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Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in children and adolescents. Respecting the age of the patients and the tumor aggressiveness, investigation of the molecular mechanisms of RMS tumorigenesis is directed toward the identification of novel therapeutic targets. To contribute to a better understanding of the molecular pathology of RMS, we investigated ankyrin repeat domain 1 (ANKRD1), designated as a potential marker for differential diagnostics. In this study, we used three RMS cell lines (SJRH30, RD, and HS-729) to assess its expression profile, intracellular localization, and turnover. They express wild-type ANKRD1, as judged by the sequencing of the open reading frame. Each cell line expressed a different amount of ANKRD1 protein, although the transcript level was similar. According to western blot analysis, ANKRD1 protein was expressed at detectable levels in the SJRH30 and RD cells (SJRH30 > RD), but not in the HS-729, even after immunoprecipitation. Immunocytochemistry revealed nuclear and cytoplasmic localization of ANKRD1 in all examined cell lines. Moreover, the punctate pattern of ANKRD1 staining in the nuclei of RD and HS-729 cells overlapped with coilin, indicating its association with Cajal bodies. We have shown that RMS cells are not able to overexpress ANKRD1 protein, which can be attributed to its proteasomal degradation. The unsuccessful attempt to overexpress ANKRD1 in RMS cells indicates the possibility that its overexpression may have detrimental effects for RMS cells and opens a window for further research into its role in RMS pathogenesis and for potential therapeutic targeting., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Prolonged bleeding from arteriovenous fistulas (AVF) and arteriovenous grafts (AVG) associates with worse outcomes; Within the hemodialysis unit these outcomes include anemia and quality of life disruptions, and outside the hemodialysis unit includes fatal hemorrhage. However, various guidelines for AVF/AVG bleeding management inside and outside the hemodialysis unit lack consensus., Methods: A scoping review was conducted of four databases, from inception to 17 February 2024. The study population was hemodialysis patients experiencing bleeding from AVF or AVG. Studies that assessed non-operative management were included., Results: Sixteen studies met inclusion criteria. Most (14/16) addressed post-cannulation bleeding from AVF/AVG within the dialysis unit. Compared with standard dressings, hemostatic dressings (chitosan-, cellulose- or thrombin-based) decreased post-cannulation bleeding time at arterial and venous site 35.7%-84.0% ( P  < .05) and 38.5%-78.7% ( P  < .05), respectively. Use of chitosan-based dressings decreased percentage of patients bleeding 4-min post-cannulation by 16.3%-39.2%. One pilot observational study demonstrated no access thromboses or infections with short-term use of a compression device within the hemodialysis unit. However, the role of compression devices and tourniquets within the dialysis unit remains unclear, despite widespread use. Long-term AVF/AVG survival was not reported in any study. Limited research confirms that devices are effective in prevention of catastrophic out-of-hospital bleeding. It remains uncertain if device availability enhances patient confidence in managing out-of-hospital bleeding. This may impact patient choices around dialysis modality, access and transplant, but this remains uncertain., Conclusions: In hemodialysis patents with bleeding from AVF/AVG, several alternative dressings or devices decrease post-cannulation bleeding time within the hemodialysis unit. Existing research has not established criteria on when it might be appropriate to use specialized dressings. There is very limited research on methods to control bleeding from AVF/AVG outside the hemodialysis unit. More data are required before evidence-based guidelines can be made. Recommendations for future research are provided., Competing Interests: B.T., A.F. and E.M. have completed unpaid work with Glia Inc., a not-for-profit organization that makes low-price, open-sourced medical devices for low- and middle-income countries. Glia Inc. is currently developing a device to manage post-cannulation bleeding, and this study was completed as part of the preparation for device development., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Purpose: Sarcomas are rare and heterogenic tumors with unclear etiology. They develop in bone and connective tissue, mainly in pediatric patients. To increase efficacy of current therapeutic options, natural products showing selective toxicity to tumor cells are