Towards automated detection of depression from brain structural magnetic resonance images

Introduction : Depression is a major issue worldwide and is seen as a significant health problem. Stigma and patient denial, clinical experience, time limitations, and reliability of psychometrics are barriers to the clinical diagnoses of depression. Thus, the establishment of an automated system that could detect such abnormalities would assist medical experts in their decision-making process. This paper reviews existing methods for the automated detection of depression from brain structural magnetic resonance images (sMRI).Methods : Relevant sources were identified from various databases and online sites using a combination of keywords and terms including depression, major depressive disorder, detection, classification, and MRI databases. Reference lists of chosen articles were further reviewed for associated publications.Results : The paper introduces a generic structure for representing and describing the methods developed for the detection of depression from sMRI of the brain. It consists of a number of components including acquisition and preprocessing, feature extraction, feature selection, and classification.Conclusion : Automated sMRI-based detection methods have the potential to provide an objective measure of depression, hence improving the confidence level in the diagnosis and prognosis of depression.

Making visible the invisible act of doping

This paper describes the construction of the visual space of surveillance by the global anti-doping apparatus, it is a space inhabited daily by professional cyclists. Two principal mechanisms of this apparatus will be discussed—the Whereabouts System and the Biological Passport; in order to illustrate how this space is constructed and how it visualises the invisible act of doping. These mechanisms act to supervise and govern the professional cyclist and work to classify them as either clean or dirty in terms of the use of prohibited doping substances or methods. Contrary to the analysis of liberal anti-doping scholars such as Hanstad, Loland and Møller this paper argues that Foucault’s Panopticon paradigm is a useful tool for the analysis of this apparatus. The Whereabouts System and Biological Passport are the instruments by which the anti-doping apparatus intensifies the construction of the space of surveillance in professional sport. This space of surveillance not only locates and makes visible the physical location of each individual cyclist, but it also makes visible their internal bodily functions, in this case the composition and the fluctuations of the composition of their blood. In making the cyclist visible the instruments do not allow the cause of doping, or the event of doping to be known or observed. Rather what they do is cast the body in terms of abnormalities of time, place or blood. In the case of an abnormality of the cyclist’s blood, the cause itself cannot be identified with any certainty, all that is made visible is a suggestion, or a probability, that doping may have occurred. The ultimate effects are twofold—an internalisation and continual monitoring of one’s self as well as by the authorities, and a radical change in the nature and the definition of the offence of doping. No longer is it positive evidence of doping that is punishable, but what becomes punishable is an abnormality, in the cyclist’s location, or their body, which suggests a probability that the invisible act of doping may have occurred. In the course of this process accepted manners of proving an offence by the use of scientific evidence and expert commentary are transformed. The Whereabouts System and the Biological Passport open up a new manner in which the invisible can be visualised. Through the discourse and the attendant commentary of the expert a new alliance between doping and the law is constructed. The result is a redistribution of the way in which the law visualises and treats the symptoms (the signifier) and the signified act of doping. The Whereabouts System and Biological Passport are the instruments by which the anti-doping apparatus intensifies the construction of the space of surveillance in professional sport. This space of surveillance not only locates and makes visible the physical location of each individual cyclist, but it also makes visible their internal bodily functions, in this case the composition and the fluctuations of the composition of their blood. In making the cyclist visible the instruments do not allow the cause of doping, or the event of doping to be known or observed. Rather what they do is cast the body in terms of abnormalities of time, place or blood. In the case of an abnormality of the cyclists’s blood, the cause itself cannot be identified with any certainty, all that is made visible is a suggestion, or a probability, that doping may have occurred. The ultimate effects are twofold—an internalisation and continual monitoring of one’s self as well as by the authorities, and a radical change in the nature and the definition of the offence of doping. No longer is it positive evidence of doping that is punishable, but what becomes punishable is an abnormality, in the cyclist’s location, or their body, which suggests a probability that the invisible act of doping may have occurred. In the course of this process accepted manners of proving an offence by the use of scientific evidence and expert commentary are transformed. The Whereabouts System and the Biological Passport open up a new manner in which the invisible can be visualised. Through the discourse and the attendant commentary of the expert a new alliance between doping and the law is constructed. The result is a redistribution of the way in which the law visualises and treats the symptoms (the signifier) and the signified act of doping.

