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Neuregulin1/ErbB4 Signaling Induces Cardiomyocyte Proliferation and Repair of Heart Injury

SummaryMany organs rely on undifferentiated stem and progenitor cells for tissue regeneration. Whether differentiated cells themselves can contribute to cell replacement and tissue regeneration is a controversial question. Here, we show that differentiated heart muscle cells, cardiomyocytes, can be induced to proliferate and regenerate. We identify an underlying molecular mechanism for controlling this process that involves the growth factor neuregulin1 (NRG1) and its tyrosine kinase receptor, ErbB4. NRG1 induces mononucleated, but not binucleated, cardiomyocytes to divide. In vivo, genetic inactivation of ErbB4 reduces cardiomyocyte proliferation, whereas increasing ErbB4 expression enhances it. Injecting NRG1 in adult mice induces cardiomyocyte cell-cycle activity and promotes myocardial regeneration, leading to improved function after myocardial infarction. Undifferentiated progenitor cells did not contribute to NRG1-induced cardiomyocyte proliferation. Thus, increasing the activity of the NRG1/ErbB4 signaling pathway may provide a molecular strategy to promote myocardial regeneration

Schwannoma of the Hypoglossal Nerve Mimicking Carotid Body Paraganglioma

Carotid body paragangliomas (CBPs) clinically present as highly vascularized cervical masses with a pathognomonic localization at the carotid artery bifurcation. Following ultrasonography and MRI/CT imaging, surgical resection with optional preoperative embolization is considered as the treatment of choice in most cases. We herein present the case of a 60-year-old female with characteristic clinical signs and imaging findings of a right-sided CBP who finally went to surgical treatment. Intraoperatively, the tumor showed an adherent growth to the hypoglossal nerve that had to be partially resected, resulting in a postoperative nerve palsy. Histological examination of the resected tumor revealed the unexpected diagnosis of a hypoglossal nerve schwannoma. To the best of our knowledge, we herein present the third case reported in the literature of a unilateral hypoglossal schwannoma located at the carotid bifurcation mimicking clinical symptoms, imaging and intraoperative findings of a CBP

Complete remission of an early-stage laryngeal cancer under combined pembrolizumab and chemotherapy treatment of a synchronous lung adenocarcinoma

Background: Anti-PD1-Checkpoint inhibition (CI) is an established treatment of recurrent and/or metastatic head and neck cancer. A potential beneft from CI in early-stage disease that is usually treated by radiation or surgery has not been investigated so far and is currently not addressed in clinical trials. Case presentation: A 58-year-old man was diagnosed with a cT2 supraglottic laryngeal cancer and a synchronous metastasized adenocarcinoma of the lung. As the patient refused any treatment of his laryngeal cancer, he received combined immune-chemotherapy according to the KEYNOTE-189 protocol. After 4 cycles of pembrolizumab/carboplatin/pemetrexed, the patient showed a complete remission of his laryngeal cancer with a clear shrinkage of the mediastinal and hilar lung cancer metastases. After 21 cycles of maintenance therapy, the lung adenocarcinoma shows a stable disease status with no signs of any residual or recurrent laryngeal cancer. Conclusions: Anti-PD1-CI may be a treatment option also for early-stage HNSCC with excellent functional outcome when established therapies are not available

A novel adenovirus of Western lowland gorillas (Gorilla gorilla gorilla)

Adenoviruses (AdV) broadly infect vertebrate hosts including a variety of primates. We identified a novel AdV in the feces of captive gorillas by isolation in cell culture, electron microscopy and PCR. From the supernatants of infected cultures we amplified DNA polymerase (DPOL), preterminal protein (pTP) and hexon gene sequences with generic pan primate AdV PCR assays. The sequences in-between were amplified by long-distance PCRs of 2 - 10 kb length, resulting in a final sequence of 15.6 kb. Phylogenetic analysis placed the novel gorilla AdV into a cluster of primate AdVs belonging to the species Human adenovirus B (HAdV-B). Depending on the analyzed gene, its position within the cluster was variable. To further elucidate its origin, feces samples of wild gorillas were analyzed. AdV hexon sequences were detected which are indicative for three distinct and novel gorilla HAdV-B viruses, among them a virus nearly identical to the novel AdV isolated from captive gorillas. This shows that the discovered virus is a member of a group of HAdV-B viruses that naturally infect gorillas. The mixed phylogenetic clusters of gorilla, chimpanzee, bonobo and human AdVs within the HAdV-B species indicate that host switches may have been a component of the evolution of human and non-human primate HAdV-B viruses

