Increasing rates of cervical cancer in young women in England: an analysis of national data 1982–2006

background: In England, cervical cancer is the second most common cancer in women aged under 35 years. Overall incidence of cervical cancer has decreased since the introduction of the national screening programme in 1988 but recent trends of incidence in young women have not been studied in detail. methods: Information on 71 511 incident cases of cervical cancer in England, 1982–2006, in 20–79-year-olds was extracted from a national cancer registration database. Changes in incidence were analysed by age group, time period and birth cohort. Poisson regression was used to estimate annual percentage change (APC). results: Overall incidence, during 1982–2006, fell significantly from 213 to 112 per million person years. However, in 20–29-year-olds, after an initial fall, incidence increased significantly during 1992–2006, (APC 2.16). In 30–39-year-olds incidence stabilised during the latter part of the study period. The pattern was most marked in the North East, Yorkshire and the Humber and East Midlands regions. Birth cohorts that were initially called for screening between 60–64 and 35–39 years of age show an incidence peak soon after the age of presumed first screen, whereas younger birth cohorts show a peak at about 35 years of age. Incidence in the 1977–1981 birth cohort has increased relative to that among women born between 1962 and 1976. conclusion: These results have implications for cervical screening, human papilloma virus vaccination and other public health interventions targeting young people

TOM40 Mediates Mitochondrial Dysfunction Induced by α-Synuclein Accumulation in Parkinson's Disease.

Alpha-synuclein (α-Syn) accumulation/aggregation and mitochondrial dysfunction play prominent roles in the pathology of Parkinson's disease. We have previously shown that postmortem human dopaminergic neurons from PD brains accumulate high levels of mitochondrial DNA (mtDNA) deletions. We now addressed the question, whether alterations in a component of the mitochondrial import machinery -TOM40- might contribute to the mitochondrial dysfunction and damage in PD. For this purpose, we studied levels of TOM40, mtDNA deletions, oxidative damage, energy production, and complexes of the respiratory chain in brain homogenates as well as in single neurons, using laser-capture-microdissection in transgenic mice overexpressing human wildtype α-Syn. Additionally, we used lentivirus-mediated stereotactic delivery of a component of this import machinery into mouse brain as a novel therapeutic strategy. We report here that TOM40 is significantly reduced in the brain of PD patients and in α-Syn transgenic mice. TOM40 deficits were associated with increased mtDNA deletions and oxidative DNA damage, and with decreased energy production and altered levels of complex I proteins in α-Syn transgenic mice. Lentiviral-mediated overexpression of Tom40 in α-Syn-transgenic mice brains ameliorated energy deficits as well as oxidative burden. Our results suggest that alterations in the mitochondrial protein transport machinery might contribute to mitochondrial impairment in α-Synucleinopathies

Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48

Dysregulated mitochondrial function is a hallmark of immune-mediated inflammatory diseases. Cytochrome c oxidase (CcO), which mediates the rate-limiting step in mitochondrial respiration, is remodeled during development and in response to changes of oxygen availability, but there has been little study of CcO remodeling during inflammation. Here, we describe an elegant molecular switch mediated by the bifunctional transcript C15orf48, which orchestrates the substitution of the CcO subunit NDUFA4 by its paralog C15ORF48 in primary macrophages. Expression of C15orf48 is a conserved response to inflammatory signals and occurs in many immune-related pathologies. In rheumatoid arthritis, C15orf48 mRNA is elevated in peripheral monocytes and proinflammatory synovial tissue macrophages, and its expression positively correlates with disease severity and declines in remission. C15orf48 is also expressed by pathogenic macrophages in severe coronavirus disease 2019 (COVID-19). Study of a rare metabolic disease syndrome provides evidence that loss of the NDUFA4 subunit supports proinflammatory macrophage functions

Tight control of disease activity fails to improve body composition or physical function in rheumatoid arthritis patients

Objective. RA typically features “rheumatoid cachexia” (loss of muscle mass (MM) and excessive fat mass (FM), especially trunk FM), which contributes to physical disability. Since rheumatoid cachexia is driven by inflammation, it would be anticipated that the success of tight control of disease activity, such as “treat-to-target” (T2T), in attenuating inflammation would benefit body composition and physical function. This cross-sectional study assessed the impact of T2T on body composition and objectively-assessed function in RA patients

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Comparison of Bayesian and frequentist approaches in modelling risk of preterm birth near the Sydney Tar Ponds, Nova Scotia, Canada