Gastrointestinal microbiology in autistic spectrum disorder : a review

Cases of autism have frequently been reported in association with gastrointestinal problems. These observations have stimulated investigations into possible abnormalities of intestinal microbiota in autistic patients. The objectives of this paper were to review the possible involvement and mechanisms of gastrointestinal microbiota in autistic spectrum disorder and explain the possible role of gastrointestinal microbiota in the condition. This review addresses the possible involvement of bacteria, viruses and fungi, and their products in autism. Direct viral damage of neurons or disruption of normal neurodevelopment by immune elements such as cytokines, nitric oxide and bacterial products, including lipopolysaccharides, toxins and metabolites, have been suggested to contribute to autistic pathology. Numerous intestinal microbial abnormalities have been reported in individuals with autism. Research to date exploring possible gastrointestinal problems and infection in autism has been limited by small and heterogeneous samples, study design flaws and conflicting results. Furthermore, interventions designed to modify the intestinal microbial population of autistic patients are few and limited in their generalisation. In order to bring clarity to this field, high-quality and targeted investigations are needed to explore the role of gastrointestinal microbiology in autism. To this end, several promising avenues for future research are suggested.

Faecal microbiota of individuals with autism spectrum disorder

Many children with autistic spectrum disorders (ASDs) suffer from gastrointestinal problems such as diarrhoea, constipation and abdominal pain. Such symptoms may be due to a disruption of the indigenous gut microbiota promoting the overgrowth of potentially pathogenic micro-organisms. These observations have stimulated investigations into possible abnormalities of intestinal microbiota in autistic patients. The purpose of the present study was to determine if a relationship exists between ASD severity (mild – severe) and GI microbial populations. The faecal microbiota of 22 male and 6 female participants with ASDs (aged 7 ± 6 years) were analyzed by standard microbial culture methods and compared within-group (based on ASD severity) and with a standard laboratory reference range. Comparisons between children with mild ASD and those with moderate to severe ASD, as well as comparisons to a neurotypical control group previously reported, revealed that no significant differences appear to exist in the composition of the gut microbiota. Nevertheless, examination of each individual’s gut microbial composition showed 10 cases of unusual findings witch means 1out of 3 cases have unusual microbiota. Our data do not support consistent GI microbial abnormalities in ASD children, but the findings do suggest that aberrations may be found in a minority subset of ASD children. Further studies are required to determine the possible association between the microbiota and gastrointestinal dysfunctions in a subset of children with both ASD and gastro-intestinal problems.

Characteristics and outcomes of patients requiring unplanned transfer from subacute to acute care

The study aims to identify the reasons for, and outcomes from, unplanned transfers from subacute care to acute care. A retrospective patient record review of patients requiring unplanned transfer from subacute to an acute care emergency department (ED) from 1 July 2008 to 30 June 2009 was undertaken. Data collected included patient demographics, clinical characteristics in preceding transfer, and on ED arrival and outcome data. There were 136 patients included in the study with a median age of 81 years. The most common reasons for transfer were respiratory problems and altered conscious state. In the 24 h preceding transfer, 92.6% of patients had ≥ 1 physiological abnormality and 10.3% of patients had no physiological parameters documented. On ED arrival, 75% of patients had physiological abnormalities. Hospital admission occurred in 75% of patients and the inpatient mortality rate was 14.7%. Factors associated with inpatient mortality were tachypnoea and severe hypoxaemia in 24 h preceding transfer and tachypnoea, hypoxaemia, hypoxaemia, severe hypoxaemia and hypothermia on ED arrival. Patients requiring unplanned transfer had higher inpatient mortality than older hospital users. Reasons for unplanned transfer reflect known predictors of in-hospital adverse events so predictive use of physiological data and patient characteristics might optimize patient safety.

