Fibre-supplemented tube feeding in the hospitalised elderly

OBJECTIVES: To evaluate the effect of fibre supplementation in enteral feeding on bowel function in hospitalised geriatric patients, and to assess its metabolic and nutritional efficiency. DESIGN: Prospective randomised controlled trial with stratification for diabetes. SETTING: Department of Geriatrics at the University of Antwerp. SUBJECTS: During 30 months (January 2000-June 2002) every hospitalised patient requiring tube feeding was assessed for eligibility (n = 183). Finally 172 patients (19% diabetics) were randomised. METHODS: An enteral nutritional regimen consisting of 30 kcal/kg in 2000 ml with a calorie/nitrogen ratio of 156 with or without fibre was instituted. At weekly intervals, stool output was qualitatively evaluated by recording frequency, volume (small <1/2 cup, large >1/2 cup) and consistency (solid-formed, soft-pasty or liquid-watery). Nutritional and metabolic effects were evaluated through laboratory analysis. RESULTS: Overall mortality was 24% with a trend for excess mortality in diabetic patients (33.3% versus 21.6% in non-diabetics; P = 0.176). There was no difference in duration of feeding between the fibre group (27.5 days; 95% CI = 19.1-35.9) and the no fibre group (27.9 days; 95% CI = 20.2-35.5). In the fibre-supplemented group, stool frequency was lower (4.1 per week; 95% CI = 3.7-4.6) than in controls (6.3 per week; 95% CI = 5.6-6.9). Qualitatively, stool consistency was higher (P < 0.001) but no difference in volume was noted. There were no differences in final laboratory parameters between groups. CONCLUSIONS: Fibre supplementation improved bowel function with reduced stool frequency and more solid stool consistency. It did not affect the nutritional efficiency of enteral feeding in hospitalised geriatric patients. Diabetes may be a risk factor for mortality in malnourished patients requiring tube feeding.     

Relative stability of alexithymia and openness to emotions in one psychiatric day hospital setting

Alexithymia (literally, difficulty finding words for emotions) and openness to emotions (OE: referring to the cognitive representation, communication, regulation, perception of internal and external bodily sensations, and social restriction of emotions) are strongly linked to psychopathology. The absolute and relative stability hypotheses were tested in order to determine whether significant changes occurred on these constructs after therapy, a condition where changes were expected for both constructs. Negative attitudes toward treatment (NTI) and perceived social support (PSS) were expected to significantly predict alexithymia and OE. Patients (N = 179) who participated in this longitudinal study filled in the Toronto Alexithymia Scale, the Dimensions of Openness to Emotions Scale, the NTI subscale, the Multidimensional Scale of Perceived Social Support, and the Social Desirability Scale. After treatment, we observed significant decrease of all alexithymia scores and significant increases of three OE scores, that is, cognitive representation, communication, and regulation of emotions. Regression analyses revealed that gender, age, NTI, and PSS were significant predictors of alexithymia and OE. NTI strongly predicted lower OE levels and higher alexithymia levels, whereas PSS had opposite predicting effects on these constructs. In conclusion, the significant changes, and the moderate to high correlational levels observed between before and after alexithymia and OE scores, strengthen the relative stability hypothesis for both constructs. In addition, PSS represents a protective factor and NTI a vulnerability indicator for therapists. Our aim is to optimize treatment by providing therapists treating emotion difficulties a more concrete array of variables that potentially either promote or subvert recovery.     

Electrical stimulation promotes the proliferation of human keratinocytes,increases the production of keratin 5 and 14, and increases the phosphorylation of ERK1/2 and p38 MAP kinases

Effective wound healing remains a significant clinical challenge in reducing patient morbidity and improving quality of life. Wound healing is a complex process involving the endogenous electrical field. The electrical field can contribute to wound healing by activating keratinocytes to promote reepithelialization. The objective of this study was to determine the effects of exogenous electrical stimulation (ES) on human keratinocyte viability and proliferation and on production of IL‐6, IL‐8, and keratins (K5 and K14) and to investigate the activated signalling pathways in keratinocytes exposed to ES. Keratinocytes were cultured under ES at different intensities for 6 or 24 hr. Cell proliferation, cytokines and growth factors, K5 and K14, as well as phosphorylated ERK1/2 and p38 MAP kinases, were evaluated. The results showed that the keratinocytes exposed to ES between 100 and 150 mV/mm for 6 or 24 hr showed a significantly increased proliferation rate. However, a 24 hr exposure to 200 mV/mm revealed no significant effect in cell growth. ES at 100 and 200 mV/mm for 6 hr increased the secretion of epidermal growth factor and vascular endothelial growth factor, and the production of K5 and K14. K14 was more sensitive than K5 to ES. However, ES down‐regulated the secretions of IL‐6 and IL‐8. Finally, ES increased the phosphorylation of ERK1/2 and p38 MAP kinases. Overall results suggested that ES can be useful in supporting skin wound healing by activating keratinocytes.     

