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New bioactive scaffolds with improved mechanical properties, biocompatibility and providing structural support for bone tissue are being developed for use in the treatment of bone defects. In this study, we have synthesized bioactive scaffolds consisting of biphasic calcium phosphate (BCP) and zirconia-Mullite (2ZrO2·[3Al2O3 ·2 SiO2] (ZAS)) (BCPZAS) combined with polymers matrix of polycaprolactone (PCL)-alginate (Alg)-chitosan (Chi) (Chi/Alg-PCL) (BCPZAS@Chi/Alg-PCL). The composite material scaffolds were prepared by a blending technique. The microstructure, mechanical, bioactivity and in vitro biological properties with different ratios of BCP to ZAS of 10, 31, 11, 13 and 01 wt% in polymer matrix were analyzed. Selleckchem 4-MU Microstructure analysis showed a successful incorporation of the BCPZAS particles with an even distribution of them within the polymer matrix. The mechanical properties were found to gradually decrease with increasing the ratio of ZAS particles in the scaffolds. The highest compressive strength was 42.96 ± 1.01MPa for the 31 wt% BCP to ZAS mixing. Bioactivity test, the BCPZAS@Chi/Alg-PCL composite could induce apatite formation in simulate body fluid (SBF). In-vitro experiment using UMR-106 osteoblast-like cells on BCPZAS@Chi/Alg-PCL composite scaffold showed that there is cell attachment to the scaffolds with proliferation. These experimental results demonstrate that the BCPZAS@Chi/Alg-PCL composite especially for the BCPZAS at 31 wt% could be utilized as a scaffold for bone tissue engineering applications.

To investigate the association between subjective pain intensity and objective parameters obtained from two autonomic function tests in a longitudinal study targeting acute pain model in otolaryngology-head and neck region pupillary light reflex (PLR) and heart rate variability (HRV).

We enrolled 35 patients with acute otolaryngology-head and neck region inflammatory disorders at pre-treatment stage. The acute inflammatory disorders were defined as acute tonsillitis, peritonsillar abscess, acute epiglottitis, acute sinusitis, and deep neck space abscess. Patients underwent a numeric rating scale (NRS) to monitor subjective pain intensity, PLR, and HRV as objective tests at 4 time-points during the follow-up term. As main outcome variables, we used 15 analyzable PLR/HRV parameters. To improve robustness of conclusions about the association between NRS and PLR/HRV parameters, we prepared four linear mixed-effects models (LMMs) including predictor variables such as NRS, sociodemographic factors, and individuccurate parameter estimation in the longitudinal study.Particle radiography (pRad) has been proposed and investigated as a promising tool for particle therapy as it provides a water equivalent thickness (WET) image of the patient. In single-event particle imaging, for each measured particle, the related most likely path (MLP) through the object is estimated to account for multiple Coulomb scattering (MCS). In previous studies, the accuracy limit of the MLP has been used to determine the spatial resolution limit. In this work, we investigate the limit of the spatial resolution achievable with different pRad algorithms based on a theoretical model of the particle scattering for an ideal beam and detector. link2 First, we investigate binning the particles in a plane seated at the depth of the object of interest (plane-of-interest binning; PIB) and extend existing theoretical considerations also to objects not located in the binning plane. We use this to model the spatial resolution in case of binning the particles directly at the front or rear tracker (FTB and RTB, respectively). Further, we investigate evenly distributing the particles' WET along their trajectory into pixel channels and creating the pRad image as channel mean (along-path-binning; APB). Monte Carlo simulations are used to qualitatively investigate the different algorithms and to validate the theoretical predictions. We show that projecting the scattered particle paths onto a single image will inevitably result in a limited spatial resolution lower than expected from only the MLP uncertainty. Only in the case where the depth of a feature is known and used as binning depth for PIB, the spatial resolution of that feature is equal to the path estimation accuracy. For the APB algorithm the spatial resolution decreases with increasing depth in the object, especially if the true particle path through the object would be known. The derived theoretical models will be useful for future development of improved pRad reconstruction algorithms.

To identify the relative positions of the ultimate RBE, at a LET value of LET

(where the LET-RBE turnover point occurs independently of dose), and of the maximum LET (LET

) for a range of ions from protons to Iron ions.

For a range of relativistic velocities (β), the kinetic energies, LET values and ranges for each ion are obtained using SRIM software. For protons and helium ions, the LET changes with β are plotted and LET

is compared with LET

For all the ions studied the residual ranges of particles at LET

and LET

are subtracted to provide the physical separation (S) between LET

and LET

.

Graphical methods are used to show the above parameters for protons and helium ions. For all the ions studied, LET

occurs at kinetic energies which are higher than those at LET

, so the ultimate maximal RBE occurs proximal to the Bragg peak for individual particles and not beyond it, as is commonly supposed. The distance S, between LET

and LET

, appears to increase linearly with the atomic charge vtraversed by a single particle.

The association between dysregulated thyroid hormone function and cancer risk is inconclusive, especially among different age groups and uncommon malignancies. We sought to determine the relation of TSH and free T4 levels with overall cancer risk as well as risk of specific cancer types.

Data on thyroid hormone profile was collected from 375 635 Israeli patients with no prior history of cancer. link3 Cancer cases were identified via the Israel National Cancer Registry. Cox proportional hazards model was used to assess hazard ratios for overall cancer as well as 20 cancer subgroups.

