Influence of antecedent lymphoid surgery on the odds of acquiring rheumatoid arthritis

The occurrence of rheumatoid arthritis (RA) and the extent of antecedent lymphoid surgeries was examined using case control study methods. Two hundred sixty-four patients with definite or classic RA were considered and 283 patients with rheumatic diseases presumably of nonimmunologic origin were used as controls. The odds for developing RA were found to be significantly higher for patients with multiple lymphoid surgeries (tonsillectomy and adenoidectomy or tonsillectomy and adenoidectomy plus appendectomy) and exhibited a gradient, increasing with more extensive surgery. Significant rank correlations were found in patients with RA between the age at tonsillectomy and the rheumatoid factor (RF) titer. An earlier tonsillectomy correlated with lower titers of RF. A significant decrease of serum RF titer was also seen in patients with RA subjected to tonsillectomy, adenoidectomy and appendectomy. We conclude that antecedent removal of lymphoid tissue from the tonsils, adenoids and appendix constitutes a risk factor predisposing to RA. Moreover, this risk seems related to the quantity of lymphoid tissue removed.     

Ethnicity and social deprivation independently influence metabolic control in children with type 1 diabetes

AIMS/HYPOTHESIS: This study was performed to evaluate the influence of ethnicity and socioeconomic status (SES) on metabolic control in a population-based cohort of children with type 1 diabetes mellitus, and to evaluate whether any relationship between ethnicity and HbA(1c) is mediated by SES. METHODS: We performed a retrospective review of all patients under age 16 years with type 1 diabetes (n = 555) from 1995 to 2005 in the greater Auckland region, New Zealand. Diabetes care variables and HbA(1c) values were collected prospectively, during clinic visits. RESULTS: The mean population HbA(1c) was 8.3 +/- 1.3%. Maori and Pacific patients had poorer metabolic control than their European counterparts (9.1% and 9.3% vs 8.1%, p < 0.001) and higher rates of moderate to severe hypoglycaemia (31.1 and 24.8 vs 14.9 events/100 patient-years, p = 0.03). In multiple linear regression analysis, both ethnicity and SES were independently associated with HbA(1c) (p < 0.001). Other factors associated with higher HbA(1c) level were longer duration of diabetes, higher insulin dose, lower BMI z score and less frequent blood glucose monitoring (p < 0.001). CONCLUSIONS/INTERPRETATION: Both ethnicity and SES independently influenced metabolic control in a large, unselected population of children with type 1 diabetes. Irrespective of SES, Maori and Pacific youth with type 1 diabetes were at greater risk of both moderate to severe hypoglycaemia and long-term complications associated with poor metabolic control.     

Regulatory Actions of Toll-Like Receptor 2 (TLR2) and TLR4 in Leishmania donovani Infection in the Liver

In livers of susceptible but self-curing C57BL/6 mice, intracellular Leishmania donovani infection enhanced Toll-like receptor 4 (TLR4) and TLR2 gene expression. In the liver, infected TLR4^−/− mice showed reduced gamma interferon (IFN-γ), tumor necrosis factor (TNF), and inducible nitric oxide synthase (iNOS) mRNA expression, higher-level and slowly resolving infection, delayed granuloma formation, and little response to low-dose chemotherapy; in serum, the ratio of IFN-γ to interleukin 10 (IL-10) activity was decreased by 50%. In contrast, in TLR2^−/− mice, control of liver infection, parasite killing, and granuloma assembly were accelerated and chemotherapy''s efficacy enhanced. In livers of infected TLR2^−/− mice, mRNA expression was not increased for inflammatory cytokines or iNOS or decreased for IL-10; however, the serum IFN-γ/IL-10 ratio was increased 6.5-fold and minimal responses to IL-10 receptor blockade suggested downregulated IL-10. In established infection in wild-type mice, blockading TLR2 induced parasite killing and triggering TLR4 strengthened resistance and promoted chemotherapy''s effect. Thus, in experimental L. donovani infection in the liver, TLR4 signaling upregulates and TLR2 signaling downregulates macrophage antileishmanial activity, making both receptors potential therapeutic targets in visceral leishmaniasis for engagement (TLR4) or blockade (TLR2).     

