Tea Consumption Reduces the Incidence of Neurocognitive Disorders: Findings from the Singapore Longitudinal Aging Study.

OBJECTIVES: To examine the relationships between tea consumption habits and incident neurocognitive disorders (NCD) and explore potential effect modification by gender and the apolipoprotein E (APOE) genotype. DESIGN: Population-based longitudinal study. SETTING: The Singapore Longitudinal Aging Study (SLAS). PARTICIPANTS: 957 community-living Chinese elderly who were cognitively intact at baseline. MEASUREMENTS: We collected tea consumption information at baseline from 2003 to 2005 and ascertained incident cases of neurocognitive disorders (NCD) from 2006 to 2010. Odds ratio (OR) of association were calculated in logistic regression models that adjusted for potential confounders. RESULTS: A total of 72 incident NCD cases were identified from the cohort. Tea intake was associated with lower risk of incident NCD, independent of other risk factors. Reduced NCD risk was observed for both green tea (OR=0.43) and black/oolong tea (OR=0.53) and appeared to be influenced by the changing of tea consumption habit at follow-up. Using consistent non-tea consumers as the reference, only consistent tea consumers had reduced risk of NCD (OR=0.39). Stratified analyses indicated that tea consumption was associated with reduced risk of NCD among females (OR=0.32) and APOE ε4 carriers (OR=0.14) but not males and non APOE ε4 carriers. CONCLUSION: Regular tea consumption was associated with lower risk of neurocognitive disorders among Chinese elderly. Gender and genetic factors could possibly modulate this association.

Impact of duration of untreated psychosis and premorbid intelligence on cognitive functioning in patients with first-episode schizophrenia.

BACKGROUND: The neurotoxic hypothesis suggests that psychosis is toxic to the brain leading to clinical consequences. In this study, we hypothesized that a longer duration of untreated psychosis (DUP) in first episode schizophrenia (FES) patients is associated with poorer cognitive functioning, and that higher premorbid intelligence buffers against DUP-related cognitive impairment. METHOD: Eighty-one FES patients completed a neuropsychological battery, the Brief Assessment of Cognition in Schizophrenia (BACS). Composite scores of the BACS, which were normalized to a matched healthy control of seventy-three subjects, were used as an index of general cognition. A median split using the Wide Range Achievement Test-Reading Test scores was used to divide the patients into low versus high premorbid IQ groups. Hierarchical linear regression was performed to examine predictors of general cognition, including DUP. RESULTS: Longer DUP was found to be a significant predictor of poorer general cognition. In addition, DUP predicted general cognition in the low premorbid IQ group but not in the high premorbid IQ group. CONCLUSIONS: Our findings demonstrate that longer DUP in FES patients is associated with worse cognitive scores, and that this association is more pronounced in a subgroup of patients who have lower premorbid intelligence. Our results suggest the importance of earlier identification and management of patients with low premorbid IQ, given that their cognition may be more vulnerable to the toxicity of psychosis.

Support of vulnerable patients throughout TB treatment in the UK.

Despite well-established treatment regimens, tuberculosis (TB) remains a public health burden; it disproportionately affects poor and marginalized populations who may not have access to social support, including migrants, homeless people and those dependent on drugs or alcohol. There is a clearly demonstrated need for housing and other appropriate social support, as part of a package of integrated clinical and social care. However, TB prevention and control efforts in the UK often do not address the specific vulnerabilities of these groups and it can be a challenge to support the continued TB treatment of these underserved populations. This challenge is exacerbated by complex issues concerning funding, immigration and the law. In this paper, we have reviewed current UK guidance and legislation, discussed several case studies and highlighted examples of existing models of community support for TB patients. Finally, we lay out our recommendations for ensuring a co-ordinated, whole system approach to successful TB treatment.

Refining the latent structure of neuropsychological performance in schizophrenia.

