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BACKGROUND: Despite advances in techniques for olfactory neuroblastoma (ONB), such as unilateral cranial resection, preserving the patientâ™s sense of smell remains a challenge. This study aimed to examine the effectiveness of post-operative olfactory training in patients who underwent unilateral resection of ONB. METHODS: This retrospective cohort study assessed the effect of post-operative olfactory training on olfactory preservation in patients with ONB undergoing unilateral cranial resection. Patients were divided into training intervention (n = 5) and non-intervention (n = 6) groups. Olfactory tests were conducted pre-operatively and at multiple post-operative intervals. RESULTS: Partial olfactory function was preserved in all cases in the training intervention group, whereas only 17% of cases in the non-intervention group maintained partial olfactory function. Significant improvements in olfactory test scores were observed in the training intervention group compared with the non-intervention group. CONCLUSIONS: Our findings suggest that post-operative olfactory training could aid in olfactory preservation for patients with ONB after unilateral cranial resection. However, these results should be interpreted with caution, and further research with larger cohorts and extended follow-up periods is needed to confirm these observations.
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Estesioneuroblastoma Olfatorio , Neoplasias Nasales , Trastornos del Olfato , Humanos , Estesioneuroblastoma Olfatorio/cirugía , Estudios Retrospectivos , Trastornos del Olfato/etiología , Masculino , Femenino , Neoplasias Nasales/cirugía , Persona de Mediana Edad , Adulto , Complicaciones Posoperatorias , Olfato/fisiología , AncianoRESUMEN
BACKGROUND: Chronic rhinosinusitis (CRS) is a common disease, and endoscopic sinus surgery (ESS) is widely performed. However, there is no consensus regarding postoperative pain control after ESS, and postoperative opioid abuse is a problem in many countries. Acetaminophen is reportedly effective for postoperative pain control. Preemptive analgesia has received more attention lately, wherein pain is prevented before it occurs. In this study, we assessed the use of acetaminophen for preemptive analgesia during the perioperative period in ESS. METHODOLOGY: This is a retrospective study of 175 patients who underwent ESS, septoplasty, and bilateral inferior turbinate mucosal resection at our hospital from April 2016 to February 2018. In total, 82 patients received 1,000 mg of acetaminophen during surgery and 4 hours after the first dose, while 93 patients did not receive it routinely. We compared these two groups. The primary outcome was the need to use additional analgesics prescribed by the ward physician and the secondary outcomes included postoperative pain, postoperative bleeding, reoperation, blood pressure, and body temperature. RESULTS: The use of additional oral and intravenous analgesics was significantly reduced in the patients who received acetaminophen perioperatively. CONCLUSION: Preemptive analgesia during the perioperative period of ESS could lead to satisfactory postoperative pain control.
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Analgesia , Analgésicos Opioides , Acetaminofén , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Estudios RetrospectivosRESUMEN
This mini review describes the current status and challenges regarding institutionalisation of wastewater surveillance systems against COVID-19. Monitoring SARS-CoV-2 in wastewater has been proposed to be a potential tool to understand the actual prevalence of COVID-19 in the community, and it could be an effective approach to monitor the trend during the COVID-19 pandemic. However, challenges to institutionalise wastewater surveillance systems are still abundant and unfolding at a rapid rate given that the international understanding regarding the scientific knowledge and socio-political impacts of COVID-19 are in the developing stages. To better understand the existing challenges and bottlenecks, a comparative study between Japan, Viet Nam, and Indonesia was carried out in the present study. Through gaining a better understanding of common issues as well as issues specific to each country, we hope to contribute to building a robust multistakeholder system to monitor SARS-CoV-2 in wastewater as an effective disease surveillance system for COVID-19.
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COVID-19 , Pandemias , Aguas Residuales , Humanos , Indonesia , Japón , SARS-CoV-2 , VietnamRESUMEN
The Editors-in-Chief have retracted this article [1]. Serious concerns have been raised about the data presented [2], and after careful consideration and additional investigation the Editors-in-Chief no longer have confidence in this article.
