Bahcelievler

Researchers are investigating how mechanical loading and bone loss affect the relationship between motor neuron activity and H-reflex amplitude, focusing on postmenopausal women with osteoporosis. Weight-bearing exercises like running, jumping, and whole-body vibration are known to benefit bone health, but the exact neuroregulatory mechanisms remain unclear. Two main mechanisms are proposed: spinal reflexes from muscle spindles and a bone myoregulation reflex (BMR) involving load-sensitive bone cells called osteocytes. The study aims to test whether H-reflex suppression during mechanical loading is mainly due to osteocyte-mediated BMR and if this suppression is reduced in osteoporosis due to fewer or less functional osteocytes. The study measures H-reflex during five different mechanical load levels on the right leg and during whole-body vibration using a specialized vibration platform. Participants stand on both feet with a force sensor under the right heel to monitor weight distribution. Surface EMG electrodes record muscle activity while electrical stimulation is applied to the tibial nerve to evoke H-reflexes. Measurements include H-reflex amplitude at loads from 10% to 100% body weight and during 1-minute whole-body vibrations at 30 Hz. The bone myoregulation reflex is also assessed using 10-second whole-body vibrations at four frequencies. Data acquisition and analysis are conducted with advanced equipment and software. Participants will undergo repeated H-reflex testing under different loading and vibration conditions, with real-time feedback to maintain target weight. Researchers will analyze EMG activity, H-reflex amplitude, and latency of reflexes to understand motor neuron responses and bone reflex mechanisms. The primary outcome is the H-reflex amplitude measured during testing. The study involves women aged 18 to 65, including those with osteoporosis and healthy controls. Safety and data normality will be monitored, and statistical tests will compare reflex responses across conditions.

Researchers are evaluating the effectiveness of brenetafusp (IMC-F106C) combined with nivolumab compared to standard nivolumab treatments in people who have advanced melanoma that has not been treated before. This study focuses on participants who have a specific genetic marker called HLA-A*02:01 and aims to understand how these treatments affect the progression of their cancer. The study is a phase 3, randomized, controlled trial, which helps ensure reliable comparison between the different treatment regimens. Participants in this study will receive either brenetafusp plus nivolumab or standard nivolumab regimens, which may include nivolumab alone or in combination with relatlimab. These treatments are given by intravenous infusion, with specific dosing of the drugs as concentrates for infusion. The study compares these approaches to see which is more effective in controlling the melanoma. During the study, participants will be closely monitored for disease progression and overall health. Researchers will use scans and other assessments to measure progression-free survival, which is the time participants live without their disease worsening, followed for up to about 45 months. Safety and response to treatment will be regularly evaluated to better understand the effects of the therapies over time.

Researchers are studying the effects of Adagrasib alone and combined with pembrolizumab in adults with advanced or metastatic non-small cell lung cancer (NSCLC) who have the KRAS G12C mutation. The Phase 2 part evaluates these treatments in patients who are candidates for first-line therapy, with different groups based on their PD-L1 tumor proportion scores (TPS). The Phase 3 part compares the combination of Adagrasib and pembrolizumab against pembrolizumab alone in patients with NSCLC having PD-L1 TPS of 50% or higher. In Phase 2, there are three patient groups: two with PD-L1 TPS less than 1% randomized to receive either Adagrasib monotherapy or Adagrasib plus pembrolizumab, and one group with PD-L1 TPS of 1% or higher treated with the combination. Adagrasib is given orally at doses of 400 mg twice daily or 600 mg twice daily depending on the group, while pembrolizumab is administered intravenously at 200 mg every three weeks. Phase 3 patients are randomized to receive either Adagrasib 400 mg twice daily plus pembrolizumab 200 mg every three weeks or pembrolizumab alone. Participants will undergo various assessments including brain imaging, tumor measurements, and evaluations of safety and treatment effects over 22 months in Phase 2 and 36 months in Phase 3. Researchers will monitor efficacy, safety, and drug levels, as well as patient-reported outcomes and genetic biomarkers. The study includes patients with untreated or previously treated brain metastases under specific conditions and excludes those with prior systemic treatments for advanced NSCLC or certain brain lesion characteristics.

Researchers are evaluating the effectiveness and safety of givinostat compared to hydroxyurea in patients with high-risk polycythemia vera (PV) who have the JAK2V617F mutation. PV is a chronic condition that increases the risk of blood clots and can progress to more severe diseases like myelofibrosis or leukemia. High-risk patients are those aged 60 or older or those with a history of blood clots. Current treatments often do not fully control symptoms or long-term risks in these patients. The study involves two treatment groups receiving oral medications: givinostat or hydroxyurea. Dosages of both drugs are adjusted based on side effects or how well the treatment is working, aiming for an optimal dose. The core treatment phase is a pivotal phase 3 trial designed to show whether givinostat is more effective than hydroxyurea. Patients who finish this phase may continue receiving givinostat in an extended treatment phase to collect additional long-term safety and efficacy data. Participants will be assessed regularly, including monitoring blood counts and clinical response up to week 48. The main outcome measured is the proportion of patients who achieve a response by week 48, evaluated between weeks 25 and 48. Safety monitoring includes heart rhythm checks and other clinical evaluations. Eligible patients must meet specific criteria related to diagnosis, risk factors, and treatment needs, and those who complete the core phase successfully may enter the extended phase for further observation.