Review of past and present research on aflatoxin in Uganda

Uganda is a landlocked country located in Eastern Africa covering an area of about 241,000 km2. Its climate is tropical, with  most parts of it receiving bimodal rainfall of 500 to 2000 mm per annum, and an average temperature of 25 oC. These  temperatures and the humid environment are optimum for growth of Aspergillus flavus/parasiticus and subsequent production of aflatoxins in the produce. The country was among those in the world where aflatoxin studies were first conducted following their discovery, in the 1960s and, during that time, hepatoma frequency was related to aflatoxin content of food. The objective of this paper is to review the past and present status of aflatoxin research in Uganda by considering the epidemiology, measurement, research, promoting factors, control strategies and problems associated with this toxin in the country. It is  revealed that aflatoxin contamination has been studied mainly in maize and groundnuts, and aflatoxin B1 is the most prevalent in the country. More studies have been done on foods sampled at the market level than on-farm level. There is more aflatoxin contamination of  foods in markets, than those stored by farmers, with some having levels above the FDA/WHO recommended limits of 20 ppb. However, no strategies for controlling aflatoxin contamination of food and food products in Uganda have been reported. It is concluded that aflatoxin contamination of agricultural produce is a big problem in the country, and this is  attributed to inadequate research, lack of proper sampling and analytical procedures; poor legislation and lack of awareness of the problem by farmers, traders, processors and consumers. Therefore in order to reduce the  potential hazard of aflatoxins,  government of Uganda through the Ministries of  Health, and Agriculture, Animal Industry and Fisheries; together with the  Uganda National Bureau of Standards, should put into place information dissemination and training programs for farmers,  traders and consumers on proper pre- and  post-harvest aflatoxin management strategies. To reduce further this potential   hazard, regulations for monitoring susceptible produce from buying points to retail markets should be put in place and strict measures on the quality of food at both household and market levels be enforced by all policy makers.Key words: Uganda, aflatoxin, contamination, maize, groundnutsL’Ouganda est un pays enclavé situé en Afrique orientale, qui couvre une superficie de près de 241.000 km2. Son climat est tropical, la plupart de ses régions  reçoivent des pluies bimodales de 500 à 2000 mm par an, et la température moyenne est de 25 oC. Ces températures et l’environnement humide sont optimaux pour la culture et la croissance d’Aspergillus  flavus/parasiticus et la production subséquente d’aflatoxines dans ses produits. L’Ouganda compte parmi les premiers pays du monde où des études sur les aflatoxines ont été menées aussitôt après la découverte de ces dernières dans les années  1960. A cette époque, la fréquence de l’hépatome a été associée à la teneur en aflatoxine dans les aliments. L’objectif du présent document est d’évaluer l’état des recherches passées et actuelles sur l’aflatoxine en Ouganda en considérant  l’épidémiologie, les mesures, les  recherches, les facteurs de promotion, les stratégies de contrôle et les problèmes associés  à cette toxine dans le pays. Il a été révélé que la contamination par aflatoxine a été étudiée principalement dans le maïs et l’arachide, et l’aflatoxine B1 est la plus prévalente dans le pays. Des études ont été effectuées sur les aliments pris comme échantillons plus au niveau du marché qu’au niveau des champs. Il y a plus de contamination par aflatoxine dans les aliments exposés au marché que dans les aliments conservés par les cultivateurs, certains aliments ayant des niveaux supérieurs aux limites de 20 ppb recommandées par l’OMS/FDA (organisme gouvernemental de contrôle pharmaceutique et alimentaire). Cependant, aucune  stratégie de contrôle de la contamination par aflatoxine d’aliments et de produits alimentaires en  Ouganda n’a été rapportée. La conclusion est que la contamination des produits agricoles par aflatoxine est un grand  problème qui se pose dans le  pays, et ceci est dû à des facteurs tels que des recherches inadéquates, le manque  d’échantillonnage approprié et de procédures analytiques; une mauvaise législation et aussi parce que les agriculteurs, les  commerçants, les agents de la   transformation industrielle et les consommateurs ne sont pas au courant du  problème. Par  conséquent, pour réduire les possibilités des dangers présentés par les aflatoxines, le Gouvernement de l’Ouganda, par le  biais des Ministères de la santé, de l’agriculture, de l’industrie animale et de la pêche, conjointement avec le Bureau National de vérification des Normes en Ouganda (Uganda National Bureau of Standards), devrait mettre en place des programmes de diffusion d’informations et de formation à l’intention des cultivateurs, des commerçants et des consommateurs sur des  stratégies de gestion de l’aflatoxine avant et après la récolte. Dans le souci de réduire davantage ce danger éventuel, des  règlements visant à contrôler des  produits sensibles depuis les points d’achat jusqu’aux marchés de vente en détail   devraient être mis en place et des mesures strictes relatives à la qualité des  aliments aussi bien au niveau des ménages qu’au marché devraient être mises en application par tous les décideurs.Mots-clés: Ouganda, aflatoxine, contamination, maïs, arachides

