Search

Mobility is a key aspect of active ageing enabling participation and autonomy into later life. Remaining active brings multiple physical but also social benefits leading to higher levels of well-being. With globally increasing levels of urbanisation alongside demographic shifts meaning in many parts of the world this urban population will be older people, the challenge is how cities should evolve to enable so-called active ageing. This paper reports on a co-design study with 117 participants investigating the interaction of existing urban spaces and infrastructure on mobility and well-being for older residents (aged 55 + years) in three cities. A mixed method approach was trialled to identify locations beneficial to subjective well-being and participant-led solutions to urban mobility challenges. Spatial analysis was used to identify key underlying factors in locations and infrastructure that promoted or compromised mobility and well-being for participants. Co-designed solutions were assessed for acceptability or co-benefits amongst a wider cross-section of urban residents (n = 233) using online and face-to-face surveys in each conurbation. Our analysis identified three critical intersecting and interacting thematic problems for urban mobility amongst older people: The quality of physical infrastructure; issues around the delivery, governance and quality of urban systems and services; and the attitudes and behaviors of individuals that older people encounter. This identified complexity reinforces the need for policy responses that may not necessarily involve design or retrofit measures, but instead might challenge perceptions and behaviors of use and access to urban space. Our co-design results further highlight that solutions need to move beyond the generic and placeless, instead embedding specific locally relevant solutions in inherently geographical spaces, populations and processes to ensure they relate to the intricacies of place.

INTRODUCTION The aim of this study was to investigate the prevalence of risk factors for primary squamous cell carcinoma (SCC) of the bladder. MATERIALS A total of 90 cases of primary SCC of the bladder were identified through multicentre analysis. Patient demographics, stage and grade of cancer at presentation, management and outcomes were recorded. The presence of known risk factors (catheter use, neuropathic bladder, smoking history, recurrent urinary tract infection and bladder stones) was also documented. RESULTS Over half of the patients had at least one identifiable risk factor for the development of primary bladder SCC: 13.9% of patients had a history of catheter use (clean intermittent self-catheterisation [CISC] in 11.1%), 10.0% of patients had a neuropathic bladder, 27.8% were smokers or ex-smokers and 20.0% had a documented history of recurrent urinary tract infection. Statistical analysis of the results showed no association between risk factors and grade of tumour at presentation. CONCLUSIONS These data further support the association between primary bladder SCC and several of the well documented risk factors for its development. Chronic use of CISC may confer a greater risk for development of SCC than thought previously. Further evidence of the role of CISC in primary SCC is required to justify routine screening and to determine exactly when surveillance of the bladder should begin for this group of patients.

This paper describes the design and evaluation of a Web Accessibility Information Resource (WebAIR) for supporting web developers to create and evaluate accessible websites. WebAIR was designed with web developers in mind, recognising their current working practices and acknowledging their existing understanding of web accessibility. We conducted an evaluation with 32 professional web developers in which they used either WebAIR or an existing accessibility information resource, the Web Content Accessibility Guidelines, to identify accessibility problems. The findings indicate that several design decisions made in relation to the language, organisation, and volume of WebAIR were effective in supporting web developers to undertake web accessibility evaluations.

The proportion of older adults in the population is rapidly increasing and the proportion of younger adults to care for them is decreasing. Part of the solution to support older adults in living independently is to provide them with appropriate assistive technologies. To develop technologies that are effective for older adults we need methodologies that are appropriate for working with this user group. Yet there is little systematic research on how to work with older adults and how to adapt methods already used with younger adults. This paper reports on three case studies which investigated the use focus groups, expert evaluations and user evaluations with older adults. In the case of focus groups, the size of the focus group was investigated; for expert evaluations, an existing set of heuristics for evaluating apps for older adults was investigated; for user evaluations, a low-fidelity prototype design was evaluated using think-aloud protocols.

Older adults benefit from unstructured, lifestyle-based activity that can be carried out in people's houses, neighbourhoods, and the built environment. Technological solutions may support physical activity and encourage wellbeing. To ensure such technology is suitable for, and usable by, older adults, it is crucial they are involved in all stages of design. Participatory design methodologies facilitate collaboration and engagement with potential users. We examine the suitability of participatory design for collaborating and engaging with older adults. Participatory design workshops were conducted with 33 older adults in the UK with the aim of designing mobile applications to support and promote physical activity and wellbeing in the built environment. As well as summarising the outcome of these workshops, the paper outlines several methodological issues relating to the suitability of participatory design for involving older adults in the technology design process.

