Treatment with human growth hormone in patients with Prader-Labhart-Willi syndrome reduces body fat and increases muscle mass and physical performance

Twelve children with documented Prader-Labhart-Willi syndrome were treated with human growth hormone (24 U/m2/week) during 1 year. The children were divided into three groups: group 1: overweight and prepubertal (n = 6, age 3.8-7.0 years); group 2: underweight and prepubertal (n = 3, age 0.6-4.1 years); group 3: pubertal (n = 3, age 9.2-14.6 years). In group 1, height increased from -1.7 SD to -0.6 SD, while weight decreased from 1.1 SD to 0.4 SD, with a dramatic drop in weight for height from 3.8 SD to 1.2 SD. Hand length increased from -1.5 SD to -0.4 SD and foot length from -2.5 SD to -1.4 SD. Body fat, measured by dual X-ray energy absorptiometry, dropped by a third, whereas muscle mass increased by a fourth. Physical capability (Wingate test) improved considerably. The children were reported to be much more active and capable. In group 2, similar changes were seen, but weight for height increased, probably because muscle mass increase exceeded fat mass decrease. Changes in group 3 were similar as in group 1, even though far less distinct. Conclusion: Growth hormone treatment in Prader-Labhart-Willi syndrome led to dramatic changes: distinct increase in growth velocity, height and muscle mass, as well as an improvement in physical performance. Fat mass and weight for height decreased in the initially overweight children, and weight for height increased in underweight childre

Microfluidics: From Crystallization to Serial Time-Resolved Crystallography

Capturing protein structural dynamics in real-time has tremendous potential in elucidating biological functions and providing information for structure-based drug design. While time-resolved structure determination has long been considered inaccessible for a vast majority of protein targets, serial methods for crystallography have remarkable potential in facilitating such analyses. Here, we review the impact of microfluidic technologies on protein crystal growth and X-ray diffraction analysis. In particular, we focus on applications of microfluidics for use in serial crystallography experiments for the time-resolved determination of protein structural dynamics

Monitoring Ion Channel Function In Real Time Through Quantum Decoherence

In drug discovery research there is a clear and urgent need for non-invasive detection of cell membrane ion channel operation with wide-field capability. Existing techniques are generally invasive, require specialized nano structures, or are only applicable to certain ion channel species. We show that quantum nanotechnology has enormous potential to provide a novel solution to this problem. The nitrogen-vacancy (NV) centre in nano-diamond is currently of great interest as a novel single atom quantum probe for nanoscale processes. However, until now, beyond the use of diamond nanocrystals as fluorescence markers, nothing was known about the quantum behaviour of a NV probe in the complex room temperature extra-cellular environment. For the first time we explore in detail the quantum dynamics of a NV probe in proximity to the ion channel, lipid bilayer and surrounding aqueous environment. Our theoretical results indicate that real-time detection of ion channel operation at millisecond resolution is possible by directly monitoring the quantum decoherence of the NV probe. With the potential to scan and scale-up to an array-based system this conclusion may have wide ranging implications for nanoscale biology and drug discovery.Comment: 7 pages, 6 figure

Sensing electric fields using single diamond spins

The ability to sensitively detect charges under ambient conditions would be a fascinating new tool benefitting a wide range of researchers across disciplines. However, most current techniques are limited to low-temperature methods like single-electron transistors (SET), single-electron electrostatic force microscopy and scanning tunnelling microscopy. Here we open up a new quantum metrology technique demonstrating precision electric field measurement using a single nitrogen-vacancy defect centre(NV) spin in diamond. An AC electric field sensitivity reaching ~ 140V/cm/\surd Hz has been achieved. This corresponds to the electric field produced by a single elementary charge located at a distance of ~ 150 nm from our spin sensor with averaging for one second. By careful analysis of the electronic structure of the defect centre, we show how an applied magnetic field influences the electric field sensing properties. By this we demonstrate that diamond defect centre spins can be switched between electric and magnetic field sensing modes and identify suitable parameter ranges for both detector schemes. By combining magnetic and electric field sensitivity, nanoscale detection and ambient operation our study opens up new frontiers in imaging and sensing applications ranging from material science to bioimaging

Major biological obstacles for persistent cell-based regeneration of articular cartilage

