What can imaging tell us about cognitive impairment and dementia?

Dementia is a contemporary global health issue with far reaching consequences, not only for affected individuals and their families, but for national and global socio-economic conditions. The hallmark feature of dementia is that of irreversible cognitive decline, usually affecting memory, and impaired activities of daily living. Advances in healthcare worldwide have facilitated longer life spans, increasing the risks of developing cognitive decline and dementia in late life. Dementia remains a clinical diagnosis. The role of structural and molecular neuroimaging in patients with dementia is primarily supportive role rather than diagnostic, American and European guidelines recommending imaging to exclude treatable causes of dementia, such as tumor, hydrocephalus or intracranial haemorrhage, but also to distinguish between different dementia subtypes, the commonest of which is Alzheimer’s disease. However, this depends on the availability of these imaging techniques at individual centres. Advanced magnetic resonance imaging (MRI) techniques, such as functional connectivity MRI, diffusion tensor imaging and magnetic resonance spectroscopy, and molecular imaging techniques, such as 18F fluoro-deoxy glucose positron emission tomography (PET), amyloid PET, tau PET, are currently within the realm of dementia research but are available for clinical use. Increasingly the research focus is on earlier identification of at risk preclinical individuals, for example due to family history. Intervention at the preclinical stages before irreversible brain damage occurs is currently the best hope of reducing the impact of dementia.     

What has microdialysis shown us about the metabolic milieu within exercising skeletal muscle?

Microdialysis provides insight to the metabolic changes in the interstitial space during muscle contractions. This review examines the contribution that interstitial muscle-derived compounds may play in exercise-induced hyperemia and the exercise pressor reflex.     

What could posturography tell us about balance in essential tremor?

BackgroundEssential tremor (ET) is a neurological disorder characterized primarily by action tremor. Balance impairments in ET patients were formerly considered to be uncommon and simply age-related. However quantitative assessment with posturography has revealed impairments in control of both static and dynamic balance.Research questionThe aim of the present study is to assess postural stability with different posturographic techniques in ET patients.MethodsA prospective cross-sectional study conducted in two University Hospitals. Eleven patients diagnosed with essential tremor and twelve healthy controls were included. Balance assessment were performed with: sensory organization test (SOT) and limits of stability (LOS) of the computer dynamic posturography (CDP), results of free-field body sway analysis with mobile posturography (Vertiguard®), modified timed up and go test (TUG), Dizziness handicap inventory (DHI) and activities-specific balance confidence scale (ABC).ResultsPatients with ET showed poorer scores in the SOT than controls for composite balance and somatosensory input. They also performed worse in LOS tests and Vertiguard® device indicated a higher risk of falling. There were no differences in the modified TUG. The mean score of DHI was 15.64 and 85.16 for ABC.SignificancePosturography assessment (CDP and Vertiguard®) is more accurate in showing balance impairment in ET patients than clinical evaluation (modified TUG). Balance impairment involves deteriorated processing of somatosensory input which could be explained by cerebellar dysfunction. Balance deficits could be included into future diagnostic criteria.     

What do single-fiber studies tell us about exercise training?

Many exercise programs designed by trainers have the specific aim to enhance strength, endurance, or power of certain muscle groups to improve athletic performance. Muscle training is also an important component of rehabilitation to limit atrophy associated with immobilization, aging, or disease. To optimize exercise interventions, a good understanding of the response to various training programs and the identification of the mechanisms that influence muscle function are required. Changes in the performance of muscle contraction are associated, among other things, with muscle fiber-type expression and functional properties of the contractile apparatus. Chemically skinned, single fibers is the only model that allows study of the mechanical properties of human muscle fibers as a function of the expression of myosin heavy-chain isoforms. Recently, this model has been used to explore the functional adaptations after different types of solicitations. The current results of the literature indicate that cross-sectional area and force of a specific fiber type are enhanced after resistance training, whereas maximal unloaded shortening velocity is increased by endurance training. Plyometric training improves both fiber force and shortening velocity. Fiber peak power is increased after resistance or plyometric training, and on a long-term basis it is decreased after endurance training. Studies on elderly individuals indicate that this population may react differently with respect to some single-fiber adaptations after training. Generally, training regimens tend to decrease the proportion of type IIx fibers. The available data in the literature make it possible to formulate recommendations applicable to sport science and rehabilitation.     

Do reactive oxygen species regulate skeletal muscle glucose uptake during contraction?