The patient experience of radiotherapy for breast cancer: A qualitative investigation as part of the SuPPORT 4 All study

IntroductionBreast cancer is a global health problem with 2.09 million cases of breast cancer diagnosed worldwide in 2018. With an increase in breast cancer survival attention has now focussed on the impact treatment side effects can have on the quality of life for women during survivorship. The aim of the SuPPORT 4 All project is to develop a support bra for use during radiotherapy, that can reduce normal tissue toxicity (for women with larger breasts) and provide accuracy, dignity and modesty for all women. The first stage of the project involved a co-design process to understand the current patient experience where no support bra or modesty device is used.MethodA participatory co-design methodology was adopted. Workshops were held with patient representatives (n = 9) to seek understanding of experience during radiotherapy; a total of three workshops over 4 h. The workshops were audio recorded and framework analysis was adopted to identify key patient experiences.ResultsTwelve categories and twenty-six sub categories were identified specific to patient experience. Patient concerns focussed on information provision, Healthcare Practitioner (HCP) knowledge of breast lymphoedema, lack of choice, experiences of being naked, and feelings of disempowerment.ConclusionsA number of areas were identified that had negative effects on overall patient experience.Implications for practicePractitioners should consider patient dignity when configuring services to support patient needs regarding undressing, outside or inside the linear accelerator room. Additionally, practitioners should have an understanding of the impact permanent tattoos may have on some patients’ wellbeing and the impact that breast lymphoedema has on patient quality of life. Practitioners should also consider methods to encourage patient empowerment during radiotherapy; supporting patient self-monitoring of side-effects may be one way to facilitate this.     

Comparative impacts of two major hurricane seasons on the Neuse River and western Pamlico Sound ecosystems

Ecosystem-level impacts of two hurricane seasons were compared several years after the storms in the largest lagoonal estuary in the U.S., the Albemarle-Pamlico Estuarine System. A segmented linear regression flow model was developed to compare mass-water transport and nutrient loadings to a major artery, the Neuse River Estuary (NRE), and to estimate mean annual versus storm-related volume delivery to the NRE and Pamlico Sound. Significantly less water volume was delivered by Hurricane Fran (1996), but massive fish kills occurred in association with severe dissolved oxygen deficits and high contaminant loadings (total nitrogen, total phosphorus, suspended solids, and fecal bacteria). The high water volume of the second hurricane season (Hurricanes Dennis, Floyd, and Irene in 1999) delivered generally comparable but more dilute contaminant loads, and no major fish kills were reported. There were no discernable long-term adverse impacts on water quality. Populations of undesirable organisms, such as toxic dinoflagellates, were displaced down-estuary to habitats less conducive for growth. The response of fisheries was species-dependent: there was no apparent impact of the hurricanes on commercial landings of bivalve molluscs or shrimp. In contrast, interacting effects of hurricane floodwaters in 1999 and intensive fishing pressure led to striking reductions in blue crabs. Overall, the data support the premise that, in shallow estuaries frequently disturbed by hurricanes, there can be relatively rapid recovery in water quality and biota, and benefit from the scouring activity of these storms.     

The alpha 5 beta 1 integrin supports survival of cells on fibronectin and up-regulates Bcl-2 expression.

Anchorage-dependent cells that are prevented from attaching to an extracellular matrix substrate stop proliferating and may undergo apoptosis. Cell adhesion to a substrate is mediated by the integrin family of cell surface receptors, which are known to elicit intracellular signals upon cell adhesion. We show here that Chinese hamster ovary cells expressing the alpha 5 beta 1 integrin, which is a fibronectin receptor, do not undergo apoptosis upon serum withdrawal when the cells are plated on fibronectin. However, the alpha v beta 1 integrin, which is also a fibronectin receptor and binds fibronectin on the same RGD motif as alpha 5 beta 1, did not prevent apoptosis on fibronectin of the same cells. The cytoplasmic domain of the integrin alpha 5 subunit was required for the alpha 5 beta 1-mediated cell survival on fibronectin. The fibronectin-mediated survival effect appeared to be independent of the level of tyrosine phosphorylation of the focal adhesion kinase, which is induced by integrin-mediated cell attachment. The expression of the Bcl-2 protein, which counteracts apoptosis, was elevated in cells attaching to fibronectin through alpha 5 beta 1; cells attaching through alpha v beta 1 survived only if exogenous Bcl-2 was provided. Thus, alpha 5 beta 1, but not the closely related alpha v beta 1 integrin, appears to suppress apoptotic cell death through the Bcl-2 pathway.