Purpose: Patients with Mycoplasma pneumoniae pneumonia (MPP) can develop atelectasis, and some cases of atelectasis may persist for over 4 weeks. However, the risk factors for the development and persistence of atelectasis ( > 4 weeks) in children with MPP and their clinical characteristics remain understudied. We aimed to investigate the clinical characteristics and associated factors of MPP with atelectasis in children. Methods: We retrospectively analyzed the medical records of 477 children with MPP treated at Pusan National University Yangsan Hospital from November 2014 to March 2020. Demographics, clinical information, laboratory data, and radiological findings were collected from all patients. The patients were divided into 2 groups according to the presence of atelectasis with MPP. The group with atelectasis was further divided into 2 groups according to whether atelectasis was improved. Results: Among 477 children with MPP, 105 developed atelectasis, and 34 showed persistent atelectasis. Children with atelectasis had longer lengths of hospitalization than children without atelectasis. High lactate dehydrogenase (LDH) levels and whole lobar consolidation were independently associated factors for presenting with atelectasis, and long macrolide therapy duration before admission ( > 3 days) was related to persistent atelectasis ( > 4 weeks). Conclusion High LDH levels and whole lobar consolidation were independent associated factors for presenting with atelectasis, and a long macrolide therapy duration before admission was associated with persistent atelectasis. Careful observation and management of children with these associated factors for atelectasis will improve the prognosis of children with MPP.

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.

The pathophysiological implications of aldosterone and adrenomedullin in the cardiac ventricular hypertrophy were examined. Male Sprague-Dawley rats were treated with deoxycorticosterone acetate (DOCA)-salt and monocrotaline (MCT) to selectively elicit left and right ventricular (LV, RV) hypertrophy, respectively. The mRNA expression of aldosterone synthase and adrenomedullin in LV and RV was determined by reverse transcription-polymerase chain reaction. The expression of aldosterone synthase and adrenomedullin was increased in LV, while not altered significantly in RV of DOCA-salt-treated rats. On the contrary, the expression was not significantly altered in LV, but increased in RV of MCT-treated rats. The enhanced expression of aldosterone synthase may be causally related with the development of ventricular hypertrophy, and the increased expression of adrenomedullin may act as a counter-regulatory mechanism.
Adrenomedullin* ; Aldosterone Synthase* ; Aldosterone* ; Animals ; Desoxycorticosterone ; Humans ; Hypertrophy ; Hypertrophy, Right Ventricular* ; Male ; Monocrotaline ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger

BACKGROUND: The present study was aimed to examine the regulation of aquaporin (AQP)-2 water channels in the kidney following blood volume depletion. METHODS: Male Sprague-Dawley rats were acutely blood volume-depleted by withdrawal of arterial blood up to 2% of body weight. The expression of AQP2 mRNA and protein was determined by reverse transcription - polymerase chain reaction and Western blot analysis, respectively, in the inner medulla of the kidney 1 and 3 hours after the hemorrhage. RESULTS: The mRNA expression of AQP2 was significantly increased 1 hour after the bleeding. However, neither the shuttling nor the total abundance of AQP2 proteins was significantly altered. On the contrary, 3 hours after the bleeding, the expression of AQP2 proteins as well as that of AQP2 mRNA was significantly increased. The shuttling of AQP2 proteins was also increased. CONCLUSION: These results suggest that an increased expression of AQP2 channels in the kidney may confer one of compensatory mechanisms restoring the circulating volume in an acute hypovolemic state.
Animals ; Aquaporin 2* ; Aquaporins* ; Blood Volume* ; Blotting, Western ; Body Weight ; Hemorrhage ; Humans ; Hypovolemia ; Kidney* ; Male ; Polymerase Chain Reaction ; Rats* ; Rats, Sprague-Dawley ; Reverse Transcription ; RNA, Messenger

The present study was aimed to determine whether nitric oxide (NO) plays a role in the regulation of aquaporin (AQP) channels in the kidney. Male Brattleboro rats (250~300 g body weight) were used. The experimental group was treated with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/L drinking water) for 1 week, and cotreated with indomethacin (5 mg/kg, twice a day, i.p.) for the last two days. Control groups were treated with either L-NAME for 1 week, indomethacin for 2 days, or without any drug treatment. The abundance of AQP1, AQP2 and AQP3 proteins in the kidney was determined by Western blot analysis. Indomethacin downregulated AQP channels, whereas L-NAME by itself showed no significant effects on them. The indomethacin-induced downregulation of AQP2 and AQP3 was significantly blunted in L-NAME-treated rats, while that of AQP1 was not affected. These results suggest that endogenous NO, when stimulated, may downregulate AQP channels that are specifically regulated by AVP/cAMP pathway in the kidney.
Animals ; Aquaporin 3 ; Aquaporins* ; Blotting, Western ; Down-Regulation* ; Drinking ; Humans ; Indomethacin ; Kidney ; Male ; NG-Nitroarginine Methyl Ester ; Nitric Oxide* ; Rats* ; Rats, Brattleboro

