delays.

    PubMed

    Raab, Melinda; Dunst, Carl J; Hamby, Deborah W

    2018-02-27

    The purpose of the study was to isolate the sources of variations in the rates of response-contingent learning among young children with multiple disabilities and significant developmental delays randomly assigned to contrasting types of early childhood intervention. Multilevel, hierarchical linear growth curve modelling was used to analyze four different measures of child response-contingent learning where repeated child learning measures were nested within individual children (Level-1), children were nested within practitioners (Level-2), and practitioners were nested within the contrasting types of intervention (Level-3). Findings showed that sources of variations in rates of child response-contingent learning were associated almost entirely with type of intervention after the variance associated with differences in practitioners nested within groups were accounted for. Rates of child learning were greater among children whose existing behaviour were used as the building blocks for promoting child competence (asset-based practices) compared to children for whom the focus of intervention was promoting child acquisition of missing skills (needs-based practices). The methods of analysis illustrate a practical approach to clustered data analysis and the presentation of results in ways that highlight sources of variations in the rates of response-contingent learning among young children with multiple developmental disabilities and significant developmental delays. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  9. VEGF attenuated increase of outward delayed-rectifier potassium currents in hippocampal neurons induced by focal ischemia via PI3-K pathway.

    PubMed

    Wu, K W; Yang, P; Li, S S; Liu, C W; Sun, F Y

    2015-07-09

    We recently indicated that the vascular endothelial growth factor (VEGF) protects neurons against hypoxic death via enhancement of tyrosine phosphorylation of Kv1.2, an isoform of the delayed-rectifier potassium channels through activation of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway. The present study investigated whether VEGF could attenuate ischemia-induced increase of the potassium currents in the hippocampal pyramidal neurons of rats after ischemic injury. Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) to induce brain ischemia. The whole-cell patch-clamp technique was used to record the potassium currents of hippocampal neurons in brain slices from the ischemically injured brains of the rats 24h after MCAO. We detected that transient MCAO caused a significant increase of voltage-gated potassium currents (Kv) and outward delayed-rectifier potassium currents (IK), but not outward transient potassium currents (IA), in the ipsilateral hippocampus compared with the sham. Moreover, we found that VEGF could acutely, reversibly and voltage-dependently inhibit the ischemia-induced IK increase. This inhibitory effect of VEGF could be completely abolished by wortmannin, an inhibitor of PI3-K. Our data indicate that VEGF attenuates the ischemia-induced increase of IK via activation of the PI3-K signaling pathway. Published by Elsevier Ltd.

  10. Theory of time-dependent rupture in the Earth

    NASA Technical Reports Server (NTRS)

    Das, S.; Scholz, C. H.

    1980-01-01

    Fracture mechanics is used to develop a theory of earthquake mechanism which includes the phenomenon of subcritical crack growth. The following phenomena are predicted: slow earthquakes, multiple events, delayed multiple events (doublets), postseismic rupture growth and afterslip, foreshocks, and aftershocks. The theory predicts a nucleation stage prior to an earthquake, and suggests a physical mechanism by which one earthquake may 'trigger' another.

  11. Tumor growth delay by adjuvant alternating electric fields which appears non-thermally mediated.

    PubMed

    Castellví, Quim; Ginestà, Mireia M; Capellà, Gabriel; Ivorra, Antoni

    2015-10-01

    Delivery of the so-called Tumor Treatment Fields (TTFields) has been proposed as a cancer therapy. These are low magnitude alternating electric fields at frequencies from 100 to 300 kHz which are applied continuously in a non-invasive manner. Electric field delivery may produce an increase in temperature which cannot be neglected. We hypothesized that the reported results obtained by applying TTFields in vivo could be due to heat rather than to electrical forces as previously suggested. Here, an in vivo study is presented in which pancreatic tumors subcutaneously implanted in nude mice were treated for a week either with mild hyperthermia (41 °C) or with TTFields (6 V/cm, 150 kHz) and tumor growth was assessed. Although the TTFields applied singly did not produce any significant effect, the combination with chemotherapy did show a delay in tumor growth in comparison to animals treated only with chemotherapy (median relative reduction=47%). We conclude that concomitant chemotherapy and TTFields delivery show a beneficial impact on pancreatic tumor growth. Contrary to our hypothesis, this impact is non-related with the induced temperature increase. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Contribution of Schedule Delays to Cost Growth: How to Make Peace with a Marching Army

    NASA Technical Reports Server (NTRS)

    Majerowicz, Walt; Bitten, Robert; Emmons, Debra; Shinn, Stephen A.

    2016-01-01

    Numerous research papers have shown that cost and schedule growth are interrelated for NASA space science missions. Although there has shown to be a strong correlation of cost growth with schedule growth, it is unclear what percentage of cost growth is caused by schedule growth and how schedule growth can be controlled. This paper attempts to quantify this percentage by looking at historical data and show detailed examples of how schedule growth influences cost growth. The paper also addresses a methodology to show an alternate approach for assessing and setting a robust baseline schedule and use schedule performance metrics to help assess if the project is performing to plan. Finally, recommendations are presented to help control schedule growth in order to minimize cost growth for NASA space science missions.

  13. Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

    PubMed Central

    Bhattacharya, Sushant; Aggarwal, Rangoli; Singh, Vijay Pal; Ramachandran, Srinivasan; Datta, Malabika

    2015-01-01

    Delayed wound healing is a major complication associated with diabetes and is a result of a complex interplay among diverse deregulated cellular parameters. Although several genes and pathways have been identified to be mediating impaired wound closure, the role of microRNAs (miRNAs) in these events is not very well understood. Here, we identify an altered miRNA signature in the prolonged inflammatory phase in a wound during diabetes, with increased infiltration of inflammatory cells in the basal layer of the epidermis. Nineteen miRNAs were downregulated in diabetic rat wounds (as compared with normal rat wound, d 7 postwounding) together with inhibited levels of the central miRNA biosynthesis enzyme, Dicer, suggesting that in wounds of diabetic rats, the decreased levels of Dicer are presumably responsible for miRNA downregulation. Compared with unwounded skin, Dicer levels were significantly upregulated 12 d postwounding in normal rats, and this result was notably absent in diabetic rats that showed impaired wound closure. In a wound-healing specific quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) array, 10 genes were significantly altered in the diabetic rat wound and included growth factors and collagens. Network analyses demonstrated significant interactions and correlations between the miRNA predicted targets (regulators) and the 10 wound-healing specific genes, suggesting altered miRNAs might fine-tune the levels of these genes that determine wound closure. Dicer inhibition prevented HaCaT cell migration and affected wound closure. Altered levels of Dicer and miRNAs are critical during delayed wound closure and offer promising targets to address the issue of impaired wound healing. PMID:26602065

  14. Ecotype-specific improvement of nitrogen status in European grasses after drought combined with rewetting

    NASA Astrophysics Data System (ADS)

    Arfin Khan, Mohammed A. S.; Kreyling, Juergen; Beierkuhnlein, Carl; Jentsch, Anke

    2016-11-01

    Drought stress and associated low soil moisture can decrease N status of forage plants by reducing nitrogen (N) uptake. Conversely, rainfall and associated favorable soil moisture can improve plant N status. Yet, it is unclear to which degree drought combined with rewetting can buffer negative effects of drought on N status of forage plants and their populations. Here, we compared shoot N status (N concentration, total N uptake and C/N ratio) of four temperate grass species. Particularly, we investigated ecotypes (populations) grown from seeds from four to six European provenances/species after a drought treatment combined with rewetting (10 day harvest delay) versus continuously watered conditions for control. The experimental combination of drought and rewetting significantly increased shoot N concentration (+96%), N uptake (+31%); and decreased C/N ratio (-46%), biomass production (-29%) and C concentration (-1.4%) compared to control. Shoot N status was found to be different between target grass species and also within their populations under drought combined with rewetting treatment. Presumably drought-adapted populations did not perform better than populations from moist sites indicating no evidence of local adaptation. The drought combined with rewetting event could buffer the negative effects of drought. Shoot N status of grasses after drought and rewetting even exceeded control plants. This surprising finding can potentially be explained by higher N uptake, lack of growth dilution effects or delayed plant maturation. Furthermore, within-species shoot N status responses to drought combined with rewetting event were ecotype-specific, hinting at diverse responses of different population. For rangeland management, we recommend that if a drought event occurs during the growing season, harvesting should be delayed beyond a following rain event.

  15. The influence of delaying judgments of learning on metacognitive accuracy: a meta-analytic review.

    PubMed

    Rhodes, Matthew G; Tauber, Sarah K

    2011-01-01

    Many studies have examined the accuracy of predictions of future memory performance solicited through judgments of learning (JOLs). Among the most robust findings in this literature is that delaying predictions serves to substantially increase the relative accuracy of JOLs compared with soliciting JOLs immediately after study, a finding termed the delayed JOL effect. The meta-analyses reported in the current study examined the predominant theoretical accounts as well as potential moderators of the delayed JOL effect. The first meta-analysis examined the relative accuracy of delayed compared with immediate JOLs across 4,554 participants (112 effect sizes) through gamma correlations between JOLs and memory accuracy. Those data showed that delaying JOLs leads to robust benefits to relative accuracy (g = 0.93). The second meta-analysis examined memory performance for delayed compared with immediate JOLs across 3,807 participants (98 effect sizes). Those data showed that delayed JOLs result in a modest but reliable benefit for memory performance relative to immediate JOLs (g = 0.08). Findings from these meta-analyses are well accommodated by theories suggesting that delayed JOL accuracy reflects access to more diagnostic information from long-term memory rather than being a by-product of a retrieval opportunity. However, these data also suggest that theories proposing that the delayed JOL effect results from a memorial benefit or the match between the cues available for JOLs and those available at test may also provide viable explanatory mechanisms necessary for a comprehensive account.

