Antiproliferative Role of Natural and Semi-Synthetic Tocopherols on Colorectal Cancer Cells Overexpressing the Estrogen Receptor β.

Estrogen receptor β (ERβ) is the most highly expressed subtype in the colon epithelium and mediates the protective effect of estrogen against the development of colon cancer. Indeed, the expression of this receptor is inversely related to colorectal cancer progression. Structurally estrogen-like compounds, including vitamin E components, affect cell growth by binding to ERs.

The Presence of the Endocannabinoid System in an In Vitro Model of Gorham-Stout Disease and Its Possible Role in the Pathogenesis.

Gorham-Stout syndrome (GSD), also known as disappearing bone disease, is an extremely rare bone disorder, characterized by a huge bone loss, which is followed by a lack of new matrix deposition and an excessive proliferation of both blood vessels and lymphatics. Unfortunately, the biological causes of GSD are still unknown. Recent studies that have tried to understand the etiopathogenesis of GSD have been principally focused on the vascular and osteoclastogenic aspects, not considering the possibility of a lack of osteoblast function.

Three-year treatment with anti-CGRP monoclonal antibodies modifies migraine course: the prospective, multicenter I-GRAINE study.

Objectives: To determine whether extending anti-CGRP mAb treatment beyond 3 years influences migraine course, we analyzed migraine frequency during the first month of treatment discontinuation following three 12-month treatment cycles (Ts).

Methods: This multicenter, prospective, real-world study enrolled 212 patients with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who completed three consecutive Ts of subcutaneous anti-CGRP mAbs. Discontinuation periods (D1, D2, D3) were defined as the first month after T1, T2, and T3, respectively.

NET Models Meeting 2024 white paper: the current state of neuroendocrine tumour research models and our future aspirations.

Current models for the study of neuroendocrine tumours (NETs) are severely limited. While (e.g.

Lung Recruitment Before Surfactant Administration in Extremely Preterm Neonates: 2-Year Follow-Up of a Randomized Clinical Trial.

Importance: A multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes.

Objective: To examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units.

Design, Setting, And Participants: This was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy.

Evaluating the Effectiveness, Tolerability, and Safety of Eptinezumab in High-Frequency and Chronic Migraine in Real World: EMBRACE-The First Italian Multicenter, Prospective, Real-Life Study.

We conducted a multicenter, prospective study (EMBRACE) evaluating the real-life effectiveness, safety, and tolerability of eptinezumab (100 mg/300 mg)-a monoclonal antibody targeting the calcitonin-gene-related peptide (anti-CGRP mAb)-in high-frequency episodic migraine (HFEM) or chronic migraine (CM). The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at weeks 9-12 compared to baseline. The secondary endpoints included changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), Migraine Disability Assessment Scale (MIDAS), Migraine Interictal Burden Scale (MIBS-4), and responder rates.

Irisin and Its Role in Postmenopausal Osteoporosis and Sarcopenia.

Menopause, an extremely delicate phase in a woman's life, is characterized by a drop in estrogen levels. This decrease has been associated with the onset of several diseases, including postmenopausal osteoporosis and sarcopenia, which often coexist in the same person, leading to an increased risk of fractures, morbidity, and mortality. To date, there are no approved pharmacological treatments for sarcopenia, while not all of those approved for postmenopausal osteoporosis are beneficial to muscles.

Impact of multiple treatment cycles with anti-CGRP monoclonal antibodies on migraine course: focus on discontinuation periods. Insights from the multicenter, prospective, I-GRAINE study.

Objectives: While a single 12-month treatment cycle (TrC) with anti-CGRP mAbs is not disease-modifying for most patients, there is limited understanding of the effects of multiple TrCs on migraine course. We evaluated whether a second TrC might modify the migraine course by comparing the occurrence of migraine relapse after discontinuation of the second TrC to that following the cessation of the first TrC.

Methods: In a real-life, multicenter, prospective study we considered all consecutive patients diagnosed with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and treated with any anti-CGRP mAbs for ≥ 2 consecutive 12-month TrCs who were responders at week 12.

Ultra-late response (> 24 weeks) to anti-CGRP monoclonal antibodies in migraine: a multicenter, prospective, observational study.

Objective: Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a ≥ 50% reduction in monthly migraine days (MMD) at 12 weeks compared to baseline (responders). However, approximately half of the patients not responding to anti-CGRP mAbs ≤ 12 weeks do respond ≤ 24 weeks (late responders). We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only > 24 weeks (ultra-late responders).

Early Respiratory Physiotherapy versus an Individualized Postural Care Program for Reducing Mechanical Ventilation in Preterm Infants: A Randomised Controlled Trial.

Background: Tactile stimulation manoeuvres stimulate spontaneous breathing in preterm newborns. The aim of this study is to evaluate the effect of early respiratory physiotherapy on the need for mechanical ventilation during the first week of life in preterm infants with respiratory failure.

Methods: This is a monocentric, randomised controlled trial.

Calcifediol: Mechanisms of Action.

