Dutch translation and cultural adaptation of new LYMPH-Q- scales measuring impact on work and lymphedema worry

Background: Breast cancer-related lymphedema (BCRL) is a significant complication of breast cancer treatment that can impact patients’ quality of life. This study focuses on the translation and cultural adaptation of two new LYMPH-Q scales ‘Impact on Work’ and ‘Lymphedema worry’ into Dutch to assess the work-related challenges and worries experienced by patients with BCRL in the Netherlands. Methods: The translation process followed established guidelines from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the World Health Organization (WHO). Forward and back translations, expert panel reviews, cognitive debriefing interviews with patients with BCRL, and proofreading were conducted to refine the Dutch translation of the scales. The translation aimed to ensure conceptual equivalence and cultural relevance. Results: The translation process resulted in the Dutch versions of the LYMPH-Q ‘Impact on Work’ and ‘Lymphedema worry’ scales. The forward translation revealed discrepancies in meaning, word order and synonyms. The back translation and review resulted in changes in item formulation. The expert panel meeting and cognitive debriefing interviews provided valuable input for further refinement. Conclusion: The translated LYMPH-Q ‘Impact on Work’ and ‘Lymphedema worry’ scales provide healthcare professionals with an instrument to assess and monitor the impact of BCRL on work-related challenges and on worries. This comprehensive translation process, involving patients with BCRL and experts, ensured the linguistic accuracy, cultural relevance, and clarity of the Dutch versions. The translated scales will contribute to a better understanding of the multifaceted impact of BCRL and facilitate the development of tailored interventions to improve patients’ well-being and functional outcomes.</p

Dutch translation and cultural adaptation of new LYMPH-Q- scales measuring impact on work and lymphedema worry

Background: Breast cancer-related lymphedema (BCRL) is a significant complication of breast cancer treatment that can impact patients’ quality of life. This study focuses on the translation and cultural adaptation of two new LYMPH-Q scales ‘Impact on Work’ and ‘Lymphedema worry’ into Dutch to assess the work-related challenges and worries experienced by patients with BCRL in the Netherlands. Methods: The translation process followed established guidelines from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the World Health Organization (WHO). Forward and back translations, expert panel reviews, cognitive debriefing interviews with patients with BCRL, and proofreading were conducted to refine the Dutch translation of the scales. The translation aimed to ensure conceptual equivalence and cultural relevance. Results: The translation process resulted in the Dutch versions of the LYMPH-Q ‘Impact on Work’ and ‘Lymphedema worry’ scales. The forward translation revealed discrepancies in meaning, word order and synonyms. The back translation and review resulted in changes in item formulation. The expert panel meeting and cognitive debriefing interviews provided valuable input for further refinement. Conclusion: The translated LYMPH-Q ‘Impact on Work’ and ‘Lymphedema worry’ scales provide healthcare professionals with an instrument to assess and monitor the impact of BCRL on work-related challenges and on worries. This comprehensive translation process, involving patients with BCRL and experts, ensured the linguistic accuracy, cultural relevance, and clarity of the Dutch versions. The translated scales will contribute to a better understanding of the multifaceted impact of BCRL and facilitate the development of tailored interventions to improve patients’ well-being and functional outcomes.</p

Hair Follicle Mesenchyme-Associated PD-L1 Regulates T-Cell Activation Induced Apoptosis: A Potential Mechanism of Immune Privilege

