Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell–derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55+) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.

Background/Aims: Platelet-derived growth factor receptor alpha-positive (PDGFRα + ) cells function in the purinergic regulation of gastrointestinal motility, and purines are reportedly inhibitory neurotransmitters in the enteric nervous system. We explore the distribution and function of PDGFRα + cells related to purinergic inhibitory neurotransmission in human right and left colons. Methods: Human colonic segments were prepared with mucosa and submucosa intact, and the circular muscle tension and longitudinal muscle tension were recorded. Purinergic neurotransmitters were administered after recording the regular contractions.Immunohistochemistry was performed on the circular muscle layers. Intracellular recording was performed on the colonic muscular layer. SK3, P2RY1, and PDGFR-α mRNA expression was tested by quantitative real-time polymerase chain reaction (qPCR). Results: Adenosine triphosphate (ATP) treatment significantly decreased the frequency and area under the curve (AUC) of the segmental contraction in right and left colons. Beta-nicotinamide adenine dinucleotide (β-NAD) decreased the frequency in the right colon and the amplitude, frequency and AUC in the left colon. Apamin significantly increased frequency and AUC in the left colon, and after apamin pretreatment, ATP and β-NAD did not change segmental contractility. Through intracellular recordings, a resting membrane potential decrease occurred after ATP administration; however, the degree of decrease between the right and left colon was not different. PDGFRα +Conclusion Purines reduce right and left colon contractility similarly, and purinergic inhibitory neurotransmission can be regulated by PDGFRα+ cells in the human colon.

Objective: Recently data has been accumulated regarding the role of coping strategies in the relationship between stress and sleep quality. Therefore, we set out to identify the mediating effects of coping strategies between stress and sleep quality. Methods: A online-based cross-sectional study was performed using the Perceived Stress Scale-10, the Pittsburgh Sleep Quality Index, and a simplification of the 60-item Coping Orientation to Problems Experienced (Brief COPE) inventory in the nonclinical adult sample. The 24 items of Brief COPE were categorized into four factors (social support, problem solving, avoidance, positive thinking). Then, we used the PROCESS macro to conduct the multiple mediation analysis for the four coping styles as potential mediators in the relationship between stress and sleep quality, and an additional subgroup analysis was examined to identify a gender difference for the mediation effect. Results: As a group, four coping styles mediated significantly the association between perceived stress and poor sleep quality. And avoidance has maintained its significance thought all regression analyses. Finally, this results remained as same in the females. Conclusion The effect of perceived stress on poor sleep quality was mediated by coping strategies, especially by avoidance. Thus, further research should consider the coping styles of individuals to reduce the influence of stress on sleep quality.

