Vitamin D3 supplementation does not modify cardiovascular risk profile of adults with inadequate vitamin D status.

PURPOSE: The Nutrition Societies in Germany, Austria, and Switzerland recommend a daily intake of 20 µg vitamin D3 for adults when endogenous synthesis is absent. The current study aimed to elucidate whether this vitamin D3 dose impacts cardiovascular risk markers of adults during the winter months. METHODS: The study was conducted in Halle (Saale), Germany (51o northern latitude) as a placebo-controlled, double-blinded, randomised trial (from January to April). A total of 105 apparently healthy subjects (male and female, 20-71 years old) were included. Subjects were randomly allocated to two groups. One group received a daily 20-µg vitamin D3 dose (n = 54), and the other group received a placebo (n = 51) for 12 weeks. Outcome measures included blood pressure, heart rate, concentrations of renin, aldosterone, serum lipids and vascular calcification markers, and haematologic variables such as pro-inflammatory monocytes. RESULTS: Blood pressure and systemic cardiovascular risk markers remained unchanged by vitamin D3 supplementation, although serum 25-hydroxyvitamin D3 increased from 38 ± 14 to 73 ± 16 nmol/L at week 12. The placebo and vitamin D groups did not differ in their final cardiovascular risk profile. CONCLUSION: Daily supplementation of 20 µg vitamin D3 during winter is unlikely to change cardiovascular risk profile.

Comparison of Corneal Diameter and Anterior Chamber Depth Measurements Using 4 Different Devices.

PURPOSE: To evaluate the reliability and validity of anterior chamber depth (ACD) and corneal diameter [white-to-white (WTW) distance] measurements with 4 devices as well as applicability of these values in predicting the anterior chamber angle diameter evaluated by optical coherence tomography for implantation of lenses in the anterior chamber. METHODS: In this prospective randomized case series, we measured ACD and WTW distance in one eye of 40 healthy subjects with Pentacam HR, IOL Master 500, LenStar 900, and Visante OCT. RESULTS: When comparing WTW distance with anterior chamber angle diameter measured by Visante OCT coefficient of repeatability and limits of agreement ranges were 0.5 and 1.1 mm for IOL Master, 0.5 and 1.1 mm for Pentacam HR, and 0.6 and 1.1 mm for LenStar (P < 0.05 in all cases), respectively. Coefficient of repeatability and limits of agreement ranges were 0.3 and 0.6 mm for IOL Master, 0.3 and 0.5 mm for Pentacam HR, and 0.3 and 0.6 mm for LenStar, respectively, compared with ACD measured by Visante OCT; however, P was not significant in any of the cases. P value was also not significant when comparing IOL Master, LenStar, and Pentacam in terms of ACD and WTW distance with each other. CONCLUSIONS: Unlike previous groups analyzing the ACD and WTW distance we found no significant difference between the measurements by different automatic devices. We consequently expect no difference in clinical outcome when measurements for WTW distance or ACD are performed with any of the devices listed above.

Highly sensitive SnO2 sensor via reactive laser-induced transfer.

Gas sensors based on tin oxide (SnO2) and palladium doped SnO2 (Pd:SnO2) active materials are fabricated by a laser printing method, i.e. reactive laser-induced forward transfer (rLIFT). Thin films from tin based metal-complex precursors are prepared by spin coating and then laser transferred with high resolution onto sensor structures. The devices fabricated by rLIFT exhibit low ppm sensitivity towards ethanol and methane as well as good stability with respect to air, moisture, and time. Promising results are obtained by applying rLIFT to transfer metal-complex precursors onto uncoated commercial gas sensors. We could show that rLIFT onto commercial sensors is possible if the sensor structures are reinforced prior to printing. The rLIFT fabricated sensors show up to 4 times higher sensitivities then the commercial sensors (with inkjet printed SnO2). In addition, the selectivity towards CH4 of the Pd:SnO2 sensors is significantly enhanced compared to the pure SnO2 sensors. Our results indicate that the reactive laser transfer technique applied here represents an important technical step for the realization of improved gas detection systems with wide-ranging applications in environmental and health monitoring control.

Vitamin D3 supplementation: Response and predictors of vitamin D3 metabolites - A randomized controlled trial.

