Site specific differences in vBMD and geometry in postmenopausal women with primary hyperparathyroidism.

PURPOSE: Primary Hyperparathyroidism (PHPT) is associated with catabolic effects at both trabecular and cortical bone. Mechanical loading is one of the most important natural anabolic stimuli for bone at all ages. The present study was designed to assess the impact of PHPT on vBMD and bone geometry using peripheral quantitative computed tomography (pQCT) at the radius and tibia, sites with similar structural characteristics, but subject to different loading conditions. METHODS: We evaluated the impact of PHPT on bone, by comparing the z-scores of volumetric Bone Mineral Density (vBMD) and indices of bone geometry simultaneously at the tibia and the radius by pQCT, skeletal sites with similar structure, but subject to different loading conditions. Forty-one postmenopausal women with PHPT and 79 controls, comprised the study group. RESULTS: At both trabecular and cortical sites, vBMD and bone geometry indices were significantly lower in patients compared with controls. In patients with PHPT, apart from a lower z-score for total vBMD (p = 0.01) at the radius, there was no other difference between the radius and the tibia at the trabecular sites. On the contrary, at cortical sites, the z-scores of cortical bone mineral content (p = 0.02), cortical vBMD (p = 0.01) and cortical cross-sectional area (p = 0.05) were significantly lower at the radius compared with the tibia, indicating that cortical bone at the weight bearing tibia might be less affected by the catabolic actions of continuous parathyroid hormone (PTH) exposure. PTH levels were positively associated with the difference in z-scores of cort BMD (r = 0.439, p < 0.01) indicating that in more severe cases, as expressed by higher PTH levels, the deleterious effects at the non-weight bearing radius might be accentuated. CONCLUSION: We found that in postmenopausal women with PHPT, both trabecular and cortical bone are adversely affected. However, at the weight bearing tibia as compared with the radius, the deleterious effects, especially on cortical bone, seem to be attenuated. TRIAL REGISTRATION NUMBER: NCT05426512, 21/06/2022, "retrospectively registered".

Skin solitons.

Recently, the concept of skin effect has gained considerable attention in the context of non-Hermitian photonics. The experimental realization of Hatano-Nelson systems in optical coupled cavities has provided the opportunity to consider the effect of optical nonlinearity. In this work, we probe the interplay between Kerr nonlinearity and non-Hermiticity in a Hatano-Nelson lattice. In particular, we examine the relation between self-focusing and the skin effect under single-channel excitation. Moreover, we numerically identify skin soliton solutions, which exhibit power threshold and spatial asymmetry.

An investigation into the cytotoxic effects of microbubbles and their constituents on osteosarcoma and bone marrow stromal cells.

BACKGROUND: Ultrasound-responsive microbubbles offer a means of achieving minimally invasive, localised drug delivery in applications including regenerative medicine. To facilitate their use, however, it is important to determine any cytotoxic effects they or their constituents may have. The aim of this study was to test the hypothesis that phospholipid-shelled microbubbles are non-toxic to human bone-derived cells at biologically-relevant concentrations. METHODS: Microbubbles were fabricated using combinations of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC), polyoxyethylene(40) stearate (PEG40S) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene-glycol)-2000] (DSPE-PEG2000). Microbubble size and concentration were measured as a function of time and temperature by optical microscopy. Effects on MG63 osteosarcoma and human bone marrow stromal cells (BMSCs) were measured for up to 72 h by assay for viability, metabolic activity and proliferation. RESULTS: DBPC:DSPE-PEG2000 microbubbles were significantly more stable than DSPC:PEG40S microbubbles under all conditions tested. Serum-containing medium had no detrimental effect on microbubble stability, but storage at 37 °C compared to at 4 °C reduced stability for both preparations, with almost complete dissolution of microbubbles at times ≥24 h. DSPC:PEG40S microbubbles had greater inhibitory effects on cell metabolism and growth than DBPC:DSPE-PEG2000 microbubbles, with PEG40S found to be the principle inhibitory component. These effects were only evident at high microbubble concentrations (≥20% (v/v)) or with prolonged culture (≥24 h). Increasing cell-microbubble contact by inversion culture in a custom-built device had no inhibitory effect on metabolism. CONCLUSIONS: These data indicate that, over a broad range of concentrations and incubation times, DBPC:DSPE-PEG2000 and DSPC:PEG40S microbubbles have little effect on osteoblastic cell viability and growth, and that PEG40S is the principle inhibitory component in the formulations investigated.

