A new phylogenetic group of Propionibacterium acnes

Immunofluorescence microscopy-based identification of presumptive Propionibacterium acnes isolates, using the P. acnes-specific mAb QUBPa3, revealed five organisms with an atypical cellular morphology. Unlike the coryneform morphology seen with P. acnes types I and II, these isolates exhibited long slender filaments (which formed large tangled aggregates) not previously described in P. acnes. No reaction with mAbs that label P. acnes types IA (QUBPa1) and II (QUBPa2) was observed. Nucleotide sequencing of the 16S rRNA gene (1484 bp) revealed the isolates to have between 99.8 and 99.9 % identity to the 16S rRNA gene of the P. acnes type IA, IB and II strains NCTC 737, KPA171202 and NCTC 10390, respectively. Analysis of the recA housekeeping gene (1047 bp) did reveal, however, a greater number of conserved nucleotide polymorphisms between the sequences from these isolates and those from NCTC 737 (98.9 % identity), KPA171202 (98.9 % identity) and NCTC 10390 (99.1 % identity). Phylogenetic investigations demonstrated that the isolates belong to a novel recA cluster or lineage distinct from P. acnes types I and II. We now propose this new grouping as P. acnes type III. The prevalence and clinical importance of this novel recA lineage amongst isolates of P. acnes remains to be determined.

Quantification of pathological lesions in the frontal and temporal lobe of ten patients diagnosed with Pick's disease

The densities of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) in the frontal and temporal lobe were determined in ten patients diagnosed with Pick's disease (PD). The density of PB was significantly higher in the dentate gyrus granule cells compared with the cortex and the CA sectors of the hippocampus. Within the hippocampus, the highest densities of PB were observed in sector CA1. PC were absent in the dentate gyrus and no significant differences in PC density were observed in the remaining brain regions. With the exception of two patients, the densities of SP and NFT were low with no significant differences in mean densities between cortical regions. In the hippocampus, the density of NFT was greatest in sector CA1. PB and PC densities were positively correlated in the frontal cortex but no correlations were observed between the PD and AD lesions. A principal components analysis (PCA) of the neuropathological variables suggested that variations in the densities of SP in the frontal cortex, temporal cortex and hippocampus were the most important sources of heterogeneity within the patient group. Variations in the densities of PB and NFT in the temporal cortex and hippocampus were of secondary importance. In addition, the PCA suggested that two of the ten patients were atypical. One patient had a higher than average density of SP and one familial patient had a higher density of NFT but few SP.

Statnote 2: describing the normal

If a sample of measurements comes from a population that is normally distributed, we can use several statistics to describe our sample, such as the mean, SD, and CV. In addition, we can determine how atypical an individual measurement has to be before we would consider it not to be a member of a specific population. Furthermore, we can use our sample to make inferences about the population from which the sample is drawn including making estimates of the population mean and fitting confidence intervals to a sample mean.

Antibody detection of Burkholderia pseudommallei and Burkholderia mallei

Monoclonal and polyclonaI antibodies have been produced for use in immunological assays for the detection of Burkholderia pseudomallei and Burkholderia mallei. Monoclonal antibodies recognising a high molecular weight polysaccharide material found in some strains of both species have been shown to be effective in recognising B. pseudomallei and B. mallei and distinguishing them from other organisms. The high molecular weight polysaccharide material is thought to be the capsule of B. pseudomallei and B. mallei and may have important links with virulence. B. pseudomallei and B. mallei are known to be closely related, sharing many epitopes, but antigenic variation has been demonstrated within both the species. The lipopolysaccharide from strains of B. pseudomal/ei and B. mallei has been isolated and the silver stain profiles found to be visually very similar. A monoclonal antibody raised to B. mallei LPS has been found to recognise both B. mallei and B. pseudomallei strains. However, in a small number of B. pseudomallei strains a visually atypical LPS profile has been demonstrated. A monoclonal ant ibody rai sed against this atypical LPS showed no recognition of the typical LPS profile of either B. mallei or B. pseudomallei. This atypical LPS structure has not been reported and may be immunologically distinct from the typical LPS. Molecular biology and antibody engineering techniques have been used in an attempt to produce single-chain antibody fragments reactive to B. pseudomallei. Sequencing of one of the single-chain antibody fragments produced showed high homology with murine immunoglobulin genes, but none of the single-chain antibody fragments were found to be specific to B. pselldomallei.