BACKGROUND & AIMS: Large parts of the population are insufficiently supplied with vitamin D, in particular when endogenous synthesis is absent. Therefore many health care providers recommend the use of vitamin D supplements. The current study aimed to investigate the efficacy of an once-daily oral dose of 20 µg vitamin D3 to improve the vitamin D status and to evaluate predictors of response. METHODS: The study was conducted as a double-blind, randomized, placebo-controlled parallel trial from January till April 2013. In total, 105 subjects (20-71 years) were allocated to receive either a vitamin D3 supplement (20 µg/d) or a placebo for 12 weeks. Circulating levels of vitamin D3 metabolites such as the 25(OH)D3 and the 24,25(OH)2D3, and biomarkers of calcium and phosphate metabolism were quantified. RESULTS: The 25(OH)D3 serum concentrations in the placebo group decreased from 38 ± 15 nmol/L at baseline to 32 ± 14 nmol/L and 32 ± 13 nmol/L at weeks 8 and 12 of the study, respectively (p < 0.01). In the vitamin D3 group, the serum 25(OH)D3 concentration increased from 38 ± 14 nmol/L at baseline to 70 ± 15 nmol/L and 73 ± 16 nmol/L at weeks 8 and 12 of vitamin D3 supplementation (p < 0.001), respectively. As a result, 94% of the vitamin D3-supplemented participants reached 25(OH)D3 concentrations of ≥50 nmol/L and thereof 46% attained 25(OH)D3 levels of ≥75 nmol/L until the end of the study. The extent of the 25(OH)D3 increase upon vitamin D3 supplementation depended on 25(OH)D3 baseline levels, age, body weight and circulating levels of triglycerides. In contrast to 25(OH)D3, the response of 24,25(OH)2D3 to the vitamin D3 treatment was affected only by baseline levels of 24,25(OH)2D3 and age. CONCLUSIONS: The average improvement of 25(OH)D3 levels in individuals who received 20 µg vitamin D3 per day during the winter months was 41 nmol/L compared to individuals without supplementation. As a result almost all participants with the vitamin D3 supplementation attained 25(OH)D3 concentrations of 50 nmol/L and higher. The suitability of 24,25(OH)2D3 as a marker of vitamin D status needs further investigation. Clinical trial registration number at clinicaltrials.gov: NCT01711905.

Efficacy of fish intake on vitamin D status: a meta-analysis of randomized controlled trials.

BACKGROUND: It is well known that fish is the major natural source of vitamin D in the diet; therefore, this meta-analysis investigated the influence of fish consumption in randomized controlled trials (RCTs) on serum 25-hydroxyvitamin D [25(OH)D] concentrations. OBJECTIVE: A literature search was carried out in Medline, Embase, Web of Science, and the Cochrane Library (up to February 2014) for RCTs that investigated the effect of fish consumption on 25(OH)D concentrations in comparison to other dietary interventions. RESULTS: Seven articles and 2 unpublished study data sets with 640 subjects and 14 study groups met the inclusion criteria and were included in this meta-analysis. Compared with controls, the consumption of fish increased 25(OH)D concentrations, on average, by 4.4 nmol/L (95% CI: 1.7, 7.1 nmol/L; P < 0.0001, I(2) = 25%; 9 studies).The type of the fish also played a key role: the consumption of fatty fish resulted in a mean difference of 6.8 nmol/L (95% CI: 3.7, 9.9 nmol/L; P < 0.0001, I(2) = 0%; 7 study groups), whereas for lean fish the mean difference was 1.9 nmol/L (95% CI: -2.3, 6.0 nmol/L; P < 0.38, I(2) = 37%; 7 study groups). Short-term studies (4-8 wk) showed a mean difference of 3.8 nmol/L (95% CI: 0.6, 6.9 nmol/L; P < 0.02, I(2) = 38%; 10 study groups), whereas in long-term studies (∼6 mo) the mean difference was 8.3 nmol/L (95% CI: 2.1, 14.5 nmol/L; P < 0.009, I(2) = 0%; 4 study groups). CONCLUSION: As the major food source of vitamin D, fish consumption increases concentrations of 25(OH)D, although recommended fish intakes cannot optimize vitamin D status.

Cavitands incorporating a Lewis acid dinickel chelate function as receptors for halide anions.