Higher order exceptional points in infinite lattices.

One of the hallmarks of non-Hermitian photonics is the existence of unique degeneracies, the so-called higher order exceptional points (HEPs). So far, HEPs have been examined mostly in finite coupled systems. In this paper, we present a systematic way to construct infinite optical waveguide lattices that exhibit exceptional points of higher order. The spectral properties and the sensitivity of these lattices around such points are investigated by employing the method of pseudospectra.

Transient growth and dissipative exceptional points.

In the context of non-Hermitian photonics, we study the physics of transient growth in coupled waveguide systems that exhibit higher-order exceptional points. We demonstrate the counterintuitive effect of transient growth despite the decaying spectrum, which is a direct consequence of the underlying modal nonorthogonality. Eigenvalue analysis fails to capture the power dynamics and thus we have to rely on methods of nonmodal stability theory, namely singular value decomposition and pseudospectra. The relation between the order of the exceptional point and transient growth is also examined. Our work provides a general methodology that can be applied to any non-Hermitian system that contains complex elements with more loss than gain, and exploits the boundaries of transient amplification in dissipative environments.

Nonlinear scattering by non-Hermitian multilayers with saturation effects.

We theoretically investigate the optical properties of a one-dimensional non-Hermitian dispersive layered system with saturable gain and loss. We solve the nonhomogeneous Helmholtz equation perturbatively by applying the modified transfer matrix method and we obtain closed-form expressions for the reflection or transmission coefficients for TM incident waves. The nonreciprocity of the scattering process can be directly inferred from the analysis of the obtained expressions. It is shown that by tuning the parameters of the layers we can effectively control the impact of nonlinearity on the scattering characteristics of the non-Hermitian layered structure. In particular, we investigate the asymmetric and nonreciprocal characteristics of the reflectance and transmittance of multilayered parity-time (PT)-symmetric slab. We demonstrate that incident electromagnetic wave may effectively tunnel through the PT-symmetric multilayered structures with zero reflection. The effect of nonlinearity to the scattering matrix eigenvalues is systematically examined.

A Multicenter Study to Evaluate Harmonization of Assays for C-Terminal Telopeptides of Type I Collagen (ß-CTX): A Report from the IFCC-IOF Committee for Bone Metabolism (C-BM).

BACKGROUND: Biochemical bone turnover markers are useful tools to assess bone remodeling. C-terminal telopeptide of type I collagen (ß-CTX) has been recommended as a reference marker for bone resorption in research studies. METHODS: We describe the results of a multicenter study for routine clinical laboratory assays for ß-CTX in serum and plasma. Four centers (Athens GR, Copenhagen DK, Liege BE and Sheffield UK) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers' instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method, and Concordance correlation coefficient for ß-CTX values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. Two pools of serum were finally prepared and sent to the four centers to be measured in 5-plicates on 5 consecutive days with the different methods. RESULTS: We identified significant variations between methods and between centers although comparison results were generally more consistent in plasma compared to serum. We developed univariate linear regression equations to predict Roche Elecsys®, IDS-iSYS, or IDS ELISA ß-CTX results from any other assay and a multivariable model including the site of analysis, the age, and weight of the patient. The coefficients of determination (R2) increased from approximately 0.80 in the univariate model to approximately 0.90 in the multivariable one, with the site of analysis being the major contributing factor. Results observed on the pools also suggest that long-term storage could explain the difference observed with the different methods on serum. CONCLUSION: Our results show large within- and between-assay variation for ß-CTX measurement, particularly in serum. Stability of the analyte could be one of the explanations. More studies should be undertaken to overcome this problem. Until harmonization is achieved, we recommend measuring ß-CTX by the same assay on EDTA plasma, especially for research purposes in large pharmacological trials where samples can be stored for long periods before they are assayed.

