Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses:A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory disease has only scarcely been studied in PCDLBCL-LT patients. Therefore, in this retrospective cohort study, 73 primary/pre-treatment and relapsed/refractory biopsies of 57 patients with PCDLBCL-LT were molecularly characterized with triple FISH and targeted next-generation sequencing for 52 B-cell-lymphoma-relevant genes, including paired analysis in 16 patients. In this cohort, 95% of patients harboured at least one of the three main driver alterations (mutations in MYD88/CD79B and/or CDKN2A-loss). In relapsed/refractory PCDLBCL-LT, these oncogenic aberrations were persistently present, demonstrating genetic stability over time. Novel alterations in relapsed disease affected mostly CDKN2A, MYC, and PIM1. Regarding survival, only MYC rearrangements and HIST1H1E mutations were statistically significantly associated with an inferior outcome. The stable presence of one or more of the three main driver alterations (mutated MYD88/CD79B and/or CDKN2A-loss) is promising for targeted therapies addressing these alterations and serves as a rationale for molecular-based disease monitoring, improving response evaluation and early identification and intervention of disease relapses in these poor-prognostic PCDLBCL-LT patients

Strain differentiation of polioviruses with monoclonal antibodies.

Panels of monoclonal antibodies raised against different poliovirus type 1, 2 and 3 strains, were tested in a micro-neutralization test and in a micro-enzyme linked immunosorbent assay against a large number of poliovirus strains. The results were compared with those obtained with the classical system of serodifferentiation using strain specific cross-absorbed antisera. For this purpose a theoretical pattern fitting computer program was developed, in which each strain could be compared with all the other strains of which the serological data had been stored in the memory of the computer. The results obtained with the panels of monoclonal antibodies coincided well with those obtained with the cross-absorbed antisera. Especially for the identification of virus isolates related to the Sabin vaccine strains, these panels of monoclonal antibodies proved to be valuable tools

The evaluation of a physical method for the quantification of inactivated poliovirus particles and its relationship to D-antigenicity and potency testing in rats.

The use of a density gradient procedure for the quantification of intact, inactivated poliovirus particles in vaccine preparations is described. The procedure is both sensitive and highly reproducible and the results correlate with those of potency tests in rats and with D-antigen content as measured by ELISA. Because of the occasional ambiguity observed with D-antigen assays, it is suggested that the density gradient procedure will provide valuable additional information for the in vitro assessment of inactivated poliovirus preparations

Production and potential use of monoclonal antibodies against polio viruses.

Lymphocyte hybridomas secreting monoclonal antibodies against different strains of polio virus type 1, 2, or 3 have been produced. For this purpose Balb/C mice were immunized with purified and inactivated virus suspensions and their splenocytes were fused with P3X63Ag8 mouse myeloma cells. Screening for antibody production was performed in an enzyme-linked immunosorbent assay (ELISA). Antibodies were produced either in cell culture or in Balb/C mice by passaging the hybridomas as solid or ascitic tumors, after they had been cloned at least three times by limiting dilutions in microtiter plates. Specificities of a number of these monoclonal antibodies were determined in the ELISA and in a neutralization test using different polio virus subtypes. The results indicate that for epidemiological studies monoclonal antibodies may prove to be very useful tools. Also the use of monoclonal antibodies for vaccine production (affinity chromatography; characterization of viral substructures) and routine vaccine control purpose (antigen quantification; neutralization of vaccine virus) seems attractive. Two of the neutralizing monoclonal antibodies against polio virus type 1, showed a selective immunoprecipitation with VP1, which suggests that VP1 is an important polypeptide for the induction of neutralizing antibody in vivo

Knowledge About Dementia Among Family Caregivers With a Turkish or Moroccan Immigrant Background: Development and Validation of a Dementia Knowledge Scale

Objective: To describe the development and validation of the Dementia Knowledge Scale (DKS) among family caregivers with a Turkish or Moroccan immigrant background. Methods: The 11 items of the DKS, selected by professionals and people with a Turkish or Moroccan background, were translated and adapted in Turkish and Dutch. The feasibility, comprehensibility and appropriateness of the 2 language versions were examined. Subsequently, both languages were assessed among caregivers from these groups. The internal consistency of both language versions was determined by calculating Cronbach’s α. The known group validity was determined by comparing mean scores between subgroups. Results: Both language versions of the DKS were considered feasible, comprehensible, and appropriate. A total of 117 caregivers with a Turkish background completed the Turkish version of the DKS and 110 with a Moroccan background the Dutch version. The Turkish version showed adequate internal consistency but the Dutch version did not. No differences were found in mean scores between those with a low level of education versus those with a higher level; those who frequently provided care versus those who did so less frequently; and those who lived together with a person with dementia versus those who did not. Conclusions: The DKS is feasible, comprehensible and reliable and can be used among groups with an immigrant background. Practice Implications: The DKS provides insight into various aspects of dementia knowledge, including knowledge about risk factors and symptoms, among caregivers with a Turkish or Moroccan background, and thereby supports the development of tailored education for these groups

Effects of an educational intervention on health-related quality of life among family caregivers of people with dementia with a Turkish or Moroccan immigrant background: Insights from a cluster randomised controlled trial.