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The Editors-in-Chief have retracted this article [1]. Serious concerns have been raised about the data presented [2], and after careful consideration and additional investigation the Editors-in-Chief no longer have confidence in this article. All authors were contacted and did not respond to correspondence about this retraction.
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The prefrontal cortex (PFC) is sensitive to the stress exposure and involved in stress coping. And the effects of gum chewing on the stress have been studied using NIRS. However, when measuring NIRS on PFC during gum chewing, blood flows in shallow tissues (scalp, skin, muscle) might be affected. A NIRS used in the present study first, which has a short distance (1 cm) and the usual (3 cm) source-detector (S-D) regression, can allow eliminating shallow tissues effect of gum chewing. The aim of this study was to investigate the hypothesis that gum chewing activates the right prefrontal cortex (PFC) in stress coping against negative sounds (NS) from the International Affective Digitized Sounds-2 (IADS) as a mental stress task. NS showed activation in the right PFC. There was a significant difference between NS, and NS with Gum, where NS with Gum showed an increased PFC activity, increased alpha wave appearance rate, a higher value in heart rate level, and a higher VAS score indicating 'pleasant'. Gum chewing activated right PFC activity while exposed to negative sounds from IADS as a mental stress task.
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Goma de Mascar , Masticación , Sonido , Estrés Psicológico , Adaptación Psicológica , Adulto , Femenino , Humanos , Masculino , Corteza Prefrontal/fisiología , Corteza Prefrontal/efectos de la radiación , Sonido/efectos adversos , Estrés Psicológico/terapia , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Diphenylarsinic acid (DPAA) intoxication caused by drinking contaminated well water was found in Kamisu, Japan. The symptoms indicated cerebellar-brainstem and temporo-occipital involvement. However, it remains unclear how it affects the human brain. To elucidate the effect of DPAA on the human brain, we analyzed cerebral blood flow (CBF) data after the drinking of DPAA-contaminated water was stopped and investigated the correlation between DPAA exposure level and CBF by single-photon emission computed tomography (CBF-SPECT). METHODS: The DPAA-exposed inhabitants (n = 78) were divided into 35 symptomatic and 43 asymptomatic subjects and compared with 38 healthy controls. The DPAA concentration in nails or hair and well water was measured using a high-performance liquid chromatography system and coupled plasma mass spectrometry after adequate extraction treatment. CBF-SPECT data, obtained within 1 year after the drinking of contaminated well water was stopped, were analyzed by statistical parametric mapping. We also examined the relationship between variations in CBF-SPECT signals and variations in DPAA concentrations in the hair or nails of the subjects. RESULTS: Compared with control subjects, CBF in symptomatic DPAA-exposed subjects was significantly lower in the occipital lobe, including the cuneus and inferior occipital gyri. The DPAA concentration in the nails or hair of subjects was inversely and significantly related to their CBF. CONCLUSION: These data suggest that CBF-SPECT may be useful as a clinical marker to infer the effect of accumulated DPAA on the brain.
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Intoxicación por Arsénico/fisiopatología , Arsenicales/análisis , Circulación Cerebrovascular/efectos de los fármacos , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Agua Potable/efectos adversos , Agua Potable/análisis , Femenino , Cabello/química , Humanos , Masculino , Persona de Mediana Edad , Uñas/química , Lóbulo Occipital/irrigación sanguínea , Lóbulo Occipital/efectos de los fármacos , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
The cross sections of the ^{7}Be(n,α)^{4}He reaction for p-wave neutrons were experimentally determined at E_{c.m.}=0.20-0.81 MeV slightly above the big bang nucleosynthesis (BBN) energy window for the first time on the basis of the detailed balance principle by measuring the time-reverse reaction. The obtained cross sections are much larger than the cross sections for s-wave neutrons inferred from the recent measurement at the n_TOF facility in CERN, but significantly smaller than the theoretical estimation widely used in the BBN calculations. The present results suggest the ^{7}Be(n,α)^{4}He reaction rate is not large enough to solve the cosmological lithium problem, and this conclusion agrees with the recent result from the direct measurement of the s-wave cross sections using a low-energy neutron beam and the evaluated nuclear data library ENDF/B-VII.1.
