Antagonistic effects of Streptococcus and Lactobacillus probiotics in pharyngeal biofilms.

Direct antagonism towards pathogens including Streptococcus pyogenes is a proposed mechanism of pharyngeal probiosis but off-target effects on the symbiotic microbiota of the throat are possible and may be beneficial, harmful or neutral. We have assessed the bacteriological effects of two candidate Lactobacillus probiotics and the established pharyngeal probiotic Streptococcus salivarius K12. Antagonism towards S. pyogenes and potential off-target effects were determined using sessile monospecies biofilms and pharyngeal microcosms, respectively. The candidate probiotics were antagonistic towards S. pyogenes (rank order of increasing potency, Lactobacillus acidophilus < Lactobacillus plantarum < Streptococcus salivarius) in the absence of significant acidification or cell-cell contact. Streptococcus salivarius and L. plantarum caused significant reductions in viable counts of streptococci in pharyngeal microbiotas, whilst S. salivarius also caused reductions in staphylococci. In contrast, changes in pharyngeal eubacterial DNA profiles were limited overall. In summary, the three candidate probiotics suppressed axenic Streptococcus pyogenes biofilms by mechanisms that did not depend on cell-cell contact or acidification and did not markedly destabilize complex pharyngeal microbiotas derived from healthy individuals. SIGNIFICANCE AND IMPACT OF THE STUDY: Candidate probiotic bacteria deployed to prevent or treat bacterial pharyngitis will interact with the target bacteria such as Streptococcus pyogenes as well as with the microbiota of the throat, where off-target effects are possible. Three candidate probiotics Lactobacillus acidophilus, Lactobacillus plantarum and Streptococcus salivarius reduced viability within extant S. pyogenes biofilms through the elaboration of diffusible factors other than fermentation acids but did not markedly disrupt ex situ pharyngeal microcosms. This work demonstrates the application of in vitro pharyngeal models in the preclinical testing of the safety and efficacy of candidate pharyngeal probiotics.

Deficiency of brain structural sub-network underlying post-ischaemic stroke apathy.

BACKGROUND AND PURPOSE: This study aimed to reveal the structural basis of post-ischaemic stroke apathy, especially in relation to disruptions in structural connectivity. METHODS: Eighty-eight participants were included. The Apathy Evaluation Scale, clinician version, was used to characterize the severity of apathy. Diffusion tensor imaging tractography was used to examine white matter integrity and to reconstruct white matter networks using 90 nodes based on the automated anatomical labeling atlas. The degree for each node was extracted to determine the relationship to the severity of apathy. RESULTS: Apathy was not significantly associated with damage to any single brain region. The degrees of 24 nodes (limbic system, three nodes; frontal lobe, six; basal ganglia, two; temporal lobe, three; parietal lobe, three; insula, two; occipital lobe, five) were significantly correlated to the Apathy Evaluation Scale scores. These 24 nodes constituted an apathy-related sub-network and its global and local efficiencies were negatively correlated with apathy levels (global, r = -0.54, P < 0.01; local, r = -0.64, P < 0.01). Multivariate logistic regression indicated that decreased global efficiency of this sub-network was an independent risk factor for apathy (odds ratio 0.03, 95% confidence interval 0.01-0.04, P = 0.007). Efficiencies of the non-apathy-related sub-network (the remaining 66 nodes) did not correlate or predict the presence of apathy. CONCLUSIONS: Post-stroke apathy is not due to the dysfunction of a single region or circuit. Rather, it results from disconnection of a complex sub-network of brain regions. This provides new insights into the neuroanatomical basis of post-stroke apathy.

Italian standardization of the Apples Cancellation Test.

