The preparation of colloidally stable, self-assembled materials with tailorable solid or hollow two-dimensional (2D) structures represents a major challenge. We describe the formation of uniform, ...monodisperse rectangular platelet micelles of controlled size by means of seeded-growth methods that involve the addition of blends of crystalline-coil block copolymers and the corresponding crystalline homopolymer to cylindrical micelle seeds. Sequential addition of different blends yields solid platelet block comicelles with concentric rectangular patches with distinct coronal chemistries. These complex nano-objects can be subject to spatially selective processing that allows their disassembly to form perforated platelets, such as well-defined hollow rectangular rings. The solid and hollow 2D micelles provide a tunable platform for further functionalization and potential for a variety of applications.
Approximately 12% of apparently previously cognitively well patients undergoing anaesthesia and noncardiac surgery will develop symptoms of cognitive dysfunction after their procedure. Recent ...articles in this Journal have highlighted the difficulties of confirming any clear links between anaesthesia and cognitive dysfunction, in part because of the lack of consistency regarding definition and diagnosis. Postoperative cognitive dysfunction (POCD) is usually self-limiting and rarely persists in the longer term, although plausible biological mechanisms for an impact on brain protein deposition do exist. Clinical research studies are frequently confounded by a lack of agreed definitions and consistency of testing. Preoperative assessment of neurocognitive function and risk factor identification is imperative in order to ascertain the true extent of POCD and any causative link to anaesthesia and surgery. At present a multidisciplinary care bundle approach to risk factor stratification and reduction is the most attractive management plan based on evidence of slight benefit from individual interventions. As yet no individual anaesthetic technique, drug or mode of monitoring has been proved to reduce the incidence of POCD. Providing patients with appropriate and accurate information can be difficult because of conflicting evidence. The Royal College of Anaesthetists’ patient liaison group has produced a useful patient information leaflet that is designed to provide guidance in discussions of individual risks whilst considerable uncertainties remain.
The neuroprotective function of the blood–brain barrier (BBB) presents a major challenge for drug delivery to the central nervous system (CNS). Critical to this function, BBB membrane transporters ...include the ATP‐binding cassette (ABC) transporters, which limit drug penetration across the BBB, and the less‐well‐studied solute carrier (SLC) transporters. In this work, expression profiling of 359 SLC transporters, comparative expression analysis with kidney and liver, and immunoassays in brain microvessels (BMVs) identified previously unknown transporters at the human BBB.
Clinical Pharmacology & Therapeutics (2013); 94 6, 636–639. doi:10.1038/clpt.2013.175
The purpose of this paper is to address some of the paradoxical issues and perceptions regarding animal fats and the related effects on meat quality and consumer perceptions. Meat scientists have ...been studying carcass characteristics for many years and although the factors that influence the accumulation, distribution and composition of carcass fat in livestock have been extensively researched, the role, value and perceptions of animal fats in meat quality differ significantly in importance between producers, abattoirs, butchers, retailers and consumers.
Fat and long-chain fatty acids, whether in adipose tissue or muscle, contribute to important aspects of meat quality and are central to the nutritional and sensory values of meat. In this review the nutritional value of fat, as well as the importance of fat in terms of carcass and meat quality will be highlighted. The ‘quality’ of meat depends greatly on the socio-demographic backgrounds of the consumer. The aim is to focus on the global importance of fat in the carcass to the producer, processor and consumer.
There is currently no clear cut definition for fat quality because the acceptability and perceived quality of fat varies significantly in terms of quantity, colour, consistency and chemical composition in different species of livestock around the world. The association between animal fats and human health is critical and recommendations by health professionals range from excluding fats altogether to a moderate consumption of fats due to their essential role in the body. Recently the emphasis has shifted away from fat quantity to fat quality. Despite these recommendations and years of bad publicity in terms of the adverse affects of animal fats in human health, the livestock industry seems reluctant to shift its focus to fat quality rather than quantity. This approach may adversely affect future meat consumption by consumers who are becoming increasingly critical about the food they eat.
Summary
Background
Psychological distress among people with psoriasis may lead to elevated risks of suicide and nonfatal self‐harm.
Objectives
To investigate psychiatric comorbidity, psychotropic ...medication prescribing and risk of suicidality in people with psoriasis.
Methods
A cohort of patients with psoriasis (1998–2014) was delineated using the Clinical Practice Research Datalink, with linkage to Hospital Episode Statistics and Office for National Statistics mortality records. Each patient with psoriasis was matched with up to 20 patients without psoriasis on age, sex and general practice. A stratified Cox regression model was used to estimate the hazard ratios (HRs) for suicide or nonfatal self‐harm risks adjusted for socioeconomic status.