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BACKGROUND: Prostaglandin D2 (PGD2 ) is primarily produced by mast cells and is contributing to the nasal symptoms including nasal obstruction and rhinorrhea. OBJECTIVE: This study aimed to evaluate the efficacy and safety of a novel PGD2 receptor 1 (DP1) antagonist, ONO-4053, in patients with seasonal allergic rhinitis (SAR). METHODS: This study was a multicenter, randomized, double-blind, parallel-group study of patients with SAR. Following a one-week period of placebo run-in, patients who met the study criteria were randomized to either the ONO-4053, leukotriene receptor antagonist pranlukast, or placebo group for a two-week treatment period. A total of 200 patients were planned to be randomly assigned to receive ONO-4053, pranlukast, or placebo in a 2:2:1 ratio. Nasal and eye symptoms were evaluated. RESULTS: Both ONO-4053 and pranlukast had higher efficacy than placebo on all nasal and eye symptoms. ONO-4053 outperformed pranlukast in a total of three nasal symptom scores (T3NSS) as well as in individual scores for sneezing, rhinorrhea, and nasal itching. For T3NSS, the Bayesian posterior probabilities that pranlukast was better than placebo and ONO-4053 was better than pranlukast were 70.0% and 81.6%, respectively, suggesting that ONO-4053 has a higher efficacy compared with pranlukast. There was no safety-related issue in this study. CONCLUSIONS: We demonstrated that the efficacy of ONO-4053 was greater than that of pranlukast with a similar safety profile. This study indicates the potential of ONO-4053 for use as a treatment for SAR (JapicCTI-142706).
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Cromonas/uso terapéutico , Antagonistas de Leucotrieno/uso terapéutico , Receptores de Prostaglandina/antagonistas & inhibidores , Rinitis Alérgica Estacional/tratamiento farmacológico , Adulto , Degranulación de la Célula/inmunología , Cromonas/administración & dosificación , Cromonas/efectos adversos , Quimioterapia Combinada , Femenino , Humanos , Antagonistas de Leucotrieno/administración & dosificación , Antagonistas de Leucotrieno/efectos adversos , Masculino , Mastocitos/inmunología , Mastocitos/metabolismo , Persona de Mediana Edad , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/metabolismo , Índice de Severidad de la Enfermedad , Evaluación de Síntomas , Resultado del Tratamiento , Adulto JovenRESUMEN
Cognitive function tends to decrease with aging, therefore maintenance of this function in an aging society is an important issue. The role of chewing in nutrition is important. Although several studies indicate that gum chewing is thought to improve cognitive function, it remains debatable whether gum-chewing does in fact improve cognitive function. The Stroop test is a psychological tool used to measure cognition. A shorter reaction time indicates a mean higher behavioral performance and higher levels of oxy-Hb concentration. fNIRS is a powerful, non-invasive imaging technique offering many advantages, including compact size, no need for specially equipped facilities, and the potential for real-time measurement. The left dorsolateral prefrontal cortex (DLPFC) seems to be mainly involved in the Stroop task.The aim of the present study was to investigate the hypothesis that gum-chewing changes cerebral blood flow in the left DLPFC during the Stroop test, and also changes the reaction time. Fourteen healthy volunteers (mean age 26.9 years) participated in this study after providing written informed consent. A piece of tasteless gum weighing 1.0 g was used. Each session was designed in a block manner, i.e. 4 rests (30 s) and 3 blocks of task (30 s). A computerized Stroop test was used (including both congruent and incongruent Stroop tasks) which calculates a response time automatically. The Binominal test was used for comparisons (p < 0.05). The results show activation of the left DLPFC during the Stroop task and that gum chewing significantly increases responses/oxy-Hb concentration and significantly shortens the reaction time.