<p>Abstract</p> <p>Background</p> <p>This study compares the Bayesian and frequentist (non-Bayesian) approaches in the modelling of the association between the risk of preterm birth and maternal proximity to hazardous waste and pollution from the Sydney Tar Pond site in Nova Scotia, Canada.</p> <p>Methods</p> <p>The data includes 1604 observed cases of preterm birth out of a total population of 17559 at risk of preterm birth from 144 enumeration districts in the Cape Breton Regional Municipality. Other covariates include the distance from the Tar Pond; the rate of unemployment to population; the proportion of persons who are separated, divorced or widowed; the proportion of persons who have no high school diploma; the proportion of persons living alone; the proportion of single parent families and average income. Bayesian hierarchical Poisson regression, quasi-likelihood Poisson regression and weighted linear regression models were fitted to the data.</p> <p>Results</p> <p>The results of the analyses were compared together with their limitations.</p> <p>Conclusion</p> <p>The results of the weighted linear regression and the quasi-likelihood Poisson regression agrees with the result from the Bayesian hierarchical modelling which incorporates the spatial effects.</p

Targeting Cattle-Borne Zoonoses and Cattle Pathogens Using a Novel Trypanosomatid-Based Delivery System

Trypanosomatid parasites are notorious for the human diseases they cause throughout Africa and South America. However, non-pathogenic trypanosomatids are also found worldwide, infecting a wide range of hosts. One example is Trypanosoma (Megatrypanum) theileri, a ubiquitous protozoan commensal of bovids, which is distributed globally. Exploiting knowledge of pathogenic trypanosomatids, we have developed Trypanosoma theileri as a novel vehicle to deliver vaccine antigens and other proteins to cattle. Conditions for the growth and transfection of T. theileri have been optimised and expressed heterologous proteins targeted for secretion or specific localisation at the cell interior or surface using trafficking signals from Trypanosoma brucei. In cattle, the engineered vehicle could establish in the context of a pre-existing natural T. theileri population, was maintained long-term and generated specific immune responses to an expressed Babesia antigen at protective levels. Building on several decades of basic research into trypanosomatid pathogens, Trypanosoma theileri offers significant potential to target multiple infections, including major cattle-borne zoonoses such as Escherichia coli, Salmonella spp., Brucella abortus and Mycobacterium spp. It also has the potential to deliver therapeutics to cattle, including the lytic factor that protects humans from cattle trypanosomiasis. This could alleviate poverty by protecting indigenous African cattle from African trypanosomiasis

A multi-disciplinary education process related to the discharging of children from hospital when the child has been diagnosed with type 1 diabetes - a qualitative study

<p>Abstract</p> <p>Background</p> <p>Worldwide, insulin-dependent type 1 diabetes is one of the most frequently diagnosed long-term endocrine disorders found in children and the incidences of this diseased is still increasing. In Sweden the routines are, according to national guidelines, when the child is diagnosed with type 1 diabetes, the child and its family remains at the hospital for about two weeks. There is limited knowledge about how a diabetes team handles a child and its family from admission to discharge, therefore the purpose of this study was to seek a deeper understanding of how the diabetes team's parent/child education process works, from admission to discharge, among families with a child newly diagnosed with type 1 diabetes.</p> <p>Methods</p> <p>Qualitative data collection was used. Four focus-group interviews, with a sample of three diabetes teams from different paediatric hospitals in the south western part of Sweden, were conducted and the data recorded on tape and then analysed using qualitative content analysis.</p> <p>Results</p> <p>The results indicate that achieving a status of self-care on the part of the patient is the goal of the diabetes education programme. Part of the programme is aimed at guiding the child and its parents towards self-help through the means of providing them with knowledge of the disease and its treatment to enable the whole family to understand the need for cooperation in the process. To do this requires an understanding, by the diabetes team, of the individualities of the family in order to gain an overall picture.</p> <p>Conclusion</p> <p>The results of this study show that the diabetes education programme is specifically designed for each family using the internationally recommended clinical practice guidelines with its specific aims and objectives. Achieving the families' willingness to assist in the self-care of the child care is the goal of the parent education process. To achieve this, the paediatric diabetes specialist nurse and the diabetes specialist paediatrician immediately and deliberately start the process of educating the family using a programme designed to give them the necessary knowledge and skills they will need to manage their child's type 1 diabetes at home.</p