  16. Overexpression of a cotton gene that encodes a putative transcription factor of AP2/EREBP family in Arabidopsis affects growth and development of transgenic plants.

    PubMed

    Zhou, Ying; Xia, Hui; Li, Xiao-Jie; Hu, Rong; Chen, Yun; Li, Xue-Bao

    2013-01-01

    In the study, a gene encoding a putative ethylene response factor of AP2/EREBP family was isolated from cotton (Gossypium hirsutum) and designated as GhERF12. Sequence alignment showed that GhERF12 protein contains a central AP2/ERF domain (58 amino acids) with two functional conserved amino acid residues (ala14 and asp19). Transactivation assay indicated that GhERF12 displayed strong transcription activation activity in yeast cells, suggesting that this protein may be a transcriptional activator in cotton. Quantitative RT-PCR analysis showed that GhERF12 expression in cotton was induced by ACC and IAA. Overexpression of GhERF12 in Arabidopsis affected seedling growth and development. The GhERF12 transgenic plants grew slowly, and displayed a dwarf phenotype. The mean bolting time of the transgenic plants was delayed for about 10 days, compared with that of wild type. Further study revealed that some ethylene-related and auxin-related genes were dramatically up-regulated in the transgenic plants, compared with those of wild type. Collectively, we speculated that GhERF12, as a transcription factor, may be involved in regulation of plant growth and development by activating the constitutive ethylene response likely related to auxin biosynthesis and/or signaling.

  17. ATM-dependent DNA damage checkpoint functions regulate gene expression in human fibroblasts

    PubMed Central

    Zhou, Tong; Chou, Jeff; Zhou, Yingchun; Simpson, Dennis A.; Cao, Feng; Bushel, Pierre R.; Paules, Richard S.; Kaufmann, William K.

    2013-01-01

    The relationships between profiles of global gene expression and DNA damage checkpoint functions were studied in cells from patients with ataxia telangiectasia (AT). Three telomerase-expressing AT fibroblast lines displayed the expected hypersensitivity to ionizing radiation (IR) and defects in DNA damage checkpoints. Profiles of global gene expression in AT cells were determined at 2, 6 and 24 h after treatment with 1.5 Gy IR or sham-treatment, and were compared to those previously recognized in normal human fibroblasts. Under basal conditions 160 genes or ESTs were differentially expressed in AT and normal fibroblasts, and these were associated by gene ontology with insulin-like growth factor binding and regulation of cell growth. Upon DNA damage, 1091 gene mRNAs were changed in at least two of the three AT cell lines. When compared with the 1811 genes changed in normal human fibroblasts after the same treatment, 715 were found in both AT and normal fibroblasts, including most genes categorized by gene ontology into cell cycle, cell growth and DNA damage response pathways. However, the IR-induced changes in these 715 genes in AT cells usually were delayed or attenuated in comparison to normal cells. The reduced change in DNA-damage-response genes and the attenuated repression of cell-cycle-regulated genes may account for the defects in cell cycle checkpoint function in AT cells. PMID:17699107

  18. Overexpression of a Cotton Gene That Encodes a Putative Transcription Factor of AP2/EREBP Family in Arabidopsis Affects Growth and Development of Transgenic Plants

    PubMed Central

    Li, Xiao-Jie; Hu, Rong; Chen, Yun; Li, Xue-Bao

    2013-01-01

    In the study, a gene encoding a putative ethylene response factor of AP2/EREBP family was isolated from cotton (Gossypium hirsutum) and designated as GhERF12. Sequence alignment showed that GhERF12 protein contains a central AP2/ERF domain (58 amino acids) with two functional conserved amino acid residues (ala14 and asp19). Transactivation assay indicated that GhERF12 displayed strong transcription activation activity in yeast cells, suggesting that this protein may be a transcriptional activator in cotton. Quantitative RT-PCR analysis showed that GhERF12 expression in cotton was induced by ACC and IAA. Overexpression of GhERF12 in Arabidopsis affected seedling growth and development. The GhERF12 transgenic plants grew slowly, and displayed a dwarf phenotype. The mean bolting time of the transgenic plants was delayed for about 10 days, compared with that of wild type. Further study revealed that some ethylene-related and auxin-related genes were dramatically up-regulated in the transgenic plants, compared with those of wild type. Collectively, we speculated that GhERF12, as a transcription factor, may be involved in regulation of plant growth and development by activating the constitutive ethylene response likely related to auxin biosynthesis and/or signaling. PMID:24194949

  19. Myeloid Cell COX-2 deletion reduces mammary tumor growth through enhanced cytotoxic T-lymphocyte function

    PubMed Central

    Chen, Edward P.; Markosyan, Nune; Connolly, Emma; Lawson, John A.; Li, Xuanwen; Grant, Gregory R.; Grosser, Tilo; FitzGerald, Garret A.; Smyth, Emer M.

    2014-01-01

    Cyclooxygenase-2 (COX-2) expression is associated with poor prognosis across a range of human cancers, including breast cancer. The contribution of tumor cell-derived COX-2 to tumorigenesis has been examined in numerous studies; however, the role of stromal-derived COX-2 is ill-defined. Here, we examined how COX-2 in myeloid cells, an immune cell subset that includes macrophages, influences mammary tumor progression. In mice engineered to selectively lack myeloid cell COX-2 [myeloid-COX-2 knockout (KO) mice], spontaneous neu oncogene-induced tumor onset was delayed, tumor burden reduced, and tumor growth slowed compared with wild-type (WT). Similarly, growth of neu-transformed mammary tumor cells as orthotopic tumors in immune competent syngeneic myeloid-COX-2 KO host mice was reduced compared with WT. By flow cytometric analysis, orthotopic myeloid-COX-2 KO tumors had lower tumor-associated macrophage (TAM) infiltration consistent with impaired colony stimulating factor-1-dependent chemotaxis by COX-2 deficient macrophages in vitro. Further, in both spontaneous and orthotopic tumors, COX-2-deficient TAM displayed lower immunosuppressive M2 markers and this was coincident with less suppression of CD8+ cytotoxic T lymphocytes (CTLs) in myeloid-COX-2 KO tumors. These studies suggest that reduced tumor growth in myeloid-COX-2 KO mice resulted from disruption of M2-like TAM function, thereby enhancing T-cell survival and immune surveillance. Antibody-mediated depletion of CD8+, but not CD4+ cells, restored tumor growth in myeloid-COX-2 KO to WT levels, indicating that CD8+ CTLs are dominant antitumor effectors in myeloid-COX-2 KO mice. Our studies suggest that inhibition of myeloid cell COX-2 can potentiate CTL-mediated tumor cytotoxicity and may provide a novel therapeutic approach in breast cancer therapy. PMID:24590894

  20. Growth and Psychological Development in Postoperative Patients With Anterior Encephaloceles.

    PubMed

    Dutta, Hemonta Kumar; Khangkeo, Chow Wachana; Baruah, Kaberi; Borbora, Debasish

    2017-06-01

    Anterior encephaloceles are rare malformations that are frequently associated with other brain anomalies. This study evaluates the growth and psychological development of children following encephalocele repair. Growth and psychological assessment was done in 24 children with only encephalocele (group I); nine children with encephalocele and hydrocephalus (group II); seven children with encephalocele, hydrocephalus, and secondary malformations (group III); and 40 apparently healthy control subjects. Psychological assessment was done by evaluating intelligence and temperament. Single-stage repair was performed in 38 children, and two underwent multistage repair. Major postoperative complications were noted in three individuals. The follow-up period ranged from 12 to 168 months, and during this time the growth velocity declined significantly among group II and group III patients when compared with control subjects. After adjusting the body mass index for age, our data revealed that group III participants had a significantly (P = 0.02) lower body mass index than the control group. Group III also had poor indices for intelligence quotient (P ≤ 0.01) and temperament (P ≤ 0.01). Female patients had lower temperament indices when compared with unaffected females with regard to approach withdrawal (P ≤ 0.01), mood (P = 0.026), and intensity (P = 0.03). Overall, increased disease severity adversely affected the psychological indices. Individuals with anterior encephalocele without associated intracranial defects had excellent postoperative outcomes in terms of growth and psychological developments. Hydrocephalus and agenesis of corpus callosum had the least impact on psychological development. However, the presence of secondary brain defects led to developmental delays. Gender differences in temperament may suggest a need for distinct treatment regimens to assess psychosocial well-being for males and females. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Using a Novel Absolute Ontogenetic Age Determination Technique to Calculate the Timing of Tooth Eruption in the Saber-Toothed Cat, Smilodon fatalis.