The mechanisms regulating skeletal muscle glucose uptake during contraction remain poorly defined. Recent studies suggest reactive oxygen species may be an important signaling intermediate for the regulation of skeletal muscle glucose uptake during ex vivo contraction but less important during more physiological conditions, such as in situ muscle contraction in rodents and during exercise in humans.     

Singlet oxygen in vivo – it is all about intensity

Recently we could establish detection of singlet oxygen phosphorescence in sarcoma mouse models in vivo. Modern NIR-PMTs in combination with Time-Correlated Multi Photon Counting allow for direct supervision of photosensitizer activity, even from outside the animal [1]. Positioning of the tip of an optical multi-mode fiber bundle directly above the skin combines site-selective pulsed excitation and detection.The presented work addresses the influence of illumination intensity on the amount and locations of singlet oxygen generation in tumor tissue. We use time-resolved optical detection at the typical emission wavelength around 1270 nm and close to it at 1200 nm to determine the phosphorescence kinetics. The discussed data comprise in vivo measurements in tumor-laden HET-CAM [2] and mice. The results show that too intense illumination is a major issue, affecting many PDT treatments and all singlet oxygen measurements in vivo reported so far. Outside of the blood vessels, oxygen consumption due to chemical quenching of the vast majority of generated singlet oxygen may exceed the diffusion-limited supply. Whether or not this results in local anoxia depends on the local drug concentration and the illumination intensity [3].In most cases, singlet oxygen generation is limited to the blood vessels and walls, while photosensitizers in the surrounding tissue will likely not partake.Being a limitation for the treatment on one hand, on the other this finding offers a new method for tumor diagnosis when using photosensitizers exploiting the EPR effect. Using a new method that we call “robust data analysis” on the phosphorescence kinetics measured for our polymer-bound photosensitizers, which circulate in the blood stream for a long time and extravasate mainly in the tumor, yielded convincing results to support its applicability for tumor diagnostics.In contrast to high intensity PDT, some papers reported successful treatment with nanoparticular drugs using much lower illumination intensity [4]. The question of whether with such illumination singlet oxygen is indeed generated in areas outside of vessels and walls is addressed by numerical analysis. Based on the assumption that all detected luminescence kinetics at around 1270 nm comprise mainly two components, singlet oxygen phosphorescence from photosensitizers and phosphorescence from the photosensitizer triplet state, we may simulate expected kinetics for lower illumination intensities. In addition, we discuss how to perform measurements at such low intensities.     

Is skeletal muscle oxidative capacity decreased in old age?

In humans, decreases in cardiac output play an important role in the age-related decrease in whole-body oxidative capacity. What remains less clear is whether a decline in skeletal muscle oxidative capacity is also an inevitable consequence of aging, as a number of other factors that could affect oxidative capacity also change with age, including: physical activity, health status, fibre-type composition, rates of protein synthesis and muscle blood supply. Both in vitro studies using muscle biopsy tissue and in vivo studies using 31P-magnetic resonance spectroscopy are used to study muscular oxidative capacity. Using these methodologies, researchers have found age-associated reductions in the oxidative capacities of specific muscles. In most cases, however, the influence of physical activity has not been adequately controlled, making it difficult to evaluate the effects of age itself from those of lifestyle changes associated with aging. Upon critical evaluation of the existing literature, the following picture regarding the effect of age on muscle oxidative capacity appears: although the maximum level of muscular oxidative capacity attainable through training may decline with age, much of the age-associated decline in oxidative function is related to the reductions in fitness and/or habitual physical activity that typically occur in this population. Future studies in this area must account for the health and activity status of their study participants.     

Severe obesity: evidence for a deranged metabolic program in skeletal muscle?

Severe obesity is increasing at a disproportionate rate compared with milder grade obesity. Our research group has obtained evidence indicative of an "obesity metabolic program" in skeletal muscles of severely obese individuals, which may be determined genetically or epigenetically. We believe that this represents a paradigm shift in thinking about metabolic regulation in obesity.     

What do the X and Y chromosomes tell us about sex and gender in forensic case analysis?

Sex determination can be particularly crucial in forensic casework such as rape cases or cases of missing persons. Biological traces have to be genetically typed and the classification of the sex is of great importance for further investigations. Lately, several papers were published on reliability of sex determination by genetic typing of amelogenin gene-specific fragments. Problems may arise not only from false detection (or non-detection) of amelogenin-specific fragments, but also in cases of chimerism (bone marrow transplants) or micro chimerism (pregnant women carrying male fetuses), and from the possible discrepancies between the biological gender and the (forensic relevant) legal gender in the personal identity documents. The phenotype based classification of the legal gender may contradict the genetic sex under several conditions as there are genetic diversity, intersex conditions and transsexualism. The forensic relevance of the possible misinterpretation (sex is not necessarily legal gender) should not be underestimated.     