The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease

Neuronal intermediate filament inclusion disease (NIFID), a rare form of frontotemporal lobar degeneration (FTLD), is characterized neuropathologically by focal atrophy of the frontal and temporal lobes, neuronal loss, gliosis, and neuronal cytoplasmic inclusions (NCI) containing epitopes of ubiquitin and neuronal intermediate filament proteins. Recently, the 'fused in sarcoma' (FUS) protein (encoded by the FUS gene) has been shown to be a component of the inclusions of familial amyotrophic lateral sclerosis with FUS mutation, NIFID, basophilic inclusion body disease, and atypical FTLD with ubiquitin-immunoreactive inclusions (aFTLD-U). To further characterize FUS proteinopathy in NIFID, and to determine whether the pathology revealed by FUS immunohistochemistry (IHC) is more extensive than a-internexin, we have undertaken a quantitative assessment of ten clinically and neuropathologically well-characterized cases using FUS IHC. The densities of NCI were greatest in the dentate gyrus (DG) and in sectors CA1/2 of the hippocampus. Anti-FUS antibodies also labeled glial inclusions (GI), neuronal intranuclear inclusions (NII), and dystrophic neurites (DN). Vacuolation was extensive across upper and lower cortical layers. Significantly greater densities of abnormally enlarged neurons and glial cell nuclei were present in the lower compared with the upper cortical laminae. FUS IHC revealed significantly greater numbers of NCI in all brain regions especially the DG. Our data suggest: (1) significant densities of FUS-immunoreactive NCI in NIFID especially in the DG and CA1/2; (2) infrequent FUS-immunoreactive GI, NII, and DN; (3) widely distributed vacuolation across the cortex, and (4) significantly more NCI revealed by FUS than a-internexin IHC.

Planning for cycling in the West Midlands

The issues involved in planning for pedal cyclists are examined with reference to the West Midlands County. Working with a local cycling campaign group, the researcher uses action research methods to investigate and influence the campaign. Development of cycle planning is traced through the literature, focusing on bicycle ownership, bicycle use and cycling policy. UK practice is contrasted with the integrated approach of other countries. An extensive bibliography is provided. Local authority cycle planning through the TPP process is systematically assessed over three years. This provides a context for the information regarding cycling in the West Midlands. Existing data is presented from the 1981 Census and local police road accident and bicycle theft records. The developing relationship between the local authority and the cycle campaign group is narrated in detail, explaining the problems that can beset efforts to improve conditions for cyclists. The researcher was closely involved in this interaction, particularly with policy and a major public inquiry. A survey of the Cycle Campaign Network indicates that the local group was not atypical. To provide information relevant to the local campaign and for effective local planning, a survey of 3,500 West Midlands residents was conducted using a novel combination of questionnaires and interviews. It shows that 1) Bicycle ownership and use is considerably higher than indicated by the 1978/9 National Travel Survey 2) Cycling is most import to certain disadvantaged sections of the community, particularly the young, those without access to a car and in the lower SEGs. The broader issues of transport policy are discussed, concluding that cycling is regarded as a marginal activity and that changes in general transport policy, land use planning and fiscal arrangements are necessary conditions for cycle planning to succeed. An integrated package of cycling measures involving engineering, education, enforcement and encouragement is also required. Recommendations are made concerning central government, local authorities and cycle campaign groups. Subjects for further research are identified.

