240 research outputs found

    Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

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    PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P < 0.001), age, bisphosphonate use, and rodding (P < 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

    The CD14 functional gene polymorphism -260 C>T is not involved in either the susceptibility to Chlamydia trachomatis infection or the development of tubal pathology

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    BACKGROUND: The functional polymorphism -260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the transcriptional activity and results in a higher CD14 receptor density. Individuals carrying the T/T genotype also have significantly higher serum levels of soluble CD14. The T allele of this polymorphism has recently been linked to Chlamydia pneumoniae infection. We investigated the role of the CD14 -260 C>T polymorphism in the susceptibility to and severity (defined as subfertility and/or tubal pathology) of C. trachomatis infection in Dutch Caucasian women. METHODS: The different CD14 -260 C>T genotypes were assessed by PCR-based RFLP analysis in three cohorts: 1) A cohort (n = 576) of women attending a STD clinic, 2) a cohort (n = 253) of women with subfertility, and 3) an ethnically matched control cohort (n = 170). The following variables were used in the analysis: In cohort 1 the CT-DNA status, CT IgG serology status, self-reported symptoms and in cohort 2, the CT IgG serology status and the tubal status at laparoscopy. RESULTS: In the control cohort the CC, CT and TT genotype distribution was: 28.2%, 48.2%, and 23.5% respectively. No differences were found in the overall prevalence of CD14 -260 genotypes (28.1%, 50.7%, and 21.2%) in cohort 1 when compared to the control cohort. Also no differences were observed in women with or without CT-DNA, with or without serological CT responses, with or without symptoms, or in combinations of these three variables. In subfertile women with tubal pathology (cohort 2, n = 50) the genotype distribution was 28.0%, 48.0%, and 24.0% and in subfertile women without tubal pathology (n = 203), 27.6%, 49.3% and 23.2%. The genotype distribution was unchanged when CT IgG status was introduced in the analyses. CONCLUSION: The CD14 -260 C>T genotype distributions were identical in all three cohorts, showing that this polymorphism is not involved in the susceptibility to or severity of sequelae of C. trachomatis infection

    CRF1-R Activation of the Dynorphin/Kappa Opioid System in the Mouse Basolateral Amygdala Mediates Anxiety-Like Behavior

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    Stress is a complex human experience and having both rewarding and aversive motivational properties. The adverse effects of stress are well documented, yet many of underlying mechanisms remain unclear and controversial. Here we report that the anxiogenic properties of stress are encoded by the endogenous opioid peptide dynorphin acting in the basolateral amygdala. Using pharmacological and genetic approaches, we found that the anxiogenic-like effects of Corticotropin Releasing Factor (CRF) were triggered by CRF1-R activation of the dynorphin/kappa opioid receptor (KOR) system. Central CRF administration significantly reduced the percent open-arm time in the elevated plus maze (EPM). The reduction in open-arm time was blocked by pretreatment with the KOR antagonist norbinaltorphimine (norBNI), and was not evident in mice lacking the endogenous KOR ligand dynorphin. The CRF1-R agonist stressin 1 also significantly reduced open-arm time in the EPM, and this decrease was blocked by norBNI. In contrast, the selective CRF2-R agonist urocortin III did not affect open arm time, and mice lacking CRF2-R still showed an increase in anxiety-like behavior in response to CRF injection. However, CRF2-R knockout animals did not develop CRF conditioned place aversion, suggesting that CRF1-R activation may mediate anxiety and CRF2-R may encode aversion. Using a phosphoselective antibody (KORp) to identify sites of dynorphin action, we found that CRF increased KORp-immunoreactivity in the basolateral amygdala (BLA) of wildtype, but not in mice pretreated with the selective CRF1-R antagonist, antalarmin. Consistent with the concept that acute stress or CRF injection-induced anxiety was mediated by dynorphin release in the BLA, local injection of norBNI blocked the stress or CRF-induced increase in anxiety-like behavior; whereas norBNI injection in a nearby thalamic nucleus did not. The intersection of stress-induced CRF and the dynorphin/KOR system in the BLA was surprising, and these results suggest that CRF and dynorphin/KOR systems may coordinate stress-induced anxiety behaviors and aversive behaviors via different mechanisms