Objective: : The purpose of this study was to identify risk factors for distal adding on (AO) or distal junctional kyphosis (DJK) in adolescent idiopathic scoliosis (AIS) treated by posterior spinal fusion (PSF) to L3 with a minimum 2-year follow-up. Methods: : AIS patients undergoing PSF to L3 by two senior surgeons from 2000–2010 were analyzed. Distal AO and DJK were deemed poor radiographic results and defined as >3 cm of deviation from L3 to the center sacral vertical line (CSVL), or >10° angle at L3–4 on the posterior anterior- or lateral X-ray at ultimate follow-up. New stable vertebra (SV) and neutral vertebra (NV) scores were defined for this study. The total stability (TS) score was the sum of the SV and NV scores. Results: : Ten of 76 patients (13.1%) were included in the poor radiographic outcome group. The other 66 patients were included in the good radiographic outcome group. Lower Risser grade, more SV-3 (CSVL doesn’t touch the lowest instrumented vertebra [LIV]) on standing and side bending films, lesser NV and TS score, rigid L3–4 disc, more rotation and deviation of L3 were identified risk factors for AO or DJK. Age, number of fused vertebrae, curve correction, preoperative coronal/sagittal L3–4 disc angle did not differ significantly between the two groups. Multiple logistic regression results indicated that preoperative Risser grade 0, 1 (odds ratio [OR], 1.8), SV-3 at L3 in standing and side benders (OR, 2.1 and 2.8, respectively), TS score -5, -6 at L3 (OR, 4.4), rigid disc at L3–4 (OR, 3.1), LIV rotation >15° (OR, 2.9), and LIV deviation >2 cm from CSVL (OR, 2.2) were independent predictive factors. Although there was significant improvement of the of Scoliosis Research Society-22 average scores only in the good radiographic outcome group, there was no significant difference in the scores between the groups. Conclusion : The prevalence of AO or DJK at ultimate follow-up for AIS with LIV at L3 was 13.1%. To prevent AO or DJK following fusion to L3, we recommend that the CSVL touch L3 in both standing and side bending, TS score is -4 or less, the L3/4 disc is flexible, L3 is neutral (<15°) and ≤2 cm from the midline and the patient is ≥ Risser 2.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Objective: : The purpose of this study was to identify risk factors for distal adding on (AO) or distal junctional kyphosis (DJK) in adolescent idiopathic scoliosis (AIS) treated by posterior spinal fusion (PSF) to L3 with a minimum 2-year follow-up. Methods: : AIS patients undergoing PSF to L3 by two senior surgeons from 2000–2010 were analyzed. Distal AO and DJK were deemed poor radiographic results and defined as >3 cm of deviation from L3 to the center sacral vertical line (CSVL), or >10° angle at L3–4 on the posterior anterior- or lateral X-ray at ultimate follow-up. New stable vertebra (SV) and neutral vertebra (NV) scores were defined for this study. The total stability (TS) score was the sum of the SV and NV scores. Results: : Ten of 76 patients (13.1%) were included in the poor radiographic outcome group. The other 66 patients were included in the good radiographic outcome group. Lower Risser grade, more SV-3 (CSVL doesn’t touch the lowest instrumented vertebra [LIV]) on standing and side bending films, lesser NV and TS score, rigid L3–4 disc, more rotation and deviation of L3 were identified risk factors for AO or DJK. Age, number of fused vertebrae, curve correction, preoperative coronal/sagittal L3–4 disc angle did not differ significantly between the two groups. Multiple logistic regression results indicated that preoperative Risser grade 0, 1 (odds ratio [OR], 1.8), SV-3 at L3 in standing and side benders (OR, 2.1 and 2.8, respectively), TS score -5, -6 at L3 (OR, 4.4), rigid disc at L3–4 (OR, 3.1), LIV rotation >15° (OR, 2.9), and LIV deviation >2 cm from CSVL (OR, 2.2) were independent predictive factors. Although there was significant improvement of the of Scoliosis Research Society-22 average scores only in the good radiographic outcome group, there was no significant difference in the scores between the groups. Conclusion : The prevalence of AO or DJK at ultimate follow-up for AIS with LIV at L3 was 13.1%. To prevent AO or DJK following fusion to L3, we recommend that the CSVL touch L3 in both standing and side bending, TS score is -4 or less, the L3/4 disc is flexible, L3 is neutral (<15°) and ≤2 cm from the midline and the patient is ≥ Risser 2.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

PURPOSE: Inhaled corticosteroids (ICSs) are often considered an empirical therapy in the management of patients with cough. However, ICS responsiveness is difficult to interpret in daily clinical practice, as the improvements may include placebo effects or self-remission. We aimed to evaluate ICS and placebo treatment effects in adult patients with cough. METHODS: Electronic databases were searched for studies published until June 2018, without language restriction. Randomized controlled trials reporting the effects of ICSs compared with placebo in adult patients with cough were included. Random effects meta-analyses were conducted to estimate the treatment effects. Therapeutic gain was calculated by subtracting the percentage change from baseline in the cough score in the ICS treatment group from that in the placebo treatment group. RESULTS: A total of 9 studies were identified and 8 studies measuring cough severity outcomes were included for meta-analyses. Therapeutic gain from ICSs ranged from −5.0% to +94.6% across the studies included; however, it did not exceed +22%, except for an outlier reporting very high therapeutic gains (+45.6% to +94.6%, depending on outcomes). Overall ICS treatment effects in cough severity outcomes were small-to-moderate (standardized mean difference [SMD], −0.38; 95% confidence interval [CI], −0.54, −0.23), which were comparable between subacute and chronic coughs. However, pooled placebo treatment effects were very large in subacute cough (SMD, −2.58; 95% CI, −3.03, −2.1), and modest but significant in chronic cough (SMD, −0.46; 95% CI, −0.72, −0.21). CONCLUSIONS: Overall therapeutic gain from ICSs is small-to-moderate. However, placebo treatment effects of ICS are large in subacute cough, and modest but still significant in chronic cough. These findings indicate the need for careful interpretation of ICS responsiveness in the management of cough patients in the clinic, and also for rigorous patient selection to identify ICS-responders.
Adrenal Cortex Hormones ; Adult ; Cough ; Humans ; Overall ; Patient Selection ; Placebo Effect ; Steroids

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.
Antineoplastic Agents ; Asian Continental Ancestry Group ; Drug Therapy ; Education ; Endometrial Neoplasms ; Female ; Gyeonggi-do ; Humans ; Immunotherapy ; Korea ; Ovarian Neoplasms ; Radiotherapy ; Uterine Cervical Neoplasms

The original version of this article contained wrong information of an author which should be changed.