Regulation of signal transduction by calcitonin gene-related peptide receptors

Calcitonin gene-related peptide (CGRP) plays a pivotal role in migraine, activating its cognate receptor to initiate intracellular signalling. This atypical receptor comprises a distinct assembly, made up of a G protein-coupled receptor (GPCR), a single transmembrane protein, and an additional protein that is required for Ga(s) coupling. By altering the expression of individual receptor components, it might be possible to adjust cellular sensitivity to CGRP. In recognition of the increasing clinical significance of CGRP receptors, it is timely to review the signalling pathways that might be controlled by this receptor, how the activity of the receptor itself is regulated, and our current understanding of the molecular mechanisms involved in these processes. Like many GPCRs, the CGRP receptor appears to be promiscuous, potentially coupling to several G proteins and intracellular pathways. Their precise composition is likely to be cell type-dependent, and much work is needed to ascertain their physiological significance.

Probing the neurocognitive trajectories of children's reading skills

Emerging evidence of the high variability in the cognitive skills and deficits associated with reading achievement and dysfunction promotes both a more dimensional view of the risk factors involved, and the importance of discriminating between trajectories of impairment. Here we examined reading and component orthographic and phonological skills alongside measures of cognitive ability and auditory and visual sensory processing in a large group of primary school children between the ages of 7 and 12 years. We identified clusters of children with pseudoword or exception word reading scores at the 10th percentile or below relative to their age group, and a group with poor skills on both tasks. Compared to age-matched and reading-level controls, groups of children with more impaired exception word reading were best described by a trajectory of developmental delay, whereas readers with more impaired pseudoword reading or combined deficits corresponded more with a pattern of atypical development. Sensory processing deficits clustered within both of the groups with putative atypical development: auditory discrimination deficits with poor phonological awareness skills; impairments of visual motion processing in readers with broader and more severe patterns of reading and cognitive impairments. Sensory deficits have been variably associated with developmental impairments of literacy and language; these results suggest that such deficits are also likely to cluster in children with particular patterns of reading difficulty. © 2012 Elsevier Ltd.

How brand attribute typicality and consumer commitment moderate the influence of comparative advertising

This study examines how product attribute typicality and brand commitment influence the effects of comparative versus non-comparative ads on brand attitudes. Employing perspectives from the literatures on typicality and commitment, the study examines the effects of commitment to the comparison brand on the effectiveness of comparative versus non-comparative advertising. A between-informants experiment uses data from 466 student informants. It is hypothesized that (a) when the attribute under consideration is typical (atypical), among comparison brand committed informants, a non-comparative ad is more (no more) persuasive than a comparative ad, (b) when the attribute under consideration is typical, among comparison brand non-committed informants, a comparative ad is more persuasive than a non-comparative ad, and (c) when the attribute under consideration is atypical, among comparison brand non-committed informants, a comparative ad is likely to be more persuasive than a non-comparative ad, but the effect will be weaker than in the case of a typical attribute. Hypothesis (a) is supported while (b) has directional support. The results support a three-way interaction between consumer commitment, attribute typicality, and type of advertisement. The findings are relevant to a variety of contexts, such as markets characterized by high levels of market share and commitment for the market leader as well as fragmented markets where market share and commitment levels are low.