Objectives: . Age-related hearing loss (ARHL), or presbycusis, is caused by disorders of sensory hair cells and auditory neurons. Many studies have suggested that the accumulation of mitochondrial DNA damage, the production of reactive oxygen species, noise, inflammation, and decreased antioxidant function are associated with subsequent cochlear senescence in response to aging stress. Long non-coding RNA (lncRNA) has been reported to play important roles in various diseases. However, the function of lncRNA in ARHL remains unclear. In this study, we analyzed the common expression profiles of messenger RNA (mRNA) and lncRNA through ARHL-related RNA-sequencing datasets. Methods: . We selected and downloaded three different sets of RNA-sequencing data for ARHL. We performed differential expression analysis to find common mRNA and lncRNA profiles in the cochleae of aged mice compared to young mice. Gene Ontology (GO) analysis was used for functional exploration. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to validate mRNAs and lncRNAs. In addition, we performed trans target prediction analysis with differentially expressed mRNAs and lncRNAs to understand the function of these mRNAs and lncRNAs in ARHL. Results: . We identified 112 common mRNAs and 10 common lncRNAs in the cochleae of aged mice compared to young mice. GO analysis showed that the 112 upregulated mRNAs were enriched in the defense response pathway. When we performed qRT-PCR with 1 mM H2O2-treated House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, the qRT-PCR results were consistent with the RNA-sequencing analysis data. lncRNA-mRNA networks were constructed using the 10 common lncRNAs and 112 common mRNAs in ARHL. Conclusion . Our study provides a comprehensive understanding of the common mRNA and lncRNA expression profiles in ARHL. Knowledge of ARHL-associated mRNAs and lncRNAs could be useful for better understanding ARHL and these mRNAs and lncRNAs might be a potential therapeutic target for preventing ARHL.

Cyclophosphamide is alkylating agent used in the treatment of various solid tumors. Mucosal irritation by acrolein, the metabolite of cyclophosphamide, is believed to cause various symptoms of cystitis. The thiol compound, sodium 2-mercaptoethane sulfonate (Mesna), has been found to inactivate acrolein. We present an unusual case of a 64-year-old woman, who was treated as chronic cystitis. Her symptoms did not improve, so she was treated with Mesna under the assumption of cyclophosphamide induced cystitis; her symptoms then improved.
Acrolein ; Cyclophosphamide* ; Cystitis* ; Female ; Humans ; Mesna* ; Middle Aged ; Sodium

Temporal bone fracture and blunt head trauma was once considered as contraindication for the surgery. Increasing numbers of successful cochlear implantation are being reported. However, the outcome of cochlear implantation in severe damaged brain is unclear. A multichannel cochlear implant was successfully implanted in a 33-year-old man who had both sensorineural deafness, left hemiplegia due to bilateral transverse temporal bone fractures and severe right brain damage after a traffic accident.
Accidents, Traffic ; Adult ; Brain ; Brain Injuries* ; Cerebral Cortex* ; Cochlear Implantation* ; Cochlear Implants* ; Craniocerebral Trauma ; Deafness ; Hemiplegia ; Humans ; Skull Fractures ; Temporal Bone

Despite the well-established nature of bromate-induced ototoxicity, cochlear implantation after bromate intoxication has been rarely documented. We hereby present a case of a 51-year-old female deafened completely after bromate ingestion. Her hearing was not restored by systemic steroid treatment and hearing aids were of no use. A cochlear implantation was performed on her right ear 3 months after the bromate ingestion. In bromate intoxication cases, early monitoring of hearing level is necessary and other drugs with potential ototoxicity should be avoided. The outcome of cochlear implantation was excellent in this case of bromate-induced deafness.
Cochlear Implantation* ; Cochlear Implants* ; Deafness ; Ear ; Eating ; Female ; Hearing ; Hearing Aids ; Hearing Loss, Sudden* ; Humans ; Middle Aged