Preferences of People Living with HIV for Long-Acting Antiretroviral Treatment in Germany: Evidence from a Discrete Choice Experiment.

OBJECTIVE: This study aimed to elicit preferences for attributes of current and novel long-acting antiretroviral therapy for human immunodeficiency virus treatment. METHODS: Primary survey data were collected (July-October 2022) on a sample of 333 people living with human immunodeficiency virus in Germany from a patient recruitment agency. Respondents were invited by e-mail to respond to a web-based questionnaire. After performing a systematic literature review, we conducted qualitative semi-structured interviews to identify and select the key attributes of drug therapy for patients' preferences for human immunodeficiency virus treatment. Based on this, a discrete choice experiment survey elicited preferences for long-acting antiretroviral therapy characteristics, including the type of medication, frequency of dosing, the location of treatment, the risk of both short-term and long-term side effects, as well as possible interactions with other medications or (party) drugs. A statistical data analysis was performed using multinomial logit models. An additional latent class multinomial logit was performed to evaluate subgroup differences. RESULTS: Overall, 226 respondents (86% male, mean age 46.1 years) were included in the analysis. The frequency of dosing (36.1%) and the risk of long-term side effects (28.2%) had the greatest influence on preferences. The latent class analysis identified two patient groups. While the first class (n = 135; 87% male, mean age 44.4 years) found the frequency of dosing (44.1%) to be most important, the second class (n = 91; 85% male, mean age 48.6 years) focused on the risk of long-term side effects (50.3%). The evaluation of structural variables showed that male respondents, those living in small cities or villages, and those with better health status results were significantly more likely to be assigned to the second class (p < 0.05 each). CONCLUSIONS: All attributes included in our survey were important to participants when choosing an antiretroviral therapy. We found evidence that the frequency of dosing as well as the risk of long-term side effects have a particular impact on the acceptance of novel therapy regimens and should be considered in order to optimize adherence and satisfaction.

[Specific Workloads among Employees with a Migration Background in Nursing and Geriatric Care: A Systematic Review]. / Spezifische Arbeitsbelastungen bei Mitarbeitenden mit Migrationshintergrund in der Kranken- und Altenpflege: Ein systematisches Review.

BACKGROUND: Multimorbidity, increasing numbers of chronically ill patients and demographic change are leading to increased care costs in Germany with an increasing shortage of staff in skilled nursing and geriatric care. In this context, more and more caregivers with a migration background of the 1st generation (PmMH) are being recruited and integrated into existing (corporate) cultures. This represents an important starting point for a permanent and needs-based supply landscape. THE AIM OF THE STUDY: The aim of the study was to identify and analyze the specific stresses of PmMH at the workplace in nursing and geriatric care MATERIAL AND METHODS: A systematic literature search was carried out in relevant specialist databases (Pubmed, PsychInfo, Web of Science, Cochrane), supplemented by an extended snowball and hand search. This was followed by a descriptive presentation of the results of the study content, which in a subsequent step was iteratively brought together and consolidated into thematic categories by several people. RESULTS: A total of 15 publications were identified as relevant and included in the analysis. Specific, migration-associated stress factors could be identified. In particular, the categories: "Discrimination and racism", "Language and communication problems" and "Cultural adjustment" characterized the (collaborative) work in nursing and care for the elderly and led to additional stress for employees and patients. DISCUSSION: The present review article identified and summarized specific burdens of PmMH. At this point it can be assumed that these affect both PmMH and patients. So far, operational concepts do not seem to be able to adequately solve the challenges, so that effective, sustainable approaches have to be found. The extent to which the specificed stress factors only affect PmMH is not considered in this context, so that further research is needed.

Exogenous expression of synaptotagmin XIII suppresses the neoplastic phenotype of a rat liver tumor cell line through molecular pathways related to mesenchymal to epithelial transition.

The molecular pathogenesis of hepatocellular carcinoma is well-studied but not completely understood. We utilized a microcell-hybrid model of tumor suppression in rat liver tumor cells to facilitate the identification of liver tumor suppressor genes located on human chromosome 11. These investigations confirmed a liver tumor suppressor locus at human 11p11.2, identified Wt1 as a potential effector of 11p11.2-mediated tumor suppression, and subsequently identified human SYT13 as a strong candidate for the 11p11.2 liver tumor suppressor gene. In the studies presented here, we introduced SYT13 into the GN6TF rat liver tumor cell line to characterize a functional role for SYT13 in this model system. Transfected clones expressing an SDS-resistant dimer form of the SYT13 protein displayed induction of Wt1 gene expression and a significant attenuation of the neoplastic phenotype exhibited by the parental tumor cell line. Saturation densities and anchorage-independent growth of SYT13 dimer-positive cell lines were reduced in vitro, and tumorigenicity was significantly decreased or ablated in syngeneic host rats in vivo. In addition, restoration of the contact-inhibited, epithelioid morphology observed in normal liver epithelial cells accompanied ectopic expression of the SYT13 protein dimer, suggesting that SYT13 may be mediating an epithelial differentiation coordinate with tumor suppression in these cells. Accordingly, the expression of E-cadherin (Cdh1) mRNA was increased >100-fold in SYT13-dimer-positive cell lines and the Cdh1 transcriptional repressor Snail was decreased >3-fold in these cells compared to the parental tumor cells. These studies combine to suggest that SYT13 is a liver tumor suppressor gene and that its function may be mediated through pathways implicated in mesenchymal to epithelial transition.

