Summary measures of population health (SMPHs) have been used to estimate the burden of diseases. Among various type of SMPHs, disability adjusted life year (DALY) and healthy life expectancy (HALE) have been calculated in the global and national burden of disease studies. In order to calculate DALY and HALE, disability weight is an essential element. Disability weights quantify the level of disability for health states or diseases and have values between 0 (full health) to 1 (being dead). In this study, we reviewed the main disability weights studies and determined their meaning and limitations. Furthermore, we provided the whole process of typical disability weight study and reviewed key issues as follows: health state or disease description development, panel composition, valuation method, validation of disability weight, cross-cultural variability in health state or disease, and so on. The results from this study will be helpful to conduct future disability weight studies for adapting disability weights and developing new methodologies.
Life Expectancy ; Quality-Adjusted Life Years ; Weights and Measures

Posterior reversible leukoencephalopathy syndrome (PRES) is characterized by transient headache, altered mental functioning, seizures, and loss of vision associated with findings of predominantly posterior cerebral lesions on imaging studies. Magnetic resonance imaging typically shows bilateral hyperintensity on T2 weighted imaging and fluid attenuated inversion recovery imaging, predominantly in the parieto-occipital region. The common etiologies of PRES include eclampsia, renal impairment, immunosuppressive treatment, cancer chemotherapy, autoimmune diseases, and hypertension. The prognosis is usually benign when adequate treatment is initiated immediately. Otherwise, delay in diagnosis and treatment may lead to permanent neurological sequelae. We report on the case of a 24-year-old man who presented with the characteristics of PRES with acute carbon monoxide poisoning.
Autoimmune Diseases ; Carbon Monoxide Poisoning* ; Carbon Monoxide* ; Carbon* ; Diagnosis ; Drug Therapy ; Eclampsia ; Female ; Headache ; Hypertension ; Leukoencephalopathies* ; Magnetic Resonance Imaging ; Poisoning ; Posterior Leukoencephalopathy Syndrome ; Pregnancy ; Prognosis ; Seizures ; Young Adult

Posterior reversible leukoencephalopathy syndrome (PRES) is characterized by transient headache, altered mental functioning, seizures, and loss of vision associated with findings of predominantly posterior cerebral lesions on imaging studies. Magnetic resonance imaging typically shows bilateral hyperintensity on T2 weighted imaging and fluid attenuated inversion recovery imaging, predominantly in the parieto-occipital region. The common etiologies of PRES include eclampsia, renal impairment, immunosuppressive treatment, cancer chemotherapy, autoimmune diseases, and hypertension. The prognosis is usually benign when adequate treatment is initiated immediately. Otherwise, delay in diagnosis and treatment may lead to permanent neurological sequelae. We report on the case of a 24-year-old man who presented with the characteristics of PRES with acute carbon monoxide poisoning.
Autoimmune Diseases ; Carbon Monoxide Poisoning* ; Carbon Monoxide* ; Carbon* ; Diagnosis ; Drug Therapy ; Eclampsia ; Female ; Headache ; Hypertension ; Leukoencephalopathies* ; Magnetic Resonance Imaging ; Poisoning ; Posterior Leukoencephalopathy Syndrome ; Pregnancy ; Prognosis ; Seizures ; Young Adult

Purpose: To report two cases of early onset oculopharyngeal muscular dystrophy, which were suspected to be chronic progressive external ophthalmoplegia.Case summary: Case 1, a 15-year-old male and Case 2, a 13-year-old male brother, visited the clinic with persistent diplopia 6 years prior. The older brother’s best-corrected visual acuity was 0.6 in both eyes and showed an exodeviation of 25 prism diopters. Bilateral ptosis was observed with ocular muscle movement limitations in all directions, and bilateral macular edema was found on fundus examinations. The younger brother had a best-corrected visual acuity of 1.0 in both eyes and showed exodeviation of 45 prism diopters. Bilateral ptosis and ocular muscle movement limitations were also observed. Both patients were suspected to have chronic progressive external ophthalmoplegia and were referred to a neurologist for a neurological examination and muscle biopsy. The muscle biopsies showed that both patients were diagnosed with oculopharyngeal muscular dystrophy. Conclusions It is important, initially, to report a case of early onset oculopharyngeal muscular dystrophy that has eyelid and eye movement symptoms, but no other typical symptoms.