Results
At baseline, among 56 961 and 876 919 patients with and without psoriasis, higher prevalence for histories of alcohol misuse, bipolar disorder, depression, anxiety disorders, self‐harm and psychotropic drug prescription were observed. The deprivation‐adjusted HR indicated lower suicide risk in people with psoriasis HR 0·59, 95% confidence interval (CI) 0·41–0·85. The risk of suicide varied according to age: it was lower in people with psoriasis diagnosed at ≥ 40 years (HR 0·38, 95% CI 0·21–0·66), whereas there was no difference in risk of suicide in people with psoriasis diagnosed before age 40 years (HR 0·92, 95% CI 0·58–1·46). Conversely, there was a small increased risk for self‐harm (HR 1·15, 95% CI 1·04–1·27) associated with psoriasis.
Conclusions
The prevalence of mental illness was raised in people with psoriasis, and this may lead to a greater risk of self‐harm. Nevertheless, having psoriasis does not appear to be associated with an increased risk of suicide. Healthcare professionals caring for patients with psoriasis should continue to monitor and tackle effectively the psychological needs of these individuals.
What's already known about this topic?
Psychosocial comorbidity is common in patients with psoriasis.
Earlier studies have tried to examine the risk of suicide, but were limited by power to examine the risk of this rare outcome.
What does this study add?
The overall risk of suicide in people with psoriasis was 40% lower than in peers without the condition.
The risk of suicide varied according to age: it was 60% lower among individuals with psoriasis diagnosed at ≥ 40 years than in people without the disease of the same age group, whereas if the diagnosis occurred prior to age 40 years there was no difference in risk between the two groups.
Conversely, there was a 15% increase in self‐harm risk in the psoriasis group vs. the general population.
Plain language summary available online
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ModBase (http://salilab.org/modbase) is a database of annotated comparative protein structure models. The models are calculated by ModPipe, an automated modeling pipeline that relies primarily on ...Modeller for fold assignment, sequence-structure alignment, model building and model assessment (http://salilab.org/modeller/). ModBase currently contains 10,355,444 reliable models for domains in 2,421,920 unique protein sequences. ModBase allows users to update comparative models on demand, and request modeling of additional sequences through an interface to the ModWeb modeling server (http://salilab.org/modweb). ModBase models are available through the ModBase interface as well as the Protein Model Portal (http://www.proteinmodelportal.org/). Recently developed associated resources include the SALIGN server for multiple sequence and structure alignment (http://salilab.org/salign), the ModEval server for predicting the accuracy of protein structure models (http://salilab.org/modeval), the PCSS server for predicting which peptides bind to a given protein (http://salilab.org/pcss) and the FoXS server for calculating and fitting Small Angle X-ray Scattering profiles (http://salilab.org/foxs).
Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of ...genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (r
= 0.24, p = 1.8 × 10
versus r
= -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10
). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.
Cloud feedbacks are the leading cause of uncertainty in climate sensitivity. The complex coupling between clouds and the large‐scale circulation in the tropics contributes to this uncertainty. To ...address this problem, the coupling between clouds and circulation in the latest generation of climate models is compared to observations. Significant biases are identified in the models. The implications of these biases are assessed by combining observations of the present day with future changes predicted by models to calculate observationally constrained feedbacks. For the dynamic cloud feedback (i.e., due to changes in circulation), the observationally constrained values are consistently larger than the model‐only values. This is due to models failing to capture a nonlinear minimum in cloud brightness for weakly descending regimes. Consequently, while the models consistently predict that these regimes increase in frequency in association with a weakening tropical circulation, they underestimate the positive cloud feedback associated with this increase.
Plain Language Summary
Climate models are crucial for understanding the impacts of climate change. Yet there are significant differences between models even for the global mean temperature increase due to a doubling of carbon dioxide concentrations (known as the climate sensitivity). These differences in climate sensitivity are largely due to differences in cloud responses to warming between the models (known as cloud feedbacks). Cloud feedback uncertainty is particularly large for tropical clouds. One reason for this is the two‐way interactions between clouds and the large‐scale circulation. This remains relatively poorly understood and involves processes that occur at a wide range of scales which cannot be captured by climate models. This study examines relationships between clouds and circulation in the tropics in the latest generation of climate models. Cloud feedbacks can be separated into dynamic (changes in circulation) and thermodynamic (changes in cloud for a given circulation regime) components. We use this framework to calculate the cloud feedbacks models would predict if the relationships between clouds and circulation matched observations. This results in an increase in the dynamic component of the cloud feedback which is due to the models' failure to capture the observed nonlinear relationships between clouds and circulation.