    PubMed

    Wysocki, M Aleksander; Feranec, Robert S; Tseng, Zhijie Jack; Bjornsson, Christopher S

    2015-01-01

    Despite the superb fossil record of the saber-toothed cat, Smilodon fatalis, ontogenetic age determination for this and other ancient species remains a challenge. The present study utilizes a new technique, a combination of data from stable oxygen isotope analyses and micro-computed tomography, to establish the eruption rate for the permanent upper canines in Smilodon fatalis. The results imply an eruption rate of 6.0 millimeters per month, which is similar to a previously published average enamel growth rate of the S. fatalis upper canines (5.8 millimeters per month). Utilizing the upper canine growth rate, the upper canine eruption rate, and a previously published tooth replacement sequence, this study calculates absolute ontogenetic age ranges of tooth development and eruption in S. fatalis. The timing of tooth eruption is compared between S. fatalis and several extant conical-toothed felids, such as the African lion (Panthera leo). Results suggest that the permanent dentition of S. fatalis, except for the upper canines, was fully erupted by 14 to 22 months, and that the upper canines finished erupting at about 34 to 41 months. Based on these developmental age calculations, S. fatalis individuals less than 4 to 7 months of age were not typically preserved at Rancho La Brea. On the whole, S. fatalis appears to have had delayed dental development compared to dental development in similar-sized extant felids. This technique for absolute ontogenetic age determination can be replicated in other ancient species, including non-saber-toothed taxa, as long as the timing of growth initiation and growth rate can be determined for a specific feature, such as a tooth, and that growth period overlaps with the development of the other features under investigation.

  2. Candida albicans infection delays duodenal ulcer healing in cysteamine-induced duodenal ulcers in rats.

    PubMed

    Jin, Longxue; Yoshida, Masashi; Nakamura, Tetsuya; Ishikawa, Hideki; Wakabayashi, Go; Tanabe, Minoru; Kawachi, Shigeyuki; Shinoda, Masahiro; Saikawa, Yoshiro; Wada, Norihito; Kameyama, Kaori; Kumai, Koichiro; Kubota, Tetsuro; Sano, Katsuko; Nagao, Keisuke; Amagai, Masayuki; Kitagawa, Yuko; Kitajima, Masaki

    2008-11-01

    A low curability of ulcers infected with Candida has been reported in the literature. The aim of the study reported here was to investigate experimentally whether Candida infection affects the healing of ulcers. Candida albicans (the Candida group) or saline (the control group) was administered intragastrically into rats with a cysteamine-induced duodenal ulcer. The duodenal lesions, vascular endothelial growth factor A (VEGF-A) and proliferating cell nuclear antigen (PCNA) were assessed. On Day 7 post-administration, 70.4% rats of the Candida group had a duodenal ulcer compared with 33.3% in the control group (P < 0.05). The duodenal ulcer in the Candida group was significantly larger and deeper than that in the control group. The number of VEGF-A- and PCNA-positive cells was smaller and the area of VEGF-A expression was lower in the Candida group. Using a rat model, we have demonstrated that Candida infection can delay the wound healing process of duodenal ulcers by means of a low expression of VEGF-A and PCNA.

  3. Say-Meyer syndrome: additional manifestations in a new patient and phenotypic assessment.

    PubMed

    Salinas-Torres, Victor M

    2015-07-01

    In 1981, Say and Meyer described a seemingly X-linked recessive syndrome of trigonocephaly, short stature, and developmental delay. Here, I present a new patient and review eight patients from the literature examining the nature and phenotypic differences. A Mexican 10-year-old boy with Say-Meyer syndrome is described. Additionally, he had C6 vertebral right pedicle agenesis, brachymesophalangy of the fifth fingers, bilateral widening of Sylvian fissure, and white matter amplitude as novel observed findings of the syndrome. This appears to be the first Say-Meyer syndrome patient with extracranial skeletal anomalies. In light of these manifestations, a detailed comparative phenotypic analysis of published patients revealed a heterogeneous syndrome with a significant clinical variability. Moreover, increasing evidence points to a variable expressivity of the same autosomal dominant mutation. Accordingly, it is proposed that Say-Meyer syndrome should be considered in those patients with the combination of trigonocephaly/metopic synostosis, short stature, developmental delay including prenatal and postnatal growth disorders, craniofacial dysmorphic features (especially hypotelorism), structural CNS anomalies (mainly white matter involvement), conductive hearing loss, seizures, and cardiovascular abnormalities.

  4. Evaluation of the antioxidant effect of ganghwayakssuk (Artemisia princeps Pamp.) extract alone and in combination with ascorbic acid in raw chicken patties.

    PubMed

    Hwang, K E; Kim, H W; Choi, Y S; Lee, S Y; Yeo, E J; Ham, Y K; Choi, S M; Lee, M A; Kim, C J

    2013-12-01

    We investigated the inhibition of lipid oxidation of raw chicken patties by the antioxidants ascorbic acid (Aa), ganghwayakssuk extracts (GE), and their combination (Aa + GE). All antioxidant combinations were effective at delaying lipid oxidation compared with the control or Aa. A combination of Aa + GE (0.05% Aa + 0.2% GE) was the most effective for delaying lipid oxidation (TBA reactive substances, conjugated dienes, and peroxide formation). The color values of all samples were significantly affected by adding GE. Additionally, the redness, color difference, and hue values of all treatments, except for Aa, were lower than those of the control as the amount of GE increased. The total viable bacterial counts of samples with GE 0.2 and Aa + GE 0.2 were significantly affected during storage (P < 0.05). The results suggest that adding an antioxidant combination reduced the oxidative stress and microbial growth of raw chicken patties stored for 12 d under normal refrigeration temperature, which may extend the shelf life of chicken patties.

  5. Factors affecting professional delay in diagnosis and treatment of oral cancer in Iran.

    PubMed

    Esmaelbeigi, Farhad; Hadji, Maryam; Harirchi, Iraj; Omranipour, Ramesh; vand Rajabpour, Mojtaba; Zendehdel, Kazem

    2014-04-01

    Oral cancer is the most common malignant tumor among head and neck cancers. Delay in diagnosis affects the treatment and prognosis of oral cancer. We measured the professional delay in the diagnosis and its attributes in the Cancer Institute of Iran, the largest referral center for oral cancer patients in the country.  We interviewed oral cancer patients to measure the delay and used case-control approach to study association of various prognostic factors with professional delay and tumor stage. Out of 206 patients, 71.4% were diagnosed at the advanced stage. The median of the patient, professional and total delays were 45, 86 and 140 day, receptively. In the univariate model, prescription of medicines like analgesics (OR = 5.3, 95% CI 2.2-12.9) and history of dental procedure (OR=6.8, 95% CI 1.7-26.9) were associated with higher risk of delay compared to patient who were biopsied from the beginning. History of loose teeth increased risk of delay 4 times (OR = 4.0, 95% CI 1.6-9.8). Patients with primary education had 70% lower risk of delay compared to the illiterate patients (OR = 0.3, 95% CI 0.1-0.7) and the risk was lower among patients who had diploma (OR = 0.04, 95% CI 0-0.7) and college education (OR = 0.1, 95% CI 0-0.4). The delayed patients were diagnosed in more advanced stage compared to the patients without delay (OR = 2.1, 95% CI 1.0-4.4). Development of a national guideline for follow-up of oral lesions, training and awareness of health care professionals about oral cancer diagnosis may decrease the delay and improve the oral cancer outcome in Iran.

  6. Laser activation of a nutrient medium and antibiotic solutions and its estimation by of bacteria growth dynamics

    NASA Astrophysics Data System (ADS)

    Malov, Alexander N.; Neupokoeva, Anna V.; Kokorina, Lubov A.; Simonova, Elena V.

    2016-11-01

    A laser photomodifacation of nutrient mediums and antibiotics results at the microbiological supervision of bacteria colonies growth are discussed. It is experimentally shown, that on the irradiated media there is a delay of bacterial colonies growth number. Influence of laser radiation on activity of an antibiotic also is experimentally studied. It is revealed, that laser photomodifacation increases antimicrobic activity of a preparation. The mechanism of biological solutions activation is connected with the phenomenon laser nanoclusterization. Parameters of bacteria growth bacteria growth dynamics allow to numerically estimate degree of laser activation of nutrient mediums and pharmaceutical preparations.

  7. Health of children adopted from Ethiopia.

    PubMed

    Miller, Laurie C; Tseng, Beverly; Tirella, Linda G; Chan, Wilma; Feig, Emily

    2008-09-01

    Since 2000, American families have adopted 1,700 children from Ethiopia. Little is known about the health and development of these children. Retrospective chart review of the arrival health status of all 50 (26F:24M) children from Ethiopia/Eritrea seen in the International Adoption Clinic. Prior to adoption, most children resided with relatives; 36% were >18 months old prior to entry into care. More than 50% were true orphans, often due to HIV. Arrival age ranged from 3 months to 15 years (mean +/- SD 4 years +/- 43.8 months). At arrival, growth z scores were near-average (weight -.59, height -.64, head circumference -.09); significantly better than adopted children Guatemala, China, or Russia seen in our clinic. However, some Ethiopian children were significantly growth delayed (WAZ < or =-2, 8%, HAZ 12%, HCZ 18%). Age at adoption did not relate to growth delays. Medical issues on arrival included intestinal parasites (53%, [14% with > or =3 types]), skin infections (45%), dental caries (25%), elevated liver transaminases (20%), latent tuberculosis (18%), and hepatitis B (2%). Age-appropriate vaccines had been administered in 15-77% of children (depending on specific vaccine). Behavior problems were uncommon. Gross/fine motor and cognitive skills were approximately 86% of expected for age. Age correlated inversely with developmental scores for cognition (r = -.49, P = .003). Five children had age reassignments. Ethiopian/Eritean adoptees differ from other groups of internationally adopted children: they reside for relatively long periods of time with relatives prior to institutionalization, often have uncertain ages, exhibit few behavioral problems at arrival, have better growth, and may have less severe developmental delays. Whether these differences at arrival predict better outcomes for the Ethiopian/Eritrean children is unknown.