Hemispatial neglect due to right parieto-temporo-frontal lesions has a negative impact on the success of rehabilitation, resulting in poor functional gain. Recent research has shown that different types of neglect can impact in a different way on rehabilitation outcomes. The availability of a sensitive test, useful for distinguishing egocentric and allocentric forms of neglect, may be clinically important as all current clinical instruments fail to distinguish between these forms of disturbance, yet they differentially predict outcome. The Apples Test is a new instrument useful to evaluate both egocentric and allocentric forms of neglect. In order to establish Italian norms for this diagnostic instrument the test was administered to a sample of 412 healthy people of both genders (201 M and 211 F), aged from 20 to 80 years enrolled from 14 different rehabilitation centers in Italy. Based on the data, we established pathological performance cut-offs for the accuracy score (total omission errors), the asymmetry score for egocentric neglect (omission error difference), the asymmetry score for allocentric neglect (commission error difference) and execution time. The usefulness of the Apples Test for diagnostic purposes is illustrated by presenting three patients with different forms of neglect (egocentric, allocentric and mixed neglect).

A process-specific approach in the study of normal aging deficits in cognitive control: What deteriorates with age?

Bearing in mind that cognitive control is a complex function that includes several processes, it is not clear exactly which ones deteriorate with age. In fact, controversial results have been found. For example, some studies indicate that age-related deficits are observed in proactive and not in reactive control, others show that it is reactive control that is impaired and not proactive control, and some studies find no deficits at all (e.g., Kopp, Lange, Howe, & Wessel, 2014; Xiang et al., 2016). One possible reason is that the contribution of different processes to the deterioration of cognitive control was investigated separately, i.e., without testing all processes within the same paradigm. Therefore, the main goal of the present experiment was to study the impact of normal aging on several processes related to cognitive control within the same task, which included both Simon and Spatial Stroop trials. The study focused on the following processes: generation of conflict measured by automatic response capture (i.e., stronger task-irrelevant information processing compared to task-relevant information processing); conflict detection; and control implementation (which can be reactive control, both within trials and across trials, and proactive control, as a task-set strategy). The results showed larger automatic response capture for older adults when facing a stimulus-response conflict (Simon) but not a stimulus-stimulus conflict (Spatial Stroop). Similarly, older adults also showed larger detection effects for both conflicts. However, regarding control implementation, they only showed difficulties in inhibiting the early automatic response capture (within-trial reactive control) but not reactive control across trials or proactive control. In conclusion, it seems that older adults are more affected by the presence of task-irrelevant information, especially when it comes to resolving stimulus-response conflict. However, they showed no impairments in their ability to implement cognitive control both across trials and as a task-set strategy.

The relationship between specific cognitive impairment and behaviour in Prader-Willi syndrome.

BACKGROUND: Individuals with Prader-Willi syndrome (PWS) have been shown to demonstrate a particular cognitive deficit in attention switching and high levels of preference for routine and temper outbursts. This study assesses whether a specific pathway between a cognitive deficit and behaviour via environmental interaction can exist in individuals with PWS. METHODS: Four individuals with PWS participated in a series of three single-case experiments including laboratory-based and natural environment designs. Cognitive (computer-based) challenges placed varying demands on attention switching or controlled for the cognitive demands of the tasks while placing no demands on switching. Unexpected changes to routines or expectations were presented in controlled games, or imposed on participants' natural environments and compared with control conditions during which no unexpected changes occurred. Behaviour was observed and heart rate was measured. RESULTS: Participants showed significantly increased temper outburst related behaviours during cognitive challenges that placed demands on attention switching, relative to the control cognitive challenges. Participants showed significantly increased temper outburst related behaviours when unexpected changes occurred in an experimental or the natural environment compared with when no changes occurred. CONCLUSIONS: Difficult behaviours that could be triggered reliably in an individual by a specific cognitive demand could also be triggered via manipulation of the environment. Results suggest that a directional relationship between a specific cognitive deficit and behaviour, via environmental interaction, can exist in individuals with PWS.

The Urinary Tract Microbiome in Older Women Exhibits Host Genetic and Environmental Influences.

