In the past 25 years, there have been continuous advances in the diagnosis of disease throughout the body owing to the introduction of new technology and the experience gained with its use. However, ...the imaging and evaluation of complicated cystic lesions of the kidneys frequently remains a difficult problem. The classification of renal cystic lesions suggested 25 years ago, now referred to as the Bosniak renal cyst classification, remains pertinent to the diagnosis and management of these difficult-to-diagnose complicated cystic masses.
The 18R and 14H long-period stacking ordered structures formed in Mg–Y–Zn alloys are examined systematically using electron diffraction and high-angle annular dark-field scanning transmission ...electron microscopy. In contrast to that reported in previous studies, the 18R structure is demonstrated to have an
ordered base-centred monoclinic lattice, with Y and Zn atoms having an
ordered arrangement in the closely packed planes. Furthermore, the composition of 18R is suggested to be Mg
10Y
1Zn
1, instead of the Mg
12Y
1Zn
1 composition that is commonly accepted. The 14H structure is also
ordered. It has a hexagonal unit cell; the
ordered distribution of Y and Zn atoms in the unit cell is similar to that in the 18R and its composition is Mg
12Y
1Zn
1. The 18R unit cell has three ABCA-type building blocks arranged in the same shear direction, while the 14H unit cell has two ABCA-type building blocks arranged in opposite shear directions.
Huntington's disease is a progressive neurological disorder that starts insidiously with motor, cognitive or psychiatric disturbance, and progresses through a distressing range of symptoms to end ...with a devastating loss of function, both motor and executive. There is a growing awareness that, in addition to cognitive and psychiatric symptoms, there are other important non-motor symptoms in HD, including sleep and circadian abnormalities. It is not clear if sleep–wake changes are caused directly by HD gene-related pathology, or if they are simply a consequence of having a neurodegenerative disease. From a patient point of view, the answer is irrelevant, since sleep and circadian disturbances are deleterious to good daily living, even in neurologically normal people. The assumption should be that, at the very least, sleep and/or circadian disturbance in HD patients will contribute to their symptoms. At worst, they may contribute to the progressive decline in HD. Here I review the state of our understanding of sleep and circadian abnormalities in HD. I also outline a set of simple rules that can be followed to improve the chances of a good night's sleep, since preventing any ‘preventable’ symptoms is the a logical first step in treating disease. The long-term impact of sleep disruption in HD is unknown. There have been no large-scale systematic studies of in sleep in HD. Furthermore, there has never been a study of the efficacy of pharmaceuticals that are typically used to treat sleep deficits in HD patients. Thus treatment of sleep disturbance in HD is necessarily empirical. A better understanding of the relationship between sleep/circadian abnormalities and HD pathology is needed, if treatment of this aspect of HD is to be optimized.
► There is substantial evidence for sleep abnormalities in HD. ► Circadian abnormalities are also evident in HD patients. ► Circadian clock abnormalities are clearly present in brain and periphery of HD mice. ► Sleep–wake deficits could contribute to cognitive decline in HD. ► Treating sleep deficits might delay cognitive and emotional decline in HD.
Since the identification of the causative gene in Huntington's disease (HD), a number of animal models of this disorder have been developed. A frequently asked question is: which of these models most ...closely recapitulates the human disease? In this Review, we provide an overview of the currently available animal models of HD in the context of the clinical features of the disease. In doing so, we highlight their strengths and limitations for modelling specific symptoms of the disease. This should highlight the animal model that is best suited to address a particular question of interest and, ultimately, to expedite the discovery of treatments that will prevent or slow the progression of HD.
