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Older adults with lower limb fractures often harbor concerns about losing their mobility, fearing a loss of independence. It is vital to develop strategies that foster their active engagement in the rehabilitation process. The present protocol aims to create a care pathway tailored to motivate individuals with lower limb fractures to adhere to rehabilitation. We will develop an observational, cross-sectional, and descriptive study using the Delphi data-gathering approach. Purposive sampling will recruit a panel of healthcare professionals and experts who care for patients with lower limb fractures. Aligned with the Delphi method, a series of iterative rounds will be developed to gather consensus around the motivational strategies used by health professionals in the rehabilitation of people with lower limb fractures. We will employ the Qualtrics platform for data collection and analysis, and a consensus target of 75% has been predetermined. For quantitative data analysis, we will use descriptive statistics encompassing a range of measures, including count, mean, standard deviation, median, minimum, maximum, and range. An inductive thematic analysis procedure will be employed to extract meaningful themes and patterns from qualitative data. The study results are expected to significantly impact clinical practice by creating a specialized care pathway to motivate individuals with lower limb fractures to adhere to rehabilitation. Adopting these explicit standards by professionals will ensure uniform and high-quality care.

Among gynecologic malignancies, ovarian cancer is the third most prevalent and the most common cause of death, especially due to diagnosis at an advanced stage together with resistance to therapy. As a solid tumor grows, cancer cells in the microenvironment are exposed to regions of hypoxia, a selective pressure prompting tumor progression and chemoresistance. We have previously shown that cysteine contributes to the adaptation to this hypoxic microenvironment, but the mechanisms by which cysteine protects ovarian cancer cells from hypoxia-induced death are still to be unveiled. Herein, we hypothesized that cysteine contribution relies on cellular metabolism reprogramming and energy production, being cysteine itself a metabolic source. Our results strongly supported a role of xCT symporter in energy production that requires cysteine metabolism instead of hydrogen sulfide (H2S) per se. Cysteine degradation depends on the action of the H2S-synthesizing enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and/or 3-mercaptopyruvate sulfurtransferase (MpST; together with cysteine aminotransferase, CAT). In normoxia, CBS and CSE inhibition had a mild impact on cysteine-sustained ATP production, pointing out the relevance of CAT + MpST pathway. However, in hypoxia, the concomitant inhibition of CBS and CSE had a stronger impact on ATP synthesis, thus also supporting a role of their hydrogen sulfide and/or cysteine persulfide-synthesizing activity in this stressful condition. However, the relative contributions of each of these enzymes (CBS/CSE/MpST) on cysteine-derived ATP synthesis under hypoxia remains unclear, due to the lack of specific inhibitors. Strikingly, NMR analysis strongly supported a role of cysteine in the whole cellular metabolism rewiring under hypoxia. Additionally, the use of cysteine to supply biosynthesis and bioenergetics was reinforced, bringing cysteine to the plateau of a main carbon sources in cancer. Collectively, this work supports that sulfur and carbon metabolism reprogramming underlies the adaptation to hypoxic microenvironment promoted by cysteine in ovarian cancer.