Vitamin D and bone metabolism in Graves' disease: a prospective study.

PURPOSE: Vitamin D and osteoporosis in Graves' disease (GD) have been examined in cross-sectional studies with divergent results. Here, we prospectively studied vitamin D metabolism and bone health in patients with newly diagnosed GD. METHODS: Thirty consecutive patients with de novo overt thyrotoxicosis diagnosed with GD were included. At diagnosis, none of the patients were treated with vitamin D or anti-osteoporotic drugs. All patients were initially treated with antithyroid drugs. Blood samplings were taken at baseline and at 6 weeks, 3, 6, 12 and 24 months after treatment start. Serum levels of 25OHD3, 1,25OH2D3, calcium, parathyroid hormone (PTH), and C-terminal telopeptides of Type I collagen (CTX-I) were analysed. Bone mineral density (BMD) was measured at baseline, and 1 and 2 years after treatment initiation. RESULTS: At diagnosis, patients with GD did not have vitamin D deficiency. There were no significant correlations between levels of 25OHD3 and thyrotoxicosis. Upon treatment of the thyrotoxicosis, serum calcium fell transiently, and PTH and 1,25OH2D3 increased. 25OHD3 fell within the normal range and stabilised at 6 months. CTX-I fell over 12 months, BMD increased significantly up to 2 years, p = 0.002, < 0.001 and 0.005 in the spine, left total hip and left femoral neck, respectively. CONCLUSIONS: The present data underline that thyrotoxicosis has a negative impact on bone health and demonstrate fine-tuned dynamics in bone and vitamin D metabolism. Upon treatment, bone health improved over a follow-up period of 24 months despite rising PTH. Increased conversion of 25OHD3 to 1,25OH2D3 occurs during treatment of GD.

Serum thyroglobulin is associated with orbitopathy in Graves' disease.

PURPOSE: Serum thyroglobulin levels are often elevated in Graves' disease (GD) and in most cases decrease during treatment. Its relation to Graves' orbitopathy (GO) has not been clarified. Previously, a risk of GO has been linked to smoking, TSH receptor stimulation, high TSH-receptor antibodies (TRAb), low thyroid peroxidase and thyroglobulin antibodies (TPOAb, TgAb). METHODS: We examined Tg levels in 30 consecutive patients with GD were given drug therapy (methimazole + thyroxine) for up to 24 months. GO was identified by clinical signs and symptoms. 17 patients had GO, 11 of whom had it at diagnosis while 6 developed GO during treatment. During the study, 5 subjects were referred to radioiodine treatment, 3 to surgery. The remaining 22 subjects (GO n = 12, non-GO n = 10) completed the drug regimen. RESULTS: At diagnosis, Tg levels in GO patients (n = 11) were higher (84, 30-555 µg/L, median, range) than in non-GO patients (n = 19) (38, 3.5-287 µg/L), p = 0.042. Adding the 6 subjects who developed eye symptoms during treatment to the GO group (n = 17), yielded p = 0.001 vs. non-GO (n = 13). TRAb tended to be higher, while TPOAb and TgAb tended to be lower in the GO group. For the 22 patients who completed the drug regimen, Tg levels were higher in GO (n = 12) vs. non-GO (n = 10), p = 0.004, whereas TRAb levels did not differ. CONCLUSION: The data may suggest that evaluation of thyroglobulin levels in GD could contribute to identify patients at increased risk of developing GO. Possibly, thyroidal release of Tg in GD reflects a disturbance that also impacts retroorbital tissues.

Passive leg-lifting in heart failure patients predicts exercise-induced rise in left ventricular filling pressures.