Landfills are the final stage in the life cycle of many products containing per- and polyfluoroalkyl substances (PFASs) and their presence has been reported in landfill leachate. The concentrations ...of 70 PFASs in 95 samples of leachate were measured in a survey of U.S. landfills of varying climates and waste ages. National release of PFASs was estimated by coupling measured concentrations for the 19 PFASs where more than 50% of samples had quantifiable concentrations, with climate-specific estimates of annual leachate volumes. For 2013, the total volume of leachate generated in the U.S. was estimated to be 61.1 million m
, with 79% of this volume coming from landfills in wet climates (>75 cm/yr precipitation) that contain 47% of U.S. solid waste. The mass of measured PFASs from U.S. landfill leachate to wastewater treatment plants was estimated to be between 563 and 638 kg for 2013. In the majority of landfill leachate samples, 5:3 fluorotelomer carboxylic acid (FTCA) was dominant and variations in concentrations with waste age affected total estimated mass. There were six PFASs that demonstrated significantly higher concentrations in leachate from younger waste compared to older waste and six PFAS demonstrated significant variation with climate.
Persons with motor complete spinal cord injury, signifying no voluntary movement or sphincter function below the level of injury but including retention of some sensation, do not recover independent ...walking. We tested intense locomotor treadmill training with weight support and simultaneous spinal cord epidural stimulation in four patients 2.5 to 3.3 years after traumatic spinal injury and after failure to improve with locomotor training alone. Two patients, one with damage to the mid-cervical region and one with damage to the high-thoracic region, achieved over-ground walking (not on a treadmill) after 278 sessions of epidural stimulation and gait training over a period of 85 weeks and 81 sessions over a period of 15 weeks, respectively, and all four achieved independent standing and trunk stability. One patient had a hip fracture during training. (Funded by the Leona M. and Harry B. Helmsley Charitable Trust and others; ClinicalTrials.gov number, NCT02339233 .).
A growing body of research suggests that a lack of social connectedness is strongly related to current depression and increases vulnerability to future depression. However, few studies speak to the ...potential benefits of fostering social connectedness among persons already depressed or to the protective properties of this for future depression trajectories. We suggest that this may be in part because connectedness tends to be understood in terms of (difficult to establish) ties to specific individuals rather than ties to social groups. The current study addresses these issues by using population data to demonstrate that the number of groups that a person belongs to is a strong predictor of subsequent depression (such that fewer groups predicts more depression), and that the unfolding benefits of social group memberships are stronger among individuals who are depressed than among those who are non-depressed. These analyses control for initial group memberships, initial depression, age, gender, socioeconomic status, subjective health status, relationship status and ethnicity, and were examined both proximally (across 2 years, N = 5055) and distally (across 4 years, N = 4087). Depressed respondents with no group memberships who joined one group reduced their risk of depression relapse by 24%; if they joined three groups their risk of relapse reduced by 63%. Together this evidence suggests that membership of social groups is both protective against developing depression and curative of existing depression. The implications of these results for public health and primary health interventions are discussed.
•There has been little uptake of evidence that social support reduces depression.•We propose that research with depressed samples using concrete measures is needed.•Social group memberships predicted lower depression 2 years and 4 years later.•Among those depressed at baseline, groups were protective against relapse.•Joining and maintaining groups may be a viable, cost-effective intervention.
Two new large animal models of Huntington's disease (HD) have been developed recently, an old world monkey (macaque) and a sheep. Macaques, with their large brains and complex repertoire of behaviors ...are the 'gold-standard' laboratory animals for testing cognitive function, but there are many practical and ethical issues that must be resolved before HD macaques can be used for pre-clinical research. By contrast, despite their comparable brain size, sheep do not enjoy a reputation for intelligence, and are not used for pre-clinical cognitive testing. Given that cognitive decline is a major therapeutic target in HD, the feasibility of testing cognitive function in sheep must be explored if they are to be considered seriously as models of HD. Here we tested the ability of sheep to perform tests of executive function (discrimination learning, reversal learning and attentional set-shifting). Significantly, we found that not only could sheep perform discrimination learning and reversals, but they could also perform the intradimensional (ID) and extradimensional (ED) set-shifting tasks that are sensitive tests of cognitive dysfunction in humans. Their performance on the ID/ED shifts mirrored that seen in humans and macaques, with significantly more errors to reach criterion in the ED than the ID shift. Thus, sheep can perform 'executive' cognitive tasks that are an important part of the primate behavioral repertoire, but which have never been shown previously to exist in any other large animal. Sheep have great potential, not only for use as a large animal model of HD, but also for studying cognitive function and the evolution of complex behaviours in normal animals.
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