The urinary microbiome is a relatively unexplored niche that varies with gender. Urinary microbes, especially in aging populations, are associated with morbidity. We present a large-scale study exploring factors defining urinary microbiome composition in community-dwelling older adult women without clinically active infection. Using 1,600 twins, we estimate the contribution of genetic and environmental factors to microbiome variation. The urinary microbiome is distinct from nearby sites and unrelated to stool microbiome with more Actinobacteria, Fusobacteria and Proteobacteria, but fewer Bacteroidetes, Firmicutes and Verrumicrobia. A quarter of variants had heritability estimates greater than 10% with most heritable microbes having potential clinical relevance, including Escherichia-Shigella linked to urinary tract infections. Age, menopausal status, prior UTI, and host genetics were top factors defining the urobiome with increased microbial diversity tending to associate with older age. These findings highlight the distinct composition of the urinary microbiome and significant contributions of host genetics.

Associations between repetitive questioning, resistance to change, temper outbursts and anxiety in Prader-Willi and Fragile-X syndromes.

BACKGROUND: The behavioural phenotypes of Prader-Willi (PWS) and Fragile-X (FraX) syndromes both comprise repetitive behaviours with differences between the profiles. In this study we investigated the context and antecedents to the repetitive behaviours and the association with other behavioural phenotypic characteristics in order to generate testable hypotheses regarding the cause of the behaviours. METHOD: The parents or carers of 46 children with PWS (mean age 14.1 years; 20 girls), and 33 boys with FraX (mean age 13.11 years) were interviewed about their children's repetitive behaviour in a semi-structured format. RESULTS: Children showed negative emotional behaviour (PWS: 87.0%; FraX: 79.4%) and repetitive questions (PWS: 78.3%; FraX: 73.5%) following changes in routine or expectations. Significantly more temper outbursts were reported to follow changes in children with PWS (89.1%) compared with boys with FraX (41.2%) (chi(2) = 20.93; P < 0.001). Anxiety that was frequently associated with repetitive and self-injurious behaviours in boys with FraX, followed changes in significantly more boys with FraX (76.5%) compared with children with PWS (6.5%) (chi(2) = 43.19, P < 0.001). DISCUSSION: On the basis of these reports and existing literature, we hypothesise that decreases in predictability are aversive to children with PWS and FraX. We also hypothesise that these children have a propensity to show a syndrome-related pattern of behaviour (temper outbursts in PWS and displays of anxiety in FraX) when an event in the environment has this aversive property. We hypothesise that questions may be reinforcing to children in their own right by increasing the predictability of the environment. We outline how a specific cognitive deficit in the endophenotypes associated with both PWS and FraX could be investigated as a potential explanation for the hypothesised aversive properties of decreased predictability.

A specific pathway can be identified between genetic characteristics and behaviour profiles in Prader-Willi syndrome via cognitive, environmental and physiological mechanisms.

BACKGROUND: Behavioural phenotypes associated with genetic syndromes have been extensively investigated in order to generate rich descriptions of phenomenology, determine the degree of specificity of behaviours for a particular syndrome, and examine potential interactions between genetic predispositions for behaviour and environmental influences. However, relationships between different aspects of behavioural phenotypes have been less frequently researched and although recent interest in potential cognitive phenotypes or endophenotypes has increased, these are frequently studied independently of the behavioural phenotypes. METHOD: Taking Prader-Willi syndrome (PWS) as an example, we discuss evidence suggesting specific relationships between apparently distinct aspects of the PWS behavioural phenotype and relate these to specific endophenotypic characteristics. RESULTS: The framework we describe progresses through biological, cognitive, physiological and behavioural levels to develop a pathway from genetic characteristics to behaviour with scope for interaction with the environment at any stage. CONCLUSIONS: We propose this multilevel approach as useful in setting out hypotheses in order to structure research that can more rapidly advance theory.

From both sides now: crossover effects influence navigation in patients with unilateral neglect.