The halide binding properties of the cavitand [Ni2(L(Me2H4))](2+) (4) are reported. Cavitand 4 exhibits a chelating N3Ni(µ-S)2NiN3 moiety with two square-pyramidal Ni(II)N3S2 units situated in an anion binding pocket of ∼4 Å diameter formed by the organic backbone of the (L(Me2H4))(2-) macrocycle. The receptor reacts with fluoride, chloride (in MeCN/MeOH), and bromide (in MeCN) ions to afford an isostructural series of halogenido-bridged complexes [Ni2(L(Me2H4))(µ-Hal)](+) (Hal = F(-) (5), Cl(-) (6), and Br(-) (7)) featuring a N3Ni(µ-S)2(µ-Hal)NiN3 core structure. No reaction occurs with iodide or other polyatomic anions (ClO4(-), NO3(-), HCO3(-), H2PO4(-), HSO4(-), SO4(2-)). The binding events are accompanied by discrete UV-vis spectral changes, due to a switch of the coordination geometry from square-pyramidal (N3S2 donor set in 4) to octahedral in the halogenido-bridged complexes (N3S2Hal donor environment in 5-7). In MeCN/MeOH (1/1 v/v) the log K11 values for the 1:1 complexes are 7.77(9) (F(-)), 4.06(7) (Cl(-)), and 2.0(1) (Br(-)). X-ray crystallographic analyses for 4(ClO4)2, 4(I)2, 5(F), 6(ClO4), and 7(Br) and computational studies reveal a significant increase of the intramolecular distance between two propylene groups at the cavity entrance upon going from F(-) to I(-) (for the DFT computed structure). In case of the receptor 4 and fluorido-bridged complex 5, the corresponding distances are nearly identical. This indicates a high degree of preorganization of the [Ni2(L(Me2H4))](2+) receptor and a size fit mismatch of the receptor binding cavity for anions larger than F(-).

Bioavailability of vitamin D(2) and D(3) in healthy volunteers, a randomized placebo-controlled trial.

BACKGROUND: The bioequivalence of the different forms of vitamin D, ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3), has been questioned. Earlier studies have suggested that vitamin D2 is less biologically active than vitamin D3. OBJECTIVE AND DESIGN: In a parallel study, we tested the effects of supplementation with 50-µg/d doses of vitamin D2 or D3 or a placebo over a period of 8 weeks on 25(OH)D2, 25(OH)D3, their sum 25(OH)D (primary outcome variables), and PTH in healthy volunteers applying a double-blind, randomized study design. The study was conducted during the winter of 2012 in Halle (Saale), Germany, at latitude 51°47N, when UVB irradiation is virtually absent. Blood samples for the determinations of vitamin D status and PTH were collected at baseline and after 4 and 8 weeks of supplementation. RESULTS: In the placebo group (n = 19), 25(OH)D3 decreased from 39.4 ± 14.2 to 31.1 ± 12.4 nmol/L after 8 weeks (P < .01). In the vitamin D3 group (n = 42), the concentrations of 25(OH)D3 increased from 41.5 ± 22.8 nmol/L at baseline to 88.0 ± 22.1 nmol/L after 8 weeks (P < .01). In the group receiving vitamin D2 (n = 46), the 25(OH)D2 concentrations increased significantly, whereas the 25(OH)D3 concentration fell from 36.4 ± 13.3 nmol/L at baseline to 16.6 ± 6.3 nmol/L after 8 weeks (P < .01). The total 25(OH)D was not different between the groups at baseline but differed significantly between the groups after 4 and 8 weeks (P < .001). CONCLUSIONS: Vitamin D3 increases the total 25(OH)D concentration more than vitamin D2. Vitamin D2 supplementation was associated with a decrease in 25(OH)D3, which can explain the different effect on total 25(OH)D.

Binuclear nickel complexes with an edge sharing bis(square-pyramidal) N3Ni(µ-S2)NiN3 core: synthesis, characterization, crystal structure and magnetic properties.

The synthesis of the novel macrocyclic octadentate amino-thiophenolate ligand H(2)L2 (3,7,11,19,23,27-hexaaza-33,34-dithiol-15,31-di(tert-butyl)-tricyclo[27,3,1(13.17)]-tetratriaconta-1(32),13,15,17(34),29,30-hexane) and its ability to support binuclear nickel(II) complexes with dithiolato-bridged square-pyramidal Ni(II) ions are reported. H(2)L2 is obtained as the hexahydrobromide salt from a Schiff-base condensation reaction between 1,2-bis(4-tert-butyl-2,6-diformylphenylthio)ethane and bis(3-aminopropyl)amine followed by two successive reductions with NaBH(4) and Na/NH(3). The ligand forms a green, paramagnetic, binuclear nickel(II) complex dication [Ni(II)(2)L2](2+), which can be isolated as a ClO(4)(-) (4) or BPh(4)(-) salt (5). The binuclear nickel(II) complex contains a central N(3)Ni(µ-S)(2)NiN(3) core with two square-pyramidal coordinated Ni(II) ions. The [Ni(2)L2](2+) dication does not bind further coligands, in striking contrast to the behaviour of the parent [Ni(2)L1](2+) dication supported by the smaller (L1)(2-) macrocycle (containing diethylenetriamine in place of the dipropylenetriamine units) which readily binds a variety of other coligands (L') to form bisoctahedral [Ni(2)L1(L')](+) structures. The unusual behaviour of 4 relates to two different N configurations which leads to a steric shielding of the third bridging position by the CH(2)-groups of the dipropylenetriamine chains. An analysis of the temperature-dependent magnetic susceptibility data of 5 reveals the presence of a weak antiferromagnetic exchange interaction between the spins of the nickel(II) ions with a value for the magnetic exchange coupling constant J of -23.5 cm(-1) (H = -2JS(1)S(2)). These results are further substantiated by DFT calculations.