BACKGROUND: Elucidating the cognitive architecture of schizophrenia promises to advance understanding of the clinical and biological substrates of the illness. Traditional cross-sectional neuropsychological approaches differentiate impaired from normal cognitive abilities but are limited in their ability to determine latent substructure. The current study examined the latent architecture of abnormal cognition in schizophrenia via a systematic approach. METHOD: Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were carried out on a large neuropsychological dataset including the Brief Assessment of Cognition in Schizophrenia, Continuous Performance Test, Wisconsin Card Sorting Test, Benton Judgment of Line Orientation Test, and Wechsler Abbreviated Scale of Intelligence matrix reasoning derived from 1012 English-speaking ethnic Chinese healthy controls and 707 schizophrenia cases recruited from in- and out-patient clinics. RESULTS: An initial six-factor model fit cognitive data in healthy and schizophrenia subjects. Further modeling, which accounted for methodological variance between tests, resulted in a three-factor model of executive functioning, vigilance/speed of processing and memory that appeared to best discriminate schizophrenia cases from controls. Factor analytic-derived g estimands and conventionally calculated g showed similar case-control discrimination. However, agreement analysis suggested systematic differences between both g indices. CONCLUSIONS: Factor structures derived in the current study were broadly similar to those reported previously. However, factor structures between schizophrenia subjects and healthy controls were different. Roles of factor analytic-derived g estimands and conventional composite score g were further discussed. Cognitive structures underlying cognitive deficits in schizophrenia may prove useful for interrogating biological substrates and enriching effect sizes for subsequent work.

Asymmetry of lexico-semantic processing in schizophrenia changes with disease progression.

BACKGROUND: Are anomalies of cerebral asymmetry integral to the disease process? Here, we examined the influence of age, chronicity and age of onset of illness in 34 patients with early onset schizophrenia and 20 controls in relation to structural asymmetries of the temporal lobe and performance asymmetries on a semantic language lexical decision task. METHODS: Volumetric MRI and a novel divided visual field probe of lateralised lexico-semantic language were assessed in patients with early onset schizophrenia (EOS) and controls. Novel ratios of age-illness overlap and directional asymmetry were developed in order to examine the association of chronicity factors to asymmetry. RESULTS: Loss of laterality on the lexical decision task and discordant structural asymmetry were correlated with duration of illness but were not seen in younger, less chronic patients. Reduced lateral processing speed, and discordant structural asymmetry were associated with greater proportion of lifetime schizophrenia. CONCLUSION: Although the conclusions are limited by the cross sectional nature of the study, anomalies of cerebral asymmetry in early onset patients may be an index of disease progression, and reflect directly on the disease process.

The utility and benefits of clinical neuropsychology in Asia.

Neuropsychological evaluation is the clinical practice of identifying and measuring impairments in mental functions in the context of a patient's mental strengths and preserved abilities for the purposes of diagnosis, rehabilitation planning, and long-term care. Best practice approaches to the medical management of neurodegenerative, neurological and psychiatric illness have lead to increasing demand for neuropsychological services. The simultaneous challenges of Asias' increasing adult and rapidly ageing population underscore the need for consideration of the role of neuropsychological services in day-to-day clinical practice. Here, we outline the clinical utility of neuropsychological assessment and indications for its use in general psychiatric practice.

Attenuation of an avian pathogenic Escherichia coli strain due to a mutation in the rpsL gene.

The diseases caused by pathogenic Escherichia coli constitute a major economic loss to the poultry industry. The development of a live oral E. coli vaccine to prevent or reduce diseases in poultry had been the objective of our work. Four spontaneous streptomycin-dependent (str-dependent) mutants were generated from a virulent avian strain that contains a mutation in the fur region of the chromosome. Genetic analysis of the mutants indicated that the str-dependent phenotype was due to a base change of C --> T at base 272 in the rpsL gene. The mutants were tested for attenuation using the day-old chick model. Day-old birds, in groups of 20, were either challenged with 10(6) colony-forming units (CFU) of the str-dependent mutant, the parent strain (containing the fur mutation), or the wild-type strain without the fur mutation. The parent strain and the wild-type strain were highly virulent, and 80% or more of the birds died. None of the birds challenged with the str-dependent mutants died, indicating attenuation of the mutants. The protective effect of the mutant as a live vaccine against the challenge with 10(6) CFU of the wild-type strain EC317 was investigated. Vaccination by both aerosol (day 1) and oral (days 14 and 28) routes using 10(8) CFU of the str-dependent mutant (EC1598) had no effect on the occurrence of cellulitis in the birds. Two vaccinations given as aerosol on day 1 and given orally on day 14 also had no significant effect on the occurrence of systemic lesions. Three immunizations on days 1, 14, and 28 resulted in a significant reduction in the number of birds with systemic lesions. Antibody titers prior to challenge were not predictive of outcome of challenge.