Eye movement problems and differential diagnosis of the parkinsonian syndromes

Differential clinical diagnosis of the parkinsonian syndromes, viz., Parkinson’s disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) can be difficult. Eye movement problems, however, are a chronic complication of many of these disorders and may be a useful aid to diagnosis. Hence, the presence in PSP of vertical supranuclear gaze palsy, fixation instability, lid retraction, blepharospasm, and apraxia of eyelid opening and closing is useful in separating PD from PSP. Moreover, atypical features of PSP include slowing of upward saccades, moderate slowing of downward saccades, the presence of a full range of voluntary vertical eye movements, a curved trajectory of oblique saccades, and absence of square-wave jerks. Downgaze palsy is probably the most useful diagnostic clinical symptom of PSP. By contrast, DLB patients are specifically impaired in both reflexive and saccadic execution and in the performance of more complex saccadic eye movement tasks. Problems in convergence in DLB are also followed by akinesia and rigidity. Abnormal ocular fixation may occur in a significant proportion of MSA patients along with excessive square-wave jerks, a mild supranuclear gaze palsy, a gaze-evoked nystagmus, a positioning down-beat nystagmus, mild-moderate saccadic hypometria, impaired smooth pursuit movements, and reduced vestibulo-ocular reflex (VOR) suppression. There may be considerable overlap between the eye movement problems characteristic of the various parkinsonian disorders, but taken together with other signs and symptoms, can be a useful aid in differential diagnosis, especially in the separation of PD and PSP.

Brain structural changes associated with chronicity and antipsychotic treatment in schizophrenia

Accumulating evidence suggest a life-long impact of disease related mechanisms on brain structure in schizophrenia which may be modified by antipsychotic treatment. The aim of the present study was to investigate in a large sample of patients with schizophrenia the effect of illness duration and antipsychotic treatment on brain structure. Seventy-one schizophrenic patients and 79 age and gender matched healthy participants underwent brain magnetic resonance imaging (MRI). All images were processed with voxel based morphometry, using SPM5. Compared to healthy participants, patients showed decrements in gray matter volume in the left medial and left inferior frontal gyrus. In addition, duration of illness was negatively associated with gray matter volume in prefrontal regions bilaterally, in the temporal pole on the left and the caudal superior temporal gyrus on the right. Cumulative exposure to antipsychotics correlated positively with gray matter volumes in the cingulate gyrus for typical agents and in the thalamus for atypical drugs. These findings (a) indicate that structural abnormalities in prefrontal and temporal cortices in schizophrenia are progressive and, (b) suggest that antipsychotic medication has a significant impact on brain morphology. © 2009 Elsevier B.V. and ECNP.

The development of Cannabidiol as a psychiatric therapeutic:a review of its antipsychotic efficacy and possible underlying pharmacodynamic mechanisms

Cannabidiol (CBD), a once-considered inert cannabis constituent, is one of two primary constituents of cannabis, alongside delta-9-tetrahydrocannabinol (?9-THC/THC). In the last 30 years, CBD has become implicated with a range of pharmaceutical mechanisms of great therapeutic interest and utility. This review details the literature speculating CBD’s attenuation of psychotic symptoms, particularly in light of a marked elevation in mean THC concentrations, and a concomitant decline in CBD concentrations in the prevalent U.K street market cannabis derivatives since c. 2000. CBD is purported to exhibit pharmacology akin to established atypical antipsychotics, whilst THC has been implicated with the precipitation of psychosis, and the induction of associated symptoms. The aim of the review was to clarify the conjecture surrounding CBD’s antipsychotic efficacy, before going on to detail prominent theories about its associated pharmacodynamics. Were CBD’s antipsychotic efficacy established, then there is potential for major latent anthropological repercussions to manifest, such as significant elevations in psychosis manifestations in the U.K. The review found a largely affirmative body of evidence asserting CBD’s antipsychotic efficacy. CBD exhibited capacity to attenuate natural and artificially induced psychoses in both animal and human cohorts, the latter of which included individuals considered resistant to conventional treatment. CBD also shows promising potential for use as an antipsychotic drug for Parkinson’s disease (PD) patients with psychosis, owing to its low rate of extra-pyramidal side-effect induction. A range of potential pharmacological mechanisms behind CBD’s neuroleptic pharmacology are outlined, with particular emphasis on its prevention of the hydrolysis and reuptake of the endogenous cannabinoid, anandamide. However, given the nebular aetiological basis for psychoses, explicit conclusions on how CBD attenuates psychotic symptoms remains to be determined.