Due to its essential role in calcium and phosphate homeostasis, the secosteroid hormone calcitriol has received growing attention over the last few years. Calcitriol, like other steroid hormones, may function through both genomic and non-genomic mechanisms. In the traditional function, the interaction between the biologically active form of vitamin D and the vitamin D receptor (VDR) affects the transcription of thousands of genes by binding to repeated sequences present in their promoter region, named vitamin D-responsive elements (VDREs).

Very-low-calorie ketogenic diet vs hypocaloric balanced diet in the prevention of high-frequency episodic migraine: the EMIKETO randomized, controlled trial.

Background: Migraine is the second world's cause of disability. Among non-pharmacological treatments, nutritional intervention, particularly ketogenic diet, represents one of the most promising approaches.

Methods: This a prospective, single center, randomized, controlled study aimed at evaluating the efficacy of a very low-calorie ketogenic diet (VLCKD) compared to a hypocaloric balanced diet (HBD) in migraine prophylaxis in patients affected by high-frequency episodic migraine (HFEM) with a Body Mass Index (BMI) > 27 kg/m.

Calcifediol: Why, When, How Much?

Vitamin D deficiency is a constantly growing health problem worldwide. Adults affected with hypovitaminosis D could experience negative consequences on their musculoskeletal system and extra-skeletal health. In fact, an optimal vitamin D status is essential to ensure the correct bone, calcium, and phosphate homeostasis.

Parathyroid carcinoma: molecular therapeutic targets.

Parathyroid carcinoma (PC) is an extremely rare malignant tumor of the parathyroid glands, accounting for less than 1% of primary hyperparathyroidism, commonly characterized by severe and unmanageable hypercalcemia, aggressive behavior, high metastatic potential, and poor prognosis. PC manifests prevalently as a sporadic tumor and only occasionally it is part of congenital syndromic and non-syndromic endocrine diseases. Molecular pathogenesis of this form of parathyroid tumor is not fully elucidated and it appears to be caused by multiple genetic and epigenetic drivers, differing among affected patients and not yet clearly stated in distinguishing PC from the benign parathyroid adenoma (PA).

Late Response to Anti-CGRP Monoclonal Antibodies in Migraine: A Multicenter Prospective Observational Study.

Objectives: To assess the frequency and characteristics of late responders (>12 weeks) to monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP).

Methods: This is a multicenter (n = 16) prospective real-life study considering all consecutive adults with high-frequency or chronic migraine treated with anti-CGRP mAbs for ≥24 weeks. We defined responder patients with a ≥50% reduction from baseline in monthly migraine/headache days at weeks 9-12 and late responders as those achieving a ≥50% reduction only afterward.

Respiratory Management of the Preterm Infant: Supporting Evidence-Based Practice at the Bedside.

Extremely preterm infants frequently require some form of respiratory assistance to facilitate the cardiopulmonary transition that occurs in the first hours of life. Current resuscitation guidelines identify as a primary determinant of overall newborn survival the establishment, immediately after birth, of adequate lung inflation and ventilation to ensure an adequate functional residual capacity. Any respiratory support provided, however, is an important contributing factor to the development of bronchopulmonary dysplasia.

Early and sustained efficacy of fremanezumab over 24-weeks in migraine patients with multiple preventive treatment failures: the multicenter, prospective, real-life FRIEND2 study.

Background: To verify the long-term (24-week) efficacy, safety, and tolerability of fremanezumab in real-life patients with high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM: ≥ 15 days/month), and multiple preventive treatment failures.

Methods: This is a prospective, cohort, real-life study at 28 headache centers on consecutive patients affected by HFEM or CM with multiple preventive treatment failures who were prescribed subcutaneous fremanezumab (225 mg monthly/675 mg quarterly) for ≥ 24 weeks. Primary endpoint was the change in monthly migraine days (MMDs) in HFEM and monthly headache days (MHDs) in CM at weeks 21-24 compared to baseline.

Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs.

Osteoporosis is characterized by the alteration of bone homeostasis due to an imbalance between osteoclastic bone resorption and osteoblastic bone formation. Estrogen deficiency causes bone loss and postmenopausal osteoporosis, the pathogenesis of which also involves oxidative stress, inflammatory processes, and the dysregulation of the expression of microRNAs (miRNAs) that control gene expression at post-transcriptional levels. Oxidative stress, due to an increase in reactive oxygen species (ROS), proinflammatory mediators and altered levels of miRNAs enhance osteoclastogenesis and reduce osteoblastogenesis through mechanisms involving the activation of MAPK and transcription factors.

Autophagy-Related ncRNAs in Pancreatic Cancer.

Pancreatic cancer (PC) is a malignancy accounting for only 3% of total cancers, but with a low 5-year relative survival rate. Approximately 80% of PC patients are diagnosed at a late stage when the disease has already spread from the primary site. Despite advances in PC treatment, there is an urgently needed for the identification of novel therapeutic strategies for PC, particularly for patients who cannot undergo classical surgery.