In considering the role of place in supporting positive well-being choices for all, including older people, there has been an almost exclusive focus on issues of design in the public realm. Emerging findings from the Co-Motion project suggest that the experience of being out and about can be also facilitated or profoundly damaged by the attitudes and behaviours of fellow public realm users.

Parkinson's disease (PD) is neuropathologically characterized as an alpha-synucleinopathy. Alpha-synuclein-containing inclusions are stained as Lewy bodies and Lewy neurites in the brain, which are the pathological hallmark of PD. However, alpha-synuclein-containing inclusions in PD are not restricted to the central nervous system, but are also found in peripheral tissues. Alpha-synuclein levels can also be measured in body fluids. The aim of this study was to conduct a systematic review of available evidence to determine the utility of alpha-synuclein as a peripheral biomarker of PD. We searched PubMed (1948 to 26 May 2013), Embase (1974 to 26 May 2013), the Cochrane Library (up to 26 May 2013), LILACS (up to 26 May 2013) and CINAHL (up to 26 May 2013) for the studies of alpha-synuclein in peripheral tissues or body fluids in PD. A total of 49 studies fulfilled the search criteria. Peripheral tissues such as colonic mucosa showed a sensitivity of 42-90% and a specificity of 100%; submandibular salivary glands showed sensitivity and specificity of 100%; skin biopsy showed 19% sensitivity and 80% specificity in detecting alpha-synuclein pathology. CSF alpha-synuclein had 71-94% sensitivity and 25-53% specificity for distinguishing PD from controls. Plasma alpha-synuclein had 48-53% sensitivity and 69-85% specificity. Neither plasma nor CSF alpha-synuclein is presently a reliable marker of PD. This differs from alpha-synuclein in solid tissue samples of the enteric and autonomic nervous system, which offer some potential as a surrogate marker of brain synucleinopathy., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: MRI is routinely used in the investigation of colovesical fistulae at our institute. Several papers have alluded to its usefulness in achieving the diagnosis; however, there is a paucity of literature on its imaging findings. Our objective was to quantify the MRI characteristics of these fistulae., Methods: We selected all cases over a 4-year period with a final clinical diagnosis of colovesical fistula which had been investigated with MRI. The MRI scans were reviewed in a consensus fashion by two consultant uroradiologists. Their MRI features were quantified., Results: There were 40 cases of colovesical fistulae. On MRI, the fistula morphology consistently fell into three patterns. The most common pattern (71%) demonstrated an intervening abscess between the bowel wall and bladder wall. The second pattern (15%) had a visible track between the affected bowel and bladder. The third pattern (13%) was a complete loss of fat plane between the affected bladder and bowel wall. MRI correctly determined the underlying aetiology in 63% of cases., Conclusions: MRI is a useful imaging modality in the diagnosis of colovesical fistulae. The fistulae appear to have three characteristic morphological patterns that may aid future diagnoses of colovesical fistulae. To the authors' knowledge, this is the first publication of the MRI findings in colovesical fistulae.

A current challenge is to define the biological characteristics of colon tumor cells resistant to chemotherapy. Distinct sub-populations of mucus-secreting cells were previously obtained from the colon cancer cell line HT-29 after long-term treatment with the anti-cancer drugs, 5-fluorouracil (5-FU) and methotrexate (MTX). Since mucins are increasingly implicated as playing a role in carcinogenesis, we studied the pattern of mucin expression in two HT-29 clones of mucus-secreting and two clones of enterocyte-like phenotype which differ in their capacity to resist to 5-FU and/or MTX. The expression of both transmembrane (MUC1, MUC3, MUC4) and secreted gel-forming (MUC2, MUC5AC, MUC5B, MUC6) mucins in clones was studied by northern and/or western blotting. The four HT-29 clones showed three cellular phenotypes: (1) The mucus-secreting clone HT29-5F12 consists of unpolarized cells with mucus secretions that have anti-colonic mucin immunoreactivity, and mainly expresses MUC2 and is resistant to 5-FU and sensitive to MTX; (2) The mucus-secreting clone HT29-5M21 forms a monolayer of polarized cells with strong anti-gastric mucin immunoreactivity and mainly expresses MUC5AC and MUC5B and is resistant to MTX and sensitive to 5-FU; (3) The two enterocyte-like clones, HT29-5F7 and HT29-5M12 are resistant to both MTX and 5-FU and express mainly MUC1 and MUC5B, respectively. These clones which originate from a same colorectal tumour and display different patterns of mucin expression as well as differing resistance to MTX and 5-FU will make useful in vitro models for studying the potential role of mucins or other biological markers in drug resistance pathways.