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Goma de Mascar , Masticación/fisiología , Test de Stroop , Adulto , Envejecimiento/psicología , Atención/fisiología , Cognición/fisiología , Femenino , Lateralidad Funcional/fisiología , Humanos , Masculino , Proyectos Piloto , Corteza Prefrontal/fisiología , Tiempo de Reacción/fisiología , Espectroscopía Infrarroja Corta , Adulto JovenRESUMEN
BACKGROUND: The transcription factor, zinc finger protein 143 (ZNF143), positively regulates many cell-cycle-related genes. The ZNF143 would show high expression of multiple solid tumours related closely to cancer cell growth, similar to the widely accepted Ki67 (MIB-1) protein, but the underlying mechanisms for ZNF143 remain unclear. We investigated the association of ZNF143 expression with clinicopathological features and prognoses of patients with lung adenocarcinoma. METHODS: Expressions of ZNF143 and MIB-1 were immunohistochemically analysed in 183 paraffin-embedded tumour samples of patients with lung adenocarcinoma. The ZNF143 expression was considered to be strong when >30% of the cancer cells demonstrated positive staining. RESULTS: Strong ZNF143+ expression showed a significantly close relationship to pathologically moderate to poor differentiation and highly invasive characteristics. The ZNF143 positivity potentially induced cell growth of lung adenocarcinoma, correlated significantly with high MIB-1 labelling index (⩾10%). Univariate and multivariate analyses demonstrated that both strong ZNF143+ and the high MIB-1 index group have only and significantly worse survival rates. CONCLUSIONS: The combination of strong ZNF143 expression and high MIB-1 index potentially predicts high proliferating activity and poor prognosis in patients with lung adenocarcinoma, and may offer a therapeutic target against ZNF143.
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Adenocarcinoma/química , Antígeno Ki-67/análisis , Neoplasias Pulmonares/química , Proteínas de Neoplasias/análisis , Transactivadores/análisis , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Diferenciación Celular , División Celular , Femenino , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Índice Mitótico , Datos de Secuencia Molecular , Clasificación del Tumor , Invasividad Neoplásica , Proteínas de Neoplasias/inmunología , Fragmentos de Péptidos/inmunología , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Transactivadores/inmunología , Resultado del TratamientoRESUMEN
Cytosolic 3,5,3'-triiodo-l-thyronine-binding protein plays pivotal roles in the regulation of intracellular 3,5,3'-triiodo-l-thyronine concentration in vivo. The expression of the protein, which is identical to µ-crystallin, is regulated by various factors. To elucidate the mechanisms of its expression, we evaluated the promoter transactivity and insulin signaling via the AP-1 site in the promoter. The isolated 600 bp human and 1976 bp mouse 5'-flanking regions were cloned in a luciferase reporter plasmid. The luciferase activity was estimated in GH3, dRLh-84, HEK293, and insulin receptor-overexpressing CHO-IR cells. The effects of 12-O-tetradecanoylphorbol 13-acetate and insulin on µ-crystallin mRNA expression were evaluated in various cells. The region between -200 and the transcriptional start site was crucial for constitutive expression in µ-crystallin-expressing dRLh-84 cells. This region contained an AP-1 site. 12-O-Tetradecanoylphorbol 13-acetate increased the level of µ-crystallin mRNA expression in HEK 293 cells. The compound also increased luciferase activity through the promoter. Mutation in the AP1 site diminished the response to the compound. The promoter was also activated by insulin treatment in CHO-IR cells. Insulin treatment increased µ-crystallin mRNA expression in Raw264.7 cells, but decreased in HEK293, P19, and dRLH-84 cells. The expression of µ-crystallin was regulated through the AP-1 site in the promoter. The signals related to AP-1 activation, such as insulin signaling may have diverse effects on µ-crystallin mRNA expression.
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Cristalinas/química , Cristalinas/genética , Regiones Promotoras Genéticas , Triyodotironina/metabolismo , Regulación hacia Arriba , Animales , Sitios de Unión , Línea Celular , Cristalinas/metabolismo , Genes Reporteros , Humanos , Insulina/metabolismo , Ratones , Unión Proteica , Acetato de Tetradecanoilforbol/metabolismo , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Activación Transcripcional , Cristalinas muRESUMEN
Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by combined systemic degeneration of the dentatofugal and pallidofugal pathways. We investigated a candidate gene and found that DRPLA patients had an expanded CAG trinucleotide repeat in a gene on the short arm of chromosome 12. The repeat size varied from 7-23 in normal individuals. In patients one allele was expanded to between 49-75 repeats or occasionally even more. Expansion was usually associated with paternal transmission and only occasionally with maternal transmission. Repeat size showed a close correlation with age of onset of symptoms and disease severity. We conclude that DRPLA is the seventh genetic disorder known to be associated with expansion of an unstable trinucleotide repeat.