Dependence of the chemical properties of macrocyclic [Ni(II)(2)L(µ-O(2)CR)](+) complexes on the basicity of the carboxylato coligands (L(2-) = macrocyclic N(6)S(2) ligand).

The dependence of the properties of mixed ligand [Ni(II)(2)L(µ-O(2)CR)](+) complexes (where L(2-) represents a 24-membered macrocyclic hexaamine-dithiophenolato ligand) on the basicity of the carboxylato coligands has been examined. For this purpose 19 different [Ni(II)(2)L(µ-O(2)CR)](+) complexes (2-20) incorporating carboxylates with pK(b) values in the range 9 to 14 have been prepared by the reaction of [Ni(II)(2)L(µ-Cl)](+) (1) and the respective sodium or triethylammonium carboxylates. The resulting carboxylato complexes, isolated as ClO(4)(-) or BPh(4)(-) salts, have been fully characterized by elemental analyses, IR, UV/vis spectroscopy, and X-ray crystallography. The possibility of accessing the [Ni(II)(2)L(µ-O(2)CR)](+) complexes by carboxylate exchange reactions has also been examined. The main findings are as follows: (i) Substitution reactions between 1 and NaO(2)CR are not affected by the basicity or the steric hindrance of the carboxylate. (ii) Complexes 2-20 form an isostructural series of bisoctahedral [Ni(II)(2)L(µ-O(2)CR)](+) compounds with a N(3)Ni(µ-SR)(2)(µ-O(2)CR)NiN(3) core. (iii) They are readily identified by their ν(as)(CO) and ν(s)(CO) stretching vibration bands in the ranges 1684-1576 cm(-1) and 1428-1348 cm(-1), respectively. (iv) The spin-allowed (3)A(2g) → (3)T(2g) (ν(1)) transition of the NiOS(2)N(3) chromophore is steadily red-shifted by about 7.5 nm per pK(b) unit with increasing pK(b) of the carboxylate ion. (v) The less basic the carboxylate ion, the more stable the complex. The stability difference across the series, estimated from the difference of the individual ligand field stabilization energies (LFSE), amounts to about 4.2 kJ/mol [Δ(LFSE)(2,18)]. (vi) The "second-sphere stabilization" of the nickel complexes is not reflected in the electronic absorption spectra, as these forces are aligned perpendicularly to the Ni-O bonds. (vii) Coordination of a basic carboxylate donor to the [Ni(II)(2)L](2+) fragment weakens its Ni-N and Ni-S bonds. This bond weakening is reflected in small but significant bond length changes. (viii) The [Ni(II)(2)L(µ-O(2)CR)](+) complexes are relatively inert to carboxylate exchange reactions, except for the formato complex [Ni(II)(2)L(µ-O(2)CH)](+) (8), which reacts with both more and less basic carboxylato ligands.

Monolithic silicon chip for immunofluorescence detection on single magnetic beads.

While fluorescence detection is widely used for bioassays owing to its high sensitivity, a complete fluorescent microscopy setup, comprised of a light source, optical filters, a microscope body, and a camera, still is bulky equipment, compromising its use in a point-of-care environment. Here we propose an integrated monolithic silicon chip for integrated magnetic manipulation and optical detection of fluorescently labeled magnetic beads. Our approach permits microscopeless measurement of the fluorescence of a single microparticle. We demonstrate the viability of this approach by the detection of cancer biomarker 5D10 monoclonal antibodies (mAbs) in a noncompetitive sandwich immunoassay performed on the surface of magnetic beads, in a phosphate buffered saline-bovine serum albumin (PBS-BSA) solution, with a detection limit of 1 ng mL(-1).