Harvesting the photoexcited holes on a photocatalytic proton reduction metal-organic framework.

The highly porous titanium based metal-organic framework NH2-MIL-125(Ti) has recently attracted significant attention in the field of photocatalysis as a promising material for H+ reduction. This work reveals charge transfer upon visible light illumination from this MOF to two different charge acceptors, as an alternative to sacrificial electron donors. Charge transfer is demonstrated through a combined spectroscopic study between this MOF and: (1) 2-(1H-pyrazol-3-yl)phenol, a molecule that functionally mimics the tyrosine-histidine pair, responsible for shuttling the holes to the oxygen evolving centre in natural photosynthesis, and (2) TEMPO, a well known and stable radical. Charge transfer of the holes from the MOF to these occluded molecules takes place on the picosecond time scale. This work suggests that, by coupling a stable and recyclable charge acceptor to the photogenerated holes, the charges can be utilised for oxidation reactions and, thus, link the reduction to the oxidation reactions in water splitting.

Anionic and cationic Hofmeister effects are non-additive for guanidinium salts.

To understand specific ion effects on a molecular level we explore the effect of salts on the rotational mobility of a model amide using dielectric spectroscopy. Based on our previous studies on the effect of strong denaturing anions or cations, here we study the additivity of the anionic and cationic effect. Using salts consisting of denaturing spherical anions and spherical cations we find such salts to affect the amide according to what one expects based on the additive activity of the individual ions. The guanidinium (Gdm+) cation appears to be a notable exception, as our results suggest that GdmI (and accordingly GdmSCN) is less efficient in hindering the rotation of the amide than KI or GdmCl.

Misclassification of cardiometabolic health when using body mass index categories in NHANES 2005-2012.

The United States Equal Employment Opportunity Commission has proposed rules allowing employers to penalize employees up to 30% of health insurance costs if they fail to meet 'health' criteria, such as reaching a specified body mass index (BMI). Our objective was to examine cardiometabolic health misclassifications given standard BMI categories. Participants (N=40 420) were individuals aged 18+ in the nationally representative 2005-2012 National Health and Nutrition Examination Survey. Using the blood pressure, triglyceride, cholesterol, glucose, insulin resistance and C-reactive protein data, population frequencies/percentages of metabolically healthy versus unhealthy individuals were stratified by BMI. Nearly half of overweight individuals, 29% of obese individuals and even 16% of obesity type 2/3 individuals were metabolically healthy. Moreover, over 30% of normal weight individuals were cardiometabolically unhealthy. There was no significant race-by-BMI interaction, but there was a significant gender-by-BMI interaction, F(4,64)=3.812, P=0.008. Using BMI categories as the main indicator of health, an estimated 74 936 678 US adults are misclassified as cardiometabolically unhealthy or cardiometabolically healthy. Policymakers should consider the unintended consequences of relying solely on BMI, and researchers should seek to improve diagnostic tools related to weight and cardiometabolic health.

Correction: Quantifying transient interactions between amide groups and the guanidinium cation.

Correction for 'Quantifying transient interactions between amide groups and the guanidinium cation' by V. Balos et al., Phys. Chem. Chem. Phys., 2015, 17, 28539-28543.

Perceived weight status and risk of weight gain across life in US and UK adults.

BACKGROUND: Correctly identifying oneself as being overweight is presumed to be a prerequisite to successful weight management. The present research examined the effect that perceiving oneself as being 'overweight' has on risk of future weight gain in US and UK adults. METHODS: Data from three longitudinal studies; US National Longitudinal Study of Adolescent Health (Add Health) 2001/2002-2008/2009, UK National Child Development Study (NCDS) 1981-2002/2004, and Midlife in the United States (MIDUS) 1995/1996-2004/2005, were used to examine the impact of perceiving oneself as being overweight on weight gain across adulthood in over 14 000 US and UK adults. RESULTS: Participants who perceived their weight status as being overweight were at an increased risk of subsequent weight gain. This effect was observed irrespective of weight status at baseline and whether weight status perceptions were accurate or inaccurate. In the MIDUS sample, perceiving oneself as being overweight was associated with overeating in response to stress and this mediated the relationship between perceived overweight and weight gain. CONCLUSIONS: Perceiving oneself as being 'overweight' is counter-intuitively associated with an increased risk of future weight gain among US and UK adults.

Quantifying transient interactions between amide groups and the guanidinium cation.

We study the interaction of the guanidinium cation, a widely used protein denaturant, with amide groups, the common structural motif of proteins. Our results provide evidence for direct contact between guanidinium and ∼2 amide groups, but the interaction is transient and weaker than for other cations with high charge-density.