The immune privilege (IP) of hair follicles (HFs) has been well established in previous studies. However, whether cultured HF cells still exhibit IP properties, the individual factors involved in this process, and the detailed mechanisms that drive and maintain IP, are largely unidentified. We found preferential expression of IP-associated genes in cultured HF dermal papilla and dermal sheath cup cells (DSCCs) compared with non-follicular fibroblasts (FBs) at passage 4, suggesting a potential for functional IP. Notably, programmed cell death 1 ligand 1 (PD-L1) was significantly upregulated in DSCCs and dermal papilla cells relative to FBs. IFNγ secretion from peripheral blood mononuclear cells (PBMCs) co-cultured with histoincompatible DSCCs was significantly lower than with FB and higher percentages of early apoptotic, Annexin V+ cells were observed in PBMC co-cultured with DSCCs. Knockdown of PD-L1 translation by silencing interfering RNA in DSCCs enabled increased IFNγ secretion by PBMCs, whereas transfection of pCMV6-XL4/hPD-L1 in FB significantly reduced IFNγ secretion and increased apoptosis in co-cultured PBMCs. We also found that apoptosis in allogeneic T cells induced by DSCCs was largely dependent on the mitochondrial pathway. Our study suggests IP properties are exhibited in cultured DSCCs in part through expression of negative co-signaling molecule PD-L1

Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P<0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation

The role of somatostatin expression in hair follicle immune privilege

The hair follicle is a mini-organ, consisting of many different types and groups of cells, capable of frequent remodeling and cycles of growth. Immune privilege (IP) is believed to exist in the anagen growth stage of the hair follicle (HF). Previous studies using immunohistology have illustrated unique downregulation of major histocompatibility complex Class I in the HF bulb, as well as expression of immunosuppressive factors in the bulge region. However, quantitative studies and functional studies to clearly demonstrate IP in HF cells are required. My goal was to examine the middle (hair fiber and sheaths) and lower (bulb) portion of the human HF to identify a novel functional mechanism of IP. My hypothesis was that the bulb and the middle third of the hair follicle have functional immune privilege capabilities. In an in vitro experiment, I found that HF cells appeared to suppress histo-incompatible peripheral blood mononuclear cell (PBMC) IFN-gamma secretion relative to epidermal cells. I screened expression of IP-related genes in HFs relative to interfollicular epidermis by quantitative real-time RT-PCR. Briefly, I found significant downregulation of all Class I and Class II HLAs examined in the bulb and sheaths. There were also several genes coding for immunosuppressant secretory factors significantly upregulated in the sheath. Most notably, somatostatin (SST) was significantly upregulated in the sheath 5.9-fold and in the bulb 94.2-fold relative to non-follicular epidermis. This led me to investigate the hypothesis that SST contributes to IP in hair follicles. I found strong expression of SST in the outer root sheath by immunohistochemistry and significant secretion of SST from HF sheath cells compared to epidermal cells in culture. PBMCs cultured with allogeneic immuno-stimulatory epidermal cells and SST secreted significantly less IFN-gamma than controls. Additionally, a SST antagonist drug appeared to interfere with the immunosuppressive effect of sheath cells in culture with allogeneic PBMCs. In summary, these experiments give further evidence in support of HF IP and show that HF bulb or sheath cells may be beneficial in allogeneic transplantation. In principle, SST may have potential as a treatment for scarring alopecia or other inflammatory hair loss disorders.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat

CCAAT-enhancer binding protein-β expression and elevation in Alzheimer's disease and microglial cell cultures.

CCAAT-enhancer binding proteins are transcription factors that help to regulate a wide range of inflammatory mediators, as well as several key elements of energy metabolism. Because C/EBPs are expressed by rodent astrocytes and microglia, and because they are induced by pro-inflammatory cytokines that are chronically upregulated in the Alzheimer's disease (AD) cortex, we have investigated whether C/EBPs are expressed and upregulated in the AD cortex. Here, we demonstrate for the first time that C/EBPβ can be detected by Western blots in AD and nondemented elderly (ND) cortex, and that it is significantly increased in AD cortical samples. In situ, C/EBPβ localizes immunohistochemically to microglia. In microglia cultured from rapid autopsies of elderly patient's brains and in the BV-2 murine microglia cell line, we have shown that C/EBPβ can be upregulated by C/EBP-inducing cytokines or lipopolysaccharide and exhibits nuclear translocation possibly indicating functional activity. Given the known co-regulatory role of C/EBPs in pivotal inflammatory mechanisms, many of which are present in AD, we propose that upregulation of C/EBPs in the AD brain could be an important orchestrator of pathogenic changes

C/EBPβ confocal fluorescent immunocytochemistry in human microglia cultures.