  8. Describing-function analysis of a ripple regulator with slew-rate limits and time delays

    NASA Technical Reports Server (NTRS)

    Wester, Gene W.

    1990-01-01

    The effects of time delays and slew-rate limits on the steady-state operating points and performance of a free-running ripple regulator are evaluated using describing-function analysis. The describing function of an ideal comparator (no time delays or slew rate limits) has no phase shift and is independent of frequency. It is found that turn-on delay and turn-off delay have different effects on gain and phase and cannot be combined. Comparator hysteresis affects both gain and phase; likewise, time delays generally affect both gain and phase. It is found that the effective time delay around the feedback loop is one half the sum of turn-on and turn-off delays, regardless of whether the delays are caused by storage time or slew rate limits. Expressions are formulated for the switching frequency, switch duty ratio, dc output, and output ripple. For the case of no hysteresis, a simple, graphical solution for the switching frequency is possible, and the resulting switching frequency is independent of first-order variations of input or load.

  9. Linear-phase delay filters for ultra-low-power signal processing in neural recording implants.

    PubMed

    Gosselin, Benoit; Sawan, Mohamad; Kerherve, Eric

    2010-06-01

    We present the design and implementation of linear-phase delay filters for ultra-low-power signal processing in neural recording implants. We use these filters as low-distortion delay elements along with an automatic biopotential detector to perform integral waveform extraction and efficient power management. The presented delay elements are realized employing continuous-time OTA-C filters featuring 9th-order equiripple transfer functions with constant group delay. Such analog delay enables processing neural waveforms with reduced overhead compared to a digital delay since it does not requires sampling and digitization. It uses an allpass transfer function for achieving wider constant-delay bandwidth than all-pole does. Two filters realizations are compared for implementing the delay element: the Cascaded structure and the Inverse follow-the-leader feedback filter. Their respective strengths and drawbacks are assessed by modeling parasitics and non-idealities of OTAs, and by transistor-level simulations. A budget of 200 nA is used in both filters. Experimental measurements with the chosen filter topology are presented and discussed.

  10. Evidence for a Transketolase-Mediated Metabolic Checkpoint Governing Biotrophic Growth in Rice Cells by the Blast Fungus Magnaporthe oryzae

    PubMed Central

    Fernandez, Jessie; Marroquin-Guzman, Margarita; Wilson, Richard A.

    2014-01-01

    The blast fungus Magnaporthe oryzae threatens global food security through the widespread destruction of cultivated rice. Foliar infection requires a specialized cell called an appressorium that generates turgor to force a thin penetration hypha through the rice cuticle and into the underlying epidermal cells, where the fungus grows for the first days of infection as a symptomless biotroph. Understanding what controls biotrophic growth could open new avenues for developing sustainable blast intervention programs. Here, using molecular genetics and live-cell imaging, we dismantled M. oryzae glucose-metabolizing pathways to reveal that the transketolase enzyme, encoded by TKL1, plays an essential role in facilitating host colonization during rice blast disease. In the absence of transketolase, Δtkl1 mutant strains formed functional appressoria that penetrated rice cuticles successfully and developed invasive hyphae (IH) in rice cells from primary hyphae. However, Δtkl1 could not undertake sustained biotrophic growth or cell-to-cell movement. Transcript data and observations using fluorescently labeled histone H1:RFP fusion proteins indicated Δtkl1 mutant strains were alive in host cells but were delayed in mitosis. Mitotic delay could be reversed and IH growth restored by the addition of exogenous ATP, a metabolite depleted in Δtkl1 mutant strains. We show that ATP might act via the TOR signaling pathway, and TOR is likely a downstream target of activation for TKL1. TKL1 is also involved in controlling the migration of appressorial nuclei into primary hyphae in host cells. When taken together, our results indicate transketolase has a novel role in mediating - via ATP and TOR signaling - an in planta-specific metabolic checkpoint that controls nuclear migration from appressoria into primary hyphae, prevents mitotic delay in early IH and promotes biotrophic growth. This work thus provides new information about the metabolic strategies employed by M. oryzae to enable rice cell colonization. PMID:25188286

  11. Effects of nerve growth factor (NGF) on blood vessels area and expression of the angiogenic factors VEGF and TGFbeta1 in the rat ovary

    PubMed Central

    Julio-Pieper, Marcela; Lara, Hernán E; Bravo, Javier A; Romero, Carmen

    2006-01-01

    Background Angiogenesis is a crucial process in follicular development and luteogenesis. The nerve growth factor (NGF) promotes angiogenesis in various tissues. An impaired production of this neurotrophin has been associated with delayed wound healing. A variety of ovarian functions are regulated by NGF, but its effects on ovarian angiogenesis remain unknown. The aim of this study was to elucidate if NGF modulates 1) the amount of follicular blood vessels and 2) ovarian expression of two angiogenic factors: vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGFbeta1), in the rat ovary. Results In cultured neonatal rat ovaries, NGF increased VEGF mRNA and protein levels, whereas TGFbeta1 expression did not change. Sectioning of the superior ovarian nerve, which increases ovarian NGF protein content, augmented VEGF immunoreactivity and the area of capillary vessels in ovaries of prepubertal rats compared to control ovaries. Conclusion Results indicate that NGF may be important in the maintenance of the follicular and luteal vasculature in adult rodents, either indirectly, by increasing the expression of VEGF in the ovary, or directly via promoting the proliferation of vascular cells. This data suggests that a disruption on NGF regulation could be a component in ovarian disorders related with impaired angiogenesis. PMID:17096853

  12. Custom fabrication of biomass containment devices using 3-D printing enables bacterial growth analyses with complex insoluble substrates

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

    Nelson, Cassandra E.; Beri, Nina R.; Gardner, Jeffrey G.

    Physiological studies of recalcitrant polysaccharide degradation are challenging for several reasons, one of which is the difficulty in obtaining a reproducibly accurate real-time measurement of bacterial growth using insoluble substrates. Current methods suffer from several problems including (i) high background noise due to the insoluble material interspersed with cells, (ii) high consumable and reagent cost and (iii) significant time delay between sampling and data acquisition. A customizable substrate and cell separation device would provide an option to study bacterial growth using optical density measurements. To test this hypothesis we used 3-D printing to create biomass containment devices that allow interactionmore » between insoluble substrates and microbial cells but do not interfere with spectrophotometer measurements. Evaluation of materials available for 3-D printing indicated that UV-cured acrylic plastic was the best material, being superior to nylon or stainless steel when examined for heat tolerance, reactivity, and ability to be sterilized. Cost analysis of the 3-D printed devices indicated they are a competitive way to quantitate bacterial growth compared to viable cell counting or protein measurements, and experimental conditions were scalable over a 100-fold range. The presence of the devices did not alter growth phenotypes when using either soluble substrates or insoluble substrates. Furthermore, we applied biomass containment to characterize growth of Cellvibrio japonicus on authentic lignocellulose (non-pretreated corn stover), and found physiological evidence that xylan is a significant nutritional source despite an abundance of cellulose present.« less

  13. Custom fabrication of biomass containment devices using 3-D printing enables bacterial growth analyses with complex insoluble substrates

    DOE PAGES

    Nelson, Cassandra E.; Beri, Nina R.; Gardner, Jeffrey G.

