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It has been postulated that cancer stem cells (CSCs) are involved in all aspects of human cancer, although the mechanisms governing the regulation of CSC self-renewal in the cancer state remain poorly defined. In the literature, both the pro- and anti-oncogenic activities of autophagy have been demonstrated and are context-dependent. Mounting evidence has shown augmentation of CSC stemness by autophagy, yet mechanistic characterization and understanding are lacking. In the present study, by generating stable human lung CSC cell lines with the wild-type TP53 (A549), as well as cell lines in which TP53 was deleted (H1229), we show, for the first time, that autophagy augments the stemness of lung CSCs by degrading ubiquitinated p53. Furthermore, Zeb1 is required for TP53 regulation of CSC self-renewal. Moreover, TCGA data mining and analysis show that Atg5 and Zeb1 are poor prognostic markers of lung cancer. In summary, this study has elucidated a new CSC-based mechanism underlying the oncogenic activity of autophagy and the tumor suppressor activity of p53 in cancer, i.e., CSCs can exploit the autophagy-p53-Zeb1 axis for self-renewal, oncogenesis, and progression.<br /><br /> Spinal cord injury (SCI) often leads to impairment of the respiratory system. In fact, respiratory insufficiency is a significant cause of mortality and morbidity following SCI, related to the extent and level of the neurologic injury and its effects on the respiratory muscles (reduction in respiratory muscle strength and fatigue due to a reduction in inspiratory capacity, atelectasis and ineffective coughing). Less commonly recalled is the fact that autonomic dysreflexia (AD) is the result of parasympathetic imbalance. However, AD results from a massive, unrestrained outpouring of norepinephrine from the peripheral sympathetic ganglia. More accurately, the vagal (parasympathetic) response to this sympathetic discharge may have been responsible for the respiratory changes reported. This is not described in medical literature, although breathing difficulty is named as a common symptom and sign. The objective of this report is to describe a clinical case for the first time, that of T4 AIS (American spinal injth episodes of AD and highlights the need to look at this possibility.<br /><br />To date, the association between AD and acute respiratory insufficiency has not been described in spinal cord injury or rehabilitation literature. This case draws attention for the first time to the possibility that respiratory insufficiency is one of the signs associated with episodes of AD and highlights the need to look at this possibility.The self-renewal transcription factor Nanog and the phosphoinositide 3-kinase (PI3K)-Akt pathway are known to be essential for maintenance of mesenchymal stem cells. We evaluated their contribution to the maintenance of CD133(+) cancer stem-like cells (CSCs) and spheroid-forming cells in patient-derived cell lines from three human sarcoma subtypes HT1080 fibrosarcoma, SK-LMS-1 leiomyosarcoma, and DDLS8817 dedifferentiated liposarcoma. Levels of Nanog and activated Akt were significantly higher in sarcoma cells grown as spheroids or sorted for CD133 expression to enrich for CSCs. shRNA knockdown of Nanog decreased spheroid formation 10- to 14-fold, and reversed resistance to both doxorubicin and radiation in vitro and in H1080 flank xenografts. In the HT1080 xenograft model, doxorubicin and Nanog knockdown reduced tumor growth by 34% and 45%, respectively, and the combination reduced tumor growth by 74%. Using a human phospho-kinase antibody array, Akt1/2 signaling, known to regulate Nanog, was found to be highly activated in sarcoma spheroid cells compared with monolayer cells. Pharmacologic inhibition of Akt using LY294002 and Akt1/2 knockdown using shRNA in sarcoma CSCs decreased Nanog expression and spheroid formation and reversed chemotherapy resistance. Akt1/2 inhibition combined with doxorubicin treatment of HT1080 flank xenografts reduced tumor growth by 73%. Finally, in a human sarcoma tumor microarray, expression of CD133, Nanog, and phospho-Akt were 1.8- to 6.8-fold higher in tumor tissue compared with normal tissue. Together, these results indicate that the Akt1/2-Nanog pathway is critical for maintenance of sarcoma CSCs and spheroid-forming cells, supporting further exploration of this pathway as a therapeutic target in sarcoma.Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Although activator of HSP90 ATPase activity 1 (AHA1) is reported to be a potential oncogene, its role in osteosarcoma progression remains largely unclear. Since metabolism reprogramming is involved in tumorigenesis and cancer metastasis, the relationship between AHA1 and cancer metabolism is unknown. In this study, we found that AHA1 is significantly overexpressed in osteosarcoma and related to the prognosis of osteosarcoma patients. AHA1 promotes the growth and metastasis of osteosarcoma both in vitro and in vivo. Mechanistically, AHA1 upregulates the metabolic activity to meet cellular bioenergetic needs in osteosarcoma. Notably, we identified that isocitrate dehydrogenase 1 (IDH1) is a novel client protein of Hsp90-AHA1. Furthermore, the IDH1 protein level was positively correlated with AHA1 in osteosarcoma. And IDH1 overexpression could partially reverse the effect of AHA1 knockdown on cell growth and migration of osteosarcoma. Moreover, high IDH1 level was also associated with poor prognosis of osteosarcoma patients. This study demonstrates that AHA1 positively regulates IDH1 and metabolic activity to promote osteosarcoma growth and metastasis, which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.<br /><br /> Schwannomas are the second most common type of intra-dural lesions involving the thoracic spine. They are frequently seen as solid and heterogeneous lesions. Totally cystic thoracic schwannomas represent a rare pathological schwannoma variant, with only four cases reported in the English literature to our knowledge.