Disturbed appetite patterns and nutrient intake in peritoneal dialysis patients.

OBJECTIVE: Malnutrition is common among peritoneal dialysis (PD) patients. Reduced nutrient intake contributes to this. It has long been assumed that this reflects disturbed appetite. We set out to define the appetite profiles of a group of PD patients using a novel technique. DESIGN: Prospective, cross-sectional comparison of PD patients versus controls. SETTING: Teaching hospital dialysis unit. PATIENTS: 39 PD patients and 42 healthy controls. INTERVENTION: Visual analog ratings were recorded at hourly intervals to generate daily profiles for hunger and fullness. Summary statistics were generated to compare the groups. Food intake was measured using 3-day dietary records. MAIN OUTCOME MEASURES: Hunger and fullness profiles. Derived hunger and fullness scores. RESULTS: Controls demonstrated peaks of hunger before mealtimes, with fullness scores peaking after meals. The PD profiles had much reduced premeal hunger peaks. A postmeal reduction in hunger was evident, but the rest of the trace was flat. The PD fullness profile was also flatter than in the controls. Mean scores were similar despite the marked discrepancy in the profiles. The PD group had lower peak hunger and less diurnal variability in their hunger scores. They also demonstrated much less change in fullness rating around mealtimes, while the mean and peak fullness scores were little different. The reported nutrient intake was significantly lower for PD. CONCLUSION: The data suggest that PD patients normalize their mean appetite perception at a lower level of nutrient intake than controls, suggesting that patient-reported appetite may be misleading in clinical practice. There is a loss of the usual daily variation for the PD group, which may contribute to their reduced food intake. The technique described here could be used to assess the impact of interventions upon the abnormal PD appetite profile.     

In utero central nervous system damage in pyruvate dehydrogenase deficiency

Pyruvate dehydrogenase deficiency is among the most common causes of congenital lactic acidosis. We describe siblings with congenital lactic acidosis due to a deficiency of pyruvate dehydrogenase complex. The findings of computed tomography and pathologic studies suggest that central nervous system damage had occurred in utero. These observations have implications for treatment and outcome in patients with enzymatic defects causing congenital lactic acidosis.     

Molecular insights into the transcriptional regulatory role of thyroid hormones in ovarian cancer

The regulation of cancer‐relevant genes by the thyroid hormones, 3, 5, 3′‐Triiodo‐L‐thyronine (T3) and L‐thyroxine (T4), was recently acknowledged. However, limited data exists on the hormonal effects on gene expression in ovarian cancer, a gynecological malignancy associated with a low cure rate. The expression of fifteen genes involved in DNA repair, cell cycle, apoptosis, and tumor suppression was evaluated in OVCAR‐3 and A2780 cell lines, using real‐time PCR following short incubation with T3 (1 nM) or T4 (100 nM). The thyroid hormones downregulated the expression of the majority of genes examined. Support for the involvement of the MAPK and PI3K in thyroid hormone‐mediated gene expression was shown for a set of genes. FAS expression was inhibited in A2780 cells, while an unexpected induction was demonstrated in OVCAR‐3 cells. An analogous effect on the protein levels of FAS receptor and its soluble form was demonstrated by Western blotting. We further established, using primer sets that discriminate between the different RNA isoforms, that the hormones increase the mRNA levels of both coding and non‐coding FAS mRNAs. The prevalence of these isoforms, using The Cancer Genome Atlas (TCGA) analysis, was significantly more abundant in 17 cancer types, including ovarian cancer, compared to normal tissues. Our results highlight the role of thyroid hormones in the expression of cancer‐relevant‐genes in ovarian cancer and provide an important insight into the pathways by which mitogenic and anti‐apoptotic effects are exerted.     

Nano-Diamino-Tetrac (NDAT) Enhances Resveratrol-Induced Antiproliferation by Action on the RRM2 Pathway in Colorectal Cancers

