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The Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) as well as the T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) are rare types of malignant lymphomas. Both NLPHL and THRLBCL are frequently observed in middle-aged men with THRLBCL presenting frequently with an advanced Ann-Arbor stage with B-symptoms and associated with more aggressive courses.3 However, due to the limited number of tumor cells in the tissue of both NLPHL and THRLBCL, limited numbers of studies have been conducted on these lymphomas and current results are mainly based on general molecular genetic studies.
In order to obtain a better understanding for these disease forms as well as possible changes in their nuclear and cytoplasmatic sizes, the following study relied on the comparison of the different NLPHL forms and THRLBCL in terms of nuclear size and nuclear volume. This was carried out using both 2D and 3D analysis. During the 2D analysis of nuclear size and nuclear volume no significant differences could be presented between those groups. However, the 3D analysis of NLPHL and THRLBCL pointed out a slightly enlarged nuclear volume in THRLBCL. Furthermore, the analysis indicated a significantly increased cytoplasmatic size of THRLBCL compared to NLPHL forms. Nevertheless, differences occurred not only between the tumor cells of both disease forms, but also the T cells presented a larger nuclear volume in THRLBCL. B cells, which were considered as the control group, did not demonstrate any significant differences between the different groups. The presented results suggest an increased activity of T cells in THRLBCL, which is most likely to be interpreted as a response against the surrounding tumor cells and probably limits the proliferation of the tumor cells. Based on these results, the importance of 3D analysis is also evident due to the fact that it is clearly superior to 2D analysis. For a better understanding of both disease forms, it is therefore recommended to use the 3D technique in combination with molecular genetic analysis in future research.
Classical Hodgkin lymphoma (cHL) is one of the most common malignant lymphomas in Western Europe. The nodular sclerosing subtype of cHL (NS cHL) is characterised by a proliferation of fibroblasts in the tumour microenvironment, leading to fibrotic bands surrounding the lymphoma infiltrate. Several studies have described a crosstalk between the tumour cells of cHL, the Hodgkin- and Reed-Sternberg (HRS) cells, and cancerassociated fibroblasts (CAF). However, to date a deep molecular understanding of these fibroblasts is lacking. Aim of the present study therefore was a comprehensive
characterisation of these fibroblasts. Moreover, only a few studies describe the interplay of HRS cells and CAF. The paracrine communication and direct interaction of these two
cellular fractions have been investigated within this study. Finally, the influence of a few HRS cells within a lymph node orchestrate the mere alteration of its architecture and
morphology. Gene expression and methylation profiles of fibroblasts isolated from primary lymph node suspensions revealed persistent differences between fibroblasts obtained from NS cHL and lymphadenitis. NS cHL derived fibroblasts exhibit a myofibroblastic - inflammatory phenotype characterised by MYOCD, CNN1 and IL-6 expression. TIMP3, an inhibitor of matrix metalloproteinases, was strongly upregulated in NS cHL fibroblasts, likely contributing to the accumulation of collagen in sclerotic bands of NS cHL. Treatment by luteolin could reverse this fibroblast phenotype and decrease TIMP3 secretion. NS cHL fibroblasts showed enhanced proliferation when they were exposed to soluble factors released from HRS cells. For HRS cells, soluble
factors from fibroblasts were not sufficient to protect them from Brentuximab-Vedotin(BV) induced cell death. However, HRS cells adherent to fibroblasts were protected from BV-induced injury. The cHL specific interaction of both cell fractions reveals an initiation of inflammatory key regulators such as IL13 and IL4. Among important adhesion molecules known from literature the blocking of integrin beta 1 solely interrupted the adhesion of HRS cells to CAF. In summary, this study proves the stable reprograming of CAF phenotype and expression derived from NS cHL. It presents a suitable in vitro model for studying the interaction of HRS cells and CAF by paracrine factors and adherence. Most importantly the observations confirm the importance of fibroblasts for HRS cellsĀ“ inflammatory niche and cell survival associated with TIMP3 which probably acts as a major factor to the typical accumulation of fibrosis observed in NS cHL.
Malaria is an environmental disease, influenced not only by physical and biological environmental factors but also by socio-cultural ones. These factors affect each other, and, in turn, cause the disease in endemic areas. Some factors that cause the high morbidity rate associated with the disease include climate change, physical environment that varies geographically, socio-economic circumstances, and human behaviour in the affected areas. Other risk factors include housing conditions and poor sanitation, lack of hygiene practices, and inadequate health services in endemic areas. Efforts to eliminate malaria have been a topic at various public health meetings for decades. However, in Indonesia, malaria continues to be one of the leading causes of morbidity and mortality. The research aimed to analyse and model the critical variables associated with malaria in endemic areas of Indonesia. So, this included relationships between malaria and both socio-demographic variables and physical environments. The research is in three parts, adding value to a model that determines malaria in Indonesia.
This dissertation follows a cross-sectional design survey. The research data in this PhD dissertation is drawn from four sources: routine reporting of malaria from provincial health departments in South Sumatra; the national basic health research data (IDN acronym: Riskesdas); climate data from the Meteorology, Climatology, and Geophysics Climatological Agency (IDN acronym: BMKG); spatial data from Geospatial Information Agency (IDN acronym: BIG). This study takes a holistic approach, integrating the following univariate, bivariate, and multivariable logistic regressions, to establish a modelling determinant of malaria. Additionally, the researchers compared the performance of both Geographically Weighted Regression (GWR) and Ordinary Least Square (OLS). It also used some statistical analysis software tools for data processing, analysis, visualisation, and the development of the model as follows: Statistical Package for the Social Sciences (SPSS), Stata, Aeronautical Reconnaissance Coverage Geographic Information System (ArcGIS) 10.3, and GWR 4.0 version 4.0.90 for Windows.
The prevalence of malaria varied according to the local area, which, in turn, was related to the local physical environment that varied geographically. The determinants for malaria cases varied locally and regionally as well. Rural areas with a high percentage of households keeping livestock/pets showed a higher proportion of malaria prevalence than the national average. Other socio-demographic risk factors included gender, age, occupation, knowledge about healthcare, protection against mosquito bites, and condition of dwellings. This study reveals that the independent variables - "rainfall", "altitude", and "distance from mosquito resting sites in the forest," in global OLS analysis- are significantly associated with malaria cases in South Sumatra, Indonesia.
On the other hand, in the GWR analysis, the determinants of malaria cases at the village level vary geographically. Therefore, it is essential for the decision maker, the government, to acquire a more in-depth understanding of region-specific, ecological factors that influence confirmed malaria cases. The findings lead to the recommendation for developing sustainable regional malaria control programs and incentivising malaria elimination efforts, particularly at the village level. In another setting, the research led to the conclusion that the presence of mid-sized livestock comprised a significant risk factor for contracting malaria in rural Indonesia. The recommendation, especially for the study area, is to employ integrated vector management (IVM), for example, the simultaneous implementation of insecticide-treated bed nets (ITNs) and insecticide-treated livestock (ITL). Other factors such as socio-demographic and use of health care facilities were also crucial as they related to malaria prevalence. Further, the research leads to the recommendation for increased education and increased promotion and utilisation of the health care framework to promote knowledge and awareness of villagers on how to protect themselves from Anopheles bites. Finally, improving information concerning the availability of health care services and access to various health facilities in endemic areas is essential.