extensively investigated. Here, we evaluated antitumor activity of bacterial pigment violacein in osteosarcoma (OS) and rhabdomyosarcoma (RMS) cell lines., Methods: The toxicity of violacein was assessed in vitro and in vivo, using MTT assay and FET test. The effect of violacein on cell migration was monitored by wound healing assay, cell death by flow cytometry, uptake of violacein by fluorescence microscopy, generation of reactive oxygen species (ROS) by DCFH-DA assay and lipid peroxidation by TBARS assay., Results: Violacein IC 50 values for OS and RMS cells were in a range from 0.35 to 0.88 µM. Its selectivity toward malignant phenotype was confirmed on non-cancer V79-4 cells, and it was safe in vivo, for zebrafish embryos in doses up to 1 µM. Violacein induced apoptosis and affected the migratory potential of OS and RMS cells. It was found on the surfaces of tested cells. Regarding the mechanism of action, violacein acted on OS and RMS cells independently of oxidative signaling, as judged by no increase in intracellular ROS generation and no lipid peroxidation., Conclusion: Our study provided further evidence that reinforces the potential of violacein as an anticancer agent and candidate to consider for improvement of the effectiveness of traditional OS and RMS therapies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Innate and adaptive immune responses exert their role in CIDP pathogenesis through cytokine production. Single-nucleotide polymorphisms (SNPs) may alter cytokine gene expression, with a potential influence on the pathogenesis of autoimmune diseases. However, cytokine gene SNPs have not been assessed in CIDP patients yet. We assessed functional SNPs in the genes encoding IL-10 (rs1800896, rs1800871, rs1800872 and rs3024505), IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227), IFN-γ (rs2430561), GM-CSF (rs25882) and IL-17F (rs11465553) in a cohort of 88 CIDP patients and 486 healthy controls (HCs) via qPCR. We found an association of SNP in the IL10 promotor and CIDP occurrence. Major homozygotes (AA) were more frequent in the HCs compared to CIDP patients ( p = 0.049), but the GA genotype prevailed among the patients ( p = 0.032). A lower frequency of the C allele was observed for rs1800871 and rs1800872 in CIDP patients compared to the HCs ( p = 0.048). A higher proportion of A carriers at position -1082 (rs1800896) (presumed to be a low IL-10 producer) was noted in patients with milder disability (low INCAT). All mild-INCAT patients were C carriers for rs1800871 and rs1800872 in IL10 ( p = 0.038). Furthermore, the IL6 rs1800795 GG genotype was more frequent in patients ( p = 0.049) and the CG heterozygote in the HCs ( p = 0.013). Among the CIDP patients, being a G carrier for this SNP was associated with a higher frequency of type 2 diabetes (T2D) compared to being a non-carrier ( p = 0.032). Our data indicate a possible association of the IL10 and IL6 SNPs with CIDP, but also with disease severity and T2D occurrence. Given the paucity of CIDP patients, multicentric studies are necessary to draw definite conclusions on these associations.

AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolic and immune functions mainly through the inhibition of the mechanistic target of rapamycin (mTOR)-dependent anabolic pathways and the activation of catabolic processes such as autophagy. The AMPK/mTOR signaling pathway and autophagy markers were analyzed by immunoblotting in blood mononuclear cells of 20 healthy control subjects and 23 patients with an acute demyelinating form of Guillain-Barré syndrome (GBS). The activation of the liver kinase B1 (LKB1)/AMPK/Raptor signaling axis was significantly reduced in GBS compared to control subjects. In contrast, the phosphorylated forms of mTOR activator AKT and mTOR substrate 4EBP1, as well as the levels of autophagy markers LC3-II, beclin-1, ATG5, p62/sequestosome 1, and NBR1 were similar between the two groups. The downregulation of LKB1/AMPK signaling, but not the activation status of the AKT/mTOR/4EBP1 pathway or the levels of autophagy markers, correlated with higher clinical activity and worse outcomes of GBS. A retrospective study in a diabetic cohort of GBS patients demonstrated that treatment with AMPK activator metformin was associated with milder GBS compared to insulin/sulphonylurea therapy. In conclusion, the impairment of the LKB1/AMPK pathway might contribute to the development/progression of GBS, thus representing a potential therapeutic target in this immune-mediated peripheral polyneuropathy., Competing Interests: The authors declare no conflict of interest. The sponsors had no role in the design, execution, interpretation, or writing of the study.