What checkers actually check:an eye tracking study of inhibitory control and working memory

Background - Not only is compulsive checking the most common symptom in Obsessive Compulsive Disorder (OCD) with an estimated prevalence of 50–80% in patients, but approximately ~15% of the general population reveal subclinical checking tendencies that impact negatively on their performance in daily activities. Therefore, it is critical to understand how checking affects attention and memory in clinical as well as subclinical checkers. Eye fixations are commonly used as indicators for the distribution of attention but research in OCD has revealed mixed results at best. Methodology/Principal Finding - Here we report atypical eye movement patterns in subclinical checkers during an ecologically valid working memory (WM) manipulation. Our key manipulation was to present an intermediate probe during the delay period of the memory task, explicitly asking for the location of a letter, which, however, had not been part of the encoding set (i.e., misleading participants). Using eye movement measures we now provide evidence that high checkers’ inhibitory impairments for misleading information results in them checking the contents of WM in an atypical manner. Checkers fixate more often and for longer when misleading information is presented than non-checkers. Specifically, checkers spend more time checking stimulus locations as well as locations that had actually been empty during encoding. Conclusions/Significance - We conclude that these atypical eye movement patterns directly reflect internal checking of memory contents and we discuss the implications of our findings for the interpretation of behavioural and neuropsychological data. In addition our results highlight the importance of ecologically valid methodology for revealing the impact of detrimental attention and memory checking on eye movement patterns.

Analysis of the pore of the unusual major intrinsic protein channel, yeast Fps1p

Fps1p is a glycerol efflux channel from Saccharomyces cerevisiae. In this atypical major intrinsic protein neither of the signature NPA motifs of the family, which are part of the pore, is preserved. To understand the functional consequences of this feature, we analyzed the pseudo-NPA motifs of Fps1p by site-directed mutagenesis and assayed the resultant mutant proteins in vivo. In addition, we took advantage of the fact that the closest bacterial homolog of Fps1p, Escherichia coli GlpF, can be functionally expressed in yeast, thus enabling the analysis in yeast cells of mutations that make this typical major intrinsic protein more similar to Fps1p. We observed that mutations made in Fps1p to "restore" the signature NPA motifs did not substantially affect channel function. In contrast, when GlpF was mutated to resemble Fps1p, all mutants had reduced activity compared with wild type. We rationalized these data by constructing models of one GlpF mutant and of the transmembrane core of Fps1p. Our model predicts that the pore of Fps1p is more flexible than that of GlpF. We discuss the fact that this may accommodate the divergent NPA motifs of Fps1p and that the different pore structures of Fps1p and GlpF may reflect the physiological roles of the two glycerol facilitators.

The influence of patient's age on clinical decision-making about coronary heart disease in the USA and the UK

This paper examines UK and US primary care doctors' decision-making about older (aged 75 years) and midlife (aged 55 years) patients presenting with coronary heart disease (CHD). Using an analytic approach based on conceptualising clinical decision-making as a classification process, it explores the ways in which doctors' cognitive processes contribute to ageism in health-care at three key decision points during consultations. In each country, 56 randomly selected doctors were shown videotaped vignettes of actors portraying patients with CHD. The patients' ages (55 or 75 years), gender, ethnicity and social class were varied systematically. During the interviews, doctors gave free-recall accounts of their decision-making. The results do not establish that there was substantial ageism in the doctors' decisions, but rather suggest that diagnostic processes pay insufficient attention to the significance of older patients' age and its association with the likelihood of co-morbidity and atypical disease presentations. The doctors also demonstrated more limited use of 'knowledge structures' when diagnosing older than midlife patients. With respect to interventions, differences in the national health-care systems rather than patients' age accounted for the differences in doctors' decisions. US doctors were significantly more concerned about the potential for adverse outcomes if important diagnoses were untreated, while UK general practitioners cited greater difficulty in accessing diagnostic tests.