Equal-intensity waves in non-Hermitian media.

A novel type of waves is examined in the context of non-Hermitian photonics. We can identify a class of complex guided structures that support localized paraxial solutions whose intensity distribution is exactly the same as the intensity of a corresponding solution in homogeneous media (free or bulk space). In other words, intensity-wise the two solutions are identical and their phase is different by a factor exp[iθ(x,y)]. The non-Hermitian potential is determined by the phase θ, as well as the amplitude and phase of the bulk space solution that contributes to the imaginary and real part of the potential, respectively. That way we can connect the plane waves and Gaussian beams of free space to constant-intensity waves and what we call the equal-intensity waves (EI waves) in non-Hermitian media. Such a relation allows us to study three different physical problems: Propagating EI waves inside random media, interface lattice solitons, and moving solitons in photonic waveguide structures with free-space characteristics. The relation of EI waves to unidirectional invisibility and Bohmian photonics is also examined.

Harmonization of commercial assays for PINP; the way forward.

International Federation of Clinical Chemistry and Laboratory Medicine and The International Osteoporosis Foundation Joint Committee on Bone Metabolism believes that the harmonization of PINP assays is an achievable and practical goal. INTRODUCTION: In order to examine the agreement between current commercial assays, a multi-center study was performed for PINP in serum and plasma. METHODS: The automated methods for PINP (Roche Cobas and IDS iSYS) gave similar results. A significant proportional bias was observed between the two automated assays and the Orion radioimmunoassay (RIA) for PINP. RESULTS: Results from other published studies comparing PINP values among these three assays broadly support our findings. Taken together, these results confirm that harmonized PINP measurements exist between the two automated assays (Roche Cobas and IDS iSYS) when the eGFR is > 30 mL/min/1.73m2, but a significant bias exists between the Orion RIA and the two automated assays. CONCLUSION: Therefore, in subjects with normal renal function, PINP results reported by the Roche Cobas and IDS iSYS assays are similar and may be used interchangeably, and similar reference intervals and treatment targets could be applied for the two automated assays. Harmonization between the automated assays and the RIA is potentially possible with the use of common calibrators and the development of a reference method for PINP. This should also help ensure that any new commercial assay developed in the future will attain similar results. IOF and IFCC are committed to working together towards this goal with the cooperation of the reagent manufacturing industry.

Monitoring of air pollution levels related to Charilaos Trikoupis Bridge.

Charilaos Trikoupis bridge is the longest cable bridge in Europe that connects Western Greece with the rest of the country. In this study, six air pollution monitoring campaigns (including major regulated air pollutants) were carried out from 2013 to 2015 at both sides of the bridge, located in the urban areas of Rio and Antirrio respectively. Pollution data were statistically analyzed and air quality was characterized using US and European air quality indices. From the overall campaign, it was found that air pollution levels were below the respective regulatory thresholds, but once at the site of Antirrio (26.4 and 52.2µg/m3 for PM2.5 and ΡΜ10, respectively) during the 2nd winter period. Daily average PM10 and PM2.5 levels from two monitoring sites were well correlated to gaseous pollutant (CO, NO, NO2, NOx and SO2) levels, meteorological parameters and factor scores from Positive Matrix Factorization during the 3-year period. Moreover, the elemental composition of PM10 and PM2.5 was used for source apportionment. That analysis revealed that major emission sources were sulfates, mineral dust, biomass burning, sea salt, traffic and shipping emissions for PM10 and PM2.5, for both Rio and Antirrio. Seasonal variation indicates that sulfates, mineral dust and traffic emissions increased during the warm season of the year, while biomass burning become the dominant during the cold season. Overall, the contribution of the Charilaos Trikoupis bridge to the vicinity air pollution is very low. This is the result of the relatively low daily traffic volume (~10,000 vehicles per day), the respective traffic fleet composition (~81% of the traffic fleet are private vehicles) and the speed limit (80km/h) which does not favor traffic emissions. In addition, the strong and frequent winds further contribute to the rapid dispersion of the emitted pollutants.

