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BackgroundLaryngopharyngeal reflux (LPR) disease has many symptoms such as globus pharyngeus, excessive throat clearing and hoarseness. The aim of this study was to investigate the effect of stellate ganglion block (SGB) in addition to proton pump inhibitors (PPI) on LPR.MethodsFifty patients complaining of more than 3 typical LPR symptoms for over 3 months were enrolled in the study. The P group took PPI for 8 weeks. The SP group took PPI and interwent a series of 8 SGB procedure once a week during the period of treatment. The blocks were performed one at a time unilaterally on the right and left stellate ganglions by injecting 1% mepivacaine 6 ml. We evaluated the reflux symptom index (RSI) before treatment and following 4 weeks and 8 weeks of treatment in both groups.ResultsAfter 4 weeks of treatment, the RSI of the P group decreased, but not significantly, to 16.6 ± 6.8 compared with the baseline value of 19.2 ± 2.7 (P = 0.093), whereas the RSI of the SP group decreased significantly to 9.8 ± 3.3 compared with the baseline value of 19.0 ± 4.7 (P = 0.000). After 8 weeks of treatment, the RSI of the P group decreased significantly to 13.7 ± 6.7 (P = 0.001) and the RSI of the SP group also decreased significantly to 7.7 ± 3.4 (P = 0.000). There were significant differences in the RSI between the two groups after 4 weeks (P = 0.000) and 8 weeks (P = 0.001) of treatment.ConclusionsThe symptoms of LPR improved earlier when PPI therapy was combined with SGB compared with PPI therapy alone.

Background: Dormant leukemia stem cells (LSC) promote therapeutic resistance and leukemic progression as a result of unbridled activation of stem cell gene expression programs. Thus, we hypothesized that 1) deregulation of the hedgehog (Hh) stem cell self-renewal and cell cycle regulatory pathway would promote dormant human LSC generation and 2) that PF-04449913, a clinical antagonist of the GLI2 transcriptional activator, smoothened (SMO), would enhance dormant human LSC eradication. Methods: To test these postulates, whole transcriptome RNA sequencing (RNA-seq), microarray, qRT-PCR, stromal co-culture, confocal fluorescence microscopic, nanoproteomic, serial transplantation and cell cycle analyses were performed on FACS purified normal, chronic phase (CP) chronic myeloid leukemia (CML), blast crisis (BC) phase CML progenitors with or without PF-04449913 treatment. Results: Notably, RNA-seq analyses revealed that Hh pathway and cell cycle regulatory gene overexpression correlated with leukemic progression. While lentivirally enforced GLI2 expression enhanced leukemic progenitor dormancy in stromal co-cultures, this was not observed with a mutant GLI2 lacking a transactivation domain, suggesting that GLI2 expression prevented cell cycle transit. Selective SMO inhibition with PF-04449913 in humanized stromal co-cultures and LSC xenografts reduced downstream GLI2 protein and cell cycle regulatory gene expression. Moreover, SMO inhibition enhanced cell cycle transit and sensitized BC LSC to tyrosine kinase inhibition in vivo at doses that spare normal HSC. Conclusion: In summary, while GLI2, forms part of a core HH pathway transcriptional regulatory network that promotes human myeloid leukemic progression and dormant LSC generation, selective inhibition with PF-04449913 reduces the dormant LSC burden thereby providing a strong rationale for clinical trials predicated on SMO inhibition in combination with TKIs or chemotherapeutic agents with the ultimate aim of obviating leukemic therapeutic resistance, persistence and progression. [ABSTRACT FROM AUTHOR]

The molecular etiology of human progenitor reprogramming into self-renewing leukemia stem cells (LSC) has remained elusive. Although DNA sequencing has uncovered spliceosome gene mutations that promote alternative splicing and portend leukemic transformation, isoform diversity also may be generated by RNA editing mediated by adenosine deaminase acting on RNA (ADAR) enzymes that regulate stem cell maintenance. In this study, whole-transcriptome sequencing of normal, chronic phase, and serially transplantable blast crisis chronic myeloid leukemia (CML) progenitors revealed increased IFN-? pathway gene expression in concert with BCR-ABL amplification, enhanced expression of the IFN-responsive ADAR1 p150 isoform, and a propensity for increased adenosine-to-inosine RNA editing during CML progression. Lentiviral overexpression experiments demonstrate that ADAR1 p150 promotes expression of the myeloid transcription factor PU.1 and induces malignant reprogramming of myeloid progenitors. Moreover, enforced ADAR1 p150 expression was associated with production of a misspliced form of GSK3β implicated in LSC self-renewal. Finally, functional serial transplantation and shRNA studies demonstrate that ADAR1 knockdown impaired in vivo self-renewal capacity of blast crisis CML progenitors. Together these data provide a compelling rationale for developing ADAR1-based LSC detection and eradication strategies. [ABSTRACT FROM AUTHOR]

Background: Neck and shoulder pain (NSP) is fairly common in adolescents, which is associated with a high prevalence of NSP found during adulthood as well; therefore, its significance during adolescence should not be under estimated. We surveyed the prevalence of recurrent NSP, lifestyle, and risk factors in Korean high school students, and examined the influence of recurrent NSP on the quality of life. Methods: Nine hundred thirty one male students (16-19 years old) from two academic high schools in Seoul were included in this study. The survey consisted of a questionnaire to assess the prevalence of recurrent NSP, with questions regarding having an occurrence more than once a week, characteristics of NSP, activity and lifestyle of the students, and the risk factors for recurrent NSP . A 36-item Short Form questionnaire was also examined. Results: We found that 44.3% of the high school students surveyed had recurrent NSP (more than once a week) and the overall prevalence of NSP was 79.1%. The average sitting time was 10.2 ± 2.7 h/day. 59.0% did not sit straight, 14.7% used assisting devices during reading, and 11.9% answered that they stretched regularly. Found from their self assessed health, frequent fatigue and frequent depressed mood presented significant associations with the higher prevalence of recurrent NSP. Conclusions: Korean high school students had a high prevalence of recurrent NSP. Clinical attention is needed for the prevention and resolution of recurrent NSP found in high school students. [ABSTRACT FROM AUTHOR]

Two different prototype mobile telemedicine systems were constructed for use in the emergency room. They could transmit physiological signals as well as video pictures and sound. One device, the mobile emergency bed (MEB), was powered by battery and had a wireless connection to the local-area network (LAN). For the other, the mobile emergency server (MES), a patient monitor, video-camera and microphone were connected by a radio-frequency link to a server. A functional evaluation and a clinical evaluation (by 12 emergency doctors in six emergency centres) were performed on both prototypes. The bandwidth and the video quality of the MEB were better than those of the MES, because of the digital transmission of the wireless LAN. The MES was better for directing patient treatment and teleconsultation; the MEB was better for static patients in the emergency centre. In general, the MES was more suitable for practical emergency telemedicine work. [ABSTRACT FROM AUTHOR]