Insertion (12;9)(p13;q34q34): a cryptic rearrangement involving ABL1/ETV6 fusion in a patient with Philadelphia-negative chronic myeloid leukemia.

We report a rare cryptic ins(12;9)(p13;q34q34), a chromosomal abnormality involving the ABL1 (9q34) and the ETV6 (alias TEL; 12p13) genes, detectable only by fluorescence in situ hybridization (FISH), in a patient with Philadelphia-negative chronic myeloid leukemia (CML). Using reverse 4',6-diamidino-2-phenylindole banding on metaphase cells, FISH analysis with BCR/ABL dual-fusion and ETV6 break-apart probes showed that a third ABL signal was inserted into 12p, splitting the ETV6 signal into two adjacent signals. CML patients with an ABL1/ETV6 fusion historically have demonstrated a variable and sometimes transient response to treatment with imatinib mesylate, which was also the case in the present patient.

Re-expression of tumorigenicity after attenuation of human synaptotagmin 13 in a suppressed microcell hybrid cell line.

Human chromosome 11p11.2 contains a putative liver tumor suppressor locus that was identified using a microcell hybrid cell line-based model of tumor suppression. Transcription mapping of suppressed microcell hybrid cell lines suggests that human SYT13 represents a strong candidate for the 11p11.2 tumor suppressor gene. Other evidence suggests that the putative 11p11.2 tumor suppressor gene (SYT13 or some other) may modulate the tumorigenic potential of neoplastic liver cell lines through direct or indirect regulation of the rat Wt1 tumor suppressor gene. To characterize a functional role for SYT13 in liver tumor suppression, we employed RNAi to attenuate SYT13 expression in a suppressed microcell hybrid cell line (GN6TF-11neoCX4). SYT13-attenuated cells display aggressive phenotypic properties that are similar to or indistinguishable from the parental tumor cells (GN6TF), including altered cellular morphologies, disrupted contact inhibition, elevated saturation densities, restoration of anchorage-independent growth and increased tumorigenicity in vivo. Moreover, SYT13 attenuation and re-expression of tumorigenicity in GN6TF-11neoCX4-derived cell lines was accompanied by a significant decrease of Wt1 expression. In contrast, the phenotypic properties of scrambled-control cells were similar to the suppressed microcell hybrid cells and Wt1 expression was unaffected. These observations combine to establish that: i) human SYT13 functions as a liver tumor suppressor gene that complements a molecular defect in GN6TF rat liver tumor cells resulting in a normalized cellular phenotype in vitro and suppression of tumorigenicity in vivo; ii) RNAi-mediated attenuation of SYT13 expression restores the neoplastic phenotype of GN6TF-11neoCX4 microcell hybrid cells, consistent with the function of a liver tumor suppressor gene; and iii) loss of Wt1 expression is important for the re-establishment of tumorigenic potential by GN6TF-11neoCX4 microcell hybrid cells after attenuation of SYT13.

Variant acute promyelocytic leukemia translocation (15;17) originating from two subsequent balanced translocations involving the same chromosomes 15 and 17 while preserving the PML/RARA fusion.

Fluorescence in situ hybridization (FISH) analysis of the bone marrow of a 24-year-old man diagnosed with acute promyelocytic leukemia (APL) revealed a variant pattern with one fusion signal instead of the typical two fusions expected with the probe set used. The combined FISH and conventional chromosome analyses suggested that two subsequent translocations had occurred in this patient involving the same chromosomes 15 and 17. As the prognostic outcome in APL is strictly associated with the presence of a PML/RARA fusion, it is useful and necessary to perform both cytogenetic and FISH analyses of a variant t(15;17) to determine the status of the PML/RARA fusion.

Isolated del(14)(q21) in a case of precursor B-cell acute lymphoblastic leukemia.