Extracellular polysaccharides associated with thin aggregative fimbriae of Salmonella enterica serovar enteritidis.

Lipopolysaccharide (LPS) O polysaccharide was identified as the principle factor impeding intercellular formation of intact thin aggregative fimbriae (Tafi) in Salmonella enterica serovar Enteritidis. The extracellular nucleation-precipitation assembly pathway for these organelles was investigated by quantifying fimbrial formation between deltaagfA (AgfA recipient) and deltaagfB (AgfA donor) cells harboring mutations in LPS (galE::Tn10) and/or cellulose (deltabcsA) synthesis. Intercellular complementation could be detected between deltaagfA and deltaagfB strains only when both possessed the galE mutation. LPS O polysaccharide appears to be an impenetrable barrier to AgfA assembly between cells but not within individual cells. The presence of cellulose did not restrict Tafi formation between cells. Transmission electron microscopy of w+ S. enterica serovar Enteritidis 3b cells revealed diffuse Tafi networks without discernible fine structure. In the absence of cellulose, however, individual Tafi fibers were clearly visible, appeared to be occasionally branched, and showed the generally distinctive appearance described for Escherichia coli K-12 curli. A third extracellular matrix component closely associated with cellulose and Tafi was detected on Western blots by using immune serum raised to whole, purified Tafi aggregates. Cellulose was required to tightly link this material to cells. Antigenically similar material was also detected in S. enterica serovar Typhimurium and one diarrheagenic E. coli isolate. Preliminary analysis indicated that this material represented an anionic, extracellular polysaccharide that was distinct from colanic acid. Therefore, Tafi in their native state appear to exist as a complex with cellulose and at least one other component.

'Seeing old people with real problems like leaving the gas on': students' and tutors' reflections after piloting the second phase of a new, community based course for second-year medical students.

This short communication presents the results of an evaluation carried out with tutors and students at the end of the pilot phase of a new, community-based teaching course for second year students at St Bartholomew's and the Royal London School of Medicine and Dentistry. Students were placed with different community-based healthcare teams in East London. The aims of the course were to enable students to observe, and be part of, the work of the multidisciplinary team, and to experience the continuing care of patients with chronic illnesses within the community.

Structure and characterization of AgfB from Salmonella enteritidis thin aggregative fimbriae.

The agfBAC operon of Salmonella enteritidis encodes thin aggregative fimbriae, fibrous, polymeric structures primarily composed of AgfA fimbrins. Although uncharacterized, AgfB shows a 51 % overall amino acid sequence similarity to AgfA. Using AgfB epitope-specific antiserum, AgfB was detected as a minor component of whole, purified fimbriae. Like AgfA, AgfB was released from purified fimbriae by >70 % formic acid, whereupon both AgfA-AgfA and AgfA-AgfB dimers as well as monomers were detected. This suggested that AgfB may form specific, highly stable, structural associations with AgfA in native fimbrial filaments, associations that were weakened in structurally unstable fibers derived from AgfA chimeric fimbrial mutants. Detailed sequence comparisons between AgfA and AgfB showed that AgfB harbored a similar fivefold repeated sequence pattern (x(6)QxGx(2)NxAx(3)Q), and contained structural motifs similar to the parallel beta helix model proposed for AgfA. Molecular modeling of AgfB revealed a 3D structure remarkably similar to that of AgfA, the structures differing principally in the surface disposition of non-conserved, basic, acidic and non-polar residues. Thus AgfB is a fimbrin-like structural homologue of AgfA and an integral, minor component of native thin aggregative fimbrial fibers. AgfB from an agfA deletion strain was detected as a non-fimbrial, SDS-insoluble form in the supernatant and was purified. AgfA from an agfB deletion strain was found in both SDS-soluble and insoluble, non-fimbrial forms. No AgfA-AgfA dimers were detected in the absence of AgfB. Fimbriae formation by intercellular complementation between agfB and agfA deletion strains could not be shown under a variety of conditions, indicating that AgfA and AgfB are not freely diffusible in S. enteritidis. This has important implications on the current assembly hypothesis for thin aggregative fimbriae.