    2016-09-21

    Physiological studies of recalcitrant polysaccharide degradation are challenging for several reasons, one of which is the difficulty in obtaining a reproducibly accurate real-time measurement of bacterial growth using insoluble substrates. Current methods suffer from several problems including (i) high background noise due to the insoluble material interspersed with cells, (ii) high consumable and reagent cost and (iii) significant time delay between sampling and data acquisition. A customizable substrate and cell separation device would provide an option to study bacterial growth using optical density measurements. To test this hypothesis we used 3-D printing to create biomass containment devices that allow interactionmore » between insoluble substrates and microbial cells but do not interfere with spectrophotometer measurements. Evaluation of materials available for 3-D printing indicated that UV-cured acrylic plastic was the best material, being superior to nylon or stainless steel when examined for heat tolerance, reactivity, and ability to be sterilized. Cost analysis of the 3-D printed devices indicated they are a competitive way to quantitate bacterial growth compared to viable cell counting or protein measurements, and experimental conditions were scalable over a 100-fold range. The presence of the devices did not alter growth phenotypes when using either soluble substrates or insoluble substrates. Furthermore, we applied biomass containment to characterize growth of Cellvibrio japonicus on authentic lignocellulose (non-pretreated corn stover), and found physiological evidence that xylan is a significant nutritional source despite an abundance of cellulose present.« less

  14. Will changes in phenology track climate change? A study of growth initiation timing in coast Douglas-fir.

    PubMed

    Ford, Kevin R; Harrington, Constance A; Bansal, Sheel; Gould, Peter J; St Clair, J Bradley

    2016-11-01

    Under climate change, the reduction of frost risk, onset of warm temperatures and depletion of soil moisture are all likely to occur earlier in the year in many temperate regions. The resilience of tree species will depend on their ability to track these changes in climate with shifts in phenology that lead to earlier growth initiation in the spring. Exposure to warm temperatures ('forcing') typically triggers growth initiation, but many trees also require exposure to cool temperatures ('chilling') while dormant to readily initiate growth in the spring. If warming increases forcing and decreases chilling, climate change could maintain, advance or delay growth initiation phenology relative to the onset of favorable conditions. We modeled the timing of height- and diameter-growth initiation in coast Douglas-fir (an ecologically and economically vital tree in western North America) to determine whether changes in phenology are likely to track changes in climate using data from field-based and controlled-environment studies, which included conditions warmer than those currently experienced in the tree's range. For high latitude and elevation portions of the tree's range, our models predicted that warming will lead to earlier growth initiation and allow trees to track changes in the onset of the warm but still moist conditions that favor growth, generally without substantially greater exposure to frost. In contrast, toward lower latitude and elevation range limits, the models predicted that warming will lead to delayed growth initiation relative to changes in climate due to reduced chilling, with trees failing to capture favorable conditions in the earlier parts of the spring. This maladaptive response to climate change was more prevalent for diameter-growth initiation than height-growth initiation. The decoupling of growth initiation with the onset of favorable climatic conditions could reduce the resilience of coast Douglas-fir to climate change at the warm edges of its distribution. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  15. Will changes in phenology track climate change? A study of growth initiation timing in coast Douglas-fir

    USGS Publications Warehouse

    Ford, Kevin R.; Harrington, Constance A.; Bansal, Sheel; Gould, Petter J.; St. Clair, Bradley

    2016-01-01

    Under climate change, the reduction of frost risk, onset of warm temperatures and depletion of soil moisture are all likely to occur earlier in the year in many temperate regions. The resilience of tree species will depend on their ability to track these changes in climate with shifts in phenology that lead to earlier growth initiation in the spring. Exposure to warm temperatures (“forcing”) typically triggers growth initiation, but many trees also require exposure to cool temperatures (“chilling”) while dormant to readily initiate growth in the spring. If warming increases forcing and decreases chilling, climate change could maintain, advance or delay growth initiation phenology relative to the onset of favorable conditions. We modeled the timing of height- and diameter-growth initiation in coast Douglas-fir (an ecologically and economically vital tree in western North America) to determine whether changes in phenology are likely to track changes in climate using data from field-based and controlled-environment studies, which included conditions warmer than those currently experienced in the tree's range. For high latitude and elevation portions of the tree's range, our models predicted that warming will lead to earlier growth initiation and allow trees to track changes in the onset of the warm but still moist conditions that favor growth, generally without substantially greater exposure to frost. In contrast, towards lower latitude and elevation range limits, the models predicted that warming will lead to delayed growth initiation relative to changes in climate due to reduced chilling, with trees failing to capture favorable conditions in the earlier parts of the spring. This maladaptive response to climate change was more prevalent for diameter-growth initiation than height-growth initiation. The decoupling of growth initiation with the onset of favorable climatic conditions could reduce the resilience of coast Douglas-fir to climate change at the warm edges of its distribution.

  16. Tall stature without growth hormone: four male patients with aromatase deficiency.

    PubMed

    Rochira, Vincenzo; Zirilli, Lucia; Maffei, Laura; Premrou, Valeria; Aranda, Claudio; Baldi, Matteo; Ghigo, Ezio; Aimaretti, Gianluca; Carani, Cesare; Lanfranco, Fabio

    2010-04-01

    From preliminary observations, GH-IGF-I seems to be compromised in men with aromatase deficiency. The GH deficiency (GHD) coexists paradoxically with tall stature, raising the question whether or not a true GHD is part of this rare syndrome. To evaluate the GH secretion in aromatase-deficient men, their GH response to the GHRH plus arginine (GHRH-ARG) test was compared with that of normal subjects. The effect of estrogen replacement treatment on the GH-IGF-I axis in aromatase-deficient men was evaluated before and during therapy. A case-control study was conducted. Four adult men with aromatase deficiency were compared with 12 normal subjects. We measured the GH response to GHRH-ARG in aromatase-deficient men (at baseline and during estrogen treatment) and in normal subjects. Basal serum IGF-I was measured in both patients and controls. The response of GH to GHRH-ARG was severely impaired in men with aromatase deficiency and resulted in significantly lower (P < 0.001) levels than in normal subjects. Although normal, serum IGF-I levels were also significantly lower (P < 0.001) than in normal subjects. Both GH peak and IGF-I concentrations were not modified by estrogen therapy in men with aromatase deficiency. In aromatase-deficient men, GH response to potent provocative stimuli is impaired and is not restored by exogenous estrogens. Furthermore, a tall stature may be reached, notwithstanding the coexistence of GHD, if a prolonged time for growth is available due to a delay in bone maturation, and other growth factors different from GH (mainly insulin) promote growth.

  17. Delayed Puberty (For Teens)

    MedlinePlus

    ... the chromosomes can interfere with normal growth processes. Turner syndrome is an example of a chromosome disorder. It ... production of sex hormones. Women who have untreated Turner syndrome are shorter than normal, are usually infertile, and ...

  18. Auxologic parameters and response to 2-year therapy with recombinant human growth hormone in growth hormone deficient children with an ectopic posterior pituitary.

    PubMed

    Kalina, Maria; Kalina-Faska, Barbara; Gruszczyńska, Katarzyna; Baron, Jan; Cisowska, Anita; Morawiec, Karolina; Biel-Lewandowska, Paulina; Małecka-Tendera, Ewa

    2015-01-01

    Structural defects of the hypothalamic-pituitary area in MRI are suggested as being a more accurate marker of growth hormone deficiency (GHD) than laboratory assays. To compare auxological characteristics in GHD children with normal pituitary (NP) function and with ectopic posterior pituitary (EPP), prior to therapy with recombinant human growth hormone (rhGH), extending the follow-up to two years following treatment. Eighty-six (86) GHD patients were divided into two groups depending on the pituitary MRI: the EPP (23 children, 3.2-16.8 years old) and the NP group (63 children, 3.3-14.8 years old). Height deficits in the population (hSD) and parents (hSD-mpSD) and the change of hSD and bone/chronological age ratio were assessed before and after 12 and 24 months of rhGH therapy. Height deficits before treatment were significantly greater in EPP compared to NP [median -4.07 (-7.06, -2.75) vs -3.15 (-4.9, -2.35) for hSD, and -3.65 (-7.06, -1.21) vs -1.83 (-4.31, -0.28) for hSD-mpSD; p<0.05]. Bone age was significantly delayed in the EPP group [0.62 (0.27, 0.92) vs 0.75 (0.21, 0.71); p<0.05]; differences remained significant during follow-up. After 12 months of rhGH therapy, EPP showed significantly greater catch-up growth compared to NP [ΔhSD=1.2 (0.42, 2.69) vs 0.74 (0.05, 1.48); p<0.05]. In the 2nd year, height velocity slowed down and was comparable in the two groups. At the conclusion of the study, hSD was similar in both groups, but hSD-mpSD was more deviated in EPP [-1.79 (-3.71, -1.21) vs -1.1 (0.98, -0.07); p<0.05]. The study showed relevant auxologic differences between EPP and NP children, as well as beneficial effects of rhGH therapy in both groups.

  19. Growing Pains from Rapid Growth: A Historical Case Study of George Fox University from 1983 to 2003

    ERIC Educational Resources Information Center

    Railsback, Gary L.

    2007-01-01

    This article is a historical case study of George Fox University (GFU) in Newberg, Oregon. Using organizational lifecycle as a theoretical framework, George Fox University had a long and delayed childhood in that it remained a small and struggling institution for most of the 20th century, and then experienced rapid growth in the late 1980s. This…

  20. The Effects of Projected Future Demand Including Very Light Jet Air-Taxi Operations on U.S. National Airspace System Delays as a Function of Next Generation Air Transportation System Airspace Capacity

    NASA Technical Reports Server (NTRS)

    Smith, Jerry; Viken, Jeff; Dollyhigh, Samuel; Trani, Antonio; Baik, Hojong; Hinze, Nicholas; Ashiabor, Senanu

    2007-01-01

    This paper presents the results from a study which investigates the potential effects of the growth in air traffic demand including projected Very Light Jet (VLJ) air-taxi operations adding to delays experienced by commercial passenger air transportation in the year 2025. The geographic region studied is the contiguous United States (U.S.) of America, although international air traffic to and from the U.S. is included. The main focus of this paper is to determine how much air traffic growth, including VLJ air-taxi operations will add to enroute airspace congestion and determine what additional airspace capacity will be needed to accommodate the expected demand. Terminal airspace is not modeled and increased airport capacity is assumed.