AIM: The aim of this study was to assess PCWP with passive leg-lifting (PLL) and exercise, in two groups of patients presenting with normal left ventricular ejection fraction (LVEF); one group with elevated NT-proBNP (eBNP), and one with normal NT-proBNP (nBNP) plasma concentration. METHODS AND RESULTS: Fifty-one patients with eBNP (NT-proBNP ≥ 125 ng/l) and LVEF > 50%, were investigated and compared with 34 patients with nBNP (NT-proBNP < 125 ng/l) and LVEF > 50%. Both groups underwent right heart catheterization (RHC) at rest, PLL and exercise. From RHC, mean pulmonary arterial pressure (mPAP), cardiac output (CO), and PCWP were measured. All nBNP patients had PCWP < 15 mmHg at rest, and a PCWP of < 25 mmHg with PLL and during exercise. Patients with eBNP had higher (p < 0.01) resting mPAP, PCWP, and mPAP/CO. These values increased with exercise; however, CO increased less in comparison with nBNP patients (p = 0.001). 20% of patients with eBNP had a PCWP > 15 mmHg at rest, this percentage increased to 47% with PLL and 41% had a PCWP > 25 mmHg during exercise. Of those with PCWP > 25 mmHg during exercise, 91% had a PCWP > 15 mmHg with PLL. A PCWP > 15 mmHg on PLL had a 91% sensitivity and 92% specificity in predicting exercise-induced PCWP of > 25 mmHg. CONCLUSION: In patients presenting with eBNP, PLL can predict which patients will develop elevated PCWP with exercise. These findings highlight the role of stress assessment.

No association between vitamin D levels around time of birth and later risk of developing oligo- and polyarticular juvenile idiopathic arthritis: a Danish case-cohort study.

OBJECTIVES: Basic and epidemiological studies on rheumatic autoimmune diseases have suggested an association between vitamin D levels around time of birth and disease risk. The literature on vitamin D and juvenile idiopathic arthritis (JIA) is scarce. We hypothesized that low levels of 25-hydroxyvitamin D [25(OH)D] around time of birth would be associated with increased risk of oligo- or polyarticular JIA. METHOD: We conducted a case-cohort study of validated cases diagnosed with oligo- and polyarticular JIA (1993-2012) and controls matched on date of birth. Cases and controls were born in the period 1983-2010. Cases were diagnosed using international criteria. The concentration of 25(OH)D was assessed from neonatal dried blood spot (DBS) samples using high-sensitivity liquid chromatography tandem mass spectrometry (LC-MS/MS). Odds ratios (ORs) were calculated using conditional logistic regression and a two-way analysis of variance (ANOVA) was used to test for season and birth year 25(OH)D variations. A total of 300 matched pairs were included in the statistical analyses. RESULTS: No significant association was found between levels of 25(OH)D and JIA risk in the adjusted model [OR (per 25 nmol/L increase) 1.2, 95% confidence interval (CI) 0.9-1.6, p = 0.2]. 25(OH)D levels were found to fluctuate significantly with season (p < 0.0001) and year (p < 0.0001). The median level of 25(OH)D was 34.4 nmol/L in cases and 31.5 nmol/L in controls. CONCLUSIONS: Our study does not support the hypothesis that a window of vulnerability exists around time of birth with regard to 25(OH)D levels and later JIA risk. Further studies should explore whether 25(OH)D levels during early pregnancy or infancy may influence JIA risk.

Health economic analyses of domiciliary dental care and care at fixed clinics for elderly nursing home residents in Sweden.

OBJECTIVES: Dental care for elderly nursing home residents is traditionally provided at fixed dental clinics, but domiciliary dental care is an emerging alternative. Longer life expectancy accompanied with increased morbidity, and hospitalisation or dependence on the care of others will contribute to a risk for rapid deterioration of oral health so alternative methods for delivering oral health care to vulnerable individuals for whom access to fixed dental clinics is an obstacle should be considered. The aim was to analyse health economic consequences of domiciliary dental care for elderly nursing home residents in Sweden, compared to dentistry at a fixed clinic. METHODS: A review of relevant literature was undertaken complemented by interviews with nursing home staff, officials at county councils, and academic experts in geriatric dentistry. Domiciliary dental care and fixed clinic care were compared in cost analyses and cost-effectiveness analyses. RESULTS: The mean societal cost of domiciliary dental care for elderly nursing home residents was lower than dental care at a fixed clinic, and it was also considered cost-effective. Lower cost of dental care at a fixed dental clinic was only achieved in a scenario where dental care could not be completed in a domiciliary setting. CONCLUSIONS: Domiciliary dental care for elderly nursing home residents has a lower societal cost and is cost-effective compared to dental care at fixed clinics. To meet current and predicted need for oral health care in the ageing population alternative methods to deliver dental care should be available.