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Cromosomas Humanos Par 12 , Enfermedades del Sistema Nervioso/genética , Secuencias Repetitivas de Ácidos Nucleicos , Alelos , Secuencia de Aminoácidos , Atrofia , Secuencia de Bases , Encéfalo/patología , Ataxia Cerebelosa/genética , Cartilla de ADN/genética , Femenino , Globo Pálido/patología , Humanos , Masculino , Datos de Secuencia Molecular , Enfermedades del Sistema Nervioso/patología , Oligodesoxirribonucleótidos/genética , LinajeRESUMEN
Seismic velocities in rocks are highly sensitive to changes in permanent deformation and fluid content. The temporal variation of seismic velocity during the preparation phase of earthquakes has been well documented in laboratories but rarely observed in nature. It has been recently found that some anthropogenic, high-frequency (>1 Hz) seismic sources are powerful enough to generate body waves that travel down to a few kilometers and can be used to monitor fault zones at seismogenic depth. Anthropogenic seismic sources typically have fixed spatial distribution and provide new perspectives for velocity monitoring. In this work, we propose a systematic workflow to seek such powerful seismic sources in a rapid and straightforward manner. We tackle the problem from a statistical point of view, considering that persistent, powerful seismic sources yield highly coherent correlation functions (CFs) between pairs of seismic sensors. The algorithm is tested in California and Japan. Multiple sites close to fault zones show high-frequency CFs stable for an extended period of time. These findings have great potential for monitoring fault zones, including the San Jacinto Fault and the Ridgecrest area in Southern California, Napa in Northern California, and faults in central Japan. However, extra steps, such as beamforming or polarization analysis, are required to determine the dominant seismic sources and study the source characteristics, which are crucial to interpreting the velocity monitoring results. Train tremors identified by the present approach have been successfully used for seismic velocity monitoring of the San Jacinto Fault in previous studies.
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OBJECTIVES: Hypovitaminosis D as a result of malnutrition or sunlight deprivation, increased bone resorption, low bone mineral density (BMD), or an increased risk of falls may contribute to an increased risk of hip fractures in patients with neurological diseases, including Alzheimer's disease, Parkinson's disease, and stroke. The purpose of this study was to clarify the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with such neurological diseases. METHODS: The English literature was searched using PubMed, and randomized controlled trials evaluating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer's disease, Parkinson's disease, and stroke were identified. The relative risk and the 95% confidence interval were calculated for individual randomized controlled trials, and a pooled data analysis (meta-analysis) was performed. RESULTS: Three randomized controlled trials were identified. Sunlight exposure improved hypovitaminosis D and increased the BMD. The relative risk (95% confidence interval) of hip fractures was 0.22 (0.05, 1.01) for Alzheimer's disease, 0.27 (0.08, 0.96) for Parkinson's disease, and 0.17 (0.02, 1.36) for stroke. The relative risk (95% confidence interval) calculated for the pooled data analysis was 0.23 (0.10, 0.56) (P = 0.0012), suggesting a significant risk reduction rate of 77%. CONCLUSION: The present meta-analysis added additional evidence indicating the efficacy of sunlight exposure for reducing the risk of hip fractures in patients with Alzheimer's disease, Parkinson's disease, and stroke.