Cancer resistance to chemotherapeutic agents is a major issue in the management of cancer patients. Overexpression of the ribonucleotide reductase regulatory subunit M2 (RRM2) has been associated with aggressive cancer behavior and chemoresistance. Nano-diamino-tetrac (NDAT) is a nanoparticulate derivative of tetraiodothyroacetic acid (tetrac), which exerts anticancer properties via several mechanisms and downregulates RRM2 gene expression in cancer cells. Resveratrol is a stilbenoid phytoalexin which binds to a specific site on the cell surface integrin αvβ3 to trigger cancer cell death via nuclear translocation of COX-2. Here we report that resveratrol paradoxically activates RRM2 gene expression and protein translation in colon cancer cells. This unanticipated effect inhibits resveratrol-induced COX-2 nuclear accumulation. RRM2 downregulation, whether achieved by RNA interference or treatment with NDAT, enhanced resveratrol-induced COX-2 gene expression and nuclear uptake which is essential to integrin αvβ3-mediated-resveratrol-induced antiproliferation in cancer cells. Elsewhere, NDAT downregulated resveratrol-induced RRM2 expression in vivo but potentiated the anticancer effect of the stilbene. These findings suggest that RRM2 appears as a cancer cell defense mechanism which can hinder the anticancer effect of the stilbene via the integrin αvβ3 axis. Furthermore, the antagonistic effect of RRM2 against resveratrol is counteracted by the administration of NDAT.     

Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome

Greig cephalopolysyndactyly syndrome (GCPS) is caused by haploinsufficiency of GLI3 on 7p13. Features of GCPS include polydactyly, macrocephaly, and hypertelorism, and may be associated with cognitive deficits and abnormalities of the corpus callosum. GLI3 mutations in GCPS patients include point, frameshift, translocation, and gross deletion mutations. FISH and STRP analyses were applied to 34 patients with characteristics of GCPS. Deletions were identified in 11 patients and the extent of their deletion was determined. Nine patients with deletions had mental retardation (MR) or developmental delay (DD) and were classified as severe GCPS. These severe GCPS patients have manifestations that overlap with the acrocallosal syndrome (ACLS). The deletion breakpoints were analyzed in six patients whose deletions ranged in size from 151 kb to 10.6 Mb. Junction fragments were found to be distinct with no common sequences flanking the breakpoints. We conclude that patients with GCPS caused by large deletions that include GLI3 are likely to have cognitive deficits, and we hypothesize that this severe GCPS phenotype is caused by deletion of contiguous genes.     

A systematic review of the job-stress intervention evaluation literature, 1990-2005

Ninety reports of systematic evaluations of job-stress interventions were rated in terms of the degree of systems approach used. A high rating was defined as both organizationally and individually focused, versus moderate (organizational only), and low (individual only). Studies using high-rated approaches represent a growing proportion of the job-stress intervention evaluation literature. Individual-focused, low-rated approaches are effective at the individual level, favorably affecting individual-level outcomes, but tend not to have favorable impacts at the organizational level. Organizationally-focused high- and moderate-rated approaches are beneficial at both individual and organizational levels. Further measures are needed to foster the dissemination and implementation of systems approaches to examining interventions for job stress.     

Semi‐Batch Emulsion Copolymerization of Vinyl Acetate and Butyl Acrylate Using Oligomeric Nonionic Surfactants

Detailed kinetic studies on semi‐batch emulsion copolymerization of vinyl acetate/butyl acrylate (VAc/BuA) (80 : 20) at 80°C were carried out using alkyl polyglucoside nonionic surfactants and ammonium persulfate as initiator. The polymerization recipe was varied with respect to the amount of initiator initially charged and continuously fed to the reactor, the surfactant concentration, the electrolyte concentration, and the monomer addition rate. Various types of alkyl polyglucosides with different hydrophilic and hydrophobic chain lengths were tested. Latex particle stabilization was shown to depend significantly on the surfactant structure and its adsorption characteristics. In general, the latex particle size distribution evolved from a bimodal to a unimodal distribution while latex destabilization was observed at high surfactant or/and high initiator concentrations. Based on experimental observations it was found that the most important factor for imparting particle stability was the hydrophilic/hydrophobic chain length ratio of the surfactant which actually controlled the balance between surface coverage and stabilizing capability.     

Barriers to STI testing among youth in a Canadian oil and gas community

Northeastern British Columbia, Canada, is undergoing in-migration of young people attracted by jobs in the oil/gas sectors. Chlamydia rates among youth ages 15-24 are increasing and exceed the provincial average by 22%. Testing for sexually transmitted infections (STIs) reduces the disease burden, contributing to prevention. We conducted ethnographic fieldwork, including interviews with 25 youth and 14 service providers, to document their perceptions regarding youth's access to STI testing. Five key barriers to access were identified: limited opportunities for access, geographic inaccessibility, local social norms, limited information, and negative interactions with providers. To address youths' needs, we recommend active STI prevention and testing service delivery models that incorporate a locally tailored public awareness campaign, outreach to oil/gas workers, condom distribution, expanded clinic hours and drop-in STI testing, specialized training for health care providers, and inter-sectoral partnerships between public health, non-profit organizations, and industry.