Auditory spatial processing in Alzheimer's disease.

: The location and motion of sounds in space are important cues for encoding the auditory world. Spatial processing is a core component of auditory scene analysis, a cognitively demanding function that is vulnerable in Alzheimer's disease. Here we designed a novel neuropsychological battery based on a virtual space paradigm to assess auditory spatial processing in patient cohorts with clinically typical Alzheimer's disease (n = 20) and its major variant syndrome, posterior cortical atrophy (n = 12) in relation to healthy older controls (n = 26). We assessed three dimensions of auditory spatial function: externalized versus non-externalized sound discrimination, moving versus stationary sound discrimination and stationary auditory spatial position discrimination, together with non-spatial auditory and visual spatial control tasks. Neuroanatomical correlates of auditory spatial processing were assessed using voxel-based morphometry. Relative to healthy older controls, both patient groups exhibited impairments in detection of auditory motion, and stationary sound position discrimination. The posterior cortical atrophy group showed greater impairment for auditory motion processing and the processing of a non-spatial control complex auditory property (timbre) than the typical Alzheimer's disease group. Voxel-based morphometry in the patient cohort revealed grey matter correlates of auditory motion detection and spatial position discrimination in right inferior parietal cortex and precuneus, respectively. These findings delineate auditory spatial processing deficits in typical and posterior Alzheimer's disease phenotypes that are related to posterior cortical regions involved in both syndromic variants and modulated by the syndromic profile of brain degeneration. Auditory spatial deficits contribute to impaired spatial awareness in Alzheimer's disease and may constitute a novel perceptual model for probing brain network disintegration across the Alzheimer's disease syndromic spectrum.<br/

Musical tasks targeting preserved and impaired functions in two dementias.

Studies of musical abilities in dementia have for the most part been rather general assessments of abilities, for instance, assessing retention of music learned premorbidly. Here, we studied patients with dementias with contrasting cognitive profiles to explore specific aspects of music cognition under challenge. Patients suffered from Alzheimer's disease (AD), in which a primary impairment is in forming new declarative memories, or Lewy body disease (PD/LBD), a type of parkinsonism in which executive impairments are prominent. In the AD patients, we examined musical imagery. Behavioral and neural evidence confirms involvement of perceptual networks in imagery, and these are relatively spared in early stages of the illness. Thus, we expected patients to have relatively intact imagery in a mental pitch comparison task. For the LBD patients, we tested whether executive dysfunction would extend to music. We probed inhibitory skills by asking for a speeded pitch or timbre judgment when the irrelevant dimension was held constant or also changed. Preliminary results show that AD patients score similarly to controls in the imagery tasks, but PD/LBD patients are impaired relative to controls in suppressing some irrelevant musical dimensions, particularly when the required judgment varies from trial to trial

Physiological phenotyping of dementias using emotional sounds.