Achieving the World Health Organisation (WHO) cervical cancer elimination target of fewer than four new cases per 100,000 woman-years requires scaling up HPV vaccination of girls, cervical screening, and pre-cancer and cancer treatment. We reviewed data from four high-income colonised countries (Australia, Canada, Aotearoa New Zealand (NZ), and the United States (US)) to identify how each is currently performing compared to the cervical cancer incidence elimination and triple-intervention targets, nationally and in Indigenous women. We also summarise barriers and enablers to meeting targets for Indigenous women. To achieve elimination, cervical cancer incidence must be reduced by 74% in Indigenous women in Australia, and 63% in Maori women in NZ; data were not published in sufficient detail to compare incidence in Indigenous women in Canada or the US to the WHO target. Only Australia meets the vaccination coverage target, but uptake appears comparatively equitable within Australia, NZ and the US, whereas there appears to be a substantial gap in Canada. Screening coverage is lower for Indigenous women in all four countries though the differential varies by country. Currently, only Australia universally offers HPV-based screening. Data on pre-cancer and cancer treatment were limited in all countries. Large inequities in cervical cancer currently exist for Indigenous peoples in Australia, Canada, New Zealand and the US, and elimination is not on track for all women in these countries. Current data gaps hinder improvements. These countries must urgently address their systemic failure to care and provide health care for Indigenous women., (Copyright © 2020. Published by Elsevier Inc.)

Striated muscle signaling protein and transcriptional regulator ANKRD2 participates in myogenesis, myogenic differentiation, muscle adaptation and stress response. It is preferentially expressed in slow, oxidative fibers of mammalian skeletal muscle. In this study, we report on characterization of chicken ANKRD2. The chicken ANKRD2 coding region contains 1002 bp and encodes a 334-amino acid protein which shares approximately 58% identity with human and mouse orthologs, mostly in the conserved region of ankyrin repeats. Comprehensive analysis of the ANKRD2 gene and protein expression in adult chicken demonstrated its predominant expression in red muscles of thigh and drumstick, compared to white muscle. It was not detected in heart and white pectoral muscle. Uneven expression of ANKRD2 in chicken skeletal muscles, observed by immunohistochemistry, was attributed to its selective expression in slow, oxidative, type I and fast, oxidative-glycolytic, type IIA myofibers. Association of chicken ANKRD2 with phenotypic differences between red and white muscles points to its potential role in the process of myofiber-type specification. In addition to expression in slow oxidative myofibers, as demonstrated for mammalian protein, chicken ANKRD2 was also detected in fast fibers with mixed oxidative and glycolytic metabolism. This finding suggests that ANKRD2 is responsive to metabolic differences between types of avian myofibers and orientates future studies towards investigation of its role in molecular mechanisms of myofiber-type-specific gene expression.

Purpose : Although the benefits of physical activity, healthy eating, and weight management for breast cancer survivors are well established, little is known about how best to promote these practices among women diagnosed before age 40 years. We conducted a qualitative study to explore young breast cancer survivors' beliefs and practices regarding physical activity, nutrition, and weight management. Methods : Semi-structured interviews were conducted with 12 women (M age =36 years, SD=3.4) who were within 5 years of breast cancer diagnosis. Data were analyzed using thematic analysis. Results : Participants' accounts revealed several tensions between the factors motivating them to engage in physical activity, healthy eating, and weight management and those deterring them. Tensions were captured within three themes: (1) prolonging life with a healthy lifestyle versus enjoying living; (2) perceiving benefits versus barriers, and; (3) seeking social connection versus protecting the self from social threats. Participants also noted preferences, which if considered could help them maintain healthy lifestyle practices. Conclusions : Although young breast cancer survivors value physical activity, healthy eating, and weight management, they are constantly weighing the benefits of these practices against their perceived drawbacks. To facilitate long-term participation among young breast cancer survivors, future programing must address their conflicting beliefs and priorities.Implications for RehabilitationPhysical activity, healthy eating, and weight management can play an important role in the health and wellbeing of breast cancer survivors.Young breast cancer survivors experience a 'tug-of-war' between the factors motivating them to be active and eat healthy and those deterring them.Following treatment for breast cancer, young women would benefit from tailored lifestyle-based programing that addresses their conflicting beliefs and priorities.Tailored programing might involve strategically scheduled program times or flexible programs designed to include the participation of family and friends.