<br /><br /> We report an 80-year-old male who presented with upper back pain for 3 months. Magnetic resonance imaging (MRI) showed a cystic lesion at the level of T6-T7 with peripheral contrast enhancement. The lesion was removed in total surgically with complete resolution of the patient's symptoms.<br /><br /> The diagnosis of cystic schwannomas is often delayed due to the paucity of symptoms and the lack of meticulous investigation. [https://www.selleckchem.com/products/SB590885.html https://www.selleckchem.com/products/SB590885.html] The presence of rim enhancement on contrast-enhanced MRI may be the only clue for the diagnosis. It is important to consider cystic schwannomas in the differential diagnosis of cystic spinal lesions since the best surgical outcome is strongly related to earlier diagnosis and total resection of the lesion.<br /><br />The diagnosis of cystic schwannomas is often delayed due to the paucity of symptoms and the lack of meticulous investigation. The presence of rim enhancement on contrast-enhanced MRI may be the only clue for the diagnosis. It is important to consider cystic schwannomas in the differential diagnosis of cystic spinal lesions since the best surgical outcome is strongly related to earlier diagnosis and total resection of the lesion.<br /><br /> Of the 23 cases of spinal intradural-extramedullary ependymomas which have been reported to date, 11 were diagnosed as anaplastic. Here we present a very rare case of a thoracic intradural-extramedullary (not intramedullary) anaplastic ependymoma in an adult along with a literature review.<br /><br /> A 29-year-old man presented with rapidly progressive gait disturbance, a sensory-deficit below the trunk and urination disorders that had begun a few months earlier. Magnetic resonance imaging of his thoracic spine revealed a dorsal-located intradural-extramedullary tumor at T4-5. The rapid deterioration of his symptoms within several months led him to refer to our department for surgery. Within one month the size of tumor increased to involve the T4-6 level, consequently worsening his gait disturbance. He underwent surgery and tumor mass was resected. However, there was leptomeningeal dissemination of the tumor cells on the surface of cord. A near-total resection was therefore achieved. Histopathology revealed the resecareful and serial follow-up is necessary for this individual.The transmission of SARS-CoV-2 is a major Public Health problem that is influenced by a number of factors. Recently it has been hypothesized that this transmission may be reduced during the summer due to the warm temperatures. On the other hand, the potential association between the high number of SARS-CoV-2 infections and air pollution is being studied. This relationship was already proven during the SARS outbreak in 2002. This article reviewed the scientific evidence to date regarding the possible influence of environmental temperature and air pollution on the transmission of SARS-CoV-2. It is concluded that the annual seasons and, therefore, the temperature do not seem to influence the spread of the virus. In addition, air pollutants facilitate infection and mortality from the virus.<br /><br /> The public health strategies adopted for the containment of COVID-19 have generated psychosocial stressors that act as risk factors for alcohol consumption. The objectives of this study were to establish whether alcohol risk consumption varied during COVID-19 confinement, and how these variations manifested as a function of different sociodemographic variables.<br /><br /> The study was conducted during confinement with 3,779 participants in Spain. We used an online survey with sociodemographic variables (sex, age and employment situation) and AUDIT-C. link2 Frequency and mean difference analysis were performed (Student t, ANOVA and Kruskal-Wallis) to establish intra-group variations before the pandemic compared to during confinement, and intergroup for each time period, reporting effect size.<br /><br /> Alcohol risky consumption presented high prevalence rates before confinement (25,9% of alcohol consumers), showing a general decrease during confinement (15,1%), both in men (X<br /><br /> =224,829; p&lt;0,001) and women (X<br /><br /> =214,324; p&lt;0,decreased in a generalized way during the confinement by COVID-19, but the changes in prevalence and risk index were dependent on sociodemographic variables. It is recommended that these findings are considered in the design of public health policies and strategies.<br /><br />The alcohol risky consumption decreased in a generalized way during the confinement by COVID-19, but the changes in prevalence and risk index were dependent on sociodemographic variables. It is recommended that these findings are considered in the design of public health policies and strategies.BACKGROUND Myasthenic crisis is a condition characterized by the sudden onset of myasthenic weakness involving the respiratory muscles and requires ventilatory support to prevent death. This is a case report of respiratory failure in a 43-year-old man as the first presentation of myasthenia gravis. CASE REPORT A 43-year-old man with underlying hypertension and a lacunar stroke with good muscle-power recovery presented with severe community-acquired pneumonia, complicated with respiratory failure requiring invasive ventilatory support. He responded well to the intravenous antibiotic therapy and after 1 week of treatment, he was hemodynamically stable and his septic parameters improved. However, he persistently failed to maintain adequate spontaneous respiratory effort after the removal of the ventilatory support and had to be reintubated multiple times. There was no other identifiable cause for the worsening respiratory failure. He had no clinical features or muscle weakness suggestive of myasthenia gravis. link3 However, his blood test was positive for serum anti-acetylcholine receptor antibodies and repetitive nerve stimulation tests showed the characteristic decremental response of compound muscle action potential amplitude, in keeping with the diagnosis of myasthenia gravis.