We present a case of del(14)(q21) as a sole abnormality in a 4-year-old boy diagnosed with precursor B-cell acute lymphoblastic leukemia (pre-B ALL). To our knowledge, this is the first case of isolated del(14)(q21) in pre-B ALL. Two pretreatment bone marrow samples obtained 5 days apart were analyzed by cytogenetics. The G-banded karyotypes of the two samples were similar, differing only in the ratio of normal/abnormal metaphases detected. Both samples showed a del(14)(q21) as the only abnormality. Fluorescence in situ hybridization performed using the probes TEL/AML1 and immunoglobulin heavy chain (IGH) showed no fusion involving the TEL and AML1 genes and only a single IGH signal in 20% of the interphase cells analyzed.

Proteinase 3 sidesteps caspases and cleaves p21(Waf1/Cip1/Sdi1) to induce endothelial cell apoptosis.

BACKGROUND: Emerging data raise possibilities of a complex and specific biologic role for leukocyte-derived proteases in substrate processing and in signaling pathways. Neutrophil proteinase 3 (PR3) is a caspase-like protease that enters endothelial cells, cleaves nuclear factor-kappaB (NF-kappaB), and induces sustained JNK activation, implying that the major cell cycle inhibitor p21 may be inactivated. Cleavage of p21 by caspase-3 is reported to be required for endothelial cell apoptosis. We hypothesized that PR3 may target p21. METHODS: Human umbilical vein endothelial cells (HUVEC) were treated with or without PR3 (5 microg/mL) from 0 hours or up to 8 hours, and analyzed for changes in cell cycle control proteins by immunoblotting, immunofluorescence and flow cytometry. RESULTS: PR3 exposure resulted in cleavage of p21 between Thr80 and Gly81, loss of nuclear p21 by cytoplasmic sequestration and depletion of p21 from cyclin/cyclin-dependent kinase (CDK) complexes. Examination of cyclins D and E, p53, Rb, and p27 revealed a largely nonproliferative expression profile. Cells arrested in G1 were more susceptible to PR3 effects. We examined inflamed human colonic tissue and found a fragment similar in size to that generated by PR3 in HUVEC. Granzyme B, a T-cell homologue of PR3 that cleaves caspase substrates, also cleaves p21 between Asp62 and Phe63. A reported substrate of granzyme B and caspases, Bid, is cleaved by PR3 signifying commonality of substrates among these proteases. CONCLUSION: A theme is developing that the granulocyte protease, PR3, is an exogenous caspase-like molecule that can sidestep intracellular caspase functions at sites of inflammation.

Identification of candidate liver tumor suppressor genes from human 11p11.2 by transcription mapping of microcell hybrid cell lines.

Our previous studies utilized a microcell hybrid (MCH) cell line-based functional model of tumor suppression to localize a liver tumor suppressor to human chromosome 11, map the suppressor locus to a <1-Mb region within human 11p11.2, and identify a number of expressed sequence tags (ESTs) and genes that represent candidate liver tumor suppressor genes. The Human Genome Project has recently positioned a number of additional genes, ESTs, and predicted genes within the human 11p11.2 liver tumor suppressor region. In this study, we analyzed 26 ESTs and genes (known and predicted) that have been localized to human 11p11.2. Four of these ESTs/genes (FLJ23598, FLJ10450, KIAA1580, SYT13) mapped to the minimal tumor suppressor region of human 11p11.2, the smallest region conferring suppression of tumorigenicity in the MCH cell lines. Each of these ESTs/genes were expressed among an index panel of suppressed MCH cell lines (derived from GN6TF rat liver tumor cells), suggesting that these ESTs/genes represent excellent candidates for the human 11p11.2 liver tumor suppressor gene. To verify the candidate status of these sequences, 8 additional MCH cell lines (derived from GN3TG and GP10TA rat liver tumor cells) were analyzed. Three ESTs/genes (FLJ23598, FLJ10450, KIAA1580) proved to be less than ideal candidates, based upon their loss from suppressed MCH cell lines (DNA deletion), and/or their retention and expression in a non-suppressed MCH cell line. In contrast, SYT13 is present in the DNA from all suppressed MCH cell lines (n=10), and is deleted in a non-suppressed MCH cell line. Furthermore, SYT13 mRNA is expressed in 100% of suppressed cell lines, and is not expressed in the non-suppressed MCH cell line or in MCH-derived tumor cell lines (n=6). These results suggest that SYT13 is an excellent candidate for the human 11p11.2 liver tumor suppressor gene based upon its: i) location within the human 11p11.2 liver tumor suppressor region; ii) loss from the DNA of a non-suppressed MCH cell line that lacks the human 11p11.2 liver tumor suppressor region; iii) expression among suppressed MCH cell lines; and iv) lack of expression by MCH-derived tumor cell lines.