Objective: Peptic ulcer disease is a condition in which an important role has infection with H. pylori. The most common complication of peptic ulcer is bleeding. The presence of H. pylori triggers local and systemic cytokine signaling which may affect processes such as healing, gastric or duodenal rupture, and carcinogenesis. In this study, we examined the concentrations of IL-1β, IL-6, IL-10, TNF, TGF-β and IL-17A in serum by enzyme immunoassay and their mRNA expressions in periulcer biopsies obtained from patients with bleeding peptic ulcer by means of real-time-PCR., Results: We have shown that pro-inflammatory IL-6 and TNF concentrations in serum were significantly higher in patients who were infected with H. pylori, while the concentrations of TGF-β and IL-17A were significantly lower compared to non-infected subjects. IL-17A expression in periulcer mucosa was significantly higher in patients who were infected with H. pylori, while the expression of other cytokines, there was no significant difference compared to non-infected controls. Considering higher serum concentrations in non-infected subjects and higher IL-17A expression in mucosal tissue of infected patients, our data support the studies that found IL-17A has protective role in eradication of H. pylori infection in infected patients.

Autophagy, a process of controlled self-digestion which regulates cell homeostasis, is involved in innate and adaptive immunity. We investigated the expression of autophagy genes and autophagic activity in distinct lymphocyte populations in treatment-naive MS patients. The mRNA and protein levels of autophagy-related (ATG)5, required for autophagosome formation, were increased in CD4 + and CD4 - T cells, but not B cells of MS patients compared to control subjects. The expression of other investigated autophagy genes, as well as the autophagic activity, did not significantly differ between the two groups. ATG5 mRNA levels in CD4 + T cells from MS patients were positively correlated with those of the proinflammatory cytokine tumor necrosis factor. These data suggest that autophagy-independent increase in ATG5 expression might be associated with the proinflammatory capacity of T cells in multiple sclerosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: Transplantation is the best treatment option for end stage kidney disease. The most common early complications in post-transplant period are acute rejection (AR) of the graft and delayed graft function (DGF). The underlying mechanisms in these events are heterogeneous and at least in part involve cytokine genes which regulate immune response to allograft. We have investigated whether functional single nucleotide polymorphisms (SNP) in the genes encoding IFN-γ (IFNG), TNF (TNFA), IL-10 (IL10) and p40 subunit of IL-12/IL-23 (IL12B) could predict risk of AR and DGF in kidney allograft recipients., Methods: Our study involved 152 kidney transplant recipients on standard immunosuppressive regimen which included calcineurin inhibitors, mycophenolic acid derivatives and corticosteroids. Genotyping of IFNG, TNFA, IL10 and IL12B was performed using commercial TaqMan assays., Results: We found association between the carriers of AA genotype of IL12B +1188A/C polymorphism (rs3212227) and a lower rate of DGF (p = 0.037, OR = 0.45, 95% CI = 0.21-0.96), implying protective role of A allele in the pathogenesis of DGF in kidney transplant recipients, whereas no such association was observed with AR. None of the analyzed SNPs in TNFA (-308G/A), IFNG (+874T/A), IL10 (-1082G/A, -819T/C, -592C/A) were associated with AR or DGF in our patients., Conclusions: Our study shows a preliminary evidence that the AA genotype of rs3212227 SNP in the IL12B gene might be associated with a lower risk for DGF after kidney transplantation. In the future, additional well-designed large studies are required for the validation of our results., (Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.)