INTRODUCTION: Emotional behavioral disturbances are hallmarks of many dementias but their pathophysiology is poorly understood. Here we addressed this issue using the paradigm of emotionally salient sounds. METHODS: Pupil responses and affective valence ratings for nonverbal sounds of varying emotional salience were assessed in patients with behavioral variant frontotemporal dementia (bvFTD) (n = 14), semantic dementia (SD) (n = 10), progressive nonfluent aphasia (PNFA) (n = 12), and AD (n = 10) versus healthy age-matched individuals (n = 26). RESULTS: Referenced to healthy individuals, overall autonomic reactivity to sound was normal in Alzheimer's disease (AD) but reduced in other syndromes. Patients with bvFTD, SD, and AD showed altered coupling between pupillary and affective behavioral responses to emotionally salient sounds. DISCUSSION: Emotional sounds are a useful model system for analyzing how dementias affect the processing of salient environmental signals, with implications for defining pathophysiological mechanisms and novel biomarker development

Music Perception in Dementia.

Despite much recent interest in music and dementia, music perception has not been widely studied across dementia syndromes using an information processing approach. Here we addressed this issue in a cohort of 30 patients representing major dementia syndromes of typical Alzheimer's disease (AD, n = 16), logopenic aphasia (LPA, an Alzheimer variant syndrome; n = 5), and progressive nonfluent aphasia (PNFA; n = 9) in relation to 19 healthy age-matched individuals. We designed a novel neuropsychological battery to assess perception of musical patterns in the dimensions of pitch and temporal information (requiring detection of notes that deviated from the established pattern based on local or global sequence features) and musical scene analysis (requiring detection of a familiar tune within polyphonic harmony). Performance on these tests was referenced to generic auditory (timbral) deviance detection and recognition of familiar tunes and adjusted for general auditory working memory performance. Relative to healthy controls, patients with AD and LPA had group-level deficits of global pitch (melody contour) processing while patients with PNFA as a group had deficits of local (interval) as well as global pitch processing. There was substantial individual variation within syndromic groups. Taking working memory performance into account, no specific deficits of musical temporal processing, timbre processing, musical scene analysis, or tune recognition were identified. The findings suggest that particular aspects of music perception such as pitch pattern analysis may open a window on the processing of information streams in major dementia syndromes. The potential selectivity of musical deficits for particular dementia syndromes and particular dimensions of processing warrants further systematic investigation

A physiological signature of sound meaning in dementia.

The meaning of sensory objects is often behaviourally and biologically salient and decoding of semantic salience is potentially vulnerable in dementia. However, it remains unclear how sensory semantic processing is linked to physiological mechanisms for coding object salience and how that linkage is affected by neurodegenerative diseases. Here we addressed this issue using the paradigm of complex sounds. We used pupillometry to compare physiological responses to real versus synthetic nonverbal sounds in patients with canonical dementia syndromes (behavioural variant frontotemporal dementia - bvFTD, semantic dementia - SD; progressive nonfluent aphasia - PNFA; typical Alzheimer's disease - AD) relative to healthy older individuals. Nonverbal auditory semantic competence was assessed using a novel within-modality sound classification task and neuroanatomical associations of pupillary responses were assessed using voxel-based morphometry (VBM) of patients' brain MR images. After taking affective stimulus factors into account, patients with SD and AD showed significantly increased pupil responses to real versus synthetic sounds relative to healthy controls. The bvFTD, SD and AD groups had a nonverbal auditory semantic deficit relative to healthy controls and nonverbal auditory semantic performance was inversely correlated with the magnitude of the enhanced pupil response to real versus synthetic sounds across the patient cohort. A region of interest analysis demonstrated neuroanatomical associations of overall pupil reactivity and differential pupil reactivity to sound semantic content in superior colliculus and left anterior temporal cortex respectively. Our findings suggest that autonomic coding of auditory semantic ambiguity in the setting of a damaged semantic system may constitute a novel physiological signature of neurodegenerative diseases

Evaluation of injectable nucleus augmentation materials for the treatment of intervertebral disc degeneration

Back pain affects a person's health and mobility as well as being associated with large health and social costs. Lower back pain is frequently caused by degeneration of the intervertebral disc. Current operative and non-operative treatments are often ineffective and expensive. Nucleus augmentation is designed to be a minimally invasive method of restoring the disc to its native healthy state by restoring the disc height, and mechanical and/or biological properties. The majority of the candidate materials for nucleus augmentation are injectable hydrogels. In this review, we examine the materials that are currently under investigation for nucleus augmentation, and compare their ability to meet the design requirements for this application. Specifically, the delivery of the material into the disc, the mechanical properties of the material and the biological compatibility are examined. Recommendations for future testing are also made

Profiles of white matter tract pathology in frontotemporal dementia.