Designing a community-based fourth-year obstetrics and gynaecology module: an example of innovative curriculum development.

INTRODUCTION: This paper describes the design and evaluation of the community-based obstetrics and gynaecology module at St Bartholomew's and the Royal London School of Medicine and Dentistry. This module sets out to comply with the General Medical Council's recommendations of encouraging students to consider the community perspective, and places less emphasis on a disease-orientated approach. OBJECTIVES: The development of the module, issues of improving student acceptance of the course, staff development and the benefits of community teaching in obstetrics and gynaecology are discussed. MODULE ORGANIZATION: The 2-week module precedes the 8-week hospital obstetrics and gynaecology firms that occur in the fourth undergraduate year. The course is organized into three components: general practice, departmental teaching, and self-directed learning. Students are allocated to general practices for their clinical teaching, for eight sessions. Seven departmental sessions are run by the Academic Department of General Practice and Primary Care. These include a review of the students' self-directed learning. EVALUATION AND CONCLUSION: Evaluation data are reported for the three components of the course. Overall the majority of students rated the module as useful, GP attachments being most favourably received. The majority of students have grasped the basic obstetric and gynaecological history and examination skills and found this useful before starting their hospital firms. Aspects of a specialist subject, such as, obstetrics and gynaecology, can be taught successfully in the community and GP tutors are, as yet, an untapped source of excellent obstetric and gynaecology teaching.

Doctor in the house: the medical student as academic, attendant and apprentice?

It is contended that change in the health services should be accompanied by a re-examination of medical education. Changes in professional roles and practices, specialist training and the location of patient care should be more central to informing change in undergraduate medical education. Although innovation in undergraduate curricula is taking place, much of this is in relation to improvement in educational methods. We would argue that these initiatives need to be more firmly linked to the realities of delivering healthcare today.

Salmonella enteritidis fimbriae displaying a heterologous epitope reveal a uniquely flexible structure and assembly mechanism.

Two distinct Salmonella fimbrins, AgfA and SefA, comprising thin aggregative fimbriae SEF17 and SEF14, respectively, were each genetically engineered to carry PT3, an alpha-helical 16-amino acid Leishmania T-cell epitope derived from the metalloprotease gp63. To identify regions within AgfA and SefA fimbrins amenable to replacement with this epitope, PCR-generated chimeric fimbrin genes were constructed and used to replace the native chromosomal agfA and sefA genes in Salmonella enteritidis. Immunoblot analysis using anti-SEF17 and anti-PT3 sera demonstrated that all ten AgfA chimeric fimbrin proteins were expressed by S. enteritidis under normal growth conditions. Immunoelectron microscopy confirmed that eight of the AgfA::PT3 proteins were effectively assembled into cell surface-exposed fimbriae. The PT3 replacements in AgfA altered Congo red (CR) binding, cell-cell adhesion and cell surface properties of S. enteritidis to varying degrees. However, these chimeric fimbriae were still highly stable, being resistant to proteinase K digestion and requiring harsh formic acid treatment for depolymerization. In marked contrast to AgfA, none of the chimeric SefA proteins were expressed or assembled into fimbriae. Since each PT3 replacement constituted over 10% of the AgfA amino acid sequence and all ten replacements collectively represented greater than 75% of the entire AgfA primary sequence, the ability of AgfA to accept large sequence substitutions and still assemble into fibers is unique among fimbriae and other structural proteins. This structural flexibility may be related to the novel fivefold repeating sequence of AgfA and its recently proposed structure Proper formation of chimeric fimbrial fibers suggests an unusual assembly mechanism for thin aggregative fimbriae which tolerates aberrant structures. This study opens a range of possibilities for Salmonella thin aggregative fimbriae as a carrier of heterologous epitopes and as an experimental model for studies of protein structure.