  1. More on the Liang Bua finds and modern human cretins.

    PubMed

    Oxnard, Charles; Obendorf, Peter J; Kefford, Ben J; Dennison, John

    2012-12-01

    Brown (2012: LB1 and LB6 Homo floresiensis are not modern human (Homo sapiens) cretins, Journal of Human Evolution) makes errors of fact, omission and interpretation. Brown's comments refer, among others, to (1) delayed growth and development indicated by unfused epiphyses, (2) postcranial limb proportions: limbs to trunk, between limbs, and within limbs, (3) postcranial bone torsions and angles, (4) postcranial robusticity, real and apparent, (5) skull features, and (6) cretinism on Flores. In each of these areas, much information about cretins is incorrect and much information (Oxnard et al., 2010) comparing the Liang Bua remains with cretins is ignored. Copyright © 2012 Elsevier GmbH. All rights reserved.

  2. Transformational Impact of Health Information Technology on the Clinical Practice of Child and Adolescent Psychiatry.

    PubMed

    Peters, Todd E

    2017-01-01

    Compared with other medical specialties, psychiatrists have been slower adopters of health information technology (IT) practices, such as electronic health records (EHRs). This delay in implementation could compromise patient safety and impede integration into accountable care organizations and multidisciplinary treatment settings. This article focuses on optimizing use of EHRs for clinical practice, leveraging health IT to improve quality of care, and focusing on the potential for future growth in health IT in child and adolescent psychiatric practice. Aligning with other medical fields and focusing on transparency of mental health treatment will help psychiatrists reach parity with other medical specialties. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Aurora A Is Critical for Survival in HPV-Transformed Cervical Cancer.

    PubMed

    Gabrielli, Brian; Bokhari, Fawzi; Ranall, Max V; Oo, Zay Yar; Stevenson, Alexander J; Wang, Weili; Murrell, Melanie; Shaikh, Mushfiq; Fallaha, Sora; Clarke, Daniel; Kelly, Madison; Sedelies, Karin; Christensen, Melinda; McKee, Sara; Leggatt, Graham; Leo, Paul; Skalamera, Dubravka; Soyer, H Peter; Gonda, Thomas J; McMillan, Nigel A J

    2015-12-01

    Human papillomavirus (HPV) is the causative agent in cervical cancer. HPV oncogenes are major drivers of the transformed phenotype, and the cancers remain addicted to these oncogenes. A screen of the human kinome has identified inhibition of Aurora kinase A (AURKA) as being synthetically lethal on the background of HPV E7 expression. The investigational AURKA inhibitor MLN8237/Alisertib selectively promoted apoptosis in the HPV cancers. The apoptosis was driven by an extended mitotic delay in the Alisertib-treated HPV E7-expressing cells. This had the effect of reducing Mcl-1 levels, which is destabilized in mitosis, and increasing BIM levels, normally destabilized by Aurora A in mitosis. Overexpression of Mcl-1 reduced sensitivity to the drug. The level of HPV E7 expression influenced the extent of Alisertib-induced mitotic delay and Mcl-1 reduction. Xenograft experiments with three cervical cancer cell lines showed Alisertib inhibited growth of HPV and non-HPV xenografts during treatment. Growth of non-HPV tumors was delayed, but in two separate HPV cancer cell lines, regression with no resumption of growth was detected, even at 50 days after treatment. A transgenic model of premalignant disease driven solely by HPV E7 also demonstrated sensitivity to drug treatment. Here, we show for the first time that targeting of the Aurora A kinase in mice using drugs such as Alisertib results in a curative sterilizing therapy that may be useful in treating HPV-driven cancers. ©2015 American Association for Cancer Research.

  4. Omega-3 fatty acid supplementation delays the progression of neuroblastoma in vivo.

    PubMed

    Gleissman, Helena; Segerström, Lova; Hamberg, Mats; Ponthan, Frida; Lindskog, Magnus; Johnsen, John Inge; Kogner, Per

    2011-04-01

    Epidemiological and preclinical studies have revealed that omega-3 fatty acids have anticancer properties. We have previously shown that the omega-3 fatty acid docosahexaenoic acid (DHA) induces apoptosis of neuroblastoma cells in vitro by mechanisms involving intracellular peroxidation of DHA by means of 15-lipoxygenase or autoxidation. In our study, the effects of DHA supplementation on neuroblastoma tumor growth in vivo were investigated using two complementary approaches. For the purpose of prevention, DHA as a dietary supplement was fed to athymic rats before the rats were xenografted with human neuroblastoma cells. For therapeutic purposes, athymic rats with established neuroblastoma xenografts were given DHA daily by gavage and tumor growth was monitored. DHA levels in plasma and tumor tissue were analyzed by gas liquid chromatography. DHA delayed neuroblastoma xenograft development and inhibited the growth of established neuroblastoma xenografts in athymic rats. A revised version of the Pediatric Preclinical Testing Program evaluation scheme used as a measurement of treatment response showed that untreated control animals developed progressive disease, whereas treatment with DHA resulted in stable disease or partial response, depending on the DHA concentration. In conclusion, prophylactic treatment with DHA delayed neuroblastoma development, suggesting that DHA could be a potential agent in the treatment of minimal residual disease and should be considered for prevention in selected cases. Treatment results on established aggressive neuroblastoma tumors suggest further studies aiming at a clinical application in children with high-risk neuroblastoma. Copyright © 2010 UICC.

  5. Photoperiod cues and patterns of genetic variation limit phenological responses to climate change in warm parts of species' range: Modeling diameter-growth cessation in coast Douglas-fir.

    PubMed

    Ford, Kevin R; Harrington, Constance A; St Clair, J Bradley

    2017-08-01

    The phenology of diameter-growth cessation in trees will likely play a key role in mediating species and ecosystem responses to climate change. A common expectation is that warming will delay cessation, but the environmental and genetic influences on this process are poorly understood. We modeled the effects of temperature, photoperiod, and seed-source climate on diameter-growth-cessation timing in coast Douglas-fir (an ecologically and economically vital tree) using high-frequency growth measurements across broad environmental gradients for a range of genotypes from different seed sources. Our model suggests that cool temperatures or short photoperiods can induce cessation in autumn. At cool locations (high latitude and elevation), cessation seems to be induced primarily by low temperatures in early autumn (under relatively long photoperiods), so warming will likely delay cessation and extend the growing season. But at warm locations (low latitude or elevation), cessation seems to be induced primarily by short photoperiods later in autumn, so warming will likely lead to only slight extensions of the growing season, reflecting photoperiod limitations on phenological shifts. Trees from seed sources experiencing frequent frosts in autumn or early winter tended to cease growth earlier in the autumn, potentially as an adaptation to avoid frost. Thus, gene flow into populations in warm locations with little frost will likely have limited potential to delay mean cessation dates because these populations already cease growth relatively late. In addition, data from an abnormal heat wave suggested that very high temperatures during long photoperiods in early summer might also induce cessation. Climate change could make these conditions more common in warm locations, leading to much earlier cessation. Thus, photoperiod cues, patterns of genetic variation, and summer heat waves could limit the capacity of coast Douglas-fir to extend its growing season in response to climate change in the warm parts of its range. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  6. Comparing Teacher-Directed and Computer-Assisted Constant Time Delay for Teaching Functional Sight Words to Students with Moderate Intellectual Disability

    ERIC Educational Resources Information Center

    Coleman, Mari Beth; Hurley, Kevin J.; Cihak, David F.

    2012-01-01

    The purpose of this study was to compare the effectiveness and efficiency of teacher-directed and computer-assisted constant time delay strategies for teaching three students with moderate intellectual disability to read functional sight words. Target words were those found in recipes and were taught via teacher-delivered constant time delay or…

  7. Predictors of delayed social maturation and mental health disorders in young adults chronically ill since childhood.

    PubMed

    Kokkonen, E R; Kokkonen, J; Moilanen, I

    2001-01-01

    To ascertain the influence of juvenile-onset chronic physical diseases and associating factors of social environment on delayed social maturation and mental health disorders in young adults, we analysed a group of 407 (184 female, 223 male) subjects with these conditions and compared the results with those of 123 (63 female, 60 male) healthy controls studied at the age of 19-25 years. The social maturation index was formed on the basis of a demographic interview, which also reviewed the state of social development and the family situation during childhood. Mental health disorders were assessed with a Present State Examination (PSE) interview analysed with the CATEGO program. With regard to social maturation at least half of the patients and controls were doing well, whereas for 29% (CI(95), 25%-33%) of the patients and 17% (CI(95), 10%-24%) of the controls the index showed delayed maturation. Subjects with poor social maturation were found most often among the disabled patients but also among the patients without severe diseases. The prevalence of PSE-CATEGO-identified psychiatric syndromes was equal in the patients and the controls (22% versus 20%). However, the patients with severe or disabling diseases had more severe psychiatric syndromes. The prevalences of depressive syndromes were also equal, but the depression of the patients was more often a profound affective disorder. Male sex, poor scholastic and vocational success, and social problems in the family during childhood were significantly associated with poor social maturation. On the other hand, the most significant predictors of mental health problems in young adults were female sex, family distress during childhood, and a severe disease. Juvenile-onset physical disease was considered to delay social maturation in some subjects and to deepen or modulate the clinical picture of mental health disorders. It is concluded that juvenile-onset physical diseases combined with family-related factors affect in different ways the social growth and psychiatric well-being. The results suggest that the subjects with chronic diseases during childhood should be thoroughly assessed by a child psychiatrist to evaluate the orientation of psychological development and the impact of the child's disease on the family and to ensure balanced psychological and social growth.