Unilateral neglect is a challenging disorder that pervades a range of behaviours following stroke and hampers recovery. Although a preponderance of clinical studies measure performance on a range of bedside assessments, including line bisection and cancellation tasks, there have been calls for studies to embrace more relevant functional measures. Here, for the first time, we present data from two separate tasks that characterise the performance of seven patients with unilateral neglect when navigating a power wheelchair. The tasks involved negotiating an obstacle course and steering a central path between gaps of different sizes. Results from the obstacle course confirmed the clinical observation and predicted bias of contralesional errors. However, the second task revealed a robust "crossover" effect. Patients deviated to the ipsilesional side for large gaps but deviated increasingly contralesionally when steering through small gaps in behaviour that was analogous to that previously shown on line bisection tasks. Contrary to being seen as an unintuitive finding, further analysis of these errors suggests that patients are giving disproportionate weight to the location of the ipsilesional object when plotting a midline course between two objects. Our results provide a platform for further studies to investigate the modulation and rehabilitation of this important skill.

Comparing action disorganization syndrome and dual-task load on normal performance in everyday action tasks.

The term 'action disorganization syndrome' has been used to describe patients with selective impairments in carrying out multi-step everyday tasks, which are not linked to motor deficits. We used a range of everyday life tasks to examine the effects on a patient with ADS of having related distractors present during task performance. The presence of related distractors increased omission errors in the patient. In a second experiment we assessed whether we could mimic this pattern of deficit when normal participants carried out the everyday tasks and a secondary task was imposed to place demands on executive processes. Secondary task load produced a general increase in errors in the controls and reduced the number of self-correcting responses, but there were no proportional increases in omission errors. Control participants and patients with ADS may suffer from demands on different processes involved in the performance of everyday actions. We discuss the implications for understanding everyday actions.

A new species of Sarcocystis (Apicomplexa: Sarcocystidae) from the black bear (Ursus americanus).

Infection with Sarcocystis species is common in herbivores but is rare in bears. Histological sections of 374 black bears (Ursus americanus) from Pennsylvania were examined for sarcocysts. In total, 3 sarcocysts were found in 3 bears, with 1 sarcocyst per section. Sarcocysts from 2 bears were considered a new species, Sarcocystis ursusi. Sarcocysts of S. ursusi n. sp. were microscopic and contained only bradyzoites. By light microscopy, the sarcocyst wall was thin (< 0.5 microm thick) and had minute serrations. Ultrastructurally, the serrations on the sarcocyst wall consisted of villar protrusions (Vp) that were mostly 0.5 microm long. The Vp had bundles of electron-dense microtubules that were as wide as long; these microtubules extended deep into the ground substance layer, a feature that distinguished this species from unnamed sarcocysts from black bear. Bradyzoites were 4.8-6.0 microm long. The sarcocyst from the third bear was structurally different from S. ursusi; its sarcocyst wall was approximately 2 microm thick and had finger-like villi on the cyst wall giving the sarcocyst wall a striated appearance.

Detection by action: neuropsychological evidence for action-defined templates in search.

How do we detect a target in a cluttered environment? Here we present neuropsychological evidence that detection can be based on the action afforded by a target. A patient showing symptoms of unilateral neglect following damage to the right fronto-temporal-parietal region was slow and sometimes unable to find targets when they were defined by their name or even by a salient visual property (such as their color). In contrast, he was relatively efficient at finding a target defined by the action it afforded. Two other patients with neglect showed an opposite pattern; they were better at finding a target defined by its name. The data suggest that affordances can be effective even when a brain lesion limits the use of other properties in search tasks. The findings give evidence for a direct pragmatic route from vision to action in the brain.

Preliminary validation study of the Russian Birmingham Cognitive Screen.