Background: Maltase-glucoamylase enzyme plays an important role in starch digestion. Glucoamylase deficiency is reported to cause chronic diarrhea in infants, but its role in dyspeptic children is unknown., Methods: Glucoamylase and other disaccharidase specific activities were assayed from duodenal biopsy specimens in 44 children aged 0.5-18 years (mean, 10 +/- 5 years) undergoing endoscopy to evaluate dyspeptic symptoms. All subjects had normal duodenal histology. Intestinal organ culture was used to evaluate synthesis and processing of maltase-glucoamylase. Sequencing of the maltase-glucoamylase coding region was performed in subjects with low activity or variation of isoform in organ culture., Results: Twenty-two of the dyspeptic children had one or more disaccharidases with low specific activity. Twelve subjects (28%) had low activity of glucoamylase. Eight subjects had low activities of glucoamylase, sucrase, and lactase. Low glucoamylase activity was not correlated with the isoform phenotype of maltase-glucoamylase as described by metabolic labeling and sodium dodecyl sulfate electrophoresis. Novel nucleotide changes were not detected in one subject with low glucoamylase activity or in two subjects with variant isoforms of maltase-glucoamylase peptides., Conclusion: Twelve of 44 dyspeptic children had low specific activity of duodenal maltase-glucoamylase. Eight of these children had low specific activity of all measured disaccharidases.

Mucins encoded by the MUC genes share the common feature of having an extensive tandem repeat region that encompasses a large proportion of the coding sequence. In many of the genes this tandem repeat region shows a great deal of allelic length variation and recently studies have demonstrated person to person variation in pattern of nucleotide or amino-acid changes in the repeat units. The length and sequence variability will be discussed in this review, as will its role in disease susceptibility.

New mono- and binuclear titanium imido complexes supported by tetradentate, dianionic N(2)O(2)-donor Schiff base ligands were prepared in good yield from the readily available [Ti(NBu(t))Cl(2)(py)(3)] (1a). Thus treatment of 1a with Na(2)[substituted-salen] gave monomeric [Ti(NBu(t))(substituted-salen)] where substituted-salen = Et(2)salen (2) or Bu(t)(4)salen (4). In contrast, the binuclear complex [Ti(NBu(t)){&mgr;-(MeO)(2)salen}](2) (5) was obtained from 1a and Na(2)[(MeO)(2)salen]. The less sterically crowded compounds 2 and 5 undergo tert-butyl imide/arylamine exchange reactions to form [Ti(N-2,6-C(6)H(3)Me(2))(Et(2)salen)] (3) and [Ti(N-2,6-C(6)H(3)Me(2)){&mgr;-(MeO)(2)salen}](2) (6), respectively, whereas 4 does not exhibit this kind of reactivity. The compound 3 can also be obtained directly from Na(2)[Et(2)salen] and [Ti(N-2,6-C(6)H(3)Me(2))Cl(2)(py)(3)] (1b). Crystal data for 3: triclinic, P&onemacr;, a = 12.216(4) Å, b = 12.312(11) Å, c = 17.246(2) Å, alpha = 90.352(12) degrees, beta = 102.59(2) degrees, gamma = 104.96(2) degrees, V = 2440.3(8) Å(3), Z = 4, R = 0.051, R(w) = 0.066 for 7011 data with I > 2sigma(I). Crystal data for 5.CH(2)()Cl(2)(): orthorhombic, Pbca, a = 14.747(4) Å, b = 17.042(4) Å, c = 20.545(3) Å, V = 5163.5(13) Å(3), Z = 4, R(1) = 0.096, wR(2) = 0.086 for 3765 data with I > 2sigma(I). Crystal data for 6: monoclinic, C2/c, a = 17.902(5) Å, b = 12.411(4) Å, c = 21.068(5) Å, beta = 90.27(2) degrees, V = 4681(2) Å(3), Z = 4, R = 0.034, R(w)() = 0.039 for 3633 data with I > 2sigma(I).

We have previously shown that glucose can exert a repressive effect on the transcription of the sucrase-isomaltase (SI) gene in the differentiated enterocyte-like human colon carcinoma cell lines HT-29 and Caco-2. To characterize the region through which glucose exerts this effect, three different-length fragments of the 5'-flanking region of the human SI gene were linked to the reporter gene luciferase in an episomal vector carrying a hygromycin resistance gene. These fragments were used for transfection into a clone of the Caco-2 cell line, PF11, which has high glucose consumption and only expresses SI at high levels when cultured in the presence of a low supply of glucose. By using the stably transformed PF11 cells grown either in standard high glucose (25 mM) or in low glucose (1 mM) it was possible to show that the smallest fragment of the SI promoter, extending from bases -370 to +30, contains all the information required for the glucose repression of the reporter gene luciferase.

