Association of growth hormone deficiency (GHD) with anxiety and depression: experimental data and evidence from GHD children and adolescents.

Anxiety and depression are among the commonest emotional problems in children and young adolescents. They are encountered with even higher prevalence in children and adults with growth hormone deficiency (GHD). Alterations in the somatotropic axis, as observed in both GH/IGF1 deficiency and excess, can produce permanent changes in brain tissue structure. The growth hormone/insulin-like growth factor 1 (GH/IGF1) axis seems to exert a regulatory effect on brain function and neurogenesis, especially in the hippocampus, a brain region associated with mental and emotional disorders, such as depression and anxiety. There is evidence from animal models of the possible interrelationship of the endocrine system with the pathogenesis of emotional disorders. Moreover, clinical data support the association of GHD and mood disorders, which are often reversed by GH replacement therapy. However, the causal relationship and the mechanism underlying this association are to date obscure and remain to be clarified. The present review reports experimental data from animal models regarding the role of GH/IGF1 in emotional disorders and focuses on clinical data on the presence of these disorders in children with GHD and their response to GH therapy.

Evolution of Hashimoto thyroiditis in children with type 1 diabetes mellitus (TIDM).

OBJECTIVES: Treatment of children with Hashimoto thyroiditis (HT) and particularly of those with coexistent diabetes mellitus type 1 (TIDM) and normal/mildly elevated serum TSH is controversial. The aim of the study was to evaluate the natural course of HT in children with TIDM compared with children with no other coexistent autoimmunity and investigate for possible predictive factors of thyroid function deterioration. METHODS: Data from 96 children with HT, 32 with T1DM (23 girls, nine boys) mean (sd) age: 10.6 (2.3) years, and 64 age and sex-matched without T1DΜ (46 girls, 18 boys), mean (sd) age: 10.2 (2.9) years were evaluated retrospectively. They all had fT4 and TSH values within normal ranges and available data for at least three years' follow-up. RESULTS: During the follow-up period, 11 children (34.4%) with TIDM exhibited subclinical hypothyroidism and two children (6.2%) progressed to overt hypothyroidism compared to 12 (18.8%) and two (3.1%) among children without TIDM, respectively. Among children with HT, a higher percentage (40.6%) of children with T1DM progressed to subclinical or overt hypothyroidism, compared with children (21.9%) with similar characteristics but without TIDM or other coexistent autoimmunity. CONCLUSIONS: The annual conversion rate from euthyroidism to hypothyroidism in children with T1DM was significantly higher compared to sex and age-matched children without TIDM. Prospective randomized trials are needed to support the view of an earlier intervention therapy even in milder degrees of thyroid failure in these children.

The Role of the RANKL/RANK Axis in the Prevention and Treatment of Breast Cancer with Immune Checkpoint Inhibitors and Anti-RANKL.

The receptor activator of nuclear factor-κB (RANK) and the RANK ligand (RANKL) were reported in the regulation of osteoclast differentiation/activation and bone homeostasis. Additionally, the RANKL/RANK axis is a significant mediator of progesterone-driven mammary epithelial cell proliferation, potentially contributing to breast cancer initiation and progression. Moreover, several studies supported the synergistic effect of RANK and epidermal growth factor receptor (EGFR) and described RANK's involvement in epidermal growth factor receptor 2 (ERBB2)-positive carcinogenesis. Consequently, anti-RANKL treatment has been proposed as a new approach to preventing and treating breast cancer and metastases. Recently, RANKL/RANK signaling pathway inhibition has been shown to modulate the immune environment and enhance the efficacy of anti-CTLA-4 and anti-PD-1 monoclonal antibodies against solid tumors. Clinical and experimental trials have emerged evaluating RANKL inhibition as an enhancer of the immune response, rendering resistant tumors responsive to immune therapies. Trials evaluating the combinatorial effect of immune checkpoint inhibitors and anti-RANKL treatment in double-positive (RANK+/ERBB2+) patients are encouraging.

The Challenges in the Development of Diabetes Prevention and Care Models in Low-Income Settings.

In low- and middle-income countries (LMICs), the burden of non-communicable diseases such as diabetes is rapidly rising, overpassing the existing burden of communicable diseases. Patients with diabetes living in low-income communities face unique challenges related to lack of awareness, difficulty in accessing health care systems and medications, and consequently failure in achieving optimal diabetes management and preventing complications. Effective diabetes prevention and care models could help reduce the rising burden by standardizing guidelines for prevention and management, improving access to care, engaging community and peers, improving the training of professionals and patients and using the newest technology in the management of the disease. In this article, we review the latest research and evidence on effective models of diabetes prevention and diabetes care delivery in low- income settings. We also provide existing evidence relating to the effectiveness of these models in low-resource contexts, with the aim to highlight characteristics and strengths that make their implementation successful and long-lasting.

Historical retrospective of the SRC oncogene and new perspectives (Review).

Since its first discovery as part of the Rous sarcoma virus (RSV) genome, the c-SRC (SRC) proto-oncogene has been proved a key regulator of cancer development and progression, and thus it has been highlighted as an attractive target for anti-cancer therapeutic strategies. Though the exact mechanisms of its action are still not fully understood, SRC protein mediates crucial normal cell functions, such as cell development, proliferation and survival, and its dysregulation is considered as an oncogenic signature and a driving force for cancer initiation. In the present review, we present a flashback to the history of the Src research, while focusing on the most important milestones in the field. Moreover, we investigate the proposed regulatory mechanisms and molecules that mediate its action in order to designate putative therapeutic targets and useful prognostic and/or diagnostic tools. Furthermore, we present and discuss existing therapeutic approaches that are explored in clinical settings.