Cascaded systems analysis of photon counting detectors.

PURPOSE: Photon counting detectors (PCDs) are an emerging technology with applications in spectral and low-dose radiographic and tomographic imaging. This paper develops an analytical model of PCD imaging performance, including the system gain, modulation transfer function (MTF), noise-power spectrum (NPS), and detective quantum efficiency (DQE). METHODS: A cascaded systems analysis model describing the propagation of quanta through the imaging chain was developed. The model was validated in comparison to the physical performance of a silicon-strip PCD implemented on an experimental imaging bench. The signal response, MTF, and NPS were measured and compared to theory as a function of exposure conditions (70 kVp, 1-7 mA), detector threshold, and readout mode (i.e., the option for coincidence detection). The model sheds new light on the dependence of spatial resolution, charge sharing, and additive noise effects on threshold selection and was used to investigate the factors governing PCD performance, including the fundamental advantages and limitations of PCDs in comparison to energy-integrating detectors (EIDs) in the linear regime for which pulse pileup can be ignored. RESULTS: The detector exhibited highly linear mean signal response across the system operating range and agreed well with theoretical prediction, as did the system MTF and NPS. The DQE analyzed as a function of kilovolt (peak), exposure, detector threshold, and readout mode revealed important considerations for system optimization. The model also demonstrated the important implications of false counts from both additive electronic noise and charge sharing and highlighted the system design and operational parameters that most affect detector performance in the presence of such factors: for example, increasing the detector threshold from 0 to 100 (arbitrary units of pulse height threshold roughly equivalent to 0.5 and 6 keV energy threshold, respectively), increased the f50 (spatial-frequency at which the MTF falls to a value of 0.50) by ∼30% with corresponding improvement in DQE. The range in exposure and additive noise for which PCDs yield intrinsically higher DQE was quantified, showing performance advantages under conditions of very low-dose, high additive noise, and high fidelity rejection of coincident photons. CONCLUSIONS: The model for PCD signal and noise performance agreed with measurements of detector signal, MTF, and NPS and provided a useful basis for understanding complex dependencies in PCD imaging performance and the potential advantages (and disadvantages) in comparison to EIDs as well as an important guide to task-based optimization in developing new PCD imaging systems.

Efficacy and safety of lidocaine for treatment of neonatal seizures.

AIM: Treatment of neonatal seizures still relies primarily on phenobarbital, despite an estimated efficacy of less than 50% and concern over neurodegenerative side effects. The objective of this study was to evaluate the efficacy and safety of lidocaine as second-line treatment of neonatal seizures in infants following benzodiazepine treatment but without previous treatment with phenobarbital. METHODS: In a 10-year cohort, a retrospective chart review was conducted for all infants (gestational age ≥ 37 w, age ≤ 28 days) who had received lidocaine as second-line treatment of neonatal seizures prior to treatment with phenobarbital between January 2000 and June 2010. Infants were included if they had electroencephalographic seizures. RESULTS: Cessation of seizure activity was seen in 16 of 30 infants based on clinical and electroencephalographic features, and a probable response was seen in an additional 3 of 30 patients. Suspected adverse effects were seen in only one patient, who developed a transient bradycardia. CONCLUSION: Lidocaine has a moderate efficacy as second-line therapy following benzodiazepines for treating neonatal seizures and is not frequently associated with cardiovascular adverse effects. Lidocaine should therefore be considered in the treatment of seizures in the neonatal period to a higher extent than is the case today.

Calculated optoelectronic properties of ruthenium tris-bipyridine dyes containing oligophenyleneethynylene rigid rod linkers in different chemical environments.