Objective Gaining understanding of the health-related quality of life (HRQL) of family caregivers of people with dementia with Turkish or Moroccan immigrant backgrounds and to examine whether an educational peer group intervention can improve HRQL. Methods Understanding of HRQL and associated variables was obtained by multiple linear regression analyses. The effects of the intervention on HRQL were assessed in multilevel analyses using data collected before the start (baseline), directly after the intervention (one to two weeks after baseline) and three months after the start of the intervention. The intervention (two interactive group sessions) entailed providing information about dementia and care/support options. Results At baseline (n = 319), HRQL was moderately and significantly associated with migration background, gender, self-perceived pressure from informal care and the formal and informal support received (p < .05). The intervention had a small effect on emotional wellbeing directly after the intervention (p < .05) and on perceived general health status three months after (p < .05). Conclusion Culturally sensitive peer group education on dementia and care/support options can to some extent enhance HRQL among family caregivers in the short term. Practice implications The intervention as described in this study is recommended for supporting family caregivers of people with dementia with Turkish or Moroccan backgrounds

Explanatory models and openness about dementia in migrant communities: a qualitative study among female family carers

Background The prevalence of dementia is increasing among people with a Turkish, Moroccan and Surinamese-Creole background. Because informal care is very important in these communities, it is pertinent to see what explanations female family carers have for dementia and whether they can discuss dementia openly within the community and the family. Method Forty-one individual interviews and six focus group interviews (n = 28) were held with female Turkish, Moroccan and Surinamese Creole family carers who are looking after a close relative with dementia, and who live in The Netherlands. Qualitative analysis has been carried out, supported by the software MaxQda. Results The dominant explanations of dementia given by the female family carers interviewed are in line with what Downs et al. describe as the explanatory models ‘dementia as a normal ageing process’ and ‘dementia as a spiritual experience’. In addition, some female family carers gave explanations that were about an interplay between various factors. Turkish and Moroccan informal caregivers ascribe the causes of dementia relatively often to life events or personality traits, whereas Surinamese Creole caregivers frequently mention physical aspects, such as past dehydration. However, the explanatory model ‘dementia as a neuropsychiatric condition', which is dominant in Western cultures, was rarely expressed by the informal caregivers. The female family carers generally talked openly about the dementia with their close family, whereas particularly in the Turkish and Moroccan communities open communication within the broader communities was often hampered, e.g. by feelings of shame. Conclusions Female family carers of Turkish, Moroccan or Surinamese Creole backgrounds often consider dementia as a natural consequence of ageing, as a spiritual experience, and/or as an interplay between various factors. They feel they can talk openly about dementia within their close family, while outside the close family this is often more difficult

Family care for immigrants with dementia: The perspectives of female family carers living in the Netherlands

Background: The prevalence of dementia is increasing among non-western immigrants. It is known that family care is provided relatively often among immigrant groups. Until now, however, relatively little was known about how relatives of people with dementia in the immigrant communities perceive family care. This study therefore focuses on describing the perspectives of female Turkish, Moroccan and Surinamese Creole family carers in the Netherlands about providing family care to a close relative with dementia. Methods: Forty-one individual interviews and six focus group interviews (n=28) were held with female Turkish, Moroccan and Surinamese Creole family carers who are looking after a close relative with dementia. A qualitative analysis of the interviews has been carried out, supported by the software MaxQda. Results: Related to their cultural and religious backgrounds, female family carers with Turkish, Moroccan or Surinamese Creole origins see family care as a task that they should carry out with respect and love. They feel that family care is superior to professional care and that it is principally a task for women. If men do have a role in family care, then it generally covers non-physical aspects. Despite the fact that the family carers interviewed listed aspects that make caring for a close relative with dementia difficult, they do say that they get a great deal of satisfaction from providing this care. In Turkish and Moroccan families in particular this type of care leads to more recognition and appreciation of the daughter or daughter-in-law who is giving it. Conclusion: Family carers of Turkish, Moroccan or Surinamese Creole origin derive a great deal of satisfaction from giving family care to a relative with dementia. This fulfilment largely outweighs the burden of care. Professional support or information for these family carers can be improved by also focusing on the positive aspects of providing family care instead of an exclusive focus on reducing the burden