Background/aims: We have previously shown that in the proximal-jejunum of hypolactasic humans, just a few villus enterocytes express lactase protein and activity. In the present study, we compared the distribution of lactase messenger RNA (mRNA), protein, and activity in villus enterocytes in tissues obtained from subjects with persistent high lactase activity and those with hypolactasia., Methods: Immunohistochemical and enzymohistochemical staining was performed on closely adjacent sections of human proximal jejunum from 5 individuals with persistent high lactase activity and 32 with hypolactasia. In all the persistent and in 9 hypolactasic samples, in situ hybridization was also performed using a digoxygenin-labeled RNA probe., Results: In persistent tissues, lactase mRNA, protein, and activity were present in all villus enterocytes. In hypolactasic tissues, lactase mRNA was detected only in some villus enterocytes; some of them also expressed protein and activity, whereas others did not. In 8 of these hypolactasic samples, a variable number of villus enterocytes with lactase mRNA and protein did not express lactase activity., Conclusions: Various types of enterocytes are present even on a single villus from individuals with adult-type hypolactasia. These results show that different mechanisms control lactase expression in enterocytes on the same villus.

Mucin expression was analysed, in relation to cell growth, in parental HT-29 cells and in two populations of mucus-secreting HT-29 cells selected by adaptation to methotrexate (HT29-MTX) or 5-fluorouracil (HT29-FU). These two populations express mature mucins that differ in their immunoreactivity to antibodies against gastric (HT29-MTX) or colonic mucins (HT29-FU). In the parental population, at late confluency, only very few cells produce mucins or the MUC1 glycoprotein, this being consistent with the low level of expression of the mRNAs corresponding to the MUC1 to MUC5C mucin genes. In the HT29-MTX and HT29-FU populations, the appearance of mucus droplets, as shown by histochemistry and immunofluorescence, starts a few days after confluency, progressively involving a greater proportion of cells and reaching a steady state at late confluency. The MUC1 glycoprotein appears earlier, already being detectable in preconfluent cells. Its distribution is restricted to the apical surface of the cells and is distinct from that of the mucus droplets. In both populations the growth-related levels of MUC1 mRNA are concordant with the apparent levels of expression of the MUC1 glycoprotein. The levels of MUC2, MUC3, MUC4 and MUC5C mRNAs differ from one population to another and, within each population, according to the stage of the culture. The highest levels of MUC2 and MUC4 mRNAs are found in the HT29-FU cells, whereas the highest levels of MUC3 and MUC5C are found in the HT29-MTX cells, suggesting that the differences observed in the mature mucins expressed by either population may be related to which MUC genes are expressed. In both populations significant or even high levels of MUC mRNAs are already present in early cultures, i.e. at a stage when the mature mucins are not yet detectable, suggesting that mucin maturation is a later event.

Treatment of Caco-2 cells with forskolin (25 microM) or monensin (1 microM) has previously been shown to cause a marked decrease in the level of sucrase-isomaltase (SI) mRNA, without any effect on the expression of dipeptidylpeptidase IV (DPP-IV). In the present work, we report that there is no significant difference in the stability of SI mRNA between control and treated cells. On the other hand, we demonstrate a decrease in the transcription rate of SI mRNA which is sufficient to account for the decrease in the steady-state level of SI mRNA both in forskolin- and monensin-treated Caco-2 cells.

Background: The authors have shown that a mosaicism of brush border antigens may occur spontaneously on enterocytes of small intestine in human adult-type hypolactasia. The present paper gives another example of spontaneously occurring mosaicism as indicated by the patchy expression of blood group antigens on villus enterocytes., Methods: Thirty-five individuals were examined by immunomorphological techniques with antibodies against blood group antigens., Results: In 4 of 16 A blood group individuals, the blood group antigens were expressed only in some villus enterocytes. The individuals with this mosaic pattern were all shown to be nonsecretors. The A antigen in the positive enterocytes of these individuals was only present as the ALe(b) structure, whereas ALe(y) and ALe(d) were also present in the secretors. The patches of positive enterocytes were randomly distributed along the villus wall., Conclusions: A nonsecretor individuals express the blood group antigens only in some villus enterocytes; this mosaicism does not arise from a heterogeneous population of stem cells within the crypts but rather reflects subtle differences in the pattern of differentiation between monoclonally derived epithelial cells on the villus.