Ruthenium tris-bipyridine dyes containing oligophenyleneethynylene (OPE) rigid rod linker groups ([Ru(bpy)3]2+, [Ru(bpy)2bpy-E-Ipa]2+, [Ru(bpy)2bpy-E-Ph-E-Ipa]2+, and [Ru(bpy)2bpy-E-Bco-E-Ipa]2+, where bpy = 2,2'-bipyridine, E = ethynylene, Ph = p-phenylene, Bco = bicyclo[2.2.2]octylene, and Ipa = isophthalic acid) have been investigated using DFT and TD-DFT calculations to elucidate the influence of the rigid rod on their optoelectronic properties. Experimentally observed differences in the optical absorption for the different complexes are discussed on the basis of TD-DFT simulated absorption spectra. A comparison of the calculated optoelectronic properties of [Ru(bpy)2bpy-E-Ph-E-Ipa]2+ in different chemical environments, that is, in different solvents and with or without counter ions, suggests that both the absorption spectra and the redox properties of the dyes with OPE rods are sensitive to the environment. The calculations show that spurious low-energy charge-transfer excitations present in the TD-DFT calculations of the extended systems in vacuum are removed when the environment is included in the calculations.

Remote laser-induced breakdown spectroscopy for the detection and removal of salt on metal and polymeric surfaces.

The detection of contamination such as salt in outdoor high-voltage insulator systems and its subsequent removal are vital for a reliable transmission of electric power. Remote detection of salt on a copper metal surface was carried out by using a mobile laser-induced breakdown spectroscopy (LIBS) Lidar system with a laser wavelength of 355 nm. Detection of salt on a polymeric high-voltage insulator was obtained when an additional lens was inserted into the beam path, and the number of photons that was detected could be calculated by using a calibrated white light source. Ablative cleaning could readily be carried out with LIBS and was verified by observing the disappearance of the sodium D-line emission.

Quantum Chemical Calculations of the Influence of Anchor-Cum-Spacer Groups on Femtosecond Electron Transfer Times in Dye-Sensitized Semiconductor Nanocrystals.

Electronic properties of dye-sensitized semiconductor nanocrystals, consisting of perylene (Pe) chromophores attached to 2 nm TiO2 nanocrystals via different anchor-cum-spacer groups, have been studied theoretically using density functional theory (DFT) cluster calculations. Approximate effective electronic coupling strengths for the heterogeneous electron-transfer interaction have been extracted from the calculated electronic structures and are used to estimate femtosecond electron-transfer times theoretically. Results are presented for perylenes attached to the TiO2 via formic acid (Pe-COOH), propionic acid (Pe-CH2-CH2-COOH), and acrylic acid (Pe-CH [Formula: see text] CH-COOH). The calculated electron transfer times are between 5 and 10 fs with the formic acid and the conjugated acrylic acid bridges and about 35 fs with the saturated propionic acid bridge. The calculated electron injection times are of the same order of magnitude as the corresponding experimental values and qualitatively follow the experimental trend with respect to the influence of the different substitutions on the injection times.

Direct and indirect exposure to pets - risk of sensitization and asthma at 4 years in a birth cohort.

INTRODUCTION: There are conflicting data on the association between early exposure to pets and allergic diseases. Bias related to retrospective information on pet ownership has been addressed as a reason for distorted study results. OBJECTIVE: To elucidate how early exposure to cat and dog relates to IgE-sensitization and asthma in children at 2 and 4 years of age, in a prospective birth-cohort study. METHODS: Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors and symptoms of allergic disease at birth, one, two and four years of age. Dust samples collected from the mothers' beds at birth were analysed for Fel d 1 and Can f 1 in a subgroup of the cohort. Blood samples taken at four years from 2614 children were analysed for allergen-specific IgE to common airborne allergens. Risk associations were calculated with a multiple logistic regression model, with adjustment for potential confounders. RESULTS: A correlation was seen between allergen levels and reported exposure to cat and dog. Exposure to cat seemed to increase the risk of cat sensitization, OR (odds ratio) 1.44 (95% confidence interval 1.03-2.01), whereas dog exposure did not have any effect on dog sensitization, OR 1.16 (0.79-1.72). Dog ownership was related to a reduced risk of sensitization to other airborne allergens, OR 0.36 (0.15-0.83), and a similar tendency was seen for cat ownership OR 0.63 (0.37-1.07). Early dog ownership seemed to be associated with a lower risk of asthma, OR 0.50 (0.24-1.03), with no corresponding effect after cat ownership, OR 0.88 (0.56-1.38). CONCLUSION: Early exposure to cat seems to increase the risk of sensitization to cat but not of asthma at 4 years of age. Dog ownership, on the other hand, appears to be associated with lowered risk of sensitization to airborne allergens and asthma. Both aetiological relationships and selection effects have to be considered in the interpretation of these findings.