On the collective network of ionic liquid/water mixtures. II. Decomposition and interpretation of dielectric spectra.

This study deals with the dielectric spectra of mixtures of the ionic liquid 1-butyl-3-methyl-imidazolium (BMIM(+)) tetrafluoroborate with water at three selected mole fractions 0.767

Why are ionic liquid ions mainly associated in water? A Car-Parrinello study of 1-ethyl-3-methyl-imidazolium chloride water mixture.

In this study we present the results of a first principles molecular dynamics simulation of a single 1-ethyl-3-methyl-imidazolium chloride [C(2)C(1)im][Cl] ion pair dissolved in 60 water molecules. We observe a preference of the in plane chloride coordination with respect to the cation ring plane as compared to the energetic slightly more demanding on top coordination. Evaluation of the different radial distribution functions demonstrates that the structure of the hydration shell around the ion pair differs significantly from bulk water and that no true ion pair dissociation in terms of completely autonomous solvation shells takes place on the timescale of the simulation. In addition, dipole moment distributions of the solvent in distinct solvation shells around different functional parts of the [C(2)C(1)im][Cl] ion pair are calculated from maximally localized Wannier functions. The analysis of these distributions gives evidence for a depolarization of water molecules close to the hydrophobic parts of the cation as well as close to the anion. Examination of the angular distribution of different OH(H(2)O)-X angles in turn shows a linear coordination of chloride accompanied by a tangential orientation of water molecules around the hydrophobic groups, being a typical feature of hydrophobic hydration. Based on these orientational aspects, a structural model for the obvious preference of ion pair association is developed, which justifies the associating behavior of solvated [C(2)C(1)im][Cl] ions in terms of an energetically favorable interface between the solvation shells of the anion and the hydrophobic parts of the cation.

Electrical conductivity and translational diffusion in the 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid.

Broadband dielectric and terahertz spectroscopy (10(-2)-10(+12) Hz) are combined with pulsed field gradient nuclear magnetic resonance (PFG-NMR) to explore charge transport and translational diffusion in the 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid. The dielectric spectra are interpreted as superposition of high-frequency relaxation processes associated with dipolar librations and a conductivity contribution. The latter originates from hopping of charge carriers on a random spatially varying potential landscape and quantitatively fits the observed frequency and temperature dependence of the spectra. A further analysis delivers the hopping rate and enables one to deduce--using the Einstein-Smoluchowski equation--the translational diffusion coefficient of the charge carriers in quantitative agreement with PFG-NMR measurements. By that, the mobility is determined and separated from the charge carrier density; for the former, a Vogel-Fulcher-Tammann and for the latter, an Arrhenius temperature dependence is obtained. There is no indication of a mode arising from the reorientation of stable ion pairs.

Identification of novel regulators in T-cell differentiation of aplastic anemia patients.

BACKGROUND: Aplastic anemia (AA) is a bone marrow failure syndrome mostly characterized by an immune-mediated destruction of marrow hematopoietic progenitor/stem cells. The resulting hypocellularity limits a detailed analysis of the cellular immune response. To overcome this technical problem we performed a microarray analysis of CD3+ T-cells derived from bone marrow aspirates and peripheral blood samples of newly diagnosed AA patients and healthy volunteers. Two AA patients were additionally analyzed after achieving a partial remission following immunosuppression. The regulation of selected candidate genes was confirmed by real-time RT-PCR. RESULTS: Among more than 22,200 transcripts, 583 genes were differentially expressed in the bone marrow of AA patients compared to healthy controls. Dysregulated genes are involved in T-cell mediated cytotoxicity, immune response of Th1 differentiated T-cells, and major regulators of immune function. In hematological remission the expression levels of several candidate genes tend to normalize, such as immune regulators and genes involved in proinflammatory immune response. CONCLUSION: Our study suggests a pivotal role of Th1/Tc1 differentiated T-cells in immune-mediated marrow destruction of AA patients. Most importantly, immune regulatory genes could be identified, which are likely involved in the recovery of hematopoiesis and may help to design new therapeutic strategies in bone marrow failure syndromes.

Homeopathic arnica therapy in patients receiving knee surgery: results of three randomised double-blind trials.