  8. Expanding the clinical spectrum of chromosome 15q26 terminal deletions associated with IGF-1 resistance.

    PubMed

    O'Riordan, Aisling M; McGrath, Niamh; Sharif, Farhana; Murphy, Nuala P; Franklin, Orla; Lynch, Sally Ann; O'Grady, Michael J

    2017-01-01

    Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene on chromosome 15q26.3 is associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. Terminal deletions of chromosome 15q26 arising more proximally may also be associated with congenital heart disease, epilepsy, diaphragmatic hernia and renal anomalies. We report three additional cases of 15q26 terminal deletions with novel features which may further expand the spectrum of this rarely reported contiguous gene syndrome. Phenotypic features including neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been reported previously. Similarly, laboratory features of insulin-like growth factor 1 (IGF-1) resistance are described, including markedly elevated IGF-1 of up to +4.7 SDS. In one patient, the elevated IGF-1 declined over time and this coincided with a period of spontaneous growth acceleration. Deletions of 15q26 are a potential risk factor for aortic root dilatation, neonatal lymphedema and aplasia cutis in addition to causing growth restriction. What is Known: • Terminal deletions of chromosome 15q26 are associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. What is New: • Neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been previously described in 15q26 terminal deletions and may represent novel features. • IGF-1 levels may be increased up to 4.7 SDS.

  9. Hypoxia Response Element-Regulated MMP-9 Promotes Neurological Recovery via Glial Scar Degradation and Angiogenesis in Delayed Stroke.

    PubMed

    Cai, Hongxia; Ma, Yuanyuan; Jiang, Lu; Mu, Zhihao; Jiang, Zhen; Chen, Xiaoyan; Wang, Yongting; Yang, Guo-Yuan; Zhang, Zhijun

    2017-06-07

    Matrix metalloproteinase 9 (MMP-9) plays a beneficial role in the delayed phase of middle cerebral artery occlusion (MCAO). However, the mechanism is obscure. Here, we constructed hypoxia response element (HRE)-regulated MMP-9 to explore its effect on glial scars and neurogenesis in delayed ischemic stroke. Adult male Institute of Cancer Research (ICR) mice underwent MCAO and received a stereotactic injection of lentivirus carrying HRE-MMP-9 or normal saline (NS)/lentivirus-GFP 7 days after ischemia. We found that HRE-MMP-9 improved neurological outcomes, reduced ischemia-induced brain atrophy, and degraded glial scars (p < 0.05). Furthermore, HRE-MMP-9 increased the number of microvessels in the peri-infarct area (p < 0.001), which may have been due to the accumulation of endogenous endothelial progenitor cells (EPCs) in the peri-infarct area after glial scar degradation. Finally, HRE-MMP-9 increased the number of bromodeoxyuridine-positive (BrdU + )/NeuN + cells and the expression of PSD-95 in the peri-infarct area (p < 0.01). These changes could be blocked by vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor SU5416 and MMP-9 inhibitor 2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane (SB-3CT). Our results provided a novel mechanism by which glial scar degradation and vascular endothelial growth factor (VEGF)/VEGFR2-dependent angiogenesis may be key procedures for neurological recovery in delayed ischemic stroke after HRE-MMP-9 treatment. Therefore, HRE-MMP-9 overexpression in the delayed ischemic brain is a promising approach for neurological recovery. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  10. The impact of delayed maternity on foetal growth in Spain: An assessment by population attributable fraction.

    PubMed

    Varea, Carlos; Terán, José Manuel; Bernis, Cristina; Bogin, Barry

    2017-09-18

    Delayed childbearing is considered a risk factor for maternal-foetal health. As in other higher-income countries, in Spain age at maternity has steadily increased during the last two decades. To quantify the impact of the delay in the age at maternity on small for gestational age (SGA) categories of <3rd, 3rd-5th and 5th-10th percentiles. 2,672,350 singleton live births born to Spanish mothers in 2007-2015 were analysed. Adjusted relative risk was calculated to estimate the adjusted partial population attributable fractions (PAF p ) for mothers aged 35-39 and ≥40 years for each category of SGA considering the interaction between age at maternity and parity. Primipara 35-39 years old mothers have the highest PAF p in the three categories of SGA, with the maximum value for SGA <3rd percentile (2.57%, 95% CI 2.25, 2.88). PAF p for both primipara and multipara ≥40 years old mothers were less than 1%. PAF p for primipara older mothers increased significantly in 2007-2015 for the three categories of SGA, more clearly among those aged 35-39 years. The contribution of multipara mothers of both age groups did not increase significantly during the period. Delayed maternity is a significant adjusted risk factor for SGA, contributing to the increase of its prevalence. However, results also suggest a limited clinical impact of delayed maternity on foetal growth. Positive changes in maternal profile associated with the shift in maternal age might contribute to explain the limited impact of mothers aged 35 years and older on negative birth outcome in Spain. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  11. Impact of maternal smoking on birth size: effect of parity and sex dimorphism.

    PubMed

    Varvarigou, Anastasia A; Asimakopoulou, Aspasia; Beratis, Nicholas G

    2009-01-01

    Maternal smoking during pregnancy causes a delay of intrauterine growth. To examine the effect of maternal smoking during pregnancy on fetal growth in relationship to maternal parity, age and number of cigarettes smoked/day, and offspring's gender. We studied 2,108 term newborns (1,102 male, 1,006 female) delivered at the General University Hospital of Patras from 1994 to 2004. The 1,443 were born to mothers who did not smoke and 665 to mothers who smoked during pregnancy. Birth weight, length and head circumference were measured prospectively in all newborns. Also, maternal smoking status and number of cigarettes smoked per day, age, and parity were recorded. For the analysis, t test, one-way ANOVA, Mann-Whitney U test, Spearman rank correlation, and factorial MANOVA with covariates were used. With increasing parity, in the neonates of nonsmoking mothers there was a gradual increase of growth, whereas in neonates of smoking mothers there was a gradual decrease of growth. This effect was more pronounced in males. A significant negative main effect on growth resulted from the interaction of smoking with parity (p = 0.013), and with gender and parity (p = 0.001). There was a significant negative correlation between number of cigarettes smoked per day and growth, the strength of which increased with parity, mainly in males. Maternal smoking during pregnancy causes a delay in fetal growth, which is greater in male offspring, an effect that is enhanced with parity but is independent of maternal age. (c) 2008 S. Karger AG, Basel.

  12. Impulsive choice and pre-exposure to delays: iv. effects of delay- and immediacy-exposure training relative to maturational changes in impulsivity.

    PubMed

    Renee Renda, C; Rung, Jillian M; Hinnenkamp, Jay E; Lenzini, Stephanie N; Madden, Gregory J

    2018-04-23

    Impulsive choice describes preference for smaller, sooner rewards over larger, later rewards. Excessive delay discounting (i.e., rapid devaluation of delayed rewards) underlies some impulsive choices, and is observed in many maladaptive behaviors (e.g., substance abuse, gambling). Interventions designed to reduce delay discounting may provide therapeutic gains. One such intervention provides rats with extended training with delayed reinforcers. When compared to a group given extended training with immediate reinforcers, delay-exposed rats make significantly fewer impulsive choices. To what extent is this difference due to delay-exposure training shifting preference toward self-control or immediacy-exposure training (the putative control group) shifting preference toward impulsivity? The current study compared the effects of delay- and immediacy-exposure training to a no-training control group and evaluated within-subject changes in impulsive choice across 51 male Wistar rats. Delay-exposed rats made significantly fewer impulsive choices than immediacy-exposed and control rats. Between-group differences in impulsive choice were not observed in the latter two groups. While delay-exposed rats showed large, significant pre- to posttraining reductions in impulsive choice, immediacy-exposed and control rats showed small reductions in impulsive choice. These results suggest that extended training with delayed reinforcers reduces impulsive choice, and that extended training with immediate reinforcers does not increase impulsive choice. © 2018 Society for the Experimental Analysis of Behavior.