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Enfermedad de Alzheimer/epidemiología , Fracturas de Cadera/epidemiología , Fracturas de Cadera/prevención & control , Osteoporosis/prevención & control , Enfermedad de Parkinson/epidemiología , Accidente Cerebrovascular/epidemiología , Luz Solar , Anciano , Densidad Ósea/fisiología , Femenino , Humanos , Masculino , Osteoporosis/epidemiología , Vitamina D/administración & dosificación , Vitamina D/fisiologíaRESUMEN
A randomized controlled trial was conducted to determine the effect of 6 months of whole body vibration (WBV) exercise on physical function in postmenopausal osteoporotic women treated with alendronate. Fifty-two ambulatory postmenopausal women with osteoporosis (mean age: 74.2 years, range: 51-91 years) were randomly divided into two groups: an exercise group and a control group. A four-minute WBV exercise was performed two days per week only in the exercise group. No exercise was performed in the control group. All the women were treated with alendronate. After 6 months of the WBV exercise, the indices for flexibility, body balance, and walking velocity were significantly improved in the exercise group compared with the control group. The exercise was safe and well tolerated. The reductions in serum alkaline phosphatase and urinary cross-linked N-terminal telopeptides of type I collagen during the 6-month period were comparable between the two groups. The present study showed the benefit and safety of WBV exercise for improving physical function in postmenopausal osteoporotic women treated with alendronate.
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Terapia por Ejercicio/métodos , Osteoporosis Posmenopáusica/rehabilitación , Equilibrio Postural , Vibración/uso terapéutico , Caminata , Anciano , Anciano de 80 o más Años , Alendronato/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/tratamiento farmacológicoRESUMEN
AIMS: Endoscopic modified transseptal bi-nostril approach minimizes turbinate and olfactory mucosal invasion and ensures preservation of the turbinates and bilateral olfaction. The main objective of this study was to investigate the pre- and postoperative variations in olfactory function in patients using this approach, and the secondary objective was to investigate the complications associated with the surgical procedure. MATERIAL AND METHODS: This study is a single-center prospective cohort study using STROBE analysis. To completely protect the bilateral turbinates and olfactory epithelium, this procedure provided access to the sphenoid sinus by a transseptal approach via the left nasal cavity and by the olfactory cleft approach via the right nasal cavity without any turbinate resection. A T&T olfactometer was used to assess the mean recognition threshold of the left, right, and bilateral nasal passages before and after surgery, and complications associated with the surgical approach were investigated. OBJECTIVES: We included 27 patients who underwent endoscopic modified transseptal pituitary surgery with an olfactory and turbinate preservation approach at our hospital between April 2018 and December 2019. RESULTS: The mean postoperative recognition threshold of the right, left, and bilateral nasal cavities did not worsen (P<0.001 for all) relative to the preoperative values, and there was no difference in values between the right and left nasal cavities (P=0.85). The nasal turbinates were preserved in all patients during the study period, and no recurrence was observed. CONCLUSION: Our modified EETSA could be implemented as an approach for turbinate and olfaction preservation.
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Neoplasias Hipofisarias , Cornetes Nasales , Humanos , Cornetes Nasales/cirugía , Cavidad Nasal/cirugía , Neoplasias Hipofisarias/cirugía , Neoplasias Hipofisarias/complicaciones , Estudios Prospectivos , Complicaciones Posoperatorias/etiología , Endoscopía/métodosRESUMEN
Statins and fibrates are frequently used to treat hyperlipidemia; however, these drugs may have adverse effects such as rhabdomyolysis. The incidence of rhabdomyolysis due to fibrates and statins is low (0.0028-0.0096%) when administered as monotherapy, however it increases to 0.015-0.021% when the drugs are used in combination. The mechanism underlying myotoxicity induced by the combination of statins and fibrates is yet unclear. Here, we investigated the mechanisms underlying induced myotoxicity in rat myoblasts L6 and differentiated L6 cells (myotubes) using a combination of statins and fibrates. We found that cell death induced by a combination of fluvastatin or simvastatin with bezafibrate or fenofibrate in L6 myoblasts and myotubes was mediated by inhibition of geranylgeranyl pyrophosphate (GGPP) production. Additionally, the drug combination inhibited Rho activation in L6 myoblasts and myotube cells. In L6 myoblasts, the combination of statins and bezafibrate enhanced p27 expression and induced G1 arrest and apoptosis. Furthermore, combined treatment suppressed Akt activation and enhanced Bim expression in L6 myotubes but did not affect extracellular regulated protein kinase 1/2 activation. These results suggested that combined administration of statins and fibrates induced death of L6 myoblasts and myotube cells by inhibiting GGPP biosynthesis and Rho pathway activation. Supplementation with GGPP may be therapeutically beneficial for preventing myotoxicity associated with combined statin and fibrates treatment.