PURPOSE: Amplified mesenchymal-epithelial transition factor, MET, is a receptor tyrosine kinase (RTK) that has been considered a druggable target in non-small cell lung cancer (NSCLC). Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated. To understand the mechanisms of resistance and establish therapeutic strategies, we developed an in vitro model using the MET-amplified NSCLC cell line EBC-1. MATERIALS AND METHODS: We established capmatinib-resistant NSCLC cell lines and identified alternative signaling pathways using 3′ mRNA sequencing and human phospho-RTK arrays. Copy number alterations were evaluated by quantitative polymerase chain reaction and cell proliferation assay; activation of RTKs and downstream effectors were compared between the parental cell line EBC-1 and the resistant cell lines. RESULTS: We found that EBC-CR1 showed an epidermal growth factor receptor (EGFR)‒dependent growth and sensitivity to afatinib, an irreversible EGFR TKI. EBC-CR2 cells that had overexpression of EGFR-MET heterodimer dramatically responded to combined capmatinib with afatinib. In addition, EBC-CR3 cells derived from EBC-CR1 cells that activated EGFR with amplified phosphoinositide-3 kinase catalytic subunit α (PIK3CA) were sensitive to combined afatinib with BYL719, a phosphoinositide 3-kinase α (PI3Kα) inhibitor. CONCLUSION: Our in vitro studies suggested that activation of EGFR signaling and/or genetic alteration of downstream effectors like PIK3CA were alternative resistance mechanisms used by capmatinib-resistant NSCLC cell lines. In addition, combined treatments with MET, EGFR, and PI3Kα inhibitors may be effective therapeutic strategies in capmatinib-resistant NSCLC patients.
Carcinoma, Non-Small-Cell Lung ; Catalytic Domain ; Cell Line ; Cell Proliferation ; Humans ; In Vitro Techniques ; Parents ; Phosphotransferases ; Polymerase Chain Reaction ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; RNA, Messenger

Transient receptor potential vanilloid subtype 1 (TRPV1) was originally found in sensory neurons. Recently, it has been reported that TRPV1 is expressed in salivary gland epithelial cells (SGEC). However, the physiological role of TRPV1 in salivary secretion remains to be elucidated. We found that TRPV1 is expressed in mouse and human submandibular glands (SMG) and HSG cells, originated from human submandibular gland ducts at both mRNA and protein levels. However, capsaicin (CAP), TRPV1 agonist, had little effect on intracellular free calcium concentration ([Ca2+]i) in these cells, although carbachol consistently increased [Ca2+]i. Exposure of cells to high temperature (>43degrees C) or acidic bath solution (pH5.4) did not increase [Ca2+]i, either. We further examined the role of TRPV1 in salivary secretion using TRPV1 knock-out mice. There was no significant difference in the pilocarpine (PILO)-induced salivary flow rate between wild-type and TRPV1 knock-out mice. Saliva flow rate also showed insignificant change in the mice treated with PILO plus CAP compared with that in mice treated with PILO alone. Taken together, our results suggest that although TRPV1 is expressed in SGEC, it appears not to play any direct roles in saliva secretion via transcellular pathway.
Animals ; Baths ; Calcium ; Capsaicin ; Carbachol ; Epithelial Cells* ; Humans ; Mice ; Mice, Knockout ; Pilocarpine ; RNA, Messenger ; Saliva ; Salivary Glands* ; Sensory Receptor Cells ; Submandibular Gland ; Transcytosis*

Purpose: The aim of this study is to evaluate the effect of body mass index (BMI) on peak serum growth hormone (GH) level after GH stimulation test in children with short stature. Methods: Data were obtained from retrospective medical record reviews of those who visited the pediatric endocrine clinic at St. Vincent’s Hospital of Catholic University for short stature from January 2010 to June 2019. A total of 115 children (66 boys and 49 girls) whose height was less than the third percentile according to age and sex underwent GH stimulation testing. Results: Of the 115 subjects, 47 were diagnosed with GH deficiency (GHD) and 68 were diagnosed with idiopathic short stature (ISS). In patients with GHD, weight standard deviation score (SDS) (P<0.001) and BMI SDS (P≤0.001) were higher, and free thyroxine (T4) level (P=0.012) was lower than those in the ISS group. In total subjects, peak serum GH level after GH stimulation test showed negative correlations with weight SDS (r=-0.465, P<0.001), BMI SDS (r=-0.398, P<0.001), and thyroid stimulating hormone (r=-0.248, P=0.008) and a positive correlation with free T4 (r=0.326, P<0.001). In multiple regression analysis, BMI SDS (P=0.003) was negatively associated with peak serum GH level in GH stimulation testing after adjusting for age, sex, pubertal status, and type of pharmacological stimulus. Conclusion The BMI SDS influences peak serum GH level after GH stimulation testing. We should consider BMI factors when interpreting the results of GH stimulation testing.

