Preventing cervical cancer in rural Tanzania : a program model for health worker trainings

With a focus on Northern Tanzania, this report seeks to demonstrate the need for increased resource allocation to cervical cancer interventions, examine best practices for cervical cancer screening promotion, and develop an intervention and program evaluation framework. The intervention is a training program designed for dispensary-level healthcare providers in the Northern Zone of Tanzania and aims to increase provider awareness and knowledge of cervical cancer, and build skills among providers to educate patients on cervical cancer prevention and screening and treatment resources. This report is purely a program design and planning tool; no new data was collected, nor interventions implemented in the development of report. The first objective of the report is to develop an intervention to be presented to Foundation for Cancer Care in Tanzania (FCCT) and the second is to develop an evaluation framework to be presented to FCCT. FCCT is a non-profit agency working to bring comprehensive cancer services to the region. The program will complement existing and planned services related to cervical cancer prevention and treatment in the Northern Zone of Tanzania, and will be considered for implementation by the Foundation for Cancer Care in Tanzania (FCCT). Part I of the report reviews published literature and data to demonstrate the need for increased resource allocation to cervical cancer interventions and the appropriateness of Northern Tanzania as a case selection. Part I also examines best practices for cervical cancer screening promotion in Northern Tanzania, providing evidence from the published literature to inform Part II, the intervention design and program evaluation framework. Included in the intervention design is a logic model for change, detailed training plans and curriculum, and guidelines for selecting trainers. The report recommends appointments to a local planning team and estimates a timeline and budget for the program. Additionally, the report designs a thorough program evaluation, the objective of which is to measure the effect of training and health education materials on dispensary-level healthcare providers’ awareness, knowledge, and skills regarding cervical cancer prevention.Global Policy StudiesNursin

Interleukin-2 signalling is modulated by a labile disulfide bond in the CD132 chain of its receptor

Certain disulfide bonds present in leucocyte membrane proteins are labile and can be reduced in inflammation. This can cause structural changes that result in downstream functional effects, for example, in integrin activation. Recent studies have shown that a wide range of membrane proteins have labile disulfide bonds including CD132, the common gamma chain of the receptors for several cytokines including interleukin-2 and interleukin-4 (IL-2 and IL-4). The Cys183–Cys232 disulfide bond in mouse CD132 is susceptible to reduction by enzymes such as thioredoxin (TRX), gamma interferon-inducible lysosomal thiolreductase and protein disulfide isomerase, which are commonly secreted during immune activation. The Cys183–Cys232 disulfide bond is also reduced in an in vivo lipopolysaccharide (LPS)-induced acute model of inflammation. Conditions that lead to the reduction of the Cys183–Cys232 disulfide bond in CD132 inhibit proliferation of an IL-2-dependent T cell clone and concomitant inhibition of the STAT-5 signalling pathway. The same reducing conditions had no effect on the proliferation of an IL-2-independent T cell clone, nor did they reduce disulfide bonds in IL-2 itself. We postulate that reduction of the Cys183–Cys232 disulfide in CD132 inhibits IL-2 binding to the receptor complex. Published data show that the Cys183–Cys232 disulfide bond is exposed at the surface of CD132 and in close contact with IL-2 and IL-4 in their respective receptor complexes. In addition, mutants in these Cys residues in human CD132 lead to immunodeficiency and loss of IL-2 binding. These results have wider implications for the regulation of cytokine receptors in general, as their activity can be modulated by a ‘redox regulator’ mechanism caused by the changes in the redox environment that occur during inflammation and activation of the immune system

Dephytinisation of soyabean protein isolate with low native phytic acid content has limited impact on mineral and trace element absorption in healthy infants

Infant formulas based on soyabean protein isolate are often used as an alternative to cows'-based formulas. However, the presence of phytic acid in soya formulas has raised concern about the absorption of trace elements and minerals from these products. The aim of the present study was to evaluate mineral and trace element absorption from regular and dephytinised soya formula in healthy infants. Soyabean protein isolate with a relatively low native content of phytic acid was used for production of a regular soya formula (300 mg phytic acid/kg liquid formula) and an experimental formula was based on dephytinised soya protein isolate (<6 mg phytic acid/kg liquid formula). Using a crossover study design, apparent mineral and trace element absorptions were measured by a stable isotope technique based on 72 h faecal excretion of non-absorbed stable isotopes (Zn, Fe, Cu and Ca) and by the chemical balance technique (Mn, Zn, Cu and Ca) in nine infants (69-191 d old). Fe absorption was also measured by erythrocyte incorporation 14 d after intake. The results from the present study demonstrated that Zn absorption, measured by a stable isotope technique, was significantly greater after dephytinisation (mean value 16·7 v. 22·6 %; P=0·03). No other statistically significant differences between the two formulas were observed. The nutritional benefit of dephytinisation was marginal in the present study. Based on these results, the use of soyabean protein isolate with low native content of phytic acid should be promoted for production of soya formulas and adequate addition of ascorbic acid to enhance Fe absorption should be ensured in the product

