220 research outputs found
Women performing repetitive work: Is there a difference in the prevalence of shoulder pain and pathology in supermarket cashiers compared to the general female population?
Objectives: Shoulder disorders in the occupational environment have been widely studied, but the quality of research and methodology applied vary. Little has been done to ascertain whether shoulder pain in female repetitive workers is due to any verifiable pathology, or to compare findings with the general population. Therefore, we decided to evaluate the prevalence of self-reported shoulder pain in a group of female supermarket cashiers and in the general female population using a standardized questionnaire. Shoulder pain prevalence was then compared to imaging findings in order to assess specific and non-specific pain prevalence. Material and Methods: 196 cashiers and 302 controls filled in a standardized shoulder questionnaire and underwent an imaging examination of a shoulder. Results: The prevalence of shoulder pain was significantly higher in the group of cashiers (46.4%) than in the general population (25.5%) (OR = 1.821; 95% CI: 1.426–2.325). Specific pain prevalence was higher among the controls (19.5%) than among the cashiers (13.2%). Conclusions: The more frequent reports of shoulder pain in the supermarket cashiers are not correlated with a higher prevalence of imaging abnormalities. The causes of these more frequent complaints should be probably sought in the psycho-social and occupational environment
Cardiometabolic risk factors in MASLD patients with HCC: the other side of the coin
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) constitutes the commonest cause of chronic liver disorder worldwide, whereby affecting around one third of the global population. This clinical condition may evolve into Metabolic Dysfunction-Associated Steatohepatitis (MASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC), in a predisposed subgroup of patients. The complex pathogenesis of MASLD is severely entangled with obesity, dyslipidemia and type 2 diabetes (T2D), so far so nutritional and lifestyle recommendations may be crucial in influencing the risk of HCC and modifying its prognosis. However, the causative association between HCC onset and the presence of metabolic comorbidities is not completely clarified. Therefore, the present review aimed to summarize the main literature findings that correlate the presence of inherited or acquired hyperlipidemia and metabolic risk factors with the increased predisposition towards liver cancer in MASLD patients. Here, we gathered the evidence underlining the relationship between circulating/hepatic lipids, cardiovascular events, metabolic comorbidities and hepatocarcinogenesis. In addition, we reported previous studies supporting the impact of triglyceride and/or cholesterol accumulation in generating aberrancies in the intracellular membranes of organelles, oxidative stress, ATP depletion and hepatocyte degeneration, influencing the risk of HCC and its response to therapeutic approaches. Finally, our pursuit was to emphasize the link between HCC and the presence of cardiometabolic abnormalities in our large cohort of histologically-characterized patients affected by MASLD (n=1538), of whom 86 had MASLD-HCC by including unpublished data
The small heat shock protein B8 (HSPB8) modulates proliferation and migration of breast cancer cells
open12noBreast cancer (BC) is one of the major causes of cancer death in women and is closely related to hormonal dysregulation. Estrogen receptor (ER)-positive BCs are generally treated with anti hormone therapy using antiestrogens or aromatase inhibitors. However, BC cells may become resistant to endocrine therapy, a process facilitated by autophagy, which may either promote or suppress tumor expansion. The autophagy facilitator HSPB8 has been found overexpressed in some BC. Here we found that HSPB8 is highly expressed and differentially modulated by natural or synthetic selective ER modulators (SERMs), in the triple-positive hormone-sensitive BC (MCF-7) cells, but not in triple-negative MDA-MB-231 BC cells. Specific SERMs induced MCF-7 cells proliferation in a HSPB8 dependent manner whereas, did not modify MDA-MB-231 cell growth. ER expression was unaffected in HSPB8-depleted MCF-7 cells. HSPB8 over-expression did not alter the distribution of MCF-7 cells in the various phases of the cell cycle. Conversely and intriguingly, HSPB8 downregulation resulted in an increased number of cells resting in the G0/G1 phase, thus possibly reducing the ability of the cells to pass through the restriction point. In addition, HSPB8 downregulation reduced the migratory ability of MCF-7 cells. None of these modifications were observed, when another small HSP (HSPB1), also expressed in MCF-7 cells, was downregulated. In conclusion, our data suggest that HSPB8 is involved in the mechanisms that regulate cell cycle and cell migration in MCF-7 cells.openPiccolella, Margherita; Crippa, Valeria; Cristofani, Riccardo; Rusmini, Paola; Galbiati, Mariarita; Elena Cicardi, Maria; Meroni, Marco; Ferri, Nicola; Morelli, Federica F; Carra, Serena; Messi, Elio; Poletti, AngeloPiccolella, Margherita; Crippa, Valeria; Cristofani, Riccardo; Rusmini, Paola; Galbiati, Mariarita; Elena Cicardi, Maria; Meroni, Marco; Ferri, Nicola; Morelli, Federica F; Carra, Serena; Messi, Elio; Poletti, Angel
Distraction technique for pain reduction in Peripheral Venous Catheterization: randomized, controlled trial