The immunoglobulin heavy chain locus of the duck. Genomic organization and expression of D, J, and C region genes.

The region of the duck IgH locus extending from upstream of the proximal diversity (D) segment to downstream of the constant gene cluster has been cloned and mapped. A sequence contig of 48,796 base pairs established that the organization of the genes is D-J(H)-mu-alpha-upsilon. No evidence for a functional homologue (or remnant) of a delta gene was found. The alpha gene is in inverted transcriptional orientation; class switch to IgA expression thus requires inversion of the approximately 27-kilobase pair region that includes both mu and alpha genes. The secreted forms of duck alpha and mu are each encoded by 4 constant region exons, and the hydrophobic C-terminal regions of the membrane receptor forms of alpha and mu are encoded by one and two transmembrane exons, respectively. Putative switch (S) regions were identified for duck mu and upsilon by comparison with chicken Smu and Supsilon sequences and for duck alpha by comparison with mouse Salpha. The duck IgH locus is rich in complex variable number tandem repeats, which occupy approximately 60% of the sequenced region, and occur at a much higher frequency in the IgH locus than in other sequenced regions of the duck genome.

Circulating human antisperm antibodies recognize prostasomes.

PROBLEM: The presence of naturally occurring antisperm antibodies (ASA) is a well-known cause of infertility in men and women, but the antigens for these antibodies are usually poorly characterized. Prostasomes, organelles secreted by human prostatic acinar cells and expelled into the seminal plasma at ejaculation, can adhere to sperm cells. Thus, we have examined whether prostasomes could be an antigen for ASA. METHOD OF STUDY: We have studied the reactivity of chicken antiprostasome antibodies with sperm cells in an agglutination test and conversely the reactivity of serum positive for ASA from 20 infertile patients, with spermatozoa using flow cytometry and with purified prostasomes using enzyme-linked immunosorbent assay. RESULTS: The chicken antiprostasome antibody caused agglutination of sperm cells similarly to the agglutination observed with patients' sera. All of these patients' sera contained IgG antibodies against prostasomes. CONCLUSIONS: The high percentage of patients with antiprostasome antibodies in this study shows that prostasomes could be one of the major targets for ASA.

Prostasome-like granules from the PC-3 prostate cancer cell line increase the motility of washed human spermatozoa and adhere to the sperm.

OBJECTIVE: Prostasome-like granules are present in the PC-3 prostate cancer cells. Since the seminal prostasomes are able to promote the forward motility of human spermatozoa, we conducted a study to determine whether PC-3 prostasomes exerted effects similar to those of seminal prostasomes on buffer-washed spermatozoa from normospermic semen samples. STUDY DESIGN: We used computer-assisted sperm analysis (CASA) and immunostaining of prostasomes to find out where these granules are located on the spermatozoa. RESULTS: Addition of PC-3 prostasomes increased the proportion of motile spermatozoa from 12-15% to 50-70% (p<0.001). The optimal protein concentration of these prostasomes was 0.1mg/ml. Heat treatment of PC-3 prostasomes did not decrease their motility-promoting effect. Immunostaining with anti-prostasome monoclonal antibody (mAb78) revealed that the PC-3 prostasomes and seminal prostasomes adhered to the sperm cells. The staining, which occurred all over the spermatozoa, was intense on the mid-pieces and weaker on the sperm heads. Herewith, some prostasome component may activate the spermatic mitochondrial function, thus increasing sperm motility. CONCLUSION: It is concluded that PC-3 prostasomes bear a functional resemblance to seminal prostasomes as regards sperm motility promotion.