Neutrophil infiltration in exercise-injured skeletal muscle: how do we resolve the controversy?

Neutrophils have not consistently been detected in exercise-injured skeletal muscle and, therefore, neutrophil infiltration in this muscle has become a controversial issue. Thirty-eight animal and human studies that assessed injured muscle for neutrophils and employed acute exercise (e.g. level, uphill or downhill running, eccentric contractions, or swimming) were analysed to help clarify the relationship between neutrophil infiltration and exercise-induced muscle injury. Findings from nearly three-quarters of the reviewed studies suggest that neutrophil accumulation follows exercise-induced muscle injury. Intramuscular neutrophil infiltration was present in 85% and 55% of the animal and human studies, respectively. However, no consistent relationship between the potential damaging effect of the exercise type and neutrophil infiltration can be conclusively established from these studies. Specific animal-related factors that could influence these results include age, animal strain, catecholamines, corticosterone, acute stressors and muscle type, whereas a specific human-related influencing factor is physical activity status. Factors affecting both animal and human studies could include sex hormones, muscle sampling techniques and neutrophil detection approaches. General categories of methods that have been used to detect neutrophil infiltration are microscopy, myeloperoxidase (MPO) biochemical assay, antibody staining and white blood cell radionuclide imaging. Only studies employing white blood cell radionuclide imaging have consistently detected neutrophil infiltration. However, antibody staining with a quantitative analysis is currently the most feasible, valid and sensitive method. Research recommendations, therefore, are warranted to resolve the neutrophil infiltration controversy. We propose two approaches for animal studies. The first approach encompasses (i) studying or measuring factors that could influence neutrophil infiltration; (ii) using quantitative antibody staining analysis (in all studies and employing a panel of anti-neutrophil antibodies); (iii) examining the relationship between fibre morphological changes and neutrophil antigen expression; and (iv) developing a neutrophil antibody-radionuclide imaging technique. The second approach will yield animal findings complementing or addressing the gaps from the human exercise studies. For human studies, we suggest that (i) physical activity status is investigated; (ii) quantitative antibody staining analysis is performed (including staining injured muscle with a panel of antibodies such as anti-elastase, anti-MPO, anti-CD11b and anti-CD15 or assessing injured muscle using both immunohistochemistry and the MPO biochemical assay); and (iii) the relationship between fibre morphological changes and neutrophil antigen expression is examined. Studies that incorporate these recommendations could lead to an increased understanding of whether neutrophils are essential for the recovery from an exercise-induced muscle injury.     

Gasless abdomen in the adult: what does it mean?

OBJECTIVE: The objective of this article is to illustrate the causes of a gasless abdomen in an adult. CONCLUSION: The gasless abdomen in the adult is often interpreted as nonspecific, which does not provide useful information for the patient's physician. There are at least six causes of the gasless abdomen in the adult. A specific cause of the gasless abdomen can usually be made when the patient's history is known. The most serious cause of the gasless abdomen is small-bowel obstruction with or without ischemia.     

The ear in fetal MRI: what can we really see?

Introduction  

The aim of this study was to investigate the ability to depict the components of the ear on brain-oriented fetal MRI studies.     

Ultrasound elastography: How can it help in differentiating breast lesions?

Introduction

Elastography is considered a non-invasive imaging modality which determines the tumors according to their stiffness. Strain images representing the stiffness of the lesions compared to that of the surrounding normal tissue.

Witness evidence: can it be trusted?

Basic statistical principles are often widely misunderstood (and often mistrusted) by many members of the public at large. It comes as no shock that this also applies to legal practitioners. If there is an ignorance of the intricacies of statistics by the judiciary and counsel, it is not surprising that erroneous conclusions based on the evidence have arisen. These have even been afforded their own special designation as 'fallacies', including those of both the prosecutor and defence. Whether or not the underlying mathematics is fully understood, it is essential that practitioners can correctly interpret information provided by witnesses, expert or otherwise. This article provides one contribution in that direction toward cases that specifically involve medical situations. It considers some of the more outrageous conclusions made, and accepted, in several high profile cases and considers the evidence more carefully. The challenge is to be able to determine the likelihood that any assertion made is actually true from a statistical point of view. Examples of how to make this determination are provided, including the all-important notion of conditional probability.