To evaluate the efficacy and safety of AM-111, a c-Jun N-terminal Kinase (JNK) ligand, in patients with acute sensorineural hearing loss (ASNHL). Prospective, double-blind, randomized, placebo-controlled study with follow-up visits on Days 3, 7, 30, and 90. Twenty-five European sites (academic tertiary referral centers, private ENT practices). Approximately 210 patients aged 18 to 61 years presenting within 48 hours after acute acoustic trauma or idiopathic sudden sensorineural hearing loss with mean hearing loss of 30 dB or greater at the 3 most affected contiguous test frequencies. Single-dose intratympanic injection of AM-111 (0.4 or 2.0 mg/ml) or placebo; optionally, oral prednisolone if hearing improvement was less than 10 dB at Day 7. Efficacy was assessed by absolute hearing improvement (primary end point, Day 7), percentage hearing improvement, complete hearing recovery, speech discrimination improvement, and complete tinnitus remission. Safety was evaluated by the frequency of clinically relevant hearing deterioration and adverse events. The study failed to demonstrate a treatment benefit for the entire study population because mild-to-moderate ASNHL cases showed unexpectedly strong spontaneous recovery. In severe-to-profound ASNHL patients (threshold ≥60 dB), AM-111 0.4 mg/ml showed statistically significant, clinically relevant, and persistent improvements in hearing and speech discrimination and higher tinnitus remission compared with placebo. The study drug and the intratympanic injections were well tolerated. The study established proof of concept for AM-111 in the treatment of severe-to-profound ASNHL. Control for spontaneous hearing recovery is essential for ASNHL studies.
Industrial wine yeasts owe their adaptability in constantly changing environments to a long evolutionary history that combines naturally occurring evolutionary events with human-enforced domestication. Among the many stressors associated with winemaking processes that have potentially detrimental impacts on yeast viability, growth, and fermentation performance are hyperosmolarity, high glucose concentrations at the beginning of fermentation, followed by the depletion of nutrients at the end of this process. Therefore, in this study, we subjected three widely used industrial wine yeasts to adaptive laboratory evolution under potassium chloride (KCl)-induced osmotic stress. At the end of the evolutionary experiment, we evaluated the tolerance to high osmotic stress of the evolved strains. All of the analyzed strains improved their fitness under high osmotic stress without worsening their economic characteristics, such as growth rate and viability. The evolved derivatives of two strains also gained the ability to accumulate glycogen, a readily mobilized storage form of glucose conferring enhanced viability and vitality of cells during prolonged nutrient deprivation. Moreover, laboratory-scale fermentation in grape juice showed that some of the KCl-evolved strains significantly enhanced glycerol synthesis and production of resveratrol-enriched wines, which in turn greatly improved the wine sensory profile. Altogether, these findings showed that long-term adaptations to osmotic stress can be an attractive approach to develop industrial yeasts.
Salivary gland tumours represent about 6% of head and neck neoplasms and about 0.5% of all malignancies in humans. Tumour growth and malignant transformation are complex processes involving various actions of molecules. Furthermore, some malignant salivary gland tumours are deemed to be caused by dedifferentiation or malignant transformation of benign tumours. The mechanisms of this transformation depend on a variety of different elements, such as cell cycle regulators, oncogenes, proteins, angiogenesis factors, and adipocytokines. The authors used PubMed, Medline, and Google websites to find and review the most significant papers related to malignant transformation in benign salivary gland tumours.
Photodynamic therapy (PDT) has emerged as a promising modality for the treatment of various diseases. This non-invasive approach utilizes photosensitizing agents and light to selectively target and destroy abnormal cells, providing a valuable alternative to traditional treatments. Research studies have explored the application of PDT in different areas of the head. Research is focusing on a growing number of new developments and treatments for cancer. One of these methods is PDT. Photodynamic therapy is now a revolutionary, progressive method of cancer therapy. A very important feature of PDT is that cells cannot become immune to singlet oxygen. With this therapy, patients can avoid lengthy and costly surgeries. PDT therapy is referred to as a safe and highly selective therapy. These studies collectively highlight the potential of PDT as a valuable therapeutic option in treating the head area. As research in this field progresses, PDT may become increasingly integrated into the clinical management of these conditions, offering a balance between effectiveness and minimal invasiveness.
Head–neck cancers as a group have the 7th highest rate of incidence worldwide. The most often diagnosed disease of the head and neck is squamous cell carcinoma (90% of cases). Another specific group of tumors is brain tumors. These can be divided into primary tumors and secondary tumors associated with metastasis. Research shows that treating head and neck cancers continues to be problematic and challenging, and researchers are actively seeking new treatments that would improve survival rates and reduce side effects. Irradiation of tumor tissue with the optimal wavelength of light in photodynamic therapy (PDT) generates predominantly singlet oxygen in tissue-based photosensitizers (PSs) or reactive oxygen radicals in the case of vascular PSs leading to cellular apoptosis and necrosis. A very important feature of PDT is that cells cannot become immune to the effects of singlet oxygen or reactive oxygen radicals. However, photosensitizer (PS) transport is influenced by the specific structures of cancer tumors and the concentration of PS decreases in cells far from the vessel lumen. Therefore, PSs may not reach tumor interiors, which decreases therapy effectiveness. The use of drug carriers and 3rd generation PSs that contain biocompatible functional groups makes it possible to control transport. This review of the current literature on PDT was conducted through databases such as PubMed and Scopus. The types of publications considered included clinical studies and most of the articles included were published in English. Based on the publications collected, we conclude that researchers have demonstrated the potential of PDT as a therapeutic platform for head, neck, and brain diseases.
3 July 2020 in Advances in Clinical and Experimental Medicine
Background. Short and long-term results of microsurgical treatment with the mini-microflap technique in patients with Reinke's edema (RE) were assessed based on the phonatory and ventilatory functions of the larynx. Objectives. To assess the short and long-term results of microsurgical treatment with the mini-microflap technique in patients with RE based on the phonatory and ventilatory functions of the larynx. Material and methods. Twenty patients diagnosed with advanced stage of RE confirmed with laryngo-videostroboscopy (LVS) were enrolled in the study. Phonatory function disturbances were additionally assessed on the basis of Maximum Phonation Time (MPT) measurement, Voice Handicap Index (VHI) and Voice-Related Quality of Life (V-ROOL) questionnaires. Ventilatory function was assessed using spirometry. The aforementioned complex examinations were conducted prior to surgery and 1, 6 and 9 months following the surgery. Results. Good postsurgical results were obtained in subjective and objective evaluation, which assessed the phonatoryfunction and ventilatory parameters. Post-surgery increase in MPT, VHI and VQROL was noticed in all patients in 3 check points (p < 0.001). The results demonstrate postsurgical improvement for some LVS parameters, including assessment of glottis closure (p < 0.003) observed 6 months after the surgery. An improvement in most of the ventilation parameters was observed also 6 months after surgery (p <0.001). For the spirometry flow parameter PEF, significant improvement was noted in each check point (p1 < 0.004, p6 < 0.001, p9 < 0.001). The study revealed a correlation between phonatory parameter - MPT and PEF observed 1 month after the procedure (p = 0.026), confirming the interdependence of ventilatory efficiency and phonatory condition of larynx. Conclusions. Mini-microflap surgery brings satisfactory clinical effect in patients with advanced stages of RE by optimization of phonatory and ventilatory functions of the larynx.