INTRODUCTION: The Birmingham Cognitive Screen (BCoS) is designed for use with individuals who have acquired language impairment following stroke. Our goal was to develop a Russian version of the BCoS (Rus-BCoS) by translating the battery following cultural and linguistic adaptations and establishing preliminary data on its psychometric properties. METHOD: Fifty patients with left-hemisphere stroke were recruited, of whom 98% were diagnosed with mild to moderate aphasia. To check whether the Rus-BCoS provides stable and consistent scores, internal consistency, test-retest, and interrater types of reliability were determined. Eight participants with stroke and 20 neurologically intact participants were assessed twice. To inspect the discriminative power of the battery, 63 participants without brain impairment were tested with the Rus-BCoS. Additionally, the Russian version of the Montreal Cognitive Assessment (MoCA), Quantitative Assessment of Speech in Aphasia, and Luria's Neuropsychological Assessment Battery were used to examine convergent validity, sensitivity, and specificity of the Rus-BCoS. RESULTS: The internal consistency as well as test-retest and interrater reliability of the Rus-BCoS satisfied criteria for the research use. Performance on a majority of tasks in the battery correlated significantly with independently validated tests that putatively measure similar cognitive processes. Critically, all patients with aphasia returned nonzero scores in at least one task in all the Rus-BCoS sections, with the exception of the Controlled Attention section where two patients with severe executive control deficits could not perform. CONCLUSIONS: The Rus-BCoS shows promise as a comprehensive cognitive screening tool that can be used by clinicians working with Russian-speaking persons experiencing poststroke aphasia after much further validation and development of reliable normative standards. Given a lack of quantitative neuropsychological assessment tools in Russia, however, we contend the Rus-BCoS offers potential benefits to clinicians and patients. However, data from research studies with a broader sample of Russian speakers are needed.

Object recognition: the man who mistook his dog for a cat.

Neuropsychological studies of people with specific brain lesions have led to the theory that different parts of the brain are responsible for recognizing living and non-living objects. Now there is direct evidence from activity measurements that this is the case.

Human colour discrimination based on a non-parvocellular pathway.

BACKGROUND: Traditionally, colour information is assumed to be carried by neural channels in the parvocellular pathway and to be encoded in an opponent manner, while other, non-parvocellular, spectrally non-opponent channels are thought to play no part in colour vision. But is the parvocellular pathway the only way that colours can be discriminated in human vision? We studied two patients with cerebral achromatopsia, who lack conscious colour perception but are nevertheless able to make use of colour information. In particular, we investigated whether, in these patients, colour discrimination is mediated by the parvocellular pathway. RESULTS: The achromatopsic patients carried out a forced-choice colour- and luminance-discrimination task, and showed clear evidence of unconscious colour processing, consistent with previous studies. We added different types of luminance noise to see when this unconscious colour information could be masked. The results of the colour-discrimination-with-noise and the brightness-non-additivity experiments showed a double-dissociation between patients. This indicates that, in one patient, unconscious colour discrimination may be subserved by a spectrally non-opponent mechanism, which does not have the characteristics of the parvocellular pathway and which is responsive to fast flicker. Spectral sensitivity, contrast sensitivity and motion perception experiments confirmed that this patient lacks a working opponent parvocellular system. The second achromatopsic patient showed evidence of a residual parvocellular system. CONCLUSIONS: Our results show that chromatic discrimination need not be mediated by neural mechanisms, the parvocellular system in particular, normally assumed to subserve conscious colour perception. Such discrimination may be mediated by a neural subsystem which responds to fast flicker, is spectrally non-opponent, and supports normal motion perception.

A psychophysical investigation into the preview benefit in visual search.

In preview search, half of the distracters are presented ahead of the remaining distracters and the target. Search under these conditions is more efficient than when all the items appear together (Watson & Humphreys, 1997). We investigated the mechanisms contributing to this preview benefit using an orientation discrimination task. In a display of vertical Gabors (all equidistant from fixation) one Gabor (chosen at random) was tilted (left or right). When half the non-tilted Gabors were previewed, thresholds increased less with the number of Gabors, relative to when all the Gabors appeared together (a preview benefit). In a further experiment, orientation noise was added to some of the Gabors. When all Gabors were presented simultaneously, orientation thresholds for the target increased. The effects of noise on thresholds was reduced, however, when the noisy Gabors were presented as a preview. Furthermore, there was less effect of noise in the preview condition than when observers were cued to a subset of Gabors (with a cue presented prior to the Gabors, adjacent to their positions). Visual information can be effectively excluded from the previewed locations to a greater degree than when attention is directed to a subset of display items. The implications for understanding the mechanisms involved in preview search are discussed.