Leptin and the development of obesity and diabetes in Psammomys obesus

The recently discovered ob gene and its circulating product, leptin, may be critical factors in the control of energy balance. Recent studies in ob/ob mice, which lack circulating leptin, have shown dramatic reductions in food intake and bodyweight after leptin treatment. In addition, studies in both humans with obesity and animal models of obesity have demonstrated hyperleptinemia. Here, we report a longitudinal study examining changes in circulating leptin during the development of obesity and diabetes in Psammomys obesus. Over the 8 weeks of the study, lean animals increased their bodyweight by 154% and leptin levels remained essentially unchanged. In contrast, animals that developed obesity (223 % increase in bodyweight), hyperglycemia, and hyperinsulinemia also developed hyperleptinemia between 4 weeks and 8 weeks of age. These results demonstrate that the development of hyperleptinemia is associated with the development of obesity and subsequent metabolic abnormalities.

Creatine pretreatment prevents birth asphyxia–induced injury of the newborn spiny mouse kidney

Background:
Acute kidney injury (AKI) is a major complication for infants following an asphyxic insult at birth. We aimed to determine if kidney structure and function were affected in an animal model of birth asphyxia and if maternal dietary creatine supplementation could provide an energy reserve to the fetal kidney, maintaining cellular respiration during asphyxia and preventing AKI.

Methods:
Pregnant spiny mice were maintained on normal chow or chow supplemented with creatine from day 20 gestation. On day 38 (term ~39 d), pups were delivered by cesarean section (c-section) or subjected to intrauterine asphyxia. Twenty-four hours after insult, kidneys were collected for histological or molecular analysis. Urine and plasma were also collected for biochemical analysis.

Results:
AKI was evident at 24 h after birth asphyxia, with a higher incidence of shrunken glomeruli (P < 0.02), disturbance to tubular arrangement, tubular dilatation, a twofold increase (P < 0.02) in expression of Ngal (early marker of kidney injury), and decreased expression of the podocyte differentiation marker nephrin. Maternal creatine supplementation prevented the glomerular and tubular abnormalities observed in the kidney at 24 h and the increased expression of Ngal.

Conclusion:
Maternal creatine supplementation may prove useful in ameliorating kidney injury associated with birth asphyxia.

Further applications of doppler radar for non-contact respiratory assessment

This paper further investigates the use of Doppler radar for detecting and identifying certain human respiratory characteristics from observed frequency and phase modulations. Specifically, we show how breathing frequencies can be determined from the demodulated signal leading to identifying abnormalities of breathing patterns using signal derivatives, optimal filtering and standard statistical measures. Specifically, we report results on a robust method for distinguishing cessation of the normal breathing cycle. The proposed approach can have potential application in the management of sudden infant death syndrome(SIDS) and sleep apnea.

Estrogen-related receptor γ is an in vivo receptor of bisphenol A

Bisphenol A (BPA) is an endocrine disruptor that displays estrogenic activity. Several reports suggest that BPA may have estrogen receptor-independent effects. In zebrafish, 50 μM BPA exposure induces otic vesicle abnormalities, including otolith aggregation. The purpose of this study was to test if BPA action was mediated in vivo during zebrafish development by the orphan nuclear estrogen related receptor (ERR) γ. Combining pharmacological and functional approaches, we demonstrate that the zebrafish ERRγ mediates BPA-induced malformations in otoliths. Using different bisphenol derivatives, we show that different compounds can induce a similar otolith phenotype than BPA and that the binding affinity of these derivatives to the zebrafish ERRγ correlates with their ability to induce otolith malformations. Morpholino knockdown of ERRγ function suppresses the BPA effect on otoliths whereas overexpression of ERRγ led to a BPA-like otolith phenotype. Moreover, a subphenotypical dose of BPA (1 μM) combined with ERRγ overexpression led to a full-dose (50 μM) BPA otolith phenotype. We therefore conclude that ERRγ mediates the otic vesicle phenotype generated by BPA. Our results suggest that the range of pathways perturbed by this compound and its potential harmful effect are larger than expected.—Tohmé, M., Prud’homme, S. M., Boulahtouf, A., Samarut, E., Brunet, F., Bernard, L., Bourguet, W., Gibert, Y., Balaguer, P., Laudet, V. Estrogen-related receptor γ is an in vivo receptor of bisphenol A.