<p>Parallel wells received (A) no cytokine treatment or 50 ng/ml (B) IL-1β, (C) IL-6, or (D) TNF-α for 4 hours. Microglia treated with cytokines show increased expression and nuclear localization of C/EBPβ. All wells were imaged concurrently with the same photomultiplier tube intensity, gain, and offset settings using an Olympus Fluoview Confocal microscope–200X (scale bar = 100 µm).</p

Further psychometric validation of the BODY-Q: ability to detect change following bariatric surgery weight gain and loss

Abstract Background Recent systematic reviews have identified that current patient-reported outcome instruments have content limitations when used to measure change following bariatric surgery. The aim of this study was to measure change after bariatric surgery using the BODY-Q, a PRO instrument designed for weight loss and body contouring. Methods The BODY-Q is composed of 18 independently functioning scales and an obesity-specific symptom checklist that measure appearance, health-related quality of life (HR-QOL) and experience of health-care. The sample for this study included patients who were exploring or seeking bariatric surgery in Hamilton (Canada) at the time of the BODY-Q field-test study and who agreed to further contact from the research team. These patients were invited to complete 12 BODY-Q scales and the symptom checklist between 7 June 2016 and 29 November 2016. Data were collected online (REDCap) and via postal surveys. Clinical change was measured using paired t-tests with effect sizes and standardized response means. Results The survey was completed by 58 of 89 (65%) pre-bariatric participants from the original BODY-Q field-test sample. The non-participants did not differ from participants in terms of age, gender, ethnicity, BMI or initial BODY-Q scale scores. Participants who had undergone bariatric surgery had a mean BMI of 49 (SD = 7) at time 1 and 35 (SD = 7) at time 2. Time since bariatric surgery was on average 2 years (SD = 0.5) (range 0.4 to 3 years). Percentage total weight loss ranged from 12 to 51 (mean 31, SD = 9). The difference in the proportion of patients to report an obesity-specific symptom on the BODY-Q checklist was significantly lower at follow-up for 5 of 10 symptoms. Participants improved on BODY-Q scales measuring appearance (of abdomen, back, body, buttocks, hips/outer thighs, inner thigh), body image and physical function (p < 0.001 on paired t-tests) and social function (p = 0.002 on paired t-test). These changes were associated with moderate to large effect sizes (0.60 to 2.29) and standardized response means (0.47 to 1.35). Conclusions The BODY-Q provides a set of independently functioning scales that measure issues important to patients who undergo weight loss. BODY-Q scales were responsive to measuring clinical change associated with weight loss 2 years after bariatric surgery

C/EBPβ Western blots in AD and ND frontal lobe gray matter.

<p>When normalized to β-actin, the data show a significant increase in C/EBPβ protein expression in AD compared to ND samples (t₁₆ = 2.9, P<0.01). Summary densitometry data for the blots (mean ratios of C/EBPβ/β-actin integrated optical density values, IDV) are provided in the bottom panel.</p

C/EBPβ immunocytochemistry of cultured murine BV-2 cell line.

<p>C/EBPβ is increased both in numbers of immunopositive cells and in intensity of fluorescence in the nucleus of cells treated with (B) 1 µg/ml LPS as compared with (A) controls (scale bar = 10 µm). Some control cells were positive for C/EBPβ but the immunofluorescence was notably less intense. The average mean gray value of pixels in LPS treated cells (51.14±3.15, SEM) was significantly higher than the control (38.45±1.86, SEM) (P<0.05). Integrated density in LPS treated cells (6.87±0.42, SEM) was also significantly higher than the control (4.23±0.31, SEM) (P<0.01).</p