Iodine status and thyroid nodules in females: a comparison of Cyprus and Romania.

OBJECTIVES: The increased comparative prevalence rates of thyroid cancer in Cyprus (>EU average) led us to conduct this study on possible risk factors of thyroid nodules. Romania served as a reference with a comparative thyroid cancer prevalence < EU average. This study aimed to assess the association between urinary iodine (UI) and thyroid nodules in adult females (n = 208) from Cyprus and Romania. STUDY DESIGN: A case-control study (n = 208). METHODS: Cases were females with ultrasound-confirmed thyroid nodules and controls with confirmed absence of nodules. In both countries, subjects underwent ultrasound medical examinations, completed a questionnaire and offered a spot urine sample. RESULTS: Median UI level in Cyprus was 94 µg/L, whereas 32% of the Cypriot UI was < 50 µg/L, classifying the population as mildly iodine deficient. In Romania, both cases and controls were iodine sufficient. No significant differences (P > 0.05) in serum free thyroxin (fT4) and thyroid stimulating hormone (TSH) levels were found between cases and controls. Cases had lower median TSH levels compared with controls (1.4 mIU/L and 1.7 mIU/L, P = 0.060), but serum TSH and free thyroxin levels were within normal range. Albeit non-significant, participants with inadequate UI (<100 µg/L) had increased risk for thyroid nodules (odds ratio = 1.40, 95% confidence interval = 0.70, 2.81, P = 0.346), using multiple logistic regression after adjusting for age, body mass index, education, country and serum TSH. CONCLUSIONS: This was the first study to quantify UI levels in Cyprus. While the Romanian iodine fortification programme reflected onto its UI levels, a representative assessment of iodine status in Cyprus will address the necessity of an iodine fortification programme.

Clinical usefulness of bone turnover marker concentrations in osteoporosis.

Current evidence continues to support the potential for bone turnover markers (BTM) to provide clinically useful information particularly for monitoring the efficacy of osteoporosis treatment. Many of the limitations identified earlier remain, principally in regard to the relationship between BTM and incident fractures. Important data are now available on reference interval values for CTX and PINP across a range of geographic regions and for individual clinical assays. An apparent lack of comparability between current clinical assays for CTX has become evident indicating the possible limitations of combining such data for meta-analyses. Harmonization of units for reporting serum/plasma CTX (ng/L) and PINP (µg/L) is recommended. The development of international collaborations continues with an important initiative to combine BTM results from clinical trials in osteoporosis in a meta-analysis and an assay harmonization program are likely to be beneficial. It is possible that knowledge derived from clinical studies can further enhance fracture risk estimation tools with inclusion of BTM together with other independent risk factors. Further data of the relationships between the clinical assays for CTX and PINP as well as physiological and pre-analytical factors contributing to variability in BTM concentrations are required.

Topologically protected bound states in photonic parity-time-symmetric crystals.

Parity-time (PT)-symmetric crystals are a class of non-Hermitian systems that allow, for example, the existence of modes with real propagation constants, for self-orthogonality of propagating modes, and for uni-directional invisibility at defects. Photonic PT-symmetric systems that also support topological states could be useful for shaping and routing light waves. However, it is currently debated whether topological interface states can exist at all in PT-symmetric systems. Here, we show theoretically and demonstrate experimentally the existence of such states: states that are localized at the interface between two topologically distinct PT-symmetric photonic lattices. We find analytical closed form solutions of topological PT-symmetric interface states, and observe them through fluorescence microscopy in a passive PT-symmetric dimerized photonic lattice. Our results are relevant towards approaches to localize light on the interface between non-Hermitian crystals.

Constant-intensity waves and their modulation instability in non-Hermitian potentials.