Sex-linked neuroanatomical basis of human altruistic cooperativeness

Human altruistic cooperativeness, one of the most important components of our highly organized society, is along with a greatly enlarged brain relative to body size a spectacular outlier in the animal world. The "social-brain hypothesis" suggests that human brain expansion reflects an increased necessity for information processing to create social reciprocity and cooperation in our complex society. The present study showed that the young adult females (n = 66) showed greater Cooperativeness as well as larger relative global and regional gray matter volumes (GMVs) than the matched males (n = 89), particularly in the social-brain regions including bilateral posterior inferior frontal and left anterior medial prefrontal cortices. Moreover, in females, higher cooperativeness was tightly coupled with the larger relative total GMV and more specifically with the regional GMV in most of the regions revealing larger in female sex-dimorphism. The global and most of regional correlations between GMV and Cooperativeness were significantly specific to female. These results suggest that sexually dimorphic factors may affect the neurodevelopment of these "social-brain" regions, leading to higher cooperativeness in females. The present findings may also have an implication for the pathophysiology of autism; characterized by severe dysfunction in social reciprocity, abnormalities in social-brain, and disproportionately low probability in females.

Psychotic-like experiences in a community sample of adolescents: implications for the continuum model of psychosis and prediction of schizophrenia

Studies conducted in community samples suggest that psychotic-like experiences are common in the general population, leading to suggestions that they are either variations of normal personality or are different expressions of underlying vulnerability to psychotic disorder. Different types of psychotic symptoms may exist, some being normal variants and some having implications for mental health and functioning. The aim of the present study was to determine if different subtypes of psychotic-like experiences could be identified in a community sample of adolescents and to investigate if particular subtypes were more likely to be associated with psychosocial difficulties, that is, distress, depression and poor functioning, than other subtypes. Eight hundred and seventy-five Year 10 students from 34 schools participated in a cross-sectional survey that measured psychotic-like experiences using the Community Assessment of Psychic Experiences; depression using the Centre for Epidemiologic Studies Depression Scale; and psychosocial functioning using the Revised Multidimensional Assessment of Functioning Scale. Factor analysis was conducted to identify any subtypes of psychotic experiences. Four subtypes of psychotic-like experiences were identified: Bizarre Experiences, Perceptual Abnormalities, Persecutory Ideas, and Magical Thinking. Intermittent, infrequent psychotic experiences were common, but frequent experiences were not. Bizarre Experiences, Perceptual Abnormalities and Persecutory Ideas were strongly associated with distress, depression and poor functioning. Magical Thinking was only weakly associated with these variables. Overall these findings may suggest that infrequent psychotic-like experiences are unlikely to be a specific risk factor for onset of a psychotic disorder in community samples. Given that the different subtypes had varying associations with current difficulties it is suggested that not all subtypes confer the same risk for onset of psychotic disorder and poor outcome. Bizarre Experiences, Perceptual Abnormalities and Persecutory Ideas may represent expressions of underlying vulnerability to psychotic disorder, but Magical Thinking may be a normal personality variant.