  13. Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair

    PubMed Central

    2015-01-01

    There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays. PMID:26016986

  14. LRRK2 delays degradative receptor trafficking by impeding late endosomal budding through decreasing Rab7 activity.

    PubMed

    Gómez-Suaga, Patricia; Rivero-Ríos, Pilar; Fdez, Elena; Blanca Ramírez, Marian; Ferrer, Isidro; Aiastui, Ana; López De Munain, Adolfo; Hilfiker, Sabine

    2014-12-20

    Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD), and sequence variations at the LRRK2 locus are associated with increased risk for sporadic PD. LRRK2 contains both GTPase and kinase domains flanked by protein interaction motifs, and mutations associated with familial PD have been described for both catalytic domains. LRRK2 has been implicated in diverse cellular processes, and recent evidence pinpoints to an important role for LRRK2 in modulating a variety of intracellular membrane trafficking pathways. However, the underlying mechanisms are poorly understood. Here, by studying the classical, well-understood, degradative trafficking pathway of the epidermal growth factor receptor (EGFR), we show that LRRK2 regulates endocytic membrane trafficking in an Rab7-dependent manner. Mutant LRRK2 expression causes a slight delay in early-to-late endosomal trafficking, and a pronounced delay in trafficking out of late endosomes, which become aberrantly elongated into tubules. This is accompanied by a delay in EGFR degradation. The LRRK2-mediated deficits in EGFR trafficking and degradation can be reverted upon coexpression of active Rab7 and of a series of proteins involved in bridging the EGFR to Rab7 on late endosomes. Effector pulldown assays indicate that pathogenic LRRK2 decreases Rab7 activity both in cells overexpressing LRRK2, as well as in fibroblasts from pathogenic mutant LRRK2 PD patients when compared with healthy controls. Together, these findings provide novel insights into a previously unknown regulation of Rab7 activity by mutant LRRK2 which impairs membrane trafficking at very late stages of the endocytic pathway. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. The influence of prefire tree growth and crown condition on postfire mortality of sugar pine following prescribed fire in Sequoia National Park

    USGS Publications Warehouse

    Nesmith, Jonathan C. B.; Das, Adrian J.; O'Hara, Kevin L.; van Mantgem, Phillip J.

    2015-01-01

    Tree mortality is a vital component of forest management in the context of prescribed fires; however, few studies have examined the effect of prefire tree health on postfire mortality. This is especially relevant for sugar pine (Pinus lambertiana Douglas), a species experiencing population declines due to a suite of anthropogenic factors. Using data from an old-growth mixed-conifer forest in Sequoia National Park, we evaluated the effects of fire, tree size, prefire radial growth, and crown condition on postfire mortality. Models based only on tree size and measures of fire damage were compared with models that included tree size, fire damage, and prefire tree health (e.g., measures of prefire tree radial growth or crown condition). Immediately following the fire, the inclusion of different metrics of prefire tree health produced variable improvements over the models that included only tree size and measures of fire damage, as models that included measures of crown condition performed better than fire-only models, but models that included measures of prefire radial growth did not perform better. However, 5 years following the fire, sugar pine mortality was best predicted by models that included measures of both fire damage and prefire tree health, specifically, diameter at breast height (DBH, 1.37 m), crown scorch, 30-year mean growth, and the number of sharp declines in growth over a 30-year period. This suggests that factors that influence prefire tree health (e.g., drought, competition, pathogens, etc.) may partially determine postfire mortality, especially when accounting for delayed mortality following fire.

  16. AZD1480 delays tumor growth in a melanoma model while enhancing the suppressive activity of myeloid-derived suppressor cells

    PubMed Central

    Maenhout, Sarah K.; Four, Stephanie Du; Corthals, Jurgen; Neyns, Bart; Thielemans, Kris; Aerts, Joeri L.

    2014-01-01

    AZD1480 is a potent, competitive small-molecule inhibitor of JAK1/2 kinase which inhibits STAT3 phosphorylation and tumor growth. Here we investigated the effects of AZD1480 on the function of different immune cell populations in a melanoma model. When MO4 tumor-bearing mice were treated with AZD1480 we observed a strong inhibition of tumor growth as well as a prolonged survival. Moreover, a significant decrease in the percentage of myeloid-derived suppressor cells (MDSCs) was observed after treatment with AZD1480. However, AZD1480 enhanced the suppressive capacity of murine MDSCs while at the same time impairing the proliferative as well as the IFN-γ secretion capacity of murine T cells. The addition of AZD1480 to co-cultures of human MDSCs and T cells does not affect the suppressive activity of MDSCs but it does reduce the IFN-γ secretion and the proliferative capacity of T cells. We showed that although AZD1480 has the ability to delay the tumor growth of MO4 tumor-bearing mice, this drug has detrimental effects on several aspects of the immune system. These data indicate that systemic targeting of the JAK/STAT pathway by JAK1/2 inhibition can have divergent effects on tumor growth and anti-tumor immune responses. PMID:25149535

  17. A novel live cell imaging system reveals a reversible hydrostatic pressure impact on cell cycle progression.

    PubMed

    Brooker, Holly R; Gyamfi, Irene A; Wieckowska, Agnieszka; Brooks, Nicholas J; Mulvihill, Daniel P; Geeves, Michael A

    2018-06-21

    Life is dependent upon the ability of a cell to rapidly respond to changes in environment. Small perturbations in local environments change the ability of molecules to interact and hence communicate. Hydrostatic pressure provides a rapid non-invasive, fully-reversible method for modulating affinities between molecules both in vivo and in vitro We have developed a simple fluorescence imaging chamber that allows intracellular protein dynamics and molecular events to be followed at pressures up to 200 bar in living cells. Using yeast we investigate the impact of hydrostatic pressure upon cell growth and cell cycle progression. While 100 bar has no affect upon viability, it induces a delay in chromosome segregation, resulting in the accumulation of long-undivided-bent cells, consistent with disruption of the cytoskeletons. This delay is independent of stress signalling and induces synchronisation of cell-cycle progression. Equivalent affects were observed in Candida albicans , with pressure inducing a reversible cell-cycle delay and hyphal growth. We present a simple novel non-invasive fluorescence microscopy based approach to transiently impact molecular dynamics to visualise, dissect and study signalling pathways and cellular processes in living cells. © 2018. Published by The Company of Biologists Ltd.

  18. Diversity of pubertal testosterone changes in boys with constitutional delay in growth and/or adolescence.

    PubMed

    Kulin, H E; Finkelstein, J W; D'Arcangelo, M R; Susman, E J; Chinchilli, V; Kunselman, S; Schwab, J; Demers, L; Lookingbill, G

    1997-01-01

    In a group of 22 boys with constitutional delay in growth and/or adolescence, intermittent testosterone enanthate treatment was employed in a randomized clinical trial at multiple doses ranging from 25-100 mg every two weeks for three month periods extending over 15-21 months. Twelve of the patients displayed a prompt increase in endogenous testosterone levels during the study period, reaching levels in the adult male range (> 250 ng/dl). The remaining 10 boys showed sluggish changes in endogenous testosterone during the investigation, ranging from 35-177 ng/dl. The bone ages and testicular sizes of the two groups at study initiation did not differ though urine LH was significantly less at study entry in the slowly maturing group. The data reveal a great diversity in the pace and pattern of endogenous testosterone changes in the study population. The results also suggest that exogenous sex steroid treatment of such patients does not speed up the central nervous system processes controlling the onset and progression of puberty. Boys with delayed puberty should be followed until endogenous testosterone levels reach the adult male range in order to rule out mild gonadotropin deficits.

  19. Nakalanga Syndrome: Clinical Characteristics, Potential Causes, and Its Relationship with Recently Described Nodding Syndrome

    PubMed Central

    Föger, Kathrin; Gora-Stahlberg, Gina; Sejvar, James; Ovuga, Emilio; Jilek-Aall, Louise; Schmutzhard, Erich

    2017-01-01

    Nakalanga syndrome is a condition that was described in Uganda and various other African countries decades ago. Its features include growth retardation, physical deformities, endocrine dysfunction, mental impairment, and epilepsy, amongst others. Its cause remains obscure. Nodding syndrome is a neurological disorder with some features in common with Nakalanga syndrome, which has been described mainly in Uganda, South Sudan, and Tanzania. It has been considered an encephalopathy affecting children who, besides head nodding attacks, can also present with stunted growth, delayed puberty, and mental impairment, amongst other symptoms. Despite active research over the last years on the pathogenesis of Nodding syndrome, to date, no convincing single cause of Nodding syndrome has been reported. In this review, by means of a thorough literature search, we compare features of both disorders. We conclude that Nakalanga and Nodding syndromes are closely related and may represent the same condition. Our findings may provide new directions in research on the cause underlying this neurological disorder. PMID:28182652

  20. FOREST ECOLOGY. Pervasive drought legacies in forest ecosystems and their implications for carbon cycle models.

    PubMed

    Anderegg, W R L; Schwalm, C; Biondi, F; Camarero, J J; Koch, G; Litvak, M; Ogle, K; Shaw, J D; Shevliakova, E; Williams, A P; Wolf, A; Ziaco, E; Pacala, S

    2015-07-31

    The impacts of climate extremes on terrestrial ecosystems are poorly understood but important for predicting carbon cycle feedbacks to climate change. Coupled climate-carbon cycle models typically assume that vegetation recovery from extreme drought is immediate and complete, which conflicts with the understanding of basic plant physiology. We examined the recovery of stem growth in trees after severe drought at 1338 forest sites across the globe, comprising 49,339 site-years, and compared the results with simulated recovery in climate-vegetation models. We found pervasive and substantial "legacy effects" of reduced growth and incomplete recovery for 1 to 4 years after severe drought. Legacy effects were most prevalent in dry ecosystems, among Pinaceae, and among species with low hydraulic safety margins. In contrast, limited or no legacy effects after drought were simulated by current climate-vegetation models. Our results highlight hysteresis in ecosystem-level carbon cycling and delayed recovery from climate extremes. Copyright © 2015, American Association for the Advancement of Science.

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