In all of the diverse areas of science where waves play an important role, one of the most fundamental solutions of the corresponding wave equation is a stationary wave with constant intensity. The most familiar example is that of a plane wave propagating in free space. In the presence of any Hermitian potential, a wave's constant intensity is, however, immediately destroyed due to scattering. Here we show that this fundamental restriction is conveniently lifted when working with non-Hermitian potentials. In particular, we present a whole class of waves that have constant intensity in the presence of linear as well as of nonlinear inhomogeneous media with gain and loss. These solutions allow us to study the fundamental phenomenon of modulation instability in an inhomogeneous environment. Our results pose a new challenge for the experiments on non-Hermitian scattering that have recently been put forward.

Influence of household cleaning practices on the magnitude and variability of urinary monochlorinated bisphenol A.

Low-dose health effects of BPA have not been adequately explored in the presence of BPA metabolites of chlorinated structure that may exert larger estrogenic effects than those of their parent compound. We hypothesized that chlorine-containing cleaning products used in household cleaning activities could modify the magnitude of total urinary BPA concentration measurements via the production of chlorinated BPA (ClBPA) derivatives. Our objective was to investigate the influence of typical household cleaning activities (dishwashing, toilet cleaning, mopping, laundry, etc.) on the magnitude and variability of urinary total BPA and mono-ClBPA levels in the general adult population. A cross-sectional study (n=224) included an adult (≥18 years) pool of participants from the general population of Nicosia, Cyprus. First morning urine voids were collected, and administered questionnaires included items about household cleaning habits, demographics, drinking water consumption rates and water source/usage patterns. Urinary concentrations of total BPA (range: 0.2-82 µg L(-1)), mono-ClBPA (16-340 ng L(-1)), and total trihalomethanes (0.1-5.0 µg L(-1)) were measured using gas chromatography coupled with triple quadrupole mass spectrometry and large volume injection. Linear multiple regression analysis revealed that dishwashing along with age and gender (females) were able to predict urinary mono-ClBPA levels (ng g(-1)), even after adjusting for covariates; this was not the case for urinary total BPA levels (ng g(-1)). Significant (p<0.001) association was observed between urinary mono-ClBPA and THM levels, underlying the important role of disinfectant (chlorine) in promoting formation of both ClBPA and THM. Urinary mono-ClBPA levels were measured for the first time using an appreciable sample size, highlighting the co-occurring patterns of both total BPA and mono-ClBPA. Epidemiological studies and probabilistic BPA risk assessment exercises should consider assessing daily intake estimates for chlorinated BPA compounds, as well.

Accelerating diffraction-free beams in photonic lattices.

We study nondiffracting accelerating paraxial optical beams in periodic potentials, in both the linear and the nonlinear domains. In particular, we show that only a unique class of z-dependent lattices can support a true accelerating diffractionless beam. Accelerating lattice solitons, autofocusing beams and accelerating bullets in optical lattices are systematically examined.

Household cleaning activities as noningestion exposure determinants of urinary trihalomethanes.

Previous epidemiological studies linking drinking water total trihalomethanes (THM) with pregnancy disorders or bladder cancer have not accounted for specific household cleaning activities that could enhance THM exposures. We examined the relation between household cleaning activities (washing dishes/clothes, mopping, toilet cleaning, and washing windows/surfaces) and urinary THM concentrations accounting for water sources, uses, and demographics. A cross-sectional study (n = 326) was conducted during the summer in Nicosia, Cyprus, linking household addresses to the geocoded public water pipe network, individual household tap water, and urinary THM measurements. Household tap water THM concentrations ranged between 3-129 µg L(-1), while the median (Q1, Q3) creatinine-adjusted urinary THM concentration in females (669 ng g(-1) (353, 1377)) was significantly (p < 0.001) higher than that in males (399 ng g(-1), (256, 681)). Exposure assessment, based on THM exposure equivalency units, showed that hand dishwashing, mopping, and toilet cleaning significantly (p < 0.001) increased urinary THM levels. The effect of dishwashing by females ≥36 y of age remained significant, even after adjusting for potential confounders. No significant (p > 0.05) association was observed between ingestion-based THM exposure equivalency units and urinary THM. Noningestion routes of THM exposures during performance of routine household cleaning activities were shown for the first time to exert a major influence on urinary THM levels. It is warranted that future pregnancy-birth cohorts include monitoring of noningestion household THM exposures in their study design.