Low spatial frequency contrast sensitivity deficits in migraine are not visual pathway selective

Some people who experience migraine demonstrate reduced visual contrast sensitivity that is measurable between migraines. Contrast sensitivity loss to low spatial frequency gratings has been previously attributed to possible impairment of magnocellular pathway function. This study measured contrast sensitivity using low spatial frequency targets (0.25–4 c/deg) where the adaptation aspects of the stimuli were designed to preferentially assess either magnocellular or parvocellular pathway function (steady and pulsed pedestal technique). Twelve people with migraine with measured visual field abnormalities and 17 controls participated. Subjects were tested foveally and at 10° eccentricity. Foveally, there was no significant difference in group mean contrast sensitivity. At 10°, the migraine group demonstrated reduced contrast sensitivity for both the stimuli designed to assess magnocellular and parvocellular function (P < 0.05). The functional deficits measured in this study infer that abnormalities of the low spatial frequency sensitive channels of both pathways contribute to contrast sensitivity deficits in people with migraine.

Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle

The present study examined the acute effects of metformin on fatty acid (FA) metabolism in oxidative soleus (SOL) and glycolytic epitrochlearis (EPT) rodent muscle. SOL and EPT were incubated for either 30 or 180 min in the absence or presence of 2 mM metformin and with or without insulin (10 mU/ml). Metformin did not alter basal FA metabolism but countered the effects of insulin on FA oxidation and incorporation into triacylglyerol (TAG). Specifically, metformin prevented the insulin-induced suppression of FA oxidation in SOL but did not alter FA incorporation into lipid pools. In contrast, in EPT metformin blunted the incorporation of FA into TAG when insulin was present but did not alter FA oxidation. In SOL, metformin resulted in a 50% increase in AMP-activated protein kinase α2 activity and prevented the insulin-induced increase in malonyl-CoA content. In both fiber types, basal and insulin-stimulated glucose oxidation were not significantly altered by metformin. All effects were similar regardless of whether they were measured after 30 or 180 min. Because increased muscle lipid storage and impaired FA oxidation have been associated with insulin resistance in this tissue, the ability of metformin to reverse these abnormalities in muscle FA metabolism may be a part of the mechanism by which metformin improves glucose clearance and insulin sensitivity. The present data also suggest that increased glucose clearance is not due to its enhanced subsequent oxidation. Additional studies are warranted to determine whether chronic metformin treatment has similar effects on muscle FA metabolism.

Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-α

IL-6 and TNF-α have been associated with insulin resistance and type 2 diabetes. Furthermore, abnormalities in muscle fatty acid (FA) metabolism are strongly associated with the development of insulin resistance. However, few studies have directly examined the effects of either IL-6 or TNF-α on skeletal muscle FA metabolism. Here, we used a pulse-chase technique to determine the effect of IL-6 (50-5,000 pg/ml) and TNF-α (50-5,000 pg/ml) on FA metabolism in isolated rat soleus muscle. IL-6 (5,000 pg/ml) increased exogenous and endogenous FA oxidation by ≃50% (P < 0.05) but had no effect on FA uptake or incorporation of FA into endogenous lipid pools. In contrast, TNF-α had no effect on FA oxidation but increased FA incorporation into diacylglycerol (DAG) by 45% (P < 0.05). When both IL-6 (5,000 pg/ml) and insulin (10 mU/ml) were present, IL-6 attenuated insulin's suppressive effect on FA oxidation, increasing exogenous FA oxidation (+37%, P < 0.05). Furthermore, in the presence of insulin, IL-6 reduced the esterification of FA to triacylglycerol by 22% (P < 0.05). When added in combination with IL-6 or leptin (10 μg/ml), the TNF-α-induced increase in DAG synthesis was inhibited. In conclusion, the results demonstrate that IL-6 plays an important role in regulating fat metabolism in muscle, increasing rates of FA oxidation, and attenuating insulin's lipogenic effects. In contrast, TNF-α had no effect on FA oxidation but increased FA incorporation into DAG, which may be involved in the development of TNF-α-induced insulin resistance in skeletal muscle.

Function and structure of the mirror neuron system in autism

 Utilizing MRI, this thesis identified wide-spread brain abnormalities in autism. White matter deficits were more pronounced in the left hemisphere, attributable to atypical myelination. Regarding the mirror neuron system, functional anomalies were situated in the right, dorsal, premotor cortex which further demonstrated reduced functional connectivity with the inferior parietal lobule.