OBJECTIVES: We investigated the effectiveness of homeopathic Arnica montana on postoperative swelling and pain after arthroscopy (ART), artificial knee joint implantation (AKJ), and cruciate ligament reconstruction (CLR). DESIGN: Three randomised, placebo-controlled, double-blind, sequential clinical trials. SETTING: Single primary care unit specialised in arthroscopic knee surgery. PARTICIPANTS: Patients suffering from a knee disease that necessitated arthroscopic surgery. INTERVENTIONS: Prior to surgery, patients were given 1 x 5 globules of the homeopathic dilution 30x (a homeopathic dilution of 1:10(30)) of arnica or placebo. Following surgery, 3 x 5 globules were administered daily. PRIMARY OUTCOME MEASURES: The primary outcome parameter was difference in knee circumference, defined as the ratio of circumference on day 1 (ART) or day 2 (CLR and AKJ) after surgery to baseline circumference. RESULTS: A total of 227 patients were enrolled in the ART (33% female, mean age 43.2 years;), 35 in the AKJ (71% female, 67.0 years), and 57 in the CLR trial (26% female; 33.4 years). The percentage of change in knee circumference was similar between the treatment groups for ART (group difference Delta=-0.25%, 95% CI: -0.85 to 0.41, p=0.204) and AKJ (Delta=-1.68%, -4.24 to 0.77, p=0.184) and showed homeopathic arnica to have a beneficial effect compared to placebo in CLR (Delta=-1.80%, -3.30 to -0.30, p=0.019). CONCLUSIONS: In all three trials, patients receiving homeopathic arnica showed a trend towards less postoperative swelling compared to patients receiving placebo. However, a significant difference in favour of homeopathic arnica was only found in the CLR trial.

Intestinal immunity of Escherichia coli NISSLE 1917: a safe carrier for therapeutic molecules.

The development of novel approaches that allow accurate targeting of therapeutics to the intestinal mucosa is a major task in the research on intestinal inflammation. For the first time, a live genetically modified bacterial strain has been approved by Dutch authorities as a therapeutic agent for experimental therapy of intestinal bowel disease (IBD) in humans. Genetically modified probiotics can very well be used as carriers for localized antigen delivery into the intestine. Therapeutic safety, however, of such a carrier organism, is crucial, especially when a specific probiotic strain has to be used under diseased conditions. In this study, we tested the potential of Escherichia coli NISSLE 1917 to serve as a safe carrier for targeted delivery of recombinant proteins to the intestinal mucosa. In a well-defined and very sensitive immunological system, we demonstrate that intestinal recombinant E. coli NISSLE 1917 has no effect on migration, clonal expansion and activation status of specific CD4+ T cells, neither in healthy mice nor in animals with acute colitis. Furthermore, recombinant E. coli NISSLE 1917 has no effect on the induction or breakdown of peripheral T-cell tolerance in an autoimmune environment. The excellent colonization properties of E. coli NISSLE 1917 render this strain an ideal candidate as carrier organism for gut-focused in situ synthesis of therapeutic molecules.

[Lead deposits in bone--the roentgen picture as a demonstration method?]. / Bleieinlagerung im Knochen--Röntgenaufnahme als Nachweismethode?

Current concepts concerning the deposition, distribution and radiological demonstration of lead in the skeleton were investigated in five series of rats; some of these were young and others more than a year old. 10 mg of lead acetate/kg body weight were administered over a period of five to 41 days, giving a minimum of 8.4 mg and maximum of 40.4 mg of lead. A comparable control group was given similar amounts of sodium acetate. The distribution and concentration of lead in the femur was determined by the use of 210Pb. Contact autoradiographs showed band-shaped lead accumulation in the endosteal and periosteal growth regions. The degree of darkening depended on the amount of lead administered and permitted a rather coarse quantitative relationship to be drawn. Measurements of radioactivity produced similar distribution patterns. The relationship of lead concentration of epi- and metaphysis to the diaphysis averaged 2:1. The factor mainly responsible for lead deposition depended on the metabolic potential of the tissue, which itself depends largely on the growth regions. Radiologically, there was definite evidence of demineralization in the areas of lead deposition; this could be confirmed histologically by lack of trabeculae, thinning of the cortex and destruction of bone matrix. Despite its much greater absorption co-efficient, the tiny quantities of lead, compared with the bone mass (even in the highest concentrations in our experiments) cannot be detected radiologically. Biophysical calculations have been made which indicate that similar conditions occur in man. Radiological examination of the skeleton, which is used as a screening method for chronic lead poisoning, is not suitable for this purpose.

[99mTc-MAG3 and 131I-OIH in patients with kidney insufficiency and with normal kidneys]. / 99mTc-MAG3 und 131J-OIH bei niereninsuffizienten und nierengesunden Patienten.