Protein kinase C isotypes required for phorbol-ester induction of stromelysin-1 in rat fibroblasts

The phorbol-ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is a potent inducer of the metalloproteinase stromelysin in fibroblasts in vivo and in several cultured cell lines. Rat-1 and Rat-2 fibroblasts, however, do not respond to TPA stimulation by induction of stromelysin gene activity, although collagenase promoter-mediated activity is induced threefold by TPA treatment in these cells. We determined that rat fibroblasts expressed protein kinase C (PKC) α, PKCδ, PKCϵ, and PKCζ but neither the mRNA nor the protein for PKCβ. When Rat-2 fibroblasts were stably transfected with an expression vector producing PKCβ, however, TPA treatment of these variants resulted in a 3.1-fold induction of stromelysin promoter-mediated luciferase activity compared with a 1.3-fold induction in parental Rat-2 cells (P < 0.002). Transient transfection of PKCϵ produced a small but significant increase in TPA-stimulation of both stromelysin- and collagenase-mediated gene expression. These results suggest that there are PKC isotype-specific signaling pathways that can differentially regulate matrix metalloproteinase gene expression. © 1996 Wiley-Liss, Inc.     

Redirecting the complete T cell receptor/CD3 signaling machinery towards native antigen via modified T cell receptor

We show that a chimeric T cell receptor (TCR) β chain consisting of a single-chain Fv portion derived from a monoclonal antibody and the full TCR β chain is able to assemble functionally with endogenous TCR/CD3 components and transfer the antibody specificity as well as the TCR specificity into TCRβ⁻ as well as into TCRβ⁺ T cells. This allows the incorporation new non-major histocompatibility complex-restricted ligand specificities into the intact TCR/CD3 complex which can exploit the full range of biological activities of the endogenous TCR signaling machinery. This approach can provide wider opportunities to redirect T cells to virus or tumor antigen-bearing cells.     

Risk stratification in breast cancer screening: Cost-effectiveness and harm-benefit ratios for low-risk and high-risk women

In mammography screening programmes, women are screened according to a one-size-fits-all principle. Tailored screening, based on risk levels, may lead to a better balance of benefits and harms. With microsimulation modelling, we determined optimal mammography screening strategies for women at lower (relative risk [RR] 0.75) and higher (RR 1.8) than average risk of breast cancer, eligible for screening, using the incremental cost-effectiveness ratio (ICER) of current uniform screening in the Netherlands (biennial [B] 50-74) as a threshold ICER. Strategies varied by interval (annual [A], biennial, triennial [T]) and age range. The number of life-years gained (LYG), breast cancer deaths averted, overdiagnosed cases, false-positive mammograms, ICERs and harm-benefit ratios were calculated. Optimal risk-based screening scenarios, below the threshold ICER of €8883/LYG, were T50-71 (€7840/LYG) for low-risk and B40-74 (€6062/LYG) for high-risk women. T50-71 screening in low-risk women resulted in a 33% reduction in false-positive findings, a similar reduction in costs and improved harm-benefit ratios compared to the current screening schedule. B40-74 in high-risk women led to an increase in screening benefit, compared to current B50-74 screening, but a relatively higher increase in false-positive findings. In conclusion, optimal screening consisted of a longer interval and lower stopping age than current uniform screening for low-risk women, and a lower starting age for high-risk women. Extending the interval for women at lower risk from biennial to triennial screening reduced harms and costs while maintaining most of the screening benefit.     

Analysis of the skin of mice humanized for the immune system

Development of new immunotherapeutic strategies relies on the ability to activate the right cells at the right place and at the right moment and on the capacity of these cells to home to the right organ(s). Skin delivery has shown high potency for immunotherapeutic administration. However, an adequate in vivo model of human skin immunity is still a critical bottleneck. We demonstrated here that the skin of human immune system mice is colonized by human hematopoietic cells, mainly human T cells and that complementation with human antigen‐presenting cells at the vaccination site allowed the induction of an immune response.     

PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome

Usher syndrome is a genetically heterogeneous recessive disease characterized by hearing loss and retinitis pigmentosa (RP). It frequently presents with unexplained, often intrafamilial, variability of the visual phenotype. Although 9 genes have been linked with Usher syndrome, many patients do not have mutations in any of these genes, suggesting that there are still unidentified genes involved in the syndrome. Here, we have determined that mutations in PDZ domain–containing 7 (PDZD7), which encodes a homolog of proteins mutated in Usher syndrome subtype 1C (USH1C) and USH2D, contribute to Usher syndrome. Mutations in PDZD7 were identified only in patients with mutations in other known Usher genes. In a set of sisters, each with a homozygous mutation in USH2A, a frame-shift mutation in PDZD7 was present in the sister with more severe RP and earlier disease onset. Further, heterozygous PDZD7 mutations were present in patients with truncating mutations in USH2A, G protein–coupled receptor 98 (GPR98; also known as USH2C), and an unidentified locus. We validated the human genotypes using zebrafish, and our findings were consistent with digenic inheritance of PDZD7 and GPR98, and with PDZD7 as a retinal disease modifier in patients with USH2A. Pdzd7 knockdown produced an Usher-like phenotype in zebrafish, exacerbated retinal cell death in combination with ush2a or gpr98, and reduced Gpr98 localization in the region of the photoreceptor connecting cilium. Our data challenge the view of Usher syndrome as a traditional Mendelian disorder and support the reclassification of Usher syndrome as an oligogenic disease.