Background and aim of the work: Procedural pain during Peripheral Venous Catheterization (PVC) is a significant issue for patients. Reducing procedure-induced pain improves the quality of care and reduces patient discomfort. We aimed to compare a non-pharmacological technique (distraction) to anaesthetic cream (EMLA) for the reduction of procedural pain during PVC, in patients undergoing Computerized Tomography (CT) or Nuclear Magnetic Resonance (NMR) with contrast. Methods: This is a Prospective, Randomized Controlled Trial. The study was carried out during the month of October 2015. A total of 72 patients undergoing PVC were randomly assigned to the experimental group (distraction technique, n=36) or control group (EMLA, n=36). After PVC, pain was evaluated by means of the numeric pain-rating scale (NRS). Pain perception was compared by means of Mann-Whitney Test. Results: The average pain in the distraction group was 0.69 (SD±1.26), with a median value of 0. The average pain in the EMLA group was 1.86 (SD±1.73), with a median value of 2. The study showed a significant improvement from the distraction technique (U=347, p<.001, r=.42) with respect to the local anaesthetic in reducing pain perception. Conclusions/Implication for practice: Distraction is more effective than local anaesthetic in reducing of pain-perception during PVC insertion. This study is one of few comparing the distraction technique to an anaesthetic. It confirms that the practitioner-patient relationship is an important point in nursing assistance, allowing the establishment of trust with the patient and increasing compliance during the treatment process
Designing innovative research pathways for the advancement of design research: IASDR 2023 Doctoral and Postgraduate Consortium
The paper explores relevant themes for design research that arose from research works proposed for IASDR2023 and developed by doctoral candidates and recent master's degree graduates. Particular attention has been paid to research investigations that reflect on the theme of Life-Changing Design, specifically examining how design is responding to the transformations occurring in the contemporary period. Reflections on the soft impact of technologies, in particular digital technologies, on daily life are accompanied by an analysis of innovations and challenges faced by healthcare systems, products, and services. This is followed by an examination of social innovation themes and practices, and the development of new principles of inclusity. A concluding contribution highlights the requirement to identify innovative approaches to design education extending beyond recognized methodologies to implement personal and technical skills of new generations of designers
Aberrant Autophagic Response in The Muscle of A Knock-in Mouse Model of Spinal and Bulbar Muscular Atrophy
Spinal and bulbar muscular atrophy (SBMA) is characterized by loss of motoneurons and sensory neurons, accompanied by atrophy of muscle cells. SBMA is due to an androgen receptor containing a polyglutamine tract (ARpolyQ) that misfolds and aggregates, thereby perturbing the protein quality control (PQC) system. Using SBMA AR113Q mice we analyzed proteotoxic stress-induced alterations of HSPB8-mediated PQC machinery promoting clearance of misfolded proteins by autophagy. In muscle of symptomatic AR113Q male mice, we found expression upregulation of Pax-7, myogenin, E2-ubiquitin ligase UBE2Q1 and acetylcholine receptor (AchR), but not of MyoD, and of two E3-ligases (MuRF-1 and Cullin3). TGF beta 1 and PGC-1 alpha were also robustly upregulated. We also found a dramatic perturbation of the autophagic response, with upregulation of most autophagic markers (Beclin-1, ATG10, p62/SQSTM1, LC3) and of the HSPB8-mediated PQC response. Both HSPB8 and its co-chaperone BAG3 were robustly upregulated together with other specific HSPB8 interactors (HSPB2 and HSPB3). Notably, the BAG3: BAG1 ratio increased in muscle suggesting preferential misfolded proteins routing to autophagy rather than to proteasome. Thus, mutant ARpolyQ induces a potent autophagic response in muscle cells. Alteration in HSPB8-based PQC machinery may represent muscle-specific biomarkers useful to assess SBMA progression in mice and patients in response to pharmacological treatments
The protein quality control system in motoneuron diseases
Spinal and bulbar muscular atrophy (SBMA) is a motoneuronal diseases caused by an elogated polyglutamine (polyQ) tract in the androgen receptor (AR). The polyQ expansion causes the AR protein to misfold and the binding with the ligand testosterone triggers a cascade of events, including ARpolyQ aggregation, that led to motoneuron death. The intracellular accumulation of misfolded ARpolyQ both altered the protein quality control system (PQC) and impaired the protective mechanisms deputed to refolding and clearance of misfolded proteins. In PQC, the molecular chaperones allow the refolding or the clearance of the misfolded proteins through the Ubiquitin Proteasome system (UPS) or the autophagic pathway. Moreover, emerging evidence reveal that ARpolyQ toxicity is not related only to motoneuron degeneration but also skeletal muscle damage plays a primary role in SBMA.
AIM: The aim of the study was both to unravell the contribution of PQC in SBMA and to find molecular and pharmacological approaches for modulating PQC as potential therapeutic target.
Methods: Western blot and filter retardation assay were used to analyse the biochemical properties of ARpolyQ and the protein level of PQC markers. RT-qPCR was used to quantify the mRNA expression of PQC genes in presence of ARpolyQ.
Results:
In SBMA motoneuronal cell line, we demonstrated that both UPS and autophagic pathway are impaired or blocked, leading to ARpolyQ accumulation into the aggregates. Moreover, analysis in SBMA animal model showed that in the spinal cord and in the skeletal muscle, the PQC could differ considerably in how degrading the mutant and misfolded ARpolyQ.
In these conditions of PQC impairment we tested, in SBMA cell model, the overexpression of the small heat shock protein B8 (HspB8), involved in the autophagic pathway. HpB8 led to the autophagic removal of misfolded ARpolyQ, restorating the intracellular autophagic flux. Interestingly, we found that trehalose, a known autophagic stimulator, was able to induce the HspB8 expression and to facilitate the ARpolyQ clearance. Then, we tested the combined treatment of trehalose with Bicalutamide, an antiandrogen. Bicalutamide is able to slow down AR nuclear translocation and to retain it into the cytoplasm, where the autophagic pathway is active. Bicalutamide and trehalose showed synergic activity in the degradation of ARpolyQ.
Conclusions: the PQC plays a crucial role in SBMA, the modulation of its activity with trehalose and Bicalutamide might be a promising approach for this no cure disease
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