    A gastrointestinal rotavirus infection mouse model for immune modulation studies

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    <p>Abstract</p> <p>Background</p> <p>Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R<sup>ÂŽ</sup>) could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection.</p> <p>Methods</p> <p>BALB/c mice were treated by gavage once daily with Gastrogard-R<sup>ÂŽ </sup>from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV) at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM) virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH) responses were also measured.</p> <p>Results</p> <p>Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R<sup>ÂŽ </sup>were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R<sup>ÂŽ</sup>. Mice receiving Gastrogard-R<sup>ÂŽ </sup>however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected.</p> <p>Conclusions</p> <p>Preventing RRV-induced diarrhea by Gastrogard-R<sup>ÂŽ </sup>early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection.</p

    Spectral reflectance properties of iridescent pierid butterfly wings

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    The wings of most pierid butterflies exhibit a main, pigmentary colouration: white, yellow or orange. The males of many species have in restricted areas of the wing upper sides a distinct structural colouration, which is created by stacks of lamellae in the ridges of the wing scales, resulting in iridescence. The amplitude of the reflectance is proportional to the number of lamellae in the ridge stacks. The angle-dependent peak wavelength of the observed iridescence is in agreement with classical multilayer theory. The iridescence is virtually always in the ultraviolet wavelength range, but some species have a blue-peaking iridescence. The spectral properties of the pigmentary and structural colourations are presumably tuned to the spectral sensitivities of the butterflies’ photoreceptors

    The Radiation Issue in Cardiology: the time for action is now

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    The "radiation issue" is the need to consider possible deterministic effects (e.g., skin injuries) and long-term cancer risks due to ionizing radiation in the risk-benefit assessment of diagnostic or therapeutic testing. Although there are currently no data showing that high-dose medical studies have actually increased the incidence of cancer, the "linear-no threshold" model in radioprotection assumes that no safe dose exists; all doses add up in determining cancer risks; and the risk increases linearly with increasing radiation dose. The possibility of deterministic effects should also be considered when skin or lens doses may be over the threshold. Cardiologists have a special mission to avoid unjustified or non-optimized use of radiation, since they are responsible for 45% of the entire cumulative effective dose of 3.0 mSv (similar to the radiological risk of 150 chest x-rays) per head per year to the US population from all medical sources except radiotherapy. In addition, interventional cardiologists have an exposure per head per year two to three times higher than that of radiologists. The most active and experienced interventional cardiologists in high volume cath labs have an annual exposure equivalent to around 5 mSv per head and a professional lifetime attributable to excess cancer risk on the order of magnitude of 1 in 100. Cardiologists are the contemporary radiologists but sometimes imperfectly aware of the radiological dose of the examination they prescribe or practice, which can range from the equivalent of 1-60 mSv around a reference dose average of 10-15 mSv for a percutaneous coronary intervention, a cardiac radiofrequency ablation, a multi-detector coronary angiography, or a myocardial perfusion imaging scintigraphy. A good cardiologist cannot be afraid of life-saving radiation, but must be afraid of radiation unawareness and negligence

    Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer

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    Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P<0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P<0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, −2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy

    Light in the Polar Night

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    How much light isa vailable for biological processes during Polar Night? This question appears simple enough. But the reality is that conventional light sen- sors for measuring visible light (~350 to ~700 nm) have not been sensitive enough to answer it. Beyond this technical challenge, “light” is a general term that must be qualified in terms of “light climate” before it has meaning for biological systems. In this chapter, we provide an answer to the question posed above and explore aspects of light climate during Polar Night with relevance to biology, specifically, how Polar Night is defined by solar elevation, atmospheric light in Polar Night and its propaga- tion underwater, bioluminescence in Polar Night and the concept of Polar Night as a deep-sea analogue, light pollution, and future perspectives. This chapter focuses on the quantity and quality of light present during Polar Night, while subsequent chapters in this volume focus on specific biological effects of this light for algae (Chap. “Marine Micro- and Macroalgae in the Polar Night”), zooplankton (Chaps.“Zooplankton in the Polar Night” and “Biological Clocks and Rhythms in Polar Organisms”), and fish (Chap. “Fish Ecology in the Polar Night”)
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