In this study, 23 808 cases of cancer were detected over median follow up of 10.9 years. Among patients younger than 50 at inclusion, TSH in the hyperthyroid range, elevated free T4 and subclinical hyperthyroidism were associated with increased cancer risk (HR 1.3, 1.28 and 1.31, respectively). In contrast, patients 50 or older with clinical hyperthyroidism were at lower cancer risk (HR 0.64). Elevated TSH was associated with decreased risk of prostate cancer (HR 0.67). Log-TSH elevation was associated with decreased risk of thyroid cancer (HR 0.82) and increased risk of melanoma (HR 1.11) and uterine cancer (HR 1.27). Elevated free T4 was associated with increased lung cancer risk (HR 1.54), while free T4 levels above the normal range and clinical hyperthyroidism were related to lower colorectal cancer risk (HR 0.59 and 0.08, respectively).

Thyroid hormones display opposing effects on cancer risk, based on patient age and cancer type.

Thyroid hormones display opposing effects on cancer risk, based on patient age and cancer type.

Androgens are important modulators of immune cell function. The local generation of active androgens from circulating precursors is an important mediator of androgen action in peripheral target cells or tissues. We aimed to characterize the activation of classic and 11-oxygenated androgens in human peripheral blood mononuclear cells (PBMCs).

PBMCs were isolated from healthy male donors and incubated ex vivo with precursors and active androgens of the classic and 11-oxygenated androgen pathways. Steroids were quantified by liquid chromatography-tandem mass spectrometry. The expression of genes encoding steroid-metabolizing enzymes was assessed by quantitative PCR.

PBMCs generated eight-fold higher amounts of the active 11-oxygenated androgen 11-ketotestosterone than the classic androgen testosterone from their respective precursors. We identified the enzyme AKR1C3 as the major reductive 17β-hydroxysteroid dehydrogenase in PBMCs responsible for both conversions and found that within the PBMC compartment nrs to the anti-viral immune defense. This potentially links intracrine 11-oxygenated androgen generation to the previously observed decreased NK cell cytotoxicity and increased infection risk in primary adrenal insufficiency. In addition, we show that PBMCs continue to generate 11-ketotestosterone if the cellular component of whole blood samples is not removed in a timely fashion, which could affect measurements of this active androgen in routine clinical biochemistry.

While vitamin D regulates immune cells, little is known about it in autoimmune Addison's disease (AAD). We investigated the vitamin D status in AAD patients from five European populations to assess its deficiency. In addition, we studied two case-control cohorts for vitamin D metabolism and pathway genes.

Cross-sectional study.

A total of 1028 patients with AAD from Germany (n = 239), Italy (n = 328), Norway (n = 378), UK (n = 44) and Poland (n = 39) and 679 controls from Germany (n = 301) and Norway (n = 378) were studied for 25(OH)D3 (primary objective). Secondary objectives (1,25(OH)2D3 and pathway genes) were examined in case-controls from Germany and Norway correlating 25(OH)D3 and single nucleotide polymorphisms within genes encoding the vitamin D receptor (VDR), 1-α-hydroxylase (CYP27B1), 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1) and vitamin D binding protein (GC/DBP).

Vitamin D deficiency (25(OH)D3 10-20 ng/mL) was highly prevalent in AAD patients (34-57%), 5-22% were severely deficient (<10 ng/mL), 28-38% insufficient (20-30 ng/mL) and only 7-14% sufficient (>30 ng/mL). Lower 25(OH)D3 and 1,25(OH)2D3 levels were observed both in Norwegian and German AAD (P = 0.03/0.003 and P = 1 × 10-5/< 1 × 10-7, respectively) the former was associated with CYP2R1 (rs1553006) genotype G. Whereas controls achieved sufficient median 25(OH)D3 in summers (21.4 to 21.9 ng/mL), AAD patients remained largely deficient (18.0 to 21.2 ng/mL) and synthesize less 1,25(OH)2D3.

Vitamin D deficiency and insufficiency are highly prevalent in AAD patients. The vitamin D status of AAD may be influenced by genetic factors and suggests individual vitamin D requirements throughout the year.

Vitamin D deficiency and insufficiency are highly prevalent in AAD patients. The vitamin D status of AAD may be influenced by genetic factors and suggests individual vitamin D requirements throughout the year.

To investigate the impact of age, obesity and metabolic parameters on 13 circulating steroids in reproductive and menopausal age. To define reference intervals (RIs).

Cross-sectional.

Three hundred and twenty five drug-free, healthy and eumenorrheic women were selected from the general population. Independent relationships of LC-MS/MS-determined steroid levels with age, BMI and metabolic parameters were estimated. Reference sub-cohorts were defined for calculating upper and lower limits in reproductive age, menstrual phases and menopause, and these were compared with limits in dysmetabolic sub-cohorts.

Lower androgens, pro-androgens and estrogens, but higher cortisol and metabolites were found in menopausal compared to reproductive age women. Androgens and precursors decreased during reproductive age (P < 0.001-P = 0.002) but not after menopause. 17OH-progesterone decreased with BMI (P = 0.006) and glucocorticoids with waist circumference (P < 0.001P = 0.002) in reproductive age, but increased with triglycerides (P=0.

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