PASD1: a promising target for the immunotherapy of haematological malignancies

In general, there is a lack of good immunotherapy targets within the spectrum of haematological malignancies. However haematopoietic stem cell transplants and continuing antigen discovery have allowed further insight into how further improvements in outcomes for patients might be achieved. Most patients with haematological malignancies can be treated with conventional therapies such as radio- and chemotherapy and will attain first remission. However the removal of residual diseased cells is essential to prevent relapse and its associated high mortality. PASD1 is one of the most tissue restricted cancer-testis (CT) antigens with expression limited to primary spermatagonia in healthy tissue. However, characterisation of PASD1 expression in cancers has been predominantly focussed on haematological malignancies where the inappropriate expression of PASD1 was first identified. PASD1 has one of the highest frequencies of expression of all CT antigens in acute myeloid leukaemia, with some suggestion of its role as a biomarker in diffuse large B-cell lymphoma. Here we describe the characterisation of the function and expression patterns of PASD1 in cell lines and primary tissues. Development of DNA vaccines targeting PASD1 epitopes demonstrate effective ex vivo T-cell responses in terms of IFNγ secretion and tumour cell killing. Of particular note these vaccines have led to the destruction of cells which process and present endogenous PASD1 indicating that effectively primed CTLs could kill PASD1-positive tumour cells

Histopathological Changes in Endometrial Biopsies of Patients with Abnormal Uterine Bleeding

Introduction: Abnormal uterine bleeding (AUB) is one of the commonest complaints leading to endometrial sampling by endometrial biopsy or curettage. Histopathological analysis revealed various patterns ranging from normal endometrium to malignancy and histopathological examination helps in the diagnosis of these diseases presenting with abnormal uterine bleeding. Objective: To assess the causes of AUB in reproductive, perimenopausal and menopausal women. Methodology: This is a retrospective study that includes a total of 375patients’specimens of endometrial biopsies which were clinically diagnosed as AUB in the department of pathology, faculty of medicine, the university of Benghazi from January 2009 to March 2010. The age of the patient ranged from 20 -80 years, and the mean age was (47.38yr). The patient was categorized into 3 groups with 198 cases in the perimenopausal age group,103 cases in the postmenopausal age group and only 74 cases in the reproductive age group. Results: in this study, the prevalence of non-neoplastic endometrial change was commonly seen in the perimenopausal and reproductive age groups (58.2%), (26.8%) respectively, whereas few cases in the postmenopausal age group (15%). The neoplastic endometrial changes (benign, premalignant, malignant) were commonly seen among the perimenopausal age group, followed by the postmenopausal age group, while neoplasia was rare in the reproductive age group. Conclusion: The causes of AUB depend on the age of the patient. In the reproductive age group, AUB was due to hormonal imbalance, while in perimenopausal and postmenopausal women it was generally due to hyperplasia and malignancy

Optimal Sizing of Standalone PV-Wind Hybrid Energy System in Rural Area North Egypt

This paper studies the sizing of stand-alone renewable energy system applied in rural areas in the north of Egypt. The available renewable energy sources in these areas are investigated to be integrated to supply the different types of electrical loads. The quality and quantity of these sources over various weather and climate changes are studied to construct a robust energy system. The load demand in such areas is determined according to all activities require electrical energy. This study considers the different economic levels and technologies which affect the load demand value. The technique and economical indices required to obtain the optimal are investigated and applied in the various estimated cases. The genetic algorithm (GA) technique is applied to determine the size and number of photovoltaic panels and wind turbines. The obtained solution takes into account the loss of power supply probability and the minimization of system cost. This study presents an essential phase in the sustainable development of such rural areas

Infrequent expression of the Cancer-Testis antigen, PASD1, in ovarian cancer

Ovarian cancer is very treatable in the early stages of disease; however, it is usually detected in the later stages, at which time, treatment is no longer as effective. If discovered early (Stage I), there is a 90% chance of five-year survival. Therefore, it is imperative that early-stage biomarkers are identified to enhance the early detection of ovarian cancer. Cancer-testis antigens (CTAs), such as Per ARNT SIM (PAS) domain containing 1 (PASD1), are unique in that their expression is restricted to immunologically restricted sites, such as the testis and placenta, which do not express MHC class I, and cancer, making them ideally positioned to act as targets for immunotherapy as well as potential biomarkers for cancer detection where expressed. We examined the expression of PASD1a and b in a number of cell lines, as well as eight healthy ovary samples, eight normal adjacent ovarian tissues, and 191 ovarian cancer tissues, which were predominantly stage I (n = 164) and stage II (n = 14) disease. We found that despite the positive staining of skin cancer, only one stage Ic ovarian cancer patient tissue expressed PASD1a and b at detectable levels. This may reflect the predominantly stage I ovarian cancer samples examined. To examine the restriction of PASD1 expression, we examined endometrial tissue arrays and found no expression in 30 malignant tumor tissues, 23 cases of hyperplasia, or 16 normal endometrial tissues. Our study suggests that the search for a single cancer-testes antigen/biomarker that can detect early ovarian cancer must continue

Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms’ Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8–1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients

Language support for immigrant children: a study of state schools in the UK and US