Renal clearance of 99mTc-mercaptoacetyltriglycine (MAG3) and 131J-orthoidohippurate (OIH) were compared by simultaneous measurement in 50 patients. Renal time-activity-curves of both radiopharmaceuticals were compared in 50 patients. With regard to the clearance, good correlation (r = 0.95) with a mean ratio MAG3-/OIH-clearance of 0.62 was found. No significant difference between patients with normal (n = 30) and impaired (n = 20) renal function could be demonstrated. Renal time activity curves and relative renal function showed good correspondence in patients with normal (n = 13) and impaired (n = 7) renal function. It is concluded that MAG3 may be used as substitute for OIH in patients with normal and impaired renal function.

[A comparison of different methods of calculating clearances using 99mTc-mercaptoacetyltriglycine and 123I- or 131I-ortho-iodohippuric acid]. / Vergleich verschiedener Clearance-Berechnungs-methoden bei Verwendung von 99mTc-Mercaptoacetyltriglycin sowie 123J- oder 131J-Orthojod-hippursäure.

Using labelled MAG3 (n = 172) or OIH (n = 102) the results of three different techniques of calculating renal clearance were compared. The following techniques were used: Tauxe (single plasma concentration determination), Oberhausen (modified, combined partial body and plasma disappearance clearance) and Winkler (partial body clearance). For OIH, linear regression analysis revealed a positive correlation of Tauxe and Oberhausen clearances with a correlation coefficient (r) of 0.90 and a mean ratio (mean) Oberhausen/Tauxe clearances of 1.03. For MAG3, the Oberhausen values were found to be significantly lower than the Tauxe values with an equally good correlation. For this radiopharmaceutical the Winkler values were significantly higher than the Tauxe and Oberhausen values. For OIH, no such difference was noted. However, the correlation coefficient was significantly lower. Whereas with the Tauxe method, a mean ratio MAG3-/OIH clearances of 0.62 was observed in an earlier investigation, from the present data a ratio of 0.53 is calculated for the Oberhausen clearance. The difference between the Tauxe and Oberhausen clearances with MAG3 is of importance when comparing clearance values obtained with clearance calculation techniques and for establishing normal values for the MAG3 clearance.

Effect of pigmentation on the drug deposition in hair of grey-haired subjects.

The hair samples of 15 grizzled patients with a permanent medical treatment by amitriptyline, carbamazepine, chlorprothixene, diclofenac, doxepine, indomethacine, maprotiline or metoclopramide, or with a chronic heroin and cocaine abuse were separated into white and pigmented fibers and both fractions were independently investigated by GC-MS. The drugs were found in pigmented fibers as well as in white fibers, but the concentrations in the white fibers were smaller than in the pigmented ones for the most of the samples investigated. The concentration ratio of the drugs or their metabolites in both hair fractions (white/pigmented) was found to be between 0.09 and 1.57 (mean 0.70, 30 concentration pairs). There are large differences in this ratio between different subjects with the same drug, whereas for different drugs in the same subject in many cases similar ratios were measured. As a reason a different grade of pigmentation of the hair and the influence of the drug structure are discussed. From these results it follows that the natural hair colour is an important parameter in the evaluation of drug concentration in hair.

Structural and concentration effects on the deposition of tricyclic antidepressants in human hair.

In order to elucidate the possibility of a long-term compliance analysis the hair samples of 56 patients, who were under a permanent treatment with tricyclic antidepressants, were analyzed for amitriptyline, clomipramine, doxepine, imipramine and maprotiline as well as their nor-metabolites. The hair concentrations varied between 0.4 and 40 ng/mg with no strong difference between the five drugs. In comparison to the therapeutic plasma levels described in literature the nor-metabolites always accumulate less in hair than drugs. No correlation was found between the hair concentration and the daily dose. The investigation of the full hair length in 3-cm sections for several examples of all five drugs shows that they can be detected in normally kept hair at least 1 year after intake.

Case study of bovine dermatitis caused by oat straw infected with Fusarium sporotrichioides.

A dermatitis characterised by discrete, raised, plaque-like and cracked skin lesions of variable sizes on the udder, the hind quarters, the lips and muzzle of all the cows in a herd was suspected of being caused by the oat straw used in bedding, after initial feed analysis and skin culture were negative for toxins and dermatophytes. Mycological analysis indicated an extensive infestation of the oat straw by Fusarium sporotrichioides, a toxic mould, and an immunochemical assay indicated dermatotoxic trichothecenes in the straw (0.22 microgram/g dried straw). An ethyl acetate extract of the straw induced a necrotic response on shaved rat skin. Ingestion of the toxic bedding straw and inhalation of toxic straw dust probably also caused the internal haemorrhage and lung emphysema observed in the two cows that died. The regression of the dermatitis and the recovery of general herd health after the withdrawal of the oat straw further supported the diagnosis.