Purpose: The aim of this study is to evaluate the effect of body mass index (BMI) on peak serum growth hormone (GH) level after GH stimulation test in children with short stature. Methods: Data were obtained from retrospective medical record reviews of those who visited the pediatric endocrine clinic at St. Vincent’s Hospital of Catholic University for short stature from January 2010 to June 2019. A total of 115 children (66 boys and 49 girls) whose height was less than the third percentile according to age and sex underwent GH stimulation testing. Results: Of the 115 subjects, 47 were diagnosed with GH deficiency (GHD) and 68 were diagnosed with idiopathic short stature (ISS). In patients with GHD, weight standard deviation score (SDS) (P<0.001) and BMI SDS (P≤0.001) were higher, and free thyroxine (T4) level (P=0.012) was lower than those in the ISS group. In total subjects, peak serum GH level after GH stimulation test showed negative correlations with weight SDS (r=-0.465, P<0.001), BMI SDS (r=-0.398, P<0.001), and thyroid stimulating hormone (r=-0.248, P=0.008) and a positive correlation with free T4 (r=0.326, P<0.001). In multiple regression analysis, BMI SDS (P=0.003) was negatively associated with peak serum GH level in GH stimulation testing after adjusting for age, sex, pubertal status, and type of pharmacological stimulus. Conclusion The BMI SDS influences peak serum GH level after GH stimulation testing. We should consider BMI factors when interpreting the results of GH stimulation testing.

Purpose: To analyze growth patterns over 2 years after birth according to preterm infant birth weight and length percentiles. Methods: Anthropometric measurements of 82 preterm infants were retrospectively reviewed. Preterm infants with birth weight or length below the 10th percentile were classified as small for gestational age (SGA) (n=19) and those between the 10th and 89th percentile as appropriate for gestational age (AGA) (n=63). The association between the length standard deviation score (SDS) at 2 years of corrected age and clinical factors were analyzed. Results: The length SDS of the SGA group was significantly increased at 6 months (-1.30±1.71) and 24 months (-0.97±1.06) of corrected age. The length SDS was lower in the SGA group than those in the AGA group at 6 months (-1.30±1.71 vs. -0.25±1.15, P=0.004), 18 months (-0.97±1.39 vs. -0.03±1.29, P=0.015), and 24 months (-0.97±1.06 vs. -0.29±1.12, P=0.022,). The percentage of children with a length SDS of <-2 (growth failure) at 24 months was 15.8% in the SGA group and 4.8% in the AGA group (P=0.108). Multiple linear regression analysis demonstrated that length at 24 months of corrected age was negatively correlated with birth length below the 10th percentile (coefficient β=-0.91, P=0.001) and duration of stay in the neonatal intensive care unit (NICU) (coefficient β=-0.01, P=0.001). Conclusion Despite the fact that catch-up growth occurs during the early period of infancy in a large portion of preterm SGA infants, a significant portion of these infants show growth failure at 24 months of age. Growth over 2 years after birth is affected by birth length and duration of stay in the NICU in preterm children.

With proper guidance, virtual reality (VR) can provide psychiatric therapeutic strategies within a simulated environment. The visuo-haptic-based multimodal feedback VR solution has been developed to improve anxiety symptoms through immersive experience and feedback. A proof-of-concept study was performed to investigate this VR solution. Nine subjects recently diagnosed with panic disorder were recruited, and seven of them eventually completed the trial. Two VR sessions were provided to each subject. Depression, anxiety, and VR sickness were evaluated before and after each session. Although there was no significant effect of the VR sessions on psychiatric symptoms, we could observe a trend of improvement in depression, anxiety, and VR sickness. The VR solution was effective in relieving subjective anxiety, especially in panic disorder without comorbidity. VR sickness decreased over time. This study is a new proof-of-concept trial to evaluate the therapeutic effect of VR solutions on anxiety symptoms using visuo-haptic-based multimodal feedback simultaneously.