Enzymatic and immunohistological analyses of lactase were performed at different stages of development and within different regions of the small intestine of the rabbit and rat. As previously reported, there seems to be a sharp decline of lactase activity on weaning but variable and higher levels of activity are seen in adult animals. Two monoclonal antibodies to rat lactase were available to study the protein in rats. Four monoclonal antibodies to human lactase were shown to cross-react with rabbit lactase and used for the rabbit studies. Immunohistological analysis of small intestine of adult rabbits and rats showed residual lactase protein within the enterocytes throughout the small intestine. In the middle of the small intestine (lower jejunum, upper ileum), uniform staining of the brush border was observed. In the proximal and distal regions, a patchy pattern of staining was observed. This pattern, which resembles that observed in adult hypolactasic humans, indicates an underlying heterogeneity of enterocyte differentiation.

The complete sequence of the 6 kb cDNA and the 5' genomic structure are reported for the gene coding for the human intestinal brush border hydrolase sucrase-isomaltase. The human sucrase-isomaltase cDNA shows a high level of identity (83%) with that of the rabbit enzyme, indicating that the protein shares the same structural domains in both species. In addition to the previously reported homology with lysosomal alpha-glucosidase, the sucrase and isomaltase subunits also appear to be homologous to a yeast glucoamylase. A 14 kb human genomic clone has been isolated which includes the first three exons and the first two introns of the gene, as well as 9.5 kb 5' to the major start site of transcription. The first exon comprises 62 bp of untranslated sequence and the second starts exactly at the initiation ATG codon. Typical CAAT and TATA boxes are seen upstream of the first exon. A genetic polymorphism is described which involves a PstI site in the second intron. Southern blotting, sequencing and mRNA studies indicate that the structures of the sucrase-isomaltase gene and its mRNA are unaltered in the two human colon cancer cell lines Caco-2 and HT-29 in comparison with normal human small intestine.

Immunohistological analysis of the expression of lactase protein in adults with hypolactasia has been carried out using monoclonal antibodies. Eight different antibodies that recognize at least three distinct epitopes on the lactase protein each gave the same result. Strong brush border staining was observed in all the lactase-persistent adults. No staining at all was detected in 9 of the hypolactasic subjects. In the remaining 12 individuals a mosaic pattern of expression was observed: small patches of enterocytes stained strongly, whereas the surrounding areas showed no staining at all. Sucrase-isomaltase, in contrast, showed no such mosaicism in these or in any of the other individuals. The mosaicism observed in the 12 hypolactasic individuals suggests that the differentiation of the columnar cells along the villus is not homogeneous. Furthermore, the existence of two patterns of expression of the lactase protein in the lactase-deficient individuals (i.e., absence of protein and mosaicism), if characteristic of the entire length of the intestine of the individuals tested, would suggest the existence of two phenotypes of adult-type hypolactasia in the population studied.

Two monoclonal antibodies raised against native horse alcohol dehydrogenase (HADH) bind preferentially to the enzyme attached to solid supports and recognize the denatured and carboxymethylated HADH subunits. Both antibodies cross-react with the human class I isoenzymes but do not recognize the class III ADH isoenzyme. Protease digestion, electrophoresis and HPLC have been used to identify the linear epitope which is contained in the sequence Pro344-Glu357 of the HADH subunit.

Hybridization analysis of mRNA with a cDNA probe for human sucrase-isomaltase, pulse-chase experiments with L-[35S]-methionine followed by SDS-PAGE, and immunofluorescence detection of sucrase-isomaltase were used to analyze the level(s) at which forskolin interferes with the expression of the enzyme in Caco-2 cells in culture. Three effects are observed in Caco-2 cells treated with forskolin: 1) a marked decrease in the level of sucrase-isomaltase mRNA, 2) a marked decrease in the biosynthesis of the enzyme without any alteration of its stability, and 3) an almost total inhibition of its transport to the brush border membrane. All three effects are reversible when the drug is removed from the culture medium, though this reversibility is asynchronous: transport to the brush border membrane resumes after 24 h, sucrase-isomaltase mRNA levels are back to the normal after 5 days, whereas the biosynthesis of the enzyme, although increasing progressively, remains lower than in control cells, even 10 days after removal of the drug. The possibility that some effects are directly dependent on cAMP and others a consequence of changes in glucose metabolism is discussed.