Background: Both aerobic training (AT) and resistance training (RT) have multidimensional health benefits for older adults including increased life expectancy and decreased risk of chronic diseases. However, the volume (i.e., frequency*time) of AT combined with RT in which untrained older adults can feasibly and safely participate remains unclear. Thus, our primary objective was to investigate the feasibility and safety of a high-volume exercise program consisting of twice weekly AT combined with twice weekly RT (i.e., four times weekly exercise) on a group of untrained older adults. In addition, we investigated the effects of the program on physical function, aerobic capacity, muscular strength, and explored factors related to participant adherence., Methods: We recruited eight inactive older adults (65+ years) to participate in a 6-week, single-group pre-post exercise intervention, consisting of 2 days/week of AT plus 2 days/week of progressive RT for 6 weeks. We recorded program attendance and monitored for adverse events during the course of the program. Participants were tested at both baseline and follow-up on the following: (1) physical function (i.e., timed-up-and-go test (TUG) and short physical performance battery (SPPB)), (2) aerobic capacity (VO 2 max) using the modified Bruce protocol; and (3) muscular strength on the leg press and lat pull-down. Post intervention, we performed qualitative semi-structured interviews of all participants regarding their experiences in the exercise program. We used these responses to examine themes that may affect continued program adherence to a high-volume exercise program., Results: We recorded an average attendance rate of 83.3% with the lowest attendance for one session being five out of eight participants; no significant adverse events occurred. Significant improvements were observed for SPPB score (1.6; 95% CI: [0.3, 2.9]), VO 2 max (8.8 ml/kg/min; 95% CI: [2.8, 14.8]), and lat pull-down strength (11.8 lbs; 95% CI: [3.3, 20.2]). Qualitative results revealed two themes that promote older adults' adherence: (1) convenience of the program and (2) the social benefits of exercise., Conclusions: Our findings suggest untrained older adults can be successful at completing twice weekly AT combined with twice weekly progressive RT; however, these exercise programs should be group-based in order to maintain high adherence.

Cytokines produced by helper T (Th)1 cells, Th17 and regulatory T cells (Treg) are involved in multiple sclerosis (MS) immunopathogenesis. Interferon (IFN)-β alters the numerous genes' expression, but how this alteration affects the treatment response is still elusive. We assessed relative gene expression of nineteen Th1/Th17/Treg-associated mediators in peripheral blood mononuclear cells and plasma levels of GM-CSF, IL-17A and IL-17F, in relapsing-remitting MS (RRMS) patients before IFN-β1b treatment initiation and at 6, 12, 24 and 36 months of therapy. All mRNA levels changed significantly during the IFN-β1b therapy. Higher IL-12Rβ2 mRNA levels were associated with lower risk of relapse. Despite recent reports regarding role of GM-CSF in MS, our study failed to demonstrate its significance as therapy response biomarker, both on the mRNA and protein level., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: To review the empirical qualitative literature on cancer survivors' experiences of the return to work process in order to develop strategies for health and vocational professionals to facilitate return to work., Methods: A rigorous systematic search of five databases was completed to identify relevant qualitative studies published between Jan 2000 and July 2013. All potentially relevant titles and abstracts were reviewed by two reviewers. For studies that met eligibility, the full-text articles were obtained and assessed for quality. The collected evidence was then synthesized using meta-ethnography methods., Results: In total, 39 studies met the eligibility criteria and passed the quality assessment. The synthesis of these studies demonstrated that cancer diagnosis and treatment represented a major change in individuals' lives and often resulted in individuals having to leave full-time work, while undergoing treatment or participating in rehabilitation. Thus, many survivors wanted to return to some form of gainful or paid employment after treatment and rehabilitation. However, there was also evidence that the meaning of paid employment could change following cancer. Return to work was found to be a continuous process that involved planning and decision-making with respect to work readiness and symptom management throughout the process. Nine key factors were identified as relevant to work success. These include four related to the person (i.e., symptoms, work abilities, coping, motivation), three related to environmental supports (i.e., family, workplace, professionals), and two related to the occupation (i.e., type of work/demands, job flexibility). Finally, issues related to disclosure of one's cancer status and cancer-related impairments were also found to be relevant to survivors' return to work experiences., Conclusions: This review reveals that cancer survivors experience challenges with maintaining employment and returning to work following cancer and may require the coordinated support of health and vocational professionals., Implications for Cancer Survivors: Cancer survivors need integrated support from health and vocational professionals (e.g., assistance with defining work goals, determining work readiness, determining how symptoms may impact work performance, suggesting workplace supports, and accommodations) to maintain and return to work after cancer diagnosis and treatment. These supports need to be provided throughout the recovery and rehabilitation process.