Non cell autonomous upregulation of CDKN2 transcription linked to progression of chronic hepatitis C disease

Chronic hepatitis C virus infection (C-HC) is associated with higher mortality arising from hepatic and extrahepatic disease. This may be due to accelerated biological aging; however, studies in C-HC have thus far been based solely on telomere length as a biomarker of aging (BoA). In this study, we have evaluated CDKN2 locus transcripts as alternative BoAs in C-HC. Our results suggest that C-HC induces non-cell-autonomous senescence and accelerates biological aging. The CDKN2 locus may provide a link between C-HC and increased susceptibility to age-associated diseases and provides novel biomarkers for assessing its impact on aging processes in man

The impact of King James II on the departments of the royal household

The primary subjects of the thesis are the political activities of the king's servants and the administration of the departments of the royal household during the reign of James II. In order to provide essential background, it does not confine itself just to that reign and so contains new information about the court of Charles II. In chapters one and two the reasons why James appointed the senior servants that he did in 1685 are discussed in order to establish how far they were determined by policy considerations. Chapter three explains the major administrative reforms implemented at the beginning of the reign. These are related to changes which had taken place under his predecessor and the way in which these changes had been interpreted by observers is used to understand the implications of James' s reforms. The repercussions of James's catholicism are dealt with in the fourth chapter which looks at the provisions made for catholic worship at court and attempts to calculate how many catholics were appointed by him to court offices. In the fifth chapter the way in which the other servants responded to the king's pro-catholic policies are discussed. The conclusion that they had mixed feelings but felt obliged to obey is developed in the following chapter analysing events leading up to James's downfall. The strength of James's domestic position is stressed. The final chapter assesses the size of the changes in the personnel of the court in 1689, together with the extent to which those who had been James's servants chose to go with him into exile. It also shows that much of what William III did represented a rejection of James's policies within the royal household

The Chemistry and Sources of Fructose and Their Effect on its Utility and Health Implications

Fructose is a significant component in natural foods and has become one of the most prevalent sweeteners added in the manufacture of food. Fructose is also used as a pharmaceutical excipient and derivatives of fructose are exploited as renewable chemical building blocks. Herein we discuss the chemistry and sources of this monosaccharide and how these factors affect the utility and health implications of fructose

Suppression of X-rays during an optical outburst of the helium dwarf nova KL Dra

KL Dra is a helium accreting AM CVn binary system with an orbital period close to 25 mins. Approximately every 60 days there is a 4 mag optical outburst lasting ~10 days. We present the most sensitive X-ray observations made of an AM CVn system during an outburst cycle. A series of eight observations were made using XMM-Newton which started shortly after the onset of an optical outburst. We find that X-rays are suppressed during the optical outburst. There is some evidence for a spectral evolution of the X-ray spectrum during the course of the outburst. A periodic modulation is seen in the UV data at three epochs -- this is a signature of the binary orbital or the super-hump period. The temperature of the X-ray emitting plasma is cooler compared to dwarf novae, which may suggest a wind is the origin of a significant fraction of the X-ray flux.Comment: Accepted by MNRA

Factors associated with spontaneous clearance of chronic hepatitis C virus infection

Background &amp; Aims: Spontaneous clearance of chronic hepatitis C virus (HCV) infection (CHC) is rare. We conducted a retrospective case-control study to identify rates and factors associated with spontaneous clearance of CHC. Methods: We defined cases as individuals who spontaneously resolved CHC, and controls as individuals who remained chronically infected. We used data obtained on HCV testing between 1994 and 2013 in the West of Scotland to infer case/control status. Specifically, untreated patients with ⩾2 sequential samples positive for HCV RNA ⩾6 months apart followed by ⩾1 negative test, and those with ⩾2 positive samples ⩾6 months apart with no subsequent negative samples were identified. Control patients were randomly selected from the second group (4/patient of interest). Case notes were reviewed and patient characteristics obtained. Results: 25,113 samples were positive for HCV RNA, relating to 10,318 patients. 50 cases of late spontaneous clearance were identified, contributing 241 person-years follow-up. 2,518 untreated, chronically infected controls were identified, contributing 13,766 person-years follow-up, from whom 200 controls were randomly selected. The incidence rate of spontaneous clearance was 0.36/100 person-years follow-up, occurring after a median 50 months’ infection. Spontaneous clearance was positively associated with female gender, younger age at infection, lower HCV RNA load and co-infection with hepatitis B virus. It was negatively associated with current intravenous drug use. Conclusions: Spontaneous clearance of CHC occurs infrequently but is associated with identifiable host and viral factors. More frequent HCV RNA monitoring may be appropriate in selected patient groups. Lay summary: Clearance of hepatitis C virus infection without treatment occurs rarely once chronic infection has been established. We interrogated a large Scottish patient cohort and found that it was more common in females, patients infected at a younger age or with lower levels of HCV in the blood, and patients co-infected with hepatitis B virus. Patients who injected drugs were less likely to spontaneously clear chronic infection