Reducing the time of co-incubation of gametes in human in-vitro fertilization has no beneficial effects.

Reports concerning the benefit of reducing the co-incubation time of gametes in connection with IVF have been conflicting. The present randomized study was undertaken to determine whether a reduced co-incubation time would improve the embryo development and consequently the pregnancy and implantation rates. Oocytes from 87 patients were collected and half the oocytes from each patient (n = 488, group A) were randomized to 2 h incubation and the other half (n = 504, group B) to overnight incubation. The oocytes were then cultured according to our standard procedure. Significant difference (P = 0.02) was observed between the two groups regarding fertilization rate and polyspermy (group A 72.5%, 3% and group B 80.5%, 6% respectively). However, no difference was observed in further development and morphology of the embryos. The two embryos with the best morphological score were selected for transfer. No significant difference was found between the different transfer groups regarding positive serum HCG and implantation rate. CONCLUSION: The present results and results from previously published studies indicate that the most important factor in connection with the culture method currently used is the amount of sperm added for co-incubation. This should be optimized to reduce the concentration of harmful sperm waste products and create optimal culture conditions.

Does pronuclear morphology and/or early cleavage rate predict embryo implantation potential?

A total of 340 patients referred for in-vitro fertilization was included in a retrospective, comparative study in which zygotes were studied regarding alignment and polarization of nucleolar precursor bodies (NPB) and also early cleavage in relation to implantation and pregnancy rates for the 680 transferred embryos. At assessment of the pronucleus 18-19 h after sperm injection, NPB were checked for alignment/polarization. Twenty-six hours after sperm insemination the zygotes were assessed for early cleavage. At embryo transfer the two embryos with the best morphological score, irrespective of polarization and early cleavage, were selected for transfer. The overall rate of positive HCG tests 17 days after embryo transfer was 42% and the implantation rate 23%. Fourteen percent of the patients received two embryos with polarized NPB, with a positive HCG test of 51%. Embryo transfer with early-cleaved embryos was carried out in 21% of the cycles, with a pregnancy rate of 45%. Embryos with polarized NPB and/or early cleavage were transferred in 34% of the cycles, with a pregnancy rate of 51%, compared with a pregnancy rate of 38% when none of the embryos fulfilled these criteria (P-value 0.02). In this study the pregnancy rate was significantly higher when one or two embryos were polarized and/or early cleaved. It is concluded that in a cohort of morphologically good embryos, assessment for alignment/polarization of NPB and/or early cleavage can, together with conventional morphological criteria, serve as a simple non-invasive method for selection of embryos with high implantation potential.

Variability of the immunoglobulin light chain in the Siberian sturgeon, Acipenser baeri.

All sturgeon VL segments isolated in this study belong to a single family, VLI, which can be divided into two subfamilies. Of the 79 cDNA clones isolated, 76 belong to the larger subfamily, VLIa, and only 3 clones constitute the smaller subfamily, VLIb. To evaluate variability, the Shannon entropy was estimated for each individual amino acid position, and to facilitate comparisons of variability between species the mean entropy of the CDR regions was calculated. In such a comparison, the sturgeon was found to have CDR1 and CDR3 variability approaching those found in mouse and clawed frog, but showed very low variability for CDR2. Amino acid position 50 does however display variability in the range of mouse and clawed frog. It is further confirmed that the sturgeon has numerous J segments, but that the junctional diversity does not contribute greatly to the diversity of the light chain. Comparisons of cDNA clones and a genomic VL segment indicate that the VL undergoes changes, particularly in the CDR regions, in a manner that can be explained by somatic hypermutation and/or gene conversion.