Short SULF1/SULF2 splice variants predominate in mammary tumours with a potential to facilitate receptor tyrosine kinase-mediated cell signalling

The relative roles of SULF1 and SULF2 enzymes in tumour growth are controversial, but short SULF1/SULF2 splice variants predominate in human mammary tumours despite their non-detectable levels in normal mammary tissue. Compared with the normal, the level of receptor tyrosine kinase (RTK) activity was markedly increased in triple-positive mammary tumours during later stages of tumour progression showing increased p-EGFR, p-FGFR1 and p-cMet activity in triple-positive but not in triple-negative tumours. The abundance of catalytically inactive short SULF1/SULF2 variants permits high levels of HS sulphation and thus growth driving RTK cell signalling in primary mammary tumours. Also observed in this study, however, was increased N-sulphation detected by antibody 10E4 indicating that not only 6-O sulphation but also N-sulphation may contribute to increased RTK cell signalling in mammary tumours. The levels of such increases in not only SULF1/SULF2 but also in pEGFR, pFGFR1, p-cMet and Smad1/5/8 signalling were further enhanced following lymph node metastasis. The over-expression of Sulf1 and Sulf2 variants in mammary tumour-derived MDA-MB231 and MCF7 cell lines by transfection further confirms Sulf1-/Sulf2-mediated differential modulation of growth. The short variants of both Sulf1 and Sulf2 promoted FGF2-induced MDA-MB231 and MCF7 in vitro growth while full-length Sulf1 inhibited growth supporting in vivo mammary tumour cell signalling patterns of growth. Since a number of mammary tumours become drug resistant to hormonal therapy, Sulf1/Sulf2 inhibition could be an alternative therapeutic approach to target such tumours by down-regulating RTK-mediated cell signalling

A care pathway approach to identifying factors that impact on diagnosis of heart disease in British Pakistani women

Purpose – The authors examined the cardiac care pathway with the aim of identifying factors that impact on diagnosis and treatment of coronary heart disease in British Pakistani women. Design/methodology/approach – This is an exploratory qualitative study. In depth interviews and focus groups with an opportunistic sample of Pakistani women and a purposive sample of clinicians working at different points along the care pathway were conducted. The authors used a pathways to care approach to illustrate how their individual and cumulative effect may contribute to differential receipt of treatment, including revascularisation, and health inequalities. Findings – Four major issues were identified: complex life circumstances; ‘‘atypical’’ presentation and ymptomatology; problems related to investigative testing; and poor communication. Mapping these barriers onto the Pathways to Care Model provided valuable insight into their impact on patients’progression through the different stages of the care pathway. Research limitations/implications – Adopting a care pathway approach demonstrated how individual factors have an impact at several points along the care pathway. It indicated where further, more detailed enquiry is merited and where intervention studies might usefully be directed to improve care. Practical implications – Examining the whole care pathway identified areas of service improvement that merit a co-ordinated response. Originality/value – The framework provided by the Pathways to Care Model offered insight into the causes of the previously observed attenuation in women’s progress along the cardiac diagnosis and treatment pathway and is an important first step to addressing this health inequality in a holistic way. Keywords Health, Gender, Inequalities, Women, Ethnicity, United Kingdom, Ethnic minorities, Personal health Paper type Research paper </p

Dysregulated cancer cell transdifferentiation into erythrocytes is an additional metabolic stress in hepatocellular carcinoma

A number of human and canine hepatocellular carcinoma tissues showed clear signs of hypoxia indicated by HIF1α-activation and the presence of large clusters of cells resembling erythrocytes at different stages of nuclear elimination without any defined endothelial cell lining or blood vessel walls. Differentiated erythrocytic identity of such cells in hepatocellular carcinoma tissues was apparent from their non-nucleated and evolving basophilic to eosinophilic staining characteristics. In addition to the fully differentiated non-nucleated mesenchymal cell clusters, the onset of erythroblastic transdifferentiation was apparent from the activation of Glycophorin A, a marker of erythrocytic progenitors, in some epithelial cancer cells. Activation of canonical Wnt signalling in such tumours was apparent from the expression of Wnt2 ligand and active β-catenin translocation into the nucleus indicating Wnt signalling to be one of the key signalling pathways participating in such cell transdifferentiation. Sonic hedgehog and bone morphogenetic protein signalling along with Sulf1/Sulf2 activation was also observed in such hepatocellular carcinoma tissue samples. The presence of stem cell markers and the cell signalling pathways associated with erythropoiesis, and the detection of messenger RNAs for both α and β haemoglobins, support the assumption that hepatocellular carcinoma cells have the potential to undergo cell fate change despite this process being dysregulated as indicated by the lack of simultaneous generation of endothelial cell lining. Lack of blood vessel walls or endothelial cell lining around erythrocytic clusters was confirmed by non-detection of multiple blood vessel markers such as vWF, CD146 and smooth muscle α-actin that were clearly apparent in normal and unaffected adjacent regions of hepatocellular carcinoma livers. In addition to the activation of Glycophorin A, transdifferentiation of some hepatocellular carcinoma hepatocytes into other cell fates was further confirmed by the activation of some stem cell markers, for example, NANOG and OCT4 transcription factors, not only by reverse transcription polymerase chain reaction but also by their restricted expression in such cells at protein level

Validation of Dried Tube Specimen (DTS) as Internal Quality Control for HIV testing in Blood Banks