Differential nasal swab cytology represents a valuable tool for therapy monitoring but not prediction of therapy response in chronic rhinosinusitis with nasal polyps treated with Dupilumab

Introduction: Chronic Rhinosinusitis with nasal polyps (CRSwNP) is a common chronic disease with a high impact on patients’ quality of life. If conservative and surgical guideline treatment cannot sufficiently control disease burden, biologicals can be considered as a comparably new treatment option that has revolutionized CRSwNP therapy since the first approval of Dupilumab in 2019. With the aim to select patients who benefit from this new treatment and to find a marker for therapy monitoring, we investigated the cellular composition of nasal mucous membranes and inflammatory cells of patients suffering from CRSwNP and undergoing Dupilumab therapy using non-invasive nasal swab cytology. Methods: Twenty CRSwNP patients with the indication for Dupilumab therapy have been included in this prospective clinical study. In total, five study visits were conducted with ambulatory nasal differential cytology using nasal swabs starting with the beginning of therapy and followed by visits every 3 months for 12 months. First, these cytology samples were stained with the May-GrunwaldGiemsa method (MGG) and the percentage of ciliated cells, mucinous cells, eosinophil cells, neutrophil cells, and lymphocytes was analyzed. Secondly, an immunocytochemical (ICC) ECP-staining was performed to detect eosinophil granulocytes. Additionally, during each study visit the nasal polyp score, SNOT20 questionnaire, olfactometry, the total IgE concentration in peripheral blood as well as the eosinophil cell count in peripheral blood were recorded. The change of parameters was evaluated over one year and the correlation between clinical effectiveness and nasal differential cytology was analyzed. Results: In both MGG (p<0.0001) and ICC analysis (p<0.001) a significant decrease of eosinophils was seen under Dupilumab treatment. When patients were divided into a Eo-low- (<21%) and Eo-high- (≥21%) group according to the percentage eosinophils in nasal swab catology in the first study visit, the Eo-highgroup showed a greater change of eosinophils over time (D17.82) compared to the Eo-low-group (D10.67) but, however, no better response to therapy. The polyp score, SNOT20 questionnaire, and total IgE concentration in peripheral blood showed a significant decrease during the observation period (p<0.0001). Discussion: Nasal swab cytology as an easy-to-apply diagnostic method allows detection and quantification of the different cell populations within the nasal mucosa at a given time. The nasal differential cytology showed a significant decrease of eosinophils during Dupilumab therapy and can therefore be used as non-invasvive method for monitoring therapy success of this cost intensive therapy and potentially can allow an optimized individual therapy planning and management for CRSwNP patients. Since the validity of initial nasal swab eosinophil cell count as a predictive biomarker for therapy response was limited in our study, additional studies including larger number of participants will be necessary to further evaluate the potential benefits for clinical practice of this new diagnostic method

Система управления вторичным источником постоянного напряжения в системе автономного электропитания

Объектом исследования является повышающий преобразователь напряжения, входящий в состав зарядного устройства аккумуляторной батареи автомобиля. В процессе исследования проводился расчет элементов повышающего преобразователя, выбор аккумуляторной батареи, выбор солнечной панели. Были выбраны средства защиты зарядного устройства. Исследована работа ППН. Произведено имитационное моделирование работы повышающего преобразователя как с обратной связью так и без неё в программе LTspice. Был написан программный код системы управления преобразователем, генерирующий ШИМ сигнал, формируемый по уровню напряжения обратной связи.The subject of the study is an increase in the voltage converter that is part of the battery charger of the car. The research process included the calculation of elements of the step-up converter, the selection of a battery, and the selection of a solar panel. You have chosen to protect your charger. The work of par. A simulation simulation of the work of the step-up converter has been performed, both with and without the feedback in the LTSpice program. You have written the code for the converter control system that generates the PWM signal that is generated by the voltage level of the feedback

Pott's puffy tumor: a need for interdisciplinary diagnosis and treatment

Pott’s puffy tumor (PPT) is an infection of the frontal sinus with subperiosteal and intracranial abscess formation and one of the rare entities in pediatrics. We present a series of four cases of PPT that occurred in two children (6 and 9 years) and in two young adults (17 and 19 years). All patients were treated by an interdisciplinary team of pediatric, neurosurgical, ENT, radiological, and neuroradiological specialists. Antibiotic treatment was combined with single endoscopic surgery in one case and combined endoscopic sinus surgery with an open transcranial approach to drain intracranial abscess formation in three cases. It is important to be aware that PPT occurs in children with the finding of intracranial abscess formation. Therefore, a close interdisciplinary cooperation for successful treatment is needed in this rare disease