In recent decades, immigrants, refugees and asylum seekers have sought a new way of life in large numbers, often leaving their countries of origin behind in search of places that offer a better way of life. The purpose of this study was to investigate how elementary and middle school students in state schools in Reading, England (primarily speakers of Asian languages), and Richmond, Virginia (primarily speakers of Spanish), were supported academically, when most children’s first language was not English. The authors were interested in exploring whether or not there were cultural or structural differences in the way each country helped or hindered these students as they progressed through the school systems. Three UK schools in a district of approximately 100,000 and three US schools in a district of approximately 250,000 were the focus of this exploration from 2000 to 2003. Findings indicated that there were cultural and legislative differences and similarities. Teachers and administrators in both countries attempted to provide services with limited and sometimes diminishing resources. Community support varied based on resources, attitudes toward various ethnic groups, and the coping strategies adopted by these groups in their new environments. Marked differences appeared with regard to the manner in which assessments took place and how the results were made available to the public

Systematic review of the role of social inclusion within sustainable urban developments

Rapid urbanisation presents multiple opportunities, but also poses challenges for equitable distribution of gains from socio-economic developments. This systematic review explored the role of social inclusion within the urban sustainability agenda. Sustainable urban developments were conceptualised as comprising environmental, spatial, social and economic perspectives; and social inclusion as entailing access to core services (healthcare) and resources (food). A search of five databases and grey literature returned 1,015 articles; 26 papers were included following screening using pre-determined criteria. Data was analysed thematically. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed. Most included studies were from North America and few were from Africa and Asia. More empirical than conceptual studies were found, and more focused on food than healthcare. Social inclusion was generally included within the urban sustainability but was often an autonomous component, rather than mainstreamed, within urban sustainability. Social inclusion was mostly related to multiple elements of sustainability, with the greatest focus on combinations of environmental, social and economic opportunities for under privileged groups. However, less consideration was given to gender, ethnicity and other aspects of intersectionality. Multiple theories contributed to transferability of lessons. Key policy implications include prioritising the most vulnerable socially excluded populations, ensuring equal representation in urban planning, designing people-centred systems, building partnerships with communities, considering socio-cultural-political-economic contexts, and recognising both intended and unintended effects. More research is needed in low and middle-income countries (LMICs) on the role of social inclusion in achieving sustainable development, using cross-disciplinary approaches

Note on the special fillet fatty acid composition of the dwarf carp (Cyprinus carpio carpio) living in thermal Lake Hévíz, Hungary

Fatty acid (FA) composition of the fillet and the intestinal content of dwarf common carp (Cyprinus carpio carpio) living in Lake Hévíz was determined in wintertime collected samples and results were compared to widespread literature data on carp. Fillet FA profile of the thermally adapted (28 oC) Hévíz dwarf carps differed from profiles originated from divergent culture and feeding conditions in the overall level of saturation. Fillet myristic acid proportions largely exceeded all literature data in spite of poor dietary supply. Fillet fatty acid results indicate the effects of thermal adaptation (high saturation level) and the correlative effects of feed components rich in omega-3 fatty acids, with special respect to docosahexaenoic acid. With the application of discriminant factor analysis the Hévíz sample was accurately differentiated from the literature data on carp fillet fatty acid profile, mostly based on C14:0, C18:1 n9, C18:2 n6, C20:1 n9 and C20:4 n6 FAs. In summary, fillet FA profile suggested thermal adaptation, location specificity and the ingestion of algal and bacterial material

Association of depression with newly diagnosed type 2 diabetes among adults aged between 25 to 60 years in Karachi, Pakistan

<p>Abstract</p> <p>Background</p> <p>The combination of depression with type 2 diabetes is a public health problem. If diabetes is managed in its initial phase, the morbidity and mortality due to this combination may be prevented at an early stage. Therefore, we aimed to determine the association of depression with newly diagnosed type 2 diabetes among adults aged between 25 to 60 years in Karachi, Pakistan.</p> <p>Methods</p> <p>From July 2006 to September 2007, a matched case control study (n = 592) was conducted in Civil Hospital, Karachi. Incident cases of type 2 diabetes (n = 296) diagnosed within one month were recruited from diabetic Out Patient Department (OPD) of Civil Hospital, Karachi. They were matched on age and sex with controls (n = 296), who were attendants sitting in the medical out patient department of the same hospital, recruited on the basis of absence of classical symptoms of polyuria and polydispia along with random blood glucose level of <200 mg/dl measured by a glucometer. Depression was identified by the Siddiqui Shah Depression Scale. Conditional logistic regression was applied to examine the association of depression and other independent variables with newly diagnosed type 2 diabetes at 95% C.I. and P < 0.05.</p> <p>Results</p> <p>The study comprised of 592 subjects with 432(73%) males and 160(27%) females. Depression was significantly associated with newly diagnosed type 2 diabetes having mild level (mOR: 3.86; 95%CI: 2.22,6.71) and moderate to severe level (mOR: 3.41; 95%CI: 2.07,5.61). History of (h/o) gestational diabetes (mOR: 2.83; 95%CI: 1.05,7.64), family h/o diabetes (mOR: 1.59; 95%CI: 1.04,2.43), nuclear family (mOR: 1.75; 95%CI: 1.14,2.69), BMI (mOR: 1.62; 95%CI: 1.01,2.60 for obese and mOR: 2.12; 95%CI: 1.19,3.79 for overweight vs healthy to underweight) were also significantly associated with outcome, adjusting for age, sex, marital status, h/o smoking and h/o high BP.</p> <p>Conclusions</p> <p>Diabetics should be screened simultaneously for depression and concomitant preventive strategies for gestational diabetes, nuclear family and high BMI should also be used to prevent mortality/morbidity among patients between 25 to 60 years of age.</p