BACKGROUND: Serological testing for HIV is mandatory in every blood bank to prevent its transmission by transfusion. The practice of third party internal controls is however uncommon. Most often cited reason for this is the cost, lack of easy access to reliable material and the need for freezers for storage of plasma. We explore an alternative cost-effective method for production and maintenance of in-house controls to overcome these issues. AIM OF THE STUDY: Validation of Dried tube specimen (DTS) from HIV positive blood donor plasma as a low cost, stable material for use as Internal Quality Control material in blood banks. METHODS AND MATERIALS: Fresh frozen plasma prepared from consenting blood donors, confirmed HIV positive by serological and molecular methods was retained over a period of six months and pooled (4 bags). Equal numbers of seronegative FFP bags were pooled together. Aliquots of 20μl were made in plastic micro-centrifuge tubes and air dried overnight in a biosafety cabinet at room temperature. These samples were stored at 2-6⁰ C refrigerators and tested once every week on a variety of platforms that included three rapid tests, a second generation ELISA and a fourth generation Chemiluminescence immunoassay. A fourth generation ELISA was included on a monthly basis. This protocol was followed over a 6 month period to study extended stability of the control material. RESULTS: Epidata™, MS Excel ™ and SPSS™ were used to tabulate and analyse the data. A total of 109 positive samples (DTS aliquots) were tested with 100% samples showing consistent positive results on all the platforms over the test period of 6 months. Similarly the negative samples (n=109) showed consistent negative results on all assay platforms over the six month period. It was observed that the procedure for reconstitution of DTS if not followed rigorously resulted in change of expected results. CONCLUSION: The plasma in the form of DTS maintained stability when stored at 2-8°C, over the study period of 6 months. The results were consistent and samples did not show any deterioration. Issues to be highlighted include the need to follow stringent safety measures when handling the plasma during preparation and the reconstitution of the DTS prior to use. This provides evidence that the DTS can be a modality for production of cost effective stable in-house control material for resource restricted countries

Implementing a mobile diagnostic unit to increase access to imaging and laboratory services in western Kenya.

Access to basic imaging and laboratory services remains a major challenge in rural, resource-limited settings in sub-Saharan Africa. In 2016, the Academic Model Providing Access to Healthcare programme in western Kenya implemented a mobile diagnostic unit (MDU) outfitted with a generator-powered X-ray machine and basic laboratory tests to address the lack of these services at rural, low-resource, public health facilities. The objective of this paper is to describe the design, implementation, preliminary impact and operational challenges of the MDU in western Kenya. Since implementing the MDU at seven rural health facilities serving a catchment of over half a million people, over 4500 chest radiographs have been performed, with one or more abnormalities detected in approximately 30% of radiographs. We observed favorable feedback and uptake of MDU services by healthcare workers and patients. However, various operational challenges in the design and construction of the MDU and the transmission and reporting of radiographs in remote areas were encountered. Our experience supports the feasibility of deploying an MDU to increase access to basic radiology and laboratory services in rural, resource-limited settings

Correlation of anthropometric indices by cardio vascular index in young adult having obesity

Background: The aim of this study is to correlate anthropometric indices with hemodynamic vascular changes in young adult obese patients. Methods: It is case-control study, 140 patients were recruited. Which were divided into two group i.e., study group=70 and control group=70. Anthropometric measurement waist circumference (WC) and total body fat percentage (TBF%) of each patient is compared with right brachial pulse wave velocity (PWV) (dominant hand). Results: Obese individuals had high levels of PWV as compared with non obese patients. Study suggested that cardiovascular parameter levels were significantly increased in obese patients, these same patients gradually progress towards the hypertensive condition. Conclusions: Changes in cardiac function are common in obese patients, hence, there is need for periodical assessment of the cardiac function and anthropometric measurement and PWV as cardiac markers in obese patients proves to be an early and simple tool to give warning signal for the patients to take early preventive measures

Imidacloprid poisoning: a modern foe

Imidacloprid is a relatively new insecticide in the chloronicotinyl nitroguanidine class. Imidacloprid has a wide variety of uses; it is used on cotton and vegetable crops, turf grass and ornamental plant products, in indoor and outdoor cockroach control products and in termite control products. Imidacloprid acts as a competitive inhibitor at nicotinic acetylcholine receptors in the nervous system resulting in impairment of normal nerve function. Scientific literature on human imidacloprid poisoning has been relatively sparse. We report three subjects who presented with imidacloprid poisoning

Improving capacity in ethnicity and health research: report of a tailored programme for NHS Public Health practitioners

Aim: To determine whether an intervention designed to enhance research capacity among commissioners in the area of ethnicity and health was feasible and impactful, and to identify programme elements that might usefully be replicated elsewhere. Background: How healthcare commissioners should be equipped to understand and address multiethnic needs has received little attention to-date. Being able to mobilise and apply evidence is a central element of the commissioning process that requires development. Researching ethnicity and health is widely recognised as challenging and several prior interventions have aimed to enhance competence in this area. These have, however, predominantly taken place in North America and have not been evaluated in detail. Methods: An innovative research capacity development programme was delivered to public health staff within a large healthcare commissioning organisation in England. Evaluation methodology drew on ‘pluralistic’ evaluation principles and included formative and summative elements. Participant evaluation forms gave immediate feedback during the programme. Participants also provided feedback at two weeks and 12 months after the programme ended. In addition, one participant and one facilitator provided reflective accounts of the programme's strengths and weaknesses, and programme impact was traced through ongoing partnership work. Findings: The programme was well received and had a tangible impact on knowledge, confidence and practice for most participants. Factors important to success included: embedding learning within the participants’ work context; ensuring a balance between theory and practical tips to enhance confidence; and having sustained interaction between trainers and participants. Despite positive signs, the challenging nature of the topic was highlighted, as were wider structural and cultural factors that impede progress in this area. Although it is unrealistic to expect such programmes to have a major impact on commissioning practices, they may well make an important contribution to raising the confidence and competence of staff to undertake work in this area.</p