Hyaline articular cartilage, the load-bearing tissue of the joint, has very limited repair and regeneration capacities. The lack of efficient treatment modalities for large chondral defects has motivated attempts to engineer cartilage constructs in vitro by combining cells, scaffold materials and environmental factors, including growth factors, signaling molecules, and physical influences. Despite promising experimental approaches, however, none of the current cartilage repair strategies has generated long lasting hyaline cartilage replacement tissue that meets the functional demands placed upon this tissue in vivo. The reasons for this are diverse and can ultimately result in matrix degradation, differentiation or integration insufficiencies, or loss of the transplanted cells and tissues. This article aims to systematically review the different causes that lead to these impairments, including the lack of appropriate differentiation factors, hypertrophy, senescence, apoptosis, necrosis, inflammation, and mechanical stress. The current conceptual basis of the major biological obstacles for persistent cell-based regeneration of articular cartilage is discussed, as well as future trends to overcome these limitations

Short-term prediction of threatening and violent behaviour in an Acute Psychiatric Intensive Care Unit based on patient and environment characteristics

<p>Abstract</p> <p>Background</p> <p>The aims of the present study were to investigate clinically relevant patient and environment-related predictive factors for threats and violent incidents the first three days in a PICU population based on evaluations done at admittance.</p> <p>Methods</p> <p>In 2000 and 2001 all 118 consecutive patients were assessed at admittance to a Psychiatric Intensive Care Unit (PICU). Patient-related conditions as actuarial data from present admission, global clinical evaluations by physician at admittance and clinical nurses first day, a single rating with an observer rated scale scoring behaviours that predict short-term violence in psychiatric inpatients (The Brøset Violence Checklist (BVC)) at admittance, and environment-related conditions as use of segregation or not were related to the outcome measure Staff Observation Aggression Scale-Revised (SOAS-R). A multiple logistic regression analysis with SOAS-R as outcome variable was performed.</p> <p>Results</p> <p>The global clinical evaluations and the BVC were effective and more suitable than actuarial data in predicting short-term aggression. The use of segregation reduced the number of SOAS-R incidents.</p> <p>Conclusions</p> <p>In a naturalistic group of patients in a PICU segregation of patients lowers the number of aggressive and threatening incidents. Prediction should be based on clinical global judgment, and instruments designed to predict short-term aggression in psychiatric inpatients.</p> <p>Trial registrations</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00184119">NCT00184119</a>/<a href="http://www.clinicaltrials.gov/ct2/show/NCT00184132">NCT00184132</a></p

Image formation properties and inverse imaging problem in aperture based scanning near field optical microscopy

Aperture based scanning near field optical microscopes are important instruments to study light at the nanoscale and to understand the optical functionality of photonic nanostructures. In general, a detected image is affected by both the transverse electric and magnetic field components of light. The discrimination of the individual field components is challenging as these four field components are contained within two signals in the case of a polarization resolved measurement. Here, we develop a methodology to solve the inverse imaging problem and to retrieve the vectorial field components from polarization and phase resolved measurements. Our methodology relies on the discussion of the image formation process in aperture based scanning near field optical microscopes. On this basis, we are also able to explain how the relative contributions of the electric and magnetic field components within detected images depend on the chosen probe. We can therefore also describe the influence of geometrical and material parameters of individual probes within the image formation process. This allows probes to be designed that are primarily sensitive either to the electric or magnetic field components of light

Investigating the conservatism-disgust paradox in reactions to the COVID-19 pandemic: A reexamination of the interrelations among political ideology, disgust sensitivity, and pandemic response

Research has documented robust associations between greater disgust sensitivity and (1) concerns about disease, and (2) political conservatism. However, the COVID-19 disease pandemic raised challenging questions about these associations. In particular, why have conservatives-despite their greater disgust sensitivity-exhibited less concern about the pandemic? Here, we investigate this "conservatism-disgust paradox" and address several outstanding theoretical questions regarding the interrelations among disgust sensitivity, ideology, and pandemic response. In four studies (N = 1,764), we identify several methodological and conceptual factors-in particular, an overreliance on self-report measures-that may have inflated the apparent associations among these constructs. Using non-self-report measures, we find evidence that disgust sensitivity may be a less potent predictor of disease avoidance than is typically assumed, and that ideological differences in disgust sensitivity may be amplified by self-report measures. These findings suggest that the true pattern of interrelations among these factors may be less "paradoxical" than is typically believed