👤 Gabriele Sales

Acromegaly, primarily caused by GH-secreting pituitary neuroendocrine tumors (GH-PitNETs), in about half of cases exhibits resistance to somatostatin receptor ligands (SRLs), making surgery the primary treatment. Recent evidence suggests that glucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression in a subset of GH-PitNETs contributes to disease heterogeneity, particularly in tumors showing a paradoxical GH rise after glucose load, which are associated with a less aggressive phenotype and better first-generation SRLs response. This study investigated the functional role of GIPR in somatotroph cells by generating stable human GIPR-expressing GH3 cells (GH3hGIPR) and comparing them with empty vector controls. Functional assays demonstrated that GIPR activation induces cAMP/PKA and MAPK/ERK signaling, enhances GH and prolactin secretion, and increases intracellular calcium oscillations, dependent on extracellular calcium influx. Transcriptomic analysis revealed differential gene expression patterns linked to cell motility, neuronal development, and extracellular matrix remodeling in GH3hGIPR cells, aligning with clinical observations in GIPR+ tumors. However, GIPR overexpression did not alter cell proliferation or viability, suggesting that its role in tumor behavior may depend on additional molecular or epigenetic factors. These findings highlight the importance of GIPR signaling in somatotroph cell function and its potential influence on therapeutic responses, though further studies are needed to clarify its contribution to tumorigenesis and SRL sensitivity. Show less

Suicide prevention in nursing homes requires a deeper understanding of the psychological mechanisms underlying suicidal ideation. This study aimed to identify mental health profiles in institutionalized older adults based on risk and protective variables, and to explore their association with suicidal ideation. A total of 231 older adults (60-97 years) from nine Spanish nursing homes were assessed on depression, hopelessness, perceived burden, purpose in life, resilience, and self-efficacy. Latent Profile Analysis (LPA) was used to identify distinct profiles, and ANCOVA tested differences in suicidal ideation across groups. Four psychological profiles were identified: (1) High Risk (high symptomatology, low protection), (2) Burdensomeness (low depression and hopelessness, high burden), (3) Weakened Strengths (low symptomatology, low resources), and (4) Optimal Mental Health (low risk, high protection). Suicidal ideation levels differed significantly across profiles, and these differences remained after controlling for age, sex, and perceived health. The High Risk group showed the highest levels of suicidal ideation, whereas the Optimal Mental Health group showed the lowest. These profiles offer a basis for more personalized and effective prevention interventions tailored to each group's risk-protection balance. Screening for suicidal ideation in nursing homes should incorporate both risk factors (depression, hopelessness, perceived burden) and protective factors (resilience, purpose in life, self-efficacy). A person-centered approach allows gerontologists to tailor prevention strategies to specific psychological profiles. Show less