Despite considerable interest in improving clinical and neurobiological characterisation of frontotemporal dementia and in defining the role of brain network disintegration in its pathogenesis, information about white matter pathway alterations in frontotemporal dementia remains limited. Here we investigated white matter tract damage using an unbiased, template-based diffusion tensor imaging (DTI) protocol in a cohort of 27 patients with the behavioral variant of frontotemporal dementia (bvFTD) representing both major genetic and sporadic forms, in relation both to healthy individuals and to patients with Alzheimer's disease. Widespread white matter tract pathology was identified in the bvFTD group compared with both healthy controls and Alzheimer's disease group, with prominent involvement of uncinate fasciculus, cingulum bundle and corpus callosum. Relatively discrete and distinctive white matter profiles were associated with genetic subgroups of bvFTD associated with MAPT and C9ORF72 mutations. Comparing diffusivity metrics, optimal overall separation of the bvFTD group from the healthy control group was signalled using radial diffusivity, whereas optimal overall separation of the bvFTD group from the Alzheimer's disease group was signalled using fractional anisotropy. Comparing white matter changes with regional grey matter atrophy (delineated using voxel based morphometry) in the bvFTD cohort revealed co-localisation between modalities particularly in the anterior temporal lobe, however white matter changes extended widely beyond the zones of grey matter atrophy. Our findings demonstrate a distributed signature of white matter alterations that is likely to be core to the pathophysiology of bvFTD and further suggest that this signature is modulated by underlying molecular pathologies. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc

Melody Processing Characterizes Functional Neuroanatomy in the Aging Brain

The functional neuroanatomical mechanisms underpinning cognition in the normal older brain remain poorly defined, but have important implications for understanding the neurobiology of aging and the impact of neurodegenerative diseases. Auditory processing is an attractive model system for addressing these issues. Here, we used fMRI of melody processing to investigate auditory pattern processing in normal older individuals. We manipulated the temporal (rhythmic) structure and familiarity of melodies in a passive listening, ‘sparse’ fMRI protocol. A distributed cortico-subcortical network was activated by auditory stimulation compared with silence; and within this network, we identified separable signatures of anisochrony processing in bilateral posterior superior temporal lobes; melodic familiarity in bilateral anterior temporal and inferior frontal cortices; and melodic novelty in bilateral temporal and left parietal cortices. Left planum temporale emerged as a ‘hub’ region functionally partitioned for processing different melody dimensions. Activation of Heschl’s gyrus by auditory stimulation correlated with the integrity of underlying cortical tissue architecture, measured using multi-parameter mapping. Our findings delineate neural substrates for analyzing perceptual and semantic properties of melodies in normal aging. Melody (auditory pattern) processing may be a useful candidate paradigm for assessing cerebral networks in the older brain and potentially, in neurodegenerative diseases of later life

Delayed auditory feedback simulates features of nonfluent primary progressive aphasia.

The pathophysiology of nonfluent primary progressive aphasia (nfvPPA) remains poorly understood. Here, we compared quantitatively speech parameters in patients with nfvPPA versus healthy older individuals under altered auditory feedback, which has been shown to modulate normal speech output. Patients (n=15) and healthy volunteers (n=17) were recorded while reading aloud under delayed auditory feedback [DAF] with latency 0, 50 or 200 ms and under DAF at 200 ms plus 0.5 octave upward pitch shift. DAF in healthy older individuals was associated with reduced speech rate and emergence of speech sound errors, particularly at latency 200 ms. Up to a third of the healthy older group under DAF showed speech slowing and frequency of speech sound errors within the range of the nfvPPA cohort. Our findings suggest that (in addition to any anterior, primary language output disorder) these key features of nfvPPA may reflect distorted speech input signal processing, as simulated by DAF. DAF may constitute a novel candidate pathophysiological model of posterior dorsal cortical language pathway dysfunction in nfvPPA