Key Points
Climate models miss key details of the observed links between tropical clouds and circulation, notably for common weak subsidence regimes
Using observations to constrain thermodynamic and dynamic cloud feedbacks in models increases the dynamic and hence total feedback
This is due to subtle nonlinear changes in the observed SW cloud radiative effect across circulation regimes that the models predict will change in frequency
Plectin crosslinks intermediate filaments to their targets in different tissues. Defects in plectin cause epidermolysis bullosa simplex (EBS), muscular dystrophy (MD), and sometimes pyloric atresia. ...Association of EBS with a myasthenic syndrome (MyS) was documented in a single patient in 1999.
To analyze the clinical, structural, and genetic aspects of a second and fatal case of EBS associated with a MyS and search for the genetic basis of the disease in a previously reported patient with EBS-MD-MyS.
Clinical observations; histochemical, immunocytochemical, and electron microscopy studies of skeletal muscle and neuromuscular junction; and mutation analysis.
An African American man had EBS since early infancy, and progressive muscle weakness, hyperCKemia, and myasthenic symptoms refractory to therapy since age 3 years. Eventually he became motionless and died at age 42 years. At age 15 years, he had a marked EMG decrement, and a reduced miniature endplate potential amplitude. The myopathy was associated with dislocated muscle fiber organelles, structurally abnormal nuclei, focal plasmalemmal defects, and focal calcium ingress into muscle fibers. The neuromuscular junctions showed destruction of the junctional folds, and remodeling. Mutation analysis demonstrated a known p.Arg2319X and a novel c.12043dupG mutation in PLEC1. The EBS-MD-MyS patient reported in 1999 also carried c.12043dupG and a novel p.Gln2057X mutation. The novel mutations were absent in 200 Caucasian and 100 African American subjects.
The MyS in plectinopathy is attributed to destruction of the junctional folds and the myopathy to defective anchoring of muscle fiber organelles and defects in sarcolemmal integrity.
Increasing evidence shows that physical activity is associated with reduced risk for depression, pointing to a potential modifiable target for prevention. However, the causality and direction of this ...association are not clear; physical activity may protect against depression, and/or depression may result in decreased physical activity.
To examine bidirectional relationships between physical activity and depression using a genetically informed method for assessing potential causal inference.
This 2-sample mendelian randomization (MR) used independent top genetic variants associated with 2 physical activity phenotypes-self-reported (n = 377 234) and objective accelerometer-based (n = 91 084)-and with major depressive disorder (MDD) (n = 143 265) as genetic instruments from the largest available, nonoverlapping genome-wide association studies (GWAS). GWAS were previously conducted in diverse observational cohorts, including the UK Biobank (for physical activity) and participating studies in the Psychiatric Genomics Consortium (for MDD) among adults of European ancestry. Mendelian randomization estimates from each genetic instrument were combined using inverse variance weighted meta-analysis, with alternate methods (eg, weighted median, MR Egger, MR-Pleiotropy Residual Sum and Outlier PRESSO) and multiple sensitivity analyses to assess horizontal pleiotropy and remove outliers. Data were analyzed from May 10 through July 31, 2018.
MDD and physical activity.
GWAS summary data were available for a combined sample size of 611 583 adult participants. Mendelian randomization evidence suggested a protective relationship between accelerometer-based activity and MDD (odds ratio OR, 0.74 for MDD per 1-SD increase in mean acceleration; 95% CI, 0.59-0.92; P = .006). In contrast, there was no statistically significant relationship between MDD and accelerometer-based activity (β = -0.08 in mean acceleration per MDD vs control status; 95% CI, -0.47 to 0.32; P = .70). Furthermore, there was no significant relationship between self-reported activity and MDD (OR, 1.28 for MDD per 1-SD increase in metabolic-equivalent minutes of reported moderate-to-vigorous activity; 95% CI, 0.57-3.37; P = .48), or between MDD and self-reported activity (β = 0.02 per MDD in standardized metabolic-equivalent minutes of reported moderate-to-vigorous activity per MDD vs control status; 95% CI, -0.008 to 0.05; P = .15).
Using genetic instruments identified from large-scale GWAS, robust evidence supports a protective relationship between objectively assessed-but not self-reported-physical activity and the risk for MDD. Findings point to the importance of objective measurement of physical activity in epidemiologic studies of mental health and support the hypothesis that enhancing physical activity may be an effective prevention strategy for depression.
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