Previewing distracters reduces their effective contrast.

In a visual search task, when half the distracters are presented earlier than the remainder ('previewed'), observers find the target item more efficiently than when all the items are presented together -- the preview benefit. We measured psychometric functions for contrast increments on Gabors that were presented as a valid preview for subsequent search, and when they were a non-predictive (dummy) preview. Sensitivity to contrast increments was lower (rightwards shift of the psychometric function) on valid, compared to dummy previews. This is consistent with an account of the preview benefit in terms of active inhibition, equivalent to lowering the contrast of previewed items that are being actively ignored.

Self-bias modulates saccadic control.

We present novel data on the role of attention in eliciting enhanced processing of stimuli associated with self. Participants were required to make pro- or anti-saccades according to whether learned shape-label pairings matched or mismatched. When stimuli matched participants were required to make an anti-saccade, and when the stimuli mismatched a pro-saccade was required. We found that anti-saccades were difficult to make to stimuli associated with self when compared to stimuli associated with a friend and a stranger. In contrast, anti-saccades to friend-stimuli were easier to make than anti-saccades to stranger-stimuli. In addition, a correct anti-saccade to a self-associated stimulus disrupted subsequent pro-saccade trials, relative to when the preceding anti-saccade was made to other stimuli. The data indicate that self-associated stimuli provide a strong cue for explicit shifts of attention to them, and that correct anti-saccades to such stimuli demand high levels of inhibition (which carries over to subsequent pro-saccade trials). The self exerts an automatic draw on attention.

Identifying the causal mechanisms of the quiet eye.

Scientists who have examined the gaze strategies employed by athletes have determined that longer quiet eye (QE) durations (QED) are characteristic of skilled compared to less-skilled performers. However, the cognitive mechanisms of the QE and, specifically, how the QED affects performance are not yet fully understood. We review research that has examined the functional mechanism underlying QE and discuss the neural networks that may be involved. We also highlight the limitations surrounding QE measurement and its definition and propose future research directions to address these shortcomings. Investigations into the behavioural and neural mechanisms of QE will aid the understanding of the perceptual and cognitive processes underlying expert performance and the factors that change as expertise develops.

The Vivax Surveyor: Online mapping database for Plasmodium vivax clinical trials.

INTRODUCTION: Recurrent P. vivax infections are associated with significant morbidity and mortality. Although radical cure can reduce recurrent infection, it is confounded by antimalarial resistance and the lack of safe and effective hypnozoitocidal treatment. This study documents the available literature of published clinical trials of P. vivax, providing an up to date, online, open access tool to view and download available information. METHODS: A systematic review was conducted according to PRISMA guidelines to identify prospective P. vivax therapeutic clinical trials with at least 28 days follow-up published between 1st January 1960 and 12th October 2016. Treatment arms and evidence of chloroquine resistance were mapped to trial sites. RESULTS: Since 1960, a total of 1152 antimalarial clinical trials with a minimum 28 days follow-up have been published, of which 230 (20.0%) enrolled patients with P. vivax and were included. Trials were conducted in 38 countries: 168 (73.0%) in the Asia-Pacific, 13 (5.7%) in Africa and 43 (18.7%) in the Americas. The proportion of antimalarial trials assessing P. vivax rose from 10.7% (12/112) in 1991-1995, to 24.9% (56/225) in 2011-2015. Overall, 188 (81.7%) P. vivax trials included a chloroquine treatment arm, either alone or in combination with primaquine, and 107 (46.5%) trials included a chloroquine treatment arm with early primaquine to assess radical cure. There has been a recent increase in treatment arms with artemisinin derivatives. Of the 131 sites in which chloroquine resistance could be quantified, resistance was present in 59 (45.0%) sites in 15 endemic countries. CONCLUSIONS: Over the last 20 years there has been a substantial increase in clinical research on the treatment of P. vivax, which has generated a greater awareness of the global extent of chloroquine resistance. The WWARN open access, online interactive map provides up to date information of areas where drug resistant P. vivax is emerging.